1 00:00:06,776 --> 00:00:08,211 >> ALL RIGHT, WE'RE READY TO 2 00:00:08,211 --> 00:00:09,011 START THIS MORNING. 3 00:00:09,011 --> 00:00:11,047 I JUST WANTED TO SAY A FEW 4 00:00:11,047 --> 00:00:12,582 THINGS BEFORE WE GET 5 00:00:12,582 --> 00:00:12,915 STARTED. 6 00:00:12,915 --> 00:00:14,517 AGAIN, FOR THOSE OF YOU WHO 7 00:00:14,517 --> 00:00:19,322 MAY NOT HAVE BEEN HERE 8 00:00:19,322 --> 00:00:21,123 YESTERDAY, MOLLY WAGSTER ON 9 00:00:21,123 --> 00:00:23,226 THE NATIONAL INSTITUTE OF 10 00:00:23,226 --> 00:00:25,928 AGING AND THERE IS A KEY 11 00:00:25,928 --> 00:00:27,663 CARD UP HERE ON THE PODIUM 12 00:00:27,663 --> 00:00:29,632 SO IF IT BELONGS TO ANY OF 13 00:00:29,632 --> 00:00:31,801 YOU, YOU CAN CLAIM IT LATER. 14 00:00:31,801 --> 00:00:34,670 WE HAVE TWO MORE SESSIONS 15 00:00:34,670 --> 00:00:36,239 TODAY, BOTH EXTREMELY 16 00:00:36,239 --> 00:00:37,673 EXCITING AND AS EXCITING AS 17 00:00:37,673 --> 00:00:39,609 THE ONES WE HAD YESTERDAY 18 00:00:39,609 --> 00:00:42,445 AND SO PLEASED TO SEE ALL OF 19 00:00:42,445 --> 00:00:43,279 YOU BACK. 20 00:00:43,279 --> 00:00:48,251 WE WILL -- THIS SESSION WILL 21 00:00:48,251 --> 00:00:49,685 GO UNTIL ABOUT 10:20 A.M. 22 00:00:49,685 --> 00:00:51,587 AND THEN WE HAVE A FAIRLY 23 00:00:51,587 --> 00:00:52,622 BRIEF BREAK SPECIAL THEN 24 00:00:52,622 --> 00:00:54,123 START WITH THE FINAL SESSION 25 00:00:54,123 --> 00:00:54,924 OF THE SUMMIT. 26 00:00:54,924 --> 00:00:57,860 WE SHOULD BE WINDING UP 27 00:00:57,860 --> 00:00:59,896 AROUND A LITTLE AFTER 28 00:00:59,896 --> 00:01:01,664 1:00 SO I JUST WANTED TO 29 00:01:01,664 --> 00:01:03,266 GIVE Y'ALL THOSE NOTES AND 30 00:01:03,266 --> 00:01:04,867 SORT OF REMINDERS OF HOW THE 31 00:01:04,867 --> 00:01:08,437 DAY IS GOING TO GO TODAY. 32 00:01:08,437 --> 00:01:10,339 AGAIN, WE REALLY APPRECIATE 33 00:01:10,339 --> 00:01:11,507 EVERYONE BEING HERE AGAIN 34 00:01:11,507 --> 00:01:13,476 AND LOOKING FORWARD TO 35 00:01:13,476 --> 00:01:14,110 EXCITING PRESENTATIONS FOR 36 00:01:14,110 --> 00:01:21,017 THE REST OF THE SUMMIT. 37 00:01:21,017 --> 00:01:23,686 THANK YOU. 38 00:01:23,686 --> 00:01:24,687 >> GOOD MORNING, EVERYONE, 39 00:01:24,687 --> 00:01:28,224 WE WELCOME YOU TO SESSION 5, 40 00:01:28,224 --> 00:01:29,125 COMORBIDITIES AND SLEEP 41 00:01:29,125 --> 00:01:29,558 ENVIRONMENT. 42 00:01:29,558 --> 00:01:33,129 WE HAVE SOME TERRIFIC LINEUP 43 00:01:33,129 --> 00:01:34,630 OF SPEAKERS THIS MORNING. 44 00:01:34,630 --> 00:01:37,199 I AM JENNIFER BIZON FROM THE 45 00:01:37,199 --> 00:01:38,134 UNIVERSITY OF FLORIDA, I 46 00:01:38,134 --> 00:01:40,436 SHOULD SAY AND OUR SESSION 47 00:01:40,436 --> 00:01:42,838 THIS MORNING IS GOING TO 48 00:01:42,838 --> 00:01:45,241 START WITH GINA POE TELLING 49 00:01:45,241 --> 00:01:47,376 US ABOUT SLEEP FEATURES AND 50 00:01:47,376 --> 00:01:48,678 HOW AGING INFLUENCES THEM 51 00:01:48,678 --> 00:01:54,550 AND THEN WE'RE GOING TO MOVE 52 00:01:54,550 --> 00:01:57,186 TO KRISTEN OH CONNELL WHO 53 00:01:57,186 --> 00:02:03,793 WILL TALK ABOUT HOW GENETIC 54 00:02:03,793 --> 00:02:05,628 ENVIRONMENT WITH SECTION IS 55 00:02:05,628 --> 00:02:10,333 IMPORTANT IN HER RESEARCH 56 00:02:10,333 --> 00:02:12,902 AND THEN CHRISTINE YAFFE 57 00:02:12,902 --> 00:02:14,503 WILL TALK ABOUT THE 58 00:02:14,503 --> 00:02:16,973 IMPORTANCE OF LIFE COURSE 59 00:02:16,973 --> 00:02:21,310 APPROACH TO AGING AND 60 00:02:21,310 --> 00:02:23,279 MICHELLE MIEIKE WILL TALK 61 00:02:23,279 --> 00:02:25,948 ABOUT THE INFLUENCE OF 62 00:02:25,948 --> 00:02:27,149 ALZHEIMER'S DISEASE ON 63 00:02:27,149 --> 00:02:27,550 BIOMARKERS. 64 00:02:27,550 --> 00:02:29,785 SO I WILL NOT TAKE ANYMORE 65 00:02:29,785 --> 00:02:31,487 TIME AND INTRODUCE THE 66 00:02:31,487 --> 00:02:35,791 SPEAKERS AND START WITH GINA 67 00:02:35,791 --> 00:02:37,860 POE FROM UNIVERSITY OF 68 00:02:37,860 --> 00:02:38,661 CALIFORNIA-LOS ANGELES AND 69 00:02:38,661 --> 00:02:40,896 THE TITLE OF HER TALK IS 70 00:02:40,896 --> 00:02:42,531 SLEEP FEATURES IMPACTED BY 71 00:02:42,531 --> 00:02:43,766 THE AGING ENVIRONMENT. 72 00:02:43,766 --> 00:02:45,267 >> THANK YOU SO MUCH, 73 00:02:45,267 --> 00:02:47,670 JENNIFER, I AM COMING OFF A 74 00:02:47,670 --> 00:02:49,972 RED EYE FLIGHT SO I AM THE 75 00:02:49,972 --> 00:02:51,540 EPITOME OF NOT SLEEPING AND 76 00:02:51,540 --> 00:02:53,709 AGING SO YOU WILL SEE WHAT 77 00:02:53,709 --> 00:02:54,343 THAT DOES. 78 00:02:54,343 --> 00:02:54,710 [LAUGHTER] 79 00:02:54,710 --> 00:02:56,879 ALL RIGHT, SO THIS IS MY 80 00:02:56,879 --> 00:02:57,680 GRANDSON. 81 00:02:57,680 --> 00:03:00,282 HE IS SIX MONTHS OLD AND YOU 82 00:03:00,282 --> 00:03:03,586 CAN SEE AT THIS AGE ON THE 83 00:03:03,586 --> 00:03:04,887 SLIDE THAT THEY ARE SLEEPING 84 00:03:04,887 --> 00:03:07,189 A LOT AND THAT A LOT OF THAT 85 00:03:07,189 --> 00:03:08,991 SLEEP IS RAPID EYE MOVEMENT 86 00:03:08,991 --> 00:03:09,358 SLEEP. 87 00:03:09,358 --> 00:03:11,460 BUT AS WE GET OLDER AND 88 00:03:11,460 --> 00:03:14,630 OLDER, WE GET LESS AND LESS 89 00:03:14,630 --> 00:03:16,365 REM SLEEP AND ALSO AS YOU 90 00:03:16,365 --> 00:03:18,567 CAN SEE WHEN WE GET VERY 91 00:03:18,567 --> 00:03:29,045 MUCH OLDER, WE GET A LOT 92 00:03:35,951 --> 00:03:41,557 LESS SLOWER SLEEP AND WE'LL 93 00:03:41,557 --> 00:03:51,901 TALK WITH THAT. 94 00:03:51,901 --> 00:04:00,509 SO YOU CAN SEE HERE, THE BIG 95 00:04:00,509 --> 00:04:02,511 BLUE IS SLOW E SLEEP AND I 96 00:04:02,511 --> 00:04:03,813 DREW THE EEG ON TOP OF THIS 97 00:04:03,813 --> 00:04:05,881 SO YOU CAN SEE WHAT THIS 98 00:04:05,881 --> 00:04:06,415 LOOKS LIKE. 99 00:04:06,415 --> 00:04:10,853 IS A WE GO FROM WAKEFULNESS 100 00:04:10,853 --> 00:04:13,989 INTO SLEEP AND THEN DEEP 101 00:04:13,989 --> 00:04:15,691 SLOW A STREET AND THAT IS 102 00:04:15,691 --> 00:04:18,461 THE STAGE THAT GETS IMPACTED 103 00:04:18,461 --> 00:04:19,962 AS WE GET OLDER AND I WILL 104 00:04:19,962 --> 00:04:23,466 TELL YOU WHAT THAT WILL DO 105 00:04:23,466 --> 00:04:30,106 TO US AND THEN THE SPINDLES 106 00:04:30,106 --> 00:04:33,275 OF ANY ONE PERSON IS LINKED 107 00:04:33,275 --> 00:04:39,181 TO IQ AND WHERE WE'RE 108 00:04:39,181 --> 00:04:40,783 TRANSFERRING FROM THE HIPPO 109 00:04:40,783 --> 00:04:42,618 CAMPUS TO THE CORTEX AND 110 00:04:42,618 --> 00:04:45,488 THEN THERE IS THE SLOW REM 111 00:04:45,488 --> 00:04:48,224 SLEEP WHICH IS WHAT BABIES 112 00:04:48,224 --> 00:04:56,632 HAVE IN EYE AMOUNTS. 113 00:04:56,632 --> 00:04:58,901 THE HIPPO CAMPUS, IT IS 114 00:04:58,901 --> 00:05:02,271 REALLY BEAUTIFUL AND RELATED 115 00:05:02,271 --> 00:05:03,906 TO WAKEFULNESS AND THEN WE 116 00:05:03,906 --> 00:05:06,642 HAVE THE SLOW A SLEEP THAT 117 00:05:06,642 --> 00:05:07,510 RELATES TO MEMORY. 118 00:05:07,510 --> 00:05:12,314 AND EACH OF THREES HAVE A 119 00:05:12,314 --> 00:05:13,516 DIFFERENT NEUROCHEMICAL 120 00:05:13,516 --> 00:05:13,883 RESPONSE. 121 00:05:13,883 --> 00:05:15,851 DURING THE EARLY STAGES, YOU 122 00:05:15,851 --> 00:05:22,424 HAVE LOTS OF ACETYLCHOLINE 123 00:05:22,424 --> 00:05:30,766 IN YOUR BRAIN, THE REM, NOR 124 00:05:30,766 --> 00:05:35,938 HE HAVE FLYNN AND THEN 125 00:05:35,938 --> 00:05:37,806 SEROTONIN IN THE SLOW A 126 00:05:37,806 --> 00:05:43,078 SLEEP AND YOU REALLY NEED 127 00:05:43,078 --> 00:05:44,680 ACETYLCHOLINE TO GO TO ZERO 128 00:05:44,680 --> 00:05:47,183 IN THE BRAIN TO SET UP THE 129 00:05:47,183 --> 00:05:49,552 SLOW WAVES AND ANIMALS THAT 130 00:05:49,552 --> 00:05:51,620 DON'T SLEEP, THE ONE THING 131 00:05:51,620 --> 00:05:57,226 THAT CHANGES IS THE 132 00:05:57,226 --> 00:05:58,394 ACETYLCHOLINE WHERE IT 133 00:05:58,394 --> 00:05:59,195 CASHES INTO NOTHING. 134 00:05:59,195 --> 00:06:00,896 SO ALL THE TRANSMITTERS I 135 00:06:00,896 --> 00:06:04,867 HAVE HERE ARE DOWN TO ALMOST 136 00:06:04,867 --> 00:06:07,136 NOTHING, AND THIS IS THAT 137 00:06:07,136 --> 00:06:09,238 UNIQUE TIME WHEN THE BRAIN 138 00:06:09,238 --> 00:06:11,540 IS REALLY SHUT OFF TO THE 139 00:06:11,540 --> 00:06:12,675 OUTSIDE WORLD AND 140 00:06:12,675 --> 00:06:18,614 TRANSFERRING MEMORIES FROM 141 00:06:18,614 --> 00:06:20,449 THE HIPPOCAMPUS TO THE 142 00:06:20,449 --> 00:06:30,993 CORTEX AND THEN THERE IS THE 143 00:06:45,207 --> 00:06:48,711 AND THIS IS REALLY IMPORTANT 144 00:06:48,711 --> 00:06:50,112 TO REFRESH OUR BRAINS FOR 145 00:06:50,112 --> 00:06:50,546 THE NEXT DAY. 146 00:06:50,546 --> 00:06:53,415 SO THIS IS NOT MY RESEARCH 147 00:06:53,415 --> 00:06:56,385 BUT THE RESEARCH OF DOZENS 148 00:06:56,385 --> 00:06:58,320 OF RESEARCHERS SO WHAT SLOW 149 00:06:58,320 --> 00:07:07,029 WAVE SLEEP WE KNOW NOW IS 150 00:07:07,029 --> 00:07:08,163 BUILD CONNECTIONS IN TEN 151 00:07:08,163 --> 00:07:12,167 TIMES THE AMOUNT IT DOES IN 152 00:07:12,167 --> 00:07:13,702 WAKEFULNESS. 153 00:07:13,702 --> 00:07:20,276 WE CLEAR THE GARBAGE THROUGH 154 00:07:20,276 --> 00:07:22,745 THE GLMPHATIC SYSTEM AND THE 155 00:07:22,745 --> 00:07:26,015 PROTEINS IN THE EXTRA 156 00:07:26,015 --> 00:07:28,417 CELLULAR SPACE GETS CLEARED 157 00:07:28,417 --> 00:07:32,888 AND THEN WE CONVERT THE 158 00:07:32,888 --> 00:07:34,523 ADENOCINE THAT HAS BUILT UP 159 00:07:34,523 --> 00:07:38,861 WITH THE BREAKDOWN OF ATP, 160 00:07:38,861 --> 00:07:40,562 THE MITOCHONDRIA GET REALLY 161 00:07:40,562 --> 00:07:43,332 BUSY DURING THIS STAGE AND 162 00:07:43,332 --> 00:07:45,834 BREAK DOWN THE ATP MORE THAN 163 00:07:45,834 --> 00:07:48,771 IT DOES IN WAKEFULNESS AND 164 00:07:48,771 --> 00:07:49,605 IT REDUCES ANXIETY. 165 00:07:49,605 --> 00:07:51,707 WE HAVE NO IDEA WHAT THIS IS 166 00:07:51,707 --> 00:07:53,676 YET BUT WE KNOW THAT IS A 167 00:07:53,676 --> 00:07:54,576 REALLY IMPORTANT FUNCTION. 168 00:07:54,576 --> 00:07:58,914 HERE IS A STUDY BY MICHELLE 169 00:07:58,914 --> 00:07:59,715 CRAFT'S LAB, SORRY, I DON'T 170 00:07:59,715 --> 00:08:01,450 HAVE THE REFERENCE ON IT BUT 171 00:08:01,450 --> 00:08:04,019 YOU CAN SEE THE ASSOCIATION 172 00:08:04,019 --> 00:08:08,090 BETWEEN SLOW WAVE SLEEP AND 173 00:08:08,090 --> 00:08:09,425 ANXIETY IS HUGE AND BIGGER 174 00:08:09,425 --> 00:08:10,893 THAN ANYTHING ELSE. 175 00:08:10,893 --> 00:08:14,530 IF ALL YOU CAN DO IS LIGHT 176 00:08:14,530 --> 00:08:16,031 SLEEP AND DOZING, YOU HAVE 177 00:08:16,031 --> 00:08:18,867 MORE ANXIETY BUT IF YOU GET 178 00:08:18,867 --> 00:08:21,704 REALLY BIG JUICY SLOW WAVE 179 00:08:21,704 --> 00:08:23,305 SLEEP, YOUR ANXIETY LEVELS 180 00:08:23,305 --> 00:08:28,277 ARE LOWER THE NEXT DAY. 181 00:08:28,277 --> 00:08:31,280 SO HERE IS THE BOLUS OF OUR 182 00:08:31,280 --> 00:08:34,283 SLEEP, IF WE GO TO BED WHEN 183 00:08:34,283 --> 00:08:36,552 THE MELATONIN LEVELS ARE 184 00:08:36,552 --> 00:08:38,087 ALIGNED IN SLEEP, MEN AND 185 00:08:38,087 --> 00:08:43,192 WOMEN GET A BIG BOLUS OF 186 00:08:43,192 --> 00:08:44,893 GROWTH HORMONE ASSOCIATED 187 00:08:44,893 --> 00:08:45,828 WITH PROTEIN SYNTHESIS ALL 188 00:08:45,828 --> 00:08:47,896 OVER THE BODY BUT ESPECIALLY 189 00:08:47,896 --> 00:08:48,797 THE BRAIN. 190 00:08:48,797 --> 00:08:51,767 HERE IS THIS OLD SLIDE FROM 191 00:08:51,767 --> 00:08:53,369 1990 SHOWING IN SLOW A 192 00:08:53,369 --> 00:08:55,204 STREET AT THE VERY BOTTOM 193 00:08:55,204 --> 00:08:56,805 THERE, THE IMAGE AT THE 194 00:08:56,805 --> 00:08:58,207 BOTTOM IS A CROSS-SECTION OF 195 00:08:58,207 --> 00:08:59,141 A RAT'S BRAIN AND YOU CAN 196 00:08:59,141 --> 00:09:02,544 SEE THAT IS THE TIME WHEN 197 00:09:02,544 --> 00:09:05,214 AMINO ACIDS ARE REALLY 198 00:09:05,214 --> 00:09:06,815 INCORPORATED INTO PROTEIN 199 00:09:06,815 --> 00:09:08,183 WHERE WAKEFULNESS AND REM 200 00:09:08,183 --> 00:09:11,286 SLEEP AT THE TOP ARE NOT 201 00:09:11,286 --> 00:09:12,855 REALLY AS EFFICIENT. 202 00:09:12,855 --> 00:09:15,357 SO HERE IS SLOW WAVE SLEEP 203 00:09:15,357 --> 00:09:18,093 CLEARING THE BRAIN, I LIKEN 204 00:09:18,093 --> 00:09:21,697 IT TO A BILLING PUMP TIME 205 00:09:21,697 --> 00:09:23,198 AND WITH EVERY SLOW WAVE, 206 00:09:23,198 --> 00:09:25,501 THE NEURONS ARE FIRING AND 207 00:09:25,501 --> 00:09:27,469 AT THE TROUGHS, THE NEURONS 208 00:09:27,469 --> 00:09:31,974 ARE NOT FIRING AND IT IS A 209 00:09:31,974 --> 00:09:33,375 ASYNCHRONOUS TIME OF FIRING 210 00:09:33,375 --> 00:09:35,010 AND NOT FIRING AND EVERY 211 00:09:35,010 --> 00:09:36,945 TIME THEY FIRE, THEY EXPAND 212 00:09:36,945 --> 00:09:38,414 THE BRAIN 15 PERCENT AND 213 00:09:38,414 --> 00:09:42,718 THEN WHEN THEY ARE NOT 214 00:09:42,718 --> 00:09:43,652 FIRING, THEY CONTRACT AGAIN 215 00:09:43,652 --> 00:09:46,555 AND I THINK OF THAT AS A 216 00:09:46,555 --> 00:09:47,389 BILLING PUMP. 217 00:09:47,389 --> 00:09:56,198 SO IT HAS BEEN SHOWN TO 218 00:09:56,198 --> 00:09:58,367 CLEAR THE AMALOID BETA FROM 219 00:09:58,367 --> 00:10:03,605 THE BRAIN AND THAT HAPPENS 220 00:10:03,605 --> 00:10:04,540 THROUGH THE GLYMPHATIC AND 221 00:10:04,540 --> 00:10:09,511 THE FIRST AREA TO REALLY 222 00:10:09,511 --> 00:10:20,055 DEGENERATE IS THE LOCUS AND 223 00:10:21,056 --> 00:10:23,158 THE LOW FUNCTIONING IS 224 00:10:23,158 --> 00:10:24,159 ASSOCIATED WITH STRESSFUL 225 00:10:24,159 --> 00:10:25,194 CONDITIONS AND WOULD CAUSE 226 00:10:25,194 --> 00:10:27,596 POOR SLEEP IN A POSITIVE 227 00:10:27,596 --> 00:10:29,865 FEEDBACK LOOP BETWEEN 228 00:10:29,865 --> 00:10:33,402 ANXIETY, STRESS AND POOR 229 00:10:33,402 --> 00:10:35,437 SLEEP AND THEN ALSO THE LACK 230 00:10:35,437 --> 00:10:37,873 OF THE ABILITY TO CLEAR THIS 231 00:10:37,873 --> 00:10:38,640 PROTEIN. 232 00:10:38,640 --> 00:10:39,942 SO DISTURBED SLEEP AND 233 00:10:39,942 --> 00:10:40,943 SMALLER SLOW WAVES REALLY 234 00:10:40,943 --> 00:10:43,479 COULD BE A CAUSATIVE FACTOR 235 00:10:43,479 --> 00:10:44,646 FOR DEMENTIA SO THAT IS 236 00:10:44,646 --> 00:10:46,915 SOMETHING TO KEEP IN MIND. 237 00:10:46,915 --> 00:10:48,884 SO HERE IS AN IMAGE UNLIKE 238 00:10:48,884 --> 00:10:50,853 THE ONE I SHOWED YOU BEFORE 239 00:10:50,853 --> 00:10:52,821 OF A DISTURBED NIGHT SLEEP 240 00:10:52,821 --> 00:10:53,455 AND UNFORTUNATELY, WAY TOO 241 00:10:53,455 --> 00:10:55,457 MANY OF US HAVE A NIGHT 242 00:10:55,457 --> 00:10:56,758 SLEEP LIKE THIS FOR WHATEVER 243 00:10:56,758 --> 00:10:58,260 REASON AND I WILL TALK ABOUT 244 00:10:58,260 --> 00:10:58,827 THOSE REASONS. 245 00:10:58,827 --> 00:11:01,063 SO WHO GETS A POOR NIGHT'S 246 00:11:01,063 --> 00:11:01,830 SLEEP? 247 00:11:01,830 --> 00:11:04,900 A LOT OF PEOPLE. 248 00:11:04,900 --> 00:11:05,567 SO WHAT HAPPENS? 249 00:11:05,567 --> 00:11:08,537 ONE OF THE CORRELATES OF A 250 00:11:08,537 --> 00:11:10,405 POOR NIGHT'S SLEEP IS AGING. 251 00:11:10,405 --> 00:11:12,341 OF COURSE IT IS VARIABLE IN 252 00:11:12,341 --> 00:11:14,810 DIFFERENT PEOPLE WHEN THEY 253 00:11:14,810 --> 00:11:16,845 START -- THE SLEEP STARTS 254 00:11:16,845 --> 00:11:20,716 AGING BUT THIS IS AN IMAGE 255 00:11:20,716 --> 00:11:23,485 ON THE LEFTHAND SIDE OF A 256 00:11:23,485 --> 00:11:25,621 POPULATION OF OLDER 257 00:11:25,621 --> 00:11:28,257 SUBJECTS, AGE 51 TO 85, HALF 258 00:11:28,257 --> 00:11:30,192 OF WHOM ARE FEMALE AND IT 259 00:11:30,192 --> 00:11:33,061 SHOWS THAT IN THE RED, IN 260 00:11:33,061 --> 00:11:35,564 THE FRONT IS BIG BEAUTIFUL 261 00:11:35,564 --> 00:11:36,665 JUICY SLOW WAVES AND THERE 262 00:11:36,665 --> 00:11:38,667 IS NOT VERY MUCH OF THAT 263 00:11:38,667 --> 00:11:40,602 COMPARED IT A YOUNGER 264 00:11:40,602 --> 00:11:41,737 POPULATION AGES 18 TO 23 265 00:11:41,737 --> 00:11:44,406 WHICH YOU CAN SEE HAS A LOT 266 00:11:44,406 --> 00:11:47,075 MORE RED AND BLACK WHICH IS 267 00:11:47,075 --> 00:11:49,044 LARGE AMPLITUDE SLOW WAVES 268 00:11:49,044 --> 00:11:50,479 ON THE FRONTAL CORTEX. 269 00:11:50,479 --> 00:11:52,414 AND THEN ON THE RIGHT END 270 00:11:52,414 --> 00:11:55,918 SIDE, YOU CAN SEE THE PEAK 271 00:11:55,918 --> 00:11:57,553 TO PEAK AMPLITUDE OF THE 272 00:11:57,553 --> 00:11:58,787 SLOW WAVES GOES DOWN. 273 00:11:58,787 --> 00:12:00,756 THE GRAY ONES ARE OLDER 274 00:12:00,756 --> 00:12:02,991 INDIVIDUALS, RED IS FEMALE 275 00:12:02,991 --> 00:12:05,627 AND GRAY IS MALE AND YOU CAN 276 00:12:05,627 --> 00:12:07,362 SEE BOTH FEMALES AND MALES, 277 00:12:07,362 --> 00:12:09,298 THE AMPLITUDE OF OUR SLOW 278 00:12:09,298 --> 00:12:12,701 WAVES DECREASES AS WE AGE. 279 00:12:12,701 --> 00:12:15,904 SO SLOW WAVE SLEEP ALSO IS 280 00:12:15,904 --> 00:12:17,506 MORE FRAGMENTED AND SLOW 281 00:12:17,506 --> 00:12:19,308 WAVES THEMSELVES ARE LESS 282 00:12:19,308 --> 00:12:20,809 DENSE SO ALTOGETHER, THE 283 00:12:20,809 --> 00:12:23,111 QUALITY OF SLOW WAVE SLEEP 284 00:12:23,111 --> 00:12:24,513 GOES DOWN WITH AGING AND IT 285 00:12:24,513 --> 00:12:26,214 IS REALLY ALMOST THE LARGEST 286 00:12:26,214 --> 00:12:27,149 THING THAT CHANGES ABOUT 287 00:12:27,149 --> 00:12:29,518 SLEEP AS WE GET OLDER. 288 00:12:29,518 --> 00:12:32,621 SO HERE IS SHOWING THE 289 00:12:32,621 --> 00:12:34,289 DURATION OF SLOW WAVE SLEEP 290 00:12:34,289 --> 00:12:35,057 ON THE LEFT. 291 00:12:35,057 --> 00:12:36,658 YOU CAN SEE THE YOUNGER 292 00:12:36,658 --> 00:12:37,960 SUBJECTS ARE IN OPEN CIRCLES 293 00:12:37,960 --> 00:12:48,470 AND YOU CAN SEE THAT THEY 294 00:12:58,714 --> 00:13:00,449 HAVE MORE PROBABILITY ON THE 295 00:13:00,449 --> 00:13:02,084 X AXIS AND THEN THE NUMBER 296 00:13:02,084 --> 00:13:06,822 OF SLOW WAVES PER MINUTE 297 00:13:06,822 --> 00:13:08,890 DIMINISHES WITH AGE 298 00:13:08,890 --> 00:13:09,491 SIGNIFICANTLY. 299 00:13:09,491 --> 00:13:11,560 SO WHAT ELSE CAN DISTURB 300 00:13:11,560 --> 00:13:11,860 SLEEP? 301 00:13:11,860 --> 00:13:14,363 WELL, ESTROGEN -- NOT 302 00:13:14,363 --> 00:13:16,865 ESTROGEN, ACTUALLY ESTROGEN 303 00:13:16,865 --> 00:13:18,233 DOES -- OKAY, JUST TALK 304 00:13:18,233 --> 00:13:18,667 THROUGH THIS. 305 00:13:18,667 --> 00:13:23,605 SO THIS IS WHAT A ESTROCYCLE 306 00:13:23,605 --> 00:13:25,440 LOOKS LIKE IN A RAT. 307 00:13:25,440 --> 00:13:28,076 YOU CAN SEE ALL OF THE 308 00:13:28,076 --> 00:13:29,678 HORMONES IN THE SPACE ARE 309 00:13:29,678 --> 00:13:31,780 MUCH HIGHER AND IT IS NOT 310 00:13:31,780 --> 00:13:33,215 UNLIKE A WOMEN'S MENSTRUAL 311 00:13:33,215 --> 00:13:34,883 CYCLE WHEN IT IS A PHASE 312 00:13:34,883 --> 00:13:38,453 WHEN ALL OF OUR HORMONES ARE 313 00:13:38,453 --> 00:13:39,554 HIGH. 314 00:13:39,554 --> 00:13:41,289 IN A RAT, IT IS ONE DAY OF 315 00:13:41,289 --> 00:13:42,791 FOUR AND THEN IN WOMEN, 316 00:13:42,791 --> 00:13:46,561 THERE ARE A COUPLE OF DAYS 317 00:13:46,561 --> 00:13:47,796 WHERE IT RISES, LESS THAN 318 00:13:47,796 --> 00:13:49,898 HALF OF THE CYCLE WHEN OUR 319 00:13:49,898 --> 00:13:52,167 HORMONES ARE HIGH AND 320 00:13:52,167 --> 00:13:57,272 ESTROGEN ITSELF HAS EFFECTS 321 00:13:57,272 --> 00:14:03,578 ON HIPPO 322 00:14:03,578 --> 00:14:04,513 CAMPAL SYNAPTOGENESIS, LTP 323 00:14:04,513 --> 00:14:06,014 AND LEARNING AND WE DID A 324 00:14:06,014 --> 00:14:12,454 STUDY A FEW YEARS AGO WHEN 325 00:14:12,454 --> 00:14:13,855 THE PRO-ESTROUS SPACE, THE 326 00:14:13,855 --> 00:14:15,590 FEMALES HAVE VERY, VERY 327 00:14:15,590 --> 00:14:22,097 LITTLE REM SLEEP IN THE DARK 328 00:14:22,097 --> 00:14:24,166 CYCLE AND WAKEFULNESS 329 00:14:24,166 --> 00:14:25,867 INCREASES AND SLOW WAVE 330 00:14:25,867 --> 00:14:27,369 SLEEP IN PURPLE ON THE 331 00:14:27,369 --> 00:14:28,970 BOTTOM ALSO BOTTOMS OUT SO 332 00:14:28,970 --> 00:14:30,906 THESE ANIMALS ARE GETTING 333 00:14:30,906 --> 00:14:32,874 MUCH LESS SLEEP ON THE 334 00:14:32,874 --> 00:14:36,812 HIGHEST ESTROGEN PHASE, 335 00:14:36,812 --> 00:14:38,747 ESPECIALLY REM AND SLOW WAVE 336 00:14:38,747 --> 00:14:39,047 SLEEP. 337 00:14:39,047 --> 00:14:41,616 BUT THE GOOD NEWS IS THAT 338 00:14:41,616 --> 00:14:43,185 SLEEP, THE LITTLE SLEEP THAT 339 00:14:43,185 --> 00:14:45,353 THEY GET IS ACTUALLY WAY 340 00:14:45,353 --> 00:14:46,421 MORE EFFICIENT. 341 00:14:46,421 --> 00:14:49,424 YOU HAVE MORE SPINDLES PER 342 00:14:49,424 --> 00:14:52,427 MINUTE AND YOU HAVE MUCH 343 00:14:52,427 --> 00:14:54,396 BIGGER SLOW WAVE DELTA 344 00:14:54,396 --> 00:14:55,897 ACTIVITIES, THE SLOW WAVES 345 00:14:55,897 --> 00:14:58,266 OF SLOW WAVE SLEEP AND GAMMA 346 00:14:58,266 --> 00:15:01,002 IS AN COMP FEEING FASTER 347 00:15:01,002 --> 00:15:04,306 FREQUENCY SO DELTA AND GAMMA 348 00:15:04,306 --> 00:15:05,774 BOTH INCREASE DURING THIS 349 00:15:05,774 --> 00:15:07,275 LOW ESTROGEN PHASE OF SLEEP. 350 00:15:07,275 --> 00:15:09,711 SO WHAT HAPPENS WITH ALL THE 351 00:15:09,711 --> 00:15:10,145 OTHER PHASES? 352 00:15:10,145 --> 00:15:11,580 IT IS MUCH LOWER 353 00:15:11,580 --> 00:15:12,080 UNFORTUNATELY. 354 00:15:12,080 --> 00:15:13,548 SO ON THIS YOU CAN SEE MALES 355 00:15:13,548 --> 00:15:16,251 ARE IN THE OPEN CIRCLES AND 356 00:15:16,251 --> 00:15:24,860 YOU CAN SEE DURING THIS 357 00:15:24,860 --> 00:15:25,994 PRO-ESTRUS PHASE IN RED, IT 358 00:15:25,994 --> 00:15:27,629 IS BIGGER THAN ALL THE OTHER 359 00:15:27,629 --> 00:15:31,533 MALES IN THE OTHER PHASES OF 360 00:15:31,533 --> 00:15:33,235 CYCLES SO IT IS EFFICIENT 361 00:15:33,235 --> 00:15:36,505 SLEEP BUT ALL THE OTHER 362 00:15:36,505 --> 00:15:39,141 CYCLES ARE LESS EFFICIENT 363 00:15:39,141 --> 00:15:39,808 AND LESS EFFICIENT THAN 364 00:15:39,808 --> 00:15:41,409 MALES SO THAT IS NOT GOOD 365 00:15:41,409 --> 00:15:42,144 EITHER. 366 00:15:42,144 --> 00:15:44,312 SO WHAT ELSE CAN DISTURB 367 00:15:44,312 --> 00:15:44,613 SLEEP? 368 00:15:44,613 --> 00:15:45,147 NOISY ENVIRONMENTS. 369 00:15:45,147 --> 00:15:46,581 FOR EXAMPLE, LIVING IN THE 370 00:15:46,581 --> 00:15:49,918 UPPER CITY. 371 00:15:49,918 --> 00:15:50,819 HELICOPTER-PATROLLED AREAS 372 00:15:50,819 --> 00:15:55,190 LIKE LOS ANGELES, IT IS THE 373 00:15:55,190 --> 00:15:55,824 MOST HELICOPTER-PATROLLED 374 00:15:55,824 --> 00:15:56,625 CITY IN THE WORLD AND I LIVE 375 00:15:56,625 --> 00:15:58,693 THERE SO I CAN TELL YOU THE 376 00:15:58,693 --> 00:15:59,761 HELICOPTERS DO COME AT ALL 377 00:15:59,761 --> 00:16:02,130 HOURS OF THE NIGHT AND FLY 378 00:16:02,130 --> 00:16:04,666 MUCH LOWER THAN THE 379 00:16:04,666 --> 00:16:06,134 1000-FOOT FAA MINUTE AND 380 00:16:06,134 --> 00:16:07,469 CIRCLE FOR 20 MINUTES AT A 381 00:16:07,469 --> 00:16:07,769 TIME. 382 00:16:07,769 --> 00:16:09,437 AND IT IS DISTURBING AND NOT 383 00:16:09,437 --> 00:16:11,072 ONLY IS IT THE NOISE THAT 384 00:16:11,072 --> 00:16:12,440 DISTURBS YOU BUT ALSO THE 385 00:16:12,440 --> 00:16:13,608 THREAT THAT IT IMPLIES. 386 00:16:13,608 --> 00:16:20,315 SO IT IS NOT A GOOD, NOT 387 00:16:20,315 --> 00:16:20,816 GOOD. 388 00:16:20,816 --> 00:16:23,118 SO ON THE LEFT BOTTOM 389 00:16:23,118 --> 00:16:25,387 ORANGE, THE BIGGEST DARKEST 390 00:16:25,387 --> 00:16:27,556 ORANGE IS LA X SO THAT IS 391 00:16:27,556 --> 00:16:30,192 THE NOISE IF YOU LIVE IN THE 392 00:16:30,192 --> 00:16:38,099 FLIGHT PATH OF LA X AND THAT 393 00:16:38,099 --> 00:16:40,468 ISING GELWOOD, PREDOMINANTLY 394 00:16:40,468 --> 00:16:43,004 BLACK IN SOUTH L.A. 395 00:16:43,004 --> 00:16:45,040 AND IF YOU PLAY A 2 SECOND 396 00:16:45,040 --> 00:16:47,876 NOISE AT THAT LEVEL AND THEN 397 00:16:47,876 --> 00:16:50,512 OVERLAID IN THOSE COLORS ARE 398 00:16:50,512 --> 00:16:53,114 HOW MUCH HELICOPTER CIRCLING 399 00:16:53,114 --> 00:16:54,649 AT 600 TO 1000 FEET, HOW 400 00:16:54,649 --> 00:16:56,785 MUCH NOISE IT WOULD MAKE AND 401 00:16:56,785 --> 00:16:59,988 WHETHER YOU HAVE AN OPEN 402 00:16:59,988 --> 00:17:01,256 WINDOW, SINGLE PANED GLASS 403 00:17:01,256 --> 00:17:05,360 WINDOW THAT IS CLOSED AND A 404 00:17:05,360 --> 00:17:06,394 DOUBLE PANED GLASS WINDOW 405 00:17:06,394 --> 00:17:08,597 THAT IS CLOSED AND I CAN 406 00:17:08,597 --> 00:17:10,665 TELL YOU IN LOS ANGELES IN 407 00:17:10,665 --> 00:17:12,400 THE SUMMERTIME IN YOU DON'T 408 00:17:12,400 --> 00:17:13,435 HAVE AIR CONDITIONING, YOU 409 00:17:13,435 --> 00:17:14,836 HAVE THOSE WINDOWS OPEN. 410 00:17:14,836 --> 00:17:16,872 SO EVEN THAT CAN DISTURB 411 00:17:16,872 --> 00:17:19,474 YOUR SLEEP -- EVEN THAT DEEP 412 00:17:19,474 --> 00:17:21,877 SLOW WAVE SLEEP WHICH IS 413 00:17:21,877 --> 00:17:23,712 USUALLY VERY HARD TO DISTURB 414 00:17:23,712 --> 00:17:25,313 SOMEONE FROM WILL BE 415 00:17:25,313 --> 00:17:27,349 DISTURBED BY THE HELICOPTER. 416 00:17:27,349 --> 00:17:30,886 AT THE BOTTOM RED CIRCLES 417 00:17:30,886 --> 00:17:33,855 AND BLACK, YOU CAN SEE THE 418 00:17:33,855 --> 00:17:35,490 PATTERN OF CIRCLING 419 00:17:35,490 --> 00:17:36,524 HELICOPTERS IN SOUTH L.A. 420 00:17:36,524 --> 00:17:40,896 I AM DOING A STUDY TOGETHER 421 00:17:40,896 --> 00:17:43,632 WITH NICK SHAPIRO TO 422 00:17:43,632 --> 00:17:45,867 ACTUALLY FOIA THE HELICOPTER 423 00:17:45,867 --> 00:17:47,102 FLIGHT PATTERNS AND SEE WHAT 424 00:17:47,102 --> 00:17:49,838 IT IS RELATIVE TO THE 425 00:17:49,838 --> 00:17:51,072 POPULATION AND THE 426 00:17:51,072 --> 00:17:52,874 POPULATION MAKEUP AND IT IS 427 00:17:52,874 --> 00:17:53,842 A DISTURBING PICTURE. 428 00:17:53,842 --> 00:17:55,110 ANOTHER THING THAT DISTURBS 429 00:17:55,110 --> 00:17:58,413 SLEEP ESPECIALLY AS WE GET 430 00:17:58,413 --> 00:18:01,449 OLDER WHICH IS DISRUPTIVE 431 00:18:01,449 --> 00:18:02,984 SLEEP APNEA THAT GOES HIGHER 432 00:18:02,984 --> 00:18:05,553 AND HIGHER AND THAT IS A 433 00:18:05,553 --> 00:18:07,355 WEAKENING OF MUSCLE AS WE 434 00:18:07,355 --> 00:18:10,358 GET OLDER THROUGH THE NASAL 435 00:18:10,358 --> 00:18:12,327 AIRWAYS AND ALSO INCREASING 436 00:18:12,327 --> 00:18:14,029 FLAT PADS THAT PRESS ON THE 437 00:18:14,029 --> 00:18:16,331 AIR I WOULD SO THE TWO 438 00:18:16,331 --> 00:18:20,201 COMBINED TO CLOSE OFF YOUR 439 00:18:20,201 --> 00:18:23,571 AIR WAY SO EVEN IF YOUR DIVE 440 00:18:23,571 --> 00:18:26,074 FEDERAL IS TRYING TO 441 00:18:26,074 --> 00:18:28,276 RESPIRE, YOU HAVE A CLOSED 442 00:18:28,276 --> 00:18:28,710 AIRWAY. 443 00:18:28,710 --> 00:18:31,880 AND FOR IT TO BE OBSTRUCTIVE 444 00:18:31,880 --> 00:18:35,617 SLEEP APNEA, YOU HAVE TO 445 00:18:35,617 --> 00:18:38,353 HAVE FIVE DISRUPTIONS PER 446 00:18:38,353 --> 00:18:40,422 HOUR IN SLEEP AND THAT IS A 447 00:18:40,422 --> 00:18:41,890 LOT OF WAKEFULNESS AND 448 00:18:41,890 --> 00:18:43,425 PEOPLE DON'T REALIZE BECAUSE 449 00:18:43,425 --> 00:18:45,961 THEY ARE SO SLEEPY THAT THEY 450 00:18:45,961 --> 00:18:49,564 ARE WAKING SO OFTEN TO 451 00:18:49,564 --> 00:18:53,635 BREATHE BUT THIS IS 452 00:18:53,635 --> 00:18:55,804 OBSTRUCTIVE SLEEP APNEA THAT 453 00:18:55,804 --> 00:18:59,207 LIKELY INCREASES WITH AGE 454 00:18:59,207 --> 00:19:01,109 AND MEN PRIMARILY GET SLEEP 455 00:19:01,109 --> 00:19:03,645 APNEA BECAUSE THEY HAVE MORE 456 00:19:03,645 --> 00:19:06,514 FATTY TISSUE BUT WOMEN ALSO 457 00:19:06,514 --> 00:19:09,784 GET SLEEP APNEA. 458 00:19:09,784 --> 00:19:11,052 AND GOOD NEWS. 459 00:19:11,052 --> 00:19:12,087 AIR WAVE EXERCISE, SINGING 460 00:19:12,087 --> 00:19:14,756 IN THE SHOWER IS GOOD. 461 00:19:14,756 --> 00:19:16,491 MORE AIR WAVE EXERCISE, MORE 462 00:19:16,491 --> 00:19:17,792 TALKING AND SINGING YOU CAN 463 00:19:17,792 --> 00:19:19,961 DO, THE MORE TIGHTENED YOUR 464 00:19:19,961 --> 00:19:22,864 AIRWAY IS GOING TO BE AT 465 00:19:22,864 --> 00:19:24,366 NIGHT SO DON'T CRITICIZE 466 00:19:24,366 --> 00:19:26,368 ANYONE FOR TALKING OR 467 00:19:26,368 --> 00:19:27,135 SINGING ALL THE TIME. 468 00:19:27,135 --> 00:19:28,636 HUMMING IS A GOOD WAY TO DO 469 00:19:28,636 --> 00:19:29,537 IT ACTUALLY. 470 00:19:29,537 --> 00:19:30,972 AND EVEN PEOPLE THAT HAVE A 471 00:19:30,972 --> 00:19:32,907 LOT OF FAT BUT SING OPERA 472 00:19:32,907 --> 00:19:34,642 BECAUSE THEY ARE PRACTICING 473 00:19:34,642 --> 00:19:36,711 FOUR HOURS A DAY, THEY DO 474 00:19:36,711 --> 00:19:47,155 NOT HAVE SLEEP APNEA. 475 00:19:48,023 --> 00:19:54,195 OR PLAY THE DIDGIERIDOO. 476 00:19:54,195 --> 00:20:01,102 SO PEOPLE GETTING UP AT 477 00:20:01,102 --> 00:20:03,171 NIGHT, NOCTUREA AND YOU CAN 478 00:20:03,171 --> 00:20:05,340 SEE MORE THAN 50 PERCENT OF 479 00:20:05,340 --> 00:20:07,208 THE 55 TO 84-YEAR POPULATION 480 00:20:07,208 --> 00:20:09,044 SAY THEY GET UP AT LEAST 481 00:20:09,044 --> 00:20:11,112 ONCE PER MIGHT TO GO TO THE 482 00:20:11,112 --> 00:20:12,380 BATHROOM AND THAT DISTURBS 483 00:20:12,380 --> 00:20:14,215 THEIR SLEEP MORE THAN 484 00:20:14,215 --> 00:20:17,085 PHYSICAL PAIN OR CAREGIVING, 485 00:20:17,085 --> 00:20:17,819 HEALTH CONCERNS, COUGHING, 486 00:20:17,819 --> 00:20:18,953 WHATEVER IT IS, GOING TO THE 487 00:20:18,953 --> 00:20:21,689 BATHROOM AT NIGHT IS THE 488 00:20:21,689 --> 00:20:23,158 NUMBER ONE CAUSE AND IT 489 00:20:23,158 --> 00:20:26,361 HAPPENS IN WOMEN AND IN MEN 490 00:20:26,361 --> 00:20:29,831 AND ON THE X-AXIS IN DECADES 491 00:20:29,831 --> 00:20:31,666 OF LIFE, YOU CAN SEE IN 492 00:20:31,666 --> 00:20:34,035 WOMEN AND MEN GETTING UP TO 493 00:20:34,035 --> 00:20:35,303 PEE AT NIGHT INCREASES AND 494 00:20:35,303 --> 00:20:37,305 THAT IS IN TWO DIFFERENT 495 00:20:37,305 --> 00:20:37,772 STUDIES. 496 00:20:37,772 --> 00:20:39,374 YEAH, SO MY TIME IS ALMOST 497 00:20:39,374 --> 00:20:44,512 UP BUT WHY WOULD THIS AFFECT 498 00:20:44,512 --> 00:20:45,146 MEMORIES? 499 00:20:45,146 --> 00:20:46,181 REALLY MULTIPLE AROUSE 500 00:20:46,181 --> 00:20:50,418 SALARIES FOR WHATEVER WOMEN 501 00:20:50,418 --> 00:20:54,689 INCREASES THE LOCUS CERILLUS 502 00:20:54,689 --> 00:20:56,091 ACTIVITY, IF IT BECOMING 503 00:20:56,091 --> 00:20:56,791 HYPERACTIVE FOR ANY REASON, 504 00:20:56,791 --> 00:20:58,827 IT IS A POSITIVE FEEDBACK 505 00:20:58,827 --> 00:21:00,428 LOOP AND NOT GOOD. 506 00:21:00,428 --> 00:21:04,532 SO IT CHANGES THE MOLECULAR 507 00:21:04,532 --> 00:21:06,367 AND GLIAL SUPPORTS FOR 508 00:21:06,367 --> 00:21:07,769 LEARNING, YOUR EXTRA 509 00:21:07,769 --> 00:21:09,137 CELLULAR MATRIX, ALL OF THIS 510 00:21:09,137 --> 00:21:11,973 STUFF AND IT IS CONTRIBUTED 511 00:21:11,973 --> 00:21:13,708 TO BY STRESS AND THE 512 00:21:13,708 --> 00:21:19,247 ENVIRONMENT WHICH TWEAKS THE 513 00:21:19,247 --> 00:21:20,882 LOCUS CERILLUA AND WAKES YOU 514 00:21:20,882 --> 00:21:21,149 UP. 515 00:21:21,149 --> 00:21:25,620 SO THE LAST SLAVE IS HOW TO 516 00:21:25,620 --> 00:21:27,856 GET BETTER SLEEP, INCREASE 517 00:21:27,856 --> 00:21:29,824 SLOW WAVE AMPLITUDE BY 518 00:21:29,824 --> 00:21:34,429 GETTING EXERCISE DURING THE 519 00:21:34,429 --> 00:21:37,899 DAY AND AIR WAVE SLEEP, MAKE 520 00:21:37,899 --> 00:21:40,835 SURE YOUR RHYTHMS ARE 521 00:21:40,835 --> 00:21:42,203 ALIGNED THROUGH BRIGHT LIGHT 522 00:21:42,203 --> 00:21:43,738 EXPOSURE IN THE AM AND TRY 523 00:21:43,738 --> 00:21:48,376 TO FIND A WAY TO REDUCE THE 524 00:21:48,376 --> 00:21:50,411 NOISE AND POLLUTION, MAYBE 525 00:21:50,411 --> 00:21:51,546 IT WILL REQUIRE POLICY 526 00:21:51,546 --> 00:21:51,880 CHANGES. 527 00:21:51,880 --> 00:21:55,250 SO I WANT TO THANK THE 528 00:21:55,250 --> 00:21:58,319 LABORATORY AND NIH FOR MY 529 00:21:58,319 --> 00:21:59,053 FUNDING THROUGHOUT THE 530 00:21:59,053 --> 00:22:00,255 YEARS, AND THE LABORATORY, 531 00:22:00,255 --> 00:22:04,792 THANK YOU FOR YOUR 532 00:22:04,792 --> 00:22:05,560 ATTENTION. 533 00:22:05,560 --> 00:22:06,094 [APPLAUSE] 534 00:22:06,094 --> 00:22:07,328 >> THANKS SO MUCH, GINA, 535 00:22:07,328 --> 00:22:08,463 WHAT A GREAT TALK. 536 00:22:08,463 --> 00:22:14,602 SO THE NEXT TALK IS FROM 537 00:22:14,602 --> 00:22:16,204 KRISTEN OH'CONNELL AND THE 538 00:22:16,204 --> 00:22:17,672 TALK IS GENETIC INTERACTIONS 539 00:22:17,672 --> 00:22:21,976 WITH SEX AND ENVIRONMENT 540 00:22:21,976 --> 00:22:23,011 SHAPE SHAPE SLEEP AND 541 00:22:23,011 --> 00:22:24,312 FUNCTION ACROSS THE 542 00:22:24,312 --> 00:22:24,679 LIFESPAN. 543 00:22:24,679 --> 00:22:25,280 >> THANK YOU VERY MUCH, 544 00:22:25,280 --> 00:22:28,216 FIRST I WANT TO THANK THE 545 00:22:28,216 --> 00:22:30,485 ORGANIZERS, ORGANIZING 546 00:22:30,485 --> 00:22:32,353 COMMITTEE, MOLLY WAGSTER AND 547 00:22:32,353 --> 00:22:34,689 THE NIH FOR INVITING ME AND 548 00:22:34,689 --> 00:22:35,823 HAVING ME SPEAK. 549 00:22:35,823 --> 00:22:36,758 THIS IS FANTASTIC, I HAVE 550 00:22:36,758 --> 00:22:38,493 LEARNED A TON AND REALLY 551 00:22:38,493 --> 00:22:39,928 EXCITED TO BE UP HERE 552 00:22:39,928 --> 00:22:41,896 SHARING OUR WORK WITH YOU. 553 00:22:41,896 --> 00:22:42,697 SO HOPEFULLY BY NOW YOU 554 00:22:42,697 --> 00:22:45,333 UNDERSTAND THERE ARE A 555 00:22:45,333 --> 00:22:48,603 VARIETY OF MECHANISMS THAT 556 00:22:48,603 --> 00:22:51,206 INTERACT TO SHAPE THE 557 00:22:51,206 --> 00:22:54,475 COGNITIVE FUNCTION AND THE 558 00:22:54,475 --> 00:22:56,311 RATE IS AN INTERACTION 559 00:22:56,311 --> 00:22:58,513 BETWEEN BOTH YOUR 560 00:22:58,513 --> 00:22:59,214 CHRONOLOGICAL AGE, 561 00:22:59,214 --> 00:23:03,451 ENVIRONMENTAL FACTORS AND 562 00:23:03,451 --> 00:23:05,653 YOUR GENETIC BACKGROUND. 563 00:23:05,653 --> 00:23:07,388 COGNITIVE AGING IS HIGHLY 564 00:23:07,388 --> 00:23:07,956 VARIABLE. 565 00:23:07,956 --> 00:23:12,060 IT CAN BE ATTRIBUTED TO 566 00:23:12,060 --> 00:23:13,528 GENETIC FACTORS, ANYWHERE 567 00:23:13,528 --> 00:23:15,296 FROM 50 TO 80 PERCENT SO 568 00:23:15,296 --> 00:23:16,097 UNDERSTANDING THOSE 569 00:23:16,097 --> 00:23:19,167 INTERACTIONS AND WHAT THOSE 570 00:23:19,167 --> 00:23:20,201 GENETIC FACTORS ARE CAN 571 00:23:20,201 --> 00:23:23,271 POINT THIS IN THE DIRECTION 572 00:23:23,271 --> 00:23:27,108 OF NEW PARGTS OR FUNCTIONS 573 00:23:27,108 --> 00:23:27,675 TO MITIGATE COGNITIVE 574 00:23:27,675 --> 00:23:28,843 DECLINE BUT THERE ARE A 575 00:23:28,843 --> 00:23:30,545 NUMBER OF CHALLENGES BOTH IN 576 00:23:30,545 --> 00:23:33,281 HUMAN POPULATIONS AS WELL AS 577 00:23:33,281 --> 00:23:35,450 IN MOUSE MODEL ORGANISMS. 578 00:23:35,450 --> 00:23:37,685 FOR HUMANS, WE HAVE COMPLEX 579 00:23:37,685 --> 00:23:38,853 GENOMES AND WE HAVE TO THINK 580 00:23:38,853 --> 00:23:42,257 OF THIS AS A FEATURE, NOT A 581 00:23:42,257 --> 00:23:42,523 BUG. 582 00:23:42,523 --> 00:23:43,324 WE ARE INCREDIBLY DIVERSE 583 00:23:43,324 --> 00:23:45,360 AND THE WAY WE RESPOND 584 00:23:45,360 --> 00:23:46,527 ACROSS OUR ENVIRONMENT AND 585 00:23:46,527 --> 00:23:53,368 AGE IS AN IMPORTANT REASON 586 00:23:53,368 --> 00:23:54,702 WHY HUMANKIND IS AS 587 00:23:54,702 --> 00:23:56,004 INCREDIBLE AS IT IS. 588 00:23:56,004 --> 00:24:00,341 WE HAVE LONG LIFESPAN AND AS 589 00:24:00,341 --> 00:24:07,515 A SPECIES, ARE NOTORIOUSLY 590 00:24:07,515 --> 00:24:12,186 DIFFICULT TO ACCURATELY 591 00:24:12,186 --> 00:24:14,255 ASSESS, WHO REMEMBERS OUR 592 00:24:14,255 --> 00:24:14,722 CHILDHOOD? 593 00:24:14,722 --> 00:24:16,724 SO WE RELY ON SELF-REPORT 594 00:24:16,724 --> 00:24:18,493 AND MANY OF THE THINGS 595 00:24:18,493 --> 00:24:20,461 HAPPENING DURING AGING, THE 596 00:24:20,461 --> 00:24:22,163 INFLUENCE WHERE YOU END UP 597 00:24:22,163 --> 00:24:24,666 TOWARD THE END OF YOUR LIFE 598 00:24:24,666 --> 00:24:26,401 ARE OCCURRING IN MIDLIFE AND 599 00:24:26,401 --> 00:24:28,703 AS HUMANS, WE DON'T HAVE 600 00:24:28,703 --> 00:24:31,973 RELIABLE ACCESS TO THAT 601 00:24:31,973 --> 00:24:32,807 TISSUE. 602 00:24:32,807 --> 00:24:33,608 MOUSE MODELS HAVE A SOLUTION 603 00:24:33,608 --> 00:24:33,941 TO. 604 00:24:33,941 --> 00:24:35,576 THIS THEY HAVE A SHORT 605 00:24:35,576 --> 00:24:36,511 LIFESPAN, WE CAN FOLLOW 606 00:24:36,511 --> 00:24:38,079 THEM, THEY LIVE TWO, TWO AND 607 00:24:38,079 --> 00:24:39,180 A HALF YEARS. 608 00:24:39,180 --> 00:24:40,315 WE HAVE TREMENDOUSLY TO US 609 00:24:40,315 --> 00:24:41,582 CONTROL OVER THEIR 610 00:24:41,582 --> 00:24:42,283 ENVIRONMENT, WE CONTROL 611 00:24:42,283 --> 00:24:43,985 EVERYTHING MICE DO AND HAVE 612 00:24:43,985 --> 00:24:46,888 A LOT MORE PRECISION IN 613 00:24:46,888 --> 00:24:47,789 ASSESSMENT AND MEASUREMENT. 614 00:24:47,789 --> 00:24:50,425 AND OF COURSE THEY ARE 615 00:24:50,425 --> 00:24:52,260 RETRACTIBLE, WE DON'T HAVE 616 00:24:52,260 --> 00:24:54,429 CONSENT ISSUES WITH MICE AND 617 00:24:54,429 --> 00:24:55,697 WE CAN ACCESS THEIR BRAIN 618 00:24:55,697 --> 00:24:57,165 TISSUE AT ANY AGE. 619 00:24:57,165 --> 00:24:58,566 HOWEVER THERE IS ONE 620 00:24:58,566 --> 00:25:00,501 DIFFERENCE THAT HAS 621 00:25:00,501 --> 00:25:01,869 INFLUENCED THE DATA DROP 622 00:25:01,869 --> 00:25:03,137 FROM MOUSE MODELS TO HUMAN 623 00:25:03,137 --> 00:25:06,908 IS THAT IS OUR GENETIC 624 00:25:06,908 --> 00:25:07,475 BACKGROUND. 625 00:25:07,475 --> 00:25:11,746 MOST MOUSE MODELS ARE A 626 00:25:11,746 --> 00:25:13,247 SINGLE GENE STRAIN AND MOST 627 00:25:13,247 --> 00:25:13,681 OFTEN MALE. 628 00:25:13,681 --> 00:25:15,883 SO IT IS ONE OF THESE THINGS 629 00:25:15,883 --> 00:25:17,819 THAT IS A MODIFIABLE FACTOR 630 00:25:17,819 --> 00:25:19,987 AND THAT IS THE GENOME OF 631 00:25:19,987 --> 00:25:21,489 MICE AND MOST OF THE WORK I 632 00:25:21,489 --> 00:25:23,758 AM ABOUT TO TELL YOU ABOUT 633 00:25:23,758 --> 00:25:26,294 REPRESENTS A VERY LONG 634 00:25:26,294 --> 00:25:27,628 COLLABORATION WITH THE COSBY 635 00:25:27,628 --> 00:25:30,498 LOUSY LAB WHO WENT OVER THIS 636 00:25:30,498 --> 00:25:32,433 YESTERDAY SO I WON'T GO 637 00:25:32,433 --> 00:25:34,035 THROUGH IT EXCEPT WE HAVE 638 00:25:34,035 --> 00:25:35,770 TAKEN THE PANEL AND EXTENDED 639 00:25:35,770 --> 00:25:38,740 IT TO A F1 PANEL WHICH 640 00:25:38,740 --> 00:25:40,575 INTRODUCES A FEW ADVANTAGES 641 00:25:40,575 --> 00:25:43,044 INCLUDING A CONSIDERABLE 642 00:25:43,044 --> 00:25:44,712 AMOUNT OF VARIATION. 643 00:25:44,712 --> 00:25:47,515 THE BXD PANEL NOW CARRIES 644 00:25:47,515 --> 00:25:50,385 SIX MILLION VARIANTS ACROSS 645 00:25:50,385 --> 00:25:52,453 10 STRAINS, WE HAVE CREATED 646 00:25:52,453 --> 00:25:57,225 60 GIVE OR TAKE AND BY 647 00:25:57,225 --> 00:26:00,495 CREATING A BXD F1 PANEL, WE 648 00:26:00,495 --> 00:26:08,002 HAVE SOME VARIATION IN THE 649 00:26:08,002 --> 00:26:08,369 FREQUENCY. 650 00:26:08,369 --> 00:26:11,305 SO I WON'T GO INTO THE 651 00:26:11,305 --> 00:26:12,573 COGNITIVE FUNCTION OF THE 652 00:26:12,573 --> 00:26:14,742 MICE EXCEPT TO SAY MOST OF 653 00:26:14,742 --> 00:26:25,186 WHAT WE SEE IS PSEUDO 654 00:26:27,321 --> 00:26:29,524 COHORTS, WE CAN ASSESS 655 00:26:29,524 --> 00:26:30,525 COGNITIVE FUNCTION AND WHAT 656 00:26:30,525 --> 00:26:35,530 DOES THIS DO IN THE BXD F1 657 00:26:35,530 --> 00:26:36,097 PANEL? 658 00:26:36,097 --> 00:26:41,169 JUST TO ORIENT YOU ON THIS 659 00:26:41,169 --> 00:26:42,670 PANEL, YOU WILL SEE THIS IN 660 00:26:42,670 --> 00:26:45,306 A NUMBER OF MY SLIDES. 661 00:26:45,306 --> 00:26:48,042 SO WE LOOK AT THE GENETIC 662 00:26:48,042 --> 00:26:49,844 BACKGROUND, MALES AND 663 00:26:49,844 --> 00:26:52,713 FEMALES AND EACH POINT IS A 664 00:26:52,713 --> 00:26:53,881 STRAIN AND THE AVERAGE OF 665 00:26:53,881 --> 00:26:56,384 ALL THE MICE IN THAT STRAIN 666 00:26:56,384 --> 00:27:01,722 PER AGE, FROM 6, 14 AND 22 667 00:27:01,722 --> 00:27:06,761 MONTHS OF AGE THE BOX FACTOR 668 00:27:06,761 --> 00:27:07,995 IS THE POPULATION. 669 00:27:07,995 --> 00:27:10,264 THE BIGGEST DETERMINANT OF 670 00:27:10,264 --> 00:27:11,766 COGNITIVE FUNCTION AT EVERY 671 00:27:11,766 --> 00:27:15,937 AGE IS GENETIC BACK GROUPED. 672 00:27:15,937 --> 00:27:17,438 STRAINS DETERMINE MOST OF 673 00:27:17,438 --> 00:27:19,841 THIS, NOT AGE, NOT SEX. 674 00:27:19,841 --> 00:27:22,243 WE HAVE STRAINS THAT PERFORM 675 00:27:22,243 --> 00:27:24,779 EXCEPTIONALLY WELL AT YOUNG 676 00:27:24,779 --> 00:27:25,613 AGES AND LIFESPANS. 677 00:27:25,613 --> 00:27:27,248 WE ALSO HAVE STRAINS THAT 678 00:27:27,248 --> 00:27:29,083 DON'T FORM WELL EVEN AT 679 00:27:29,083 --> 00:27:30,918 YOUNG AGES AND THIS 680 00:27:30,918 --> 00:27:32,186 PARALLELS THE HUMAN 681 00:27:32,186 --> 00:27:33,221 POPULATION MUCH BETTER THAN 682 00:27:33,221 --> 00:27:34,388 A SINGLE STRAIN DOES. 683 00:27:34,388 --> 00:27:36,891 THE OTHER THING IS THERE IS 684 00:27:36,891 --> 00:27:37,725 A PROFOUND SEX DIFFERENCE 685 00:27:37,725 --> 00:27:40,194 HERE AND WE HEARD THIS A FEW 686 00:27:40,194 --> 00:27:41,496 TIMES YESTERDAY. 687 00:27:41,496 --> 00:27:43,297 OFTEN MALES AND FEMALES 688 00:27:43,297 --> 00:27:44,899 START AT THE SAME PLACE AND 689 00:27:44,899 --> 00:27:46,968 END AT THE SAME PLACE, BUT 690 00:27:46,968 --> 00:27:49,070 IT IS THE TRAJECTORY OF HOW 691 00:27:49,070 --> 00:27:50,338 THEY GET THERE AND THAT IS 692 00:27:50,338 --> 00:27:53,374 TRUE FOR MICE AS WELL. 693 00:27:53,374 --> 00:27:55,877 14 MONTHS IS LATE MIDLIFE IN 694 00:27:55,877 --> 00:27:59,280 MICE AND THEN THEY DECLINE 695 00:27:59,280 --> 00:28:01,249 FROM MIDLIFE TO OLD AGE. 696 00:28:01,249 --> 00:28:03,751 MALES ON THE OTHER HAND 697 00:28:03,751 --> 00:28:09,156 START HIGH, DECLINE IN 698 00:28:09,156 --> 00:28:11,692 MID-AGE AND THEN END UP AT 699 00:28:11,692 --> 00:28:12,693 THE SAME PLACE. 700 00:28:12,693 --> 00:28:14,061 AND LIKE HUMANS, WE HAVE A 701 00:28:14,061 --> 00:28:15,496 SURVIVAL BIAS. 702 00:28:15,496 --> 00:28:18,432 MORE OF OUR FEMALE MICE 703 00:28:18,432 --> 00:28:20,167 SURVIVE TO 22 MONTHS OF AGE 704 00:28:20,167 --> 00:28:26,040 THAN MALE MICE DO SO FEMALE 705 00:28:26,040 --> 00:28:26,974 MICE ARE OVERREPRESENTED AND 706 00:28:26,974 --> 00:28:29,577 WE HAVE STRAINS IN WHICH NO 707 00:28:29,577 --> 00:28:32,613 MALES SURVIVE THE 22 MONTHS 708 00:28:32,613 --> 00:28:33,314 OF AGE. 709 00:28:33,314 --> 00:28:37,051 SO OTHERS HAVE DONE A BETTER 710 00:28:37,051 --> 00:28:38,920 JOB OF EXPLAINING SLEEP AND 711 00:28:38,920 --> 00:28:40,087 COGNITIVE AGING THAN I CAN 712 00:28:40,087 --> 00:28:41,722 BUT THE MAIN THING TO TAKE 713 00:28:41,722 --> 00:28:44,892 AWAY FROM MY TALK IS THERE 714 00:28:44,892 --> 00:28:47,295 ARE INDIVIDUAL DIFFERENCES 715 00:28:47,295 --> 00:28:51,432 IN PHENOTYPE ITSELF THAT 716 00:28:51,432 --> 00:28:54,035 INFLUENCES SLEEP AND COG 717 00:28:54,035 --> 00:28:54,402 ANYTHING. 718 00:28:54,402 --> 00:28:55,770 PATTERNS AND HOW WE ALL 719 00:28:55,770 --> 00:28:58,506 SLEEP CAN BE ATTRIBUTED TO 720 00:28:58,506 --> 00:28:59,540 GENETIC VARIATION. 721 00:28:59,540 --> 00:29:01,509 SO NOW THAT WE HAVE A 722 00:29:01,509 --> 00:29:02,643 VARIATION OF MICE THAT 723 00:29:02,643 --> 00:29:07,248 APPROXIMATE MATES S WHAT WE 724 00:29:07,248 --> 00:29:08,749 SEE IN HUMANS, WHAT DOES 725 00:29:08,749 --> 00:29:12,019 SLEEP LIKE? 726 00:29:12,019 --> 00:29:13,654 AND GENETIC BACKGROUND NOT 727 00:29:13,654 --> 00:29:15,823 SURPRISINGLY IS THE BIGGEST 728 00:29:15,823 --> 00:29:16,324 INFLUENCE. 729 00:29:16,324 --> 00:29:18,960 SO THIS IS TOTAL SLEEP, DARK 730 00:29:18,960 --> 00:29:21,095 CYCLE, LIGHT CYCLE AND WE 731 00:29:21,095 --> 00:29:23,164 REMEMBER MICE ARE NOCTURNAL 732 00:29:23,164 --> 00:29:25,299 SO THEY SLEEP THE MOST WHEN 733 00:29:25,299 --> 00:29:26,167 LIGHTS ARE ON. 734 00:29:26,167 --> 00:29:28,202 EACH ONE OF THESE IS THE 735 00:29:28,202 --> 00:29:30,471 PERCENT SLEEP FOR A GIVEN 736 00:29:30,471 --> 00:29:30,905 STRAIN. 737 00:29:30,905 --> 00:29:32,306 SOME STRAINS WILL SLEEP 738 00:29:32,306 --> 00:29:33,641 ALMOST 70 PERCENT OF THE 739 00:29:33,641 --> 00:29:35,876 TIME IN THE LIGHT CYCLE, 740 00:29:35,876 --> 00:29:37,011 OTHERS LESS THAN 60 PERCENT 741 00:29:37,011 --> 00:29:39,313 OF THEIR TIME IS SPENT 742 00:29:39,313 --> 00:29:41,949 ASLEEP AND WE SEE JUST AS 743 00:29:41,949 --> 00:29:44,118 MUCH OR MORE VARIATION WHERE 744 00:29:44,118 --> 00:29:45,119 SOME STRAINS WILL SPEND 745 00:29:45,119 --> 00:29:46,887 ALMOST 40 PERCENT OF THAT 746 00:29:46,887 --> 00:29:50,057 CYCLE ASLEEP AND OTHERS, 747 00:29:50,057 --> 00:29:51,359 LESS THAN 20 OR 15. 748 00:29:51,359 --> 00:29:53,961 AND JUST SO YOU KNOW, THIS 749 00:29:53,961 --> 00:29:55,129 EQUATES TO TWO AND A HALF 750 00:29:55,129 --> 00:29:55,997 HOURS OF DIFFERENCE ACROSS 751 00:29:55,997 --> 00:29:56,731 THE PANEL. 752 00:29:56,731 --> 00:29:59,066 SO WE HAVE SOME MICE THAT 753 00:29:59,066 --> 00:30:00,901 GENETICALLY TEND TO BE SHORT 754 00:30:00,901 --> 00:30:02,036 SLEEPERS AND SOME THAT TEND 755 00:30:02,036 --> 00:30:03,671 TO BE LONG SLEEPERS. 756 00:30:03,671 --> 00:30:05,873 ONE OF THE OTHER BIG FACTORS 757 00:30:05,873 --> 00:30:10,077 THAT WAS ALLUDED TO IN 758 00:30:10,077 --> 00:30:13,581 GINA'S TALK IS THAT THINGS 759 00:30:13,581 --> 00:30:15,416 LIKE OBESITY AND BODY WEIGHT 760 00:30:15,416 --> 00:30:16,651 INFLUENCE SLEEP. 761 00:30:16,651 --> 00:30:18,052 THEY ALSO INFLUENCE 762 00:30:18,052 --> 00:30:19,754 COGNITION AND UNDERSTANDING 763 00:30:19,754 --> 00:30:21,022 HOW OBESITY AND DIET AND 764 00:30:21,022 --> 00:30:24,225 THESE SORT OF ENVIRONMENTAL 765 00:30:24,225 --> 00:30:26,794 FACTORS AND LIFESTYLE 766 00:30:26,794 --> 00:30:27,995 FACTORS IMPACT NORMAL 767 00:30:27,995 --> 00:30:38,072 FUNCTION AND PLASTICITY HAS 768 00:30:38,072 --> 00:30:40,408 BEEN AN INTEREST OF MY LAP 769 00:30:40,408 --> 00:30:43,811 FOR A LONG TIME. 770 00:30:43,811 --> 00:30:47,014 SO SHORT SLEEP IS ASSOCIATED 771 00:30:47,014 --> 00:30:47,715 WITH INCREASED FOOD INTAKE 772 00:30:47,715 --> 00:30:51,719 AND PREFERENCE FOR HIGHLY 773 00:30:51,719 --> 00:30:53,387 PALATABLE FOODS. 774 00:30:53,387 --> 00:30:58,426 IN ANIMAL MODELS, 775 00:30:58,426 --> 00:30:59,627 CONSUMPTION OF OBESOGENIC 776 00:30:59,627 --> 00:31:02,329 DIETS LEAD TO CIRCADIAN 777 00:31:02,329 --> 00:31:06,500 DISRUPTION AND SLEEP LOSS. 778 00:31:06,500 --> 00:31:09,270 AND HIGH FAT DIET IS 779 00:31:09,270 --> 00:31:11,639 ASSOCIATED WITH UNCOUPLING 780 00:31:11,639 --> 00:31:13,808 OF PERIPHERAL METABOLIC 781 00:31:13,808 --> 00:31:17,244 PATHWAYS FROM THE CIRCADIAN 782 00:31:17,244 --> 00:31:17,812 RHYTHM. 783 00:31:17,812 --> 00:31:22,316 SO HOW DO WE COMBINE ALL OF 784 00:31:22,316 --> 00:31:24,618 THESE FACTORS TO AGE, DIET 785 00:31:24,618 --> 00:31:25,553 AND SLEEP? 786 00:31:25,553 --> 00:31:29,290 SO USING A VERY WELL 787 00:31:29,290 --> 00:31:32,593 VALIDATED MODEL WHERE WE 788 00:31:32,593 --> 00:31:37,098 FEED THE MICE A HIGH FAT 789 00:31:37,098 --> 00:31:38,933 DIET, THE WESTERN DIET, 790 00:31:38,933 --> 00:31:40,201 STARTED AT THREE MONTHS OF 791 00:31:40,201 --> 00:31:42,169 AGE, SO FAIRLY YOUNG AND 792 00:31:42,169 --> 00:31:45,072 THEN MONITOR THEIR BODY 793 00:31:45,072 --> 00:31:48,843 WEIGHT AND PHENOTYPES. 794 00:31:48,843 --> 00:31:54,615 THIS IS A PSEUDO LAUNCH 795 00:31:54,615 --> 00:31:55,483 STUDY. 796 00:31:55,483 --> 00:31:57,785 THESE MICE GET 24 HOURS 797 00:31:57,785 --> 00:31:59,153 CONTINUOUS MONITORING OF 798 00:31:59,153 --> 00:32:00,521 METABOLISM AND BEHAVIOR FROM 799 00:32:00,521 --> 00:32:03,724 WHICH WE CAN EXTRACT SLEEP 800 00:32:03,724 --> 00:32:06,327 AND CIRCADIAN RELATED 801 00:32:06,327 --> 00:32:08,162 BEHAVIORS. 802 00:32:08,162 --> 00:32:09,630 I WILL CONCEDE THIS IS NOT 803 00:32:09,630 --> 00:32:12,133 THE GOLD STANDARD FOR THESE 804 00:32:12,133 --> 00:32:16,570 BEHAVIORS BUT DOES A GOOD 805 00:32:16,570 --> 00:32:17,538 JOB AT EXPLAINING THIS 806 00:32:17,538 --> 00:32:18,806 THROUGH THE INPUT SCREENING 807 00:32:18,806 --> 00:32:19,640 OF THOUSANDS OF MICE. 808 00:32:19,640 --> 00:32:22,843 SO THIS IS PROOF OF CONCEPT. 809 00:32:22,843 --> 00:32:27,848 THIS MODEL WORKS REALLY WELL 810 00:32:27,848 --> 00:32:29,784 AT INDUCING OBESITY 811 00:32:29,784 --> 00:32:31,585 PARTICULARLY IN MALE MICE 812 00:32:31,585 --> 00:32:33,521 WHICH IS THE MODEL FOR WHICH 813 00:32:33,521 --> 00:32:36,657 IT WAS DEVELOPED AND THERE 814 00:32:36,657 --> 00:32:40,761 IS A DIFFERENCE IN BODY SIZE 815 00:32:40,761 --> 00:32:44,799 BUT THE GENETIC BACKGROUND 816 00:32:44,799 --> 00:32:52,239 DICTATES THE SIZE AND MOST 817 00:32:52,239 --> 00:32:55,142 MICE WILL STEADILY BECOME 818 00:32:55,142 --> 00:32:55,442 OBESE. 819 00:32:55,442 --> 00:32:57,044 FOR FEMALES, IT IS A LITTLE 820 00:32:57,044 --> 00:32:57,378 LONGER. 821 00:32:57,378 --> 00:32:59,547 IT TAKES LONGER FOR FEMALE 822 00:32:59,547 --> 00:33:02,416 MICE TO GAIN WEIGHT AND 823 00:33:02,416 --> 00:33:04,218 BECOME OBESE BUT GENETIC 824 00:33:04,218 --> 00:33:06,387 BACKGROUND IS THE BIGGEST 825 00:33:06,387 --> 00:33:08,455 DRIVER HERE, IT IS NOT DIET. 826 00:33:08,455 --> 00:33:10,457 SO IT IS THE RESPONSE TO 827 00:33:10,457 --> 00:33:12,960 INDIVIDUAL VARIATION TO THAT 828 00:33:12,960 --> 00:33:13,861 ENVIRONMENTAL FACTOR THAT 829 00:33:13,861 --> 00:33:16,530 DETERMINES WHETHER AN ANIMAL 830 00:33:16,530 --> 00:33:18,399 WILL BECOME OBESE. 831 00:33:18,399 --> 00:33:19,900 SO WHAT ABOUT SLEEP, WHAT 832 00:33:19,900 --> 00:33:21,836 HAPPENS IF WE LOOK AT SLEEP 833 00:33:21,836 --> 00:33:25,172 ON THESE MICE ON A HIGH FAT 834 00:33:25,172 --> 00:33:28,709 DIET AND OBESE OR NOT. 835 00:33:28,709 --> 00:33:29,710 AND AGAIN, GENETIC VARIATION 836 00:33:29,710 --> 00:33:30,477 PLAINS MOST OF THE 837 00:33:30,477 --> 00:33:31,979 DIFFERENCES WE SEE HERE AND 838 00:33:31,979 --> 00:33:34,381 THIS IS REALLY PROFOUND FOR 839 00:33:34,381 --> 00:33:36,984 THIS TYPE OF PHENOTYPE AND 840 00:33:36,984 --> 00:33:39,887 IN MALE MICE IS EXPLAINS 3/4 841 00:33:39,887 --> 00:33:40,855 OF THE VARIATION. 842 00:33:40,855 --> 00:33:43,490 THERE IS A HUGE SEX 843 00:33:43,490 --> 00:33:45,860 DIFFERENCE AGAIN HOW MALES 844 00:33:45,860 --> 00:33:48,562 AND FEMALES RESPOND TO A 845 00:33:48,562 --> 00:33:50,397 HIGH FAT DIET AND THEIR 846 00:33:50,397 --> 00:33:51,098 SLEEP PATTERNS. 847 00:33:51,098 --> 00:33:53,000 THIS IS ONLY DARK CYCLE 848 00:33:53,000 --> 00:33:54,535 SLEEP BECAUSE THERE WAS NO 849 00:33:54,535 --> 00:33:58,739 EFFECT ON THE LIGHT CYCLE, 850 00:33:58,739 --> 00:33:59,907 ONLY GENETIC BACKGROUND. 851 00:33:59,907 --> 00:34:02,509 THE DARK CYCLE IS MUCH MORE 852 00:34:02,509 --> 00:34:03,043 VARIABLE. 853 00:34:03,043 --> 00:34:11,619 MALE MICE RESPOND TO AGE AND 854 00:34:11,619 --> 00:34:13,787 SEX AND THEY INCREASE IN THE 855 00:34:13,787 --> 00:34:16,190 DARK CYCLE WITH OLD AGE. 856 00:34:16,190 --> 00:34:16,790 FEMALES ARE DIFFERENT. 857 00:34:16,790 --> 00:34:19,827 THERE IS NO EFFECT OF SEX -- 858 00:34:19,827 --> 00:34:22,463 OR DIET, BEING ON HIGH FAT 859 00:34:22,463 --> 00:34:24,832 DIET OR BEING OBESE DOESN'T 860 00:34:24,832 --> 00:34:26,000 INFLUENCE THEIR SLEEP AND 861 00:34:26,000 --> 00:34:27,534 THEY RESPOND BY SLEEPING 862 00:34:27,534 --> 00:34:28,369 MORE, NOT LESS. 863 00:34:28,369 --> 00:34:36,277 SO IF YOU WERE TO 864 00:34:36,277 --> 00:34:37,311 ANTHROMORPHIZE ON THIS, 865 00:34:37,311 --> 00:34:39,246 MAYBE THE GREATEST VARIANT 866 00:34:39,246 --> 00:34:40,881 WOULD BE DAYTIME NAPPING. 867 00:34:40,881 --> 00:34:43,050 SO THIS IS CIRCADIAN, WE USE 868 00:34:43,050 --> 00:34:46,153 THIS AS A PROXY FOR 869 00:34:46,153 --> 00:34:47,521 CIRCADIAN DISRUPTION AND 870 00:34:47,521 --> 00:34:50,691 AGAIN TO PROVE THE POINT, 871 00:34:50,691 --> 00:34:55,129 GENETIC BACKGROUND IS THE 872 00:34:55,129 --> 00:35:02,403 BIGGEST DRIVER, GENETIC 873 00:35:02,403 --> 00:35:04,905 VARIATION IS PREDICTIVE OF 874 00:35:04,905 --> 00:35:06,640 OBESITY AND AGAIN IT IS THE 875 00:35:06,640 --> 00:35:07,474 TRAJECTORY THAT IS 876 00:35:07,474 --> 00:35:09,076 DIFFERENT, NOT THE 877 00:35:09,076 --> 00:35:09,777 DESTINATION. 878 00:35:09,777 --> 00:35:10,911 SO WHAT WE'RE REALLY 879 00:35:10,911 --> 00:35:12,546 INTERESTED IN IN MY LAB IS 880 00:35:12,546 --> 00:35:14,381 MAKING THIS LINK OF HOW DO 881 00:35:14,381 --> 00:35:16,583 WE GET FROM THIS GENETIC 882 00:35:16,583 --> 00:35:18,052 VARIATION AND ALL THESE 883 00:35:18,052 --> 00:35:19,787 INTERACTIONS TO THE ULTIMATE 884 00:35:19,787 --> 00:35:20,321 BEHAVIORAL OUTCOME? 885 00:35:20,321 --> 00:35:21,822 AND A LOT IN THE MIDDLE IS 886 00:35:21,822 --> 00:35:22,156 UNKNOWN. 887 00:35:22,156 --> 00:35:24,091 THERE IS A LOT TO FILL IN IN 888 00:35:24,091 --> 00:35:25,859 THIS GAP AND AGAIN, TO KIND 889 00:35:25,859 --> 00:35:27,661 OF REFER BACK TO THE 890 00:35:27,661 --> 00:35:30,264 COMMENTS MADE YESTERDAY 891 00:35:30,264 --> 00:35:31,966 ABOUT HOW MUCH TECHNOLOGY -- 892 00:35:31,966 --> 00:35:33,400 HOW FAR IT HAS COME IN THE 893 00:35:33,400 --> 00:35:34,802 LAST TEN YEARS, WOULD HE NOW 894 00:35:34,802 --> 00:35:39,006 HAVE THE ABILITY TO DO VERY 895 00:35:39,006 --> 00:35:40,274 DETAILED OMICS MEASUREMENTS 896 00:35:40,274 --> 00:35:42,176 IN A WAY WE COULDN'T DO EVEN 897 00:35:42,176 --> 00:35:45,245 FIVE YEARS AGO. 898 00:35:45,245 --> 00:35:52,186 SO TAKING ADVANTAGE OF THE 899 00:35:52,186 --> 00:35:54,021 RESOURCES AVAILABLE, WHERE 900 00:35:54,021 --> 00:35:59,159 WE HAVE A REALLY 901 00:35:59,159 --> 00:36:01,762 SOPHISTICATED IMAGING CORE 902 00:36:01,762 --> 00:36:08,969 AND CAN DO MASS SPEC IMAGING 903 00:36:08,969 --> 00:36:10,404 WHICH WE COULDN'T DO FIVE 904 00:36:10,404 --> 00:36:11,372 YEARS AGO. 905 00:36:11,372 --> 00:36:13,507 SO HE PRESS THE BRAIN, 906 00:36:13,507 --> 00:36:15,309 INSTEAD OF USING A 907 00:36:15,309 --> 00:36:17,011 MICROSCOPE, YOU SPRAY IT 908 00:36:17,011 --> 00:36:21,882 WITH A MATRIX AND USE THE 909 00:36:21,882 --> 00:36:25,285 PLATFORM WHICH IS OPTIMIZED 910 00:36:25,285 --> 00:36:28,222 FOR MSI AND CONVERTS THE 911 00:36:28,222 --> 00:36:29,356 SPECTRA IN FEATURES AND AN 912 00:36:29,356 --> 00:36:31,425 KNOW TATE THEM AND ALLOWS US 913 00:36:31,425 --> 00:36:41,969 TO LOOK AT LIPID PEPTIDE AND 914 00:36:43,604 --> 00:36:46,440 SO ARE WHAT DOES IT LOOK 915 00:36:46,440 --> 00:36:47,274 LIKE? 916 00:36:47,274 --> 00:36:48,976 IT DOESN'T LOOK THAT 917 00:36:48,976 --> 00:36:51,578 DIFFERENT FROM THE 918 00:36:51,578 --> 00:36:52,079 MICROSCOPY IMAGE. 919 00:36:52,079 --> 00:36:55,649 SO I WANT TO POINT OUT THERE 920 00:36:55,649 --> 00:36:57,851 IS NO ANATOMICAL OBSTRUCTIVE 921 00:36:57,851 --> 00:37:01,155 INFORMATION IN THIS BRAIN. 922 00:37:01,155 --> 00:37:02,022 THIS IS LIPIDS. 923 00:37:02,022 --> 00:37:04,058 IT LOOKS LIKE A HEAT MAP BUT 924 00:37:04,058 --> 00:37:07,061 IT IS ACTUALLY A HIGH 925 00:37:07,061 --> 00:37:08,262 DIMENSION PCA PLOT. 926 00:37:08,262 --> 00:37:10,030 THE COLORS ARE LIPIDS MOST 927 00:37:10,030 --> 00:37:11,198 SIMILAR TO ONE ANOTHER 928 00:37:11,198 --> 00:37:14,368 COMPARED TO THE OUTER BRAIN. 929 00:37:14,368 --> 00:37:17,237 THE INNER CORTICAL LAYER 930 00:37:17,237 --> 00:37:18,172 MORE SIMILAR TO ITSELF AND 931 00:37:18,172 --> 00:37:21,408 YOU COULD MAKE THAT 932 00:37:21,408 --> 00:37:22,843 COMPARISON TO EVERYTHING. 933 00:37:22,843 --> 00:37:28,248 THIS IS A LEAN LOW FAT DIET 934 00:37:28,248 --> 00:37:30,651 CHILD OR A MOUSE THAT WAS 935 00:37:30,651 --> 00:37:32,486 GIVEN THE HIGH FAT DIET AND 936 00:37:32,486 --> 00:37:33,687 YOU CAN SCAN THESE AT THE 937 00:37:33,687 --> 00:37:36,023 SAME TIME AND MAKE 938 00:37:36,023 --> 00:37:38,025 COMPARISONS AS THEY ARE 939 00:37:38,025 --> 00:37:39,960 NORMALIZED WITH EACH OTHER. 940 00:37:39,960 --> 00:37:41,862 SO THIS IS WITH RESPECT TO 941 00:37:41,862 --> 00:37:43,797 THE COMPOSITION OF THE BRAIN 942 00:37:43,797 --> 00:37:45,866 AND WE CAN DRILL DOWN ON 943 00:37:45,866 --> 00:37:47,334 SPECIFIC REGIONS AND SINCE 944 00:37:47,334 --> 00:37:49,403 WE'RE INTERESTED IN 945 00:37:49,403 --> 00:37:52,339 COGNITION HERE, WE DID THIS 946 00:37:52,339 --> 00:37:54,575 FOR THE DORSAL HIPPO CAMPUS 947 00:37:54,575 --> 00:37:56,977 AND NOW WE'RE LOOKING AT 948 00:37:56,977 --> 00:37:58,245 RELATIVE COMPOSITION 949 00:37:58,245 --> 00:38:03,317 RELATIVE TO THE HIPPOCAMPUS. 950 00:38:03,317 --> 00:38:06,420 AND THIS IS ALL LIPID 951 00:38:06,420 --> 00:38:10,491 ABUNDANCE OF WHICH THERE IS 952 00:38:10,491 --> 00:38:12,459 A TREMENDOUS VARIATION 953 00:38:12,459 --> 00:38:14,261 ACROSS THE HIPPOCAMPUS AND 954 00:38:14,261 --> 00:38:17,231 WE CAN TAKE THIS WITH EVERY 955 00:38:17,231 --> 00:38:19,066 SINGLE FEATURE WE'RE ABLE TO 956 00:38:19,066 --> 00:38:20,834 ACQUIRE AND COLLAPSE IT IN A 957 00:38:20,834 --> 00:38:22,236 SINGLE IMAGE WHICH IS REALLY 958 00:38:22,236 --> 00:38:23,837 HARD TO PROCESS AND 959 00:38:23,837 --> 00:38:24,304 INTERPRET. 960 00:38:24,304 --> 00:38:27,207 SO WE TOOK A FEW OF THOSE 961 00:38:27,207 --> 00:38:29,510 FEATURES, A FEW OF THE NAMED 962 00:38:29,510 --> 00:38:31,378 LIP PIT CLASSES AND WE CAN 963 00:38:31,378 --> 00:38:40,454 NOW SUPER IMPOSE THOSE ON TO 964 00:38:40,454 --> 00:38:42,122 OUR IMAGE, ON THE BRAIN AND 965 00:38:42,122 --> 00:38:43,290 LOOK AT THE SPECIFIC 966 00:38:43,290 --> 00:38:43,690 CLASSES. 967 00:38:43,690 --> 00:38:47,794 THESE ARE THE NINE MOST 968 00:38:47,794 --> 00:38:48,595 PROLIFICALLY ABUNDANT LIPID 969 00:38:48,595 --> 00:38:49,663 CLASSES AND NOW WHAT YOU ARE 970 00:38:49,663 --> 00:38:51,165 LOOKING AT IS THE REAL 971 00:38:51,165 --> 00:38:53,000 DIFFERENCE ACROSS THE BRAIN, 972 00:38:53,000 --> 00:38:54,401 COLORS ARE INDIVIDUAL 973 00:38:54,401 --> 00:38:56,303 PROCESSES OF LIPIDS. 974 00:38:56,303 --> 00:38:58,839 I APOLOGIZE, ONCE YOU GET UP 975 00:38:58,839 --> 00:39:00,574 TO 9, YOU START RUNNING OUT 976 00:39:00,574 --> 00:39:01,942 OF COLORS SO THERE IS A LOT 977 00:39:01,942 --> 00:39:05,712 OF THE SAME COLOR ON HERE 978 00:39:05,712 --> 00:39:07,080 BUT HOPEFULLY IT DRIVES HOME 979 00:39:07,080 --> 00:39:09,183 THE POINT THAT A FEW MONTHS 980 00:39:09,183 --> 00:39:11,585 AFTER EATING A HIGH FAT DIET 981 00:39:11,585 --> 00:39:14,121 THE LIPID CONCENTRATION 982 00:39:14,121 --> 00:39:14,721 THROUGHOUT THE BRAIN HAS 983 00:39:14,721 --> 00:39:16,690 BEGUN TO CHANGE AND THESE 984 00:39:16,690 --> 00:39:18,525 ARE GENETIC MICE SO THIS IS 985 00:39:18,525 --> 00:39:19,826 REALLY A DIET DRIVEN EFFECT. 986 00:39:19,826 --> 00:39:22,029 AND I ALSO WANT TO POINT OUT 987 00:39:22,029 --> 00:39:23,530 YOU MAY NOT BE ABLE TO READ 988 00:39:23,530 --> 00:39:25,265 THIS ON THE SLIDE, THE 989 00:39:25,265 --> 00:39:27,234 LIPIDS I AM SHOWING ARE 990 00:39:27,234 --> 00:39:29,670 IMPORTANT FOR MEMBRANE 991 00:39:29,670 --> 00:39:31,738 STRUCTURE AND FLUIDITY BUT 992 00:39:31,738 --> 00:39:34,007 THERE IS ALSO BIOSIGNALING 993 00:39:34,007 --> 00:39:35,709 WITH THIS. 994 00:39:35,709 --> 00:39:36,910 THESE ARE REALLY IMPORTANT 995 00:39:36,910 --> 00:39:38,245 LIPIDS FOR THE FUNCTION OF 996 00:39:38,245 --> 00:39:40,180 THE BRAIN AND THEY ARE 997 00:39:40,180 --> 00:39:43,684 CHANGING IN RESPONSE TO 998 00:39:43,684 --> 00:39:44,284 DIET. 999 00:39:44,284 --> 00:39:46,687 AND SO JUST TO WRAP UP, 1000 00:39:46,687 --> 00:39:49,089 HOPEFULLY I HAVE CONVINCED 1001 00:39:49,089 --> 00:39:50,724 YOU BY INCREASING THE 1002 00:39:50,724 --> 00:39:52,059 GENETIC DIFFERENCE IN THE 1003 00:39:52,059 --> 00:39:54,261 MOUSE MODELS WE CAN DO A 1004 00:39:54,261 --> 00:39:55,796 MUCH BETTER JOB OF ALIGNING 1005 00:39:55,796 --> 00:39:57,130 THESE MODELS TO THE 1006 00:39:57,130 --> 00:39:58,298 VARIATION ACROSS THE HUMAN 1007 00:39:58,298 --> 00:40:04,538 POPULATION AND DO A WEIR JOB 1008 00:40:04,538 --> 00:40:08,275 BETTER JOB OF CAPTURING 1009 00:40:08,275 --> 00:40:10,244 THAT THROUGH GENETICS AND 1010 00:40:10,244 --> 00:40:12,045 VERSATILITY AND DO A BETTER 1011 00:40:12,045 --> 00:40:13,680 JOB THROUGH THE LIFETIME 1012 00:40:13,680 --> 00:40:15,182 EXPOSURES OF HUMANS AND 1013 00:40:15,182 --> 00:40:16,316 MODEL THAT TO BETTER 1014 00:40:16,316 --> 00:40:18,151 UNDERSTAND WHAT THE 1015 00:40:18,151 --> 00:40:20,988 UNDERLYING GENETIC AND 1016 00:40:20,988 --> 00:40:22,389 MOLECULAR DRIVERS ARE TO DO 1017 00:40:22,389 --> 00:40:23,557 A BETTER JOB OF 1018 00:40:23,557 --> 00:40:26,426 UNDERSTANDING HOW WE AGE IN 1019 00:40:26,426 --> 00:40:27,194 EVERY FACET. 1020 00:40:27,194 --> 00:40:30,697 AND THEN OUR GOAL IS TO NOW 1021 00:40:30,697 --> 00:40:33,166 USE THESE ADVANCED 1022 00:40:33,166 --> 00:40:35,702 MULTIOMICS TO FILL IN THESE 1023 00:40:35,702 --> 00:40:36,169 GAPS. 1024 00:40:36,169 --> 00:40:38,138 HOW DO WE GET THE DIVERSITY, 1025 00:40:38,138 --> 00:40:39,506 WHAT ARE THE FACTORS AT 1026 00:40:39,506 --> 00:40:40,674 LEVELS WE HAVE NOT 1027 00:40:40,674 --> 00:40:44,044 PREVIOUSLY BEEN ABLE TO 1028 00:40:44,044 --> 00:40:52,052 ASSESS, LIKE LIPIDOME, 1029 00:40:52,052 --> 00:40:52,686 METABOLOME AND PEPTIDONE. 1030 00:40:52,686 --> 00:40:56,256 SO THERE ARE A LARGE NUMBER 1031 00:40:56,256 --> 00:41:03,830 OF MEMBERS IN THE LAB DOING 1032 00:41:03,830 --> 00:41:06,733 THIS WORK, AMY DUNN WHO 1033 00:41:06,733 --> 00:41:08,068 ORGANIZED THE DATA AND THOSE 1034 00:41:08,068 --> 00:41:10,037 OF YOU WORKING WITH BIG 1035 00:41:10,037 --> 00:41:11,305 DATASETS, YOU KNOW HOW GOOD 1036 00:41:11,305 --> 00:41:13,206 IT IS TO HAVE CLEANING AND 1037 00:41:13,206 --> 00:41:17,911 ORGANIZATION OF THE DATA AND 1038 00:41:17,911 --> 00:41:20,347 MIKO DID AN EXCEPTIONAL JOB 1039 00:41:20,347 --> 00:41:22,416 OF THAT BEFORE SHE WENT TO 1040 00:41:22,416 --> 00:41:22,983 GRAD SCHOOL. 1041 00:41:22,983 --> 00:41:28,622 AND THEN OF COURSE TO THANK 1042 00:41:28,622 --> 00:41:29,823 THE FUNDING AGENCIES WHO 1043 00:41:29,823 --> 00:41:34,328 HAVE FUNDED THIS WORK FOR SO 1044 00:41:34,328 --> 00:41:40,300 LONG INCLUDING THE NIH, AND 1045 00:41:40,300 --> 00:41:47,274 THE KACZOROWSKI LAB AND ALSO 1046 00:41:47,274 --> 00:41:49,209 MATHEW WHO IS WORKING ON 1047 00:41:49,209 --> 00:41:50,077 THIS. 1048 00:41:50,077 --> 00:41:50,644 THANKS VERY MUCH. 1049 00:41:50,644 --> 00:41:53,714 >> THANKS SO MUCH, KRISTEN. 1050 00:41:53,714 --> 00:42:00,587 THE NEXT TALK WILL BE 1051 00:42:00,587 --> 00:42:02,089 KRISTINE YAFFE FROM 1052 00:42:02,089 --> 00:42:03,457 UNIVERSITY OF CALIFORNIA-SAN 1053 00:42:03,457 --> 00:42:04,791 FRANCISCO AND THE TALK IS 1054 00:42:04,791 --> 00:42:06,993 IMPORTANCE OF A LIFE COURSE 1055 00:42:06,993 --> 00:42:10,430 APPROACH TO COGNITIVE AND 1056 00:42:10,430 --> 00:42:11,965 BRAIN AGE. 1057 00:42:11,965 --> 00:42:12,766 >> GOOD MORNING, REALLY 1058 00:42:12,766 --> 00:42:16,870 GREAT TO BE HERE, WANT TO 1059 00:42:16,870 --> 00:42:17,704 THANK MOLLY IN PARTICULAR 1060 00:42:17,704 --> 00:42:19,072 AND IT IS IMPORTANT TO BE 1061 00:42:19,072 --> 00:42:20,807 HERE WHICH IS WHAT WE DO, 1062 00:42:20,807 --> 00:42:22,175 LEARN FROM ONE ANOTHER AND 1063 00:42:22,175 --> 00:42:24,978 MEET NEW FRIENDS AND I LOVE 1064 00:42:24,978 --> 00:42:26,046 THE TRANSLATIONAL ASPECT 1065 00:42:26,046 --> 00:42:28,248 THAT WE'RE TALKING ABOUT OUR 1066 00:42:28,248 --> 00:42:29,416 MINDS AND TALKING ABOUT 1067 00:42:29,416 --> 00:42:30,050 PEOPLE. 1068 00:42:30,050 --> 00:42:33,019 I AM GOING TO TALK ABOUT 1069 00:42:33,019 --> 00:42:35,188 PEOPLE ALTHOUGH IT MAKES ME 1070 00:42:35,188 --> 00:42:37,124 THINK FROM PRIOR TALKS MAYBE 1071 00:42:37,124 --> 00:42:38,859 I SHOULD SWITCH TO MICE. 1072 00:42:38,859 --> 00:42:39,259 [LAUGHTER] 1073 00:42:39,259 --> 00:42:40,927 SO I WILL TALK ABOUT TWO 1074 00:42:40,927 --> 00:42:41,428 THINGS. 1075 00:42:41,428 --> 00:42:42,195 ONE, YOU HAVE HEARD ABOUT 1076 00:42:42,195 --> 00:42:44,264 THE LIFE COURSE AND I WILL 1077 00:42:44,264 --> 00:42:45,966 TRY TO CONVINCE YOU WHY A 1078 00:42:45,966 --> 00:42:48,068 LIFE APPROACH TO COGNITIVE 1079 00:42:48,068 --> 00:42:49,169 AGING IS VERY IMPORTANT AND 1080 00:42:49,169 --> 00:42:50,837 THEN I WILL TALK ABOUT THE 1081 00:42:50,837 --> 00:42:53,073 RESEARCH WORK WE HAVE FROM 1082 00:42:53,073 --> 00:42:55,709 THE TRIAL, TRYING TO IMPROVE 1083 00:42:55,709 --> 00:42:56,376 COGNITIVE AGING. 1084 00:42:56,376 --> 00:43:05,852 WHAT AM I DOING WRONG HERE? 1085 00:43:05,852 --> 00:43:07,020 THERE WE GO, OKAY. 1086 00:43:07,020 --> 00:43:11,091 WE ALL KNOW THE PHYSIOLOGIC 1087 00:43:11,091 --> 00:43:12,559 AND NEUROLOGIC CHANGES THAT 1088 00:43:12,559 --> 00:43:13,860 HAPPEN OVER AGE TAKE A LONG 1089 00:43:13,860 --> 00:43:23,270 TIME TO DEVELOP AND SO, YOU 1090 00:43:23,270 --> 00:43:24,838 KNOW, WITH RISK FACTORS AND 1091 00:43:24,838 --> 00:43:27,407 WE KNOW A LOT OF THE CHANGES 1092 00:43:27,407 --> 00:43:30,744 THAT LEAD TO AGING SUCH AS 1093 00:43:30,744 --> 00:43:31,878 VASCULAR SLEEP, PHYSICAL 1094 00:43:31,878 --> 00:43:33,180 ACTIVITY YET MOST OF OUR 1095 00:43:33,180 --> 00:43:35,715 WORK IS REALLY FOCUSED ON 1096 00:43:35,715 --> 00:43:37,350 OLDER ADULTS, PEOPLE IN 1097 00:43:37,350 --> 00:43:38,452 THEIR 60s, 70s AND 80s 1098 00:43:38,452 --> 00:43:40,654 AND I WOULD LIKE TO 1099 00:43:40,654 --> 00:43:41,855 HYPOTHESIZE THAT WE'RE 1100 00:43:41,855 --> 00:43:43,557 MISSING REALLY A CHANCE TO 1101 00:43:43,557 --> 00:43:44,391 UNDERSTAND THE WHOLE LIFE 1102 00:43:44,391 --> 00:43:46,293 COURSE AND WHAT HAS BEEN 1103 00:43:46,293 --> 00:43:48,929 HAPPENING BEFORE, MAYBE EVEN 1104 00:43:48,929 --> 00:43:49,429 STARTING IN UTERO. 1105 00:43:49,429 --> 00:43:53,333 SO IT IS HARD TO STUDY THIS, 1106 00:43:53,333 --> 00:43:53,834 RIGHT? 1107 00:43:53,834 --> 00:43:55,669 WE'RE NOT MICE, YOU KNOW AND 1108 00:43:55,669 --> 00:43:57,304 IN HUMANS, WE DON'T HAVE 1109 00:43:57,304 --> 00:43:59,506 STUDIES THAT GO FOR NIH 1110 00:43:59,506 --> 00:44:01,107 CYCLES OF FIVE YEARS AND I 1111 00:44:01,107 --> 00:44:02,843 KNOW MOLLY IS WORKING ON 1112 00:44:02,843 --> 00:44:04,578 THAT BUT YOU KNOW WE DON'T 1113 00:44:04,578 --> 00:44:06,780 HAVE A NIH STUDY THAT IS 80 1114 00:44:06,780 --> 00:44:07,180 YEARS OLD. 1115 00:44:07,180 --> 00:44:09,115 SO IT IS HARD TO STUDY THIS 1116 00:44:09,115 --> 00:44:12,118 AND YET WE'RE MISSING, I 1117 00:44:12,118 --> 00:44:14,521 THINK, THIS OPPORTUNITY TO 1118 00:44:14,521 --> 00:44:16,490 STUDY PEOPLE FOR DECADES, 1119 00:44:16,490 --> 00:44:22,295 THEIR WHOLE LIFE. 1120 00:44:22,295 --> 00:44:29,803 WE DON'T HAVE BIRTH 1121 00:44:29,803 --> 00:44:30,737 CATEGORIES, SOME COUNTRIES 1122 00:44:30,737 --> 00:44:31,004 DO. 1123 00:44:31,004 --> 00:44:33,907 THE OTHER THING IS THE RISK 1124 00:44:33,907 --> 00:44:35,175 FACTOR IS OFTEN CUMULATIVE 1125 00:44:35,175 --> 00:44:37,377 SO YOU MAY HAVE OBESITY OVER 1126 00:44:37,377 --> 00:44:38,645 50 YEARS AND THAT IS 1127 00:44:38,645 --> 00:44:40,280 DIFFERENT FOR SOMEONE WHO IS 1128 00:44:40,280 --> 00:44:40,747 70. 1129 00:44:40,747 --> 00:44:42,916 THERE MAY BE CRITICAL 1130 00:44:42,916 --> 00:44:44,384 WINDOWS FOR EXAMPLE WITH 1131 00:44:44,384 --> 00:44:45,185 HORMONES. 1132 00:44:45,185 --> 00:44:46,686 IT MIGHT BE IMPORTANT 1133 00:44:46,686 --> 00:44:50,790 WHETHER YOU GET HORMONES IN 1134 00:44:50,790 --> 00:44:53,393 PERI MENOPAUSE OR SO MUCH 1135 00:44:53,393 --> 00:44:58,098 LATER SO THESE ARE SPECIFIC 1136 00:44:58,098 --> 00:45:00,934 REASONS WHY THE LIFESPAN IS 1137 00:45:00,934 --> 00:45:01,535 IMPORTANT. 1138 00:45:01,535 --> 00:45:02,569 AGAIN, WE DON'T STUDY A LOT 1139 00:45:02,569 --> 00:45:03,336 OF THESE. 1140 00:45:03,336 --> 00:45:05,372 YOU CAN DO SOME POOLING OF 1141 00:45:05,372 --> 00:45:06,439 COHORTS WHICH OTHERS HAVE 1142 00:45:06,439 --> 00:45:09,743 DONE, YOU CAN DO ANALYTIC 1143 00:45:09,743 --> 00:45:11,678 METHODS, YOU CAN DO LIKE 1144 00:45:11,678 --> 00:45:12,579 RANDOMIZATION WHICH IS A 1145 00:45:12,579 --> 00:45:14,447 GREAT WAY TO GO, ET CETERA, 1146 00:45:14,447 --> 00:45:16,249 BUT I WANT TO SHOW YOU A 1147 00:45:16,249 --> 00:45:17,717 STUDY WE HAVE BEEN INVOLVED 1148 00:45:17,717 --> 00:45:19,519 WITH CALLED THE CARDIA STUDY 1149 00:45:19,519 --> 00:45:23,456 AND THIS IS A REALLY GREAT 1150 00:45:23,456 --> 00:45:24,124 STUDY. 1151 00:45:24,124 --> 00:45:26,793 I WANT TO INCREASE YOUR 1152 00:45:26,793 --> 00:45:28,061 AWARENESS OF THIS BECAUSE I 1153 00:45:28,061 --> 00:45:34,901 THINK IT PROVIDES A LOT OF 1154 00:45:34,901 --> 00:45:35,802 OPPORTUNITIES, ANHLBI STUDY 1155 00:45:35,802 --> 00:45:38,672 WHICH IS REALLY A COOL 1156 00:45:38,672 --> 00:45:38,972 STUDY. 1157 00:45:38,972 --> 00:45:41,841 THIS IS 5000 MEN AND WOMEN, 1158 00:45:41,841 --> 00:45:43,243 HALF BLACK, HALF WHITE, 1159 00:45:43,243 --> 00:45:45,612 PRETTY DIVERSE AND WE HAVE 1160 00:45:45,612 --> 00:45:47,480 BEEN STUDYING THEM ALMOST 40 1161 00:45:47,480 --> 00:45:48,281 YEARS. 1162 00:45:48,281 --> 00:45:52,586 THEY STARTED WHEN THEY WERE 1163 00:45:52,586 --> 00:45:54,754 IN THEIR 20s SO THE MEAN 1164 00:45:54,754 --> 00:45:55,922 AGE IS ABOUT 25 AND I AM 1165 00:45:55,922 --> 00:45:57,324 SORRY THIS MAY BE HARD TO 1166 00:45:57,324 --> 00:45:59,192 SEE BUT THE BOXES REPRESENT 1167 00:45:59,192 --> 00:46:00,860 EACH VISIT AND THAT IS THE 1168 00:46:00,860 --> 00:46:01,695 MEAN AGE. 1169 00:46:01,695 --> 00:46:03,797 SO THEY STARTED AT 25 AND 1170 00:46:03,797 --> 00:46:08,068 THEN WHEN THEY ARE 50, WE 1171 00:46:08,068 --> 00:46:09,469 START DOING COGNITIVE AND 1172 00:46:09,469 --> 00:46:10,370 BRAIN ASSESSMENTS AND THAT 1173 00:46:10,370 --> 00:46:13,940 HAS BEEN MY ROLE WITH SOME 1174 00:46:13,940 --> 00:46:14,341 COLLEAGUES. 1175 00:46:14,341 --> 00:46:15,442 AND WE'RE NOW COMING UP TO 1176 00:46:15,442 --> 00:46:16,710 THE POINT WHERE THEY ARE 1177 00:46:16,710 --> 00:46:18,945 ACTUALLY TURNING -- THEY ARE 1178 00:46:18,945 --> 00:46:19,446 IN THEIR MID-60s. 1179 00:46:19,446 --> 00:46:21,381 SO IT IS A REALLY GREAT 1180 00:46:21,381 --> 00:46:21,948 OPPORTUNITY. 1181 00:46:21,948 --> 00:46:23,083 I WILL SHOW YOU SOME OF THIS 1182 00:46:23,083 --> 00:46:27,087 WORK WE HAVE BEEN WORKING ON 1183 00:46:27,087 --> 00:46:29,322 SINCE THEY WERE 50 USING THE 1184 00:46:29,322 --> 00:46:30,190 COGNITIVE BRAIN MRI. 1185 00:46:30,190 --> 00:46:31,658 AND REALLY OUR GOAL IS TO 1186 00:46:31,658 --> 00:46:33,226 TRY TO UNDERSTAND THE LIFE 1187 00:46:33,226 --> 00:46:34,427 COURSE APPROACH. 1188 00:46:34,427 --> 00:46:36,796 HOW ARE THESE CUMULATIVE OR 1189 00:46:36,796 --> 00:46:39,032 LIFE EXPOSURES THAT OFTEN 1190 00:46:39,032 --> 00:46:40,600 ARE MODIFIABLE INKHRAOUPBS 1191 00:46:40,600 --> 00:46:47,007 COGNITIVE -- INFLUENCE 1192 00:46:47,007 --> 00:46:48,241 COGNITIVE LIFE, AS PEOPLE 1193 00:46:48,241 --> 00:46:49,643 ARE AGING AND WE HOPE THAT 1194 00:46:49,643 --> 00:46:51,745 AS THEY GET OLDER WE CAN 1195 00:46:51,745 --> 00:46:53,446 CONTINUE TO STUDY THEM. 1196 00:46:53,446 --> 00:46:55,849 WE JUST SUBMITTED A RENEWAL 1197 00:46:55,849 --> 00:46:57,817 TO STUDY THEM WHEN THEY ARE 1198 00:46:57,817 --> 00:46:58,184 65. 1199 00:46:58,184 --> 00:47:00,253 AND I WILL FOCUS ON A COUPLE 1200 00:47:00,253 --> 00:47:01,521 OF EXAMPLES JUST TO GIVE YOU 1201 00:47:01,521 --> 00:47:03,123 A FLAVOR OF WHY I THINK THIS 1202 00:47:03,123 --> 00:47:04,991 CAN BE SO POWERFUL. 1203 00:47:04,991 --> 00:47:06,860 OKAY SO THE FIRST EXAMPLE IS 1204 00:47:06,860 --> 00:47:07,727 BLOOD PRESSURE. 1205 00:47:07,727 --> 00:47:09,229 NOW WE KNOW BLOOD PRESSURE 1206 00:47:09,229 --> 00:47:10,597 IS EXTREMELY IMPORTANT FOR 1207 00:47:10,597 --> 00:47:12,999 RISK OF COGNITIVE AGING, 1208 00:47:12,999 --> 00:47:14,868 DEMENTIA, NOT TO MENTION 1209 00:47:14,868 --> 00:47:16,036 STROKE AND MRI, ET CETERA. 1210 00:47:16,036 --> 00:47:18,171 THIS IS THE WORK WE DID A 1211 00:47:18,171 --> 00:47:20,340 WHILE AGO WHERE WE SAID, 1212 00:47:20,340 --> 00:47:22,909 OKAY, WHAT IS THE BLOOD 1213 00:47:22,909 --> 00:47:23,643 PRESSURE EXPOSURE TO WHEN 1214 00:47:23,643 --> 00:47:25,145 PEOPLE WERE IN THEIR 1215 00:47:25,145 --> 00:47:26,746 MID-20s NOW ALL THE WAY TO 1216 00:47:26,746 --> 00:47:27,814 THE 50s. 1217 00:47:27,814 --> 00:47:29,582 AND THESE WERE NOT PEOPLE 1218 00:47:29,582 --> 00:47:30,216 WHO HAD HYPERTENSION. 1219 00:47:30,216 --> 00:47:32,452 THEY DID NOT MEET THE 1220 00:47:32,452 --> 00:47:33,219 CRITERIA FOR HYPERTENSION, 1221 00:47:33,219 --> 00:47:34,154 IT WAS JUST THEIR BLOOD 1222 00:47:34,154 --> 00:47:36,923 PRESSURE AND WE LOOKED AT 1223 00:47:36,923 --> 00:47:42,429 THIS HISTOLIC BLOOD PRESSURE 1224 00:47:42,429 --> 00:47:46,166 AND LOOKED AT THE AUC TO SEE 1225 00:47:46,166 --> 00:47:48,134 EXPOSURE AND WHAT YOU CAN 1226 00:47:48,134 --> 00:47:48,935 SEE PRETTY CLEARLY, THE 1227 00:47:48,935 --> 00:47:50,503 LINES ARE ALL THE COGNITIVE 1228 00:47:50,503 --> 00:47:51,905 TEXT, YOU CAN SEE THE 1229 00:47:51,905 --> 00:47:54,474 GREATER EXPOSURE IF YOU WILL 1230 00:47:54,474 --> 00:48:00,680 TO HIGH NORMAL SYSTOLIC 1231 00:48:00,680 --> 00:48:02,048 BLOOD PRESSURE, THE WORSE 1232 00:48:02,048 --> 00:48:03,083 PEOPLE DID AT HIGH FUNCTION. 1233 00:48:03,083 --> 00:48:05,085 SO IF YOU ARE HIGH NORMAL 1234 00:48:05,085 --> 00:48:06,686 FOR MANY YEARS, THIS MIGHT 1235 00:48:06,686 --> 00:48:07,954 NOT BE SUCH A GOOD THING AND 1236 00:48:07,954 --> 00:48:11,825 WE SAW THIS FOR OTHER 1237 00:48:11,825 --> 00:48:13,326 CARDIOVASCULAR RISK FACTORS 1238 00:48:13,326 --> 00:48:19,632 AS WELL. 1239 00:48:19,632 --> 00:48:20,667 RECENTLY CHRISTINE YITINKA 1240 00:48:20,667 --> 00:48:24,971 IN MY GROUP LOOKED AT THIS 1241 00:48:24,971 --> 00:48:26,573 PROCESS IN AGING USING THE 1242 00:48:26,573 --> 00:48:30,677 TIMELY AVERAGE SO TAKING IT 1243 00:48:30,677 --> 00:48:32,278 FROM MID-20s, TO 50, 55 1244 00:48:32,278 --> 00:48:35,849 AND WHAT SHE FOUND WAS USING 1245 00:48:35,849 --> 00:48:39,319 A MACHINE LEARNING BRAIN 1246 00:48:39,319 --> 00:48:41,521 AGING PATTERN THAT MOHAMMED 1247 00:48:41,521 --> 00:48:43,423 HAVAS DEVELOPED AND WHAT SHE 1248 00:48:43,423 --> 00:48:46,826 FOUND IS IF YOU HAVE SOLID 1249 00:48:46,826 --> 00:48:47,894 BLOOD PRESSURE ALL THAT 1250 00:48:47,894 --> 00:48:49,963 TIME, YOU HAVE A GREATER 1251 00:48:49,963 --> 00:48:50,530 BRAIN AGING. 1252 00:48:50,530 --> 00:48:53,500 SO THE RED LINE IS ELEVATED 1253 00:48:53,500 --> 00:48:54,634 ABOVE THE CUTOFF AND THE 1254 00:48:54,634 --> 00:48:55,835 GREEN IS NORMAL. 1255 00:48:55,835 --> 00:48:56,636 SO SHOWING THERE IS 1256 00:48:56,636 --> 00:48:58,071 SOMETHING GOING ON WITH THE 1257 00:48:58,071 --> 00:48:58,838 BRAIN AGING PATTERN. 1258 00:48:58,838 --> 00:49:01,107 THIS IS NOT WHITE MATTER, 1259 00:49:01,107 --> 00:49:11,584 JUST AN ATROPHY PATTERN. 1260 00:49:13,887 --> 00:49:16,656 AND WE HAVE DONE SOME WORK 1261 00:49:16,656 --> 00:49:18,191 ON HAVING THESE PATTERNS, 1262 00:49:18,191 --> 00:49:19,259 DIABETES, BLOOD PRESSURE AND 1263 00:49:19,259 --> 00:49:27,901 HAVING THIS IN MID-LIFE WAS 1264 00:49:27,901 --> 00:49:29,502 ASSOCIATED WITH ACCELERATED 1265 00:49:29,502 --> 00:49:33,873 VASCULAR DECLINE SO WE THINK 1266 00:49:33,873 --> 00:49:35,608 THE RISK FACTORS ARE VERY 1267 00:49:35,608 --> 00:49:37,443 IMPORTANT STARTING IN THE 1268 00:49:37,443 --> 00:49:37,944 20s. 1269 00:49:37,944 --> 00:49:40,613 SO WHAT ABOUT DEPRESSION? 1270 00:49:40,613 --> 00:49:44,884 WHAT IS GOING ON WITH THE 1271 00:49:44,884 --> 00:49:45,518 COGNITIVE DECLINE? 1272 00:49:45,518 --> 00:49:47,453 SO THIS IS WORK THAT 1273 00:49:47,453 --> 00:49:48,721 CHRISTINA HAS ALSO DONE, 1274 00:49:48,721 --> 00:49:50,123 DONE THIS DEVELOPMENT TO 1275 00:49:50,123 --> 00:49:51,791 LOOK AT THESE PATTERNS AND 1276 00:49:51,791 --> 00:49:54,294 AS MOST PEOPLE EXPECT, THERE 1277 00:49:54,294 --> 00:49:57,730 ARE NOT A LOT OF DEPRESSIVE 1278 00:49:57,730 --> 00:50:00,600 SYMPTOMS BUT SOME PEOPLE ARE 1279 00:50:00,600 --> 00:50:01,534 DECLINING, SOME INCREASING 1280 00:50:01,534 --> 00:50:02,902 AND SOME PEOPLE WHO STAY 1281 00:50:02,902 --> 00:50:04,971 HIGH AND REMAIN HIGH AND 1282 00:50:04,971 --> 00:50:07,273 THEN WHAT SHE DID, WHEN SHE 1283 00:50:07,273 --> 00:50:09,442 LOOKED AT HOW DID THESE 1284 00:50:09,442 --> 00:50:11,711 DIFFERENT PATTERNS RELATE TO 1285 00:50:11,711 --> 00:50:14,514 COGNITIVE FUNCTION, AGAIN, 1286 00:50:14,514 --> 00:50:16,082 THIS IS MIDDLE-AGE, 55, AND 1287 00:50:16,082 --> 00:50:18,651 HOW DID THIS VARY IN TERMS 1288 00:50:18,651 --> 00:50:19,552 OF MRI FINDINGS. 1289 00:50:19,552 --> 00:50:21,154 COMPARED TO THOSE WHO ARE 1290 00:50:21,154 --> 00:50:22,889 ALWAYS LOW, THOSE WHO ARE IN 1291 00:50:22,889 --> 00:50:24,624 THE DIFFERENT GROUPS, 1292 00:50:24,624 --> 00:50:27,594 HIGHER, ALWAYS HIGH, 1293 00:50:27,594 --> 00:50:29,863 INCREASING, DECREASING, HAD 1294 00:50:29,863 --> 00:50:30,530 WORSE COGNITIVE FUNCTION, 1295 00:50:30,530 --> 00:50:33,099 THIS IS ON A WORSE COGNITIVE 1296 00:50:33,099 --> 00:50:37,637 MEASURE AND HAD DIFFERENCES 1297 00:50:37,637 --> 00:50:41,541 IN TERMS OFENTORHINAL CORTEX 1298 00:50:41,541 --> 00:50:42,508 VOLUME AND AMYGDALA VOLUME. 1299 00:50:42,508 --> 00:50:43,743 SO LOOKING FROM THE HIGH 1300 00:50:43,743 --> 00:50:44,944 GROUP TO THE LOW GROUP. 1301 00:50:44,944 --> 00:50:47,213 AND THEN FROM THE INCREASING 1302 00:50:47,213 --> 00:50:48,815 GROUP TO LOW GROUP, THEY 1303 00:50:48,815 --> 00:50:50,250 ALSO HAD DIFFERENCES BUT IN 1304 00:50:50,250 --> 00:50:54,187 THIS CASE, IT WAS MORE WHITE 1305 00:50:54,187 --> 00:50:56,789 MATTER AND TOTAL GRAY 1306 00:50:56,789 --> 00:50:57,123 VOLUME. 1307 00:50:57,123 --> 00:50:58,892 SO NOW I WILL TURN TO SLEEP, 1308 00:50:58,892 --> 00:51:00,260 THE LAST THING I WANT TO 1309 00:51:00,260 --> 00:51:02,996 SHOW YOU IS SLEEP WHICH WE 1310 00:51:02,996 --> 00:51:04,597 HAVE BEAUTIFULLY HEARD ABOUT 1311 00:51:04,597 --> 00:51:05,131 TODAY. 1312 00:51:05,131 --> 00:51:07,700 THIS IS SOMETHING THAT ULANG 1313 00:51:07,700 --> 00:51:10,670 HAS DONE IN MY GROUP, 1314 00:51:10,670 --> 00:51:12,038 BEAUTIFUL WORK LOOKING AT 1315 00:51:12,038 --> 00:51:13,640 SLEEP QUALITY WHEN PEOPLE 1316 00:51:13,640 --> 00:51:15,675 ARE ABOUT 40 AND THEN 1317 00:51:15,675 --> 00:51:16,843 SHOWING THE COGNITIVE 1318 00:51:16,843 --> 00:51:18,144 FUNCTION 11 YEARS LATER WAS 1319 00:51:18,144 --> 00:51:20,280 MUCH WORSE ON A VARIETY OF 1320 00:51:20,280 --> 00:51:21,214 SLEEP PARAMETERS. 1321 00:51:21,214 --> 00:51:27,320 WE HEARD ABOUT 1322 00:51:27,320 --> 00:51:29,055 FRAGMENTATION, WAKE AFTER 1323 00:51:29,055 --> 00:51:30,890 SLEEP ONSET, TOSSING AND 1324 00:51:30,890 --> 00:51:33,326 TURNING OR SLEEP APNEA. 1325 00:51:33,326 --> 00:51:36,029 AND IN THIS CASE WE HAVE 1326 00:51:36,029 --> 00:51:36,829 SLEEP DURATION SHOWING 1327 00:51:36,829 --> 00:51:39,565 DIFFERENCES IN SLEEP 1328 00:51:39,565 --> 00:51:41,034 DURATION, SHORT SLEEP 1329 00:51:41,034 --> 00:51:42,035 DURATION WAS ASSOCIATED WITH 1330 00:51:42,035 --> 00:51:44,671 WORSE QUALITY IN TERMS OF 1331 00:51:44,671 --> 00:51:47,307 DTI AND ACTUAL WHITE MATTER 1332 00:51:47,307 --> 00:51:47,640 VOLUME. 1333 00:51:47,640 --> 00:51:49,809 SO I THINK -- I HOPE I HAVE 1334 00:51:49,809 --> 00:51:51,110 SHOWN YOU THAT THERE IS REAL 1335 00:51:51,110 --> 00:51:53,146 GOOD EVIDENCE THAT LOOKING 1336 00:51:53,146 --> 00:51:55,014 AT SOME OF THESE RISK 1337 00:51:55,014 --> 00:51:56,482 FACTORS EARLY IN LIFE MIGHT 1338 00:51:56,482 --> 00:51:58,017 BE VERY IMPORTANT IN TERMS 1339 00:51:58,017 --> 00:52:00,219 OF COGNITIVE FUNCTION IN 1340 00:52:00,219 --> 00:52:01,921 MID-LIFE AND I WILL TELL YOU 1341 00:52:01,921 --> 00:52:03,957 I THINK THIS SETS US UP. 1342 00:52:03,957 --> 00:52:06,259 WE HAVE HEARD A LOT THAT WE 1343 00:52:06,259 --> 00:52:07,327 CAN'T PICK OUR PARENTS OR 1344 00:52:07,327 --> 00:52:09,262 YOU ARE A GENETICS BUT WE 1345 00:52:09,262 --> 00:52:10,430 CAN DO SOMETHING ABOUT THESE 1346 00:52:10,430 --> 00:52:12,365 THINGS AND MAYBE WE'RE 1347 00:52:12,365 --> 00:52:13,533 STARTING TOO LATE. 1348 00:52:13,533 --> 00:52:14,500 I THINK THEY APPRAISAL 1349 00:52:14,500 --> 00:52:16,102 REALLY EARLY AND IF WE WANT 1350 00:52:16,102 --> 00:52:21,541 TO SET US UP FOR A BETTER 1351 00:52:21,541 --> 00:52:22,508 TRAJECTORY OF COGGIVE AGING, 1352 00:52:22,508 --> 00:52:25,812 WOULD HE NO HE HAD TO START 1353 00:52:25,812 --> 00:52:31,017 THIS EARLIER, PROBABLY TO DO 1354 00:52:31,017 --> 00:52:33,086 SOME MULTIDOMAIN RISK AGING, 1355 00:52:33,086 --> 00:52:34,587 AND I HAD A CONVERSATION 1356 00:52:34,587 --> 00:52:36,289 ABOUT THIS AT BREAKFAST. 1357 00:52:36,289 --> 00:52:37,824 SO WHAT IF YOU COULD MOVE 1358 00:52:37,824 --> 00:52:43,363 THE NEEDLE ON SOME OF THESE 1359 00:52:43,363 --> 00:52:43,930 RISK FACTORS? 1360 00:52:43,930 --> 00:52:46,065 WHAT IF YOU COULD MODIFY THE 1361 00:52:46,065 --> 00:52:46,766 RISK FACTORS? 1362 00:52:46,766 --> 00:52:52,005 THIS IS SOME WORK I DID WITH 1363 00:52:52,005 --> 00:52:53,606 BARNES AND SO IF YOU WOULD 1364 00:52:53,606 --> 00:52:54,907 MOVE THE NEEDLE, WHAT WOULD 1365 00:52:54,907 --> 00:52:55,808 YOU DO? 1366 00:52:55,808 --> 00:52:58,978 SO WE LOOKED AT THE RISK 1367 00:52:58,978 --> 00:53:01,748 FACTORS, SEVEN OF THEM, SOME 1368 00:53:01,748 --> 00:53:03,349 WERE MID-LIFE, OTHERS 1369 00:53:03,349 --> 00:53:06,953 LATE-LIFE AND 30 PERCENT OF 1370 00:53:06,953 --> 00:53:08,354 THE ATTRIBUTABLE RISK FOR 1371 00:53:08,354 --> 00:53:09,489 DEMENTIA AND COGNITIVE AGING 1372 00:53:09,489 --> 00:53:10,890 WOULD BE RELATED TO SOME OF 1373 00:53:10,890 --> 00:53:12,058 THESE FACTORS. 1374 00:53:12,058 --> 00:53:13,326 AND THEN WHAT WOULD HAPPEN 1375 00:53:13,326 --> 00:53:14,594 IF YOU COULD REDUCE THEM AND 1376 00:53:14,594 --> 00:53:16,596 SEE IN THE RED AND THE BLUE, 1377 00:53:16,596 --> 00:53:18,364 THIS IS 10 PERCENT, 1378 00:53:18,364 --> 00:53:19,665 20 PERCENT, SO IN OUR THE 1379 00:53:19,665 --> 00:53:21,501 EVEN ASKING PEOPLE TO 1380 00:53:21,501 --> 00:53:23,136 EXERCISE, LIKE JOIN A 1381 00:53:23,136 --> 00:53:24,070 TRIATHALON, YOU ARE JUST 1382 00:53:24,070 --> 00:53:26,472 ASKING THEM TO CHANGE THEIR 1383 00:53:26,472 --> 00:53:27,140 BEHAVIOR 10 PERCENT, 1384 00:53:27,140 --> 00:53:28,441 20 PERCENT AND AS A PUBLIC 1385 00:53:28,441 --> 00:53:29,509 HEALTH PERSON, YOU COULD 1386 00:53:29,509 --> 00:53:32,345 HAVE A BIG DOWNSTREAM EFFECT 1387 00:53:32,345 --> 00:53:38,518 ON DEMENTIA PREVALENCE AND I 1388 00:53:38,518 --> 00:53:43,356 WOULD SAY COGNITIVE AGING 1389 00:53:43,356 --> 00:53:43,990 ISSUES AS WELL. 1390 00:53:43,990 --> 00:53:46,459 SO WE HAVE LOOKED AT THIS 1391 00:53:46,459 --> 00:53:48,194 WORK, EXPANDED IT TO 40 1392 00:53:48,194 --> 00:53:48,861 VARIANTS. 1393 00:53:48,861 --> 00:53:50,496 I AM NOT SURE SOME OF THESE 1394 00:53:50,496 --> 00:53:52,565 HAVE BEEN SO CAREFULLY 1395 00:53:52,565 --> 00:53:54,634 STUDIED BUT THE IDEA HERE 1396 00:53:54,634 --> 00:53:54,967 REMAINS. 1397 00:53:54,967 --> 00:53:56,469 THIS IDEA THAT IF YOU CAN 1398 00:53:56,469 --> 00:53:58,538 CHANGE SOME OF THESE RISK 1399 00:53:58,538 --> 00:54:01,174 FACTORS, YOU ACTUALLY COULD 1400 00:54:01,174 --> 00:54:02,809 IMPROVE COGNITION AND REDUCE 1401 00:54:02,809 --> 00:54:03,776 DEMENTIA. 1402 00:54:03,776 --> 00:54:05,311 SO THIS IS ALL GREAT BUT HOW 1403 00:54:05,311 --> 00:54:07,580 DO YOU GET PEOPLE TO CHANGE 1404 00:54:07,580 --> 00:54:08,047 THEIR BEHAVIOR? 1405 00:54:08,047 --> 00:54:10,016 IT IS NOT SO EASY. 1406 00:54:10,016 --> 00:54:10,983 NIH HAS BEEN INTERESTED IN 1407 00:54:10,983 --> 00:54:13,052 THIS AND I HAD A GREAT 1408 00:54:13,052 --> 00:54:15,088 WORKSHOP WITH THE NATIONAL 1409 00:54:15,088 --> 00:54:18,091 ACADEMY OF MEDICINE AND AARP 1410 00:54:18,091 --> 00:54:19,559 HAS GOT TEN VERY INTERESTED 1411 00:54:19,559 --> 00:54:20,026 IN THIS. 1412 00:54:20,026 --> 00:54:22,261 HOW DO YOU GET PEOPLE TO 1413 00:54:22,261 --> 00:54:22,862 CHANGE THEIR BEHAVIORS? 1414 00:54:22,862 --> 00:54:24,263 I KNOW I SHOULD EXERCISE 1415 00:54:24,263 --> 00:54:25,531 MORE AND EAT BETTER AND I AM 1416 00:54:25,531 --> 00:54:28,334 NOT BAD AT IT BUT IT IS HARD 1417 00:54:28,334 --> 00:54:29,235 TO GET MOTIVATED. 1418 00:54:29,235 --> 00:54:30,269 SO WE WERE REALLY 1419 00:54:30,269 --> 00:54:31,771 INTERESTED, HOW CAN YOU 1420 00:54:31,771 --> 00:54:33,506 MOTIVATE PEOPLE AND GET THEM 1421 00:54:33,506 --> 00:54:35,374 TO ENGAGE IN RISK REDUCTION? 1422 00:54:35,374 --> 00:54:37,310 SO WE DECIDED TO DO A TRIAL 1423 00:54:37,310 --> 00:54:39,946 AND MAKE THIS PERSONALIZED. 1424 00:54:39,946 --> 00:54:42,348 ONE OF OUR THEMES OF THIS 1425 00:54:42,348 --> 00:54:44,550 CONFERENCE IS PRECISION 1426 00:54:44,550 --> 00:54:45,384 MEDICINE. 1427 00:54:45,384 --> 00:54:46,586 THIS IS PRECISION MEDICINE 1428 00:54:46,586 --> 00:54:48,688 IN TERMS OF REDUCING RISK 1429 00:54:48,688 --> 00:54:50,523 POCKET TARS. 1430 00:54:50,523 --> 00:54:54,460 SO WE DESIGNED THIS TRIAL, 1431 00:54:54,460 --> 00:54:56,863 COURTESY OF NIA, THANK YOU 1432 00:54:56,863 --> 00:55:00,833 NIA, WE DID A MULTIRISK 1433 00:55:00,833 --> 00:55:02,535 REDUCTION TRIAL AND THIS IS 1434 00:55:02,535 --> 00:55:04,370 WITH COLLEAGUES AT KAISER IN 1435 00:55:04,370 --> 00:55:04,770 SEATTLE. 1436 00:55:04,770 --> 00:55:06,739 WHAT WE FIRST DID WAS SAY 1437 00:55:06,739 --> 00:55:09,108 LET'S IDENTIFY PEOPLE WITH 1438 00:55:09,108 --> 00:55:10,276 RISK FACTORS. 1439 00:55:10,276 --> 00:55:13,246 SO THESE WERE PEOPLE WHO DID 1440 00:55:13,246 --> 00:55:15,681 NOT HAVE DEMENTIA, THEY WERE 1441 00:55:15,681 --> 00:55:18,718 OLDER, 70 AND ABOVE, BUT WE 1442 00:55:18,718 --> 00:55:20,319 WANT TO SEE IF THEY HAVE 1443 00:55:20,319 --> 00:55:24,257 COGNITIVE CHANGE OVER TIME. 1444 00:55:24,257 --> 00:55:26,259 BUT THEY HAVE TO HAVE AT 1445 00:55:26,259 --> 00:55:36,769 LEAST TWO RISK FACTORS, A 1446 00:55:37,403 --> 00:55:39,238 LIST OF EIGHT RISK FACTORS 1447 00:55:39,238 --> 00:55:40,973 AND THEY HAD TO HAVE AT 1448 00:55:40,973 --> 00:55:44,177 LEAST TWO OF THOSE. 1449 00:55:44,177 --> 00:55:46,479 OTHERS HAD A PERSONALIZED 1450 00:55:46,479 --> 00:55:46,913 INTERVENTION. 1451 00:55:46,913 --> 00:55:47,780 THEY GOT TO CHOOSE WHAT THEY 1452 00:55:47,780 --> 00:55:48,948 WANTED TO WORK ON. 1453 00:55:48,948 --> 00:55:51,150 SO WE TOLD THEM WHAT THE 1454 00:55:51,150 --> 00:55:52,285 RISK FACTORS WERE, AND THEY 1455 00:55:52,285 --> 00:55:54,620 SAID OKAY I WANT TO WORK ON 1456 00:55:54,620 --> 00:55:55,655 PHYSICAL ACTIVITY, I WANT TO 1457 00:55:55,655 --> 00:55:57,390 WORK ON MY SLEEP, I WANT TO 1458 00:55:57,390 --> 00:56:00,726 WORK ON MY HYPERTENSION AND 1459 00:56:00,726 --> 00:56:02,995 SO WE ENGAGED THEM BY THEM 1460 00:56:02,995 --> 00:56:03,963 CHOOSING WHAT THEY WANTED TO 1461 00:56:03,963 --> 00:56:05,698 WORK ON, WHAT THEY HAD FIRST 1462 00:56:05,698 --> 00:56:06,999 OF ALL, RIGHT, AND THEN WHAT 1463 00:56:06,999 --> 00:56:08,167 THEY WANTED TO WORK ON AND 1464 00:56:08,167 --> 00:56:09,569 HOW THEY WANTED TO WORK ON 1465 00:56:09,569 --> 00:56:09,969 IT. 1466 00:56:09,969 --> 00:56:11,537 DO YOU WANT TO GO TO THE 1467 00:56:11,537 --> 00:56:11,804 GYM? 1468 00:56:11,804 --> 00:56:14,073 YOU WANT TO HAVE A FIT BIT, 1469 00:56:14,073 --> 00:56:17,510 YOU WANT TO DO CDT FOR 1470 00:56:17,510 --> 00:56:18,411 INSOMNIA, WHAT DO YOU WANT 1471 00:56:18,411 --> 00:56:19,345 TO DO. 1472 00:56:19,345 --> 00:56:20,646 AND THEN OUTCOMES WERE 1473 00:56:20,646 --> 00:56:21,681 COGNITIVE FUNCTION OF COURSE 1474 00:56:21,681 --> 00:56:23,516 AND LOOKING AT THE RISK 1475 00:56:23,516 --> 00:56:24,483 FACTOR CHANGES AND QUALITY 1476 00:56:24,483 --> 00:56:25,017 OF LIFE. 1477 00:56:25,017 --> 00:56:27,186 WE HAVE HAD MUCH MORE 1478 00:56:27,186 --> 00:56:28,921 OUTCOMES BUT THIS HAPPENED, 1479 00:56:28,921 --> 00:56:31,090 WE WERE FINISHING ENROLLMENT 1480 00:56:31,090 --> 00:56:32,758 IN MARCH 2020 AND THIS WAS 1481 00:56:32,758 --> 00:56:34,026 SEATTLE WHICH WAS THE FIRST 1482 00:56:34,026 --> 00:56:35,861 CITY TO SHUT DOWN SO, YOU 1483 00:56:35,861 --> 00:56:38,297 KNOW, JUST MY LUCK, RIGHT? 1484 00:56:38,297 --> 00:56:41,167 SO ANY WAY, IT WAS ALL VERY 1485 00:56:41,167 --> 00:56:43,102 INTERESTING BUT IN THE END, 1486 00:56:43,102 --> 00:56:45,071 WE ENDED UP GOING ALL REMOTE 1487 00:56:45,071 --> 00:56:47,240 WHICH IN SOME WAYS MADE IT 1488 00:56:47,240 --> 00:56:47,707 MORE PRACTICAL. 1489 00:56:47,707 --> 00:56:49,475 SO THIS IS WHAT WE FOUND. 1490 00:56:49,475 --> 00:56:53,446 AFTER TWO YEARS, THE 1491 00:56:53,446 --> 00:56:56,115 COGNITIVE COMPOSITE, A 1492 00:56:56,115 --> 00:56:57,917 MODIFIED NEUROTEST BATTERY, 1493 00:56:57,917 --> 00:57:02,021 VERY SIMILAR TO WHAT WE USED 1494 00:57:02,021 --> 00:57:03,789 IN BINGHA AND MUCH TO MY 1495 00:57:03,789 --> 00:57:05,458 SURPRISE BECAUSE THIS WAS 1496 00:57:05,458 --> 00:57:08,728 DURING COVID, WHAT WE FOUND 1497 00:57:08,728 --> 00:57:11,497 IS THE INTERVENTION GROUP 1498 00:57:11,497 --> 00:57:13,633 IMPROVED, BOTH GROUPS 1499 00:57:13,633 --> 00:57:14,200 IMSKPRAOUFRBD MANY 1500 00:57:14,200 --> 00:57:17,970 PREVENTION TRIALS HAVE FOUND 1501 00:57:17,970 --> 00:57:19,405 COGNITIVE FUNCTION IMPROVES. 1502 00:57:19,405 --> 00:57:21,941 BUT THE INTERVENTION GROUP 1503 00:57:21,941 --> 00:57:22,475 IMPROVED MUCH MORE, 1504 00:57:22,475 --> 00:57:23,109 80 PERCENT MORE THAN THE 1505 00:57:23,109 --> 00:57:24,210 CONTROL GROUP AND YOU CAN 1506 00:57:24,210 --> 00:57:25,311 SEE THIS IS PRETTY 1507 00:57:25,311 --> 00:57:26,078 SUSTAINED. 1508 00:57:26,078 --> 00:57:31,550 THIS IS AN AVERAGE TREATMENT 1509 00:57:31,550 --> 00:57:33,719 EFFECT EVER .5 OF DEVIATION, 1510 00:57:33,719 --> 00:57:35,454 SIMILAR TO A LOT OF DRUGS, 1511 00:57:35,454 --> 00:57:37,590 MAYBE EVEN BETTER THAN SOME 1512 00:57:37,590 --> 00:57:38,758 DRUGS SO VERY EXCITED ABOUT 1513 00:57:38,758 --> 00:57:39,525 THESE RESULTS. 1514 00:57:39,525 --> 00:57:41,360 AND THEN WE LOOKED AT THE 1515 00:57:41,360 --> 00:57:43,629 RISK FACTORS, YOU KNOW, DID 1516 00:57:43,629 --> 00:57:44,897 THE RISK FACTORS CHANGE, 1517 00:57:44,897 --> 00:57:46,465 THIS IS THE SECONDARY 1518 00:57:46,465 --> 00:57:49,435 OUTCOME AND YOU SEE THE RISK 1519 00:57:49,435 --> 00:57:50,403 FACTORS DID CHANGE. 1520 00:57:50,403 --> 00:57:53,306 THE FIRST SIX MONTHS IS WHEN 1521 00:57:53,306 --> 00:57:55,708 COVID HIT SO THAT WAS 1522 00:57:55,708 --> 00:57:57,310 PROBABLY MID-2020 BUT THE 1523 00:57:57,310 --> 00:57:59,512 INTERVENTION GROUP ACTUALLY 1524 00:57:59,512 --> 00:58:00,746 STAYED THE SAME AND THE 1525 00:58:00,746 --> 00:58:02,248 CONTROL GROUP GOT WORSE AND 1526 00:58:02,248 --> 00:58:04,550 THEN YOU CAN SEE THEY SORT 1527 00:58:04,550 --> 00:58:06,919 OF REBOUNDED AND THERE WAS A 1528 00:58:06,919 --> 00:58:08,521 IMPROVEMENT IN QUALITY OF 1529 00:58:08,521 --> 00:58:10,790 LIFE AND AGAIN, SIGNIFICANT 1530 00:58:10,790 --> 00:58:12,992 ACROSS THE TWO GROUPS. 1531 00:58:12,992 --> 00:58:14,960 SO WE'RE VERY EXCITED ABOUT 1532 00:58:14,960 --> 00:58:15,261 THIS. 1533 00:58:15,261 --> 00:58:16,462 WE'RE INTERESTED IN TAKING 1534 00:58:16,462 --> 00:58:18,564 THIS TO THE NEXT STEP, 1535 00:58:18,564 --> 00:58:21,867 PROBABLY DOING A BIGGER 1536 00:58:21,867 --> 00:58:24,036 MULTI-SITE TRIAL BUT I ALSO 1537 00:58:24,036 --> 00:58:25,404 THINK WE SHOULD BE THINKING 1538 00:58:25,404 --> 00:58:27,606 SHOULD WE DO THIS IN 1539 00:58:27,606 --> 00:58:29,642 MIDLIFE, SOMETHING WE WERE 1540 00:58:29,642 --> 00:58:33,379 TALKING ABOUT THIS MORNING, 1541 00:58:33,379 --> 00:58:34,246 IS LATE-LIFE TOO MUCH? 1542 00:58:34,246 --> 00:58:35,981 YOU WILL NOT SEE MUCH 1543 00:58:35,981 --> 00:58:37,583 COGNITIVE CHANGE BUT YOU 1544 00:58:37,583 --> 00:58:39,685 COULD LOOK AT CARDIOVASCULAR 1545 00:58:39,685 --> 00:58:40,519 OUTCOMES AS WELL. 1546 00:58:40,519 --> 00:58:41,887 I HOPE I HAVE SHOWN YOU THE 1547 00:58:41,887 --> 00:58:43,155 IMPORTANCE OF THE LIFE 1548 00:58:43,155 --> 00:58:45,091 COURSE, THAT THESE RISK 1549 00:58:45,091 --> 00:58:47,893 FACTORS ARE OPERATING OVER 1550 00:58:47,893 --> 00:58:50,196 OUR WHOLE LIVES AND PROBABLY 1551 00:58:50,196 --> 00:58:52,164 EVEN EARLIER THAN WE CAN 1552 00:58:52,164 --> 00:58:55,601 STUDY IN TERMS OF CHILDHOOD 1553 00:58:55,601 --> 00:58:57,303 IN UTERO BUT I THINK WE NEED 1554 00:58:57,303 --> 00:58:58,804 TO UNDERSTAND THIS MUCH 1555 00:58:58,804 --> 00:59:01,140 BETTER, HOW DOES THIS SET US 1556 00:59:01,140 --> 00:59:01,540 UP. 1557 00:59:01,540 --> 00:59:03,743 I WOULD LOVE TO PARTNER WITH 1558 00:59:03,743 --> 00:59:05,010 KRISTEN AND HOW DO YOU 1559 00:59:05,010 --> 00:59:06,278 LOOK -- MAYBE USE THE MICE 1560 00:59:06,278 --> 00:59:07,913 TO FIND THINGS AND THEN ROLL 1561 00:59:07,913 --> 00:59:09,348 IT OUT INTO PEOPLE, I DON'T 1562 00:59:09,348 --> 00:59:10,649 KNOW BUT I THINK THERE ARE 1563 00:59:10,649 --> 00:59:11,951 SOME REALLY COOL THINGS YOU 1564 00:59:11,951 --> 00:59:14,286 CAN DO IN TERMS OF IMPROVING 1565 00:59:14,286 --> 00:59:15,654 YOUR COGNITIVE -- THIS IS 1566 00:59:15,654 --> 00:59:18,858 ALL WE TALK ABOUT, RISK AND 1567 00:59:18,858 --> 00:59:19,692 RESILIENCE REALLY, HOW DO 1568 00:59:19,692 --> 00:59:22,561 YOU GET THE BRAIN TO BE 1569 00:59:22,561 --> 00:59:23,963 RESILIENT, HOW DO YOU REDUCE 1570 00:59:23,963 --> 00:59:24,263 RISK. 1571 00:59:24,263 --> 00:59:26,332 I THINK WE NEED MORE 1572 00:59:26,332 --> 00:59:30,636 RESEARCH ON DIVERSE 1573 00:59:30,636 --> 00:59:31,036 POPULATIONS. 1574 00:59:31,036 --> 00:59:32,905 THIS CARDIA IS SOMEWHAT 1575 00:59:32,905 --> 00:59:35,207 DIVERSE BUT WE CAN DO MORE. 1576 00:59:35,207 --> 00:59:38,577 WE HAVE DONE RESEARCH 1577 00:59:38,577 --> 00:59:39,445 LOOKING AT PARTICIPATORY 1578 00:59:39,445 --> 00:59:41,714 RESEARCH AND THE RISK FACTOR 1579 00:59:41,714 --> 00:59:44,283 PROFILES ARE VERY DIFFERENT 1580 00:59:44,283 --> 00:59:45,584 PARTICULARLY WITH RECENT 1581 00:59:45,584 --> 00:59:46,385 IMMIGRANTS AND DIFFERENT 1582 00:59:46,385 --> 00:59:47,553 PLACES IN THE COUNTRY SO WE 1583 00:59:47,553 --> 00:59:48,954 NEED TO PAY ATTENTION TO 1584 00:59:48,954 --> 00:59:49,321 THAT. 1585 00:59:49,321 --> 00:59:53,092 ULTIMATELY I THINK THESE 1586 00:59:53,092 --> 00:59:54,493 PERSONALIZED APPROACHES MUST 1587 00:59:54,493 --> 00:59:57,229 BE MORE EFFECTIVE, YOU GET 1588 00:59:57,229 --> 00:59:59,198 BUY-IN FROM THE PARTICIPANTS 1589 00:59:59,198 --> 01:00:00,599 AND YOU ARE MEETING THEM 1590 01:00:00,599 --> 01:00:01,400 WHERE THEY ARE. 1591 01:00:01,400 --> 01:00:03,502 BUT FOR NOW WE DO HAVE 1592 01:00:03,502 --> 01:00:04,303 RECOMMENDED THINGS WE CAN 1593 01:00:04,303 --> 01:00:05,337 OFFER TO PEOPLE, THEY ARE 1594 01:00:05,337 --> 01:00:07,206 LOW COST, DON'T HAVE A LOT 1595 01:00:07,206 --> 01:00:10,943 OF SIDE EFFECTS, SUCH THINGS 1596 01:00:10,943 --> 01:00:15,147 AS CARDIOVASCULAR RISK 1597 01:00:15,147 --> 01:00:16,882 MODIFICATION, SLEEP, 1598 01:00:16,882 --> 01:00:17,683 HYGIENE, PHYSICAL ACTIVITY, 1599 01:00:17,683 --> 01:00:18,717 DEPRESSION OF COURSE 1600 01:00:18,717 --> 01:00:21,120 INVOLVES MORE OF A USUAL 1601 01:00:21,120 --> 01:00:21,687 PRACTITIONER APPROACH. 1602 01:00:21,687 --> 01:00:23,789 SO I WANT TO THANK YOU, THIS 1603 01:00:23,789 --> 01:00:25,291 IS MY GROUP AND SOME OF THE 1604 01:00:25,291 --> 01:00:26,459 FUNDING I SHOWED TODAY SO 1605 01:00:26,459 --> 01:00:35,367 THANK YOU SO MUCH. 1606 01:00:35,367 --> 01:00:38,938 [APPLAUSE] 1607 01:00:38,938 --> 01:00:40,439 >> THANKS SO MUCH, SUCH 1608 01:00:40,439 --> 01:00:41,440 GREAT DATA. 1609 01:00:41,440 --> 01:00:46,712 SO OUR LAST SPEAKER IS 1610 01:00:46,712 --> 01:00:48,080 MICHELLE MIELKE FROM WAKE 1611 01:00:48,080 --> 01:00:48,814 FOREST UNIVERSITY AND THE 1612 01:00:48,814 --> 01:00:52,718 TITLE OF HER TALK IS 1613 01:00:52,718 --> 01:00:54,353 INTERPRETING BLOOD-BASED 1614 01:00:54,353 --> 01:00:57,223 ALZHEIMER'S DISEASE 1615 01:00:57,223 --> 01:00:59,124 BIOMARKERS IMPACT 1616 01:00:59,124 --> 01:00:59,558 COMORBIDITIES. 1617 01:00:59,558 --> 01:01:09,034 >> THANK YOU VERY MUCH, 1618 01:01:09,034 --> 01:01:10,736 DOCTOR BIZON, LOVELY TO BE 1619 01:01:10,736 --> 01:01:14,173 HERE AND WE'RE ALL IN THIS 1620 01:01:14,173 --> 01:01:14,940 COLOR COORDINATED GROUP. 1621 01:01:14,940 --> 01:01:17,343 REALLY FUN TO FOLLOW ALL 1622 01:01:17,343 --> 01:01:21,046 THESE GREAT WOMEN. 1623 01:01:21,046 --> 01:01:24,583 MY TALK MIGHT VEER A LITTLE 1624 01:01:24,583 --> 01:01:28,454 BIT, FOCUSED ON BLOOD-BASED 1625 01:01:28,454 --> 01:01:38,931 BIOMARKERS AND HOW THEY 1626 01:01:41,033 --> 01:01:42,535 IMPACT AGING. 1627 01:01:42,535 --> 01:01:53,012 SO THE BLOOD-BASED ALDZ 1628 01:01:54,680 --> 01:01:55,214 ALZHEIMER'S BIOMARKERS AND 1629 01:01:55,214 --> 01:01:57,716 THERE IS A LOT OF ADVANTAGE 1630 01:01:57,716 --> 01:02:00,219 IN TERMS OF RESEARCH, COST 1631 01:02:00,219 --> 01:02:00,920 LIMITATIONS AND 1632 01:02:00,920 --> 01:02:04,223 ACCESSIBILITY AS WELL AS 1633 01:02:04,223 --> 01:02:05,391 INVASIVENESS. 1634 01:02:05,391 --> 01:02:05,958 SO THE TECHNOLOGICAL 1635 01:02:05,958 --> 01:02:07,560 ADVANCES THAT HAVE LED TO 1636 01:02:07,560 --> 01:02:09,528 THE DEVELOPMENT OF BLOOD 1637 01:02:09,528 --> 01:02:11,297 BASED BIOMARKERS FOR 1638 01:02:11,297 --> 01:02:12,831 ALZHEIMER'S DISEASE REALLY 1639 01:02:12,831 --> 01:02:15,100 OVER THE PAST FIVE YEARS 1640 01:02:15,100 --> 01:02:16,702 HAVE BEEN AN INCREDIBLE 1641 01:02:16,702 --> 01:02:17,169 ACCOMPLISHMENT. 1642 01:02:17,169 --> 01:02:18,504 SOME OF THESE MARKERS ARE 1643 01:02:18,504 --> 01:02:20,072 NOW AVAILABLE FOR CLINICAL 1644 01:02:20,072 --> 01:02:24,310 USE AND IN FACT SOME OF THE 1645 01:02:24,310 --> 01:02:27,179 AMINO AS SAYS ARE 1646 01:02:27,179 --> 01:02:29,348 REIMBURSABLE THERE CDC CODE. 1647 01:02:29,348 --> 01:02:30,983 MOST STUDIES TO DATE HAVE 1648 01:02:30,983 --> 01:02:33,485 FOCUSSED ON VERY WELL 1649 01:02:33,485 --> 01:02:35,087 CHARACTERIZED INDIVIDUALS IN 1650 01:02:35,087 --> 01:02:35,821 CLINICAL POPULATIONS SO 1651 01:02:35,821 --> 01:02:37,623 THERE IS STILL THIS OVERALL 1652 01:02:37,623 --> 01:02:39,325 LACK OF UNDERSTANDING AS TO 1653 01:02:39,325 --> 01:02:41,160 HOW THESE MARKERS WORK IN A 1654 01:02:41,160 --> 01:02:43,195 GENERAL POPULATION AS WELL 1655 01:02:43,195 --> 01:02:45,731 AS WHAT FACTORS MAY 1656 01:02:45,731 --> 01:02:50,569 INTERPRET THEIR LEVELS IN 1657 01:02:50,569 --> 01:02:52,237 THE POPULATION. 1658 01:02:52,237 --> 01:02:54,073 SO IN THE REST OF THESE 1659 01:02:54,073 --> 01:02:55,207 SLIDES, FIRST I WILL TALK 1660 01:02:55,207 --> 01:02:58,410 ABOUT THE IMPACT OF 1661 01:02:58,410 --> 01:02:59,545 COMORBIDITIES AND MEDICATION 1662 01:02:59,545 --> 01:03:02,081 ON A LEVEL OF INTERPRETING 1663 01:03:02,081 --> 01:03:03,349 THESE BIOMARKERS AND THEN I 1664 01:03:03,349 --> 01:03:04,850 HAVE A COUPLE MORE SLIDES ON 1665 01:03:04,850 --> 01:03:07,052 HOW TO ANALYZE THE DATA AND 1666 01:03:07,052 --> 01:03:11,490 THINKING ABOUT SOME OF THE 1667 01:03:11,490 --> 01:03:12,124 EPIDEMIOLOGICAL STUDIES 1668 01:03:12,124 --> 01:03:14,059 WHICH YOU MAY BE WORKING ON. 1669 01:03:14,059 --> 01:03:15,094 SO ORIGINALLY WHEN WE WERE 1670 01:03:15,094 --> 01:03:17,029 FIRST THING ABOUT HOW TO 1671 01:03:17,029 --> 01:03:18,163 INTERPRET THESE MARKERS IN 1672 01:03:18,163 --> 01:03:20,733 THE POPULATION, WE WERE 1673 01:03:20,733 --> 01:03:22,134 LOOKING IN THE MAYO CLINIC 1674 01:03:22,134 --> 01:03:28,240 STUDY OF AGING WHICH IS A 1675 01:03:28,240 --> 01:03:29,041 POPULATION-BASED STUDY IN 1676 01:03:29,041 --> 01:03:31,210 MINNESOTA AND HERE IN THIS 1677 01:03:31,210 --> 01:03:35,914 PARTICULAR SLIDE, WE LOOKED 1678 01:03:35,914 --> 01:03:38,984 AT PTAU181 AND PTAU217. 1679 01:03:38,984 --> 01:03:40,152 THE RESULTS ARE ESSENTIALLY 1680 01:03:40,152 --> 01:03:44,189 THE SAME SO I WILL FOCUS ON 1681 01:03:44,189 --> 01:03:44,757 P-TAU217. 1682 01:03:44,757 --> 01:03:46,492 THE BLACK IS THE ANALYSIS 1683 01:03:46,492 --> 01:03:48,427 AND THE RED IS THE AGING 1684 01:03:48,427 --> 01:03:50,896 EFFECTS AND TO GIVE YOU A 1685 01:03:50,896 --> 01:03:52,064 BASELINE COMPARISON, YOU SEE 1686 01:03:52,064 --> 01:03:54,833 ON THE BOTTOM, THIS IS THE 1687 01:03:54,833 --> 01:03:56,769 DIFFERENCE BETWEEN P-TAU 1688 01:03:56,769 --> 01:04:00,506 MEASURES BETWEEN THOSE WHO 1689 01:04:00,506 --> 01:04:01,674 ARE AMYLOID POSITIVE AND 1690 01:04:01,674 --> 01:04:05,944 THOSE WHO ARE AMYLOID 1691 01:04:05,944 --> 01:04:06,311 NEGATIVE. 1692 01:04:06,311 --> 01:04:09,715 INTERESTINGLY WHEN YOU START 1693 01:04:09,715 --> 01:04:13,852 TO SEE CHRONIC MORBIDITY 1694 01:04:13,852 --> 01:04:15,254 PARTICULARLY WITH CHRONIC 1695 01:04:15,254 --> 01:04:16,522 KIDNEY DISEASE, YOU CAN SEE 1696 01:04:16,522 --> 01:04:20,325 IT IS BASICALLY THE SAME AS 1697 01:04:20,325 --> 01:04:22,227 SOMEBODY WITHOUT AMYLOID AND 1698 01:04:22,227 --> 01:04:25,898 THIS ISN'T DRIVEN BY AMYLOID 1699 01:04:25,898 --> 01:04:27,833 POSITIVE BECAUSE EVEN IF WE 1700 01:04:27,833 --> 01:04:28,967 EXCLUDE THOSE INDIVIDUALS, 1701 01:04:28,967 --> 01:04:31,570 YOU SEE THIS VERY STRIKING 1702 01:04:31,570 --> 01:04:32,104 DIFFERENCE. 1703 01:04:32,104 --> 01:04:35,007 NOW, WE ALSO SEE LEVELS OF 1704 01:04:35,007 --> 01:04:35,974 P-TAU FOR PEOPLE WHEN A 1705 01:04:35,974 --> 01:04:40,079 HISTORY OF SMOKE AS WELL AS 1706 01:04:40,079 --> 01:04:42,147 MYOCARDIAL FUNCTION. 1707 01:04:42,147 --> 01:04:44,349 IN ADDITION, THE DATA, THIS 1708 01:04:44,349 --> 01:04:52,257 FIGURE SHOWS YOU AMYLOID 1709 01:04:52,257 --> 01:04:53,792 DATA 42-40 RATIO AND AGAIN 1710 01:04:53,792 --> 01:04:57,362 IF WE FOCUS ON CKD, WE SEE I 1711 01:04:57,362 --> 01:05:01,300 HER LEVELS FOR AMYLOID42 AS 1712 01:05:01,300 --> 01:05:06,405 WELL AS 40 BUT WHEN WE LOOK 1713 01:05:06,405 --> 01:05:11,643 AT RATIOS, SOME OF THAT IS 1714 01:05:11,643 --> 01:05:14,780 DIFFERENTIATED SO WE REALLY 1715 01:05:14,780 --> 01:05:17,549 ONLY SEE THAT IN IMPAIRED 1716 01:05:17,549 --> 01:05:18,016 GROUPS. 1717 01:05:18,016 --> 01:05:24,757 SO THERE HAVE BEEN A LOT OF 1718 01:05:24,757 --> 01:05:26,291 EVIDENCE ON THE BIOMARKERS 1719 01:05:26,291 --> 01:05:29,128 SINCE THAT STUDY BUT IT IS 1720 01:05:29,128 --> 01:05:30,662 IMPORTANT TO POINT OUT THERE 1721 01:05:30,662 --> 01:05:32,364 IS A RANGE ACROSS THE KIDNEY 1722 01:05:32,364 --> 01:05:32,898 FUNCTION. 1723 01:05:32,898 --> 01:05:35,801 SO THAT IS GENERALLY EGFR 1724 01:05:35,801 --> 01:05:37,336 LOWER THAN 90 BUT AS YOU CAN 1725 01:05:37,336 --> 01:05:39,304 SEE WITH THIS PARTICULAR 1726 01:05:39,304 --> 01:05:41,106 STUDY, EVEN THOUGH THERE IS 1727 01:05:41,106 --> 01:05:50,415 A VERY SIGNIFICANT 1728 01:05:50,415 --> 01:05:53,418 CORRELATION BETWEENGFR, NIL 1729 01:05:53,418 --> 01:05:54,686 AND GFAP, PHYSIOLOGICAL 1730 01:05:54,686 --> 01:05:59,124 IMPACTING OF THE KIDNEYS 1731 01:05:59,124 --> 01:05:59,792 AFFECTS BIOMARKERS. 1732 01:05:59,792 --> 01:06:01,426 NOW THERE ARE STUDIES THAT 1733 01:06:01,426 --> 01:06:02,995 ADJUST TO CHRONIC KIDNEY 1734 01:06:02,995 --> 01:06:04,196 DISEASE AND IT DOESN'T 1735 01:06:04,196 --> 01:06:04,830 REALLY MAKE A DIFFERENCE 1736 01:06:04,830 --> 01:06:07,466 WHEN YOU ARE LOOKING AT 1737 01:06:07,466 --> 01:06:08,433 BIOMARKERS AND COGNITION. 1738 01:06:08,433 --> 01:06:11,436 IN A COUPLE OF SLIDES, YOU 1739 01:06:11,436 --> 01:06:12,704 WILL TALK MORE ABOUT THAT 1740 01:06:12,704 --> 01:06:15,374 AND WHY THAT MIGHT BE. 1741 01:06:15,374 --> 01:06:17,743 BUT MOST OF THESE ARE GROUP 1742 01:06:17,743 --> 01:06:19,711 STUDIES WHEN ADJUSTING FOR 1743 01:06:19,711 --> 01:06:20,445 CKD. 1744 01:06:20,445 --> 01:06:21,680 HOW DOES THIS AFFECT 1745 01:06:21,680 --> 01:06:23,215 INDIVIDUALS ON A BASIS IN 1746 01:06:23,215 --> 01:06:24,316 TERMS OF DIAGNOSIS? 1747 01:06:24,316 --> 01:06:25,717 SO THIS REALLY BECAME 1748 01:06:25,717 --> 01:06:29,588 APPARENT TO US, WORKING WITH 1749 01:06:29,588 --> 01:06:31,190 MELISSA MURRAY AT 1750 01:06:31,190 --> 01:06:32,658 JACKSONVILLE WHERE YOU ARE 1751 01:06:32,658 --> 01:06:34,726 LOOKING AT THE CORRELATION 1752 01:06:34,726 --> 01:06:44,536 BETWEEN THE PLASMA BLOOD 1753 01:06:44,536 --> 01:06:47,706 MARKERS AND NEURAL 1754 01:06:47,706 --> 01:06:48,240 PATHOLOGY. 1755 01:06:48,240 --> 01:06:50,442 SO ESSENTIALLY THESE 1756 01:06:50,442 --> 01:06:52,778 INDIVIDUALS THE HIGHEST 1757 01:06:52,778 --> 01:06:55,814 P-TAU LEVELS AND WOULD HAVE 1758 01:06:55,814 --> 01:06:58,217 BEEN DIAGNOSED WITH 1759 01:06:58,217 --> 01:07:00,352 ALZHEIMER'S DISEASE BUT 1760 01:07:00,352 --> 01:07:01,286 DIDN'T HAVE SIGNIFICANT 1761 01:07:01,286 --> 01:07:04,156 FACTORS IN THE BRAIN. 1762 01:07:04,156 --> 01:07:05,757 NEARLY TWO WEEKS BEFORE 1763 01:07:05,757 --> 01:07:10,796 THEIR STUDY VISIT, THEY HAD 1764 01:07:10,796 --> 01:07:13,131 A CREATININE LEVEL OF 3.7. 1765 01:07:13,131 --> 01:07:15,734 SO AGAIN THEY COULD HAVE 1766 01:07:15,734 --> 01:07:17,336 BEEN DIAGNOSED WITH 1767 01:07:17,336 --> 01:07:18,604 ALZHEIMER'S DISEASE WHEN IN 1768 01:07:18,604 --> 01:07:22,074 FACT THEY DIDN'T HAVE THE 1769 01:07:22,074 --> 01:07:22,441 PATHOLOGY. 1770 01:07:22,441 --> 01:07:23,842 SO THERE HAS BEEN SOME WORK 1771 01:07:23,842 --> 01:07:28,947 TRYING TO FIGURE OUT HOW TO 1772 01:07:28,947 --> 01:07:30,082 MITIGATE THESE FACTORS FOR 1773 01:07:30,082 --> 01:07:32,718 THOSE WHO HAVE CHRONIC 1774 01:07:32,718 --> 01:07:34,987 KIDNEY SKIS AND SIMILAR WHEN 1775 01:07:34,987 --> 01:07:38,123 YOU USE THE 40 TO 42 RATIO, 1776 01:07:38,123 --> 01:07:41,994 SOME OF THAT WAS ATTENUATED 1777 01:07:41,994 --> 01:07:48,600 AND WHEN YOU LOOK AT THE 1778 01:07:48,600 --> 01:07:50,769 P-TAU RATIO, SOME OF THOSE 1779 01:07:50,769 --> 01:07:51,937 EFFECTS ARE MITIGATED AS 1780 01:07:51,937 --> 01:07:52,738 WELL. 1781 01:07:52,738 --> 01:07:54,806 THIS PARTICULAR STUDY LOOKED 1782 01:07:54,806 --> 01:07:57,075 AT MILD CKD PATIENTS SO 1783 01:07:57,075 --> 01:07:59,144 THERE IS ONGOING WORK BY 1784 01:07:59,144 --> 01:08:01,713 MURRAY AT THE FURMAN 1785 01:08:01,713 --> 01:08:05,918 INSTITUTE WHO ARE LOOKING AT 1786 01:08:05,918 --> 01:08:09,121 THESE RATIOS AND IN MORE 1787 01:08:09,121 --> 01:08:10,589 SEVERE CKD. 1788 01:08:10,589 --> 01:08:12,224 SO SHIFTING GEARS A LITTLE 1789 01:08:12,224 --> 01:08:14,960 BIT, I SHOWED YOU THIS 1790 01:08:14,960 --> 01:08:15,560 FIGURE. 1791 01:08:15,560 --> 01:08:17,930 WHAT I DIDN'T HIGHLIGHT WAS 1792 01:08:17,930 --> 01:08:19,998 THE ASSOCIATION BETWEEN 1793 01:08:19,998 --> 01:08:22,067 THESE MARKERS AND BMI. 1794 01:08:22,067 --> 01:08:25,404 SO WITH INCREASING BMI, WE 1795 01:08:25,404 --> 01:08:27,839 SEE DECREASING IN THE 1796 01:08:27,839 --> 01:08:28,173 MARKERS. 1797 01:08:28,173 --> 01:08:30,609 AND IN OTHER STUDIES YOU SEE 1798 01:08:30,609 --> 01:08:33,612 THE SAME THING WITH PLASMA 1799 01:08:33,612 --> 01:08:37,082 P-TAU AS WELL AS NIL AND 1800 01:08:37,082 --> 01:08:37,382 GFAS. 1801 01:08:37,382 --> 01:08:40,319 NOW WHAT MIGHT BE THE REASON 1802 01:08:40,319 --> 01:08:41,219 FOR THIS EXPLANATION? 1803 01:08:41,219 --> 01:08:42,888 THE FIRST WORK THAT REALLY 1804 01:08:42,888 --> 01:08:45,524 FOCUSED ON THIS CAME OUT IN 1805 01:08:45,524 --> 01:08:47,059 2020 LOOKING AT MS PATIENTS 1806 01:08:47,059 --> 01:08:47,893 AND CONTROLS. 1807 01:08:47,893 --> 01:08:49,895 AND THEY FOUND THERE WAS AN 1808 01:08:49,895 --> 01:08:52,164 INKRERS ASSOCIATION BETWEEN 1809 01:08:52,164 --> 01:08:55,133 BODY WEIGHT AND NFL AND THAT 1810 01:08:55,133 --> 01:08:56,501 WAS DRIVEN BY CHANGES IN 1811 01:08:56,501 --> 01:08:58,036 BLOOD VOLUME. 1812 01:08:58,036 --> 01:08:59,771 SO WITH INCREASING OBESITY 1813 01:08:59,771 --> 01:09:00,772 THERE IS INCREASING BLOOD 1814 01:09:00,772 --> 01:09:02,240 VOLUME AND THIS IS RESULTING 1815 01:09:02,240 --> 01:09:08,680 IN LOWER LEVELS OF NFL. 1816 01:09:08,680 --> 01:09:11,216 IMPORTANTLY, AGAIN, OBESITY 1817 01:09:11,216 --> 01:09:13,585 OR INCREASED BMI IN THESE 1818 01:09:13,585 --> 01:09:16,221 PATIENTS DID NOT AFFECT CSF 1819 01:09:16,221 --> 01:09:18,523 OR NFL LEVELS SO THIS IS 1820 01:09:18,523 --> 01:09:19,458 CERTAINLY A PERIPHERAL 1821 01:09:19,458 --> 01:09:19,858 PHENOMENON. 1822 01:09:19,858 --> 01:09:21,293 AND I THINK THIS HIGHLIGHTS 1823 01:09:21,293 --> 01:09:22,928 EVEN MORE WHAT THE POTENTIAL 1824 01:09:22,928 --> 01:09:27,232 EFFECT OF WHAT BMI CAN BE. 1825 01:09:27,232 --> 01:09:35,540 SO THIS STUDY BY REVLOS HAD 1826 01:09:35,540 --> 01:09:37,576 LOOKED AT P-TAU LEVELS IN 1827 01:09:37,576 --> 01:09:39,311 NORMAL PATIENTS AND COMPARED 1828 01:09:39,311 --> 01:09:41,680 THEM TO INDIVIDUALS WHO WERE 1829 01:09:41,680 --> 01:09:43,648 OVERWEIGHT AND ABOUT TO 1830 01:09:43,648 --> 01:09:45,350 UNDERGO BASS STRICK BY PASS 1831 01:09:45,350 --> 01:09:45,684 SURGERY. 1832 01:09:45,684 --> 01:09:47,119 AND I DON'T THINK I HAVE A 1833 01:09:47,119 --> 01:09:49,588 POINTER HERE BUT WHAT YOU 1834 01:09:49,588 --> 01:09:51,189 CAN SEE IS THAT INDIVIDUALS 1835 01:09:51,189 --> 01:09:53,125 WHO WERE OF NORMAL WEIGHT 1836 01:09:53,125 --> 01:09:55,193 HAD HIGHER LEVELS OF NFL 1837 01:09:55,193 --> 01:09:56,128 COMPANY PAIRED TO THOSE 1838 01:09:56,128 --> 01:09:58,864 INDIVIDUALS WHO WERE OBESE. 1839 01:09:58,864 --> 01:09:59,765 HOWEVER INTERESTINGLY, SIX 1840 01:09:59,765 --> 01:10:01,233 MONTHS LATER WHEN 1841 01:10:01,233 --> 01:10:06,204 INDIVIDUALS WENT FROM 1842 01:10:06,204 --> 01:10:14,513 AVERAGE BMI OF 41 TO 9 AT BY 1843 01:10:14,513 --> 01:10:16,481 PASS, THE LEVELS ARE NOT 1844 01:10:16,481 --> 01:10:21,219 ELEVATED AND THERE IS NO 1845 01:10:21,219 --> 01:10:21,887 DIFFERENCE BETWEEN 1846 01:10:21,887 --> 01:10:24,656 OVERWEIGHT INDIVIDUALS AND 1847 01:10:24,656 --> 01:10:25,524 MILDLY OVERWEIGHT 1848 01:10:25,524 --> 01:10:25,924 INDIVIDUALS. 1849 01:10:25,924 --> 01:10:27,692 AND I SHOULD SAY I TALKED 1850 01:10:27,692 --> 01:10:31,663 WITH SOME IN OUR DEPARTMENT 1851 01:10:31,663 --> 01:10:34,299 AND TYPICALLY WITH BY PASS 1852 01:10:34,299 --> 01:10:36,134 SURGERY, YOU SEE BETTER 1853 01:10:36,134 --> 01:10:37,436 COGNITION SO YOU WOULDN'T 1854 01:10:37,436 --> 01:10:40,439 EXPECT TO SEE ADVERSE 1855 01:10:40,439 --> 01:10:41,706 CHANGES IN 1856 01:10:41,706 --> 01:10:42,207 NEURODEGENERATION. 1857 01:10:42,207 --> 01:10:43,241 IN ADDITION, THERE IS ALSO 1858 01:10:43,241 --> 01:10:45,677 MORE WORK SUGGESTING THAT 1859 01:10:45,677 --> 01:10:47,546 BLOOD AMYLOID MAY BE 1860 01:10:47,546 --> 01:10:49,481 AFFECTED BY CARDIAC 1861 01:10:49,481 --> 01:10:50,048 CONDITIONS. 1862 01:10:50,048 --> 01:10:51,183 WE KNOW IT ACCUMULATES IN 1863 01:10:51,183 --> 01:10:53,985 THE HEART OF ALZHEIMER'S 1864 01:10:53,985 --> 01:10:55,787 PATIENTS AND SOME RECENT 1865 01:10:55,787 --> 01:10:57,489 STUDIES HAVE SHOWN THAT 1866 01:10:57,489 --> 01:11:00,926 PLASMA LEVELS OF AMYLOID 1867 01:11:00,926 --> 01:11:04,996 DATA, 40 AND 42, HIGH LEVEL, 1868 01:11:04,996 --> 01:11:09,101 ARE RISK FACTORS FOR CARDIAC 1869 01:11:09,101 --> 01:11:10,335 AND OTHER CONDITIONS. 1870 01:11:10,335 --> 01:11:20,178 NOW A RECENT STUDY SHOWED 1871 01:11:20,178 --> 01:11:23,014 THAT SACUBITRIL LOWERED THE 1872 01:11:23,014 --> 01:11:27,586 42/40 RATIO BUT NOT THE 1873 01:11:27,586 --> 01:11:32,190 CSF42/40 RATIO. 1874 01:11:32,190 --> 01:11:34,793 SO THIS PARTICULAR 1875 01:11:34,793 --> 01:11:35,827 MEDICATION INCREASES THE 1876 01:11:35,827 --> 01:11:38,530 42/40 OVER A YEAR BUT THE 1877 01:11:38,530 --> 01:11:40,365 RATIO IS SIGNIFICANTLY 1878 01:11:40,365 --> 01:11:41,633 INCREASED IN INDIVIDUALS SO 1879 01:11:41,633 --> 01:11:49,474 THIS IS A POSSIBILITY WHEN 1880 01:11:49,474 --> 01:11:53,645 AN INDIVIDUAL COMES IN AND 1881 01:11:53,645 --> 01:11:57,082 YOU NOTICE ELEVATED 42/40 IN 1882 01:11:57,082 --> 01:12:02,921 THE BLOOD, THEY MAY HAVE 1883 01:12:02,921 --> 01:12:04,689 ALZHEIMER'S ALTHOUGH THE 1884 01:12:04,689 --> 01:12:07,692 P-TAU IS A BETTER MARKER 1885 01:12:07,692 --> 01:12:08,326 WITH PARTICIPANTS. 1886 01:12:08,326 --> 01:12:11,229 I WANTED TO TALK A LITTLE ON 1887 01:12:11,229 --> 01:12:12,998 ETHNICITY BECAUSE THINKING 1888 01:12:12,998 --> 01:12:13,665 ABOUT BIOMARKERS, THERE HAS 1889 01:12:13,665 --> 01:12:16,635 BEEN A LOT OF DISCUSSION IN 1890 01:12:16,635 --> 01:12:17,302 THIS. 1891 01:12:17,302 --> 01:12:20,105 IF YOU GO BACK AND LOOK AT 1892 01:12:20,105 --> 01:12:22,040 THE BIOMARKERS, THERE ARE 1893 01:12:22,040 --> 01:12:25,544 STUDIES TO SUGGEST THAT THE 1894 01:12:25,544 --> 01:12:29,514 AD FLUID MAY BE LOWER IN 1895 01:12:29,514 --> 01:12:30,749 AFRICAN-AMERICANS THAN WHITE 1896 01:12:30,749 --> 01:12:32,484 AMERICANS AND THOSE BLACK 1897 01:12:32,484 --> 01:12:34,653 AMERICANS WHO ARE ENROLLED 1898 01:12:34,653 --> 01:12:36,621 ARE GENERALLY HIGHER 1899 01:12:36,621 --> 01:12:43,094 EDUCATED, HEALTHIER AND NOT 1900 01:12:43,094 --> 01:12:44,196 THE TYPICAL POPULATION. 1901 01:12:44,196 --> 01:12:46,831 IN TERMS OF BLOOD MARKERS, 1902 01:12:46,831 --> 01:12:49,034 SOME WE SEE DIFFERENCES AND 1903 01:12:49,034 --> 01:12:53,672 SOME WE DON'T. 1904 01:12:53,672 --> 01:12:56,374 BUT COMORBIDITY, CHRONIC 1905 01:12:56,374 --> 01:13:03,248 KIDNEY DISEASE, CARDIAC 1906 01:13:03,248 --> 01:13:03,915 DISEASE, COGNITIVE DISEASE, 1907 01:13:03,915 --> 01:13:06,985 THERE IS NOT A BIG 1908 01:13:06,985 --> 01:13:08,153 DIFFERENCE IN THE BLACK 1909 01:13:08,153 --> 01:13:09,754 VERSUS THE WHITE. 1910 01:13:09,754 --> 01:13:12,123 AND SOME REASONS THE STUDIES 1911 01:13:12,123 --> 01:13:14,426 SEE THIS AND SOME DO NOT ARE 1912 01:13:14,426 --> 01:13:15,794 THE RELEVANCE OF THESE 1913 01:13:15,794 --> 01:13:16,361 CHRONIC CONDITIONS. 1914 01:13:16,361 --> 01:13:19,464 SO SUMMARY IN TERMS OF THE 1915 01:13:19,464 --> 01:13:22,300 COMORBIDITIES, AS I SHOWED, 1916 01:13:22,300 --> 01:13:24,369 CHRONIC KIDNEY DISEASE 1917 01:13:24,369 --> 01:13:25,870 INCREASES THE ALZHEIMER'S 1918 01:13:25,870 --> 01:13:27,472 DISEASE BLOOD BIOMARKERS AND 1919 01:13:27,472 --> 01:13:29,407 ON A INDIVIDUAL LEVEL, IT 1920 01:13:29,407 --> 01:13:30,475 COULD LEAD TO FALSE 1921 01:13:30,475 --> 01:13:30,842 DIAGNOSIS. 1922 01:13:30,842 --> 01:13:33,578 THE USE OF RATIOS MAY BE 1923 01:13:33,578 --> 01:13:34,813 MORE ACCURATE BUT A LOT MORE 1924 01:13:34,813 --> 01:13:36,581 WORK NEEDS TO BE DONE 1925 01:13:36,581 --> 01:13:38,717 ESPECIALLY AT SOME OF THE 1926 01:13:38,717 --> 01:13:40,252 MORE SEVERE RANGES OF 1927 01:13:40,252 --> 01:13:42,387 CHRONIC KIDNEY DISEASE. 1928 01:13:42,387 --> 01:13:45,257 INCREASING BMI IS ASSOCIATED 1929 01:13:45,257 --> 01:13:46,625 WITH LOWER LEVELS OF 1930 01:13:46,625 --> 01:13:47,325 BIOMARKERS. 1931 01:13:47,325 --> 01:13:48,827 IT IS REALLY UNCLEAR HOW TO 1932 01:13:48,827 --> 01:13:50,028 THINK ABOUT THIS AND I WILL 1933 01:13:50,028 --> 01:13:51,196 TALK A LITTLE MORE ABOUT 1934 01:13:51,196 --> 01:13:54,566 THIS IN THE NEXT SLIDE SO I 1935 01:13:54,566 --> 01:13:55,300 WON'T PREEMPT THAT, WHETHER 1936 01:13:55,300 --> 01:13:59,037 IT IS A RISK FACTOR OR 1937 01:13:59,037 --> 01:14:00,538 PHYSIOLOGICAL BUT IT MAY BE 1938 01:14:00,538 --> 01:14:04,643 OVER TIME LOOKING AT 1939 01:14:04,643 --> 01:14:05,677 LONGITUDINAL STUDIES, 1940 01:14:05,677 --> 01:14:07,078 ADJUSTING FOR BMI MAY BE 1941 01:14:07,078 --> 01:14:07,946 IMPORTANT. 1942 01:14:07,946 --> 01:14:09,581 AND IF OLDER ADULTS ARE 1943 01:14:09,581 --> 01:14:19,557 GOING ON THESE GOP AGONISTS 1944 01:14:19,557 --> 01:14:21,293 THAT COULD LOWER BODY WEIGHT 1945 01:14:21,293 --> 01:14:22,060 AS WELL. 1946 01:14:22,060 --> 01:14:24,696 THE NEED TO EXAMINE MULTIPLE 1947 01:14:24,696 --> 01:14:26,998 CONDITIONS, THE EFFECTS OF 1948 01:14:26,998 --> 01:14:31,503 CKD AND CARDIAC AND HIGH BMI 1949 01:14:31,503 --> 01:14:33,872 IN THE BLOOD LEVELS, THERE 1950 01:14:33,872 --> 01:14:36,875 IS A LOT OF PEOPLE WHO HAVE 1951 01:14:36,875 --> 01:14:38,710 OBESITY AND CHRONIC KIDNEY 1952 01:14:38,710 --> 01:14:40,412 DISEASE SO HOW DO YOU 1953 01:14:40,412 --> 01:14:42,514 INTERPRET THE LEVELS IN 1954 01:14:42,514 --> 01:14:43,548 THOSE INDIVIDUALS? 1955 01:14:43,548 --> 01:14:45,650 SO ONE THING I REALLY WANT 1956 01:14:45,650 --> 01:14:47,585 TO TALK ABOUT IS THAT WHEN 1957 01:14:47,585 --> 01:14:49,654 WE THINK ABOUT EXAMINING 1958 01:14:49,654 --> 01:14:51,222 BLOOD BIOMARKERS IN 1959 01:14:51,222 --> 01:14:51,923 COGNITIVE AGING RESEARCH AND 1960 01:14:51,923 --> 01:14:53,391 WHAT I HAVE SHOWN YOU, YES, 1961 01:14:53,391 --> 01:14:55,393 THERE ARE A LOT OF FACTORS 1962 01:14:55,393 --> 01:14:57,362 THAT MAY AFFECT THESE BLOOD 1963 01:14:57,362 --> 01:14:58,496 MARKERS, MORE THAN I HAVE 1964 01:14:58,496 --> 01:15:00,198 SHOWN YOU TODAY, BUT THERE 1965 01:15:00,198 --> 01:15:04,102 IS A BIG DIFFERENCE BETWEEN 1966 01:15:04,102 --> 01:15:05,103 PHYSIOLOGICAL FACTORS VERSUS 1967 01:15:05,103 --> 01:15:06,571 RISK FACTORS. 1968 01:15:06,571 --> 01:15:08,406 SO SOME FACTORS THAT ARE 1969 01:15:08,406 --> 01:15:10,141 RISK FACTORS MAY AFFECT THE 1970 01:15:10,141 --> 01:15:11,176 LEVELS JUST BECAUSE THEY ARE 1971 01:15:11,176 --> 01:15:15,413 ON A DISEASE PATHWAY. 1972 01:15:15,413 --> 01:15:17,482 OTHERS MAY BE PHYSIOLOGICAL 1973 01:15:17,482 --> 01:15:20,118 FACTORS AND MAY NOT BE 1974 01:15:20,118 --> 01:15:22,153 RELATED TO ALZHEIMER'S 1975 01:15:22,153 --> 01:15:23,888 PATHOLOGY BUT MAY HAVE RISK 1976 01:15:23,888 --> 01:15:25,256 FACTORS FOR OTHER REASONS. 1977 01:15:25,256 --> 01:15:28,560 SO AS AN EXAMPLE, I 1978 01:15:28,560 --> 01:15:30,395 MENTIONED WITH CHRONIC 1979 01:15:30,395 --> 01:15:31,663 KIDNEY DISEASE, THEY DON'T 1980 01:15:31,663 --> 01:15:33,264 SEE ANY DIFFERENCE BETWEEN 1981 01:15:33,264 --> 01:15:34,699 THE BIOMARKER LEVELS AND 1982 01:15:34,699 --> 01:15:35,333 COGNITION. 1983 01:15:35,333 --> 01:15:36,334 WELL, I THINK A PRIMARY 1984 01:15:36,334 --> 01:15:38,636 REASON FOR THIS IS THAT IN 1985 01:15:38,636 --> 01:15:40,338 THE BRAIN AND KIDNEY DISEASE 1986 01:15:40,338 --> 01:15:42,741 STUDY OR THE BRAIN STUDY, 1987 01:15:42,741 --> 01:15:45,710 THEY DID NOT FIND AN 1988 01:15:45,710 --> 01:15:47,379 ASSOCIATION BETWEEN CHRONIC 1989 01:15:47,379 --> 01:15:49,447 KIDNEY DISEASE AND 1990 01:15:49,447 --> 01:15:50,749 ALZHEIMER'S PATHOLOGY. 1991 01:15:50,749 --> 01:15:54,252 SO THE CONFOUNDER HAS TO BE 1992 01:15:54,252 --> 01:15:55,887 ASSOCIATED WITH YOUR RISK 1993 01:15:55,887 --> 01:15:57,622 FACTOR AND OUTCOME AND IF IT 1994 01:15:57,622 --> 01:16:00,358 IS NOT, THEN IT IS NOT 1995 01:16:00,358 --> 01:16:01,426 NECESSARILY THE OUTCOME AND 1996 01:16:01,426 --> 01:16:03,561 SO IF YOU ADJUSTOR IT, IT 1997 01:16:03,561 --> 01:16:04,829 WILL NOT DOING ANYTHING. 1998 01:16:04,829 --> 01:16:06,898 BUT IT CLEARLY AFFECTS THE 1999 01:16:06,898 --> 01:16:07,232 LEVELS. 2000 01:16:07,232 --> 01:16:09,000 SO IN THIS CASE IT IS BETTER 2001 01:16:09,000 --> 01:16:11,069 TO ANALYZE THE DATA 2002 01:16:11,069 --> 01:16:12,704 STRATIFYING BY THAT 2003 01:16:12,704 --> 01:16:14,506 CONDITION OF INTEREST. 2004 01:16:14,506 --> 01:16:16,474 IN CONTRAST, BMI IS 2005 01:16:16,474 --> 01:16:18,676 SOMETHING, WELL, WE TALK 2006 01:16:18,676 --> 01:16:20,145 ABOUT PHYSIOLOGICAL CHANGES 2007 01:16:20,145 --> 01:16:21,713 BUT WE KNOW OBESITY IS 2008 01:16:21,713 --> 01:16:23,581 RELATED TO A LOT OF BRAIN 2009 01:16:23,581 --> 01:16:25,550 FUNCTION AS HAS BEEN TALKED 2010 01:16:25,550 --> 01:16:25,950 ABOUT TODAY. 2011 01:16:25,950 --> 01:16:28,219 SO TO BE HONEST, I AM NOT 2012 01:16:28,219 --> 01:16:31,656 EXACTLY SURE HOW TO CONSIDER 2013 01:16:31,656 --> 01:16:33,958 BMI AND OBESITY AT THIS 2014 01:16:33,958 --> 01:16:35,560 POINT BUT DEPENDING WHAT OUR 2015 01:16:35,560 --> 01:16:37,061 SPECIFIC QUESTION IS, WE 2016 01:16:37,061 --> 01:16:43,268 WILL HAVE TO AN WORK 2017 01:16:43,268 --> 01:16:45,270 THROUGH HOW TO ANALYZE THE 2018 01:16:45,270 --> 01:16:46,805 VARIOUS LEVELS. 2019 01:16:46,805 --> 01:16:50,675 LASTLY, THINKING ABOUT THE 2020 01:16:50,675 --> 01:16:52,977 INTERPRETATION OF THE 2021 01:16:52,977 --> 01:16:53,912 BIOBLOOD MARKERS. 2022 01:16:53,912 --> 01:16:55,680 THE REAL WORLD STUDIES ARE 2023 01:16:55,680 --> 01:16:56,247 NOT QUITE CLEAR. 2024 01:16:56,247 --> 01:16:59,484 MOST OF THE WORK HAS BEEN 2025 01:16:59,484 --> 01:17:03,121 DONE IN A SPECIALIZED MEMORY 2026 01:17:03,121 --> 01:17:04,355 CLINIC, HAVEN'T NECESSARILY 2027 01:17:04,355 --> 01:17:06,758 BEEN LOOKED AT IN LIGHT OF A 2028 01:17:06,758 --> 01:17:07,559 VARIETY OF CHRONIC 2029 01:17:07,559 --> 01:17:09,427 CONDITIONS AND OTHER 2030 01:17:09,427 --> 01:17:10,094 FACTORS. 2031 01:17:10,094 --> 01:17:12,797 IT IS ALSO I THINK IMPORTANT 2032 01:17:12,797 --> 01:17:15,300 TO CONSIDER THAT AD PATH 2033 01:17:15,300 --> 01:17:17,368 THOSE BEGIN DECADES PRIOR TO 2034 01:17:17,368 --> 01:17:18,403 SYMPTOMS AND INCREASE WITH 2035 01:17:18,403 --> 01:17:18,670 AGE. 2036 01:17:18,670 --> 01:17:20,705 THEREFORE THIS IS A 2037 01:17:20,705 --> 01:17:21,639 POSSIBILITY BOTH CLINICAL 2038 01:17:21,639 --> 01:17:23,908 AND RESEARCH THAT A POSITIVE 2039 01:17:23,908 --> 01:17:25,743 TEST MAY BE INS DENTAL AND 2040 01:17:25,743 --> 01:17:26,678 THIS IS PARTICULARLY 2041 01:17:26,678 --> 01:17:29,113 IMPORTANT WHEN THINKING 2042 01:17:29,113 --> 01:17:29,981 ABOUT COGNITIVE AGING. 2043 01:17:29,981 --> 01:17:33,218 SO IT IS OUTSTANDING, WE 2044 01:17:33,218 --> 01:17:35,587 HAVE THESE AD BIOMARKERS AND 2045 01:17:35,587 --> 01:17:37,455 IN THIS GROUP AS WELL AS 2046 01:17:37,455 --> 01:17:39,190 YESTERDAY, THERE IS A WHOLE 2047 01:17:39,190 --> 01:17:41,493 LOT OF OTHER MECHANISMS THAT 2048 01:17:41,493 --> 01:17:42,460 IMPACT COGNITIVE AGING IN 2049 01:17:42,460 --> 01:17:46,231 THE BRAIN AND RISK OF OTHER 2050 01:17:46,231 --> 01:17:47,031 NEURODEGENERATIVE PATHOLOGY. 2051 01:17:47,031 --> 01:17:48,867 SO EVEN IF WE'RE LOOKING AT 2052 01:17:48,867 --> 01:17:50,168 A CUT POINT AND THIS PERSON 2053 01:17:50,168 --> 01:17:52,470 MAY BE POSITIVE AND THEY 2054 01:17:52,470 --> 01:17:53,104 HAVE COGNITIVE IMPAIRMENT, 2055 01:17:53,104 --> 01:17:54,906 THAT MAY NOT BE THE SOLE 2056 01:17:54,906 --> 01:17:57,308 DRIVING FORCE OF THAT 2057 01:17:57,308 --> 01:17:57,876 COGNITIVE IMPAIRMENT. 2058 01:17:57,876 --> 01:17:59,511 THERE ARE LIKELY A LOT OF 2059 01:17:59,511 --> 01:18:00,645 OTHER FACTORS PLAYING A ROLE 2060 01:18:00,645 --> 01:18:01,246 AS WELL. 2061 01:18:01,246 --> 01:18:04,282 SO AGAIN WE NEED TO THINK 2062 01:18:04,282 --> 01:18:06,918 ABOUT THIS IN A WHOLE AND IN 2063 01:18:06,918 --> 01:18:08,987 CONTEXT AND CONSIDER OTHER 2064 01:18:08,987 --> 01:18:10,655 MECHANISMS AS WE'RE DOING 2065 01:18:10,655 --> 01:18:11,890 COGNITIVE AGING RESEARCH. 2066 01:18:11,890 --> 01:18:15,860 AND IN CLOSING, I WOULD LIKE 2067 01:18:15,860 --> 01:18:18,162 TO HIGHLIGHT THE U24 WE 2068 01:18:18,162 --> 01:18:22,166 RECENTLY FUNDED, WE CALL IT 2069 01:18:22,166 --> 01:18:23,468 THE ADAC ALZHEIMER'S 2070 01:18:23,468 --> 01:18:24,936 DIAGNOSIS IN OLDER ADULTS 2071 01:18:24,936 --> 01:18:25,870 WITH CHRONIC CONDITIONS AND 2072 01:18:25,870 --> 01:18:28,406 THE PURPOSE IS TO BUILD A 2073 01:18:28,406 --> 01:18:30,141 NATIONAL NETWORK FOCUSED ON 2074 01:18:30,141 --> 01:18:32,443 UNDERSTANDING HOW TO USE 2075 01:18:32,443 --> 01:18:34,512 BIOMARKERS FOR OLDER ADULTS 2076 01:18:34,512 --> 01:18:36,381 WITH IMPAIRMENT BUT ALSO WHO 2077 01:18:36,381 --> 01:18:37,181 HAVE CHRONIC CONDITIONS. 2078 01:18:37,181 --> 01:18:38,750 SO AS PART OF THIS NETWORK, 2079 01:18:38,750 --> 01:18:40,952 WE HAVE A EXECUTIVE 2080 01:18:40,952 --> 01:18:41,486 COMMITTEE, STEERING 2081 01:18:41,486 --> 01:18:43,888 COMMITTEE, WE HAVE THREE 2082 01:18:43,888 --> 01:18:45,757 PILOT PROJECTS AVAILABLE 2083 01:18:45,757 --> 01:18:47,692 EACH YEAR, 150,000 EACH AND 2084 01:18:47,692 --> 01:18:49,460 WE HAVE A ANNUAL MEETING. 2085 01:18:49,460 --> 01:18:54,566 OUR FIRST WILL BE IN 2086 01:18:54,566 --> 01:18:55,800 WINSTON-SALEM APRIL 29-30TH 2087 01:18:55,800 --> 01:18:57,535 AND THE FOCUSES WILL BE TO 2088 01:18:57,535 --> 01:19:02,040 BRING IN THOSE ON THE FRONT 2089 01:19:02,040 --> 01:19:03,474 LINES OF PRIMARY CARE, TO 2090 01:19:03,474 --> 01:19:04,576 UNDERSTAND WHAT THEY ARE 2091 01:19:04,576 --> 01:19:06,077 LOOKING AT IN TERMS OF 2092 01:19:06,077 --> 01:19:08,012 PATIENT QUESTIONS AND WHAT 2093 01:19:08,012 --> 01:19:08,913 GUIDELINES THEY NEED IN 2094 01:19:08,913 --> 01:19:10,315 TERMS OF GOING FORWARD AND 2095 01:19:10,315 --> 01:19:11,983 WHAT WE CAN DO TO HELP THEM 2096 01:19:11,983 --> 01:19:12,717 IN THAT SPACE. 2097 01:19:12,717 --> 01:19:14,419 WE HAVE A LOT OF WORKING 2098 01:19:14,419 --> 01:19:17,055 GROUPS AND LOOK FORWARD TO 2099 01:19:17,055 --> 01:19:18,690 ANYBODY THAT IS INTERESTED 2100 01:19:18,690 --> 01:19:21,993 IN BEING INVOLVED WITH THAT, 2101 01:19:21,993 --> 01:19:25,296 NOT JUST UNDERSTANDING THE 2102 01:19:25,296 --> 01:19:28,933 BIOMARKERS BUT THE EFFICACY 2103 01:19:28,933 --> 01:19:31,269 AND GUIDELINES SO SORRY, I 2104 01:19:31,269 --> 01:19:37,275 AM 25 SECONDS OVER BUT THANK 2105 01:19:37,275 --> 01:19:38,142 YOU. 2106 01:19:38,142 --> 01:19:38,509 [APPLAUSE] 2107 01:19:38,509 --> 01:19:39,477 >> OKAY, GREAT, THANK YOU SO 2108 01:19:39,477 --> 01:19:47,652 MUCH, THAT WAS GREAT. 2109 01:19:47,652 --> 01:19:49,354 SO WE HAVE -- COME ON UP TO 2110 01:19:49,354 --> 01:19:50,188 THE MIC IF YOU HAVE 2111 01:19:50,188 --> 01:19:51,122 QUESTIONS FOR THE SPEAKERS 2112 01:19:51,122 --> 01:19:53,891 AND I AM GOING TO START OUT 2113 01:19:53,891 --> 01:19:56,260 AND ACTUALLY ASK GINA IF YOU 2114 01:19:56,260 --> 01:20:00,331 COULD COMMENT ON SLEEP AND 2115 01:20:00,331 --> 01:20:00,698 MENOPAUSE. 2116 01:20:00,698 --> 01:20:02,667 >> THANK YOU SO MUCH FOR 2117 01:20:02,667 --> 01:20:04,102 GIVING ME THAT. 2118 01:20:04,102 --> 01:20:05,837 I REALIZED I HAD FORGOTTEN 2119 01:20:05,837 --> 01:20:08,473 WHEN I WAS TALKING ABOUT THE 2120 01:20:08,473 --> 01:20:09,741 MENSTRUAL CYCLE AND WHY THAT 2121 01:20:09,741 --> 01:20:12,110 IS RELATED TO AGING AND THAT 2122 01:20:12,110 --> 01:20:13,978 IS BECAUSE OUR CYCLES ARE 2123 01:20:13,978 --> 01:20:14,779 LOWER AND THAT MIGHT 2124 01:20:14,779 --> 01:20:15,947 CONTRIBUTE TO A POOR QUALITY 2125 01:20:15,947 --> 01:20:18,049 OF SLEEP AS WE GET OLDER. 2126 01:20:18,049 --> 01:20:19,350 ALSO IT IS POSSIBLE, AND 2127 01:20:19,350 --> 01:20:20,752 THERE IS NO RESEARCH ON 2128 01:20:20,752 --> 01:20:24,022 EITHER ONE OF THESE 2129 01:20:24,022 --> 01:20:27,058 POSSIBILITIES THAT MENSTRUAL 2130 01:20:27,058 --> 01:20:30,228 CYCLING SETS YOU UP FOR MORE 2131 01:20:30,228 --> 01:20:32,296 SUSCEPTIBILITY TO GETTING 2132 01:20:32,296 --> 01:20:34,365 ALZHEIMER'S LATER WHEN YOU 2133 01:20:34,365 --> 01:20:34,932 GO THROUGH MENOPAUSE. 2134 01:20:34,932 --> 01:20:36,734 THERE NEEDS TO BE RESEARCH 2135 01:20:36,734 --> 01:20:39,737 ON THAT. 2136 01:20:39,737 --> 01:20:40,605 >> THANK YOU. 2137 01:20:40,605 --> 01:20:42,273 >> THANK YOU FOR SUCH AN 2138 01:20:42,273 --> 01:20:43,107 INTERESTING SET OF TALKS. 2139 01:20:43,107 --> 01:20:46,544 I HAVE TWO QUESTIONS. 2140 01:20:46,544 --> 01:20:51,716 SO ONE IS FOR Dr. OH' 2141 01:20:51,716 --> 01:20:54,419 CONNELL. 2142 01:20:54,419 --> 01:20:56,320 YOU WERE USING S1 CROSSES 2143 01:20:56,320 --> 01:21:00,158 AND LIKE TO KNOW A LITTLE 2144 01:21:00,158 --> 01:21:02,093 BIT MORE WHY YOU ARE DOING 2145 01:21:02,093 --> 01:21:04,495 THAT RATHER THAN THE BXE 2146 01:21:04,495 --> 01:21:08,666 THEM AND HE WAS AS 2147 01:21:08,666 --> 01:21:09,634 INVESTIGATORS THINK THROUGH 2148 01:21:09,634 --> 01:21:11,135 THE PANELS ADDRESSING OTHER 2149 01:21:11,135 --> 01:21:11,803 KINDS OF QUESTIONS. 2150 01:21:11,803 --> 01:21:14,205 >> THE DECISION TO DO A F1 2151 01:21:14,205 --> 01:21:15,473 CROSS, COUPLE OF THINGS. 2152 01:21:15,473 --> 01:21:18,376 WE CAN CONTROL THE MATERNAL 2153 01:21:18,376 --> 01:21:19,711 ENVIRONMENT. 2154 01:21:19,711 --> 01:21:22,246 SO THE PRENATAL, LIKE 2155 01:21:22,246 --> 01:21:22,980 GESTATION, POST NATAL, ALL 2156 01:21:22,980 --> 01:21:25,683 OF THAT IS THE SAME BECAUSE 2157 01:21:25,683 --> 01:21:26,651 THE MATERNAL STRING IS THE 2158 01:21:26,651 --> 01:21:27,151 SAME. 2159 01:21:27,151 --> 01:21:32,490 A LOT OF THE GENETIC TOOL 2160 01:21:32,490 --> 01:21:33,858 STRINGS ARE BUILT ON THE 2161 01:21:33,858 --> 01:21:35,359 BACKGROUND SO THAT LIVES US 2162 01:21:35,359 --> 01:21:40,198 A WAY TO GET IN AND 2163 01:21:40,198 --> 01:21:42,900 MANIPULATE ON THE DOWNSTREAM 2164 01:21:42,900 --> 01:21:44,535 SAY FOR EXAMPLE, DISEASE. 2165 01:21:44,535 --> 01:21:46,671 SO IT GIVES US A PLATFORM WE 2166 01:21:46,671 --> 01:21:47,772 CAN BUILD ON AND BRING IN 2167 01:21:47,772 --> 01:21:54,879 CAN IN ADDITIONAL THINGS. 2168 01:21:54,879 --> 01:21:59,917 THOSE STRAINS ARE FULLY 2169 01:21:59,917 --> 01:22:03,788 INBRED SO THE H1 YOU CAN 2170 01:22:03,788 --> 01:22:05,189 HAVE A BLACK SIX. 2171 01:22:05,189 --> 01:22:06,657 IT IS NOT ANYMORE 2172 01:22:06,657 --> 01:22:10,128 CHALLENGING TO MAKE THAN THE 2173 01:22:10,128 --> 01:22:11,496 ORIGINAL BXD'S AND IT HAS 2174 01:22:11,496 --> 01:22:13,698 THE SAME LEVEL OF 2175 01:22:13,698 --> 01:22:14,732 REPRODUCIBILITY AND WITHIN 2176 01:22:14,732 --> 01:22:15,900 EACH STRAINS, THE 2177 01:22:15,900 --> 01:22:23,875 INDIVIDUALS ARE ISOGENIC. 2178 01:22:23,875 --> 01:22:25,376 SO IT ISN'T ANYMORE 2179 01:22:25,376 --> 01:22:27,812 CHALLENGING THAN JUST USING 2180 01:22:27,812 --> 01:22:28,479 THE BXD. 2181 01:22:28,479 --> 01:22:29,947 >> AND THEN THE OTHER 2182 01:22:29,947 --> 01:22:34,152 QUESTION I HAD WAS -- I'M 2183 01:22:34,152 --> 01:22:39,724 SORRY, I AM SPACING ON THAT. 2184 01:22:39,724 --> 01:22:41,025 >> ABSOLUTELY TERRIFIC 2185 01:22:41,025 --> 01:22:42,927 SITUATION, ENJOYED IT. 2186 01:22:42,927 --> 01:22:45,296 ENJOYED HEARING ABOUT THE 2187 01:22:45,296 --> 01:22:46,364 SLEEP AND CARDIOVASCULAR 2188 01:22:46,364 --> 01:22:48,733 RISK FACTORS AND WHAT THEY 2189 01:22:48,733 --> 01:22:51,135 MIGHT MEAN FOR DEMENT IS 2190 01:22:51,135 --> 01:22:53,738 THAT AND COGNITIVE DECLINE. 2191 01:22:53,738 --> 01:22:55,106 SPECIFIC QUESTION FOR 2192 01:22:55,106 --> 01:22:55,606 CHRISTINE. 2193 01:22:55,606 --> 01:22:57,542 LIKE TO MARRY MORE ABOUT THE 2194 01:22:57,542 --> 01:23:04,482 SPART TRIAL AND -- ABOUT 2195 01:23:04,482 --> 01:23:07,752 THE SMARRT TRIAL AND HOW YOU 2196 01:23:07,752 --> 01:23:08,820 PERSONALIZE THAT 2197 01:23:08,820 --> 01:23:10,621 INTERVENTION BEING SCALED IN 2198 01:23:10,621 --> 01:23:12,356 A RESEARCH CONTEXT, HOW 2199 01:23:12,356 --> 01:23:13,391 EXPENSIVE WOULD THE 2200 01:23:13,391 --> 01:23:14,492 INTRODUCTION BE AND HOW 2201 01:23:14,492 --> 01:23:16,327 WOULD YOU GO ABOUT DOING 2202 01:23:16,327 --> 01:23:16,627 THAT? 2203 01:23:16,627 --> 01:23:19,764 >> YES, TOP OF MY MIND. 2204 01:23:19,764 --> 01:23:20,331 [LAUGHTER] 2205 01:23:20,331 --> 01:23:21,833 SO WE THOUGHT A LOT ABOUT 2206 01:23:21,833 --> 01:23:22,099 IT. 2207 01:23:22,099 --> 01:23:26,003 WE TRIED TO MAKE THE SMART 2208 01:23:26,003 --> 01:23:27,405 TRIAL FAIRLY PRAGMATIC IN 2209 01:23:27,405 --> 01:23:28,773 THAT WE USE DHR. 2210 01:23:28,773 --> 01:23:30,741 THAT IS WHY I WANTED TO 2211 01:23:30,741 --> 01:23:32,076 PARTNER WITH KAISER BECAUSE 2212 01:23:32,076 --> 01:23:34,412 THEY HAVE THIS GREAT EHR AND 2213 01:23:34,412 --> 01:23:37,615 WE USE THE EHR TO IDENTIFY 2214 01:23:37,615 --> 01:23:39,917 RISK FACTORS AND THEN WE 2215 01:23:39,917 --> 01:23:41,419 VALIDATED THEM, YOU KNOW, WE 2216 01:23:41,419 --> 01:23:42,787 WANTED TO MAKE SURE THEY 2217 01:23:42,787 --> 01:23:45,156 REALLY HAD WHAT WE THOUGHT 2218 01:23:45,156 --> 01:23:47,992 THEY HAD BUT BY DID GO 2219 01:23:47,992 --> 01:23:49,060 SOMETHING QUESTIONNAIRES AND 2220 01:23:49,060 --> 01:23:49,427 MEASURES. 2221 01:23:49,427 --> 01:23:52,129 SO I THINK YOU COULD DO THAT 2222 01:23:52,129 --> 01:23:54,532 AGAIN AND THAT WAY, YOU 2223 01:23:54,532 --> 01:23:56,367 KNOW, THE RECRUITMENT IS 2224 01:23:56,367 --> 01:23:58,870 VERY EFFICIENT IN TERMS OF 2225 01:23:58,870 --> 01:24:01,072 IDENTIFYING PEOPLE AT RISK, 2226 01:24:01,072 --> 01:24:02,240 EXCLUDE PEOPLE WITH 2227 01:24:02,240 --> 01:24:03,608 DEMENTIA, ET CETERA. 2228 01:24:03,608 --> 01:24:07,778 BECAUSE OF COVID, EVERYTHING 2229 01:24:07,778 --> 01:24:09,714 ENDED UP GOING ACTUALLY BY 2230 01:24:09,714 --> 01:24:11,315 PHONE WHICH IS WHY I WAS 2231 01:24:11,315 --> 01:24:12,717 SURPRISED WE FOUND 2232 01:24:12,717 --> 01:24:13,584 SOMETHING. 2233 01:24:13,584 --> 01:24:17,755 THE OLDER ADULTS, A LOT OF 2234 01:24:17,755 --> 01:24:19,156 THEM WEREN'T AS COMFORTABLE 2235 01:24:19,156 --> 01:24:21,292 ONLINE AND A LOT OF THIS IS 2236 01:24:21,292 --> 01:24:23,327 ON PHONE AT THE END. 2237 01:24:23,327 --> 01:24:25,830 SO ACTUALLY COVID MADE THIS 2238 01:24:25,830 --> 01:24:26,998 QUITE PRACTICAL AND 2239 01:24:26,998 --> 01:24:29,100 PRAGMATIC AND WE'RE NOW 2240 01:24:29,100 --> 01:24:30,902 TRYING TO DECIDE NEXT STEPS. 2241 01:24:30,902 --> 01:24:35,539 WE HOPE TO DO A REMOTE 2242 01:24:35,539 --> 01:24:36,674 MULTI-SITE TRIAL AND I THINK 2243 01:24:36,674 --> 01:24:39,677 YOU CAN USE EHR IN A LOT OF 2244 01:24:39,677 --> 01:24:43,581 WAYS, YOU CAN EVEN USE EHR 2245 01:24:43,581 --> 01:24:45,182 FOR OUTCOMES, RISK FACTOR 2246 01:24:45,182 --> 01:24:46,250 CHANGES. 2247 01:24:46,250 --> 01:24:47,418 SO WE'RE THINKING ABOUT IT 2248 01:24:47,418 --> 01:24:49,053 AND THERE ARE A NUMBER OF 2249 01:24:49,053 --> 01:24:50,254 WAYS TO GO. 2250 01:24:50,254 --> 01:24:52,223 YOU ALLUDE DO YOU STAY WITH 2251 01:24:52,223 --> 01:24:56,794 A PRIMARY CARE MODEL, TRY TO 2252 01:24:56,794 --> 01:24:58,129 DO COMMUNITY PARTICIPATORY 2253 01:24:58,129 --> 01:24:59,897 RESEARCH, I THINK I DON'T 2254 01:24:59,897 --> 01:25:03,634 WANT TO GO WITH MORE OF A 2255 01:25:03,634 --> 01:25:04,468 ALZHEIMER'S CENTERED GROUP 2256 01:25:04,468 --> 01:25:05,836 BECAUSE I THINK THAT IS NOT 2257 01:25:05,836 --> 01:25:09,874 REALLY THE GROUP WE WANT TO 2258 01:25:09,874 --> 01:25:10,541 RECRUIT. 2259 01:25:10,541 --> 01:25:14,679 YOU KNOW, THESE ARE PEOPLE 2260 01:25:14,679 --> 01:25:16,380 AT RISK, NOT REAL COGNITIVE 2261 01:25:16,380 --> 01:25:18,549 CHANGES BUT LIKE TO TALK 2262 01:25:18,549 --> 01:25:22,186 WITH YOU MORE ABOUT IT. 2263 01:25:22,186 --> 01:25:24,789 MORE AHA, THE CDC, PEOPLE 2264 01:25:24,789 --> 01:25:26,424 ARE TRYING TO ROLL SOME OF 2265 01:25:26,424 --> 01:25:28,159 THESE THINGS OUT IN TERMS OF 2266 01:25:28,159 --> 01:25:29,093 PUBLIC POLICY SO I THINK IT 2267 01:25:29,093 --> 01:25:31,529 IS A IMPORTANT TIME TO BE 2268 01:25:31,529 --> 01:25:35,466 THINKING ABOUT THIS. 2269 01:25:35,466 --> 01:25:44,709 >> GREAT, THANK YOU. 2270 01:25:44,709 --> 01:25:45,643 [ OFF MIC ] 2271 01:25:45,643 --> 01:25:47,011 >> WANT TO HEAR YOUR 2272 01:25:47,011 --> 01:25:48,946 THOUGHTS ON EVEN THE LOCAL 2273 01:25:48,946 --> 01:25:49,780 OR NATIONAL POLICY LEVEL 2274 01:25:49,780 --> 01:25:54,085 TARGETS THAT SOME OF THESE 2275 01:25:54,085 --> 01:25:54,485 MIGHT HAVE. 2276 01:25:54,485 --> 01:25:57,822 SO WHERE DO YOU THINK THE 2277 01:25:57,822 --> 01:25:58,622 OPPORTUNITIES ARE, POLICY 2278 01:25:58,622 --> 01:26:01,025 LEVEL AND WHO ARE THE 2279 01:26:01,025 --> 01:26:01,959 PARTNERS? 2280 01:26:01,959 --> 01:26:04,328 YOU WORKED WITH AARP 2281 01:26:04,328 --> 01:26:05,763 SUBSTANTIALLY BUT HOW DO WE 2282 01:26:05,763 --> 01:26:07,431 CHANGE THINGS ON THE LOCAL 2283 01:26:07,431 --> 01:26:09,433 AND NATIONAL LEVEL WITH SOME 2284 01:26:09,433 --> 01:26:10,901 OF THESE FACTORS? 2285 01:26:10,901 --> 01:26:13,137 >> YES, THE CDC AND 2286 01:26:13,137 --> 01:26:14,271 ALZHEIMER'S ASSOCIATION HAVE 2287 01:26:14,271 --> 01:26:16,307 A PARTNERSHIP AND THEY JUST 2288 01:26:16,307 --> 01:26:17,375 ROLLED OUT THIS ROAD MAP 2289 01:26:17,375 --> 01:26:19,810 WHICH I THINK IS REALLY 2290 01:26:19,810 --> 01:26:21,612 EXCITING, TRYING TO ENGAGE 2291 01:26:21,612 --> 01:26:22,880 STATE LEVEL PUBLIC HEALTH 2292 01:26:22,880 --> 01:26:24,482 OFFICES TO TRY AND TEACH 2293 01:26:24,482 --> 01:26:25,783 PEOPLE ABOUT BRAIN HEALTH. 2294 01:26:25,783 --> 01:26:28,986 SO I REALLY THINK A LOT OF 2295 01:26:28,986 --> 01:26:30,621 THIS IS EDUCATIONAL, THAT 2296 01:26:30,621 --> 01:26:33,624 YOU KNOW A LOT OF DOCTORS 2297 01:26:33,624 --> 01:26:35,126 DON'T EVEN UNDERSTAND ABOUT 2298 01:26:35,126 --> 01:26:37,862 BRAIN HEALTH AND EVEN WHAT 2299 01:26:37,862 --> 01:26:41,565 DEMENTIA IS OR HOW YOU 2300 01:26:41,565 --> 01:26:42,299 EVALUATE IT. 2301 01:26:42,299 --> 01:26:43,334 SO ASKING THE PUBLIC TO 2302 01:26:43,334 --> 01:26:44,535 UNDERSTAND SOME OF THIS 2303 01:26:44,535 --> 01:26:46,570 STUFF IS NOT REALLY -- IT IS 2304 01:26:46,570 --> 01:26:46,971 CHALLENGING. 2305 01:26:46,971 --> 01:26:48,572 SO I THINK THERE IS A REALLY 2306 01:26:48,572 --> 01:26:50,708 IMPORTANT ROLE FOR PUBLIC 2307 01:26:50,708 --> 01:26:52,543 EDUCATION ABOUT WHAT BRAIN 2308 01:26:52,543 --> 01:26:54,011 HEALTH IS, WHAT ARE THE RISK 2309 01:26:54,011 --> 01:26:55,579 FACTORS, HOW IS THE HEART 2310 01:26:55,579 --> 01:26:57,515 CONNECTED TO THE BRAIN, HOW 2311 01:26:57,515 --> 01:26:59,517 IS PHYSICAL ACTIVITY THAT 2312 01:26:59,517 --> 01:27:01,419 MAY BE HELPFUL, WHY OVER THE 2313 01:27:01,419 --> 01:27:02,753 LIFE COURSE THIS MIGHT BE 2314 01:27:02,753 --> 01:27:03,421 HELPFUL? 2315 01:27:03,421 --> 01:27:05,222 I HAVE A COLLEAGUE IN FRANCE 2316 01:27:05,222 --> 01:27:07,091 WHO HAS DONE THIS BEAUTIFUL 2317 01:27:07,091 --> 01:27:09,693 VIDEO FOR ELEMENTARY SCHOOL, 2318 01:27:09,693 --> 01:27:11,529 CALLED MY BRAIN ROBBIE AND 2319 01:27:11,529 --> 01:27:14,265 IT IS A REALLY CUTE VIDEO 2320 01:27:14,265 --> 01:27:16,534 AND IT TEACHES ELEMENTARY 2321 01:27:16,534 --> 01:27:18,469 SCHOOL KIDS WHY THEY NEED TO 2322 01:27:18,469 --> 01:27:20,004 PROTECT THEIR BRAIN, WHETHER 2323 01:27:20,004 --> 01:27:22,540 IT IS WEARING A HELMET OR 2324 01:27:22,540 --> 01:27:22,940 EXERCISING. 2325 01:27:22,940 --> 01:27:24,408 SO I THINK THIS IS A REALLY 2326 01:27:24,408 --> 01:27:25,943 EX SOOTHING TIME IN THIS 2327 01:27:25,943 --> 01:27:29,513 COUNTRY AND OTHERS TO TRY TO 2328 01:27:29,513 --> 01:27:31,082 DO PUBLIC EDUCATION. 2329 01:27:31,082 --> 01:27:34,552 >> SCOTLAND HAS A SIMILAR 2330 01:27:34,552 --> 01:27:36,287 PROGRAM FOR PRIMARY CHILDREN 2331 01:27:36,287 --> 01:27:38,322 CALLED STARS AND IT IS 2332 01:27:38,322 --> 01:27:40,191 EXACTLY IDENTIFYING RISK 2333 01:27:40,191 --> 01:27:42,827 FACTORS, A HEALTHY DIET AND 2334 01:27:42,827 --> 01:27:49,700 SO ON SO HAPPY TO SHARE 2335 01:27:49,700 --> 01:27:50,534 THAT AS WELL. 2336 01:27:50,534 --> 01:27:53,637 >> THANKS FOR THE GREAT SET 2337 01:27:53,637 --> 01:27:58,609 OF TALKS, LIZ NIELSEN, AHEAD 2338 01:27:58,609 --> 01:28:01,445 OF THE RESEARCH AT NIA. 2339 01:28:01,445 --> 01:28:03,614 JUST FOR AWARENESS, I 2340 01:28:03,614 --> 01:28:08,586 TOTALLY RESONATE WITH YOUR 2341 01:28:08,586 --> 01:28:10,988 NEED FOR A LIFE COURSE 2342 01:28:10,988 --> 01:28:12,590 APPROACH BUT I WANTED YOU TO 2343 01:28:12,590 --> 01:28:14,925 BE AWARE WE HAVE TENS OF 2344 01:28:14,925 --> 01:28:16,393 THOUSANDS OF INDIVIDUALS 2345 01:28:16,393 --> 01:28:19,029 PHENOTYPED PARTICULARLY FOR 2346 01:28:19,029 --> 01:28:20,664 THEIR EDUCATIONAL EXPOSURES, 2347 01:28:20,664 --> 01:28:22,166 LIFE BLOOD EXPOSURES, BLOOD 2348 01:28:22,166 --> 01:28:29,106 BIOMARKERS IN A NUMBER OF 2349 01:28:29,106 --> 01:28:30,841 THESE GROUPS, PEOPLE BORN IN 2350 01:28:30,841 --> 01:28:34,812 THE 70s AND 80s. 2351 01:28:34,812 --> 01:28:35,613 A LONGITUDINAL STUDY FROM 2352 01:28:35,613 --> 01:28:37,448 HIGH SCHOOL AND BEYOND AND 2353 01:28:37,448 --> 01:28:39,783 THEN PROJECT TALENT WHICH IS 2354 01:28:39,783 --> 01:28:41,418 ACTUALLY 300,000 INDIVIDUALS 2355 01:28:41,418 --> 01:28:44,088 IN SCHOOL IN THE 60s. 2356 01:28:44,088 --> 01:28:46,257 SO THESE STUDIES REPRESENT A 2357 01:28:46,257 --> 01:28:46,991 OPPORTUNITY FOR 2358 01:28:46,991 --> 01:28:48,125 COLLABORATION IN LOOKING AT 2359 01:28:48,125 --> 01:28:51,162 THESE EXPOSURES AND I THINK 2360 01:28:51,162 --> 01:28:52,429 SOME MAY BE LESS EXPLORED 2361 01:28:52,429 --> 01:28:54,398 BECAUSE THERE IS NOT AS MUCH 2362 01:28:54,398 --> 01:28:56,133 AWARENESS IN THIS AREA IS. 2363 01:28:56,133 --> 01:28:57,401 AND THEN A SECOND COMMENT 2364 01:28:57,401 --> 01:29:00,371 AND SORT OF THE QUESTION 2365 01:29:00,371 --> 01:29:02,339 THAT Dr. COE IS TOUCHING 2366 01:29:02,339 --> 01:29:05,309 ON, HOW DO YOU TACKLE THESE 2367 01:29:05,309 --> 01:29:07,044 EXPOSURES AND THINKING IN 2368 01:29:07,044 --> 01:29:08,546 TERMS OF PREVENTION, WHAT 2369 01:29:08,546 --> 01:29:10,281 WILL BE POSSIBLE, EVEN IN 2370 01:29:10,281 --> 01:29:11,949 TAILORING TO SOMEONE IF THE 2371 01:29:11,949 --> 01:29:12,783 SLEEP ENVIRONMENT DOESN'T 2372 01:29:12,783 --> 01:29:16,487 MAKE IT POSSIBLE TO ADDRESS 2373 01:29:16,487 --> 01:29:18,689 THE SLEEP CHALLENGES FOR 2374 01:29:18,689 --> 01:29:19,456 TRANQUIL NIGHT SLEEP. 2375 01:29:19,456 --> 01:29:21,292 SO I AM CURIOUS WHERE YOU 2376 01:29:21,292 --> 01:29:23,027 SEE YOUR EFFORTS GOING 2377 01:29:23,027 --> 01:29:24,862 RELATED TO LOOKING AT THESE 2378 01:29:24,862 --> 01:29:26,263 THAT ARE MORE POP LEVEL 2379 01:29:26,263 --> 01:29:27,765 THINGS AND WHERE THAT MIGHT 2380 01:29:27,765 --> 01:29:28,499 TAKE YOU. 2381 01:29:28,499 --> 01:29:30,601 >> YES, THANK YOU SO MUCH 2382 01:29:30,601 --> 01:29:31,068 FOR THAT. 2383 01:29:31,068 --> 01:29:34,605 I THINK POLICY IS REALLY 2384 01:29:34,605 --> 01:29:36,840 IMPORTANT AND JUST ACTUALLY 2385 01:29:36,840 --> 01:29:40,244 SINCE A PRESS RELEASE OF THE 2386 01:29:40,244 --> 01:29:42,880 EARLY STUDY THAT WE DID 2387 01:29:42,880 --> 01:29:46,150 SHOWING THE HELICOPTER 2388 01:29:46,150 --> 01:29:47,751 POLICE ACTIVITY, HELICOPTER 2389 01:29:47,751 --> 01:29:49,486 POLICE ACTIVITY HAS ALREADY 2390 01:29:49,486 --> 01:29:51,188 BEEN REDUCED QUITE A BIT. 2391 01:29:51,188 --> 01:29:52,823 MAYBE IT HELPS WE HAVE A NEW 2392 01:29:52,823 --> 01:29:54,325 MAYOR AS WELL BUT POLICE 2393 01:29:54,325 --> 01:29:56,493 WERE ASKING FOR TEN MORE 2394 01:29:56,493 --> 01:29:57,628 HELICOPTERS AND THE CITY 2395 01:29:57,628 --> 01:29:58,862 SAID NO. 2396 01:29:58,862 --> 01:30:04,168 AND AGAIN, L.A. IS THE MOST 2397 01:30:04,168 --> 01:30:05,169 POLICE-SURVEILLED CITY. 2398 01:30:05,169 --> 01:30:05,436 WHY? 2399 01:30:05,436 --> 01:30:06,804 THERE IS NO NEED FOR THAT. 2400 01:30:06,804 --> 01:30:08,105 SO I THINK POLICY 2401 01:30:08,105 --> 01:30:10,407 DIFFERENCES AND JUST 2402 01:30:10,407 --> 01:30:11,508 BECOMING AWARE. 2403 01:30:11,508 --> 01:30:15,246 CITY LIGHTS, STREET LIGHTS, 2404 01:30:15,246 --> 01:30:16,614 WINDOWS, DOUBLE PANET, AIR 2405 01:30:16,614 --> 01:30:17,781 CONDITIONING, COULD HELP 2406 01:30:17,781 --> 01:30:18,649 PEOPLE PRIORITIZE THEIR 2407 01:30:18,649 --> 01:30:20,150 SLOPE IN WAYS -- AND 2408 01:30:20,150 --> 01:30:22,786 LEARNING ABOUT THE HEALTH 2409 01:30:22,786 --> 01:30:24,788 CONSEQUENCES OF POOR SLEEP. 2410 01:30:24,788 --> 01:30:27,057 IT HELPS THE CITY, THE 2411 01:30:27,057 --> 01:30:30,561 STATE, THE NATION, THE 2412 01:30:30,561 --> 01:30:36,066 WORLD, PRIORITIZE QUALITY 2413 01:30:36,066 --> 01:30:36,667 SLEEP. 2414 01:30:36,667 --> 01:30:37,501 >> JOHN FROM NORTHWEST 2415 01:30:37,501 --> 01:30:38,836 UNIVERSITY, I HAVE TWO 2416 01:30:38,836 --> 01:30:44,008 QUESTIONS FOR Dr. 2417 01:30:44,008 --> 01:30:44,508 O'CONNELL. 2418 01:30:44,508 --> 01:30:46,844 FIRST, THIS ISSUE OF MOUSE 2419 01:30:46,844 --> 01:30:47,911 DATA TO HUMANS, WOULD YOU 2420 01:30:47,911 --> 01:30:49,513 COMMENT ON THE IMPLICATIONS 2421 01:30:49,513 --> 01:30:52,483 OF YOUR FINDINGS FOR SUPER 2422 01:30:52,483 --> 01:30:52,916 AGER STUDIES? 2423 01:30:52,916 --> 01:30:56,587 SO I MEAN I AM SURE YOU HAVE 2424 01:30:56,587 --> 01:31:00,124 THOUGHT ABOUT THIS AND -- 2425 01:31:00,124 --> 01:31:02,826 >> YEAH, THAT IS A GREAT 2426 01:31:02,826 --> 01:31:04,328 QUESTION. 2427 01:31:04,328 --> 01:31:05,696 ONE OF THE ADVANTAGES OF 2428 01:31:05,696 --> 01:31:07,097 MICE BUT EVEN SOMETHING THAT 2429 01:31:07,097 --> 01:31:08,465 PEOPLE WHO WORK ON MICE 2430 01:31:08,465 --> 01:31:10,634 DON'T DO IS AGE THEIR MICE 2431 01:31:10,634 --> 01:31:12,036 LONG ENOUGH. 2432 01:31:12,036 --> 01:31:13,270 SO EVEN 22 MONTHS IS -- WE 2433 01:31:13,270 --> 01:31:16,307 HAVE MICE THAT WILL KEEP 2434 01:31:16,307 --> 01:31:16,774 GOING. 2435 01:31:16,774 --> 01:31:19,476 SO IT IS STILL CHALLENGING 2436 01:31:19,476 --> 01:31:22,112 TO GENERALIZE TO SUPER I 2437 01:31:22,112 --> 01:31:23,814 THINK AR STUDIES BUT THERE'S 2438 01:31:23,814 --> 01:31:27,151 STILL A LOT OF, I THINK, 2439 01:31:27,151 --> 01:31:28,652 PARALLELLIZATION THAT CAN BE 2440 01:31:28,652 --> 01:31:30,821 INFERRED BETWEEN OUR VERY 2441 01:31:30,821 --> 01:31:33,090 OLDEST MICE, AS LONG AS WE 2442 01:31:33,090 --> 01:31:34,158 AGE THEM OUT LONG ENOUGH AND 2443 01:31:34,158 --> 01:31:35,659 IT WILL BE THE FEMALES THAT 2444 01:31:35,659 --> 01:31:37,695 MAKE IT THAT FAR. 2445 01:31:37,695 --> 01:31:39,496 THE MALE STRAINS OFTEN 2446 01:31:39,496 --> 01:31:40,164 DON'T. 2447 01:31:40,164 --> 01:31:41,432 BUT YEAH, COMPARISONS WITH 2448 01:31:41,432 --> 01:31:43,267 THE SUPER AGER STUDIES, 2449 01:31:43,267 --> 01:31:44,501 PARTICULARLY FOR LIFE 2450 01:31:44,501 --> 01:31:46,704 COURSE, THAT IS INCREDIBLY 2451 01:31:46,704 --> 01:31:49,640 IMPORTANT TO UNDERSTAND WHAT 2452 01:31:49,640 --> 01:31:51,342 EARLIER LIFE IMPACT IS ON 2453 01:31:51,342 --> 01:31:53,077 THAT VERY, VERY LATE LIFE. 2454 01:31:53,077 --> 01:31:55,579 BUT I THINK PEOPLE WHO EVEN 2455 01:31:55,579 --> 01:31:56,747 WORK ON MOUSE MODELS, WE 2456 01:31:56,747 --> 01:31:58,615 NEED TO BE COGNIZANT OF HOW 2457 01:31:58,615 --> 01:31:59,616 OLD WE AGE THEM. 2458 01:31:59,616 --> 01:32:01,385 >> AND ALSO THE IMPORTANCE 2459 01:32:01,385 --> 01:32:04,355 OF GENES, RIGHT, THE 2460 01:32:04,355 --> 01:32:04,755 GENETICS -- 2461 01:32:04,755 --> 01:32:07,091 >> THE GENETICS ARE WHAT THE 2462 01:32:07,091 --> 01:32:08,792 LIFESPAN IS DETERMINED BY 2463 01:32:08,792 --> 01:32:09,159 GENETICS. 2464 01:32:09,159 --> 01:32:10,794 IT IS NOT EVERY STRAIN THAT 2465 01:32:10,794 --> 01:32:12,863 MAKES IT THAT FAR. 2466 01:32:12,863 --> 01:32:14,798 IT IS A SELECT SUBSTRAINS 2467 01:32:14,798 --> 01:32:19,937 THAT LIVE THAT LONG AND THAT 2468 01:32:19,937 --> 01:32:21,305 IS LONGEST DEPENDENT ON 2469 01:32:21,305 --> 01:32:21,705 BACKGROUND. 2470 01:32:21,705 --> 01:32:24,808 SO IF YOU ARE ONLY STUDYING 2471 01:32:24,808 --> 01:32:27,010 A SINGLE STRAIN OF MICE, YOU 2472 01:32:27,010 --> 01:32:28,278 CAN'T STUDY INTERACTION IF 2473 01:32:28,278 --> 01:32:30,414 YOU DON'T HAVE ANYTHING TO 2474 01:32:30,414 --> 01:32:31,248 INTERACT WITH. 2475 01:32:31,248 --> 01:32:35,652 >> AND THE OTHER QUESTION IS 2476 01:32:35,652 --> 01:32:39,823 IN YOUR -- THE TWO PICTURES 2477 01:32:39,823 --> 01:32:45,362 YOU SHOWED OR SLIDES YOU 2478 01:32:45,362 --> 01:32:46,797 SHOWED OF FAT MEASUREMENTS, 2479 01:32:46,797 --> 01:32:51,001 WAS THERE -- IT LOOKED TO ME 2480 01:32:51,001 --> 01:32:52,970 LIKE THE HIPPOCAMPUS IN THE 2481 01:32:52,970 --> 01:32:54,872 HIGH-FAT DIET WAS 2482 01:32:54,872 --> 01:32:55,439 CONSIDERABLY SMALLER. 2483 01:32:55,439 --> 01:32:57,441 IS THAT -- WAS THAT 2484 01:32:57,441 --> 01:32:59,276 ACCIDENTAL OR IS THAT WHAT 2485 01:32:59,276 --> 01:32:59,943 YOU FIND? 2486 01:32:59,943 --> 01:33:05,516 I REALIZE THOSE ARE NOT 2487 01:33:05,516 --> 01:33:08,852 HISITOLOGICAL SECTIONS -- 2488 01:33:08,852 --> 01:33:13,957 >> THEY ARE NOT HYSTOLOGICAL 2489 01:33:13,957 --> 01:33:15,192 BUT I THINK IT WOULD BE FUN 2490 01:33:15,192 --> 01:33:20,497 TO GO BACK AND DO THAT WITH 2491 01:33:20,497 --> 01:33:21,532 MORE ACCURATE HYSTOLOGY. 2492 01:33:21,532 --> 01:33:25,202 THERE IS LACK OF ABUNDANCE 2493 01:33:25,202 --> 01:33:27,871 OF LIPIDS IN THE HIPPOCAMPUS 2494 01:33:27,871 --> 01:33:32,309 SO IT IS NOT A LEAP TO 2495 01:33:32,309 --> 01:33:35,479 BELIEVE THAT IS NOT BRINGING 2496 01:33:35,479 --> 01:33:38,982 A CHANGE IN THE HIPPOCAMPUS. 2497 01:33:38,982 --> 01:33:41,618 AND THE DIFFERENCE IS REALLY 2498 01:33:41,618 --> 01:33:43,454 DIFFERENT IN CA1 BUT CA3 AND 2499 01:33:43,454 --> 01:33:45,956 THE REST IS NOT AS 2500 01:33:45,956 --> 01:33:46,390 DIFFERENT. 2501 01:33:46,390 --> 01:33:48,792 YOU KNOW, WE NOTICED THAT 2502 01:33:48,792 --> 01:33:49,059 TOO. 2503 01:33:49,059 --> 01:33:51,562 SO WHETHER IT IS REAL OR IT 2504 01:33:51,562 --> 01:33:53,597 LOOKS -- BECAUSE THERE IS 2505 01:33:53,597 --> 01:33:55,999 NO -- IT IS CRAZY BUT THERE 2506 01:33:55,999 --> 01:33:57,601 IS NO STRUCTURAL INFORMATION 2507 01:33:57,601 --> 01:33:59,870 IN THAT IMAGE, THAT WAS ALL 2508 01:33:59,870 --> 01:34:06,310 JUST LIPIDS WHICH IS 2509 01:34:06,310 --> 01:34:09,713 STRUCTURE. 2510 01:34:09,713 --> 01:34:10,280 >> THANKS. 2511 01:34:10,280 --> 01:34:11,582 >> ZOEL ALINA WITH THE 2512 01:34:11,582 --> 01:34:12,549 HEALTH INITIATIVE, 2513 01:34:12,549 --> 01:34:15,152 DEFINITELY ON THE SAME PAGE 2514 01:34:15,152 --> 01:34:16,019 CONCERNING LIFE APPROACH. 2515 01:34:16,019 --> 01:34:18,722 THIS QUESTION IS FROM Dr. 2516 01:34:18,722 --> 01:34:20,691 [ AUDIO CUTTING OUT ] 2517 01:34:20,691 --> 01:34:29,166 -- WHATTIZATION ARE 2518 01:34:29,166 --> 01:34:32,135 CONNECTION ARE YOU GIVING TO 2519 01:34:32,135 --> 01:34:35,005 OTHER FACTORS SUCH AS 2520 01:34:35,005 --> 01:34:36,373 LONELINESS, LIFE CHANGE, 2521 01:34:36,373 --> 01:34:36,773 SUPPORT -- 2522 01:34:36,773 --> 01:34:37,508 >> PEOPLE ALWAYS SAY WHAT IS 2523 01:34:37,508 --> 01:34:38,742 THE ONE THING I SHOULD DO 2524 01:34:38,742 --> 01:34:41,144 AND OF COURSE WHAT I USUALLY 2525 01:34:41,144 --> 01:34:42,980 SAY TONGUE IN CHEEK IS, 2526 01:34:42,980 --> 01:34:44,047 WELL, IMPROVE PUBLIC 2527 01:34:44,047 --> 01:34:45,949 EDUCATION IN THIS COUNTRY. 2528 01:34:45,949 --> 01:34:48,785 YOU KNOW, I SAID THE SAME 2529 01:34:48,785 --> 01:34:50,587 THING ABOUT INCOME 2530 01:34:50,587 --> 01:34:51,388 INEQUALITY AND THERE IS ONLY 2531 01:34:51,388 --> 01:34:53,590 SO MANY WAYS I COULD FIX 2532 01:34:53,590 --> 01:34:53,891 THAT. 2533 01:34:53,891 --> 01:34:55,993 SO YOUR POINT IS EXTREMELY 2534 01:34:55,993 --> 01:34:58,829 WELL TAKEN WHICH IS WHY I 2535 01:34:58,829 --> 01:35:01,798 THINK EXPANDING THIS TO, YOU 2536 01:35:01,798 --> 01:35:03,500 KNOW, NOT KAISER, IT MIGHT 2537 01:35:03,500 --> 01:35:05,335 FOR EXAMPLE BE IMPORTANT 2538 01:35:05,335 --> 01:35:06,370 TO -- YOU KNOW, BECAUSE I 2539 01:35:06,370 --> 01:35:08,038 THINK THERE ARE A LOT OF 2540 01:35:08,038 --> 01:35:09,973 RISK FACTORS THAT VARY BY 2541 01:35:09,973 --> 01:35:11,575 INCOME, OF COURSE, AND BY 2542 01:35:11,575 --> 01:35:15,913 REGION AND RACE AND 2543 01:35:15,913 --> 01:35:16,480 ETHNICITY, EMIGRATION 2544 01:35:16,480 --> 01:35:16,813 STATUS. 2545 01:35:16,813 --> 01:35:18,849 SO I THINK IT IS REALLY AN 2546 01:35:18,849 --> 01:35:19,950 OPEN QUESTION AND REALLY 2547 01:35:19,950 --> 01:35:21,218 RICH OPPORTUNITY FOR US TO 2548 01:35:21,218 --> 01:35:24,054 TRY AND DO BETTER IN THIS 2549 01:35:24,054 --> 01:35:26,256 COUNTRY IN TERMS OF, YOU 2550 01:35:26,256 --> 01:35:27,958 KNOW, PUBLIC HEALTH IN 2551 01:35:27,958 --> 01:35:29,359 GENERAL ABOUT SOME OF THESE 2552 01:35:29,359 --> 01:35:31,828 THINGS IN TERMS OF BRAIN 2553 01:35:31,828 --> 01:35:32,462 HEALTH. 2554 01:35:32,462 --> 01:35:38,402 IT IS A HARD -- HARD TO SAY 2555 01:35:38,402 --> 01:35:43,240 OTHER THAN INTRODUCING 2556 01:35:43,240 --> 01:35:45,075 QUALITY IN EDUCATION. 2557 01:35:45,075 --> 01:35:47,177 SOCIAL WAS ONE OF OUR RISK 2558 01:35:47,177 --> 01:35:49,580 FACTORS AND WE WERE ABLE TO 2559 01:35:49,580 --> 01:35:51,415 IMPROVE THAT WHICH WAS TOUGH 2560 01:35:51,415 --> 01:35:54,318 BECAUSE OF COVID SO WE HAVE 2561 01:35:54,318 --> 01:35:57,187 A PAPER THAT SHOWED COVID 2562 01:35:57,187 --> 01:36:01,458 TANKED ALL THE RISK FACTORS, 2563 01:36:01,458 --> 01:36:02,192 THE INTERVENTION GROUP THEY 2564 01:36:02,192 --> 01:36:04,361 COULDN'T ALL GO TO. 2565 01:36:04,361 --> 01:36:05,095 BUT SOCIALIZATION HAS GOT 2566 01:36:05,095 --> 01:36:07,497 TEN A LOT OF PRESS OBVIOUSLY 2567 01:36:07,497 --> 01:36:10,033 BECAUSE OF SOME OF THE 2568 01:36:10,033 --> 01:36:11,935 EMERGING RESEARCH AND THE 2569 01:36:11,935 --> 01:36:12,803 SURGEON GENERAL. 2570 01:36:12,803 --> 01:36:14,237 YOU KNOW, I THINK IT IS 2571 01:36:14,237 --> 01:36:15,172 REALLY INTERESTING AND YOU 2572 01:36:15,172 --> 01:36:16,707 KNOW IT GOES WITH OTHER 2573 01:36:16,707 --> 01:36:18,041 THINGS, TOO. 2574 01:36:18,041 --> 01:36:23,313 SO I THINK THAT 2575 01:36:23,313 --> 01:36:24,214 INTERSECTIONALITY OF 2576 01:36:24,214 --> 01:36:24,848 SOCIALIZIZATION IS REALLY 2577 01:36:24,848 --> 01:36:27,918 IMPORTANT TO LOOK AT. 2578 01:36:27,918 --> 01:36:30,887 >> THANKS A LOT FOR A GREAT 2579 01:36:30,887 --> 01:36:33,023 SESSION AND TO ALL THE 2580 01:36:33,023 --> 01:36:34,591 SPEAKERS. 2581 01:36:34,591 --> 01:36:40,764 I HAVE A QUESTION, KRISTEN, 2582 01:36:40,764 --> 01:36:41,999 REALLY IMPORTANT WORK. 2583 01:36:41,999 --> 01:36:43,767 THE ROLE OF BIOMARKERS WHERE 2584 01:36:43,767 --> 01:36:45,469 PEOPLE MIGHT USE IT FOR 2585 01:36:45,469 --> 01:36:47,471 SCREENING, PEOPLE MIGHT BE 2586 01:36:47,471 --> 01:36:49,940 ACCESSING THEM OR WANTING TO 2587 01:36:49,940 --> 01:36:51,208 ACCESS THEM BECAUSE THEY ARE 2588 01:36:51,208 --> 01:36:53,577 WORRIED ABOUT THEM IN THE 2589 01:36:53,577 --> 01:36:55,512 ABSENCE OF CLEAR CLINICAL 2590 01:36:55,512 --> 01:36:58,115 WORK IN THE DIAGNOSIS OF 2591 01:36:58,115 --> 01:36:58,682 COGNITIVE IMPAIRMENT. 2592 01:36:58,682 --> 01:37:00,217 THAT IS SOMETHING I WORRY 2593 01:37:00,217 --> 01:37:02,452 ABOUT ESPECIALLY BECAUSE I 2594 01:37:02,452 --> 01:37:04,221 HAVE PATIENTS IN MY CLINIC, 2595 01:37:04,221 --> 01:37:07,157 ONE OF WHOM HAS GOT TEN THIS 2596 01:37:07,157 --> 01:37:09,092 TEST AND WORRIED THAT THIS 2597 01:37:09,092 --> 01:37:13,530 IS BASED ON NORMS FROM A ACT 2598 01:37:13,530 --> 01:37:24,041 SUBSTRACT AN ABSTRACT ON 2599 01:37:27,177 --> 01:37:27,511 MEDICATION. 2600 01:37:27,511 --> 01:37:28,912 AND SO COMMENT ON THAT IF 2601 01:37:28,912 --> 01:37:29,579 YOU COULD. 2602 01:37:29,579 --> 01:37:34,317 AND THE SECOND QUESTION I 2603 01:37:34,317 --> 01:37:41,158 HAVE, THE SLEEP DISTURBA 2604 01:37:41,158 --> 01:37:43,260 NCE, EVEN ONE NIGHT, WILL 2605 01:37:43,260 --> 01:37:44,227 CHANGE THAT SIGNAL. 2606 01:37:44,227 --> 01:37:47,330 SO HOW IMPORTANT IS IT TO 2607 01:37:47,330 --> 01:37:48,999 ASCERTAIN HAVE YOU HAD A 2608 01:37:48,999 --> 01:37:51,001 GOOD NIGHT SLEEP OR HAVE YOU 2609 01:37:51,001 --> 01:37:52,602 BEEN SLEEPING THE LAST WEEK 2610 01:37:52,602 --> 01:37:55,172 BEFORE WE GO ON TO INTERPRET 2611 01:37:55,172 --> 01:37:56,506 WHAT THE BIOMARKERS ARE 2612 01:37:56,506 --> 01:37:57,140 TELLING US? 2613 01:37:57,140 --> 01:37:58,975 >> GREAT COMMENTS AND I AM 2614 01:37:58,975 --> 01:38:00,110 COMPLETELY IN AGREEMENT WITH 2615 01:38:00,110 --> 01:38:00,377 YOU. 2616 01:38:00,377 --> 01:38:05,048 YOU HAVE GOT SOME PEOPLE 2617 01:38:05,048 --> 01:38:07,651 COMING IN, SAY I HAVE A 2618 01:38:07,651 --> 01:38:10,887 SPLIT MARKER AND TELL ME IF 2619 01:38:10,887 --> 01:38:12,923 I AM ALZHEIMER'S AND NOT 2620 01:38:12,923 --> 01:38:14,091 UNDERSTANDING THERE IS A 2621 01:38:14,091 --> 01:38:15,025 DIFFERENCE BETWEEN SYMPTOMS 2622 01:38:15,025 --> 01:38:16,293 AND WHAT NOT AND THERE ARE A 2623 01:38:16,293 --> 01:38:18,261 LOT OF PEOPLE WALKING IN WHO 2624 01:38:18,261 --> 01:38:19,996 HAVE HAD THESE TESTS. 2625 01:38:19,996 --> 01:38:21,264 NUMBER ONE, THEY SHOULD NOT 2626 01:38:21,264 --> 01:38:23,366 BE USED FOR SCREENING 2627 01:38:23,366 --> 01:38:24,201 PURPOSES, EVEN INCLUDING 2628 01:38:24,201 --> 01:38:27,270 THOSE WHO MAY HAVE A FAMILY 2629 01:38:27,270 --> 01:38:27,671 HISTORY. 2630 01:38:27,671 --> 01:38:28,405 SECONDLY, THEY REALLY SHOULD 2631 01:38:28,405 --> 01:38:30,307 BE USED IN COMBINATION WITH 2632 01:38:30,307 --> 01:38:32,242 A WORKUP SO IT SHOULDN'T 2633 01:38:32,242 --> 01:38:34,244 EVEN JUST BE A MOCHA AND A 2634 01:38:34,244 --> 01:38:35,846 BLOOD TEST, YOU NEED TO LOOK 2635 01:38:35,846 --> 01:38:37,547 AT OTHER POTENTIAL REASONS 2636 01:38:37,547 --> 01:38:39,282 FOR THE COGNITIVE IMPAIRMENT 2637 01:38:39,282 --> 01:38:43,153 AND WHAT MIGHT BE DRIVING 2638 01:38:43,153 --> 01:38:43,587 THAT. 2639 01:38:43,587 --> 01:38:44,821 FORTUNATELY, THE DIRECT 2640 01:38:44,821 --> 01:38:45,555 CONSUMER TESTS HAVE BEEN 2641 01:38:45,555 --> 01:38:47,224 TAKEN OFF THE MARKET SO 2642 01:38:47,224 --> 01:38:48,425 THANK GOODNESS FOR THAT 2643 01:38:48,425 --> 01:38:49,559 BECAUSE I THINK THAT CAUSED 2644 01:38:49,559 --> 01:38:51,528 A LOT OF PROBLEMS. 2645 01:38:51,528 --> 01:38:53,797 THE OTHER THING THAT IS VERY 2646 01:38:53,797 --> 01:38:55,766 IMPORTANT THAT WE AREN'T 2647 01:38:55,766 --> 01:38:57,467 TALKING ABOUT ENOUGH ARE THE 2648 01:38:57,467 --> 01:39:00,270 ETHICAL AND POLICY 2649 01:39:00,270 --> 01:39:01,738 IMPLICATIONS BECAUSE AS 2650 01:39:01,738 --> 01:39:03,473 THESE FOR CLINICAL PURPOSES, 2651 01:39:03,473 --> 01:39:04,641 RIGHT DRAW -- WE ARE 2652 01:39:04,641 --> 01:39:07,010 STARTING A COUPLE OF PRIMARY 2653 01:39:07,010 --> 01:39:09,412 CARE REAL WORLD COHORT 2654 01:39:09,412 --> 01:39:13,250 STUDIES BUT WE CALL THEM 2655 01:39:13,250 --> 01:39:15,385 RESEARCH EVEN THOUGH THEY 2656 01:39:15,385 --> 01:39:17,020 ARE VERY PRAGMATIC AND WE 2657 01:39:17,020 --> 01:39:18,822 CAN KEEP THE INFORMATION OUT 2658 01:39:18,822 --> 01:39:19,923 OF MEDICAL RECORDS BUT ONCE 2659 01:39:19,923 --> 01:39:23,160 THEY ARE IN THE MEDICAL 2660 01:39:23,160 --> 01:39:25,729 RECORDS, THEY INVOLVE 2661 01:39:25,729 --> 01:39:27,430 LONG-TERM CARE AND OTHER 2662 01:39:27,430 --> 01:39:29,833 ISSUES SO WE NEED TO HAVE 2663 01:39:29,833 --> 01:39:31,434 THAT DISCUSSION WITH THE 2664 01:39:31,434 --> 01:39:33,270 PATIENT TO DISCUSS THOSE AS 2665 01:39:33,270 --> 01:39:33,837 WELL. 2666 01:39:33,837 --> 01:39:35,405 SORRY, I AM OFF TOPIC A 2667 01:39:35,405 --> 01:39:35,806 LITTLE BIT. 2668 01:39:35,806 --> 01:39:39,409 I THINK THEY CAN BE USED 2669 01:39:39,409 --> 01:39:40,043 APPROPRIATELY BUT WITHIN 2670 01:39:40,043 --> 01:39:41,611 LIMITS AND YOU ARE RIGHT, IN 2671 01:39:41,611 --> 01:39:42,879 TERMS OF SLEEP, I HAVEN'T 2672 01:39:42,879 --> 01:39:44,514 SEEN AS MANY STUDIES THAT 2673 01:39:44,514 --> 01:39:51,555 HAVE LOOKED AT SLEEP IN THE 2674 01:39:51,555 --> 01:39:53,557 BLOOD MARKERS, LIKE WITH CFS 2675 01:39:53,557 --> 01:39:55,025 AND I KNOW THERE ARE A 2676 01:39:55,025 --> 01:39:56,293 COUPLE OF STUDIES THAT 2677 01:39:56,293 --> 01:39:57,694 LOOKED AT -- OKAY, YOU ARE 2678 01:39:57,694 --> 01:39:58,662 DOING IT? 2679 01:39:58,662 --> 01:39:59,729 COMING OUT SOON? 2680 01:39:59,729 --> 01:40:01,731 BUT THERE ARE SOME STUDIES 2681 01:40:01,731 --> 01:40:03,567 THAT LOOKED AT DIET AND 2682 01:40:03,567 --> 01:40:05,535 FASTING STATUS AND HAVE SEEN 2683 01:40:05,535 --> 01:40:07,037 SOME EFFECTS THERE AND NOT 2684 01:40:07,037 --> 01:40:08,405 EXACTLY SURE HOW TO TAKE 2685 01:40:08,405 --> 01:40:12,442 THAT TO THE CLINICAL 2686 01:40:12,442 --> 01:40:12,909 INTERPRETATION. 2687 01:40:12,909 --> 01:40:13,810 >> TO FOLLOW UP ON YOUR 2688 01:40:13,810 --> 01:40:15,612 POINT, IT IS SUCH AN 2689 01:40:15,612 --> 01:40:17,113 INTERESTING AREA NOW AND 2690 01:40:17,113 --> 01:40:18,448 WE'RE AHEAD OF OURSELVES. 2691 01:40:18,448 --> 01:40:20,250 CAN YOU SAY MORE ABOUT WHY 2692 01:40:20,250 --> 01:40:22,018 YOU DON'T THINK IT SHOULD BE 2693 01:40:22,018 --> 01:40:23,053 USED FOR SCREENING? 2694 01:40:23,053 --> 01:40:24,087 BECAUSE A LOT OF PEOPLE 2695 01:40:24,087 --> 01:40:26,723 THINK IT MIGHT BE USED FOR 2696 01:40:26,723 --> 01:40:27,624 SCREENING IN THE SENSE THAT 2697 01:40:27,624 --> 01:40:29,960 YOU HAVE SOMEBODY WHO HAS 2698 01:40:29,960 --> 01:40:32,229 COGNITIVE COMPLAINTS, YOU DO 2699 01:40:32,229 --> 01:40:34,030 A MOCHA OR WHATEVER AND SOME 2700 01:40:34,030 --> 01:40:35,098 PEOPLE THINK WELL MAYBE YOU 2701 01:40:35,098 --> 01:40:37,300 DO THAT AND THEN IF IT IS 2702 01:40:37,300 --> 01:40:38,935 POSITIVE, YOU SEND THEM OFF 2703 01:40:38,935 --> 01:40:42,973 TO A SPECIALIST, AND IF NOT, 2704 01:40:42,973 --> 01:40:43,974 YOU ARE REASSURED. 2705 01:40:43,974 --> 01:40:45,175 >> THANKS FOR THAT QUESTION. 2706 01:40:45,175 --> 01:40:48,979 SO WHEN I WAS THINKING ABOUT 2707 01:40:48,979 --> 01:40:52,816 SCREENING, I WAS THINKING 2708 01:40:52,816 --> 01:40:55,418 THESE BLOOD MARKERS FOR THE 2709 01:40:55,418 --> 01:40:57,220 NEXT CHOLESTEROL TEST AS FAR 2710 01:40:57,220 --> 01:40:57,787 AS PREVENTION. 2711 01:40:57,787 --> 01:41:00,257 SO I WAS THINKING MORE IN 2712 01:41:00,257 --> 01:41:04,561 TERMS OF THAT AMONG 2713 01:41:04,561 --> 01:41:05,195 ASYMPTOMATIC INDIVIDUALS. 2714 01:41:05,195 --> 01:41:06,796 AND THERE IS A SURVEY THAT 2715 01:41:06,796 --> 01:41:07,998 HAS GONE OUT, I THINK WE 2716 01:41:07,998 --> 01:41:11,434 WILL BE PRESENTING IT AT 2717 01:41:11,434 --> 01:41:12,802 AAIC PRIMARY CARE PHYSICIANS 2718 01:41:12,802 --> 01:41:14,404 AND A THIRD OF THOSE 2719 01:41:14,404 --> 01:41:15,639 SURVEYED STATED THEY WOULD 2720 01:41:15,639 --> 01:41:18,975 USE THE BLOOD MARKERS FOR 2721 01:41:18,975 --> 01:41:20,243 ASYMPTOMATIC INDIVIDUALS IF 2722 01:41:20,243 --> 01:41:23,780 THEY HAD A FAMILY HISTORY OF 2723 01:41:23,780 --> 01:41:24,881 ALZHEIMER'S AND WERE WORRIED 2724 01:41:24,881 --> 01:41:26,549 ABOUT IT AND IN THOSE CASES, 2725 01:41:26,549 --> 01:41:28,051 IT IS NOT APPROPRIATE 2726 01:41:28,051 --> 01:41:32,956 BECAUSE WE DON'T KNOW WHAT 2727 01:41:32,956 --> 01:41:35,492 THE PROGNOSTIC VALUES OF 2728 01:41:35,492 --> 01:41:37,160 THESE BIOMARKERS ARE. 2729 01:41:37,160 --> 01:41:40,263 SO IF SOMEONE HAS IMPAIRMENT 2730 01:41:40,263 --> 01:41:42,565 AND GET THE TEST, THEN YOU 2731 01:41:42,565 --> 01:41:44,567 UNDERSTAND IT AND THAT IS 2732 01:41:44,567 --> 01:41:45,201 OKAY. 2733 01:41:45,201 --> 01:41:47,604 >> THANKS FOR THE PHENOMENAL 2734 01:41:47,604 --> 01:41:47,971 TALKS. 2735 01:41:47,971 --> 01:41:50,373 BLOWN AWAY THE LAST COUPLE 2736 01:41:50,373 --> 01:41:51,241 OF DAYS. 2737 01:41:51,241 --> 01:41:51,841 FROM THE UNIVERSITY OF 2738 01:41:51,841 --> 01:41:54,511 FLORIDA AND I HAVE TWO QUICK 2739 01:41:54,511 --> 01:42:01,551 QUESTIONS FROM Dr. 2740 01:42:01,551 --> 01:42:04,654 O'CONNELL, I AM ALSO A 2741 01:42:04,654 --> 01:42:06,456 NUTRITIONAL SCIENTIST AND 2742 01:42:06,456 --> 01:42:07,490 GET EXCITED BECAUSE THERE 2743 01:42:07,490 --> 01:42:11,094 ARE NOT MANY OF US. 2744 01:42:11,094 --> 01:42:13,930 SO THE HIGH FAT HIGH SUGAR 2745 01:42:13,930 --> 01:42:17,467 DIET, WHERE WERE THOSE 2746 01:42:17,467 --> 01:42:19,536 NUTRIENTS FROM, WERE THEY 2747 01:42:19,536 --> 01:42:27,277 PLANT BASED, ANIMAL BASED, 2748 01:42:27,277 --> 01:42:28,111 REFINED, NOT REFINED? 2749 01:42:28,111 --> 01:42:30,947 >> IT IS PLANT BASED. 2750 01:42:30,947 --> 01:42:33,950 THE FAT IS SUGAR, PLANT 2751 01:42:33,950 --> 01:42:34,484 BASED. 2752 01:42:34,484 --> 01:42:35,552 >> OKAY, AND MY SECOND 2753 01:42:35,552 --> 01:42:37,721 QUESTION IS GIVEN THE 2754 01:42:37,721 --> 01:42:38,755 GENETIC COMPONENT AND 2755 01:42:38,755 --> 01:42:41,291 GROWING EVIDENCE THAT THE 2756 01:42:41,291 --> 01:42:43,360 DIET AND NUTRIENTS CAN 2757 01:42:43,360 --> 01:42:44,828 INTERACT WITH THE EPIGENOME, 2758 01:42:44,828 --> 01:42:46,796 ARE THERE PLANS TO LOOK AT 2759 01:42:46,796 --> 01:42:48,999 THAT IN THESE MICE AND THEN 2760 01:42:48,999 --> 01:42:51,234 DO YOU THINK KNOWING YOUR 2761 01:42:51,234 --> 01:42:52,102 PROJECT, THAT YOU WOULD 2762 01:42:52,102 --> 01:42:53,570 ACTUALLY SEE SOME OF THIS 2763 01:42:53,570 --> 01:42:56,573 PASSED ON TO THE OFFSPRING 2764 01:42:56,573 --> 01:42:57,574 OF THESE ANIMALS? 2765 01:42:57,574 --> 01:43:00,043 >> I WOULD LOVE TO DO WHAT 2766 01:43:00,043 --> 01:43:02,479 YOU ARE DESCRIBING. 2767 01:43:02,479 --> 01:43:03,380 [LAUGHTER] 2768 01:43:03,380 --> 01:43:06,216 ACTUALLY THE DESIGN OF THE 2769 01:43:06,216 --> 01:43:10,887 BXD PANEL, THE DESIGN OF THE 2770 01:43:10,887 --> 01:43:12,622 F1 BXD PANEL WOULD WORK THE 2771 01:43:12,622 --> 01:43:15,058 BEST IF THE FATHERS WERE 2772 01:43:15,058 --> 01:43:17,160 WHERE THE GENETIC DIVERSITY 2773 01:43:17,160 --> 01:43:18,194 COMES FROM. 2774 01:43:18,194 --> 01:43:19,896 IF WE SWITCHED IT AND PUT 2775 01:43:19,896 --> 01:43:21,297 THE MOTHERS ON DIETS, THAT 2776 01:43:21,297 --> 01:43:22,465 IS AN INTERESTING QUESTION 2777 01:43:22,465 --> 01:43:25,869 IN AND OF ITSELF THAT BRINGS 2778 01:43:25,869 --> 01:43:27,837 IN GENETIC DIVERSITY ON X 2779 01:43:27,837 --> 01:43:29,105 WHICH WE DON'T HAVE. 2780 01:43:29,105 --> 01:43:32,642 IT IS A REALLY IMPORTANT 2781 01:43:32,642 --> 01:43:33,009 QUESTION. 2782 01:43:33,009 --> 01:43:35,779 WE DON'T HAVE PLANS TO DO IT 2783 01:43:35,779 --> 01:43:37,781 IN THE IMMEDIATE TERM, 2784 01:43:37,781 --> 01:43:41,618 LARGELY BECAUSE IT IS SUCH A 2785 01:43:41,618 --> 01:43:43,920 BIG STUDY. 2786 01:43:43,920 --> 01:43:47,257 I WILL JUST BE UPFRONT WITH 2787 01:43:47,257 --> 01:43:49,192 IT, IT IS TOUGH, BUT IT 2788 01:43:49,192 --> 01:43:51,394 SHOULD BE DONE AND VERY 2789 01:43:51,394 --> 01:43:52,762 TRACTABLE IN MICE, IT IS 2790 01:43:52,762 --> 01:43:54,697 EASY TO FOLLOW THEM AND 2791 01:43:54,697 --> 01:43:55,932 INTERVENE AND CONTROL THEIR 2792 01:43:55,932 --> 01:43:56,866 ENVIRONMENT SO SOMEONE 2793 01:43:56,866 --> 01:43:57,801 SHOULD DEFINITELY DO IT AND 2794 01:43:57,801 --> 01:44:02,405 I WOULD LOVE TO HELP AND 2795 01:44:02,405 --> 01:44:04,974 ADVISE ON HOW TO DEVELOP AND 2796 01:44:04,974 --> 01:44:05,842 EXECUTE THAT STUDY. 2797 01:44:05,842 --> 01:44:07,610 >> THEN WE NEED TO CHAT 2798 01:44:07,610 --> 01:44:08,011 MORE. 2799 01:44:08,011 --> 01:44:09,112 >> YEAH. 2800 01:44:09,112 --> 01:44:09,679 [OVERLAPPING SPEAKERS] 2801 01:44:09,679 --> 01:44:10,113 >> THANK YOU. 2802 01:44:10,113 --> 01:44:10,747 >> TO PICK UP ON THE 2803 01:44:10,747 --> 01:44:13,683 DISCUSSION ABOUT THE PLASMA 2804 01:44:13,683 --> 01:44:14,384 BIOMARKERS BECAUSE I THINK 2805 01:44:14,384 --> 01:44:15,752 THIS IS SOME OF THE MOST 2806 01:44:15,752 --> 01:44:16,820 IMPORTANT WORK TO DO BECAUSE 2807 01:44:16,820 --> 01:44:22,125 IT IS THE TIP OF THE SPEAR 2808 01:44:22,125 --> 01:44:22,792 SO TO SPEAK. 2809 01:44:22,792 --> 01:44:24,928 THIS IS NOW SOMETHING THAT 2810 01:44:24,928 --> 01:44:26,830 FOR A LARGE GROUP OF 2811 01:44:26,830 --> 01:44:28,898 INDIVIDUALS HAS A LOT OF 2812 01:44:28,898 --> 01:44:33,703 SIGNAL VALUE SO TO SEE THESE 2813 01:44:33,703 --> 01:44:41,044 OTHER GROUPS THAT DON'T HAVE 2814 01:44:41,044 --> 01:44:44,547 HETEROG ENEITY WITH SIGNAL 2815 01:44:44,547 --> 01:44:46,683 VALUE, I WOULD SURMISE THAT 2816 01:44:46,683 --> 01:44:49,219 MAYBE THE OTHERS DO BUT WE 2817 01:44:49,219 --> 01:44:56,493 DON'T KNOW IT YET. 2818 01:44:56,493 --> 01:45:02,198 SO I GUESS MAYBE I DISAGREE 2819 01:45:02,198 --> 01:45:03,433 ABOUT SCREENING, THINKING 2820 01:45:03,433 --> 01:45:05,668 ABOUT ALL THE CHALLENGES. 2821 01:45:05,668 --> 01:45:07,470 SO DO YOU IMAGINE A WORLD TO 2822 01:45:07,470 --> 01:45:17,947 MAKE THIS A HIGH SIGNAL 2823 01:45:18,882 --> 01:45:19,215 APPTOMASES. 2824 01:45:19,215 --> 01:45:22,752 >> I KNOW RACE IS A SOCIAL 2825 01:45:22,752 --> 01:45:24,821 CONSTRUCT BUT STILL WE 2826 01:45:24,821 --> 01:45:30,760 REALLY NEED TO CONSIDER THE 2827 01:45:30,760 --> 01:45:34,097 GENETIC RELATIONSHIP BETWEEN 2828 01:45:34,097 --> 01:45:35,598 APOE AND ALZHEIMER'S DISEASE 2829 01:45:35,598 --> 01:45:37,333 IS NOT PRESENT IN THE BLACK 2830 01:45:37,333 --> 01:45:38,735 POPULATION SO IT MIGHT BE 2831 01:45:38,735 --> 01:45:40,803 THAT WE REALLY NEED TO -- 2832 01:45:40,803 --> 01:45:43,106 WHAT'S THAT? 2833 01:45:43,106 --> 01:45:44,541 >> WELL, YEAH, DEPENDING ON 2834 01:45:44,541 --> 01:45:44,841 THE -- 2835 01:45:44,841 --> 01:45:45,542 >> THE OPPOSITE, YEAH. 2836 01:45:45,542 --> 01:45:47,110 >> SO QUICK AND COME BACK TO 2837 01:45:47,110 --> 01:45:48,811 THAT, THAT IS ONE THING TO 2838 01:45:48,811 --> 01:45:50,380 WATCH OUT FOR BECAUSE THERE 2839 01:45:50,380 --> 01:45:53,082 ARE CLINICAL TESTS THAT ARE 2840 01:45:53,082 --> 01:45:53,883 DEVELOPING ALGORITHMS AND 2841 01:45:53,883 --> 01:45:58,855 TAKE INTO ACCOUNT A 2842 01:45:58,855 --> 01:46:00,123 GENOTYPE IN THEIR SCORE SO 2843 01:46:00,123 --> 01:46:01,491 WOULD NOT SUGGEST USING 2844 01:46:01,491 --> 01:46:03,660 THOSE IF WE DON'T KNOW HOW 2845 01:46:03,660 --> 01:46:06,095 THEY WORK IN MORE 2846 01:46:06,095 --> 01:46:06,763 HETEROGENOUS POPULATIONS. 2847 01:46:06,763 --> 01:46:07,964 >> BASED ON YOUR QUESTIONS, 2848 01:46:07,964 --> 01:46:10,233 DOWN THE ROAD, YEAH, IDEAL 2849 01:46:10,233 --> 01:46:11,201 SITUATIONS, IT WOULD BE 2850 01:46:11,201 --> 01:46:12,702 GREAT TO HAVE THOSE AS 2851 01:46:12,702 --> 01:46:17,073 MARKERS AND THINK OF THEM AS 2852 01:46:17,073 --> 01:46:17,740 A COLLECTORAL TEST. 2853 01:46:17,740 --> 01:46:18,775 CERTAINLY THERE ARE THINGS 2854 01:46:18,775 --> 01:46:20,376 THAT NEED TO BE DONE BEFORE 2855 01:46:20,376 --> 01:46:20,677 THEN. 2856 01:46:20,677 --> 01:46:23,046 WOULD HE DO NEED TO KNOW HOW 2857 01:46:23,046 --> 01:46:24,714 THEY WORK IN HETEROGENOUS 2858 01:46:24,714 --> 01:46:25,582 POPULATIONS. 2859 01:46:25,582 --> 01:46:27,350 I WAS TALKING TO MY COWORKER 2860 01:46:27,350 --> 01:46:29,953 BEFORE THIS AND IN A LOOK 2861 01:46:29,953 --> 01:46:32,989 AHEAD STUDY WHERE THEY ARE 2862 01:46:32,989 --> 01:46:37,193 TYPE 2 2 DIABETICS AND 2863 01:46:37,193 --> 01:46:43,233 OBESE, WE ARE NOT SEEING 2864 01:46:43,233 --> 01:46:44,500 THESE MARKERS AND IN FACT 2865 01:46:44,500 --> 01:46:45,668 TAKES IT THE OTHER DIRECTION 2866 01:46:45,668 --> 01:46:48,304 SO WE NEED TO LOOK AT WHAT 2867 01:46:48,304 --> 01:46:50,240 IS REALLY GOING ON. 2868 01:46:50,240 --> 01:46:52,242 IT NEEDS TO BE MORE DIVERSE 2869 01:46:52,242 --> 01:46:54,410 TO LOOK AT SOME OF THESE 2870 01:46:54,410 --> 01:46:55,345 OTHER FACTORS BUT I THINK 2871 01:46:55,345 --> 01:46:57,947 THE QUESTION TOO IS THE 2872 01:46:57,947 --> 01:46:58,781 PROGNOSTIC INDIVIDUAL. 2873 01:46:58,781 --> 01:47:00,149 SOME INDIVIDUALS DIE WITH 2874 01:47:00,149 --> 01:47:02,452 THEIR HEADS FULL OF PLAQUES 2875 01:47:02,452 --> 01:47:05,421 AND TANGLES BUT DON'T HAVE 2876 01:47:05,421 --> 01:47:06,556 SYMPTOMS NECESSARILY SO HOW 2877 01:47:06,556 --> 01:47:08,391 DO WE PUT THAT IN THE LIGHT 2878 01:47:08,391 --> 01:47:09,459 AND UNDERSTAND WHAT THAT IS? 2879 01:47:09,459 --> 01:47:11,561 THE SECOND THING IS WE NEED 2880 01:47:11,561 --> 01:47:12,262 EDUCATION, REALLY ON THE 2881 01:47:12,262 --> 01:47:14,397 PART OF THE LAY PUBLIC AND 2882 01:47:14,397 --> 01:47:15,398 HEALTHCARE PROVIDERS AND 2883 01:47:15,398 --> 01:47:16,566 WHAT NOT BECAUSE, YOU KNOW, 2884 01:47:16,566 --> 01:47:19,402 THERE IS THIS IDEA THAT 2885 01:47:19,402 --> 01:47:23,172 ALZHEIMER'S PATHOLOGY IS THE 2886 01:47:23,172 --> 01:47:24,340 SAME AS ALZHEIMER'S DISEASE 2887 01:47:24,340 --> 01:47:25,942 DEMENTIA AND WE NEED TO 2888 01:47:25,942 --> 01:47:29,812 CHANGE THAT DISCUSSION 2889 01:47:29,812 --> 01:47:30,613 PARTICULARLY IN ASYMPTOMATIC 2890 01:47:30,613 --> 01:47:33,016 INDIVIDUALS AS A RISK 2891 01:47:33,016 --> 01:47:34,484 FACTOR, IT IS NOT 2892 01:47:34,484 --> 01:47:36,119 NECESSARILY A DIAGNOSIS OF 2893 01:47:36,119 --> 01:47:37,320 ALZHEIMER'S DISEASE. 2894 01:47:37,320 --> 01:47:39,022 AND THEN -- SORRY, I HAD ONE 2895 01:47:39,022 --> 01:47:42,625 MORE THING BUT NOW I FORGOT. 2896 01:47:42,625 --> 01:47:45,795 BUT YEAH, I DO THINK IT IS 2897 01:47:45,795 --> 01:47:46,095 BOTH. 2898 01:47:46,095 --> 01:47:47,330 SORRY, AND THE LAST THING 2899 01:47:47,330 --> 01:47:49,032 COMES BACK TO ETHICS. 2900 01:47:49,032 --> 01:47:50,566 UNTIL WE HAVE THESE POLICIES 2901 01:47:50,566 --> 01:47:51,701 IN PLACE THAT PROTECT 2902 01:47:51,701 --> 01:47:53,303 PATIENTS, I AM A LITTLE 2903 01:47:53,303 --> 01:47:55,271 BIT -- WELL, NOT JUST A 2904 01:47:55,271 --> 01:47:57,640 LITTLE BIT BUT I AM VERY 2905 01:47:57,640 --> 01:47:58,408 CONCERNED ABOUT 2906 01:47:58,408 --> 01:48:06,316 INCORPORATING THESE BLOOD 2907 01:48:06,316 --> 01:48:07,350 MARKERS AND ASYMPTOMATIC 2908 01:48:07,350 --> 01:48:07,750 INDIVIDUALS. 2909 01:48:07,750 --> 01:48:09,419 IF THEY ARE DISTRESSED NOW 2910 01:48:09,419 --> 01:48:11,321 AND WE HAVE THESE BLOOD 2911 01:48:11,321 --> 01:48:12,288 MARKERS, THEN THEY WILL 2912 01:48:12,288 --> 01:48:14,924 REALLY HAVE A LOT OF 2913 01:48:14,924 --> 01:48:15,291 PROBLEMS. 2914 01:48:15,291 --> 01:48:16,759 >> THANKS FOR THESE 2915 01:48:16,759 --> 01:48:17,260 WONDERFUL TALKS. 2916 01:48:17,260 --> 01:48:21,764 I AM FROM THE UNIVERSITY OF 2917 01:48:21,764 --> 01:48:22,131 MINNESOTA. 2918 01:48:22,131 --> 01:48:23,700 Dr. YAFFE, YOU MENTIONED 2919 01:48:23,700 --> 01:48:25,301 THE CONTROL GROUP WAS COMMON 2920 01:48:25,301 --> 01:48:26,803 IN THE PREVENTION TRIAL BUT 2921 01:48:26,803 --> 01:48:29,806 MAYBE YOU COULD COMMENT ON 2922 01:48:29,806 --> 01:48:31,274 THE HYPOTHESIZED MECHANISMS 2923 01:48:31,274 --> 01:48:34,510 BETWEEN THEM. 2924 01:48:34,510 --> 01:48:40,917 >> MOST PEOPLE THINK THAT 2925 01:48:40,917 --> 01:48:41,984 SOMEHOW A PRACTICE EFFECT 2926 01:48:41,984 --> 01:48:44,020 MAKES SENSE AND BECAUSE OF 2927 01:48:44,020 --> 01:48:45,088 THE EDUCATION, MAYBE IT WAS 2928 01:48:45,088 --> 01:48:46,689 A BIT OF ACTIVE CONTROL, I 2929 01:48:46,689 --> 01:48:47,523 DON'T KNOW. 2930 01:48:47,523 --> 01:48:49,225 WE DID SEE THE DIFFERENCE IN 2931 01:48:49,225 --> 01:48:51,060 TERMS OF RISK FACTOR CHANGE 2932 01:48:51,060 --> 01:48:54,931 BUT IT MAY BE THAT, YOU 2933 01:48:54,931 --> 01:48:57,433 KNOW, THEY -- MOST OF THE 2934 01:48:57,433 --> 01:48:59,068 CONTROL GROUP WAS ACTUALLY 2935 01:48:59,068 --> 01:48:59,535 WORSE. 2936 01:48:59,535 --> 01:49:01,337 AGAIN, SOME OF THAT COULD 2937 01:49:01,337 --> 01:49:03,206 HAVE BEEN COVID AND IT IS A 2938 01:49:03,206 --> 01:49:07,844 LITTLE HARD TO UNTANGLE BUT 2939 01:49:07,844 --> 01:49:09,812 MOST TIMES PEOPLE THINK IT 2940 01:49:09,812 --> 01:49:10,413 IS FACTOR CHANGE. 2941 01:49:10,413 --> 01:49:13,249 I HAVE A LOT OF FRIENDS IN 2942 01:49:13,249 --> 01:49:14,517 PSYCHOLOGY HERE AND THEY CAN 2943 01:49:14,517 --> 01:49:16,252 WEIGH IN BUT I THINK WE SAW 2944 01:49:16,252 --> 01:49:17,887 THAT CERTAINLY IN FINGER AND 2945 01:49:17,887 --> 01:49:22,558 A LOT OF THE MULTIDOMAIN 2946 01:49:22,558 --> 01:49:24,660 TRIALS AND A LOT OF TIMES 2947 01:49:24,660 --> 01:49:32,735 PEOPLE DO GET BETTER. 2948 01:49:32,735 --> 01:49:38,541 >> SHANDRA REYNOLDS FROM 2949 01:49:38,541 --> 01:49:39,442 UNIVERSITY OF COLORADO. 2950 01:49:39,442 --> 01:49:43,946 INTERESTS IN THE BIOMILE BY 2951 01:49:43,946 --> 01:49:46,048 MARKERS AND TRYING TO GET A 2952 01:49:46,048 --> 01:49:46,849 UNDERSTANDING OF THESE 2953 01:49:46,849 --> 01:49:48,651 BIOMARKERS AND PRIOR TO 2954 01:49:48,651 --> 01:49:48,985 MIDLIFE. 2955 01:49:48,985 --> 01:49:50,153 SEEMS TO ME WITH THE 2956 01:49:50,153 --> 01:49:51,921 DISCUSSION OF ETHICS OF 2957 01:49:51,921 --> 01:49:55,191 ROLLOUT, I THINK THERE IS A 2958 01:49:55,191 --> 01:49:55,992 REAL DEARTH OF INFORMATION 2959 01:49:55,992 --> 01:49:59,328 EARLIER IN TERMS OF HOW 2960 01:49:59,328 --> 01:50:00,363 THESE BIOMARKERS MIGHT 2961 01:50:00,363 --> 01:50:01,397 CHANGE AND WHAT 2962 01:50:01,397 --> 01:50:02,198 RECOMMENDATIONS YOU NIGHT 2963 01:50:02,198 --> 01:50:06,836 MAKE -- MIGHT MAKE IN TERMS 2964 01:50:06,836 --> 01:50:08,905 OF TRYING TO PRIORITIZE THAT 2965 01:50:08,905 --> 01:50:19,248 IN THE RESEARCH. 2966 01:50:23,286 --> 01:50:24,921 >> YEAH, SO I THINK THAT IS 2967 01:50:24,921 --> 01:50:25,721 A GOOD QUESTION. 2968 01:50:25,721 --> 01:50:27,890 WE HAVE LOOKED AT THESE 2969 01:50:27,890 --> 01:50:29,959 BIOMARKERS FROM BIRTH ON AND 2970 01:50:29,959 --> 01:50:31,594 SPECIFICALLY AT THE NFL THAT 2971 01:50:31,594 --> 01:50:34,897 HAS A SPECIFIC CUT POINT. 2972 01:50:34,897 --> 01:50:36,699 HOW THAT RELATES TO DISEASE 2973 01:50:36,699 --> 01:50:38,668 POINT AND COGNITIVE AGING I 2974 01:50:38,668 --> 01:50:43,639 DON'T THINK IS FULLY 2975 01:50:43,639 --> 01:50:44,574 UNDERSTOOD. 2976 01:50:44,574 --> 01:50:48,845 WITH P-TAU, IT DECREASED 2977 01:50:48,845 --> 01:50:51,481 WITH AGE, 65 OR 70 BUT ONLY 2978 01:50:51,481 --> 01:50:52,415 INCREASED IN INDIVIDUALS 2979 01:50:52,415 --> 01:50:54,183 THAT WERE AMYLOID POSITIVE. 2980 01:50:54,183 --> 01:50:55,852 SO AGAIN THAT WAS A 2981 01:50:55,852 --> 01:50:58,621 PRIMARILY WHITE COHORT AND 2982 01:50:58,621 --> 01:51:01,023 WE KNOW ADRD PROCESSES START 2983 01:51:01,023 --> 01:51:02,391 EARLIER IN SOME 2984 01:51:02,391 --> 01:51:03,092 UNDER-REPRESENTED MINORITIES 2985 01:51:03,092 --> 01:51:05,962 AND OTHER COHORTS AS WELL. 2986 01:51:05,962 --> 01:51:07,196 SO THERE IS ABSOLUTELY A 2987 01:51:07,196 --> 01:51:10,032 NEED IN SOME OF THE MORE 2988 01:51:10,032 --> 01:51:11,300 DIVERSE COHORTS HOW THESE 2989 01:51:11,300 --> 01:51:13,603 MARKERS CHANGE OVER TIME. 2990 01:51:13,603 --> 01:51:19,475 AND THEN WITH THE MORBIDITY, 2991 01:51:19,475 --> 01:51:20,543 TOO. 2992 01:51:20,543 --> 01:51:22,345 THE EARLY MARKERS, TOO. 2993 01:51:22,345 --> 01:51:24,146 I HAVE A COLLEAGUE WHOSE 2994 01:51:24,146 --> 01:51:27,250 THOUGHT WAS THE PTAU MAY BE 2995 01:51:27,250 --> 01:51:29,752 ELEVATED EARLY IN LIFE, THEN 2996 01:51:29,752 --> 01:51:31,220 DROPS DOWN AND INCREASES 2997 01:51:31,220 --> 01:51:32,622 AGAIN BUT WE HAVEN'T GOT TEN 2998 01:51:32,622 --> 01:51:34,457 A SAMPLE OF THAT TO BE ABLE 2999 01:51:34,457 --> 01:51:36,592 TO LOOK AT THAT ACROSS THE 3000 01:51:36,592 --> 01:51:37,226 LIFESPAN. 3001 01:51:37,226 --> 01:51:37,894 >> CAN YOU COMMENT ABOUT HOW 3002 01:51:37,894 --> 01:51:39,595 MUCH OF THE DATA IS COMING 3003 01:51:39,595 --> 01:51:42,098 FROM A SINGLE SHOT VERSUS 3004 01:51:42,098 --> 01:51:43,165 LONGITUDINAL WORK BECAUSE 3005 01:51:43,165 --> 01:51:44,066 THAT IS WHERE I THINK THERE 3006 01:51:44,066 --> 01:51:46,168 IS A REAL GAP. 3007 01:51:46,168 --> 01:51:47,103 >> I COMPLETELY AGREE WITH 3008 01:51:47,103 --> 01:51:47,436 YOU. 3009 01:51:47,436 --> 01:51:48,804 THE VAST MAJORITY IS STILL 3010 01:51:48,804 --> 01:51:51,541 SINGLE SO WHEN YOU LOOK 3011 01:51:51,541 --> 01:51:52,375 LONGITUDINALLY, IT IS 3012 01:51:52,375 --> 01:51:53,643 BASELINE AND HOW DOES THAT 3013 01:51:53,643 --> 01:51:55,578 CHANGE AND THERE IS STILL 3014 01:51:55,578 --> 01:51:58,214 NOT ENOUGH FOCUSES ON THE 3015 01:51:58,214 --> 01:51:59,015 INDIVIDUAL VARIABILITY 3016 01:51:59,015 --> 01:51:59,949 ACROSS TIME. 3017 01:51:59,949 --> 01:52:01,784 >> OKAY, WE ONLY HAVE TIME 3018 01:52:01,784 --> 01:52:04,420 FOR ONE MORE QUESTION. 3019 01:52:04,420 --> 01:52:07,690 AND THEN HOPEFULLY EVERYBODY 3020 01:52:07,690 --> 01:52:09,859 CAN ASK OTHER QUESTIONS AT 3021 01:52:09,859 --> 01:52:11,227 THE BREAK. 3022 01:52:11,227 --> 01:52:13,162 >> JOHN BRADY WITH A 3023 01:52:13,162 --> 01:52:14,564 RESEARCH FOUNDATION BUT MY 3024 01:52:14,564 --> 01:52:18,200 DAY JOB IS AS A PHYSICIANS. 3025 01:52:18,200 --> 01:52:19,835 I APPRECIATE YOUR LECTURES 3026 01:52:19,835 --> 01:52:21,170 TODAY AND SO MANY QUESTIONS 3027 01:52:21,170 --> 01:52:22,505 INVOLVING ALL OF THESE BUT 3028 01:52:22,505 --> 01:52:25,308 GIVEN THAT YOU ARE FIRST, 3029 01:52:25,308 --> 01:52:27,343 DOCTOR POE, I WAS INTERESTED 3030 01:52:27,343 --> 01:52:29,145 IN YOUR DESCRIPTION OF SEEP 3031 01:52:29,145 --> 01:52:30,913 AND HOW IT IS HEALING. 3032 01:52:30,913 --> 01:52:33,649 MY QUESTION IS GIVEN THAT WE 3033 01:52:33,649 --> 01:52:35,351 ALSO KNOW MEDITATION INDUCES 3034 01:52:35,351 --> 01:52:38,287 SLOW WAVES IN THE BRAIN, CAN 3035 01:52:38,287 --> 01:52:38,955 YOU SUBSTITUTE MEDITATION 3036 01:52:38,955 --> 01:52:40,389 DURING THE DAY FOR A LITTLE 3037 01:52:40,389 --> 01:52:42,258 BIT OF SLEEP AT NIGHT AND 3038 01:52:42,258 --> 01:52:49,532 HAS THAT BEEN SHOWN TO BE 3039 01:52:49,532 --> 01:52:50,299 REPARATIVE AS WELL? 3040 01:52:50,299 --> 01:52:51,667 >> I WOULD SAY I DON'T KNOW 3041 01:52:51,667 --> 01:53:00,276 BECAUSE WE HAVE NEVER 3042 01:53:00,276 --> 01:53:02,011 MEASURED ACETYLCHOLINE WHILE 3043 01:53:02,011 --> 01:53:04,847 WE HAD A RAT MEDITATE. 3044 01:53:04,847 --> 01:53:06,682 IT MIGHT BE THAT IS ENOUGH 3045 01:53:06,682 --> 01:53:17,059 IF IT LOWERS THE 3046 01:53:17,860 --> 01:53:18,561 ACETYLCHOLINE. 3047 01:53:18,561 --> 01:53:20,262 BUT YOU COULD ALSO TEACH 3048 01:53:20,262 --> 01:53:22,465 THEM TO DO BREATHING 3049 01:53:22,465 --> 01:53:23,733 EXERCISES SO AT LEAST GET 3050 01:53:23,733 --> 01:53:26,402 THEM TO DO MEDITATION IN 3051 01:53:26,402 --> 01:53:26,802 THAT SENSE. 3052 01:53:26,802 --> 01:53:27,303 >> THANK YOU. 3053 01:53:27,303 --> 01:53:27,937 >> JUST WANT TO SAY THANK 3054 01:53:27,937 --> 01:53:30,039 YOU TO ALL OF THE SPEAKERS 3055 01:53:30,039 --> 01:53:31,841 FOR THE GREAT TALKS AND THAT 3056 01:53:31,841 --> 01:53:36,112 WILL CLOSE OUR SESSION, 3057 01:53:36,112 --> 01:53:37,513 THANKS. 3058 01:53:37,513 --> 01:53:37,880 [APPLAUSE] 3059 01:53:37,880 --> 01:53:38,314 >> THANK YOU. 3060 01:53:38,314 --> 01:53:40,549 WE HAVE A BRIEF BREAK THIS 3061 01:53:40,549 --> 01:53:42,718 MORNING SO PLEASE BE BACK 3062 01:53:42,718 --> 01:53:48,255 AT, I THINK IT'S 10:30 A.M., 3063 01:53:51,031 --> 01:53:51,965 >> THANK YOU AND WELCOME 3064 01:53:51,965 --> 01:53:53,567 BACK TO OUR FINAL SESSION. 3065 01:53:53,567 --> 01:53:55,335 I SUSPECT SOME PEOPLE WILL 3066 01:53:55,335 --> 01:53:57,037 BE WANDERING IN AS I KICK 3067 01:53:57,037 --> 01:54:00,641 THIS OFF. 3068 01:54:00,641 --> 01:54:03,610 I ALSO WANTED TO -- THE LAST 3069 01:54:03,610 --> 01:54:04,978 SESSION OF THIS SYMPOSIUM 3070 01:54:04,978 --> 01:54:07,481 TODAY, I WANT TO THANK 3071 01:54:07,481 --> 01:54:09,249 MOLLY, JON AND ALSO DAVE FOR 3072 01:54:09,249 --> 01:54:13,320 ORGANIZING THIS AND THE 3073 01:54:13,320 --> 01:54:14,788 McKNIGHT BRAIN RESEARCH 3074 01:54:14,788 --> 01:54:16,156 FOUNDATION FOR BRINGING 3075 01:54:16,156 --> 01:54:17,858 TOGETHER SUCH AN 3076 01:54:17,858 --> 01:54:19,660 EXTRAORDINARY SET OF 3077 01:54:19,660 --> 01:54:20,294 SPEAKERS AND OPPORTUNITY. 3078 01:54:20,294 --> 01:54:22,796 AND I THINK WE HAVE BEEN 3079 01:54:22,796 --> 01:54:24,565 SEEING THIS PUSH SINCE THE 3080 01:54:24,565 --> 01:54:35,108 LAST TIME WE WON ARE SEEING 3081 01:54:42,649 --> 01:54:45,619 THIS EXTRAORDINARY SET OF 3082 01:54:45,619 --> 01:54:47,321 TECHNOLOGY, THE TESTS, HOW 3083 01:54:47,321 --> 01:54:49,089 WE CAN IMPACT THE BRAIN AND 3084 01:54:49,089 --> 01:54:51,792 AGING OF INDIVIDUALS IN THE 3085 01:54:51,792 --> 01:54:53,427 REAL WORLD AND WE HAVEN'T 3086 01:54:53,427 --> 01:54:54,361 DONE ENOUGH. 3087 01:54:54,361 --> 01:54:55,596 THERE HAVE BEEN CHALLENGES 3088 01:54:55,596 --> 01:54:58,665 AND STARTS AND THINGS THAT 3089 01:54:58,665 --> 01:55:00,534 HAVEN'T BEEN GENERALIZED IN 3090 01:55:00,534 --> 01:55:01,802 ACADEMIC SETTINGS SO THIS IS 3091 01:55:01,802 --> 01:55:06,006 ABOUT WHAT WE CAN DO BETTER, 3092 01:55:06,006 --> 01:55:06,807 THE COMPUTATIONAL 3093 01:55:06,807 --> 01:55:08,809 STRATEGIES, NEW STUDIES TO 3094 01:55:08,809 --> 01:55:10,410 GUIDE STUDIES TO BE MORE 3095 01:55:10,410 --> 01:55:12,112 EFFICIENT AND WHAT CAN WE 3096 01:55:12,112 --> 01:55:15,182 LEARN FROM TRIALS THAT ARE 3097 01:55:15,182 --> 01:55:18,452 ONGOING AND JUST COMPLETED 3098 01:55:18,452 --> 01:55:20,287 THAT HAVE HAD SOME 3099 01:55:20,287 --> 01:55:21,655 CHALLENGES AND SUCCESSES AND 3100 01:55:21,655 --> 01:55:24,391 HOW WE CAN DO BETTER SO WITH 3101 01:55:24,391 --> 01:55:29,196 THIS, I WILL CO-CHAIR WITH 3102 01:55:29,196 --> 01:55:31,732 RANDY BUCKNER AND MICHAEL 3103 01:55:31,732 --> 01:55:35,569 YASSA AND KICK IT OFF WITH 3104 01:55:35,569 --> 01:55:40,941 THE FIRST SPEAKER, 3105 01:55:40,941 --> 01:55:42,175 ANNE TRELOS HAVE UNIVERSITY 3106 01:55:42,175 --> 01:55:44,144 OF MICHIGAN ON MACHINE 3107 01:55:44,144 --> 01:55:47,781 LEARNING FOR ADAPTIVE 3108 01:55:47,781 --> 01:55:48,815 EXPERIMENTAL DESIGNS. 3109 01:55:48,815 --> 01:55:51,084 >> THANK YOU FOR HAVING ME 3110 01:55:51,084 --> 01:55:54,154 TODAY AND HELPING ME LEARN A 3111 01:55:54,154 --> 01:55:59,526 LOT MORE ABOUT THE 3112 01:55:59,526 --> 01:56:07,634 NEUROSTUDY AND I AM AN 3113 01:56:07,634 --> 01:56:09,569 ASSISTANT PROFESSOR AND JUST 3114 01:56:09,569 --> 01:56:11,405 RECENTLY GOT INTO AGING IN 3115 01:56:11,405 --> 01:56:19,379 THE LAST SIX MONTHS AGO AS I 3116 01:56:19,379 --> 01:56:29,923 MET KATHERINE KACZOWLOWSKI. 3117 01:56:31,892 --> 01:56:33,760 SO HIGH TALK WILL BE ON 3118 01:56:33,760 --> 01:56:38,665 MACHINE LEARNING FOR 3119 01:56:38,665 --> 01:56:39,466 ADAPTIVE EXPERIMENTAL 3120 01:56:39,466 --> 01:56:39,800 DESIGNS. 3121 01:56:39,800 --> 01:56:41,501 SO I PUT THREE CATEGORIES OR 3122 01:56:41,501 --> 01:56:43,103 EXAMPLES ON THE SLIDE HERE. 3123 01:56:43,103 --> 01:56:45,072 SO TENS OF THOUSANDS, 3124 01:56:45,072 --> 01:56:48,175 MILLIONS OF NEURONS YOU CAN 3125 01:56:48,175 --> 01:56:49,309 RECORD SIMULTANEOUSLY IN THE 3126 01:56:49,309 --> 01:56:55,248 BRAINS OF LIVING ANIMALS, 3127 01:56:55,248 --> 01:56:56,717 SPATIAL TEMPORAL MEASURES 3128 01:56:56,717 --> 01:57:04,024 AND THEN MOVING TOWARDS MORE 3129 01:57:04,024 --> 01:57:04,758 NATURALISTIC STIMULI OF 3130 01:57:04,758 --> 01:57:06,093 ENVIRONMENTS TO THE 3131 01:57:06,093 --> 01:57:06,493 INDIVIDUAL. 3132 01:57:06,493 --> 01:57:08,161 AND YOU SEE WE HAVE THIS 3133 01:57:08,161 --> 01:57:09,997 TRUE WEALTH OF DATA AND WHEN 3134 01:57:09,997 --> 01:57:11,865 WE ADD A TIME VARIABLE TO 3135 01:57:11,865 --> 01:57:14,668 ALL OF THIS TO STUDY THINGS 3136 01:57:14,668 --> 01:57:18,538 LIKE AGING, YOU INCREASE THE 3137 01:57:18,538 --> 01:57:19,740 DIMENSIONALITY OF YOUR DATA. 3138 01:57:19,740 --> 01:57:22,209 SO WE WOULD LIKE TO FIRST 3139 01:57:22,209 --> 01:57:23,443 MAKE CLAIMS HOW THESE 3140 01:57:23,443 --> 01:57:26,713 THOUSANDS OF NEURONS ARE 3141 01:57:26,713 --> 01:57:31,218 ACTING TOGETHER WITH COMPLEX 3142 01:57:31,218 --> 01:57:32,886 STIMULI THAT MIGHT GUIDE 3143 01:57:32,886 --> 01:57:34,855 BEHAVIOR IN THE BRAIN OF THE 3144 01:57:34,855 --> 01:57:35,255 INDIVIDUAL. 3145 01:57:35,255 --> 01:57:39,893 BUT THE TIME WE HAVE TO DO 3146 01:57:39,893 --> 01:57:49,736 EXPERIMENTS CAUSALLY TESTING 3147 01:57:49,736 --> 01:57:51,071 HYPOTHESES ALL ARE THE SAME 3148 01:57:51,071 --> 01:57:55,308 BECAUSE WE ONLY HAVE 24 3149 01:57:55,308 --> 01:57:56,176 HOURS A DAY. 3150 01:57:56,176 --> 01:57:58,612 HOW DO WE CHOOSE IN THE 3151 01:57:58,612 --> 01:58:00,981 IDEAS WE HAVE SCALING IN 3152 01:58:00,981 --> 01:58:02,916 EXPERIMENTS IN HIGH 3153 01:58:02,916 --> 01:58:07,220 DIMENSIONAL SPACES IS TO USE 3154 01:58:07,220 --> 01:58:07,954 ADAPTIVE ENVIRONMENT 3155 01:58:07,954 --> 01:58:08,355 DESIGNS. 3156 01:58:08,355 --> 01:58:11,658 IF YOU HAVE PLAYED ONE OF 3157 01:58:11,658 --> 01:58:14,027 THESE GAMES SHOWN ON THE 3158 01:58:14,027 --> 01:58:15,529 SLIDE, YOU HAVE SHOWN THE 3159 01:58:15,529 --> 01:58:18,131 ABILITY TO DO SO. 3160 01:58:18,131 --> 01:58:27,040 SO THE FIRST ONE, I THINK OF 3161 01:58:27,040 --> 01:58:31,244 A OBJECT AND THEN YOU ASK 3162 01:58:31,244 --> 01:58:32,412 QUESTIONS TO TRY TO FIGURE 3163 01:58:32,412 --> 01:58:33,914 OUT WHAT THAT IS. 3164 01:58:33,914 --> 01:58:37,017 IF I CHOOSE A DUCK, IS IT A 3165 01:58:37,017 --> 01:58:40,787 HORSE, SO ON, SO YOU PICK 3166 01:58:40,787 --> 01:58:41,822 THE NEXT QUESTION. 3167 01:58:41,822 --> 01:58:43,623 BUT WHAT IF I ASK YOU TO 3168 01:58:43,623 --> 01:58:46,026 POSE YOUR QUESTIONS IN 3169 01:58:46,026 --> 01:58:47,427 ADVANCE, WRITE THEM DOWN AND 3170 01:58:47,427 --> 01:58:49,696 HAND THEM TO ME? 3171 01:58:49,696 --> 01:58:50,831 YOU WOULD PROBABLY KNOW I 3172 01:58:50,831 --> 01:58:52,666 WAS THINKING OF A DUCK BUT 3173 01:58:52,666 --> 01:58:55,836 ONLY IF YOU KNEW A SMALLER 3174 01:58:55,836 --> 01:58:56,870 SUBSET OF WHAT I WAS 3175 01:58:56,870 --> 01:58:57,904 THINKING AHEAD OF TIME. 3176 01:58:57,904 --> 01:58:59,773 AND THE REASON THIS IS VERY 3177 01:58:59,773 --> 01:59:01,041 WITTABLE FOR YOU IS YOU ARE 3178 01:59:01,041 --> 01:59:02,309 ABLE TO LEVERAGE 3179 01:59:02,309 --> 01:59:04,010 INFORMATION, DATA AS IT IS 3180 01:59:04,010 --> 01:59:05,612 BEING ACQUIRED WHICH ALLOWS 3181 01:59:05,612 --> 01:59:06,880 YOU TO GUIDE SELECTION OF 3182 01:59:06,880 --> 01:59:11,852 THE NEXT BEST QUESTION TO 3183 01:59:11,852 --> 01:59:16,423 ASK AND SO WHAT I AM GOING 3184 01:59:16,423 --> 01:59:19,626 TO SHOW YOU IS ADAPTING THE 3185 01:59:19,626 --> 01:59:22,028 MACHINE MODEL AND HOW IT CAN 3186 01:59:22,028 --> 01:59:26,900 BE PARTICULAR TO MANY 3187 01:59:26,900 --> 01:59:33,106 NEUROMICE IN THE STUD DE. 3188 01:59:33,106 --> 01:59:36,543 SO FIRST I WILL TALK ABOUT 3189 01:59:36,543 --> 01:59:38,278 ITIVE MEASURES AND THEY HAVE 3190 01:59:38,278 --> 01:59:43,049 ABILITY TO WORK WITH DIVERSE 3191 01:59:43,049 --> 01:59:45,218 FRAME SETS. 3192 01:59:45,218 --> 01:59:48,288 THEY NEED THAT DIVERSITY TO 3193 01:59:48,288 --> 01:59:50,357 GET THE CROSS SET ACROSS THE 3194 01:59:50,357 --> 01:59:50,757 POPULATION. 3195 01:59:50,757 --> 01:59:53,693 AND IT ALLOWS US TO TUNE 3196 01:59:53,693 --> 01:59:55,629 MODELS TO SPECIFIC 3197 01:59:55,629 --> 01:59:56,263 INDIVIDUALS, PERSONALIZE 3198 01:59:56,263 --> 01:59:59,366 THEM AND I WILL TALK ABOUT 3199 01:59:59,366 --> 02:00:00,700 SOME METHODS THAT ALLOW US 3200 02:00:00,700 --> 02:00:01,968 TO DO THAT. 3201 02:00:01,968 --> 02:00:04,471 SECONDLY, THESE KIND OF 3202 02:00:04,471 --> 02:00:06,406 MODELS ALLOW US TO 3203 02:00:06,406 --> 02:00:07,641 IMMEDIATELY LEARN FROM 3204 02:00:07,641 --> 02:00:08,308 INTERVENTION RESULTS, WHICH 3205 02:00:08,308 --> 02:00:12,546 IS THE GAME OF 20 SECONDS, 3206 02:00:12,546 --> 02:00:14,181 SO ADAPTING THE STRATEGY CAN 3207 02:00:14,181 --> 02:00:16,249 ALLOW US TO BE MORE 3208 02:00:16,249 --> 02:00:17,050 EFFICIENT IN OBTAINING 3209 02:00:17,050 --> 02:00:19,186 SOMETHING OF INTEREST AS 3210 02:00:19,186 --> 02:00:21,388 WELL AS DESIGNING SOME 3211 02:00:21,388 --> 02:00:22,622 OPTIMAL ALLOCATION OF TESTS 3212 02:00:22,622 --> 02:00:24,391 WHEN YOU HAVE A LIMITED 3213 02:00:24,391 --> 02:00:25,759 NUMBER OF THEM. 3214 02:00:25,759 --> 02:00:32,165 AND THEN WE WILL TALK ABOUT 3215 02:00:32,165 --> 02:00:32,599 MALADAPTATION. 3216 02:00:32,599 --> 02:00:34,467 SO ONE KIND OF VARIATION WE 3217 02:00:34,467 --> 02:00:36,670 MIGHT WANT TO THINK ABOUT 3218 02:00:36,670 --> 02:00:38,939 INCLUDING IS IN MODELS OF 3219 02:00:38,939 --> 02:00:39,372 NEURODYNAMICS. 3220 02:00:39,372 --> 02:00:42,242 SO FIRST WE WANT TO DISCOVER 3221 02:00:42,242 --> 02:00:44,277 NEW PATTERNS OF NOURISH 3222 02:00:44,277 --> 02:00:49,249 ACTIVITY THROUGH TIME SO 3223 02:00:49,249 --> 02:00:51,117 IDENTIFY LATENT ITEMS IN OUR 3224 02:00:51,117 --> 02:00:55,755 DATA AS WE DEPLOY THE DATA. 3225 02:00:55,755 --> 02:00:58,191 SO WE MIGHT SEE BENEATH THE 3226 02:00:58,191 --> 02:01:02,662 ORANGE CIRCLE THERE IS A 3227 02:01:02,662 --> 02:01:05,398 CURVED GRAY TRAJECTORY, SOME 3228 02:01:05,398 --> 02:01:07,234 REPEATED PATTERN YOUR BRAIN 3229 02:01:07,234 --> 02:01:09,736 CAN RECOGNIZE BUT THERE IS 3230 02:01:09,736 --> 02:01:10,770 SOME VARIATION THERE. 3231 02:01:10,770 --> 02:01:12,138 RATHER THAN SEEING EACH OF 3232 02:01:12,138 --> 02:01:13,773 THESE CURVES AS A NEW 3233 02:01:13,773 --> 02:01:15,775 PATTERN OR FEATURE, WE 3234 02:01:15,775 --> 02:01:17,410 INSTEAD TO WANT CHARACTERIZE 3235 02:01:17,410 --> 02:01:19,112 THEM AS SOME SINGLE FEATURE 3236 02:01:19,112 --> 02:01:20,513 WITH VARIATION AROUND A 3237 02:01:20,513 --> 02:01:25,051 MEANS SO WE DEVELOPED A 3238 02:01:25,051 --> 02:01:26,653 MODEL INDIVIDUALIZED IN 3239 02:01:26,653 --> 02:01:31,024 MORNING THAT USE A GASEOUS 3240 02:01:31,024 --> 02:01:33,727 MIXTURE IN MARKUP MODELS AND 3241 02:01:33,727 --> 02:01:34,794 CAPTURES VARIATION. 3242 02:01:34,794 --> 02:01:36,096 SO WE ULTIMATELY STAY 3243 02:01:36,096 --> 02:01:37,097 FLEXIBLE TO THE 3244 02:01:37,097 --> 02:01:38,031 IDENTIFICATION OF NEW 3245 02:01:38,031 --> 02:01:40,100 PATTERNS AS TIME GOES ON. 3246 02:01:40,100 --> 02:01:43,837 AND SO HERE ARE SOME VIDEOS 3247 02:01:43,837 --> 02:01:46,139 OF DYNAMICS THAT THE SAME 3248 02:01:46,139 --> 02:01:48,908 ALGORITHM IS ABLE TO QUICKLY 3249 02:01:48,908 --> 02:01:51,244 LEARN HOW TO MODEL, TUNE FOR 3250 02:01:51,244 --> 02:01:51,845 A GIVEN INDIVIDUAL. 3251 02:01:51,845 --> 02:01:55,181 YOU CAN SEE WE'RE LOOKING AT 3252 02:01:55,181 --> 02:01:56,449 DATASETS, THE TOP FROM A CAT 3253 02:01:56,449 --> 02:01:58,718 AND THE BOTTOM FROM A MOUSE 3254 02:01:58,718 --> 02:02:01,388 AND IT IS THE SAME ALGORITHM 3255 02:02:01,388 --> 02:02:05,825 APPLIED TO EACH OF THESE 3256 02:02:05,825 --> 02:02:06,626 DATASETS. 3257 02:02:06,626 --> 02:02:08,461 SO CHANGING THE MODEL CAN 3258 02:02:08,461 --> 02:02:09,796 ALLOW US TO SEE NEW 3259 02:02:09,796 --> 02:02:11,197 INTERESTS AND WE HAVE SEEN 3260 02:02:11,197 --> 02:02:12,799 THIS THROUGHOUT THE SUMMIT 3261 02:02:12,799 --> 02:02:14,634 OF FINDING NEW LATE TEN 3262 02:02:14,634 --> 02:02:15,435 FEATURES. 3263 02:02:15,435 --> 02:02:18,805 BUT WHAT YOU CAN ALSO DO IS 3264 02:02:18,805 --> 02:02:20,640 USE MACHINE LEARNING DURING 3265 02:02:20,640 --> 02:02:22,175 THE ACQUISITION PROCESS AND 3266 02:02:22,175 --> 02:02:23,243 IDENTIFY WHICH QUANTITIES OF 3267 02:02:23,243 --> 02:02:25,178 INTEREST WE SHOULD BE PAYING 3268 02:02:25,178 --> 02:02:27,047 THE MOST ATTENTION TO AND 3269 02:02:27,047 --> 02:02:28,348 NOMINATE FOR FUTURE STUDIES. 3270 02:02:28,348 --> 02:02:31,384 SO HERE I AM USING DATA FROM 3271 02:02:31,384 --> 02:02:34,087 THE PUBLICATION ON THE TOP 3272 02:02:34,087 --> 02:02:36,389 RIGHT THAT LOOKS AT 3273 02:02:36,389 --> 02:02:37,424 IDENTIFYING WHICH BEHAVIORAL 3274 02:02:37,424 --> 02:02:39,259 FEATURES FROM THIS VIDEO OF 3275 02:02:39,259 --> 02:02:42,429 A MOUSE ARE FEATURES OF 3276 02:02:42,429 --> 02:02:43,496 ONGOING NEUROACTIVITY. 3277 02:02:43,496 --> 02:02:47,801 SO RATHER THAN LOOKING AT 3278 02:02:47,801 --> 02:02:51,938 PREDEFINING FEATURES OF THE 3279 02:02:51,938 --> 02:02:54,808 MOUSE, LIKE PUPIL SIZE, THEY 3280 02:02:54,808 --> 02:02:57,711 FIND INFORMATION ACROSS THE 3281 02:02:57,711 --> 02:03:01,047 CHEEK THAT ARE MORE 3282 02:03:01,047 --> 02:03:04,084 PREDICTIVE OF NEURAL 3283 02:03:04,084 --> 02:03:06,519 ACTIVITY SO IT IS NOT 3284 02:03:06,519 --> 02:03:09,556 LOOKING AT IT ALL AT ONCE 3285 02:03:09,556 --> 02:03:11,725 AND HERE YOU HAVE A 3286 02:03:11,725 --> 02:03:14,361 STREAMING FORM THAT SHOWS 3287 02:03:14,361 --> 02:03:15,762 VERY SIMILAR RESULTS IN ONLY 3288 02:03:15,762 --> 02:03:17,263 A MINUTE OR TWO OF DATA. 3289 02:03:17,263 --> 02:03:20,333 SO IF YOU LOOK AT THE BOTTOM 3290 02:03:20,333 --> 02:03:23,870 RIGHT, YOU SEE THE CON V 3291 02:03:23,870 --> 02:03:26,005 DEFENSE IN ABOUT 60 SECONDS 3292 02:03:26,005 --> 02:03:28,174 SO WE'RE ABLE TO IDENTIFY 3293 02:03:28,174 --> 02:03:29,676 THE SAME RELEVANT FEATURES 3294 02:03:29,676 --> 02:03:31,511 THAT MIGHT HAVE OTHER DEVICE 3295 02:03:31,511 --> 02:03:34,013 BE ACQUIRED, TO GO POSTDATE 3296 02:03:34,013 --> 02:03:36,416 TO AND THEN A POST TALK 3297 02:03:36,416 --> 02:03:36,783 ANALYSIS. 3298 02:03:36,783 --> 02:03:38,585 SO STARTING FROM SCRATCH, WE 3299 02:03:38,585 --> 02:03:42,021 CAN LOOK AT THESE ONGOING 3300 02:03:42,021 --> 02:03:44,290 DATASETS, NEW INFORMATION IN 3301 02:03:44,290 --> 02:03:46,860 THE MODEL AND SAY YOU SHOULD 3302 02:03:46,860 --> 02:03:48,161 INTERVENE ON THESE. 3303 02:03:48,161 --> 02:03:50,230 AND IT MAY BE DIFFERENT FOR 3304 02:03:50,230 --> 02:03:51,398 EACH INDIVIDUAL BUT TUNING 3305 02:03:51,398 --> 02:03:54,667 IT TO THE INDIVIDUAL IS VERY 3306 02:03:54,667 --> 02:03:55,034 POSSIBLE. 3307 02:03:55,034 --> 02:03:56,970 SO WHEN I TALK ABOUT HOW WE 3308 02:03:56,970 --> 02:03:59,406 CAN USE THESE KIND OF MODELS 3309 02:03:59,406 --> 02:04:01,241 THAT UPDATE THEMSELVES IN 3310 02:04:01,241 --> 02:04:03,076 RESPONSE TO NEW DATA TO HELP 3311 02:04:03,076 --> 02:04:06,045 GUIDE OUR CHOICE OF WHAT AND 3312 02:04:06,045 --> 02:04:07,747 WHERE TO MEASURE, WHAT WHAT 3313 02:04:07,747 --> 02:04:11,851 KIND OF NEW DATA IS BEST TO 3314 02:04:11,851 --> 02:04:19,359 COLLECT, AND THIS IS WORK I 3315 02:04:19,359 --> 02:04:21,327 DID AT UNIVERSITY -- 3316 02:04:21,327 --> 02:04:22,095 [INDISCERNIBLE] 3317 02:04:22,095 --> 02:04:24,664 AND HER LAB USES MODELS OF 3318 02:04:24,664 --> 02:04:25,031 ZEBRAFISH. 3319 02:04:25,031 --> 02:04:26,833 SO WE WANT TO ASK THE 3320 02:04:26,833 --> 02:04:29,969 QUESTION HOW DO WE CHOOSE 3321 02:04:29,969 --> 02:04:33,406 WHAT IS RELEVANT TO THE 3322 02:04:33,406 --> 02:04:34,174 POPULATION. 3323 02:04:34,174 --> 02:04:37,510 SO IF YOU LOOK AT THE FIGURE 3324 02:04:37,510 --> 02:04:40,547 ON THE LEFT, THIS IS A 3325 02:04:40,547 --> 02:04:43,817 MOVING RESOLUTION AT 3326 02:04:43,817 --> 02:04:44,217 45 DEGREES. 3327 02:04:44,217 --> 02:04:47,120 IT HAS NEURAL FIRING RATES, 3328 02:04:47,120 --> 02:04:48,054 EIGHT DIFFERENT DIRECTIONS 3329 02:04:48,054 --> 02:04:48,555 OF MOTION. 3330 02:04:48,555 --> 02:04:51,858 IF WE HAD LOTS OF TIME, WE 3331 02:04:51,858 --> 02:04:53,259 COULD MEASURE THIS AT 3332 02:04:53,259 --> 02:04:54,060 15-DEGREE RESOLUTION AND 3333 02:04:54,060 --> 02:04:56,429 WHAT YOU FIND IS A NEURON 3334 02:04:56,429 --> 02:04:58,131 WHO MIGHT HAVE BEEN 3335 02:04:58,131 --> 02:05:00,066 IDENTIFIED AS SELECTIVE TO 3336 02:05:00,066 --> 02:05:10,109 THAT RIGHT MOTION IS IN FACT 3337 02:05:10,109 --> 02:05:12,045 BIMODALLY STIMULATED SO LEFT 3338 02:05:12,045 --> 02:05:13,646 EYE AND RIGHT EYE AND THIS 3339 02:05:13,646 --> 02:05:15,515 GIVES YOU A BETTER PICTURE 3340 02:05:15,515 --> 02:05:18,351 OF THE NEURAL CIRCUITS AND 3341 02:05:18,351 --> 02:05:18,885 UNDERLYING FACTORS. 3342 02:05:18,885 --> 02:05:22,956 BUT THEN WHEN WE TRY TO THIS 3343 02:05:22,956 --> 02:05:24,791 IN HIGHER DIMENSIONAL SPACE, 3344 02:05:24,791 --> 02:05:26,326 EVEN TWO DIMENSIONS, THAT 3345 02:05:26,326 --> 02:05:28,962 LEAVES US WITH A PROBLEM. 3346 02:05:28,962 --> 02:05:31,130 NOW WE HAVE 600 STIMULI TO 3347 02:05:31,130 --> 02:05:32,499 PRESENT TO THOSE FISH. 3348 02:05:32,499 --> 02:05:35,001 NOW YOU ARE TALKING TENS OF 3349 02:05:35,001 --> 02:05:36,503 THOUSANDS OF THINGS YOU 3350 02:05:36,503 --> 02:05:38,538 MIGHT NEED TO MEASURE SO 3351 02:05:38,538 --> 02:05:40,006 THIS IS CLEARLY INFEASIBLE. 3352 02:05:40,006 --> 02:05:42,008 SO WHAT WE WILL DO INSTEAD 3353 02:05:42,008 --> 02:05:43,743 IS USE AN ONLINE 3354 02:05:43,743 --> 02:05:44,410 OPTIMIZATION APPROACH. 3355 02:05:44,410 --> 02:05:46,846 SO HERE BOTTOM LEFT, WE WILL 3356 02:05:46,846 --> 02:05:48,781 BE USING THE IMAGING TO GIVE 3357 02:05:48,781 --> 02:05:50,283 US THIS NEURAL ACTIVITY. 3358 02:05:50,283 --> 02:05:52,619 WE WILL START BY SHOWING A 3359 02:05:52,619 --> 02:05:53,553 PARTICULAR STIMULUS AND 3360 02:05:53,553 --> 02:05:55,054 OBSERVING THE NEURAL 3361 02:05:55,054 --> 02:05:55,421 RESPONSE. 3362 02:05:55,421 --> 02:05:59,459 WE INCORPORATE THIS INTO A 3363 02:05:59,459 --> 02:06:03,096 MODEL USING DASH AND 3364 02:06:03,096 --> 02:06:04,464 PROCESSES TO THE CURVE AND 3365 02:06:04,464 --> 02:06:07,500 THERE YOU SEE THE HEAT MAP. 3366 02:06:07,500 --> 02:06:10,770 THEN YOU GET A LOOK AT THE 3367 02:06:10,770 --> 02:06:11,437 UNCERTAINTY OF PREDICTIONS 3368 02:06:11,437 --> 02:06:21,347 AND THIS IS HOW WE USE WHAT 3369 02:06:21,347 --> 02:06:22,315 TO MAXIMIZE NEXT. 3370 02:06:22,315 --> 02:06:24,717 AND SO AS WE BASICALLY 3371 02:06:24,717 --> 02:06:27,453 CHOOSE THE NEXT SELECTION, 3372 02:06:27,453 --> 02:06:29,455 WE OBSERVE A NEW DATA POINT 3373 02:06:29,455 --> 02:06:31,824 AND ITERATE TILL WE HAVE A 3374 02:06:31,824 --> 02:06:32,859 PARTICULAR CONFIDENCE LEVEL 3375 02:06:32,859 --> 02:06:33,960 THAT THE MODEL HAS REACHED. 3376 02:06:33,960 --> 02:06:35,695 SO THIS IS JUST A QUICK 3377 02:06:35,695 --> 02:06:37,163 VIDEO OF THIS HAPPENING. 3378 02:06:37,163 --> 02:06:39,332 YOU CAN SEE NEURAL 3379 02:06:39,332 --> 02:06:41,067 RESPONSES, TUNING CURVE, 3380 02:06:41,067 --> 02:06:41,901 ESTIMATE GETTING REFINED IN 3381 02:06:41,901 --> 02:06:43,603 THE CENTER AND THEN 3382 02:06:43,603 --> 02:06:45,738 UNCERTAINTY ON THE FAR RIGHT 3383 02:06:45,738 --> 02:06:47,540 GOING TO BLACK WHICH IS 3384 02:06:47,540 --> 02:06:48,975 GOING DOWN. 3385 02:06:48,975 --> 02:06:51,010 SO WITH UNCERTAINTY, IT GOES 3386 02:06:51,010 --> 02:06:53,179 DOWN AND THIS IS WHAT ALLOWS 3387 02:06:53,179 --> 02:06:55,381 US TO KNOW WHEN WE CAN STOP 3388 02:06:55,381 --> 02:06:57,417 MEASURING AND GO ON TO THE 3389 02:06:57,417 --> 02:06:59,319 NEXT NEURON. 3390 02:06:59,319 --> 02:07:01,354 WITH UNCERTAINTIES IN MANY 3391 02:07:01,354 --> 02:07:05,625 OF THESE MODELS WE CAN 3392 02:07:05,625 --> 02:07:08,494 DEPLOY EARLY STOPPING AND 3393 02:07:08,494 --> 02:07:11,631 APPLY WHAT WE LEARNED TO 3394 02:07:11,631 --> 02:07:12,065 STRATEGIES. 3395 02:07:12,065 --> 02:07:13,733 SO WHAT MIGHT TAKE AN HOUR 3396 02:07:13,733 --> 02:07:15,335 TAKES ONLY THREE TO FIVE 3397 02:07:15,335 --> 02:07:17,070 MINUTES AND AGAIN THESE 3398 02:07:17,070 --> 02:07:18,304 METHODS CAN ADAPT THEMSELVES 3399 02:07:18,304 --> 02:07:19,472 TO A PARTICULAR INDIVIDUAL 3400 02:07:19,472 --> 02:07:22,108 OR IN THIS CASE BRAIN AREA 3401 02:07:22,108 --> 02:07:24,177 AUTOMATICALLY. 3402 02:07:24,177 --> 02:07:34,654 SO HERE WE SEE THIS IS A 3403 02:07:34,654 --> 02:07:35,588 NEURAL POPULATION MAP AND 3404 02:07:35,588 --> 02:07:39,892 YOU CAN SEE IT IS CHOOSING 3405 02:07:39,892 --> 02:07:40,693 DIFFERENT LOCATIONS 3406 02:07:40,693 --> 02:07:41,728 DEPENDING ON THE REGION 3407 02:07:41,728 --> 02:07:44,130 WHERE MORE NEURONS ARE 3408 02:07:44,130 --> 02:07:45,298 INDEED MORE MOST RESPONSIVE 3409 02:07:45,298 --> 02:07:47,567 AND IT CAN DO THIS WITHOUT 3410 02:07:47,567 --> 02:07:48,701 ANY HUMOR INTERVENTION SO 3411 02:07:48,701 --> 02:07:50,003 THE EXPERIMENTS CAN RAPIDLY 3412 02:07:50,003 --> 02:07:53,573 IDENTIFY WHERE IT SHOULD BE 3413 02:07:53,573 --> 02:08:03,983 MEASURING BASICALLY 3414 02:08:07,687 --> 02:08:08,054 ATOMICALLY. 3415 02:08:08,054 --> 02:08:14,761 SO ONE MORE SLIDE TO SHOW 3416 02:08:14,761 --> 02:08:17,196 YOU HOW WE DESIGN CAUSAL 3417 02:08:17,196 --> 02:08:19,265 EXPERIMENTS THAT CAN SCALE 3418 02:08:19,265 --> 02:08:20,533 TO HIGH DIMENSIONAL SPACES. 3419 02:08:20,533 --> 02:08:22,135 SO WE DON'T WANT TO LEARN 3420 02:08:22,135 --> 02:08:25,204 THIS ON AVERAGE BUT APPLY 3421 02:08:25,204 --> 02:08:26,506 THIS TO AN INDIVIDUAL SO WE 3422 02:08:26,506 --> 02:08:27,774 WANT TO LEARN THIS 3423 02:08:27,774 --> 02:08:30,243 EFFICIENTLY SO WE CAN 3424 02:08:30,243 --> 02:08:33,312 IDENTIFY WITH ONE PARTICULAR 3425 02:08:33,312 --> 02:08:33,913 ORGANISM. 3426 02:08:33,913 --> 02:08:36,049 AGAIN, WE USED ZEBRAFISH AND 3427 02:08:36,049 --> 02:08:40,053 WE CAN USE STIMULATION TO 3428 02:08:40,053 --> 02:08:41,354 PERTURB THE NEURONS AND 3429 02:08:41,354 --> 02:08:42,622 REFRESH SURE RESPONSES OF 3430 02:08:42,622 --> 02:08:44,557 ALL THE OTHER NEURONS IN THE 3431 02:08:44,557 --> 02:08:45,091 NETWORK. 3432 02:08:45,091 --> 02:08:48,061 SO THIS IS A PRETTY TYPICAL 3433 02:08:48,061 --> 02:08:51,698 STRAIGHT FRAMEWORK TO DO 3434 02:08:51,698 --> 02:08:51,998 THIS. 3435 02:08:51,998 --> 02:08:54,200 INTERVENE ONCE, MEASURE 3436 02:08:54,200 --> 02:08:54,834 RESPONSES, THEN INTERVENE 3437 02:08:54,834 --> 02:08:56,969 AGAIN AND YOU DO THIS FOR 3438 02:08:56,969 --> 02:09:00,707 EACH NEURON IN THE NETWORK. 3439 02:09:00,707 --> 02:09:07,780 SO FOR 100, IT WILL TAKE YOU 3440 02:09:07,780 --> 02:09:10,717 42 MINUTES. 3441 02:09:10,717 --> 02:09:12,218 IF YOU DO 1000 NEURONS, IT 3442 02:09:12,218 --> 02:09:13,286 WILL TAKE YOU DAYS. 3443 02:09:13,286 --> 02:09:17,924 SO WE DO NOT HAVE THIS TIME 3444 02:09:17,924 --> 02:09:18,424 OR INTERVENTIONS. 3445 02:09:18,424 --> 02:09:21,027 SO WHAT WE DID WAS TURN TO 3446 02:09:21,027 --> 02:09:22,528 THE STATISTICAL GROUP 3447 02:09:22,528 --> 02:09:23,229 TESTING. 3448 02:09:23,229 --> 02:09:25,164 SO HERE WE'RE NOT SELECTING 3449 02:09:25,164 --> 02:09:27,600 ONE AT A TIME BUT A GROUP OF 3450 02:09:27,600 --> 02:09:28,868 THEM SIGN OBTAIN CROSSLY. 3451 02:09:28,868 --> 02:09:31,704 WE CAN LOOK FOR NETWORK 3452 02:09:31,704 --> 02:09:33,339 RESPONSES AND MEASURE VERY 3453 02:09:33,339 --> 02:09:35,208 RAPIDLY THE FULL STRUCTURE 3454 02:09:35,208 --> 02:09:36,142 OF THE NETWORK. 3455 02:09:36,142 --> 02:09:37,710 SO NOT ONLY IS THIS FASTER 3456 02:09:37,710 --> 02:09:39,779 BECAUSE WE ARE USING 3457 02:09:39,779 --> 02:09:41,581 MULTIPLE INTERVENTIONS BUT 3458 02:09:41,581 --> 02:09:44,417 WE CAN REWRITE THIS PROBLEM 3459 02:09:44,417 --> 02:09:45,384 USING VARIATION AND THAT IS 3460 02:09:45,384 --> 02:09:47,620 AT THE BOTTOM AND WHAT THIS 3461 02:09:47,620 --> 02:09:50,957 DOES IS ALLOW US TO MEASURE 3462 02:09:50,957 --> 02:09:52,091 UNCERTAINTY IN OUR 3463 02:09:52,091 --> 02:09:52,492 EXPERIMENTS. 3464 02:09:52,492 --> 02:09:56,429 NOW WE DON'T NEED TO CHOOSE 3465 02:09:56,429 --> 02:09:58,030 RANDOM INTERVENTIONS BUT 3466 02:09:58,030 --> 02:09:59,999 INSTEAD OBSERVE THE 3467 02:09:59,999 --> 02:10:00,633 INTERVENTIONS, INCORPORATE 3468 02:10:00,633 --> 02:10:03,169 IT IN THE MODEL, SEE WHERE 3469 02:10:03,169 --> 02:10:05,004 THE MODEL IS UNSERB AND 3470 02:10:05,004 --> 02:10:07,073 CHOOSE THOSE FOR THE NEXT 3471 02:10:07,073 --> 02:10:07,607 INTERVENTION. 3472 02:10:07,607 --> 02:10:09,475 SO THIS IS AN ADAPTIVE 3473 02:10:09,475 --> 02:10:11,477 PROCEDURE SCALED REALLY WELL 3474 02:10:11,477 --> 02:10:12,578 FOR LARGE NETWORKS. 3475 02:10:12,578 --> 02:10:14,213 IF YOU LOOK AT THE DIAGRAM 3476 02:10:14,213 --> 02:10:20,319 ON THE RIGHT IT ALLOWED US 3477 02:10:20,319 --> 02:10:26,192 TO EXAMINE 10 TO THE 8TH IN 3478 02:10:26,192 --> 02:10:26,793 TWO HOURS. 3479 02:10:26,793 --> 02:10:29,462 SO I HOPE I SHOWED YOU A FEW 3480 02:10:29,462 --> 02:10:31,164 WAYS IN WHICH INCORPORATING 3481 02:10:31,164 --> 02:10:33,132 MACHINE MODELS IN A 3482 02:10:33,132 --> 02:10:34,433 EXPERIMENTAL SET AND NOT 3483 02:10:34,433 --> 02:10:36,836 JUST USING THEM FOR A TALK 3484 02:10:36,836 --> 02:10:40,373 CAN BE EXTREMELY USEFUL FOR 3485 02:10:40,373 --> 02:10:41,107 CONSIDERING POWERFUL 3486 02:10:41,107 --> 02:10:41,808 EXPERIMENTAL DESIGNS. 3487 02:10:41,808 --> 02:10:45,511 THESE CAN BE USED ACROSS 3488 02:10:45,511 --> 02:10:48,347 POPULATIONS AND TUNE MODELS 3489 02:10:48,347 --> 02:10:49,482 TO SPECIFIC INDIVIDUALS. 3490 02:10:49,482 --> 02:10:52,351 THEY ALSO ALLOW US TO 3491 02:10:52,351 --> 02:10:57,523 ACCUMULATE DATA AS ACQUIRED 3492 02:10:57,523 --> 02:11:00,459 AND EXPONENTIALLY LEARN MORE 3493 02:11:00,459 --> 02:11:01,594 EFFICIENTLY WHICH IS VERY 3494 02:11:01,594 --> 02:11:02,995 DOABLE SINCE WE HAVE A 3495 02:11:02,995 --> 02:11:04,964 LIMITED NUMBER OF TRIALS TO 3496 02:11:04,964 --> 02:11:05,331 INTERVENE. 3497 02:11:05,331 --> 02:11:07,233 I SHOULD POINT OUT THAT NONE 3498 02:11:07,233 --> 02:11:09,936 OF THESE WERE SPECIFIC TO A 3499 02:11:09,936 --> 02:11:12,805 PARTICULAR ORGANISM. 3500 02:11:12,805 --> 02:11:23,349 WE USED THEM ON MICE, FISH, 3501 02:11:25,051 --> 02:11:27,253 APAK, USING OCTOPUS AND 3502 02:11:27,253 --> 02:11:28,287 OTHER ORGANISMS AS WELL. 3503 02:11:28,287 --> 02:11:29,222 IF YOU WANT MORE INFORMATION 3504 02:11:29,222 --> 02:11:31,524 ON HOW YOU CAN INCORPORATE 3505 02:11:31,524 --> 02:11:33,459 THIS IN YOUR EXPERIMENTAL 3506 02:11:33,459 --> 02:11:34,760 DESIGNS, I WOULD BE MORE 3507 02:11:34,760 --> 02:11:36,229 THAN HAPPY TO CHAT WITH YOU 3508 02:11:36,229 --> 02:11:37,597 ABOUT IT. 3509 02:11:37,597 --> 02:11:40,199 SO WITH THAT I THANK MY LAB, 3510 02:11:40,199 --> 02:11:42,301 MY ADVISOR AND MY FUNDING 3511 02:11:42,301 --> 02:11:46,439 SOURCES. 3512 02:11:46,439 --> 02:11:47,406 THANK YOU. 3513 02:11:47,406 --> 02:11:47,773 [APPLAUSE] 3514 02:11:47,773 --> 02:11:49,275 >> THANK YOU FOR THAT 3515 02:11:49,275 --> 02:11:50,209 SPECTACULAR TALK. 3516 02:11:50,209 --> 02:11:52,478 WE WILL CONTINUE WITH Dr. 3517 02:11:52,478 --> 02:11:54,113 NATHAN PRICE FROM THORNE 3518 02:11:54,113 --> 02:11:56,716 HEALTHCARE WHO WILL BE 3519 02:11:56,716 --> 02:11:58,417 SPEAKING ABOUT TAKING 3520 02:11:58,417 --> 02:12:00,453 DIGITAL TWIN MODELS OF 3521 02:12:00,453 --> 02:12:07,226 COGNITIVE HEALTH IN AGING. 3522 02:12:07,226 --> 02:12:08,728 >> THANK YOU, GREAT TO BE 3523 02:12:08,728 --> 02:12:09,161 HERE. 3524 02:12:09,161 --> 02:12:10,663 REALLY INTERESTING TO HEAR 3525 02:12:10,663 --> 02:12:11,831 SO MANY FANTASTIC TALKS. 3526 02:12:11,831 --> 02:12:13,666 A LOT OF IDEAS OFF THE LAST 3527 02:12:13,666 --> 02:12:14,767 ONE I AM EXCITED ABOUT. 3528 02:12:14,767 --> 02:12:16,903 SO I AM GOING TO TALK A 3529 02:12:16,903 --> 02:12:18,838 LITTLE BIT TODAY ABOUT 3530 02:12:18,838 --> 02:12:20,139 DIGITAL TWIN MODELS OF 3531 02:12:20,139 --> 02:12:21,140 COGNITIVE HEALTH IN AGING 3532 02:12:21,140 --> 02:12:23,042 AND AT THE END, ESPECIALLY 3533 02:12:23,042 --> 02:12:24,443 HOW THIS LEADS US TO A 3534 02:12:24,443 --> 02:12:25,778 DIFFERENT WAY OF THINKING 3535 02:12:25,778 --> 02:12:28,080 HOW WE MIGHT DESIGN CLINICAL 3536 02:12:28,080 --> 02:12:28,414 TRIALS. 3537 02:12:28,414 --> 02:12:30,516 SO I WILL START VERY BROADLY 3538 02:12:30,516 --> 02:12:33,619 JUST IN TERMS OF MY 3539 02:12:33,619 --> 02:12:34,921 BACKGROUND AND PERSPECTIVE. 3540 02:12:34,921 --> 02:12:36,989 I AM VERY INTERESTED IN AS 3541 02:12:36,989 --> 02:12:39,759 BROADLY ACROSS OUR MEDICAL 3542 02:12:39,759 --> 02:12:40,426 AND RESEARCH ENTERPRISE ON 3543 02:12:40,426 --> 02:12:42,395 THE IDEA THAT WE INTERVENE 3544 02:12:42,395 --> 02:12:44,330 MUCH TOO LATE IN GENERAL AND 3545 02:12:44,330 --> 02:12:46,532 SPEND WAY TOO MUCH TIME 3546 02:12:46,532 --> 02:12:47,266 STUDYING ONLY LATE-STAGE 3547 02:12:47,266 --> 02:12:49,235 DISEASE AND NOT THE EARLIEST 3548 02:12:49,235 --> 02:12:51,337 TRANSITION STATES TO IT. 3549 02:12:51,337 --> 02:12:55,308 I WROTE A BOOK ON THIS WITH 3550 02:12:55,308 --> 02:12:57,476 LEE HOOD THROUGH HARVARD 3551 02:12:57,476 --> 02:12:58,344 PRESS CALLED SCIENTIFIC 3552 02:12:58,344 --> 02:13:00,880 WELLNESS AND WE HAVE BEEN 3553 02:13:00,880 --> 02:13:02,048 DOING THESE LARGE 3554 02:13:02,048 --> 02:13:03,516 LONGITUDINAL STUDIES ON 3555 02:13:03,516 --> 02:13:05,084 HEALTHY PEOPLE FOR ABOUT A 3556 02:13:05,084 --> 02:13:07,753 DECADE WHICH I AM NOT GOING 3557 02:13:07,753 --> 02:13:09,055 TO GET INTO TODAY BUT 3558 02:13:09,055 --> 02:13:11,590 RELATES TO HOW WE THINK 3559 02:13:11,590 --> 02:13:12,325 ABOUT COGNITIVE AGING AND 3560 02:13:12,325 --> 02:13:13,926 WHAT WE CAN DO. 3561 02:13:13,926 --> 02:13:14,727 WE SAW SOME BEAUTIFUL 3562 02:13:14,727 --> 02:13:16,696 EXAMPLES IN THE LAST SESSION 3563 02:13:16,696 --> 02:13:21,400 WHICH WAS REALLY FASCINATING 3564 02:13:21,400 --> 02:13:24,570 ABOUT HOW OFTEN THINGS THAT 3565 02:13:24,570 --> 02:13:26,172 HAPPEN EARLIER IN LIFE CAN 3566 02:13:26,172 --> 02:13:28,808 HAVE AN IMPACT LATER. 3567 02:13:28,808 --> 02:13:30,943 A REALLY WONDERFUL 3568 02:13:30,943 --> 02:13:31,344 PERSPECTIVE. 3569 02:13:31,344 --> 02:13:34,213 I CAME UP TO GIVE A LECTURE 3570 02:13:34,213 --> 02:13:38,351 AT RPI, DRIVING THROUGH THE 3571 02:13:38,351 --> 02:13:40,753 CORE, LISTENING TO A BOOK 3572 02:13:40,753 --> 02:13:41,921 WRITTEN 2000 YEARS AGO BY 3573 02:13:41,921 --> 02:13:43,889 SENECA AND HE WAS TALKING 3574 02:13:43,889 --> 02:13:47,693 ABOUT LONGEST LONG 3575 02:13:47,693 --> 02:13:50,229 LONGEVITY AND HAD A QUOTE I 3576 02:13:50,229 --> 02:13:51,831 REALLY LIKED AS HE WAS 3577 02:13:51,831 --> 02:13:53,666 EXPOSED TO HIS YOUNG 3578 02:13:53,666 --> 02:13:55,034 PROTEGE‘, IT MAKES A GREAT 3579 02:13:55,034 --> 02:13:56,936 DEAL OF DIFFERENCE IF A MAN 3580 02:13:56,936 --> 02:13:59,038 IS LENGTH THING IN HIS LIFE 3581 02:13:59,038 --> 02:14:00,873 OR HIS DEATH AND I THOUGHT 3582 02:14:00,873 --> 02:14:03,509 THAT A BEAUTIFUL WAY TO PUT 3583 02:14:03,509 --> 02:14:03,909 IT. 3584 02:14:03,909 --> 02:14:06,779 FOR THOSE OF US IN THE 3585 02:14:06,779 --> 02:14:07,880 LONGEVITY OR AGING SPACE, 3586 02:14:07,880 --> 02:14:10,716 THE NEXT PIECE OF ADVICE I 3587 02:14:10,716 --> 02:14:11,984 FOUND REALLY FASCINATING 3588 02:14:11,984 --> 02:14:14,387 BECAUSE HE SAID THE NEXT 3589 02:14:14,387 --> 02:14:16,088 CRAZE IS PERIODIC FASTING 3590 02:14:16,088 --> 02:14:19,525 AND WE HAVE ADVANCED TO 3591 02:14:19,525 --> 02:14:20,292 INTERMITTENT FASTING SO WE 3592 02:14:20,292 --> 02:14:22,094 HAVE COME A LONG WAY. 3593 02:14:22,094 --> 02:14:23,596 THERE WE GO. 3594 02:14:23,596 --> 02:14:25,431 SO OBVIOUSLY IN COGNITIVE 3595 02:14:25,431 --> 02:14:27,733 AGING, THIS MAKES A HUGE 3596 02:14:27,733 --> 02:14:28,134 DIFFERENCE. 3597 02:14:28,134 --> 02:14:30,102 I WROTE A PIECE FOR THE L.A. 3598 02:14:30,102 --> 02:14:31,737 TIMES AGAIN WITH LEE LAST 3599 02:14:31,737 --> 02:14:32,038 YEAR. 3600 02:14:32,038 --> 02:14:33,239 BUT ONE OF THE THINGS THAT 3601 02:14:33,239 --> 02:14:34,974 REALLY STRIKES YOU WHEN YOU 3602 02:14:34,974 --> 02:14:37,276 LOOK AT SAY ALZHEIMER'S AND 3603 02:14:37,276 --> 02:14:39,145 WHAT YOU CAN DO ABOUT IT, IS 3604 02:14:39,145 --> 02:14:42,148 WHEN YOU LOOK AT DRUGS, THEY 3605 02:14:42,148 --> 02:14:42,948 ARE HIGHLY EXPENSIVE. 3606 02:14:42,948 --> 02:14:47,753 WE HAVE SPENT, DEPENDING ON 3607 02:14:47,753 --> 02:14:48,954 THE ESTIMATE, 300 BILLION UP 3608 02:14:48,954 --> 02:14:52,158 TO SOME ESTIMATES ARE A 3609 02:14:52,158 --> 02:14:54,093 TRILLION CUMULATIVELY ON 3610 02:14:54,093 --> 02:14:54,827 ANTI-AMYLOID THERAPIES AND 3611 02:14:54,827 --> 02:14:57,296 OTHER DRUGS OVER THE DECADES 3612 02:14:57,296 --> 02:14:58,531 WITH VERY LIMITED BENEFIT. 3613 02:14:58,531 --> 02:15:00,399 HOWEVER IF YOU LOOK AT 3614 02:15:00,399 --> 02:15:06,939 PREESSENTIAL, THE 3615 02:15:06,939 --> 02:15:09,542 PREVENTION, THE EFFECTS ARE 3616 02:15:09,542 --> 02:15:12,144 YEARS AWAY AND THE AFFECT 3617 02:15:12,144 --> 02:15:13,779 SIZE MUCH LONGER AND THIS IS 3618 02:15:13,779 --> 02:15:15,414 TRUE IN COMMUNITIES AS WELL. 3619 02:15:15,414 --> 02:15:19,051 ONE OF THE REALLY STRIKING 3620 02:15:19,051 --> 02:15:19,985 FINDINGS, THE HISPANIC 3621 02:15:19,985 --> 02:15:21,487 COMMUNITY IN PARTICULAR IS 3622 02:15:21,487 --> 02:15:23,189 HIGHLY RESPONSIVE TO THAT. 3623 02:15:23,189 --> 02:15:26,425 THE ESTIMATE IS 56 PERCENT 3624 02:15:26,425 --> 02:15:28,227 OF ALZHEIMER'S IS AVOIDABLE 3625 02:15:28,227 --> 02:15:31,263 OR COULD BE LIMITED THROUGH 3626 02:15:31,263 --> 02:15:32,331 HIVE STYLE PREESSENTIAL AND 3627 02:15:32,331 --> 02:15:33,933 THAT IS MORE DATA COMING OUT 3628 02:15:33,933 --> 02:15:35,000 OF STUDIES. 3629 02:15:35,000 --> 02:15:37,503 SO WE KNOW THAT FOCUSING ON 3630 02:15:37,503 --> 02:15:39,572 COGNITIVE AGING MAKES A HUGE 3631 02:15:39,572 --> 02:15:41,207 DIFFERENCE AND THERE IS A 3632 02:15:41,207 --> 02:15:43,843 LOT YOU CAN DO OVER THESE 3633 02:15:43,843 --> 02:15:44,543 TRAJECTORIES. 3634 02:15:44,543 --> 02:15:45,778 THIS HAS BECOME LESS 3635 02:15:45,778 --> 02:15:46,846 CONTROVERSIAL OVER THE LAST 3636 02:15:46,846 --> 02:15:47,413 FEW YEARS. 3637 02:15:47,413 --> 02:15:54,353 THERE WAS A GREAT STUDY IN 3638 02:15:54,353 --> 02:15:56,355 LANCET AROUND ALZHEIMER'S 3639 02:15:56,355 --> 02:15:57,456 DISEASE, THAT THERE ARE 3640 02:15:57,456 --> 02:16:00,025 THINGS YOU CAN DO TO 3641 02:16:00,025 --> 02:16:00,826 MAINTAIN YOUR BRAIN HEALTH 3642 02:16:00,826 --> 02:16:02,795 LONGER AND YOU CAN SEE THE 3643 02:16:02,795 --> 02:16:04,730 THINGS THERE, MANY ADDRESSED 3644 02:16:04,730 --> 02:16:06,031 IN THE MEETINGS WE HAVE HAD 3645 02:16:06,031 --> 02:16:16,575 HERE OVER THE LAST COUPLE OF 3646 02:16:18,110 --> 02:16:18,577 DAYS. 3647 02:16:18,577 --> 02:16:21,180 SO COMING OUT OF DIGITAL 3648 02:16:21,180 --> 02:16:23,582 TWINS, A COLLEAGUE OF MINE 3649 02:16:23,582 --> 02:16:26,418 TOM PATTERSON MANY YEARS AND 3650 02:16:26,418 --> 02:16:30,189 COMING OUT OF SMITH CLINE, 3651 02:16:30,189 --> 02:16:31,924 HOW TO MAINTAIN BRAIN HEALTH 3652 02:16:31,924 --> 02:16:36,362 SO THIS STARTED OUT AS A 3653 02:16:36,362 --> 02:16:42,368 MODEL LOOKING AT ORDINARY 3654 02:16:42,368 --> 02:16:43,536 MODELS, THEN ADDING IN 3655 02:16:43,536 --> 02:16:45,804 UNCERTAINTY AND YOU ARE ABLE 3656 02:16:45,804 --> 02:16:47,506 TO SIMULATE TRAJECTORIES OF 3657 02:16:47,506 --> 02:16:48,440 COGNITIVE HEALTH OVER 3658 02:16:48,440 --> 02:16:48,874 LIFESPAN. 3659 02:16:48,874 --> 02:16:50,643 NOW I WILL NOT GET INTO IT 3660 02:16:50,643 --> 02:16:51,911 IN THE INTEREST OF TIME. 3661 02:16:51,911 --> 02:16:53,612 THIS HAS GIVEN ME A VERY 3662 02:16:53,612 --> 02:16:55,714 DIFFERENT VIEW I HAVE TO SAY 3663 02:16:55,714 --> 02:16:58,751 IN WHAT I THINK ARE THE MAIN 3664 02:16:58,751 --> 02:16:59,451 DRIVERS OF ALZHEIMER'S 3665 02:16:59,451 --> 02:17:00,619 DISEASE BUT ONE OF THE 3666 02:17:00,619 --> 02:17:02,121 THINGS THIS REALLY GETS AT 3667 02:17:02,121 --> 02:17:04,056 IS HOW DOES THE BRAIN 3668 02:17:04,056 --> 02:17:05,891 MAINTAIN ENOUGH ENERGY TO 3669 02:17:05,891 --> 02:17:06,592 STAY ALIVE? 3670 02:17:06,592 --> 02:17:10,462 20PERCENT OF YOUR BRAIN'S 3671 02:17:10,462 --> 02:17:15,834 ENERGY USE, 2 PERCENT 3672 02:17:15,834 --> 02:17:17,536 BIOMASS, OXYGENATION OF THE 3673 02:17:17,536 --> 02:17:20,639 BRAIN GOES DOWN AS YOU GET 3674 02:17:20,639 --> 02:17:22,474 OLDER, SOLVING THOSE GETS 3675 02:17:22,474 --> 02:17:24,176 HARDER AND HARDER, TURNS OUT 3676 02:17:24,176 --> 02:17:28,447 YOU WANT TO KEEP ASTROCYTES 3677 02:17:28,447 --> 02:17:31,951 LOW TO KEEP ENERGY LEVELS 3678 02:17:31,951 --> 02:17:38,824 HIGH DURING OXYGEN 3679 02:17:38,824 --> 02:17:39,325 DEPRIVATION. 3680 02:17:39,325 --> 02:17:40,292 APOE4 TRANSPORTS THE ENERGY 3681 02:17:40,292 --> 02:17:43,729 OUT OF THOSE CELLS AND DOES 3682 02:17:43,729 --> 02:17:45,931 IT SLOWLY, LESS EFFICIENT, 3683 02:17:45,931 --> 02:17:49,868 THEREFORE THEY DIE. 3684 02:17:49,868 --> 02:17:51,804 APO2 DOES IT QUICKLY AND 3685 02:17:51,804 --> 02:17:53,539 THEY STAY HIGH, YOU CAN 3686 02:17:53,539 --> 02:17:56,275 MODEL A LOT OF THESE IN TIME 3687 02:17:56,275 --> 02:17:58,010 AND IF YOU WANT TO CHAT 3688 02:17:58,010 --> 02:17:59,511 ABOUT THAT, HAPPY TO DO 3689 02:17:59,511 --> 02:18:00,212 THAT. 3690 02:18:00,212 --> 02:18:02,281 NOW AS MENTIONED, THIS MODEL 3691 02:18:02,281 --> 02:18:04,516 STARTS AS A MODEL OF BRAIN 3692 02:18:04,516 --> 02:18:05,751 HEALTH, MAINTAINING ENERGY, 3693 02:18:05,751 --> 02:18:07,253 TAKING OUT THE TRASH, WHAT 3694 02:18:07,253 --> 02:18:09,355 YOU DO A LOT WHEN YOU ARE 3695 02:18:09,355 --> 02:18:13,726 ASLEEP WHICH WE HEARD ABOUT 3696 02:18:13,726 --> 02:18:14,260 EARLIER. 3697 02:18:14,260 --> 02:18:15,194 MICROGLIA FUNCTIONS ALL OF 3698 02:18:15,194 --> 02:18:17,563 THOSE KIND OF THINGS IN THE 3699 02:18:17,563 --> 02:18:18,030 MODEL. 3700 02:18:18,030 --> 02:18:19,665 ONCE WE BUILT THIS MODEL TO 3701 02:18:19,665 --> 02:18:21,634 SAY HOW DO YOU MAINTAIN 3702 02:18:21,634 --> 02:18:23,035 HEALTH, THEN OF COURSE YOU 3703 02:18:23,035 --> 02:18:25,738 CAN LAYER ON TO THAT THE 3704 02:18:25,738 --> 02:18:26,839 DIFFERENT ASPECTS OF THE 3705 02:18:26,839 --> 02:18:27,973 DRIVERS OF DISEASE, RIGHT? 3706 02:18:27,973 --> 02:18:31,343 SO THIS IS JUST KIND OF A 3707 02:18:31,343 --> 02:18:31,777 SANITY CHECK. 3708 02:18:31,777 --> 02:18:33,646 SO WE DID THIS FOR 3709 02:18:33,646 --> 02:18:35,381 ALZHEIMER'S AFTER THE FACT 3710 02:18:35,381 --> 02:18:38,784 AND SO HERE THESE ARE KNOWN 3711 02:18:38,784 --> 02:18:44,790 EFFECTS OF GENETIC AND 3712 02:18:44,790 --> 02:18:46,458 LIFESTYLE RISK FACTORS. 3713 02:18:46,458 --> 02:18:49,395 I CAN SEE MY COMPLICATION 3714 02:18:49,395 --> 02:18:50,963 THERE IS GENERAL KNOWLEDGE 3715 02:18:50,963 --> 02:18:55,901 TO ANYONE IN THE ROOM BUT WE 3716 02:18:55,901 --> 02:18:59,772 KNOW APOE4 GIVING YOU HIGH 3717 02:18:59,772 --> 02:19:01,907 RISK, APOE2 LOW RISK AND SO 3718 02:19:01,907 --> 02:19:04,009 FORTH AND THEN AT THE BOTTOM 3719 02:19:04,009 --> 02:19:04,977 LISTED FROM VARIOUS PAPERS 3720 02:19:04,977 --> 02:19:09,615 SOME OF THE RISK FACTORS. 3721 02:19:09,615 --> 02:19:11,116 SO GLOMULAR FILTRATION RATE, 3722 02:19:11,116 --> 02:19:13,786 IF THAT IS HIGHWAY, YOUR 3723 02:19:13,786 --> 02:19:15,387 ALZHEIMER'S CONVERSION IS 3724 02:19:15,387 --> 02:19:19,058 LOW, VITAMIN D IS LOW, ALD 3725 02:19:19,058 --> 02:19:21,060 HYPER'S ALSO LOW. 3726 02:19:21,060 --> 02:19:22,561 CORTISOL, STRESS LEVELS ARE 3727 02:19:22,561 --> 02:19:24,630 HIGH, HIGH AND SO FORTH. 3728 02:19:24,630 --> 02:19:26,432 SO THESE ARE A COMPILATION 3729 02:19:26,432 --> 02:19:29,201 OF DATA FROM LOTS OF STUDIES 3730 02:19:29,201 --> 02:19:31,270 ON LOTS OF PAPERS ON WHAT WE 3731 02:19:31,270 --> 02:19:32,705 KNOW ABOUT THE CONVERSION 3732 02:19:32,705 --> 02:19:35,741 RATES AND HAZARD RATIOS TO 3733 02:19:35,741 --> 02:19:36,141 ALZHEIMER'S. 3734 02:19:36,141 --> 02:19:38,644 SO ONE OF THE THINGS I 3735 02:19:38,644 --> 02:19:41,380 BRIEFLY DESCRIBED WAS TO 3736 02:19:41,380 --> 02:19:42,448 GENERATE DIGITAL TWINS ON 3737 02:19:42,448 --> 02:19:45,017 THAT SO WE HAVE GENERATED 3738 02:19:45,017 --> 02:19:45,984 ABOUT 26 MILLION OF THESE ON 3739 02:19:45,984 --> 02:19:47,486 TOP OF THIS CORE MODEL. 3740 02:19:47,486 --> 02:19:49,655 ONE OF THE QUESTIONS WAS HOW 3741 02:19:49,655 --> 02:19:51,523 SIMILAR IS THIS POPULATION 3742 02:19:51,523 --> 02:19:53,359 IF YOU SIMULATE ON THESE 3743 02:19:53,359 --> 02:19:55,761 DATA AND THERE IS DATA AND 3744 02:19:55,761 --> 02:19:58,364 INSIGHTS BEHIND THE MODEL 3745 02:19:58,364 --> 02:20:00,466 FROM ABOUT 1200 CARES AND WE 3746 02:20:00,466 --> 02:20:02,534 COMPARED IT TO 30 DIFFERENT 3747 02:20:02,534 --> 02:20:03,335 CLINICAL RESEARCH STUDIES 3748 02:20:03,335 --> 02:20:05,337 AND TRIALS AND THIS IS WHAT 3749 02:20:05,337 --> 02:20:06,572 IT LOOKS LIKE. 3750 02:20:06,572 --> 02:20:08,741 WHEN YOU EVALUATE THAT 3751 02:20:08,741 --> 02:20:10,209 POPULATION, SO THE SOLID 3752 02:20:10,209 --> 02:20:12,878 LINES HERE ARE THE DIGITAL 3753 02:20:12,878 --> 02:20:14,279 POPULATION, THE FATTER LINES 3754 02:20:14,279 --> 02:20:15,981 THE ACTUAL DATA, WHAT YOU 3755 02:20:15,981 --> 02:20:18,016 FIND IS THAT POPULATION 3756 02:20:18,016 --> 02:20:20,319 LOOKS AN AWFUL LOT LIKE THE 3757 02:20:20,319 --> 02:20:20,819 ACTUAL POPULATION. 3758 02:20:20,819 --> 02:20:22,321 SO SOME OF THE THINGS I 3759 02:20:22,321 --> 02:20:26,225 MENTIONED BEFORE ON THE 3760 02:20:26,225 --> 02:20:30,129 EFFECTS OF APOE4 DYNAMICS OR 3761 02:20:30,129 --> 02:20:31,797 APOE2 DYNAMICS, BEING ABLE 3762 02:20:31,797 --> 02:20:34,433 TO EXPLAIN WHEN PEOPLE TURN 3763 02:20:34,433 --> 02:20:34,867 INTO DEMENTIA. 3764 02:20:34,867 --> 02:20:38,670 TURNS OUT IF YOU TAKE THE 3765 02:20:38,670 --> 02:20:40,172 TWO ENERGY LOWERING 3766 02:20:40,172 --> 02:20:44,209 EFFICIENCY BASED ON APOE2 3767 02:20:44,209 --> 02:20:45,711 AND APOE4, THIS GIVES YOU 3768 02:20:45,711 --> 02:20:47,446 BACK THOSE CURVES AND YOU 3769 02:20:47,446 --> 02:20:49,281 CAN CENTER THIS AROUND 3770 02:20:49,281 --> 02:20:50,949 KEEPING NEURONS ALIVE FROM A 3771 02:20:50,949 --> 02:20:51,717 ENERGETIC LEVEL. 3772 02:20:51,717 --> 02:20:53,218 SO WE GET INTO ALL THESE 3773 02:20:53,218 --> 02:20:54,720 THINGS AS WE GO THROUGH THIS 3774 02:20:54,720 --> 02:20:56,889 SO WE CAN DO SIMULATIONS, 3775 02:20:56,889 --> 02:20:59,992 AGAIN OVER TIME, THAT RELATE 3776 02:20:59,992 --> 02:21:01,059 MOLEC ULAR LEVEL DETAIL TO 3777 02:21:01,059 --> 02:21:03,262 WHAT IS HAPPENING IN 3778 02:21:03,262 --> 02:21:03,629 PATIENTS. 3779 02:21:03,629 --> 02:21:06,064 SO THIS THEN LEADS TO A 3780 02:21:06,064 --> 02:21:06,765 DIGITAL TWIN SIMULATION. 3781 02:21:06,765 --> 02:21:14,606 I WILL SHOW A VERSION OF 3782 02:21:14,606 --> 02:21:16,074 THIS HERE AND SEE HOW WELL 3783 02:21:16,074 --> 02:21:17,509 YOU CAN SEE THAT. 3784 02:21:17,509 --> 02:21:21,447 BUT WE TAKE THE RELATABLE 3785 02:21:21,447 --> 02:21:22,514 MODIFIABLE RISK FACTORS WE 3786 02:21:22,514 --> 02:21:24,249 HAVE DETERMINED, THE NEXT 3787 02:21:24,249 --> 02:21:26,652 SLIDE, BASED ON A MAN WHO IS 3788 02:21:26,652 --> 02:21:29,855 50 YEARS OLD, HAS TWO COPIES 3789 02:21:29,855 --> 02:21:34,293 OF THE APOE4 GREEN, LOW 3790 02:21:34,293 --> 02:21:42,468 VITAMIN D, SLEEPING 3791 02:21:42,468 --> 02:21:44,503 TERRIBLY, CORTISONE LEVELS 3792 02:21:44,503 --> 02:21:46,638 NOT TERRIBLY BAD, YOU CAN 3793 02:21:46,638 --> 02:21:50,142 PUT THIS KIND OF INFORMATION 3794 02:21:50,142 --> 02:21:51,877 IN, AGAIN QUITE READILY TO 3795 02:21:51,877 --> 02:21:53,479 MEASURE AND WHAT YOU GET OUT 3796 02:21:53,479 --> 02:21:56,849 OF A MODEL LIKE THIS IS A 3797 02:21:56,849 --> 02:21:57,716 PROBABILITY DISTRIBUTION. 3798 02:21:57,716 --> 02:21:59,451 SO SHOWN ON THE RIGHT HERE 3799 02:21:59,451 --> 02:22:03,822 WHERE YOU SIGH THE HISTOGRAM 3800 02:22:03,822 --> 02:22:05,190 IS A PROBABILITY 3801 02:22:05,190 --> 02:22:06,558 DISTRIBUTION. 3802 02:22:06,558 --> 02:22:08,193 GIVEN THIS PERSON'S DATA, 3803 02:22:08,193 --> 02:22:11,630 THE MOST LIKELY ONSET OF AGE 3804 02:22:11,630 --> 02:22:13,932 FOR DEMENTIA IN THIS 3805 02:22:13,932 --> 02:22:15,267 INDIVIDUAL IS AGE 61 THERE 3806 02:22:15,267 --> 02:22:18,136 IS A 99 PERCENT CHANCE THAT 3807 02:22:18,136 --> 02:22:21,240 THIS PERSON GETS TO AGE 9 3808 02:22:21,240 --> 02:22:22,808 WITHOUT HAVING ALZHEIMER'S 3809 02:22:22,808 --> 02:22:23,175 DISEASE. 3810 02:22:23,175 --> 02:22:25,777 SO THINK A BIT ABOUT THIS AS 3811 02:22:25,777 --> 02:22:27,346 GHOST FOR CHRISTMAS FUTURE, 3812 02:22:27,346 --> 02:22:28,313 YOU ARE NOT DOING 3813 02:22:28,313 --> 02:22:30,148 INTERVENTION AND WHAT IS THE 3814 02:22:30,148 --> 02:22:31,984 EXPECTATION GIVEN WHERE YOU 3815 02:22:31,984 --> 02:22:32,784 ARE AT? 3816 02:22:32,784 --> 02:22:34,286 NOW AT THE BOTTOM WHAT WE 3817 02:22:34,286 --> 02:22:38,123 HAVE IS A SERIES OF 3818 02:22:38,123 --> 02:22:38,957 INTERVENTIONS, FOCUSED ON 3819 02:22:38,957 --> 02:22:42,628 THINGS VERY SAFE TO DO IN AN 3820 02:22:42,628 --> 02:22:44,029 OTHERWISE HEALTHY 3821 02:22:44,029 --> 02:22:47,232 INDIVIDUAL, EXERCISE, SLEEP, 3822 02:22:47,232 --> 02:22:48,166 DIETARY SUPPLEMENTS, 3823 02:22:48,166 --> 02:22:49,735 NUTRITION, THINGS OF THIS 3824 02:22:49,735 --> 02:22:51,436 NATURE BUT WHAT YOU CAN SEE 3825 02:22:51,436 --> 02:22:53,672 GOING ON AT THE BOTTOM IS 3826 02:22:53,672 --> 02:22:56,275 YOU CAN CALCULATE THE 3827 02:22:56,275 --> 02:22:57,409 PERCENTILE RESPONDER YOU 3828 02:22:57,409 --> 02:23:00,012 EXPECT EACH PERSON TO BE AT 3829 02:23:00,012 --> 02:23:01,647 FOR EACH OF THESE AND THE 3830 02:23:01,647 --> 02:23:02,114 BENEFIT. 3831 02:23:02,114 --> 02:23:03,448 SO IF YOU ARE LOOKING AT THE 3832 02:23:03,448 --> 02:23:04,683 BOTTOM THERE, YOU ARE 3833 02:23:04,683 --> 02:23:09,821 LOOKING AT THINGS LIKE 3834 02:23:09,821 --> 02:23:16,862 B-COMPLEX, GETTING BRAIN 3835 02:23:16,862 --> 02:23:17,362 OXYGENATION UP, 3836 02:23:17,362 --> 02:23:18,363 PHOSPHATIDYSERINE AND SO 3837 02:23:18,363 --> 02:23:18,664 FORTH. 3838 02:23:18,664 --> 02:23:20,365 IF YOU DO THESE ONE AT A 3839 02:23:20,365 --> 02:23:21,433 TIME WHAT YOU WILL SEE AT 3840 02:23:21,433 --> 02:23:24,403 THE BOTTOM IS THE PREDICTION 3841 02:23:24,403 --> 02:23:25,671 OF CHANGE IS ZERO. 3842 02:23:25,671 --> 02:23:26,838 THERE IS NO PREDICTION OF 3843 02:23:26,838 --> 02:23:28,874 CHANGE IN ANY OF THESE CASES 3844 02:23:28,874 --> 02:23:29,741 FOR ANY SINGLE INTERVENTION 3845 02:23:29,741 --> 02:23:32,811 BUT IF YOU GO TO THE TOP 3846 02:23:32,811 --> 02:23:34,913 LINE WHERE IT SAYS AL, ALL 3847 02:23:34,913 --> 02:23:38,317 IS JUST TO MAKE THE SLIDE 3848 02:23:38,317 --> 02:23:40,152 SHORTER, YOU CAN OPTIMIZE 3849 02:23:40,152 --> 02:23:42,154 WHICHEVER ONE YOU WANT AND I 3850 02:23:42,154 --> 02:23:44,456 DON'T HAVE TIME TO GO 3851 02:23:44,456 --> 02:23:45,958 THROUGH THAT DATA BUT WE 3852 02:23:45,958 --> 02:23:49,561 BELIEVE THERE ARE SIX EXTRA 3853 02:23:49,561 --> 02:23:50,929 HEALTHY BRAIN YEARS OF LIFE 3854 02:23:50,929 --> 02:23:53,565 ON THE TABLE FOR THIS 3855 02:23:53,565 --> 02:23:54,466 INDIVIDUAL WHERE YOU CAN 3856 02:23:54,466 --> 02:23:55,300 SHIFT THAT. 3857 02:23:55,300 --> 02:23:57,369 YOU CAN TELL THEM WHAT THAT 3858 02:23:57,369 --> 02:23:59,204 IS AND TELL THEM HOW MUCH 3859 02:23:59,204 --> 02:24:00,839 BENEFIT YOU WOULD EXPECT 3860 02:24:00,839 --> 02:24:01,506 THEM TO GET. 3861 02:24:01,506 --> 02:24:03,475 TO GET A SENSE OF WHERE THIS 3862 02:24:03,475 --> 02:24:04,643 CHANGES PERSON TO PERSON, I 3863 02:24:04,643 --> 02:24:06,845 WILL RUN THROUGH A VIDEO OR 3864 02:24:06,845 --> 02:24:08,547 ANIMATION JUST SO YOU CAN 3865 02:24:08,547 --> 02:24:09,181 SEE THIS. 3866 02:24:09,181 --> 02:24:11,750 HOPEFULLY THIS WILL RUN -- 3867 02:24:11,750 --> 02:24:12,250 YES, OKAY. 3868 02:24:12,250 --> 02:24:13,452 SO THIS YOU CAN SEE. 3869 02:24:13,452 --> 02:24:14,920 I DON'T THINK WITHOUT A 3870 02:24:14,920 --> 02:24:16,521 COMPUTER I CAN PAUSE THIS 3871 02:24:16,521 --> 02:24:17,923 BUT YOU CAN SEE HOW MUCH 3872 02:24:17,923 --> 02:24:19,858 THIS IS JUMPING AROUND OR 3873 02:24:19,858 --> 02:24:21,026 HOW DIFFERENT AN 3874 02:24:21,026 --> 02:24:21,660 INDIVIDUAL'S PATTERN LOOKS 3875 02:24:21,660 --> 02:24:21,960 LIKE. 3876 02:24:21,960 --> 02:24:23,662 AND YOU WILL SEE SOME PEOPLE 3877 02:24:23,662 --> 02:24:25,998 HAVE QUITE NARROW RANGES, 3878 02:24:25,998 --> 02:24:27,966 ONLY A LITTLE BIT ON THE 3879 02:24:27,966 --> 02:24:30,235 TABLE, SOME PEOPLE HAVE BIG 3880 02:24:30,235 --> 02:24:30,702 RANGES. 3881 02:24:30,702 --> 02:24:33,271 NOW THIS RELATE BACK TO 3882 02:24:33,271 --> 02:24:36,008 ANNE'S TALK AND ESPECIALLY 3883 02:24:36,008 --> 02:24:37,843 WHEN YOU SEE THESE BROAD 3884 02:24:37,843 --> 02:24:39,344 RANGES, YOU CAN USE THE 3885 02:24:39,344 --> 02:24:40,312 MODEL TO SAY WHAT IS THE 3886 02:24:40,312 --> 02:24:41,947 NEXT THING I WOULD LIKE TO 3887 02:24:41,947 --> 02:24:44,549 MEASURE TO GET A MORE 3888 02:24:44,549 --> 02:24:45,684 FOCUSED PREDICTION ON THIS 3889 02:24:45,684 --> 02:24:47,653 INDIVIDUAL AND HOW FAR CAN I 3890 02:24:47,653 --> 02:24:49,388 PUSH THIS INTO THE FUTURE. 3891 02:24:49,388 --> 02:24:51,323 YOU CAN ALSO DO THIS FOR 3892 02:24:51,323 --> 02:24:51,857 DRUGS. 3893 02:24:51,857 --> 02:24:56,261 WE HAVE DONE THIS PROACTIVE 3894 02:24:56,261 --> 02:24:57,496 SIMULATION OF TRIN2 3895 02:24:57,496 --> 02:24:57,929 AGONISTS. 3896 02:24:57,929 --> 02:24:59,865 THAT WOULD HAVE A SIX MONTH 3897 02:24:59,865 --> 02:25:01,900 BENEFIT FOR PEOPLE AFTER 3898 02:25:01,900 --> 02:25:03,268 DIAGNOSIS BUT YOU GET A 3899 02:25:03,268 --> 02:25:06,104 CURVE WHERE THERE IS THIS 3900 02:25:06,104 --> 02:25:07,272 LONG TAIL AND THERE ARE 3901 02:25:07,272 --> 02:25:09,341 DIGITAL TWINS WE WOULD LIKE 3902 02:25:09,341 --> 02:25:12,411 AT THAT GET THREE, FOUR, 3903 02:25:12,411 --> 02:25:13,779 FIVE YEARS OF BENEFIT, AND 3904 02:25:13,779 --> 02:25:15,547 WHEN YOU RUN THE SIMULATION, 3905 02:25:15,547 --> 02:25:17,382 YOU CAN PULL BACK AND SAY 3906 02:25:17,382 --> 02:25:19,751 WHAT MAKES THEM A SUPER 3907 02:25:19,751 --> 02:25:21,486 RESPONDER, WHAT ARE THE 3908 02:25:21,486 --> 02:25:22,854 CHARACTERISTICS OF THIS 3909 02:25:22,854 --> 02:25:25,123 INDIVIDUAL AND USE THAT 3910 02:25:25,123 --> 02:25:27,192 APPROACH WITH DIFFERENT 3911 02:25:27,192 --> 02:25:28,994 STRATEGIES TO FIND DIFFERENT 3912 02:25:28,994 --> 02:25:30,395 COMBINATIONS FOR PEOPLE WHO 3913 02:25:30,395 --> 02:25:31,663 ARE SUPER RESPONDERS. 3914 02:25:31,663 --> 02:25:34,032 SO THE MAIN THING I WANT TO 3915 02:25:34,032 --> 02:25:36,301 FINISH ON HERE IS HOW THIS 3916 02:25:36,301 --> 02:25:39,171 CAN HELP US WITH 3917 02:25:39,171 --> 02:25:41,440 PERSONALIZED MEDICINE. 3918 02:25:41,440 --> 02:25:44,076 SO DIFFERENT STYLES OF TRIAL 3919 02:25:44,076 --> 02:25:44,676 DESIGN. 3920 02:25:44,676 --> 02:25:47,412 ONE EXAMPLE, FROM 3921 02:25:47,412 --> 02:25:48,013 OBSERVATIONAL STUDIES 3922 02:25:48,013 --> 02:25:50,482 ELDERLY PEOPLE WHO ARE LOW 3923 02:25:50,482 --> 02:25:53,919 IN VITAMIN D GET ALZHEIMER'S 3924 02:25:53,919 --> 02:25:55,220 MUCH SOONER THAN THOSE WHO 3925 02:25:55,220 --> 02:25:56,588 DON'T AND THAT IS ONE OF THE 3926 02:25:56,588 --> 02:25:58,423 THINGS WE KNOW OF BUT WHEN I 3927 02:25:58,423 --> 02:26:00,358 GAVE THE EXAMPLE OF THE 3928 02:26:00,358 --> 02:26:02,894 LANCET STUDY, FOR EXAMPLE, 3929 02:26:02,894 --> 02:26:05,931 WE DO NOT INCLUDE VITAMIN D 3930 02:26:05,931 --> 02:26:07,799 AS A OBSERVATION FOR 3931 02:26:07,799 --> 02:26:08,200 ALZHEIMER'S. 3932 02:26:08,200 --> 02:26:09,768 SO WHY WOULD WE NOT DO THAT? 3933 02:26:09,768 --> 02:26:13,472 WE HAVE DONE A FEW 3934 02:26:13,472 --> 02:26:14,506 RANDOMIZED CLINICAL TRIALS 3935 02:26:14,506 --> 02:26:17,576 AND VITAMIN D HAS FAILED ON 3936 02:26:17,576 --> 02:26:24,883 THOSE CLINICAL TRIALS, 3937 02:26:24,883 --> 02:26:26,485 THEREFORE WE CAN CORRELATE 3938 02:26:26,485 --> 02:26:28,887 AS WE GENERALLY DO, NO 3939 02:26:28,887 --> 02:26:31,389 CAUSATION, WE THROW IT AWAY. 3940 02:26:31,389 --> 02:26:33,358 I WOULD SAY WE'RE DOING THIS 3941 02:26:33,358 --> 02:26:33,925 TOO MUCH. 3942 02:26:33,925 --> 02:26:35,560 THESE ARE MOST OF THE 3943 02:26:35,560 --> 02:26:37,162 TRIALS, MOST OF THEM SHORT, 3944 02:26:37,162 --> 02:26:40,232 SIX MONTHS TO A YEAR, THE 3945 02:26:40,232 --> 02:26:42,968 LONGEST THREE YEARS THAT WAS 3946 02:26:42,968 --> 02:26:44,469 DONE ON PEOPLE 67.8 YEARS OF 3947 02:26:44,469 --> 02:26:44,936 AGE. 3948 02:26:44,936 --> 02:26:47,672 SO TO BE CLEAR WHEN WE DO 3949 02:26:47,672 --> 02:26:49,708 THE INTERVENTION, THE KNOWN 3950 02:26:49,708 --> 02:26:52,344 MECHANISM FOR VITAMIN D, 3951 02:26:52,344 --> 02:26:53,478 ATTEN UNITED STATES THE 3952 02:26:53,478 --> 02:26:55,413 VARIABILITY OF THE 3953 02:26:55,413 --> 02:26:57,015 CHOLESTEROL PATHWAY OVER A 3954 02:26:57,015 --> 02:26:57,749 DECADE OF LIFE. 3955 02:26:57,749 --> 02:26:59,017 WHEN WE SIMULATE THAT, IT 3956 02:26:59,017 --> 02:27:01,720 GIVES BACK TO US WHAT WE SEE 3957 02:27:01,720 --> 02:27:02,854 IN THE OBSERVATIONAL DATA 3958 02:27:02,854 --> 02:27:04,022 THAT YEAH, THIS WOULD IN 3959 02:27:04,022 --> 02:27:06,424 FACT LOWER THE CONVERSION TO 3960 02:27:06,424 --> 02:27:09,227 ALZHEIMER'S SO THAT GIVES ME 3961 02:27:09,227 --> 02:27:11,229 SOME CONFIDENCE TO THE MODEL 3962 02:27:11,229 --> 02:27:12,998 BUT THAT THE MECHANISM WOULD 3963 02:27:12,998 --> 02:27:13,465 BE EXPLANATORY. 3964 02:27:13,465 --> 02:27:16,668 NOW WHAT YOU CAN DO IN A 3965 02:27:16,668 --> 02:27:18,303 SIMULATION IS SIMULATE THE 3966 02:27:18,303 --> 02:27:19,871 EXACT TRIALS THAT WERE RUN. 3967 02:27:19,871 --> 02:27:22,407 SO WE WENT BACK, SIMULATED 3968 02:27:22,407 --> 02:27:23,708 THE TRIALS, EXACTLY THE 3969 02:27:23,708 --> 02:27:24,943 AGES, TRIALS THEY WERE 3970 02:27:24,943 --> 02:27:26,311 FOLLOWED AND SO FORTH AND 3971 02:27:26,311 --> 02:27:28,947 SAID IN THE SIMULATION GIVEN 3972 02:27:28,947 --> 02:27:29,881 THE MECHANISM WAS TOTALLY 3973 02:27:29,881 --> 02:27:32,951 EXPLAINABLE FOR WHAT YOU SAW 3974 02:27:32,951 --> 02:27:34,553 OR OBSERVED, WOULD WE HAVE 3975 02:27:34,553 --> 02:27:35,620 EXPECTED ANY OF THESE TRIALS 3976 02:27:35,620 --> 02:27:37,222 TO SHOW US A SIGNAL? 3977 02:27:37,222 --> 02:27:42,460 AND THE OWNS IS ANSWER IS 3978 02:27:42,460 --> 02:27:42,761 NO. 3979 02:27:42,761 --> 02:27:45,831 SO IN MY MIND VITAMIN D HAS 3980 02:27:45,831 --> 02:27:47,432 NOT BEEN TESTED AND ALTHOUGH 3981 02:27:47,432 --> 02:27:50,802 IT HAS NOT SUCCEEDED, IT HAS 3982 02:27:50,802 --> 02:27:52,804 NOT FAILED. 3983 02:27:52,804 --> 02:27:54,840 SO IN THE MODELS, THIS IS A 3984 02:27:54,840 --> 02:27:55,674 COMPLICATED PLOT AND THERE 3985 02:27:55,674 --> 02:27:57,742 ARE JUST A COUPLE OF MINUTES 3986 02:27:57,742 --> 02:27:59,010 LEFT BUT BASICALLY THE TIME 3987 02:27:59,010 --> 02:28:01,346 IS MUCH TOO SHORT TO HAVE AN 3988 02:28:01,346 --> 02:28:01,947 EFFECT. 3989 02:28:01,947 --> 02:28:03,982 YOU WOULD NEED TO WATCH TEN 3990 02:28:03,982 --> 02:28:06,151 YEARS IN THOSE TRIALS BEFORE 3991 02:28:06,151 --> 02:28:07,419 YOU SEE SEPARATION WHEREAS 3992 02:28:07,419 --> 02:28:09,721 ON THE RIGHT THE 3993 02:28:09,721 --> 02:28:10,388 OBSERVATIONAL TRIALS ARE 3994 02:28:10,388 --> 02:28:11,556 LONG ENOUGH. 3995 02:28:11,556 --> 02:28:13,058 SO THE BIG POINT I WANT TO 3996 02:28:13,058 --> 02:28:15,227 MAKE IN TERMS OF CLINICAL 3997 02:28:15,227 --> 02:28:17,229 TRIALS DESIGN IS I THINK THE 3998 02:28:17,229 --> 02:28:19,764 WAY WE DO PREVENTIVE 3999 02:28:19,764 --> 02:28:20,899 CLINICAL TRIALS IS REALLY 4000 02:28:20,899 --> 02:28:22,701 SUBOPTIMAL AND THE THE WAY I 4001 02:28:22,701 --> 02:28:24,769 THINK WE DO THIS THAT MAKES 4002 02:28:24,769 --> 02:28:26,371 NO SENSE, THE CURRENT 4003 02:28:26,371 --> 02:28:31,243 PARADIGM WE TEND TO RUN A 4004 02:28:31,243 --> 02:28:33,044 BLIND AND RANDOMIZED 4005 02:28:33,044 --> 02:28:34,346 CLINICAL TRIAL, THAT IS 4006 02:28:34,346 --> 02:28:36,314 GOOD, BUT WE ONLY TEST ONE 4007 02:28:36,314 --> 02:28:36,681 COMPOUND. 4008 02:28:36,681 --> 02:28:39,050 AND WHEN YOU DO THE 4009 02:28:39,050 --> 02:28:40,185 SIMULATIONS, THE ONE 4010 02:28:40,185 --> 02:28:42,821 COMPOUND IS ALMOST NEVER 4011 02:28:42,821 --> 02:28:43,722 EFFECTIVE. 4012 02:28:43,722 --> 02:28:48,693 YOU ARE DEPENDING ON SHEER 4013 02:28:48,693 --> 02:28:50,795 DUMB LUCK THAT THAT ONE 4014 02:28:50,795 --> 02:28:52,731 COMPOUND IS A PIECE OF THE 4015 02:28:52,731 --> 02:28:53,064 PUZZLE. 4016 02:28:53,064 --> 02:28:54,065 SO IT DOESN'T MATTER IF YOU 4017 02:28:54,065 --> 02:28:56,501 HAVE IN SUBJECT FOR THE 4018 02:28:56,501 --> 02:28:57,802 PATHWAY, IF INFLAMMATION IS 4019 02:28:57,802 --> 02:28:59,604 OVER, IT IS NOT ENOUGH, IT 4020 02:28:59,604 --> 02:29:01,706 IS A SMALL PIECE OF THE 4021 02:29:01,706 --> 02:29:02,107 PUZZLE. 4022 02:29:02,107 --> 02:29:03,541 SO WHAT WE FIND THEN IS IF 4023 02:29:03,541 --> 02:29:05,844 YOU DO A DIFFERENT METHOD, 4024 02:29:05,844 --> 02:29:07,345 INSTEAD OF TESTING A 4025 02:29:07,345 --> 02:29:08,847 COMPOUND, WHAT WE WILL TEST 4026 02:29:08,847 --> 02:29:11,082 IS THE TWIN MODEL ITSELF, 4027 02:29:11,082 --> 02:29:12,651 LIKE THE ALGORITHM. 4028 02:29:12,651 --> 02:29:13,752 SO THIS LETS YOU TEST ONE 4029 02:29:13,752 --> 02:29:15,787 THING SO YOU ARE NOT GETTING 4030 02:29:15,787 --> 02:29:18,490 INTO ALL THE SQUISHINESS OF 4031 02:29:18,490 --> 02:29:19,557 THINGS CHANGING ALL THE TIME 4032 02:29:19,557 --> 02:29:21,626 AS YOU ARE GOING THROUGH, SO 4033 02:29:21,626 --> 02:29:24,129 YOU TEST ONE ELEMENT BUT IT 4034 02:29:24,129 --> 02:29:25,897 IS COMPLICATED, A COMPLEX 4035 02:29:25,897 --> 02:29:26,231 OBJECT. 4036 02:29:26,231 --> 02:29:28,099 AND WHAT THAT MEANS IS YOU 4037 02:29:28,099 --> 02:29:29,834 TAKE THE MODEL, TAKE A 4038 02:29:29,834 --> 02:29:30,802 PERSON'S INDIVIDUAL DATA AND 4039 02:29:30,802 --> 02:29:33,838 EVERY PERSON WILL GET THEIR 4040 02:29:33,838 --> 02:29:34,406 OWN INDIVIDUALIZED 4041 02:29:34,406 --> 02:29:34,806 COMBINATION. 4042 02:29:34,806 --> 02:29:36,107 SO YOU ARE NOT TESTING A 4043 02:29:36,107 --> 02:29:38,510 COMPOUND BUT YOU ARE TESTING 4044 02:29:38,510 --> 02:29:39,778 IN ESSENCE YOUR ENTIRE 4045 02:29:39,778 --> 02:29:40,946 CONCEPTION OF WHAT IS 4046 02:29:40,946 --> 02:29:42,347 DRIVING THE DISEASE AND HOW 4047 02:29:42,347 --> 02:29:45,817 TO PERMIZE IT AND -- 4048 02:29:45,817 --> 02:29:46,952 PERSONALIZE IT AND WHAT YOU 4049 02:29:46,952 --> 02:29:47,752 ARE DOING. 4050 02:29:47,752 --> 02:29:49,754 AGAIN YOU ARE NOT DEPENDING 4051 02:29:49,754 --> 02:29:51,890 ON LUCK, YOU ARE GUIDING IT, 4052 02:29:51,890 --> 02:29:55,760 YOUR EFFECT SIZE IS HIGHER, 4053 02:29:55,760 --> 02:29:57,829 AND WHEN LOOKING AT VITAMIN 4054 02:29:57,829 --> 02:29:59,431 D, THIS IS CRUCIAL OR 4055 02:29:59,431 --> 02:30:00,632 ANYTHING OUT OF THE PRODUCT 4056 02:30:00,632 --> 02:30:03,101 WORLD, YOU ARE NOT TALKING 4057 02:30:03,101 --> 02:30:04,869 ABOUT A DRUG THAT WOULD TAKE 4058 02:30:04,869 --> 02:30:06,671 BILLIONS OF DOLLARS AND 4059 02:30:06,671 --> 02:30:09,741 RUNNING THE TILE THEREFORE 4060 02:30:09,741 --> 02:30:11,242 IS INFEASIBLE, NO ONE HAS 4061 02:30:11,242 --> 02:30:11,943 EVER DONE IT. 4062 02:30:11,943 --> 02:30:14,245 BUT IF YOU RUN IT THIS WAY, 4063 02:30:14,245 --> 02:30:17,115 YOU WILL GET MUCH LARGER 4064 02:30:17,115 --> 02:30:18,850 EFFECT SIZES, LOWER END, 4065 02:30:18,850 --> 02:30:19,985 MODELS THAT ARE FEASIBLE AND 4066 02:30:19,985 --> 02:30:21,519 I THINK THIS LETS US GET TO 4067 02:30:21,519 --> 02:30:23,621 A STYLE OF CLINICAL TRIAL I 4068 02:30:23,621 --> 02:30:24,289 AM EXCITED ABOUT. 4069 02:30:24,289 --> 02:30:25,724 AND IN THE INTEREST OF TIME, 4070 02:30:25,724 --> 02:30:28,126 I WILL SKIP THAT, THANK YOU, 4071 02:30:28,126 --> 02:30:36,067 AND ENTERTAIN QUESTIONS IN 4072 02:30:36,067 --> 02:30:45,076 THE BREAK, THANKS. 4073 02:30:45,076 --> 02:30:45,643 [APPLAUSE] 4074 02:30:45,643 --> 02:30:46,244 >> OKLAHOMA, CONTINUING 4075 02:30:46,244 --> 02:30:47,512 ALONG, WE WILL MOVE INTO THE 4076 02:30:47,512 --> 02:30:48,747 SECOND PART OF THIS SESSION 4077 02:30:48,747 --> 02:30:52,617 WHERE WE HAVE FOUR SPEAKERS 4078 02:30:52,617 --> 02:30:56,187 STARTING WITH ROB REINHART 4079 02:30:56,187 --> 02:30:57,689 FROM BOSTON UNIVERSITY 4080 02:30:57,689 --> 02:31:00,358 TALKING TO US ABOUT BRAIN 4081 02:31:00,358 --> 02:31:00,759 STIMULATION. 4082 02:31:00,759 --> 02:31:03,928 >> HELLO, THANK YOU, GLAD TO 4083 02:31:03,928 --> 02:31:05,964 BE HERE, THIS IS ONE DYNAMIC 4084 02:31:05,964 --> 02:31:06,898 CONFERENCE AND A REAL HONOR 4085 02:31:06,898 --> 02:31:08,099 TO SPEAK AT THIS' END. 4086 02:31:08,099 --> 02:31:09,734 SO I WOULD LIKE TO THANK MY 4087 02:31:09,734 --> 02:31:11,703 LAB MEMBERS AND FUNDING 4088 02:31:11,703 --> 02:31:12,971 AGENCIES UPFRONT. 4089 02:31:12,971 --> 02:31:15,273 THANK YOU OF COURSE TO THE 4090 02:31:15,273 --> 02:31:17,242 NIH WITH WHOM I HAVE WORKED 4091 02:31:17,242 --> 02:31:19,577 OVER THE YEARS. 4092 02:31:19,577 --> 02:31:22,080 SO JUST ONE OF THE OVER 4093 02:31:22,080 --> 02:31:26,818 ARCHING GOALS AS WE SEE IT 4094 02:31:26,818 --> 02:31:29,087 OF COGNITIVE AGING IS TO 4095 02:31:29,087 --> 02:31:31,589 DEVELOP NOVEL PROCEDURES 4096 02:31:31,589 --> 02:31:34,092 INCLUDING BRAIN STIMULATION 4097 02:31:34,092 --> 02:31:34,726 PROCEDURES TO EFFECTIVELY 4098 02:31:34,726 --> 02:31:36,594 SLOW OR THE IDEA IS TO 4099 02:31:36,594 --> 02:31:38,930 ARREST OR REVERSE COGNITIVE 4100 02:31:38,930 --> 02:31:41,132 DECLINE IN OLDER PEOPLE. 4101 02:31:41,132 --> 02:31:43,101 A PARALLEL GOAL FOR US AS 4102 02:31:43,101 --> 02:31:44,135 WELL AS IDENTIFY PARAMETERS 4103 02:31:44,135 --> 02:31:46,304 OF THOSE DISEASES THAT COULD 4104 02:31:46,304 --> 02:31:47,572 POTENTIALLY OPTIMIZE THEM 4105 02:31:47,572 --> 02:31:49,641 AND SOME OF THOSE PARAMETERS 4106 02:31:49,641 --> 02:31:51,443 THAT ARE EMERGING FROM OUR 4107 02:31:51,443 --> 02:31:53,244 LAB'S WORK, I WANT TO 4108 02:31:53,244 --> 02:31:55,146 UNDERSCORE THROUGHOUT THE 4109 02:31:55,146 --> 02:31:57,415 TALK THAT INVOLVE THE BRAIN 4110 02:31:57,415 --> 02:31:59,350 MECHANISM, SOME OF ITS 4111 02:31:59,350 --> 02:32:00,285 FEATURES, THE INTERVENTION 4112 02:32:00,285 --> 02:32:03,888 ITSELF AND THE STUDIED 4113 02:32:03,888 --> 02:32:04,289 POPULATION. 4114 02:32:04,289 --> 02:32:05,890 SO THE ROAD MAP FOR THIS 4115 02:32:05,890 --> 02:32:08,860 TALK IS TO INTRODUCE YOU TO 4116 02:32:08,860 --> 02:32:10,462 OUR THEORETICAL FRAMEWORK, 4117 02:32:10,462 --> 02:32:12,363 OUR TECHNICAL APPROACH, SOME 4118 02:32:12,363 --> 02:32:14,399 OF OUR CURRENT PROMISING 4119 02:32:14,399 --> 02:32:17,702 RESULTS AND FUTURE 4120 02:32:17,702 --> 02:32:18,103 DIRECTIONS. 4121 02:32:18,103 --> 02:32:23,441 SO THE APPROACH WE TAKE TO 4122 02:32:23,441 --> 02:32:24,809 BRAIN STIMULATION, 4123 02:32:24,809 --> 02:32:26,244 NEUROMODULATION DESIGNED, IS 4124 02:32:26,244 --> 02:32:28,546 GROUNDED IN REALLY DECADES 4125 02:32:28,546 --> 02:32:30,048 OF FUNDAMENTAL SYSTEMS 4126 02:32:30,048 --> 02:32:33,585 NEUROSCIENCE THAT VIEWS 4127 02:32:33,585 --> 02:32:36,521 COGNITION AS ARISING FROM 4128 02:32:36,521 --> 02:32:39,324 SYNC NOW IS 4129 02:32:39,324 --> 02:32:40,291 ELECTROPHYSIOLOGICAL RHYTHM 4130 02:32:40,291 --> 02:32:41,493 OR OSCILLATION. 4131 02:32:41,493 --> 02:32:43,695 SO THESE ARE RHYTHMIC 4132 02:32:43,695 --> 02:32:45,730 FLUCTUATIONS OVER TIME IN 4133 02:32:45,730 --> 02:32:48,133 BRAIN ACTIVITY OR 4134 02:32:48,133 --> 02:32:49,601 EXCITABILITY THAT DERIVE 4135 02:32:49,601 --> 02:33:00,044 FROM IN INHIBITOR AND 4136 02:33:02,180 --> 02:33:02,881 EXCITATORY POST-SYNAPTIC 4137 02:33:02,881 --> 02:33:08,520 THAT WILL SHOW UP IN THE 4138 02:33:08,520 --> 02:33:09,787 ENCEPHALOPATHY RECORDINGS. 4139 02:33:09,787 --> 02:33:10,922 OSCILLATION IS INTERESTING 4140 02:33:10,922 --> 02:33:12,857 FUNCTIONALLY BECAUSE THEY 4141 02:33:12,857 --> 02:33:14,592 ARE THOUGHT TO FACILITATE 4142 02:33:14,592 --> 02:33:16,861 PRECISE BUT FLEXIBLE BRAIN 4143 02:33:16,861 --> 02:33:20,798 COMMUNICATION AND 4144 02:33:20,798 --> 02:33:21,599 PLASTICITY. 4145 02:33:21,599 --> 02:33:26,704 TWO OF THE MOST EXTENSIVELY 4146 02:33:26,704 --> 02:33:27,505 STUDIES SYNCHRONIZATION 4147 02:33:27,505 --> 02:33:29,841 MOTIFS AS THEY ARE SOMETIMES 4148 02:33:29,841 --> 02:33:32,810 CALLED IS THE BETWEEN 4149 02:33:32,810 --> 02:33:36,181 FREQUENCY PHASED SING PAYING 4150 02:33:36,181 --> 02:33:39,684 SO WHEN TWO NEURONAL 4151 02:33:39,684 --> 02:33:41,452 ENSEMBLES ARE COORDINATED 4152 02:33:41,452 --> 02:33:43,521 WITH EACH OTHER IN THE BRAIN 4153 02:33:43,521 --> 02:33:46,958 SO THIS IS ASPECT OF NEURAL 4154 02:33:46,958 --> 02:33:47,325 ACTIVITY. 4155 02:33:47,325 --> 02:33:50,228 ANOTHER DOMINANT MOATY IS 4156 02:33:50,228 --> 02:33:53,531 BETWEEN FREQUENCY PHASE 4157 02:33:53,531 --> 02:33:54,265 AMPLITUDE SYNCHRONIZATION, 4158 02:33:54,265 --> 02:33:54,933 SOMETIMES CALLED COUPLING. 4159 02:33:54,933 --> 02:34:03,808 THIS IS A MEASURE OF THE 4160 02:34:03,808 --> 02:34:08,513 HIERARCHICAL, WHEN THE LOW 4161 02:34:08,513 --> 02:34:10,648 FREQUENCY WAVE AMPLITUDES 4162 02:34:10,648 --> 02:34:12,116 THE IN SYNC OSCILLATION. 4163 02:34:12,116 --> 02:34:14,452 SO WE HAVE TOOLS AS NEURAL 4164 02:34:14,452 --> 02:34:17,855 SCIENTISTS THAT CAN CAUSALLY 4165 02:34:17,855 --> 02:34:20,158 ISOLATE AND AUGMENT THESE 4166 02:34:20,158 --> 02:34:21,826 RHYTHMIC PATTERNS OF BRAIN 4167 02:34:21,826 --> 02:34:23,661 ACTIVITY THAT ARE IMPLICATED 4168 02:34:23,661 --> 02:34:25,496 IN COGNITIVE FUNCTION AND 4169 02:34:25,496 --> 02:34:26,231 DYSFUNCTION. 4170 02:34:26,231 --> 02:34:29,200 SO ONE OF THESE TOOLS, IN A 4171 02:34:29,200 --> 02:34:33,271 LARGER CLASS OF TOOLS IS 4172 02:34:33,271 --> 02:34:34,239 CALLED TRANSCRANIAL 4173 02:34:34,239 --> 02:34:34,872 ALTERNATING CURRENT 4174 02:34:34,872 --> 02:34:35,306 STIMULATION. 4175 02:34:35,306 --> 02:34:39,244 THIS IS A NONINVASIVE 4176 02:34:39,244 --> 02:34:40,044 SUBTHRESHOLD NEUROMODULATION 4177 02:34:40,044 --> 02:34:48,720 TOOL THAT INVOLVES APPLYING 4178 02:34:48,720 --> 02:34:50,421 EXTREMELY WEEK SONUCIDAL 4179 02:34:50,421 --> 02:34:53,258 ELECTRODES TO THE SCOPE THAT 4180 02:34:53,258 --> 02:34:54,492 INDUCES FIELD GRADIENTS IN 4181 02:34:54,492 --> 02:34:56,127 BRAIN REGIONS THAT ARE 4182 02:34:56,127 --> 02:34:57,528 IMPLICATED IN COGNITIVE 4183 02:34:57,528 --> 02:34:58,429 FUNCTION OR DYSFUNCTION, SO 4184 02:34:58,429 --> 02:35:03,034 THIS IS ONE OF THE SAFEST 4185 02:35:03,034 --> 02:35:08,439 WAYS TO NONINVASIVELY 4186 02:35:08,439 --> 02:35:10,208 STIMULATE MACROSCOPIC BRAIN 4187 02:35:10,208 --> 02:35:10,875 WORK DYNAMICS. 4188 02:35:10,875 --> 02:35:13,378 15 YEARS OF ANIMAL RESEARCH 4189 02:35:13,378 --> 02:35:16,648 SUGGEST THE ACTION 4190 02:35:16,648 --> 02:35:19,851 MECHANISMV NEURONAL IN 4191 02:35:19,851 --> 02:35:21,886 TRAINMENT AND NEURONAL IN 4192 02:35:21,886 --> 02:35:22,920 PLASTICITY. 4193 02:35:22,920 --> 02:35:24,555 SO I WANT TO BRIEFLY TAKE 4194 02:35:24,555 --> 02:35:28,493 YOU THROUGH A NUMBER OF 4195 02:35:28,493 --> 02:35:32,096 YEARS OF COLLECTIONS OF WORK 4196 02:35:32,096 --> 02:35:34,032 THAT FALL UNDER THE HEADER 4197 02:35:34,032 --> 02:35:34,999 OF STUDY 1. 4198 02:35:34,999 --> 02:35:40,338 THE UPSO THE IS WE ARE 4199 02:35:40,338 --> 02:35:43,775 FINDING FRONTAL TEMPORAL 4200 02:35:43,775 --> 02:35:45,777 HIGH RESOLUTION MULTIFOCAL 4201 02:35:45,777 --> 02:35:47,679 TACS MAY IMPROVE VISUAL 4202 02:35:47,679 --> 02:35:49,013 WORKING MEMORY IN OLDER 4203 02:35:49,013 --> 02:35:51,249 ADULTS AND I WANT TO 4204 02:35:51,249 --> 02:35:53,284 IDENTIFY PARAMETERS THAT ARE 4205 02:35:53,284 --> 02:35:54,886 IMPORTANT TO OPTIMIZE 4206 02:35:54,886 --> 02:35:56,354 STIMULATION PROCEDURES TO 4207 02:35:56,354 --> 02:35:58,323 GET BETTER MEMORY BENEFITS. 4208 02:35:58,323 --> 02:35:59,624 SO BY HIGHER RESOLUTION, I 4209 02:35:59,624 --> 02:36:01,659 AM REFERRING TO A NEWER 4210 02:36:01,659 --> 02:36:03,828 TECHNOLOGY THAT PROVIDES US 4211 02:36:03,828 --> 02:36:06,130 WITH SMALLER ELECTRODES 4212 02:36:06,130 --> 02:36:07,632 SPECIAL MANY MORE OF THEM SO 4213 02:36:07,632 --> 02:36:12,837 WE CAN FOLLOW THE CURRENT IN 4214 02:36:12,837 --> 02:36:18,176 A HIGH SPATIAL RECOGNITION 4215 02:36:18,176 --> 02:36:18,710 MATTER, MULTIFOCAL 4216 02:36:18,710 --> 02:36:21,045 STIMULATING REGIONS OF THE 4217 02:36:21,045 --> 02:36:22,980 BRAIN SIMULTANEOUSLY SO A 4218 02:36:22,980 --> 02:36:24,716 WAY TO MODULATE CONNECTION 4219 02:36:24,716 --> 02:36:25,550 WITHIN THE BRAIN. 4220 02:36:25,550 --> 02:36:28,920 THERE ARE TWO FLAVORS IN 4221 02:36:28,920 --> 02:36:32,457 THIS CONTEXT, THE ANTIPHASE, 4222 02:36:32,457 --> 02:36:35,126 DESTRUCTIVELY INTERFERING OR 4223 02:36:35,126 --> 02:36:37,929 DESYNCHRONIZING ACS THAT CAN 4224 02:36:37,929 --> 02:36:40,665 IMPEDE LONG DISTANCES AND 4225 02:36:40,665 --> 02:36:44,969 THE IN-PHASE THAT CAN 4226 02:36:44,969 --> 02:36:46,104 FACILITATE NEURONAL 4227 02:36:46,104 --> 02:36:48,639 COMMUNICATION BETWEEN 4228 02:36:48,639 --> 02:36:53,311 DISTANT BRAIN REGIONS. 4229 02:36:53,311 --> 02:36:59,050 AND THEN LASTLY, I HAVE 4230 02:36:59,050 --> 02:37:09,527 ACTUALLY PIONEERED THE 4231 02:37:10,228 --> 02:37:11,329 PHYSIOLOGY OF PEAK MEMORY. 4232 02:37:11,329 --> 02:37:13,264 SO YOU COME INTO THE LAB, 4233 02:37:13,264 --> 02:37:17,502 GET A MEMORY TEST, SEE A 4234 02:37:17,502 --> 02:37:19,737 OBJECT, THERE IS A MEMORY 4235 02:37:19,737 --> 02:37:23,808 DELAY, SEE ANOTHER OBJECT, 4236 02:37:23,808 --> 02:37:27,311 TELL US WHAT YOU SEE AND WE 4237 02:37:27,311 --> 02:37:32,316 FIND FOR WHAT HAS BEEN 4238 02:37:32,316 --> 02:37:34,352 RECOGNIZED OVER THREE 4239 02:37:34,352 --> 02:37:36,721 DECADES, THE DELAYED MATCH 4240 02:37:36,721 --> 02:37:39,891 TO EXAMINER TASK WITH MEMORY 4241 02:37:39,891 --> 02:37:41,159 AND WE PREDICTED THIS WAS 4242 02:37:41,159 --> 02:37:45,463 DUE AT LEAST PARTIALLY TO 4243 02:37:45,463 --> 02:37:47,031 ATTEN WAGES, SPECIFICALLY 4244 02:37:47,031 --> 02:37:51,969 LOW RANGE SYNCHRONIZATION 4245 02:37:51,969 --> 02:37:54,739 ACROSS THE TEMPOROFRONTAL 4246 02:37:54,739 --> 02:37:58,443 CONTEXT, THIS IS TOP DOWN ON 4247 02:37:58,443 --> 02:37:59,610 THE PROCESSING TO THE BACK 4248 02:37:59,610 --> 02:38:03,714 OF THE HEAD AS WELL AS THE 4249 02:38:03,714 --> 02:38:09,821 ATTEN WAGES, THE THETA-GAMMA 4250 02:38:09,821 --> 02:38:12,423 PHASES AMPLITUDE OF ACROSS 4251 02:38:12,423 --> 02:38:13,124 COUPLING SYNCHRONIZATION AND 4252 02:38:13,124 --> 02:38:14,392 THAT IS THOUGHT TO PLAY A 4253 02:38:14,392 --> 02:38:17,228 ROLE IN THE ACTIVE ONGOING 4254 02:38:17,228 --> 02:38:18,729 STORAGE AND PROCESSING OF 4255 02:38:18,729 --> 02:38:19,931 THE WORKING ITEMS 4256 02:38:19,931 --> 02:38:20,331 THEMSELVES. 4257 02:38:20,331 --> 02:38:23,768 AND THAT IS WHAT WE TUNED TO 4258 02:38:23,768 --> 02:38:24,335 IN 2019. 4259 02:38:24,335 --> 02:38:26,571 OLDER PEOPLE WERE REDUCED 4260 02:38:26,571 --> 02:38:28,840 IN, AGAIN, LETS ASSAY THERE 4261 02:38:28,840 --> 02:38:34,045 IS AMPLITUDE COUPLING IN THE 4262 02:38:34,045 --> 02:38:35,446 FRONTAL CORTEX AND THEN THEY 4263 02:38:35,446 --> 02:38:40,151 ARE LOSING THAT CONNECTIVITY 4264 02:38:40,151 --> 02:38:42,687 IN NEURAL SYNCHRONIZATION IN 4265 02:38:42,687 --> 02:38:45,056 THE PREFRONTAL CORTEX. 4266 02:38:45,056 --> 02:38:50,328 BUT THEY DID HAVE AN 4267 02:38:50,328 --> 02:38:54,966 INTERESTING ASSOCIATION IN 4268 02:38:54,966 --> 02:38:55,533 CONNECTIVITY. 4269 02:38:55,533 --> 02:39:03,174 SO WE USE THIS TO DESIGN 4270 02:39:03,174 --> 02:39:06,244 CROSS FREQUENCY AFS TO THE 4271 02:39:06,244 --> 02:39:08,880 MODEL, WE COMBINE EACH 4272 02:39:08,880 --> 02:39:15,253 PERSON'S FREQUENCY, THAT 4273 02:39:15,253 --> 02:39:16,287 NEURAL CONNECTIVITY MEASURE 4274 02:39:16,287 --> 02:39:23,561 IN ORDER TO ACT VIES PEOPLE 4275 02:39:23,561 --> 02:39:27,164 TO THE FOX SEE OF THE BRAIN 4276 02:39:27,164 --> 02:39:28,432 AND PHASE COUPLING AND 4277 02:39:28,432 --> 02:39:29,967 BEHAVIOR COMES ALONG FOR THE 4278 02:39:29,967 --> 02:39:32,136 RIDE SO WE CAN BOOST 4279 02:39:32,136 --> 02:39:33,704 COGNITIVE PERFORMANCE ON 4280 02:39:33,704 --> 02:39:36,908 THIS MEMORY TASK BY 4281 02:39:36,908 --> 02:39:38,809 RESURRECTING THESE NEURAL 4282 02:39:38,809 --> 02:39:40,611 CODING TECHNOLOGIES BUT 4283 02:39:40,611 --> 02:39:43,714 WITHOUT SLOWING PEOPLE DOWN, 4284 02:39:43,714 --> 02:39:44,382 RT DIDN'T CHANGE. 4285 02:39:44,382 --> 02:39:47,785 SO WE CAN MAKE PEOPLE BETTER 4286 02:39:47,785 --> 02:39:50,388 WITHOUT SLOWING THEM DOWN 4287 02:39:50,388 --> 02:39:58,696 AND AFTER ONE SHOT, 25 4288 02:39:58,696 --> 02:40:01,465 MINUTES FOR THE TEST, IT WAS 4289 02:40:01,465 --> 02:40:03,000 STATISTICALLY HIGH FOR BRAIN 4290 02:40:03,000 --> 02:40:04,368 MEASURING. 4291 02:40:04,368 --> 02:40:09,941 WE ALSO LOOKED AT THE 4292 02:40:09,941 --> 02:40:11,309 COUPLING SIGNIFICANCE, THE 4293 02:40:11,309 --> 02:40:13,377 BETTER THE COUPLING, THE 4294 02:40:13,377 --> 02:40:14,045 BETTER YOUR MEMORY. 4295 02:40:14,045 --> 02:40:16,013 AFTER 25 MINUTES OF 4296 02:40:16,013 --> 02:40:18,749 STIMULATION, WE CANNOT ONLY 4297 02:40:18,749 --> 02:40:26,223 REVISE THESE CODING MOAT 4298 02:40:26,223 --> 02:40:28,859 MOTIFFS, NOW WE CAN REVIEW 4299 02:40:28,859 --> 02:40:34,198 THEM ON THIS COUPLING LEVEL. 4300 02:40:34,198 --> 02:40:39,036 WE APPLY THE ANTIPHASE, 4301 02:40:39,036 --> 02:40:39,870 DESTRUCTIVELY ENTER VEERING 4302 02:40:39,870 --> 02:40:45,543 ATF AND SEE WE CAN INDUCE 4303 02:40:45,543 --> 02:40:46,277 DEFICIT IN MEMORY. 4304 02:40:46,277 --> 02:40:48,045 THIS IS SOMETHING WE 4305 02:40:48,045 --> 02:40:51,916 OBSERVED SOME YEARS AGO, 4306 02:40:51,916 --> 02:40:55,119 THIS BI DIRECTIONAL CONTROL 4307 02:40:55,119 --> 02:40:56,520 OF CIRCUITRY OF THE BRAIN 4308 02:40:56,520 --> 02:40:59,156 BASED ON WHAT WE'RE PULLING 4309 02:40:59,156 --> 02:41:00,524 OUT OF THE SYSTEM. 4310 02:41:00,524 --> 02:41:06,430 SO HERE WE LOOK AT HEALTHY 4311 02:41:06,430 --> 02:41:07,732 ADULTS BASED ON PHASAL 4312 02:41:07,732 --> 02:41:10,701 RELATIONSHIPS WITH THE TACS 4313 02:41:10,701 --> 02:41:12,103 AND ALSO OBSERVING IN 4314 02:41:12,103 --> 02:41:14,472 LABORATORIES ACROSS THE 4315 02:41:14,472 --> 02:41:16,674 WORLD, WE SEARCHERS ARE 4316 02:41:16,674 --> 02:41:17,708 WITNESSING A SIMILAR 4317 02:41:17,708 --> 02:41:18,042 PATTERN. 4318 02:41:18,042 --> 02:41:22,780 THIS IS THE LARGEST 4319 02:41:22,780 --> 02:41:24,682 METANALYSIS TO DATE. 4320 02:41:24,682 --> 02:41:25,616 WE RECENTLY PUBLISHED 4321 02:41:25,616 --> 02:41:28,352 ANOTHER EXPERIMENT WHERE WE 4322 02:41:28,352 --> 02:41:29,720 REPLICATED THE EXPERIMENTAL 4323 02:41:29,720 --> 02:41:31,455 FINDINGS IN THE COHORT OF 4324 02:41:31,455 --> 02:41:33,557 ALL THE PEOPLE AND EXTENDED 4325 02:41:33,557 --> 02:41:37,728 THEM, LOOKING AT FACIAL 4326 02:41:37,728 --> 02:41:38,829 SPECIFICITY AND BEHAVIORAL 4327 02:41:38,829 --> 02:41:44,268 BENEFITS WITH THE 4328 02:41:44,268 --> 02:41:44,769 PERSONALIZEDTACS. 4329 02:41:44,769 --> 02:41:47,872 THE UPSHOT HERE IS YOU CAN'T 4330 02:41:47,872 --> 02:41:48,839 STIMULATE JUST ANY PART OF 4331 02:41:48,839 --> 02:41:52,109 THE BRAIN AND SEE THESE 4332 02:41:52,109 --> 02:41:52,777 EFFECTS. 4333 02:41:52,777 --> 02:41:56,313 YOU HAVE TO AFFECT 4334 02:41:56,313 --> 02:41:58,182 SIMULTANEOUSLY FOR DOMAIN, 4335 02:41:58,182 --> 02:41:58,949 PARADIGM, STIMULUS, MORE 4336 02:41:58,949 --> 02:42:01,385 EVIDENCE TO SUGGEST WE'RE 4337 02:42:01,385 --> 02:42:03,220 REALLY LOCKING INTO A 4338 02:42:03,220 --> 02:42:04,522 MANIPULATION KIND OF 4339 02:42:04,522 --> 02:42:04,889 ACTIVITY. 4340 02:42:04,889 --> 02:42:07,892 IN TERMS OF FREQUENCY, YOU 4341 02:42:07,892 --> 02:42:10,027 CAN'T JUST CREATE ANY 4342 02:42:10,027 --> 02:42:17,635 FREQUENCY OF THE BRAIN NOR 4343 02:42:17,635 --> 02:42:22,440 CAN YOU STIMULATE FREQUENCY 4344 02:42:22,440 --> 02:42:24,742 OF THE INDIVIDUAL AND 4345 02:42:24,742 --> 02:42:27,178 FINDING IT IS PERCEPTUAL. 4346 02:42:27,178 --> 02:42:28,679 SO IT CAN IMPROVE VISUAL 4347 02:42:28,679 --> 02:42:30,081 WORKING MEMORY IN OLDER 4348 02:42:30,081 --> 02:42:31,816 PEOPLE AT LEAST IN THE 4349 02:42:31,816 --> 02:42:34,885 CONCEPT STUDY AND 4350 02:42:34,885 --> 02:42:40,925 IDENTIFYING PERSONALIZED 4351 02:42:40,925 --> 02:42:45,029 DATA TREKS SEE, ZERO DEGREE 4352 02:42:45,029 --> 02:42:50,501 LAG AND SPACE LEFT FRONTO 4353 02:42:50,501 --> 02:42:51,035 TEMPORAL. 4354 02:42:51,035 --> 02:42:55,573 SO HERE IS ANOTHER EXAMPLE 4355 02:42:55,573 --> 02:42:56,574 OF EXPERIMENTS, STUDY NUMBER 4356 02:42:56,574 --> 02:43:02,113 2 AND WHAT IS EMERGING IS 4357 02:43:02,113 --> 02:43:06,317 THE FRONTO AND PROPRIETY 4358 02:43:06,317 --> 02:43:08,486 TALL TACS MAY SELECT FOR 4359 02:43:08,486 --> 02:43:09,420 IMPROVEMENT IN AUDITORY 4360 02:43:09,420 --> 02:43:12,356 VERBAL WORKING MEMORY AND 4361 02:43:12,356 --> 02:43:14,725 LONG-TERM MEMORY IN OLDER 4362 02:43:14,725 --> 02:43:16,861 ADULTS AND THESE ARE THE 4363 02:43:16,861 --> 02:43:17,762 PARAMETERS FOR OPTIMIZING 4364 02:43:17,762 --> 02:43:18,062 HERE. 4365 02:43:18,062 --> 02:43:19,864 SO WE HAVE KNOWN FOR ALMOST 4366 02:43:19,864 --> 02:43:22,633 A CENTURY FROM EXPERIMENTAL 4367 02:43:22,633 --> 02:43:25,035 PSYCHOLOGY, IF I READ YOU A 4368 02:43:25,035 --> 02:43:27,138 LIST OF WORDS, CAN YOU 4369 02:43:27,138 --> 02:43:29,473 RECALL BACK TO ME FOR AS 4370 02:43:29,473 --> 02:43:32,343 MANY WORDS AS YOU CAN. 4371 02:43:32,343 --> 02:43:34,612 YOU HAVE THE ADVANTAGE OF 4372 02:43:34,612 --> 02:43:37,448 THE EARLY EFFECTS BASED ON 4373 02:43:37,448 --> 02:43:38,516 THE DUAL PLATFORM NETWORK 4374 02:43:38,516 --> 02:43:41,051 AND YOU ALSO HAVE AN 4375 02:43:41,051 --> 02:43:42,419 ADVANTAGE LINKED TO WORKING 4376 02:43:42,419 --> 02:43:43,120 MEMORY. 4377 02:43:43,120 --> 02:43:45,923 WE KNOW QUITE A LOT ABOUT 4378 02:43:45,923 --> 02:43:47,825 THE FUNCTIONAL ANATOMY OF 4379 02:43:47,825 --> 02:43:50,995 THE POSITIONING CURVE 4380 02:43:50,995 --> 02:43:51,462 EFFECTS. 4381 02:43:51,462 --> 02:43:53,864 THE LOBULES A PLAYER IN 4382 02:43:53,864 --> 02:43:57,802 RECENT MEMORY AND THE 4383 02:43:57,802 --> 02:44:00,104 PREFRONTO CORTEX A MAJOR 4384 02:44:00,104 --> 02:44:01,572 CONTRIBUTOR BUT WHAT WE 4385 02:44:01,572 --> 02:44:06,043 DON'T KNOW IS IF THERE ARE 4386 02:44:06,043 --> 02:44:07,778 INDIVIDUAL MECHANISMS WITHIN 4387 02:44:07,778 --> 02:44:09,346 THESE BRAIN SECTIONS THAT 4388 02:44:09,346 --> 02:44:11,549 CAN PRESERVE FUNCTION AND IF 4389 02:44:11,549 --> 02:44:13,317 THERE ARE, AND CAN BE 4390 02:44:13,317 --> 02:44:15,953 IDENTIFIED, WE CAN BRING 4391 02:44:15,953 --> 02:44:19,557 TACS TO SELECTIVELY AND 4392 02:44:19,557 --> 02:44:20,257 INDEPENDENTLY MANIPULATE 4393 02:44:20,257 --> 02:44:21,425 THESE MEMORY SYSTEMS AND 4394 02:44:21,425 --> 02:44:23,227 THAT IS PRECISELY WHAT WE 4395 02:44:23,227 --> 02:44:25,863 SET OUT TO DO IN THIS SERIES 4396 02:44:25,863 --> 02:44:28,032 OF EXPERIMENTS HEADED UP BY 4397 02:44:28,032 --> 02:44:33,470 THE POST-DOC IN THE LAB NOW, 4398 02:44:33,470 --> 02:44:35,873 WE DEFINED TWO PROCEDURES 4399 02:44:35,873 --> 02:44:38,843 AND THIS TIME WE WERE 4400 02:44:38,843 --> 02:44:41,879 INTERESTED IN SUSTAINING THE 4401 02:44:41,879 --> 02:44:45,749 BENEFITS FOR FOUR DAYS IN A 4402 02:44:45,749 --> 02:44:52,690 ROW SO WE REPEATED THE TESTS 4403 02:44:52,690 --> 02:44:54,391 FOUR TIMES IN A ROW AND WHAT 4404 02:44:54,391 --> 02:44:57,061 WE FIND IS THE SPATIAL 4405 02:44:57,061 --> 02:44:58,195 COMPONENTS OF THE MECHANISM 4406 02:44:58,195 --> 02:45:01,031 ON THE ONE HAND AND THE 4407 02:45:01,031 --> 02:45:02,066 MEMORY SYSTEM BEING 4408 02:45:02,066 --> 02:45:04,568 MANIPULATED ON THE OTHER 4409 02:45:04,568 --> 02:45:05,102 HAND. 4410 02:45:05,102 --> 02:45:06,403 IN THE BOTTOM LEFT IN THE 4411 02:45:06,403 --> 02:45:08,839 RED BOX, YOU SEE WHEN WE 4412 02:45:08,839 --> 02:45:12,243 APPLY LOW FREQUENCY, NOT 4413 02:45:12,243 --> 02:45:15,312 HIGH FREQUENCY, ENTRAINMENT 4414 02:45:15,312 --> 02:45:19,850 TO PARITAL CORTEX AND NOT 4415 02:45:19,850 --> 02:45:25,189 FRONTO TEMPORAL CORTEX, WE 4416 02:45:25,189 --> 02:45:27,725 CAN ACHIEVE IMPROVEMENT ON 4417 02:45:27,725 --> 02:45:29,760 THE WORKING EFFECT. 4418 02:45:29,760 --> 02:45:35,733 ON DAY 2, 3 AND 4, WHEN WE 4419 02:45:35,733 --> 02:45:39,103 APPLY THE RETAINMENT, WE 4420 02:45:39,103 --> 02:45:40,604 KRAUSE LONG-TERM MEMORY 4421 02:45:40,604 --> 02:45:41,405 IMPROVEMENTS. 4422 02:45:41,405 --> 02:45:43,874 ON DAY 2, 3 AND 4 AND ONE 4423 02:45:43,874 --> 02:45:46,176 MONTH POST. 4424 02:45:46,176 --> 02:45:56,720 SO THIS IS THE OUTSET OF THE 4425 02:45:57,354 --> 02:45:58,923 DOSE CURATION I WANT TO 4426 02:45:58,923 --> 02:46:00,224 UNDERSCORE, HOW MANY DAYS IT 4427 02:46:00,224 --> 02:46:02,760 TAKES FOR THE MEMORY TO COME 4428 02:46:02,760 --> 02:46:03,494 ONLINE. 4429 02:46:03,494 --> 02:46:05,362 WE DID SOMETHING UNIQUE HERE 4430 02:46:05,362 --> 02:46:08,565 WHERE WE ACQUIRED 4431 02:46:08,565 --> 02:46:10,000 PERFORMANCE DATA WITHIN THE 4432 02:46:10,000 --> 02:46:11,869 EXPERIMENT ITSELF WHICH IS 4433 02:46:11,869 --> 02:46:14,972 SELDOMLY DONE WHICH ALLOWS 4434 02:46:14,972 --> 02:46:17,107 US TO EVALUATE HOW PEOPLE 4435 02:46:17,107 --> 02:46:20,277 ARE RESPONDING TO THE MEMORY 4436 02:46:20,277 --> 02:46:22,112 BENEFIT AND WE FOUND THAT 4437 02:46:22,112 --> 02:46:26,650 THE SEEPER THAT RATE OF 4438 02:46:26,650 --> 02:46:28,719 IMPROVEMENT FOR BOTH MEMORY 4439 02:46:28,719 --> 02:46:30,220 IMPROVEMENT, THE BIGGER THE 4440 02:46:30,220 --> 02:46:31,488 BENEFITS ONE MONTH LATER. 4441 02:46:31,488 --> 02:46:34,124 WE ALSO FIND THE BASELINE 4442 02:46:34,124 --> 02:46:36,060 GENERAL COGNITIVE 4443 02:46:36,060 --> 02:46:38,162 PERFORMANCE MEASURED IN 4444 02:46:38,162 --> 02:46:39,997 LOCO, HOW PEOPLE RESPONDED 4445 02:46:39,997 --> 02:46:42,266 DURING THE PREDICTION AND 4446 02:46:42,266 --> 02:46:44,868 HOW LARGE THE BEN GETS WERE 4447 02:46:44,868 --> 02:46:46,003 ONE MONTH AFTER IT WAS OVER. 4448 02:46:46,003 --> 02:46:51,108 AND THAT IS WHAT I MEANT BY 4449 02:46:51,108 --> 02:46:52,943 COGNITION OF STUDIES AS A 4450 02:46:52,943 --> 02:46:56,981 FEATURE. 4451 02:46:56,981 --> 02:46:59,950 AT THE SPEED OF MEMORY 4452 02:46:59,950 --> 02:47:03,887 LEVEL, WE SEE PROMISING 4453 02:47:03,887 --> 02:47:05,089 RESULTS, NORTHERN IRELAND 4454 02:47:05,089 --> 02:47:06,090 MODERATE SIZE EFFECTS. 4455 02:47:06,090 --> 02:47:07,858 WE THINK THESE ARE BEING 4456 02:47:07,858 --> 02:47:09,159 UNDERESTIMATED AS TO THE 4457 02:47:09,159 --> 02:47:10,294 POWER OF THIS PROCEDURE 4458 02:47:10,294 --> 02:47:12,162 BECAUSE THERE IS A SMALL 4459 02:47:12,162 --> 02:47:14,732 NUMBER OF STUDIES TOGETHER 4460 02:47:14,732 --> 02:47:17,601 AND THE VAST MAJORITY DON'T 4461 02:47:17,601 --> 02:47:19,670 PERSONALIZE THE SIMULATION, 4462 02:47:19,670 --> 02:47:21,238 NOT MULTIFOCAL, NOT HIGH 4463 02:47:21,238 --> 02:47:21,638 DEFINITION. 4464 02:47:21,638 --> 02:47:29,580 SO WE HAVE DEVELOPED THREE 4465 02:47:29,580 --> 02:47:39,556 NOVEL HTACS ON INDIVIDUALS 4466 02:47:39,556 --> 02:47:44,495 TO IMPROVE LONG, MEDIAN AND 4467 02:47:44,495 --> 02:47:48,098 LONG-TERM MEMORY IN THESE 4468 02:47:48,098 --> 02:47:48,766 INDIVIDUALS. 4469 02:47:48,766 --> 02:47:49,233 OUR SPRAEFRPLS 4470 02:47:49,233 --> 02:47:52,336 REPRESENTATIVE IN TERMS OF 4471 02:47:52,336 --> 02:47:54,872 RACE, ETHNICITY AND SEX OF 4472 02:47:54,872 --> 02:47:57,341 THE GREATER BOSTON AREA 4473 02:47:57,341 --> 02:48:02,679 WHICH IS NOT TOO DIFFERENT 4474 02:48:02,679 --> 02:48:03,714 THAN LARGER AREAS. 4475 02:48:03,714 --> 02:48:06,383 AND THEN THE PARAMETERS FOR 4476 02:48:06,383 --> 02:48:09,386 THE ROLE, THE FREQUENCY AND 4477 02:48:09,386 --> 02:48:11,422 SPACE, DOSE AND DURATION AND 4478 02:48:11,422 --> 02:48:11,922 COGNITIVE STATUS. 4479 02:48:11,922 --> 02:48:13,557 THERE ARE A NUMBER OF FUTURE 4480 02:48:13,557 --> 02:48:14,892 DIRECTIONS I WOULD LOVE TO 4481 02:48:14,892 --> 02:48:16,493 TALK ABOUT. 4482 02:48:16,493 --> 02:48:18,929 ONE 'THEM RELATES TO 4483 02:48:18,929 --> 02:48:19,730 ALZHEIMER'S DISEASE, A 4484 02:48:19,730 --> 02:48:21,432 CLINICAL TRIAL I AM RUNNING 4485 02:48:21,432 --> 02:48:23,267 IN MY LAB RIGHT NOW SO I 4486 02:48:23,267 --> 02:48:25,636 WILL JUST SHARE SOME OF THE 4487 02:48:25,636 --> 02:48:26,136 PRELIMINARY DATA. 4488 02:48:26,136 --> 02:48:32,976 IT IS KIND OF AT THIS 4489 02:48:32,976 --> 02:48:38,048 TITILLATING AND NEW DATA SO 4490 02:48:38,048 --> 02:48:41,985 WE'RE SEEING THESE DRASTIC 4491 02:48:41,985 --> 02:48:44,621 MPI AND WITH A 25-MINUTE 4492 02:48:44,621 --> 02:48:47,591 DOSE OF THIS STIMULATED 4493 02:48:47,591 --> 02:48:50,961 BRAIN RESTORATION, WE CAN GO 4494 02:48:50,961 --> 02:48:54,832 A LONG WAY TO RECOVER THE 4495 02:48:54,832 --> 02:48:56,767 CAPACITY PARTICULARLY AT 4496 02:48:56,767 --> 02:48:58,368 LARGER LOADS WHERE THE 4497 02:48:58,368 --> 02:49:00,704 DEFICIT IS THE GREATEST. 4498 02:49:00,704 --> 02:49:02,139 THANK YOU. 4499 02:49:02,139 --> 02:49:03,006 [APPLAUSE] 4500 02:49:03,006 --> 02:49:03,874 >> THANK YOU, ROB, 4501 02:49:03,874 --> 02:49:05,676 INTERESTING TALK. 4502 02:49:05,676 --> 02:49:07,778 UP NEXT WE HAVE FRANK LIN 4503 02:49:07,778 --> 02:49:10,247 WHO JUST CAME DOWN THE 4504 02:49:10,247 --> 02:49:11,081 STREET FROM JOHNS HOPKINS 4505 02:49:11,081 --> 02:49:16,653 AND WE WILL BE HEARING ABOUT 4506 02:49:16,653 --> 02:49:17,988 HEARING INTERVENTION, 4507 02:49:17,988 --> 02:49:20,691 COGNITIVE DECLINE AND BRAIN 4508 02:49:20,691 --> 02:49:22,926 HEALTH WITH ACHIEVE 4509 02:49:22,926 --> 02:49:23,994 RANDOMIZED TRIAL. 4510 02:49:23,994 --> 02:49:24,728 >> THANK YOU, DELIGHTED TO 4511 02:49:24,728 --> 02:49:28,398 BE HERE AND THANK EVERYONE 4512 02:49:28,398 --> 02:49:28,899 FOR INVITING OUT. 4513 02:49:28,899 --> 02:49:30,367 SO THIS WILL BE A BROAD 4514 02:49:30,367 --> 02:49:32,469 OVERVIEW OF A STUDY FOCUSING 4515 02:49:32,469 --> 02:49:35,038 ON THE PRIMARY RESULT AND 4516 02:49:35,038 --> 02:49:37,107 HOW IT REALLY DIFFERED AMONG 4517 02:49:37,107 --> 02:49:37,708 STUDY POPULATIONS. 4518 02:49:37,708 --> 02:49:40,777 AS ALL OF YOU KNOW, SIGNS OF 4519 02:49:40,777 --> 02:49:47,351 A TEAM BASED SPORT, FOR A 4520 02:49:47,351 --> 02:49:50,521 MULTIPLE TIE GROUP STUDY, 4521 02:49:50,521 --> 02:49:52,256 TEN YEARS, WORKING THROUGH 4522 02:49:52,256 --> 02:49:55,559 THE GENEROUS SUPPORT OF NIA. 4523 02:49:55,559 --> 02:49:57,060 SO BRIEF BACKGROUND, WHAT 4524 02:49:57,060 --> 02:50:02,599 HAS BEEN STUDIES AND WHY, 4525 02:50:02,599 --> 02:50:05,068 MODIFIABLE RISK FACTORS AND 4526 02:50:05,068 --> 02:50:07,137 RELATED TO HEARING LOT MID 4527 02:50:07,137 --> 02:50:10,674 TO LATE IN LIFE BASED ON A 4528 02:50:10,674 --> 02:50:11,742 FRACTION OF RISK. 4529 02:50:11,742 --> 02:50:16,747 THE REASON FOR THIS IS THE 4530 02:50:16,747 --> 02:50:18,248 EPIDEMIOLOGICAL LINKING OF 4531 02:50:18,248 --> 02:50:21,118 THIS HAVE SHOWN HIGH RISK 4532 02:50:21,118 --> 02:50:25,856 RATIOS AND HEARING LOSS IS A 4533 02:50:25,856 --> 02:50:27,591 VERY COMMON PREVALENT 4534 02:50:27,591 --> 02:50:29,259 CONDITION FOR EVERYONE. 4535 02:50:29,259 --> 02:50:31,428 BEGINNING AFTER TEENAGE 4536 02:50:31,428 --> 02:50:32,829 YEARS, EVERYONE'S HEARING 4537 02:50:32,829 --> 02:50:36,567 SLOWLY DECREASES OVER A 4538 02:50:36,567 --> 02:50:40,637 LIFETIME BECAUSE OF 4539 02:50:40,637 --> 02:50:43,507 MITOTOXINS, THERE ARE 4540 02:50:43,507 --> 02:50:44,775 DIFFERING RATES BUT 4541 02:50:44,775 --> 02:50:46,476 EVERYBODY LOSES HEARING OVER 4542 02:50:46,476 --> 02:50:47,277 TIME. 4543 02:50:47,277 --> 02:50:50,380 SO WE HAVE THESE FEW 4544 02:50:50,380 --> 02:50:51,315 MECHANISMS LINKING HEARING 4545 02:50:51,315 --> 02:50:54,751 LOSS WITH A INCREASED RISK 4546 02:50:54,751 --> 02:50:55,886 WITH COGNITIVE DEMENTIA. 4547 02:50:55,886 --> 02:50:58,455 KEEP IN MIND, ALL HEARING 4548 02:50:58,455 --> 02:50:59,389 CHANGES THROUGH I THINK A 4549 02:50:59,389 --> 02:51:03,694 BUT IT MEANS YOU ARE GETTING 4550 02:51:03,694 --> 02:51:05,195 A MORE GARBLES SIGNATORY 4551 02:51:05,195 --> 02:51:06,396 CODE TO THE BRAIN SO THE 4552 02:51:06,396 --> 02:51:14,538 BRAIN HAS TO WORK HARDER TO 4553 02:51:14,538 --> 02:51:15,539 TRANSLATE THAT SIGNAL. 4554 02:51:15,539 --> 02:51:19,476 AND THEN THAT COMES AT THE 4555 02:51:19,476 --> 02:51:22,980 EXPENSE OF OTHER SYSTEMS. 4556 02:51:22,980 --> 02:51:24,881 EITHER THAT OR THE DIRECT 4557 02:51:24,881 --> 02:51:27,184 EFFECTS OF HEARING LOSS AND 4558 02:51:27,184 --> 02:51:30,587 DIRECT EFFECTS ON BRAIN 4559 02:51:30,587 --> 02:51:32,856 STRUCTURE AND FUNCTION, 4560 02:51:32,856 --> 02:51:34,558 LOOKING AT EPIDEMIOLOGICAL 4561 02:51:34,558 --> 02:51:37,160 ANIMAL STUDIES AND SOCIAL 4562 02:51:37,160 --> 02:51:37,527 ISOLATION. 4563 02:51:37,527 --> 02:51:41,265 THE REASON IT IS IMPORTANT 4564 02:51:41,265 --> 02:51:43,166 IS BECAUSE IT SUGGESTS 4565 02:51:43,166 --> 02:51:44,334 THEORETICALLY, IF YOU TREAT 4566 02:51:44,334 --> 02:51:46,169 THIS, YOU COULD MODIFY THE 4567 02:51:46,169 --> 02:51:48,772 PATHWAYS AND REDUCE THE 4568 02:51:48,772 --> 02:51:50,741 COGNITIVE DECLINE AND 4569 02:51:50,741 --> 02:51:51,441 DEMENTIA OVER TIME. 4570 02:51:51,441 --> 02:51:53,810 SO THIS IS A REALLY SIMPLE 4571 02:51:53,810 --> 02:51:54,177 QUESTION. 4572 02:51:54,177 --> 02:51:55,879 MAINLY IF WE TREAT HEARING 4573 02:51:55,879 --> 02:52:00,417 LOSS IN OLDER ADULTS, CAN WE 4574 02:52:00,417 --> 02:52:01,685 INDUCE COGNITIVE DECLINE IN 4575 02:52:01,685 --> 02:52:03,120 THREE YEARS, A SHORT PERIOD 4576 02:52:03,120 --> 02:52:06,156 OF TIME IN OLDER ADULTS. 4577 02:52:06,156 --> 02:52:10,260 SO THE MAIN OUTCOME IS 4578 02:52:10,260 --> 02:52:11,928 GLOBAL COGNITIVE DECLINE. 4579 02:52:11,928 --> 02:52:13,864 THERE ARE SOME SECONDARY 4580 02:52:13,864 --> 02:52:15,532 GLOBAL RESULTS WHEN I WON'T 4581 02:52:15,532 --> 02:52:17,267 GO OVER TODAY BUT I WILL 4582 02:52:17,267 --> 02:52:20,304 SHOW YOU THE AMYLOID DATA. 4583 02:52:20,304 --> 02:52:24,207 SO THE DESIGN PRETTY SIMPLE. 4584 02:52:24,207 --> 02:52:26,710 977 OLDER ADULTS, 70 TO 84 4585 02:52:26,710 --> 02:52:30,447 YEARS OLD, MILD TO MODERATE 4586 02:52:30,447 --> 02:52:32,049 HEARING LOSS, INTACT. 4587 02:52:32,049 --> 02:52:33,583 WE STUDIES TWO DISTINCT 4588 02:52:33,583 --> 02:52:34,751 POPULATIONS AND THIS IS 4589 02:52:34,751 --> 02:52:35,118 IMPORTANT. 4590 02:52:35,118 --> 02:52:37,421 A QUARTER OF THE COHORT CAME 4591 02:52:37,421 --> 02:52:40,424 FROM AN EXISTING 4592 02:52:40,424 --> 02:52:42,693 OBSERVATIONAL HEART HEALTH 4593 02:52:42,693 --> 02:52:45,862 STUDY AND THE OTHER THREE 4594 02:52:45,862 --> 02:52:49,266 QUARTERS CAME FROM DENOVO, 4595 02:52:49,266 --> 02:52:53,904 NEW RELY CRUDE VOLUNTEERS 4596 02:52:53,904 --> 02:52:54,404 THROUGH FACEBOOK, 4597 02:52:54,404 --> 02:52:56,406 ADVERTISEMENTS, THINGS LIKE 4598 02:52:56,406 --> 02:52:57,507 THAT. 4599 02:52:57,507 --> 02:53:01,645 THOSE TWO COHORTS ARE THEN 4600 02:53:01,645 --> 02:53:03,347 RANDOMIZED, THEN FOLLOWED 4601 02:53:03,347 --> 02:53:06,516 ANNUALLY THE NEXT SIX 4602 02:53:06,516 --> 02:53:09,052 MONTHS, AND A HOST OF OTHER 4603 02:53:09,052 --> 02:53:10,220 EXPLORATORY OUTCOMES AS 4604 02:53:10,220 --> 02:53:10,921 WELL. 4605 02:53:10,921 --> 02:53:13,090 NOW, I MENTIONED BEFORE, THE 4606 02:53:13,090 --> 02:53:15,392 ACHIEVE STUDY, IF ANY OF YOU 4607 02:53:15,392 --> 02:53:18,462 HAD TO DO A MULTI-SITE 4608 02:53:18,462 --> 02:53:20,197 TRIAL, THEY ARE HARDER TO 4609 02:53:20,197 --> 02:53:22,499 GET SET UP SO IF YOU CAN 4610 02:53:22,499 --> 02:53:23,800 COMBINE RESOURCES, IT MAKES 4611 02:53:23,800 --> 02:53:24,935 IT EASIER. 4612 02:53:24,935 --> 02:53:31,007 SO IN OUR CASE WE HAD THE 4613 02:53:31,007 --> 02:53:32,843 HELP OF ACHIEVE STUDY. 4614 02:53:32,843 --> 02:53:35,145 BASIC WE RE CRUDE 30 YEARS 4615 02:53:35,145 --> 02:53:38,215 AGO MID-LIFE ADULTS FROM A 4616 02:53:38,215 --> 02:53:40,484 RANDOM POPULATION, VOTER 4617 02:53:40,484 --> 02:53:41,418 REGISTRATION POLLS, DRIVER 4618 02:53:41,418 --> 02:53:42,686 RECORD POLLS AND RECRUITED 4619 02:53:42,686 --> 02:53:45,889 THEM INTO THE STUDY LOOKING 4620 02:53:45,889 --> 02:53:48,725 AT MIDLIFE CARDIO RISK 4621 02:53:48,725 --> 02:53:50,560 POCKET TORSION AND AGING 4622 02:53:50,560 --> 02:53:55,766 DISEASE AND FOLLOWED THEM 4623 02:53:55,766 --> 02:53:57,000 FOR MANY YEARS. 4624 02:53:57,000 --> 02:53:59,136 SO WE APPLIED THE SCREENS IN 4625 02:53:59,136 --> 02:54:00,637 THE STUDY. 4626 02:54:00,637 --> 02:54:01,638 THREE QUARTERS OF THE 4627 02:54:01,638 --> 02:54:03,507 COHORTS CAME FROM THE SAME 4628 02:54:03,507 --> 02:54:05,075 COMMUNITIES BUT NEW 4629 02:54:05,075 --> 02:54:06,209 VOLUNTEERS. 4630 02:54:06,209 --> 02:54:08,311 LITERALLY PEOPLE RESPONDED 4631 02:54:08,311 --> 02:54:18,789 TO FACEBOOK ADS, THINGS 4632 02:54:32,769 --> 02:54:34,471 LIKE THAT. 4633 02:54:34,471 --> 02:54:35,172 THE INTERVENTION, FIRST 4634 02:54:35,172 --> 02:54:37,874 THREE MONTHS OF THE STUDY 4635 02:54:37,874 --> 02:54:48,418 THEY GOT HEARING AIDS, HALF 4636 02:54:48,885 --> 02:54:54,424 OF THEM, THEN THE OTHER HALF 4637 02:54:54,424 --> 02:54:58,495 BASICALLY GOT GENERAL 4638 02:54:58,495 --> 02:55:01,364 EDUCATION, COUNSELING ON 4639 02:55:01,364 --> 02:55:02,666 HEALTHY AGING TOPICS. 4640 02:55:02,666 --> 02:55:05,769 SO EVERY THREE MONTHS, THEN 4641 02:55:05,769 --> 02:55:07,904 EVERY SIX MONTHS A FOLLOW UP 4642 02:55:07,904 --> 02:55:10,073 BOOSTER SESSION AND THERE 4643 02:55:10,073 --> 02:55:11,107 AFTER. 4644 02:55:11,107 --> 02:55:19,749 THE COGNITIVE BATTERY, ABOUT 4645 02:55:19,749 --> 02:55:30,293 45 MINUTES, ADMINISTERED BY 4646 02:55:32,929 --> 02:55:33,630 A -- 4647 02:55:33,630 --> 02:55:34,097 [INDISCERNIBLE] 4648 02:55:34,097 --> 02:55:35,232 , WE GOT ONE GLOBAL 4649 02:55:35,232 --> 02:55:36,199 COGNITION SCORE. 4650 02:55:36,199 --> 02:55:38,301 SO IF IT IS ZERO, YOU ARE 4651 02:55:38,301 --> 02:55:40,804 SMACK DAB IN THE MIDDLE AT 4652 02:55:40,804 --> 02:55:42,372 MEAN, BASELINE. 4653 02:55:42,372 --> 02:55:48,478 IF YOU ARE .05, YOU ARE HALF 4654 02:55:48,478 --> 02:55:51,214 AWAY FROM THAT, LIKEWISE IT 4655 02:55:51,214 --> 02:55:53,283 CAN CHANGE OVER TIME, 4656 02:55:53,283 --> 02:55:56,086 NECKIVE FIVE OR THREE YEARS 4657 02:55:56,086 --> 02:55:57,254 IT DECLINED OVER A THREE 4658 02:55:57,254 --> 02:55:59,022 YEAR PERIOD. 4659 02:55:59,022 --> 02:56:02,592 YOU CAN ALSO EXTRACT 4660 02:56:02,592 --> 02:56:03,360 DOMAINS, LANGUAGE 4661 02:56:03,360 --> 02:56:06,429 PRODUCTION, NOT LANGUAGE WE 4662 02:56:06,429 --> 02:56:07,564 CEPTION, CATEGORY WITH RUNS 4663 02:56:07,564 --> 02:56:08,598 IN SEE, EXECUTIVE FUNCTION 4664 02:56:08,598 --> 02:56:11,034 AND MEMORY AND PROBABLY WANT 4665 02:56:11,034 --> 02:56:12,502 TO EMPHASIZE EIGHT OF THE 4666 02:56:12,502 --> 02:56:14,871 TEN COGNITIVE TESTS ARE NOT 4667 02:56:14,871 --> 02:56:15,505 AUDITORY EXCLUSIVE. 4668 02:56:15,505 --> 02:56:17,574 SO IF SOMEONE IS NOT DOING 4669 02:56:17,574 --> 02:56:20,343 WELL ON A COGNITIVE TEST, I 4670 02:56:20,343 --> 02:56:21,478 CAN TELL YOU IT IS NOT 4671 02:56:21,478 --> 02:56:23,513 BECAUSE THEY ARE NOT HEARING 4672 02:56:23,513 --> 02:56:23,880 WELL. 4673 02:56:23,880 --> 02:56:25,682 THESE ARE VISUAL AND 4674 02:56:25,682 --> 02:56:26,316 AUDITORY TESTS. 4675 02:56:26,316 --> 02:56:29,052 OF THE TWO THAT ARE 4676 02:56:29,052 --> 02:56:30,754 AUDITORY, WE VERIFY THEIR 4677 02:56:30,754 --> 02:56:32,522 SPEECH UNDERSTANDING AND 4678 02:56:32,522 --> 02:56:35,325 WHAT I MEAN IS THEY ARE READ 4679 02:56:35,325 --> 02:56:39,963 A LIST OF SENTENCES AND 4680 02:56:39,963 --> 02:56:42,065 ASKED TO REPEAT BACK TO 4681 02:56:42,065 --> 02:56:47,637 CONFIRM THEY ARE HEARING 4682 02:56:47,637 --> 02:56:48,004 WELL. 4683 02:56:48,004 --> 02:56:49,839 AND FACE-TO-FACE, IN A QUIET 4684 02:56:49,839 --> 02:56:53,310 ROOM, YOU WOULDN'T EXPECT 4685 02:56:53,310 --> 02:56:57,047 THAT TO MODIFY TRAJECTORY 4686 02:56:57,047 --> 02:57:00,650 OVERALL BUT WE ENSURED IT 4687 02:57:00,650 --> 02:57:03,420 WAS STANDARD OVER TIME. 4688 02:57:03,420 --> 02:57:05,922 THE RECRUITING PERIOD BEGAN 4689 02:57:05,922 --> 02:57:07,257 IN JANUARY 2018. 4690 02:57:07,257 --> 02:57:09,159 ALWAYS VERY PROUD OF THE 4691 02:57:09,159 --> 02:57:11,127 FACT WE HIT 850 ON TARGET, 4692 02:57:11,127 --> 02:57:13,697 TWO WEEKS BEHIND SCHEDULE 4693 02:57:13,697 --> 02:57:14,898 AND HIT 850. 4694 02:57:14,898 --> 02:57:17,300 BECAUSE OF HOW WELL IT WAS 4695 02:57:17,300 --> 02:57:19,402 GOING, WE KEPT IT OPEN A 4696 02:57:19,402 --> 02:57:23,940 LITTLE LONGER WITH THE HELP 4697 02:57:23,940 --> 02:57:29,713 OF NI A AND NIAH. 4698 02:57:29,713 --> 02:57:30,614 AND RIGHT BEFORE THE 4699 02:57:30,614 --> 02:57:31,681 PANDEMIC HIT. 4700 02:57:31,681 --> 02:57:34,117 FULL WE RE CRUDE, EVERYONE 4701 02:57:34,117 --> 02:57:35,018 RECEIVED THEIR PRIMARY 4702 02:57:35,018 --> 02:57:35,885 INTERVENTION BEFORE THE 4703 02:57:35,885 --> 02:57:37,520 PANDEMIC BEGAN. 4704 02:57:37,520 --> 02:57:47,931 THE REASON WHY IT IS 4705 02:57:48,398 --> 02:57:52,369 IMPORTANT IS WE STUDIES 4706 02:57:52,369 --> 02:57:56,973 THESE FOR THREE YEARS AND 4707 02:57:56,973 --> 02:58:01,244 THE BASELINE ALL DONE IN 4708 02:58:01,244 --> 02:58:03,179 PERSON SO ATTESTING TO THE 4709 02:58:03,179 --> 02:58:04,481 QUALITY STAFF, AFTER THREE 4710 02:58:04,481 --> 02:58:07,450 YEARS THROUGH THE PANDEMIC, 4711 02:58:07,450 --> 02:58:09,686 COMPLETE UPDATE ON 4712 02:58:09,686 --> 02:58:12,322 90 PERCENT OF THE PEOPLE 4713 02:58:12,322 --> 02:58:13,623 THREE YEARS LATER. 4714 02:58:13,623 --> 02:58:16,393 SO ATTRITION RATE OF 4715 02:58:16,393 --> 02:58:18,461 10 PERCENT, SOME PEOPLE DIED 4716 02:58:18,461 --> 02:58:20,063 UNFORTUNATELY, SOME MOVED 4717 02:58:20,063 --> 02:58:20,730 AWAY. 4718 02:58:20,730 --> 02:58:23,033 SO THIS NORMALLY IS A TABLE 4719 02:58:23,033 --> 02:58:24,901 I WOULD SHOW STRESS BY 4720 02:58:24,901 --> 02:58:25,702 INTERVENTION VERSUS CONTROL. 4721 02:58:25,702 --> 02:58:28,071 I CAN SHOW YOU SOME THINGS 4722 02:58:28,071 --> 02:58:30,240 ARE EQUAL BECAUSE IT IS 4723 02:58:30,240 --> 02:58:32,208 RANDOMIZED BUT WHAT I AM 4724 02:58:32,208 --> 02:58:37,847 SHOWING YOU HERE IS THE 4725 02:58:37,847 --> 02:58:40,517 BASELINE CHARACTERISTICS 4726 02:58:40,517 --> 02:58:43,253 STRATIFIED BY RECRUITMENT 4727 02:58:43,253 --> 02:58:44,054 SOURCE. 4728 02:58:44,054 --> 02:58:48,091 THE DENOVO HAD FEWER RISK 4729 02:58:48,091 --> 02:58:50,593 FACTORS OF DECLINE AND 4730 02:58:50,593 --> 02:58:53,296 DEMENTIA THAN THE ARIC 4731 02:58:53,296 --> 02:58:53,797 COHORT. 4732 02:58:53,797 --> 02:58:55,999 AND YOU SEE THAT STUDY 4733 02:58:55,999 --> 02:58:57,701 POPULATION SOURCE BEING 4734 02:58:57,701 --> 02:59:00,537 REFLECTED ON THESE 4735 02:59:00,537 --> 02:59:02,305 CHARACTERISTICS. 4736 02:59:02,305 --> 02:59:05,141 SO THE ARIC COHORT IS 4737 02:59:05,141 --> 02:59:06,876 YOUNGER. 4738 02:59:06,876 --> 02:59:07,744 BLACK IS INTERESTING BECAUSE 4739 02:59:07,744 --> 02:59:10,246 THE REASON THERE IS A SKU IS 4740 02:59:10,246 --> 02:59:14,517 ONE QUARTER WAS FULLY BLACK 4741 02:59:14,517 --> 02:59:17,554 AMERICAN, SO YOU ARE SEEING 4742 02:59:17,554 --> 02:59:20,256 IT THERE WHEREAS DENOVO, YOU 4743 02:59:20,256 --> 02:59:22,425 ARE SEEING A COMMUNITY OF 4744 02:59:22,425 --> 02:59:24,060 VOLUNTEERS, MORE OF A 4745 02:59:24,060 --> 02:59:29,332 DISCREPANCY THERE. 4746 02:59:29,332 --> 02:59:33,303 ON AVERAGE, THE DENOVO HAD 4747 02:59:33,303 --> 02:59:36,606 HIGHER EDUCATION AND WOULD 4748 02:59:36,606 --> 02:59:38,875 BE RANDOMLY DIFFERENT THAN 4749 02:59:38,875 --> 02:59:42,512 THE RECRUITMENT OF A RANDOM 4750 02:59:42,512 --> 02:59:43,747 POPULATION. 4751 02:59:43,747 --> 02:59:46,082 SO RISK FACTORS, DENOVO WITH 4752 02:59:46,082 --> 02:59:49,586 A LOWER RATE OF DIABETES, 4753 02:59:49,586 --> 02:59:51,054 LESS HYPERTENSION, SEEING 4754 02:59:51,054 --> 02:59:53,356 LESS LIVING ALONE IN THE 4755 02:59:53,356 --> 02:59:55,792 DENOVO VERSUS THE ARIC 4756 02:59:55,792 --> 02:59:56,126 COHORT. 4757 02:59:56,126 --> 02:59:57,460 NOW WHAT IS INTERESTING, YOU 4758 02:59:57,460 --> 03:00:01,731 LOOK AT THE BASELINE 4759 03:00:01,731 --> 03:00:02,899 COGNITION, STANDARDIZED 4760 03:00:02,899 --> 03:00:06,269 SCORES, YOU CAN SEE THEY ARE 4761 03:00:06,269 --> 03:00:08,805 1.7 ABOVE THE MEANS WHERE 4762 03:00:08,805 --> 03:00:10,774 THE ARIC STARTS BELOW THE 4763 03:00:10,774 --> 03:00:13,009 MEAN BASED ON THIS AVERAGE 4764 03:00:13,009 --> 03:00:14,611 SO A BASELINE OF COGNITION 4765 03:00:14,611 --> 03:00:17,480 AMONG A GROUP OF VOLUNTEERS 4766 03:00:17,480 --> 03:00:19,048 VERSUS A RANDOM SAMPLE OF 4767 03:00:19,048 --> 03:00:19,516 THE POPULATION. 4768 03:00:19,516 --> 03:00:22,485 SO I AM GOING TO JUMP TO THE 4769 03:00:22,485 --> 03:00:25,488 THREE YEAR COGNITIVE 4770 03:00:25,488 --> 03:00:27,824 OUTCOMES. 4771 03:00:27,824 --> 03:00:32,362 THIS IS A BUSY STUDY BUT 4772 03:00:32,362 --> 03:00:34,597 WHAT YOU ARE SEEING THERE 4773 03:00:34,597 --> 03:00:40,270 THE CONTROL GROUP ON AVERAGE 4774 03:00:40,270 --> 03:00:43,139 DECLINED BY .202 IN TERMS OF 4775 03:00:43,139 --> 03:00:44,140 COGNITION. 4776 03:00:44,140 --> 03:00:47,644 IF YOU LOOK AT THE PURE 4777 03:00:47,644 --> 03:00:50,814 GROUP, ESSENTIALLY THE SAME. 4778 03:00:50,814 --> 03:00:53,349 SO NO DIFFERENCES IN RATES 4779 03:00:53,349 --> 03:00:54,250 OF COG DECLINE OVER THREE 4780 03:00:54,250 --> 03:00:57,420 YEARS OF THE CONTROL. 4781 03:00:57,420 --> 03:00:58,822 SO DISAPPOINTING AT FIRST. 4782 03:00:58,822 --> 03:01:03,226 IF YOU LOOK AT THE SECONDARY 4783 03:01:03,226 --> 03:01:06,162 OUTCOMES, ALMOST THE SAME 4784 03:01:06,162 --> 03:01:06,496 THING. 4785 03:01:06,496 --> 03:01:08,998 REALLY NOTHING TO WRITE HOME 4786 03:01:08,998 --> 03:01:09,465 ABOUT. 4787 03:01:09,465 --> 03:01:10,867 NOW WHAT GETS A LOT MORE 4788 03:01:10,867 --> 03:01:14,370 INTERESTING THOUGH IS ONE OF 4789 03:01:14,370 --> 03:01:16,306 OUR PRESET BY SENSITIVITY 4790 03:01:16,306 --> 03:01:18,208 ANALYSIS OVER FIVE YEARS 4791 03:01:18,208 --> 03:01:20,743 WHEN WE DESIGNED THE STUDY, 4792 03:01:20,743 --> 03:01:31,287 WE SAID WE WOULD REPLICATE 4793 03:01:31,688 --> 03:01:34,057 THE STRATEGY BASED ON 4794 03:01:34,057 --> 03:01:34,791 CONVERSATIONS. 4795 03:01:34,791 --> 03:01:35,358 WE DIDN'T REALIZE HOW 4796 03:01:35,358 --> 03:01:36,259 DIFFERENT THEY WOULD BE BUT 4797 03:01:36,259 --> 03:01:39,028 THIS IS WHAT YOU WILL SEE. 4798 03:01:39,028 --> 03:01:43,032 SO AMONG THE ARIC COPORT, A 4799 03:01:43,032 --> 03:01:45,201 RANDOM SAMPLE OF POPULATION, 4800 03:01:45,201 --> 03:01:49,205 SEEING VERY STRONG HEARING 4801 03:01:49,205 --> 03:01:50,940 AFFECTS REDUCING COGNITIVE 4802 03:01:50,940 --> 03:01:52,909 DECLINE COMPARED TO CONTROL, 4803 03:01:52,909 --> 03:01:55,345 SEEING A 48 PERCENT 4804 03:01:55,345 --> 03:01:57,547 REDUCTION IN RATES OF 4805 03:01:57,547 --> 03:01:58,715 COGNITIVE DECLINE, YOU CAN 4806 03:01:58,715 --> 03:02:07,190 SEE THEM AT THE LEFT THERE. 4807 03:02:07,190 --> 03:02:09,926 BUT IF YOU LOOK AT THE 4808 03:02:09,926 --> 03:02:11,427 DENOVO COHORT, YOU ARE 4809 03:02:11,427 --> 03:02:14,364 SEEING IN EFFECTS OF THE 4810 03:02:14,364 --> 03:02:16,332 HEARING INTERVENTION ON 4811 03:02:16,332 --> 03:02:17,467 SLOWING COGNITIVE DECLINE. 4812 03:02:17,467 --> 03:02:17,800 SO WHY? 4813 03:02:17,800 --> 03:02:21,437 AND IF YOU LOOK AT THE DATA 4814 03:02:21,437 --> 03:02:22,639 MORE CLEARLY, IT BECOMES 4815 03:02:22,639 --> 03:02:23,139 MORE CLEAR. 4816 03:02:23,139 --> 03:02:25,275 IF YOU LOOK AT THE RATES 4817 03:02:25,275 --> 03:02:28,511 AMONG THE CONTROL GROUP OF 4818 03:02:28,511 --> 03:02:32,749 3-YEAR COGNITIVE DECLINE IN 4819 03:02:32,749 --> 03:02:34,350 THE ARIC, THE .2 CHANGE IN 4820 03:02:34,350 --> 03:02:39,355 THREE YEARS AND THE DENOVO 4821 03:02:39,355 --> 03:02:42,058 CONTROLS, ONLY 1.51 SO A 4822 03:02:42,058 --> 03:02:43,593 THREE-FOLD SLOWER RATE OF 4823 03:02:43,593 --> 03:02:47,964 COG CHANGE OVER THE THREE 4824 03:02:47,964 --> 03:02:51,567 YEARS AMONG THE DENOVO 4825 03:02:51,567 --> 03:02:55,905 CONTROL VERSUS THE ARIC 4826 03:02:55,905 --> 03:02:56,506 COHORT. 4827 03:02:56,506 --> 03:02:58,675 SO FEWER RISK FACTORS THAN 4828 03:02:58,675 --> 03:03:01,811 AVERAGE THAN THE AR IC 4829 03:03:01,811 --> 03:03:02,245 COHORT. 4830 03:03:02,245 --> 03:03:04,847 SO ONE WAY OF INTERPRETING 4831 03:03:04,847 --> 03:03:07,317 THIS IS THAT A HEARING ENTER 4832 03:03:07,317 --> 03:03:11,421 VENGE IS PREDICATED ON 4833 03:03:11,421 --> 03:03:14,057 REDUCING COGNITIVE DECLINE, 4834 03:03:14,057 --> 03:03:16,659 DENOVO, VERY LITTLE 4835 03:03:16,659 --> 03:03:17,460 COGNITIVE DECLINE IN TWO 4836 03:03:17,460 --> 03:03:21,497 YEARS AND YOU CAN'T SLOW 4837 03:03:21,497 --> 03:03:22,632 DOWN SOMETHING THAT ISN'T 4838 03:03:22,632 --> 03:03:27,437 THERE TO BEGIN WITH. 4839 03:03:27,437 --> 03:03:28,671 SO WITH DENOVO, THERE IS 4840 03:03:28,671 --> 03:03:31,074 ROOM TO SLOW THAT DOWN WITH 4841 03:03:31,074 --> 03:03:33,042 OBSERVING IN THREE YEARS. 4842 03:03:33,042 --> 03:03:35,078 I WILL SHOW YOU EXPLORATORY 4843 03:03:35,078 --> 03:03:36,379 EFFECTS LOOKING AT BRAIN 4844 03:03:36,379 --> 03:03:40,350 HEALTH AND MRI DATA AND THIS 4845 03:03:40,350 --> 03:03:47,724 IS PREDICATED ON THE MAIN 4846 03:03:47,724 --> 03:03:48,958 MECHANISM, HEARING, 4847 03:03:48,958 --> 03:03:50,126 COGNITIVE DECLINE AND 4848 03:03:50,126 --> 03:03:50,994 STRUCTURE. 4849 03:03:50,994 --> 03:03:56,866 SO IS IT REDUCING RATES OF 4850 03:03:56,866 --> 03:03:58,868 BRAIN ATROPHY, CORTICO 4851 03:03:58,868 --> 03:04:00,737 THINNING, THIS IS WITHIN 4852 03:04:00,737 --> 03:04:01,137 THREE YEARS. 4853 03:04:01,137 --> 03:04:04,741 I WILL JUMP TO THE DATA. 4854 03:04:04,741 --> 03:04:08,511 THE HALF SAMPLE HAD MRI AS A 4855 03:04:08,511 --> 03:04:10,713 BASELINE AND THEN MRIS THREE 4856 03:04:10,713 --> 03:04:11,748 YEARS LATER. 4857 03:04:11,748 --> 03:04:17,453 THIS IS CORTICAL THICKNESS 4858 03:04:17,453 --> 03:04:19,322 ALL CONSTRUCTED BY CLIFF 4859 03:04:19,322 --> 03:04:21,491 JACK'S GROUP AT MAYO IN THE 4860 03:04:21,491 --> 03:04:23,092 RESEARCH LABORATORY AND WHAT 4861 03:04:23,092 --> 03:04:26,629 YOU SEE HERE AGAIN, THIS 4862 03:04:26,629 --> 03:04:28,898 EXPLORATORY DATA, NOT KEY 4863 03:04:28,898 --> 03:04:30,533 VALUES BUT THE EXPLORATORY 4864 03:04:30,533 --> 03:04:31,801 EFFECTS OF WHAT INTERVENTION 4865 03:04:31,801 --> 03:04:32,602 THEY DO. 4866 03:04:32,602 --> 03:04:34,303 WHAT WE CLEARLY SEE HERE IS 4867 03:04:34,303 --> 03:04:36,472 A CLEAR GENERAL TREND FOR 4868 03:04:36,472 --> 03:04:45,581 PROTECTIVE EFFECT ON THE 4869 03:04:45,581 --> 03:04:47,150 REDUCED CORTICAL THICKNESS. 4870 03:04:47,150 --> 03:04:55,758 SEEING A VERY CLEAR SIGNAL 4871 03:04:55,758 --> 03:04:58,928 OF REDUCED CORTICAL 4872 03:04:58,928 --> 03:04:59,295 THINNING. 4873 03:04:59,295 --> 03:05:01,064 NOW, I WILL SHOW YOU ONE 4874 03:05:01,064 --> 03:05:05,968 OTHER FOLLOW UP FIGURE AND 4875 03:05:05,968 --> 03:05:07,804 THIS IS INTEREST ANALYSIS 4876 03:05:07,804 --> 03:05:10,106 USING THE SAME DATA AS 4877 03:05:10,106 --> 03:05:12,041 BEFORE, LOOKING AT CORTICAL 4878 03:05:12,041 --> 03:05:15,778 FIXES IN EACH ROI, RED IS 4879 03:05:15,778 --> 03:05:17,613 REDUCE OVER THREE YEARS WITH 4880 03:05:17,613 --> 03:05:20,349 LESS INTERVENTION AND THE 4881 03:05:20,349 --> 03:05:25,521 BLUE TO INCREASE CORTICAL 4882 03:05:25,521 --> 03:05:27,590 BUILDING AND WHAT YOU ARE 4883 03:05:27,590 --> 03:05:30,293 SEEING HERE IS VERY STRONG 4884 03:05:30,293 --> 03:05:38,935 SIGNALS IN CERTAIN AREAS. 4885 03:05:38,935 --> 03:05:42,238 THE STRONGEST SIGNAL IS IN 4886 03:05:42,238 --> 03:05:43,973 THE FRONTAL LOBE, A CRITICAL 4887 03:05:43,973 --> 03:05:46,375 AREA FOR LANGUAGE PROCESSING 4888 03:05:46,375 --> 03:05:48,311 SO SEEING A VERY STRONG 4889 03:05:48,311 --> 03:05:50,546 SIGNAL. 4890 03:05:50,546 --> 03:05:52,081 THIS IS EXPLORATORY, NOT 4891 03:05:52,081 --> 03:05:55,952 TESTING FOR THIS BUT CLEARLY 4892 03:05:55,952 --> 03:06:01,390 RECEIVING A SIGNAL AND 4893 03:06:01,390 --> 03:06:03,392 REDUCED HEARING VERSUS THE 4894 03:06:03,392 --> 03:06:04,894 CONTROL GROUP. 4895 03:06:04,894 --> 03:06:07,763 SO BRIEF SUMMARY, IN THE 4896 03:06:07,763 --> 03:06:10,566 TOTAL COMBINED COHORT, WE'RE 4897 03:06:10,566 --> 03:06:14,203 NOT SEEING A CHANGE IN THE 4898 03:06:14,203 --> 03:06:16,239 HEARING OVER THREE YEARS. 4899 03:06:16,239 --> 03:06:17,840 USING A DIFFERENT POPULATION 4900 03:06:17,840 --> 03:06:21,244 IT COULD BE VERY DIFFERENT. 4901 03:06:21,244 --> 03:06:24,080 SEEING 48 PERCENT RELATIVE 4902 03:06:24,080 --> 03:06:28,584 REDUCTION IN COGNITIVE 4903 03:06:28,584 --> 03:06:31,120 DECLINE, .21 VERSUS 4.2 SO 4904 03:06:31,120 --> 03:06:34,557 ABOUT A .2 DIFFERENCE OVER 4905 03:06:34,557 --> 03:06:45,067 THREE YEARS AND YOU MIGHT 4906 03:06:49,672 --> 03:06:50,706 EXTRAPOLATE THE HEARING 4907 03:06:50,706 --> 03:06:53,109 INTERVENTION HAD NO EFFECT 4908 03:06:53,109 --> 03:06:54,243 ON REDUCING COGNITIVE 4909 03:06:54,243 --> 03:06:54,577 DECLINE. 4910 03:06:54,577 --> 03:06:58,781 THERE WERE STRONG EFFECTS IN 4911 03:06:58,781 --> 03:07:01,317 THE ARIC SUGGESTING THE 4912 03:07:01,317 --> 03:07:03,219 HEARING INTERVENTION MIGHT 4913 03:07:03,219 --> 03:07:04,487 REDUCE COGNITIVE DECLINE 4914 03:07:04,487 --> 03:07:07,557 WITHIN THREE YEARS IN 4915 03:07:07,557 --> 03:07:09,058 POPULATIONS AT INCREASED 4916 03:07:09,058 --> 03:07:11,561 RISK FOR COGNITIVE DECLINE. 4917 03:07:11,561 --> 03:07:15,097 NO EFFECT OBSERVED IN THE 4918 03:07:15,097 --> 03:07:19,869 DENOVO LEADING TO SLOW RATE 4919 03:07:19,869 --> 03:07:22,905 OF COG CHANGE. 4920 03:07:22,905 --> 03:07:23,873 EXPLORATORY MRI. 4921 03:07:23,873 --> 03:07:29,645 ERIC WENT OVER AND TESTED 4922 03:07:29,645 --> 03:07:35,551 COGNITIVELY EVERY FEW YEARS, 4923 03:07:35,551 --> 03:07:38,854 NOT SEEING RATES OF ERROR SO 4924 03:07:38,854 --> 03:07:42,825 YOU MAY SEE MORE TRUE RATES 4925 03:07:42,825 --> 03:07:46,195 OF CHANGE. 4926 03:07:46,195 --> 03:07:49,031 AND THEN YOU MIGHT SEE THIS 4927 03:07:49,031 --> 03:07:54,737 FOR DRUG STUDIES, RISK AND 4928 03:07:54,737 --> 03:08:04,247 BIOMARKERS BUT LESS IN THE 4929 03:08:04,247 --> 03:08:06,048 WAY OF HARD TO REACH 4930 03:08:06,048 --> 03:08:07,216 POPULATIONS ARE THE MOST 4931 03:08:07,216 --> 03:08:09,051 IMPORTANT TO REACH AND ITCH 4932 03:08:09,051 --> 03:08:10,886 OCCASIONS OF COGNITIVE 4933 03:08:10,886 --> 03:08:11,520 TESTING PRACTICE EFFECTS 4934 03:08:11,520 --> 03:08:15,658 NEEDS TO BE FULLY CONSIDERED 4935 03:08:15,658 --> 03:08:17,393 WHEN REDUCING COGNITIVE 4936 03:08:17,393 --> 03:08:18,561 DECLINE AS THE PRIMARY 4937 03:08:18,561 --> 03:08:18,894 OUTCOME. 4938 03:08:18,894 --> 03:08:20,529 >> OKAY, MOVING ALONG, WE 4939 03:08:20,529 --> 03:08:26,702 WILL HAVE JULIE WETHERELL, 4940 03:08:26,702 --> 03:08:29,338 PH.D. FROM UNIVERSITY OF 4941 03:08:29,338 --> 03:08:31,607 CALIFORNIA-SAN DIEGO AND 4942 03:08:31,607 --> 03:08:38,314 WILL TALK ABOUT MINDFULNESS 4943 03:08:38,314 --> 03:08:39,982 BASED STRESS REDUCTION AND 4944 03:08:39,982 --> 03:08:41,250 EXERCISE IN COGNITIVE 4945 03:08:41,250 --> 03:08:43,386 FUNCTION IN HEALTHO OLDER 4946 03:08:43,386 --> 03:08:43,753 ADULTS. 4947 03:08:43,753 --> 03:08:45,488 >> THANK YOU SO MUCH, GLAD 4948 03:08:45,488 --> 03:08:47,690 TO BE A PART OF THIS. 4949 03:08:47,690 --> 03:08:50,493 SO WHAT WE HAVE DISCUSSED IN 4950 03:08:50,493 --> 03:08:52,595 THE PAST, THE COGNITIVE 4951 03:08:52,595 --> 03:08:56,399 FUNCTION HAS GOT TEN QUITE A 4952 03:08:56,399 --> 03:08:58,000 BIT OF ATTENTION WITH 4953 03:08:58,000 --> 03:08:59,001 RESPECT TO COGNITIVE DECLINE 4954 03:08:59,001 --> 03:09:02,638 AND THERE ARE A NUMBER OF 4955 03:09:02,638 --> 03:09:03,172 MECHANISMS FOR THIS. 4956 03:09:03,172 --> 03:09:07,376 IN THE WAY OF EXERCISE, 4957 03:09:07,376 --> 03:09:10,212 INTRODUCTIONS AND 4958 03:09:10,212 --> 03:09:20,690 INFORMATION, CHANGES IN 4959 03:09:26,662 --> 03:09:27,963 OXYGENATION, NEUROTROPHIC 4960 03:09:27,963 --> 03:09:34,270 FACTORS, IMPROVED SINCE LYNN 4961 03:09:34,270 --> 03:09:36,072 SENSITIVITY THROUGH 4962 03:09:36,072 --> 03:09:37,206 EXERCISE, THROUGH 4963 03:09:37,206 --> 03:09:39,508 MINDFULNESS MECHANISMS WE 4964 03:09:39,508 --> 03:09:42,611 SEE MORE INCREASED ATTENTION 4965 03:09:42,611 --> 03:09:45,348 CONTROL, IMPROVED EMOTION 4966 03:09:45,348 --> 03:09:46,515 REGULATION AND REDUCED 4967 03:09:46,515 --> 03:09:47,450 COURTS SO WILL PRODUCTION. 4968 03:09:47,450 --> 03:09:53,289 SO I HAVE BEEN WORKING WITH 4969 03:09:53,289 --> 03:09:56,359 UNIVERSITY OF ST. LOUIS WITH 4970 03:09:56,359 --> 03:09:57,426 OLDER ADULTS IN PSYCHOLOGY 4971 03:09:57,426 --> 03:10:00,262 AND DECIDED TO DO A STUDY TO 4972 03:10:00,262 --> 03:10:04,266 LOOK AT OLDER ADULTS WITH 4973 03:10:04,266 --> 03:10:08,337 ANXIETY OR DEPRESSION AND 4974 03:10:08,337 --> 03:10:10,373 THEIR SUBJECTIVITY TO 4975 03:10:10,373 --> 03:10:12,975 COGNITIVE CHANGES AND DID 4976 03:10:12,975 --> 03:10:15,444 THIS THROUGH M BS R VERSUS 4977 03:10:15,444 --> 03:10:16,212 HEALTH EDUCATION. 4978 03:10:16,212 --> 03:10:18,614 RELATIVE TO HEALTH EDUCATION 4979 03:10:18,614 --> 03:10:20,649 WE SAW IMPROVED MEMORY 4980 03:10:20,649 --> 03:10:21,817 PERFORMANCE SOMEBODY UNITED 4981 03:10:21,817 --> 03:10:22,651 WITH STRESS REDUCTION AND 4982 03:10:22,651 --> 03:10:24,453 SOME EVIDENCE THAT THE 4983 03:10:24,453 --> 03:10:32,261 REDUCTION IN COURTS 4984 03:10:32,261 --> 03:10:33,329 CORTISOL MIGHT BE THE 4985 03:10:33,329 --> 03:10:36,799 MECHANISM SO THOSE FOLKS WE 4986 03:10:36,799 --> 03:10:40,202 SAW AT BASELINE WERE SUBJECT 4987 03:10:40,202 --> 03:10:45,274 TO M BS R AND HEALTH 4988 03:10:45,274 --> 03:10:45,741 EDUCATION. 4989 03:10:45,741 --> 03:10:49,145 SO USING THOSE AS PILOT 4990 03:10:49,145 --> 03:10:52,314 DATA, WE DID FUND THROUGH 4991 03:10:52,314 --> 03:10:54,283 AMA AND McKNIGHT A LARGER 4992 03:10:54,283 --> 03:10:56,652 STUDY WHERE WE ARE LOOKING 4993 03:10:56,652 --> 03:11:00,256 AT THE EFFECTS OF STRESS 4994 03:11:00,256 --> 03:11:01,257 REDUCTION, MULTICOMPONENT 4995 03:11:01,257 --> 03:11:01,891 EXERCISE INTERVENTION, WE 4996 03:11:01,891 --> 03:11:03,259 ALSO WERE GOING TO LOOK AT 4997 03:11:03,259 --> 03:11:05,795 SOME OF THE PROPOSED 4998 03:11:05,795 --> 03:11:11,867 MECHANISMS SO LOOKING AT 4999 03:11:11,867 --> 03:11:14,370 CORTISOL TO MEASURE FITNESS, 5000 03:11:14,370 --> 03:11:15,771 HYPERACTIVITY. 5001 03:11:15,771 --> 03:11:17,807 WE WERE LOOKING DOING BRAIN 5002 03:11:17,807 --> 03:11:19,875 IMAGING TO LOOK AT 5003 03:11:19,875 --> 03:11:21,410 STRUCTURAL AND FUNCTIONAL 5004 03:11:21,410 --> 03:11:22,845 CONNECTIVITY AND THEN 5005 03:11:22,845 --> 03:11:25,981 FINALLY THE MOST DISTAL 5006 03:11:25,981 --> 03:11:27,583 OUTCOMES, IMPACTS ON 5007 03:11:27,583 --> 03:11:28,617 COGNITION, SPECIFICALLY 5008 03:11:28,617 --> 03:11:29,885 MEMORY AND COGNITIVE 5009 03:11:29,885 --> 03:11:31,053 CONTROL, ALSO KNOWN AS 5010 03:11:31,053 --> 03:11:33,389 EXECUTIVE FUNCTION. 5011 03:11:33,389 --> 03:11:36,459 SO OUR EXERCISE INTERVENTION 5012 03:11:36,459 --> 03:11:37,493 INCLUDING AEROBIC ACTIVITY 5013 03:11:37,493 --> 03:11:40,896 KIND OF IN LINE WITH OUR 5014 03:11:40,896 --> 03:11:43,532 HYPOTHESIS BUT WE ALSO 5015 03:11:43,532 --> 03:11:44,667 INCLUDED BALANCE AND 5016 03:11:44,667 --> 03:11:45,534 STRENGTH AND ABILITY 5017 03:11:45,534 --> 03:11:47,336 TRAINING BECAUSE THAT IS THE 5018 03:11:47,336 --> 03:11:48,671 PACKAGE OF INTERVENTION FOR 5019 03:11:48,671 --> 03:11:50,072 OLDER PEOPLE. 5020 03:11:50,072 --> 03:11:56,011 INITIALLY FOR THE FIRST SIX 5021 03:11:56,011 --> 03:12:01,183 MONTHS, THESE PEOPLE MET IN 5022 03:12:01,183 --> 03:12:08,724 GROUPS TWICE A WEEK, A 5023 03:12:08,724 --> 03:12:12,561 GROUP OF 15 AND THEN SENT TO 5024 03:12:12,561 --> 03:12:16,232 HOME EXERCISE AND TAILORED 5025 03:12:16,232 --> 03:12:17,633 WITH PROGRESSIVELY 5026 03:12:17,633 --> 03:12:18,467 INCREASING INTENSITY. 5027 03:12:18,467 --> 03:12:20,703 SO THEIR INITIAL GOAL WAS 5028 03:12:20,703 --> 03:12:23,639 300 MINUTES A WEEK AND THEY 5029 03:12:23,639 --> 03:12:30,579 INTENSIFIED THAT THROUGH THE 5030 03:12:30,579 --> 03:12:31,280 STUDY. 5031 03:12:31,280 --> 03:12:32,348 MIND CONTROL DEMONSTRATION, 5032 03:12:32,348 --> 03:12:35,150 YOU MAY BE FAMILIAR WITH 5033 03:12:35,150 --> 03:12:37,786 THIS, IT INCLUDES 5034 03:12:37,786 --> 03:12:38,654 MEDITATION, YOGA, TAUGHT IN 5035 03:12:38,654 --> 03:12:40,322 EIGHT TWO AND A HALF HOUR 5036 03:12:40,322 --> 03:12:43,425 WEEKLY CLASSES AND THEN HE 5037 03:12:43,425 --> 03:12:44,560 ADDED MONTHLY BOOSTER 5038 03:12:44,560 --> 03:12:46,529 SESSIONS OUT TO THE 18-MONTH 5039 03:12:46,529 --> 03:12:49,131 DURATION OF THE TRIAL, DAILY 5040 03:12:49,131 --> 03:12:51,367 HOME PRACTICE WITH A GOAL OF 5041 03:12:51,367 --> 03:12:56,672 UP TO 60 PINS MINUTES BETTER 5042 03:12:56,672 --> 03:12:59,408 DAY OF MEDITATIVE PRACTICE 5043 03:12:59,408 --> 03:13:01,577 AND THEN WE USED HEALTH 5044 03:13:01,577 --> 03:13:03,846 CONTROL AND THIS WAS BASED 5045 03:13:03,846 --> 03:13:05,347 ON THE STANFORD HEALTH 5046 03:13:05,347 --> 03:13:06,148 BENEFITS PROGRAM WHICH HAS 5047 03:13:06,148 --> 03:13:08,217 BEEN THE SUBJECT OF RESEARCH 5048 03:13:08,217 --> 03:13:11,854 IN AND OF ITSELF, DESIGNED 5049 03:13:11,854 --> 03:13:14,189 TO IMPROVE SELF EFFICACY, 5050 03:13:14,189 --> 03:13:22,464 NOT CONDITION AND TALKS 5051 03:13:22,464 --> 03:13:29,138 ABOUT MINDFULNESS BUT 5052 03:13:29,138 --> 03:13:30,773 DOESN'T TALK ABOUT 5053 03:13:30,773 --> 03:13:31,440 PREVENTION. 5054 03:13:31,440 --> 03:13:34,977 SO THIS IS SOMEONE WHO MAY 5055 03:13:34,977 --> 03:13:38,247 BE TRYING TO CONTROL THEIR 5056 03:13:38,247 --> 03:13:39,548 DIET, THEIR BLOOD PRESSURE 5057 03:13:39,548 --> 03:13:42,718 AND WE DID IT WITH THE 5058 03:13:42,718 --> 03:13:44,486 INTENTION OF MINIMIZING THE 5059 03:13:44,486 --> 03:13:47,356 PLACEBO SO WE MATCHED THE M 5060 03:13:47,356 --> 03:13:50,225 BS R FOR SETTING TIME BUT 5061 03:13:50,225 --> 03:13:52,328 STILL KEPT IT LIMITED. 5062 03:13:52,328 --> 03:13:54,229 SO 18 MONTHS TOTAL, PEOPLE 5063 03:13:54,229 --> 03:13:56,031 ASSIGNED FOR THE FIRST SIX 5064 03:13:56,031 --> 03:13:59,201 MONTHS TO EITHER M BS R 5065 03:13:59,201 --> 03:14:00,235 ALONE, EXERCISE ALONE, 5066 03:14:00,235 --> 03:14:02,771 COMBINATION OR HEALTH 5067 03:14:02,771 --> 03:14:03,238 EDUCATION. 5068 03:14:03,238 --> 03:14:13,782 STUDY POPULATION TENDED TO 5069 03:14:18,020 --> 03:14:23,659 BE 580 PEOPLE, AGES 65 AND 5070 03:14:23,659 --> 03:14:26,729 OLDER, NO DEMENTIA, WE 5071 03:14:26,729 --> 03:14:33,902 COMPLETED A VERY LARGE 5072 03:14:33,902 --> 03:14:36,905 BATTERY OF TESTS, 5073 03:14:36,905 --> 03:14:40,743 NEUROPSYCHOLOGICAL, PEUF AL 5074 03:14:40,743 --> 03:14:41,877 BIOMARKERS, METABOLIC, 5075 03:14:41,877 --> 03:14:45,280 FITNESS AND PERFORMANCE, 5076 03:14:45,280 --> 03:14:47,716 NEUROIMAGING AND BEHAVIORAL 5077 03:14:47,716 --> 03:14:49,151 AND FUNCTIONAL AND THE 5078 03:14:49,151 --> 03:14:51,820 OUTCOMES I WILL TALK ABOUT 5079 03:14:51,820 --> 03:14:54,623 TODAY ARE COGNITIVE SO WHAT 5080 03:14:54,623 --> 03:14:55,891 Dr. LIN TALKED ABOUT IN 5081 03:14:55,891 --> 03:14:58,727 TERMS OF MEMORY AND 5082 03:14:58,727 --> 03:15:00,663 COGNITIVE CONTROL, WE HAD 5083 03:15:00,663 --> 03:15:03,332 SOME LIFT IN LEARNING AND 5084 03:15:03,332 --> 03:15:06,702 THEN MEASURES FROM THE NIH 5085 03:15:06,702 --> 03:15:09,571 TOOL BOX WHICH Dr. LIN 5086 03:15:09,571 --> 03:15:10,739 MENTIONED YESTERDAY FOR 5087 03:15:10,739 --> 03:15:13,008 COGNITIVE CONTROL AND THEN 5088 03:15:13,008 --> 03:15:14,977 OTHER COMPUTER BASED 5089 03:15:14,977 --> 03:15:18,414 COGNITIVE CONTROL FUNCTION. 5090 03:15:18,414 --> 03:15:24,987 OUR SAMPLE, WE ACTUALLY 5091 03:15:24,987 --> 03:15:27,990 RECRUITED A LITTLE BIT WHICH 5092 03:15:27,990 --> 03:15:38,534 IS GOOD, VERY MUCH FEMALE, 5093 03:15:38,767 --> 03:15:40,169 MAINLY NONHISPANIC WHITE, 5094 03:15:40,169 --> 03:15:42,671 NORMAL COGNITION TO START. 5095 03:15:42,671 --> 03:15:44,506 HAD SOME COLLEGE, LARGELY 5096 03:15:44,506 --> 03:15:46,842 HEALTHY BECAUSE THEY HAD TO 5097 03:15:46,842 --> 03:15:48,610 BE HEALTHY ENOUGH TO BE 5098 03:15:48,610 --> 03:15:51,280 EXPOSED TO A MILD TO 5099 03:15:51,280 --> 03:15:52,748 MODERATE EXERCISE PROGRAM, 5100 03:15:52,748 --> 03:15:55,918 THEY DID HAVE MENTAL 5101 03:15:55,918 --> 03:16:01,390 ILLNESS, AVERAGE OF THREE, A 5102 03:16:01,390 --> 03:16:02,157 THIRD IMPAIRED INSULIN 5103 03:16:02,157 --> 03:16:08,197 SENSITIVITY AND OTHER THINGS 5104 03:16:08,197 --> 03:16:09,231 AS WELL. 5105 03:16:09,231 --> 03:16:10,933 AND BOTTOM LINE IS THIS WAS 5106 03:16:10,933 --> 03:16:12,234 A IN RESULTS TRIAL. 5107 03:16:12,234 --> 03:16:14,269 WE DID NOT FIND IN OUR STUDY 5108 03:16:14,269 --> 03:16:16,371 AT LEAST THAT EITHER 5109 03:16:16,371 --> 03:16:18,240 EXERCISE OR MINDFULNESS OR 5110 03:16:18,240 --> 03:16:19,575 THE COMBINATION HAVING 5111 03:16:19,575 --> 03:16:21,543 IMPACT ON COGNITIVE FUNCTION 5112 03:16:21,543 --> 03:16:22,878 OR BRAIN VOLUMES. 5113 03:16:22,878 --> 03:16:26,281 WE DID FIND SOME MARGINAL 5114 03:16:26,281 --> 03:16:27,182 EFFECTS ON THE FUNCTIONAL 5115 03:16:27,182 --> 03:16:29,284 BRAIN WHICH I AM NOT GOING 5116 03:16:29,284 --> 03:16:33,388 TO TALK ABOUT BUT IT HAS 5117 03:16:33,388 --> 03:16:33,856 BEEN PUBLISHED. 5118 03:16:33,856 --> 03:16:34,556 GENERALLY SPEAKING, WE HAD 5119 03:16:34,556 --> 03:16:36,091 TO DO A LITTLE DIGGING THEN 5120 03:16:36,091 --> 03:16:38,494 TO TRY TO FIGURE OUT WHY 5121 03:16:38,494 --> 03:16:43,465 THIS STUDY DID NOT WORK AS 5122 03:16:43,465 --> 03:16:44,366 WE INTENDED. 5123 03:16:44,366 --> 03:16:46,769 BUT TO PROVIDE A LITTLE DATA 5124 03:16:46,769 --> 03:16:48,670 WHAT THIS LOOKS LIKE, ON THE 5125 03:16:48,670 --> 03:16:50,439 RIGHT SIDE YOU HAVE PEOPLE 5126 03:16:50,439 --> 03:16:54,743 WHO DID OR DID NOT RECEIVE M 5127 03:16:54,743 --> 03:16:57,045 BS R, COGNITIVE FUNCTIONING 5128 03:16:57,045 --> 03:16:57,946 OVER 18 MONTHS. 5129 03:16:57,946 --> 03:16:59,648 YOU MAY SEE SOME IMPROVEMENT 5130 03:16:59,648 --> 03:17:02,484 BUT WE DID A NEUROPSYCH 5131 03:17:02,484 --> 03:17:04,887 BATTERY WITHIN TWO WEEKS TO 5132 03:17:04,887 --> 03:17:06,588 GET OLDERS FOLKS FAMILIAR 5133 03:17:06,588 --> 03:17:08,190 WITH SITTING DOWN AT A 5134 03:17:08,190 --> 03:17:10,392 COMPUTER AND TAKING THESE 5135 03:17:10,392 --> 03:17:13,862 TESTS BUT BASICALLY THEY 5136 03:17:13,862 --> 03:17:15,330 APPROVED THE SAME AMOUNT 5137 03:17:15,330 --> 03:17:19,468 WITH OR WITHOUT M BS R AND 5138 03:17:19,468 --> 03:17:22,137 WITH OR WITHOUT EX SER VICE 5139 03:17:22,137 --> 03:17:23,972 AND NO INTERACTION EFFECTS 5140 03:17:23,972 --> 03:17:26,875 BUT THE SAME WAS TRUE OVER 5141 03:17:26,875 --> 03:17:29,478 18 MONTHS. 5142 03:17:29,478 --> 03:17:31,280 COGNITIVE EFFECTS WITH 5143 03:17:31,280 --> 03:17:33,682 LITTLE OR NO EXERCISE, THERE 5144 03:17:33,682 --> 03:17:35,851 WAS IMPROVEMENT UP TO SIX 5145 03:17:35,851 --> 03:17:38,854 MONTHS AND THEN PEOPLE 5146 03:17:38,854 --> 03:17:39,454 STABILIZED AFTER. 5147 03:17:39,454 --> 03:17:41,790 SO TRYING TO FIGURE OUT WHY 5148 03:17:41,790 --> 03:17:45,460 AND THE QUESTION WAS MAYBE 5149 03:17:45,460 --> 03:17:48,463 PEOPLE WEREN'T ADHERENT, 5150 03:17:48,463 --> 03:17:49,898 DOING THE THINGS WE 5151 03:17:49,898 --> 03:17:51,466 RECOMMENDED THEY DO. 5152 03:17:51,466 --> 03:17:53,669 SO WE LOOKED AT CLASS 5153 03:17:53,669 --> 03:17:55,170 PARTICIPATION, VERY EASY TO 5154 03:17:55,170 --> 03:17:56,104 MEASURE AND THE VAST 5155 03:17:56,104 --> 03:17:58,173 MAJORITY OF PEOPLE IN ALL 5156 03:17:58,173 --> 03:17:59,541 THREE GROUPS ATTENDED AT 5157 03:17:59,541 --> 03:18:01,243 LEAST 70 PERCENT OF THE 5158 03:18:01,243 --> 03:18:02,511 CLASSES SO YOU KNOW WITH 5159 03:18:02,511 --> 03:18:03,745 RESPECT TO CLASS 5160 03:18:03,745 --> 03:18:06,481 PARTICIPATION, WE HAD PRETTY 5161 03:18:06,481 --> 03:18:07,983 GOOD ADHERENCE WITH THE 5162 03:18:07,983 --> 03:18:10,219 STUDY AT THIS TIME. 5163 03:18:10,219 --> 03:18:12,521 WE COLLECTED AT-HOME 5164 03:18:12,521 --> 03:18:13,322 PRACTICE INFORMATION, 5165 03:18:13,322 --> 03:18:14,156 SELF-REPORT EARLY WHILE 5166 03:18:14,156 --> 03:18:20,963 FOLKS WERE IN THE EXERCISE 5167 03:18:20,963 --> 03:18:24,032 CLASS OR WEEKLY AND MONTHLY 5168 03:18:24,032 --> 03:18:26,768 WHERE PEOPLE HAD M BS R. 5169 03:18:26,768 --> 03:18:29,304 WE ALSO LOOKED AT 5170 03:18:29,304 --> 03:18:29,972 ASSESSMENTS WHERE THREE 5171 03:18:29,972 --> 03:18:32,708 TIMES A DAY WE ASKED THEM 5172 03:18:32,708 --> 03:18:34,409 ABOUT SLEEP AT HOME, THEIR 5173 03:18:34,409 --> 03:18:36,044 PRACTICE SO WE DID GET DATA 5174 03:18:36,044 --> 03:18:39,248 THAT WAS A LITTLE MORE 5175 03:18:39,248 --> 03:18:44,019 RELIABLE AND THE HISTOGRAMS 5176 03:18:44,019 --> 03:18:46,421 SHOW THAT PEOPLE DID REPORT 5177 03:18:46,421 --> 03:18:49,224 HOME PRACTICE AND MOST 5178 03:18:49,224 --> 03:18:51,059 REPORTED HIGH AMOUNTS OF IT. 5179 03:18:51,059 --> 03:18:54,263 SO YOU SEE ON THE LEFT GRAPH 5180 03:18:54,263 --> 03:18:56,531 NO DIFFERENCE WITH FOLKS WHO 5181 03:18:56,531 --> 03:18:59,301 DID OR DID NOT RECEIVE M BS 5182 03:18:59,301 --> 03:18:59,768 R. 5183 03:18:59,768 --> 03:19:01,803 ON THE RIGHT, FOLKS WHO 5184 03:19:01,803 --> 03:19:05,874 REPORTED HOME PRACTICE ON AT 5185 03:19:05,874 --> 03:19:09,144 LEAST 75 PERCENT OF DAYS AND 5186 03:19:09,144 --> 03:19:11,013 AGAIN NO PRACTICE BETWEEN 5187 03:19:11,013 --> 03:19:12,714 THE TWO GROUPS. 5188 03:19:12,714 --> 03:19:16,785 WITH RESPECT TO EXERCISE, NO 5189 03:19:16,785 --> 03:19:24,593 DIFFERENCE ON THE LEFT AND 5190 03:19:24,593 --> 03:19:26,028 HOME PRACTICE 70 PERCENT SO 5191 03:19:26,028 --> 03:19:27,296 SEEING THE SAME SORT OF 5192 03:19:27,296 --> 03:19:30,165 THING WITH THE FOLKS WHO 5193 03:19:30,165 --> 03:19:31,166 RECEIVED EXERCISE 5194 03:19:31,166 --> 03:19:32,100 INTERVENTION AND THOSE WHO 5195 03:19:32,100 --> 03:19:32,801 DID NOT. 5196 03:19:32,801 --> 03:19:35,671 SO THEN THE NEXT QUESTION TO 5197 03:19:35,671 --> 03:19:37,739 ASK IS MAYBE WE DIDN'T 5198 03:19:37,739 --> 03:19:40,342 ACHIEVE TARGET, MAYBE THE 5199 03:19:40,342 --> 03:19:41,710 EXERCISE WASN'T INTENSE 5200 03:19:41,710 --> 03:19:43,779 ENOUGH, MAYBE WE WEREN'T 5201 03:19:43,779 --> 03:19:45,614 MAKING A DIFFERENCE IN OUR 5202 03:19:45,614 --> 03:19:46,682 INTERVENTION. 5203 03:19:46,682 --> 03:19:57,159 SO WE LOOKED AT A LOT OF 5204 03:20:09,538 --> 03:20:13,208 DIFFERENT EMPHASES, EXERCISE 5205 03:20:13,208 --> 03:20:14,576 INFLUENCED MANY 5206 03:20:14,576 --> 03:20:16,578 PHYSIOLOGICAL AND 5207 03:20:16,578 --> 03:20:19,214 PERFORMANCE VARIABLE, AND 5208 03:20:19,214 --> 03:20:22,818 THOSE WITH INSULIN 5209 03:20:22,818 --> 03:20:23,352 SENSITIVITY, AEROBIC 5210 03:20:23,352 --> 03:20:25,787 FITNESS, STRENGTH, SLEEP 5211 03:20:25,787 --> 03:20:28,623 LATENCY AND TOTAL SLEEP 5212 03:20:28,623 --> 03:20:30,592 TIME, EVERYBODY IMPROVED ALL 5213 03:20:30,592 --> 03:20:31,393 OF THESE THINGS. 5214 03:20:31,393 --> 03:20:33,428 SO LOOKING AT THE MEMORY 5215 03:20:33,428 --> 03:20:35,030 COMPOSITE CHANGE IN THE 5216 03:20:35,030 --> 03:20:37,232 FOLKS WHO GOT EXERCISE AND 5217 03:20:37,232 --> 03:20:38,734 WE'RE COMPARING THE PEOPLE 5218 03:20:38,734 --> 03:20:41,136 WHO HAD THE MOST IMPROVEMENT 5219 03:20:41,136 --> 03:20:42,270 IN THEIR INSULIN SENSITIVITY 5220 03:20:42,270 --> 03:20:44,006 VERSUS THE ONES WHO HAVE THE 5221 03:20:44,006 --> 03:20:46,074 LEAST IMPROVEMENT AND AGAIN 5222 03:20:46,074 --> 03:20:48,110 NO SIGNIFICANT DIFFERENCES. 5223 03:20:48,110 --> 03:20:49,177 SO TARGETING ENGAGEMENT DID 5224 03:20:49,177 --> 03:20:51,246 NOT APPEAR TO BE A FACTOR 5225 03:20:51,246 --> 03:20:53,181 AND WE LOOKED AT THIS MANY 5226 03:20:53,181 --> 03:20:55,350 DIFFERENT WAYS AND I AM JUST 5227 03:20:55,350 --> 03:20:56,651 SHOWING YOU AN EXAMPLE HERE. 5228 03:20:56,651 --> 03:21:01,189 SO WHEN YOU GET RESULTS LIKE 5229 03:21:01,189 --> 03:21:03,025 THIS, OKAY, WAS IT GENUINELY 5230 03:21:03,025 --> 03:21:04,760 A NEGATIVE RESULT OR FAILED 5231 03:21:04,760 --> 03:21:05,060 TRIAL? 5232 03:21:05,060 --> 03:21:06,962 AND I WOULD ARGUE IN SOME 5233 03:21:06,962 --> 03:21:09,231 WAYS YOU KNOW I THINK WE 5234 03:21:09,231 --> 03:21:10,365 WERE PRETTY SUCCESSFUL BUT 5235 03:21:10,365 --> 03:21:13,235 WHEN YOU SAY WHAT ARE THE 5236 03:21:13,235 --> 03:21:17,039 OUTCOMES, WE FOUND THE 5237 03:21:17,039 --> 03:21:20,208 COGNITIVE RATES HAD GOOD 5238 03:21:20,208 --> 03:21:22,511 RELIABILITY AT 28, WHICH IS 5239 03:21:22,511 --> 03:21:23,678 REASONABLE. 5240 03:21:23,678 --> 03:21:24,579 POOR ADHERENCE, I SHOWED 5241 03:21:24,579 --> 03:21:26,148 THOSE DATA ALREADY THAT 5242 03:21:26,148 --> 03:21:27,883 PEOPLE WERE PRETTY ADHERENCE 5243 03:21:27,883 --> 03:21:30,419 AND THE FOLKS WHO WERE 5244 03:21:30,419 --> 03:21:31,686 ADHERENT LOOKED SIMILAR TO 5245 03:21:31,686 --> 03:21:34,723 THE FOLKS IN THE OVERALL 5246 03:21:34,723 --> 03:21:36,191 SAMPLE. 5247 03:21:36,191 --> 03:21:38,627 WERE THE INTERVENTIONS TOO 5248 03:21:38,627 --> 03:21:38,927 WEAK? 5249 03:21:38,927 --> 03:21:40,262 EXERCISE GROUP DID WHAT 5250 03:21:40,262 --> 03:21:43,632 EXERCISE SHOULD DO IN A 5251 03:21:43,632 --> 03:21:45,534 GROUP OF SEDENTARY ADULTS IN 5252 03:21:45,534 --> 03:21:47,402 TERMS OF THE OUTCOMES YOU 5253 03:21:47,402 --> 03:21:49,104 WOULD EXPECT ARE PHYSICAL 5254 03:21:49,104 --> 03:21:51,473 HEALTH, NOT SO CLEAR WITH 5255 03:21:51,473 --> 03:21:54,009 MINDFULNESS AND AGAIN THOSE 5256 03:21:54,009 --> 03:21:54,810 WHO SHOWED OBJECTIVE 5257 03:21:54,810 --> 03:21:57,813 EVIDENCE OF IMPROVEMENT BY 5258 03:21:57,813 --> 03:21:59,948 EXERCISE HAD SIMILAR 5259 03:21:59,948 --> 03:22:01,216 OUTCOMES THAN -- VERSUS 5260 03:22:01,216 --> 03:22:02,317 THOSE WHO DID NOT. 5261 03:22:02,317 --> 03:22:07,255 SO PERHAPS IT WAS THE WRONG 5262 03:22:07,255 --> 03:22:08,023 TIME OF INTERVENTION. 5263 03:22:08,023 --> 03:22:11,426 MIGHT HAVE BEEN TOO SOON. 5264 03:22:11,426 --> 03:22:16,531 HOPING OLDER ADULTS NOT ON A 5265 03:22:16,531 --> 03:22:18,300 TRAJECTORY YET PERHAPS, TOO 5266 03:22:18,300 --> 03:22:21,136 LATE, WE HAVE HEARD LOTS OF 5267 03:22:21,136 --> 03:22:22,737 STARTING THESE INTERVENTIONS 5268 03:22:22,737 --> 03:22:24,539 TILL MIDLIFE OR EARLIER SO 5269 03:22:24,539 --> 03:22:28,977 WAITING TILL THEY WERE OLDER 5270 03:22:28,977 --> 03:22:34,850 MIGHT HAVE HAD NO IMPACT. 5271 03:22:34,850 --> 03:22:38,220 TOO SHORT, HEARING ABOUT 5272 03:22:38,220 --> 03:22:38,887 LONGER INTERVENTIONS, IT IS 5273 03:22:38,887 --> 03:22:41,790 POSSIBLE THAT WAS AN ISSUE. 5274 03:22:41,790 --> 03:22:42,357 TOO LOW INTENSITY? 5275 03:22:42,357 --> 03:22:44,626 I DON'T KNOW ABOUT THAT. 5276 03:22:44,626 --> 03:22:46,228 WE KIND OF DESIGNED THIS TO 5277 03:22:46,228 --> 03:22:50,832 BE WHAT WAS RECOMMENDED IN 5278 03:22:50,832 --> 03:22:52,534 TERMS OF EXERCISE AND 5279 03:22:52,534 --> 03:22:53,435 STANDARD PROTOCOLS BUT IT IS 5280 03:22:53,435 --> 03:22:55,737 POSSIBLE THAT IS NOT ENOUGH 5281 03:22:55,737 --> 03:22:56,805 TO IMPROVE COGNITIVE 5282 03:22:56,805 --> 03:22:57,973 OUTCOMES IN OLDER PEOPLE. 5283 03:22:57,973 --> 03:23:00,108 SO HERE IS ONE OF THE 5284 03:23:00,108 --> 03:23:03,478 ISSUES, I THINK, FAILURE OF 5285 03:23:03,478 --> 03:23:04,713 RECRUITMENT. 5286 03:23:04,713 --> 03:23:07,649 MOST CLEARLY OBVIOUSLY IN 5287 03:23:07,649 --> 03:23:09,885 Dr. LIN'S STUDY, THESE 5288 03:23:09,885 --> 03:23:11,319 WERE LARGELY HEALTHY 5289 03:23:11,319 --> 03:23:11,753 PARTICIPANTS. 5290 03:23:11,753 --> 03:23:14,122 THEY WERE REQUIRED TO BE 5291 03:23:14,122 --> 03:23:15,524 SEDENTARY AND WE HAD A 5292 03:23:15,524 --> 03:23:17,559 NUMBER OF QUESTIONS TO 5293 03:23:17,559 --> 03:23:18,527 ELICIT THAT INFORMATION BUT 5294 03:23:18,527 --> 03:23:22,297 THEY HAD TO BE RANDOMIZABLE 5295 03:23:22,297 --> 03:23:25,133 AND THEY ALSO HAD TO NOT 5296 03:23:25,133 --> 03:23:27,769 HAVE DIABETES OR SOME OTHER 5297 03:23:27,769 --> 03:23:28,270 CRITERIA. 5298 03:23:28,270 --> 03:23:37,412 SO THEY WERE PRETTY HEALTHY. 5299 03:23:37,412 --> 03:23:41,816 I REMEMBER A PILOT STUDY 5300 03:23:41,816 --> 03:23:44,452 THAT SHOWED EFFECT FOR OLDER 5301 03:23:44,452 --> 03:23:45,720 ADULTS WITH ANXIETY OR 5302 03:23:45,720 --> 03:23:47,756 DEPRESSION, WE DID NOT 5303 03:23:47,756 --> 03:23:48,924 SCREEN THOSE OUT BUT VERY 5304 03:23:48,924 --> 03:23:50,992 FEW OF THESE FOLKS HAD 5305 03:23:50,992 --> 03:23:53,295 SIGNIFICANT LEVELS OF 5306 03:23:53,295 --> 03:23:55,197 ANXIETY OR DEPRESSION. 5307 03:23:55,197 --> 03:23:58,066 THESE WERE A VOLUNTEER 5308 03:23:58,066 --> 03:23:59,568 SAMPLE, LARGELY AFFLUENT, 5309 03:23:59,568 --> 03:24:00,468 HAD GOOD ACCESS TO 5310 03:24:00,468 --> 03:24:02,971 HEALTHCARE THROUGH THEIR 5311 03:24:02,971 --> 03:24:05,106 LIVES, GOOD NUTRITION, A LOT 5312 03:24:05,106 --> 03:24:08,043 OF KIND OF PRIVILEGE FACTORS 5313 03:24:08,043 --> 03:24:09,878 BASICALLY THAT MAY HAVE 5314 03:24:09,878 --> 03:24:11,446 AFFECTED OUR RESULTS. 5315 03:24:11,446 --> 03:24:14,249 AND COGNITIVELY IN FACT TO 5316 03:24:14,249 --> 03:24:15,116 START WITH. 5317 03:24:15,116 --> 03:24:16,818 SO WE ROUX CRUDE FOR PEOPLE 5318 03:24:16,818 --> 03:24:19,054 WHO WERE REPORTING SOME KIND 5319 03:24:19,054 --> 03:24:21,790 OF COGNITIVE CHANGE BUT THE 5320 03:24:21,790 --> 03:24:24,059 QUESTION IS WHAT DOES THAT 5321 03:24:24,059 --> 03:24:24,593 REPRESENT? 5322 03:24:24,593 --> 03:24:26,628 SO THERE ARE ALSO ANXIETY 5323 03:24:26,628 --> 03:24:31,166 DISORDER AND OFTEN PEOPLE 5324 03:24:31,166 --> 03:24:34,569 WHO REPORT COGNITIVE CHANGES 5325 03:24:34,569 --> 03:24:36,338 ARE MORE ANXIOUS OR 5326 03:24:36,338 --> 03:24:37,606 DEPRESSED AS OPPOSED TO 5327 03:24:37,606 --> 03:24:38,974 EARLY STAGES OF DECLINE. 5328 03:24:38,974 --> 03:24:41,476 BUT IN THIS CASE WE HAD 5329 03:24:41,476 --> 03:24:47,115 FOLKS WHO WERE VERY INTENSE 5330 03:24:47,115 --> 03:24:49,517 IN THE WAY OF COGNITION, 5331 03:24:49,517 --> 03:24:54,289 TAKING CARE OF THEIR HEALTH, 5332 03:24:54,289 --> 03:24:56,458 ACCESS TO GOOD NEWS 5333 03:24:56,458 --> 03:24:57,192 ATTRITION. 5334 03:24:57,192 --> 03:24:59,427 SO IN CONCLUSION, WE DID NOT 5335 03:24:59,427 --> 03:25:03,498 FIND COGNITIVE CHANGES WITH 5336 03:25:03,498 --> 03:25:05,467 INTERVENTION, IT DID CAST 5337 03:25:05,467 --> 03:25:09,738 DOUBT IN THIS STUDY ON THE 5338 03:25:09,738 --> 03:25:12,173 INTERVENTION ON A VOLUNTEER 5339 03:25:12,173 --> 03:25:13,308 OLDER HEALTHY SAMPLE. 5340 03:25:13,308 --> 03:25:17,345 IN THE FUTURE, I THINK IT 5341 03:25:17,345 --> 03:25:27,255 WOULD BENEFIT TO DO TESTS 5342 03:25:27,255 --> 03:25:30,659 WITH HEALTHY OLDER ADULTS, 5343 03:25:30,659 --> 03:25:34,696 MAYBE WITH INTERVENTION AND 5344 03:25:34,696 --> 03:25:36,865 IN MORE VULNERABLE OLDER 5345 03:25:36,865 --> 03:25:38,033 ADULTS, WHETHER WE ARE ABLE 5346 03:25:38,033 --> 03:25:41,336 TO KEEP THEM COGNITIVELY 5347 03:25:41,336 --> 03:25:42,704 HEALTHY LONGER. 5348 03:25:42,704 --> 03:25:44,939 SO WITH THAT I WANT TO THANK 5349 03:25:44,939 --> 03:25:47,008 THESE HUGE CROWDS OF PEOPLE 5350 03:25:47,008 --> 03:25:49,277 IN SAN DIEGO AND ST. LOUIS 5351 03:25:49,277 --> 03:25:50,745 WITHOUT WHOM WE COULD NOT 5352 03:25:50,745 --> 03:25:52,480 HAVE DONE THIS WORK AND LOOK 5353 03:25:52,480 --> 03:26:02,991 FORWARD TO QUESTIONS LATER. 5354 03:26:02,991 --> 03:26:05,627 THANK YOU. 5355 03:26:05,627 --> 03:26:06,227 [APPLAUSE] 5356 03:26:06,227 --> 03:26:11,366 >> OKAY, OUR FINAL SPEAKER. 5357 03:26:11,366 --> 03:26:13,501 ARNOLD BAKKER FROM JOHNS 5358 03:26:13,501 --> 03:26:15,236 HOPKINS UNIVERSITY AND 5359 03:26:15,236 --> 03:26:17,505 TALKING ABOUT TARGETING 5360 03:26:17,505 --> 03:26:20,475 INDIVIDUAL DIFFERENCES IN 5361 03:26:20,475 --> 03:26:25,280 HIPPO CAMPAL HYPERACTIVITY. 5362 03:26:25,280 --> 03:26:26,348 >> Translator: LAKESAL 5363 03:26:26,348 --> 03:26:27,849 STUDIES OF NEUROCOGNITIVE 5364 03:26:27,849 --> 03:26:28,149 AGING. 5365 03:26:28,149 --> 03:26:33,121 >> THANK YOU, HAPPY TO BE 5366 03:26:33,121 --> 03:26:33,555 HERE. 5367 03:26:33,555 --> 03:26:40,795 SO IF YOU TAKE RATS AND PUT 5368 03:26:40,795 --> 03:26:44,099 THEM IN A RINSE, YOU 5369 03:26:44,099 --> 03:26:45,667 QUANTIFY THEM AND SEE 5370 03:26:45,667 --> 03:26:46,601 DIFFERENCES BETWEEN AGE 5371 03:26:46,601 --> 03:26:48,303 GROUPS AND YOUNG ANIMALS 5372 03:26:48,303 --> 03:26:51,740 WITH THE AGED SHOWING A 5373 03:26:51,740 --> 03:26:53,274 WIDER RANGE OF ABILITY IN 5374 03:26:53,274 --> 03:26:55,710 THEIR PERFORMANCE AND THE 5375 03:26:55,710 --> 03:26:57,345 INTERESTING OBSERVATION THAT 5376 03:26:57,345 --> 03:26:59,147 SOME AGED ANIMALS WILL 5377 03:26:59,147 --> 03:27:00,749 PERFORM EQUIVALENT TO THEIR 5378 03:27:00,749 --> 03:27:01,683 COUNTERPARTS WHERE SOME 5379 03:27:01,683 --> 03:27:04,386 ANIMALS DO NOT AND SHOW 5380 03:27:04,386 --> 03:27:06,087 IMPAIRMENT WITH RESPECT TO 5381 03:27:06,087 --> 03:27:07,922 THE SAME TASK AS THEIR 5382 03:27:07,922 --> 03:27:10,125 YOUNGER COUNTERPARTS AND YOU 5383 03:27:10,125 --> 03:27:12,961 CAN USE THIS TO DEFINE THESE 5384 03:27:12,961 --> 03:27:13,995 TWO GROUPS. 5385 03:27:13,995 --> 03:27:15,430 THIS IS OBVIOUSLY NOT 5386 03:27:15,430 --> 03:27:16,631 LIMITED TO RATS. 5387 03:27:16,631 --> 03:27:18,099 ON THE RIGHTHAND SIDE AT THE 5388 03:27:18,099 --> 03:27:21,603 BOTTOM I AM SHOWING A GRAPH 5389 03:27:21,603 --> 03:27:27,342 THAT WAS A MEMORY PARADIGM 5390 03:27:27,342 --> 03:27:32,414 ON PRIMATES AND SEEING THE 5391 03:27:32,414 --> 03:27:34,716 SAME OR SIMILAR RESULTS AND 5392 03:27:34,716 --> 03:27:36,785 THEN I SHOW HUMAN SUBJECTS 5393 03:27:36,785 --> 03:27:41,289 WHERE WE KNOW THIS IS A 5394 03:27:41,289 --> 03:27:42,090 DIFFERENCE IN TRAJECTORIES 5395 03:27:42,090 --> 03:27:44,626 WHICH LEADS US TO ASK WHAT 5396 03:27:44,626 --> 03:27:47,896 ARE THE SUCCESSFUL AGENTS 5397 03:27:47,896 --> 03:27:49,030 VERSUS NONSUCCESSFUL AGENTS 5398 03:27:49,030 --> 03:27:52,567 AND THERE ARE MANY 5399 03:27:52,567 --> 03:27:53,935 CONTRIBUTING FACTORS TO 5400 03:27:53,935 --> 03:27:55,236 THESE TRAJECTORIES. 5401 03:27:55,236 --> 03:27:58,173 IN MY LAB, WE ARE TRYING TO 5402 03:27:58,173 --> 03:27:59,874 UNDERSTAND THE MAJOR 5403 03:27:59,874 --> 03:28:01,743 CONTRIBUTING FACTORS TO 5404 03:28:01,743 --> 03:28:02,243 MEMORY IMPAIRMENT. 5405 03:28:02,243 --> 03:28:05,046 SO IF YOU FOCUS ON MEMORY 5406 03:28:05,046 --> 03:28:06,414 IMPAIRMENT AND TAKE THOSE 5407 03:28:06,414 --> 03:28:08,316 TWO GROUPS OF ANIMALS AND 5408 03:28:08,316 --> 03:28:10,218 FOCUS ON THE AGE IMPAIRED 5409 03:28:10,218 --> 03:28:12,487 COMPARED TO THE YOUNG AND DO 5410 03:28:12,487 --> 03:28:16,024 SINGLE CELL RECORDING IN THE 5411 03:28:16,024 --> 03:28:17,992 HIPPO CAMPAL CELLS WHILE 5412 03:28:17,992 --> 03:28:20,028 NAVIGATING THROUGH THE 5413 03:28:20,028 --> 03:28:21,729 FAMILIAR ENVIRONMENT, AS 5414 03:28:21,729 --> 03:28:24,599 SEEN ON THE LEFTHAND SIDE, 5415 03:28:24,599 --> 03:28:27,068 WE SEE THE RECORDING WITH 5416 03:28:27,068 --> 03:28:34,142 YOUNG ANIMALS THAT IT 5417 03:28:34,142 --> 03:28:36,077 RAPIDLY DOES A REVIEW OF THE 5418 03:28:36,077 --> 03:28:37,779 NEW ENVIRONMENT AND THEN 5419 03:28:37,779 --> 03:28:38,546 REMEMBERS THE OLD 5420 03:28:38,546 --> 03:28:40,315 ENVIRONMENT WHEN IT IS PUT 5421 03:28:40,315 --> 03:28:40,849 BACK. 5422 03:28:40,849 --> 03:28:43,518 BUT IF YOU LOOK AT THE AGED 5423 03:28:43,518 --> 03:28:44,786 ANIMALS, THERE IS A FAILURE 5424 03:28:44,786 --> 03:28:47,155 TO UP WITH DATE OR REPRESENT 5425 03:28:47,155 --> 03:28:49,290 THE NOVEL ENVIRONMENT AS 5426 03:28:49,290 --> 03:28:50,825 CLASSIFIED ON THE BOTTOM 5427 03:28:50,825 --> 03:28:54,128 RIGHTHAND SIDE AND THIS IS 5428 03:28:54,128 --> 03:28:55,763 SPECIFIC TO THE CA3 IMPAIRED 5429 03:28:55,763 --> 03:28:58,066 ANIMAL AND DO NOT SEE THAT 5430 03:28:58,066 --> 03:29:00,535 IN THE CA1. 5431 03:29:00,535 --> 03:29:03,471 WHAT IS SHOWN IN THE FAR 5432 03:29:03,471 --> 03:29:04,973 RIGHT, THE FIRING RATE. 5433 03:29:04,973 --> 03:29:08,309 WE ARE NOTING A INCREASED 5434 03:29:08,309 --> 03:29:10,311 FIRING RATE IN THE AGED IN 5435 03:29:10,311 --> 03:29:11,179 BOTH NOVEL AND FAMILIAR 5436 03:29:11,179 --> 03:29:12,614 ENVIRONMENTS AND THAT IS 5437 03:29:12,614 --> 03:29:14,849 SOMETHING NOT SEEN IN THE 5438 03:29:14,849 --> 03:29:16,718 YOUNG ANIMALS. 5439 03:29:16,718 --> 03:29:19,153 SO THIS IN ADDITION TO A LOT 5440 03:29:19,153 --> 03:29:23,157 OF OTHER DATA LEFT TO A 5441 03:29:23,157 --> 03:29:25,793 MODEL OF NEUROCOGNITIVE 5442 03:29:25,793 --> 03:29:29,230 AGING PROPOSED BY WILSON AND 5443 03:29:29,230 --> 03:29:30,765 COLLEAGUES IN 2006 PROPOSING 5444 03:29:30,765 --> 03:29:33,368 LOSS OF INPUT FROM THE 5445 03:29:33,368 --> 03:29:36,371 CORTEX INTO THE HYPO CAMPAL 5446 03:29:36,371 --> 03:29:38,406 CIRCUITRY AS WELL AS 5447 03:29:38,406 --> 03:29:40,708 HYPERACTIVE NEURONS IN CA3 5448 03:29:40,708 --> 03:29:44,846 IS THE RESULT OF PROJECTION 5449 03:29:44,846 --> 03:29:46,548 AND UNDER CURRENT 5450 03:29:46,548 --> 03:29:49,250 COLLATERALS, INBOUNDS OF 5451 03:29:49,250 --> 03:29:51,853 THAT ACTIVATION RESULT IN 5452 03:29:51,853 --> 03:29:53,788 MEMORY IMPAIRMENT OR 5453 03:29:53,788 --> 03:29:56,391 CONTRIBUTE TO MEMORY 5454 03:29:56,391 --> 03:29:59,761 IMPAIRMENT IN THE RIGIDITY 5455 03:29:59,761 --> 03:30:00,995 OF CA3. 5456 03:30:00,995 --> 03:30:02,597 IN HUMAN SUBJECTS, THERE HAS 5457 03:30:02,597 --> 03:30:05,199 BEEN SOME EVIDENCE OF THIS 5458 03:30:05,199 --> 03:30:07,435 HYPER EXCITABILITY IN THE 5459 03:30:07,435 --> 03:30:10,305 HIPPO CAMPUS AS WELL. 5460 03:30:10,305 --> 03:30:12,140 HARVARD UNIVERSITY PUBLISHED 5461 03:30:12,140 --> 03:30:14,175 A PAPER IN 2005 SHOWING 5462 03:30:14,175 --> 03:30:17,378 INDIVIDUALS WITH ISLAND 5463 03:30:17,378 --> 03:30:18,880 COGNITIVE IMPAIRMENT SHOWING 5464 03:30:18,880 --> 03:30:22,517 IRON ACTIVITY THAT WAS NOT 5465 03:30:22,517 --> 03:30:25,086 SEEN IN THE CONTROL 5466 03:30:25,086 --> 03:30:26,788 PARTICIPANTS OR THOSE WITH 5467 03:30:26,788 --> 03:30:28,423 DEMENT THAT. 5468 03:30:28,423 --> 03:30:31,359 THIS STUDY DID NOT HAVE THE 5469 03:30:31,359 --> 03:30:35,763 DETAILS TO LOCATE THE 5470 03:30:35,763 --> 03:30:39,100 HYPERACTIVITY TO THE 5471 03:30:39,100 --> 03:30:40,935 HIPPOCAMPUS, THAT STUDY WAS 5472 03:30:40,935 --> 03:30:41,970 DONE A LITTLE LATER. 5473 03:30:41,970 --> 03:30:45,039 AND I AM SHOWING IN THE 5474 03:30:45,039 --> 03:30:47,075 BOTTOM RIGHTHAND SIDE THAT 5475 03:30:47,075 --> 03:30:51,279 THE HYPERACTIVITY CAN BE 5476 03:30:51,279 --> 03:30:53,648 LOCALIZED WITH THE SUBFUSION 5477 03:30:53,648 --> 03:30:55,216 OF THE HIPPOCAMPUS AND IS 5478 03:30:55,216 --> 03:31:04,092 NOT OBSERVED IN THE CA1. 5479 03:31:04,092 --> 03:31:10,832 AND BOTTOM RIGHTHAND, THE 5480 03:31:10,832 --> 03:31:12,100 RESULTANT CIRCUITRY. 5481 03:31:12,100 --> 03:31:16,337 SO THIS RAISES A QUESTION. 5482 03:31:16,337 --> 03:31:18,940 DICKERSON SAID THAT IT WAS 5483 03:31:18,940 --> 03:31:20,208 COMPENSATORY FOR THE 5484 03:31:20,208 --> 03:31:22,143 HIPPOCAMPUS TO MAKE UP FOR 5485 03:31:22,143 --> 03:31:23,978 LOSS AND THESE DATA 5486 03:31:23,978 --> 03:31:26,314 SUGGESTED IT MIGHT BE 5487 03:31:26,314 --> 03:31:27,515 RELATING TO AN IMPAIR 5488 03:31:27,515 --> 03:31:29,684 MOUNTLAKE TERRACE THEY ARE 5489 03:31:29,684 --> 03:31:30,284 EXPERIENCING. 5490 03:31:30,284 --> 03:31:35,490 SO THEN THE HYPOTHESIS DOES 5491 03:31:35,490 --> 03:31:37,291 REDUCING ACTIVATION OBSERVED 5492 03:31:37,291 --> 03:31:39,527 BENEFIT OR IMPAIR MOUNTLAKE 5493 03:31:39,527 --> 03:31:39,894 TERRACE? 5494 03:31:39,894 --> 03:31:45,867 IT WOULD MAKE MEMORY WORSE 5495 03:31:45,867 --> 03:31:48,403 OR REDUCING IT, IMPAIR 5496 03:31:48,403 --> 03:31:50,905 FURTHER THE PARTICIPANTS. 5497 03:31:50,905 --> 03:32:01,616 SO THE PRO AT JOHNS HOPKINS 5498 03:32:01,616 --> 03:32:03,551 USING LORAZAPAM, A 5499 03:32:03,551 --> 03:32:05,019 ANTISEIZURE MEDICATION AND 5500 03:32:05,019 --> 03:32:10,024 YOU CAN SEE ON THE BOTTOM 5501 03:32:10,024 --> 03:32:15,630 LEFTHAND SIDE, SPECIFIC 5502 03:32:15,630 --> 03:32:26,074 DOSES OF LEVETIRACETAM 5503 03:32:27,642 --> 03:32:28,876 SIGNIFICANTLY REDUCED THE 5504 03:32:28,876 --> 03:32:30,211 EFFECTS SHOWING THEY SPENT 5505 03:32:30,211 --> 03:32:35,750 FAR LESS TIME IN THE SALINE 5506 03:32:35,750 --> 03:32:36,684 THAN THE IMPAIRED GROUP. 5507 03:32:36,684 --> 03:32:39,253 SO THIS IS A TREATMENT FOR 5508 03:32:39,253 --> 03:32:40,388 EPILEPSY THAT HAS BEEN 5509 03:32:40,388 --> 03:32:41,789 AROUND FOR MANY YEARS AND WE 5510 03:32:41,789 --> 03:32:44,258 CAN TEST THIS IN A HUMAN 5511 03:32:44,258 --> 03:32:46,260 HYPOTHESIS AT WELL AND THIS 5512 03:32:46,260 --> 03:32:51,032 WAS DONE IN AN AGING STUDY 5513 03:32:51,032 --> 03:32:52,967 ON RODENTS WITH MCI. 5514 03:32:52,967 --> 03:32:54,502 SO HING THE DESIGN OF THE 5515 03:32:54,502 --> 03:32:57,805 STUDY ON THE RIGHTHAND SIDE, 5516 03:32:57,805 --> 03:32:59,307 TUCKED CROSSOVER STEIN, MCI 5517 03:32:59,307 --> 03:33:00,975 PATIENTS WERE INITIALLY 5518 03:33:00,975 --> 03:33:03,511 ASSIGNED TO A DRUG 5519 03:33:03,511 --> 03:33:04,879 CONDITION, THEY COMPLETED 5520 03:33:04,879 --> 03:33:06,714 DRUG TREATMENT FOR TWO 5521 03:33:06,714 --> 03:33:08,950 WEEKS. 5522 03:33:08,950 --> 03:33:10,685 THOSE WHO NIPPERLY WERE 5523 03:33:10,685 --> 03:33:14,288 ASSIGNED DRUGS COMPLETE A 5524 03:33:14,288 --> 03:33:15,423 WASHOUT CONDITION, THEN 5525 03:33:15,423 --> 03:33:17,158 ANOTHER TWO WEEKS AND THOSE 5526 03:33:17,158 --> 03:33:20,495 ASSIGNED TO A PLACEBO WOULD 5527 03:33:20,495 --> 03:33:22,096 COMPLETE THE WASHOUT AND 5528 03:33:22,096 --> 03:33:26,667 THEN TRANSFER BACK TO THE 5529 03:33:26,667 --> 03:33:27,835 PLACEBO GROUP THROUGHOUT THE 5530 03:33:27,835 --> 03:33:31,572 DURATION OF THE STUDY. 5531 03:33:31,572 --> 03:33:33,875 WE ENROLLED 54 MCI PATIENTS 5532 03:33:33,875 --> 03:33:35,009 ACROSS THREE DOSES OF THE 5533 03:33:35,009 --> 03:33:36,110 DRUG AND THESE ARE THE 5534 03:33:36,110 --> 03:33:39,247 RESULTS OF THAT PROOF OF 5535 03:33:39,247 --> 03:33:40,815 CONCEPT STUDY. 5536 03:33:40,815 --> 03:33:47,054 SO THE LEFTHAND BAR GRAPH 5537 03:33:47,054 --> 03:33:49,123 SHOWING THE DOSE EQUIVALENT 5538 03:33:49,123 --> 03:33:52,226 TO THAT IN ANIMALS, IN ALL 5539 03:33:52,226 --> 03:33:59,634 THREE CASES YOU SEE THE 5540 03:33:59,634 --> 03:34:03,938 LIGHT GRAY BAR THAT REFLECTS 5541 03:34:03,938 --> 03:34:05,139 HYPERACTIVITY ACROSS THE 5542 03:34:05,139 --> 03:34:07,108 HIPPOCAMPUS AND THAT HAS 5543 03:34:07,108 --> 03:34:09,177 BEEN OBSERVED IN A NUMBER OF 5544 03:34:09,177 --> 03:34:12,847 STUDIES NOW. 5545 03:34:12,847 --> 03:34:18,486 BOTH THE 62.5MG AND THE 5546 03:34:18,486 --> 03:34:20,154 125MG DOSE SIGNIFICANTLY 5547 03:34:20,154 --> 03:34:22,690 IMPROVED EXCITABILITY IN THE 5548 03:34:22,690 --> 03:34:24,892 HIPPOCAMPUS AND RESULTED IN 5549 03:34:24,892 --> 03:34:26,994 BETTER MEMORY PERFORMANCE. 5550 03:34:26,994 --> 03:34:28,863 BUT THE 250MG DID NOT LOWER 5551 03:34:28,863 --> 03:34:31,098 THE EXCITABILITY IN THE 5552 03:34:31,098 --> 03:34:33,000 HIPPOCAMPUS AND ALSO DID NOT 5553 03:34:33,000 --> 03:34:34,302 HAVE ANY MEMORY BENEFIT. 5554 03:34:34,302 --> 03:34:38,840 SO BRINGING THE ANIMAL DATA 5555 03:34:38,840 --> 03:34:40,842 BACK ON THE FAR RIGHTHAND 5556 03:34:40,842 --> 03:34:45,546 SIDE TO SHOW YOU HOW 5557 03:34:45,546 --> 03:34:47,014 COMPARABLE THESE DOSES ARE. 5558 03:34:47,014 --> 03:34:48,816 SO OF COURSE THE NEXT STEP 5559 03:34:48,816 --> 03:34:52,286 IN TERMS OF TESTING IF THE 5560 03:34:52,286 --> 03:34:56,224 HYPOTHESIS WAS SUCCESSFUL, 5561 03:34:56,224 --> 03:34:59,293 SHOWING THE HYPER 5562 03:34:59,293 --> 03:35:00,394 EXCITABILITY IS NOT 5563 03:35:00,394 --> 03:35:02,230 COMPENSATORY BUT PART OF THE 5564 03:35:02,230 --> 03:35:03,798 PROBLEM AND RAISES THE 5565 03:35:03,798 --> 03:35:06,701 QUESTION COULD THIS DOSE BE 5566 03:35:06,701 --> 03:35:09,070 USED IN MILD IMPAIRMENT 5567 03:35:09,070 --> 03:35:10,938 WHERE THEY RECOGNIZE IN 5568 03:35:10,938 --> 03:35:12,039 ALZHEIMER'S DISEASE 5569 03:35:12,039 --> 03:35:14,675 PROGRESSION IN ADDITION TO 5570 03:35:14,675 --> 03:35:17,345 HAVING ELEVATED AMYLOID 5571 03:35:17,345 --> 03:35:20,147 LEVELS AND TAU, WE SEE THIS 5572 03:35:20,147 --> 03:35:22,049 EXCITABILITY FOR A PERIOD OF 5573 03:35:22,049 --> 03:35:32,593 TIME IN CONJUNCTION WITH THE 5574 03:35:36,831 --> 03:35:37,198 CORTICO ATROPHY. 5575 03:35:37,198 --> 03:35:39,767 SO THIS IS SHOWING THE TRIAL 5576 03:35:39,767 --> 03:35:42,169 SITES ACROSS THE UNITED 5577 03:35:42,169 --> 03:35:43,204 STATES AND CANADA WHO 5578 03:35:43,204 --> 03:35:47,174 PARTICIPATED IN THE STUDY, 5579 03:35:47,174 --> 03:35:49,076 164 AND UNFORTUNATELY THIS 5580 03:35:49,076 --> 03:35:50,611 DOES OCCUR OVER THE PANDEMIC 5581 03:35:50,611 --> 03:35:52,980 WITH ALL THE CHANGES THAT 5582 03:35:52,980 --> 03:35:53,447 PRESENTED. 5583 03:35:53,447 --> 03:35:55,816 THE AVERAGE AGES HERE ON THE 5584 03:35:55,816 --> 03:35:58,920 LEFTHAND SIDE. 5585 03:35:58,920 --> 03:36:00,087 WE ACHIEVED ALMOST 5586 03:36:00,087 --> 03:36:00,855 100 PERCENT MINORITY 5587 03:36:00,855 --> 03:36:01,522 PARTICIPATION IN THE STUDY 5588 03:36:01,522 --> 03:36:07,495 BUT IT IS A LARGELY HISPANIC 5589 03:36:07,495 --> 03:36:08,396 NONWHITE POPULATION THAT 5590 03:36:08,396 --> 03:36:13,935 PARTICIPATED IN THE STUDY, 5591 03:36:13,935 --> 03:36:18,639 17 PERCENT HISPANIC OR 5592 03:36:18,639 --> 03:36:23,311 LATINO AND THE PRIMARY STUDY 5593 03:36:23,311 --> 03:36:28,816 WAS 18 MONTHS IN DURATION. 5594 03:36:28,816 --> 03:36:31,419 AGB101 IS AN EXTENDED 5595 03:36:31,419 --> 03:36:36,958 VERSION OF LOW DOSE 5596 03:36:36,958 --> 03:36:41,595 LEVETIRACETAM SO IN THESE 5597 03:36:41,595 --> 03:36:43,564 TREATMENTS WE SIMPLIFIED 5598 03:36:43,564 --> 03:36:47,735 THAT WITH THE AGB101. 5599 03:36:47,735 --> 03:36:52,640 SO WE USED THE PET IMAGING 5600 03:36:52,640 --> 03:36:53,874 AND LONGITUDINAL STRUCTURE 5601 03:36:53,874 --> 03:36:56,944 MRI AND YOU CAN SEE HERE 5602 03:36:56,944 --> 03:36:58,779 REALLY A MODEST 5603 03:36:58,779 --> 03:36:59,613 NONSIGNIFICANT IMPROVEMENT 5604 03:36:59,613 --> 03:37:02,049 COMPARED TO THE PLACEBO OVER 5605 03:37:02,049 --> 03:37:04,285 THE COURSE OF THE TRIAL 5606 03:37:04,285 --> 03:37:05,886 WHICH WAS SOMEWHAT 5607 03:37:05,886 --> 03:37:06,754 UNEXPECTED AND OBVIOUSLY 5608 03:37:06,754 --> 03:37:09,890 THERE IS A POINT THERE. 5609 03:37:09,890 --> 03:37:12,727 HOWEVER IN A PRESPECIFIED 5610 03:37:12,727 --> 03:37:19,133 SUBGROUP ANALYSIS BASED ON 5611 03:37:19,133 --> 03:37:21,335 OUR OLD FRIEND, WE DID A 5612 03:37:21,335 --> 03:37:22,903 SUBSEQUENT ANALYSIS AND ON 5613 03:37:22,903 --> 03:37:23,838 THE RIGHTHAND BOTTOM SIDE 5614 03:37:23,838 --> 03:37:25,573 YOU SEE THE EFFECT IN THE 5615 03:37:25,573 --> 03:37:27,708 OVERALL SAMPLE WAS LARGELY 5616 03:37:27,708 --> 03:37:31,746 DRIVEN BY THE FOUR CARRIERS 5617 03:37:31,746 --> 03:37:33,114 WHO AS EXPECTED WERE ALL 5618 03:37:33,114 --> 03:37:33,547 SAMPLED. 5619 03:37:33,547 --> 03:37:38,352 THEY SHOWED A RELATIVE -- 5620 03:37:38,352 --> 03:37:39,653 AGAIN, NONCONSISTENT EFFECT 5621 03:37:39,653 --> 03:37:42,923 ON THE TRIAL HOWEVER THE 5622 03:37:42,923 --> 03:37:43,891 APOE4 NONCARRIERS, YOU CAN 5623 03:37:43,891 --> 03:37:46,427 SEE THERE IS A 40 PERCENT 5624 03:37:46,427 --> 03:37:50,664 BENEFIT OVER 18 MONTHS 5625 03:37:50,664 --> 03:37:54,769 TREATMENT WITH THIS LOWER IN 5626 03:37:54,769 --> 03:37:56,971 THE HIPPOCAMPUS WHICH IS A 5627 03:37:56,971 --> 03:37:58,506 VERY MEANINGFUL BUT 5628 03:37:58,506 --> 03:37:59,573 NONSIGNIFICANT ON THE 5629 03:37:59,573 --> 03:38:02,410 PRIMARY OUTCOME OF THIS 5630 03:38:02,410 --> 03:38:03,544 PARTICULAR STUDY. 5631 03:38:03,544 --> 03:38:06,580 WE ALSO AS I MENTIONED 5632 03:38:06,580 --> 03:38:07,481 SELECTED MRI SCANS AT 5633 03:38:07,481 --> 03:38:11,052 BASELINE AND AT THE END OF 5634 03:38:11,052 --> 03:38:11,886 STUDY SHOWING PRELIMINARY 5635 03:38:11,886 --> 03:38:14,488 DATA HERE FROM A STUDY WE 5636 03:38:14,488 --> 03:38:15,456 PREVIOUSLY COMPLETED SHOWING 5637 03:38:15,456 --> 03:38:19,560 THE VOLUME CHANGE OR THE 5638 03:38:19,560 --> 03:38:22,696 SHAPE CHANGE OF THE CORTEX 5639 03:38:22,696 --> 03:38:26,167 OVER A PERIOD OF 24 MONTHS. 5640 03:38:26,167 --> 03:38:27,101 FROM THESE STUDIES, WE KNOW 5641 03:38:27,101 --> 03:38:29,470 THERE IS A SPECIFIC PATTERN 5642 03:38:29,470 --> 03:38:34,442 OF ATROPHY WITH PATIENTS 5643 03:38:34,442 --> 03:38:37,945 WITH MILD IMPAIRMENT IN THE 5644 03:38:37,945 --> 03:38:38,279 CORTEX. 5645 03:38:38,279 --> 03:38:42,516 WITH THE MCI STUDY WE 5646 03:38:42,516 --> 03:38:43,084 OBSERVED THE FOLLOWING 5647 03:38:43,084 --> 03:38:45,052 RESULTS. 5648 03:38:45,052 --> 03:38:54,628 THOSE TREATED WITH THE 101 5649 03:38:54,628 --> 03:38:56,163 SHOWED A STATISTICALLY 5650 03:38:56,163 --> 03:38:57,631 SIGNIFICANT BENEFIT OF 5651 03:38:57,631 --> 03:38:59,700 TREATMENT ON ATROPHY OF THE 5652 03:38:59,700 --> 03:39:00,601 CORTEX. 5653 03:39:00,601 --> 03:39:03,104 SO ON THE FAR LEFT GRAPH 5654 03:39:03,104 --> 03:39:04,805 UNDER A, YOU CAN SEE THE 5655 03:39:04,805 --> 03:39:07,641 VOLUME CHANGE IN THE PLACEBO 5656 03:39:07,641 --> 03:39:09,410 CONDITION FOR NONCARRIERS IS 5657 03:39:09,410 --> 03:39:10,911 APPROXIMATELY 6 PERCENT 5658 03:39:10,911 --> 03:39:12,313 CHANGE VOLUME PER YEAR -- 5659 03:39:12,313 --> 03:39:14,849 SORRY, OVER THE COURSE OF 5660 03:39:14,849 --> 03:39:15,749 THE STUDY WHICH IS 5661 03:39:15,749 --> 03:39:21,455 CONSISTENT WITH THE 5662 03:39:21,455 --> 03:39:21,889 LITERATURE. 5663 03:39:21,889 --> 03:39:23,791 THE 101 TREATMENT REDUCES 5664 03:39:23,791 --> 03:39:25,926 THAT VOLUME CHANGE DOWN TO 5665 03:39:25,926 --> 03:39:26,794 APPROXIMATELY 2 PERCENT OVER 5666 03:39:26,794 --> 03:39:35,469 THE COURSE OF THE STUDY AND 5667 03:39:35,469 --> 03:39:37,571 IN BA35, THIS IS THE TREND 5668 03:39:37,571 --> 03:39:41,175 OF THE CORTEX WITH A SIMILAR 5669 03:39:41,175 --> 03:39:43,577 ATROPHY WITH TREATMENT. 5670 03:39:43,577 --> 03:39:44,845 SO REDUCING THE 5671 03:39:44,845 --> 03:39:46,313 HYPERACTIVITY HERE DOES HAVE 5672 03:39:46,313 --> 03:39:51,585 A BENEFIT ON CLINICAL 5673 03:39:51,585 --> 03:39:52,419 COGNITIVE OUTCOME AND 5674 03:39:52,419 --> 03:39:54,555 IMPORTANT IN THIS CORTEX 5675 03:39:54,555 --> 03:39:57,892 WHICH IS CRITICAL TO THE 5676 03:39:57,892 --> 03:40:00,494 PROGRESSION OF ALZHEIMER'S 5677 03:40:00,494 --> 03:40:01,328 DISEASE/DEMENTIA. 5678 03:40:01,328 --> 03:40:03,297 SO THIS IS THE PRIOR RESULT 5679 03:40:03,297 --> 03:40:07,101 AND WERE VERY RECENTLY 5680 03:40:07,101 --> 03:40:08,836 PUBLISHED IN ALZHEIMER'S AND 5681 03:40:08,836 --> 03:40:09,203 DEMENTIA. 5682 03:40:09,203 --> 03:40:11,805 I WILL BRING YOU BACK NOW TO 5683 03:40:11,805 --> 03:40:14,808 THIS GRAPH I HAVE SHOWN YOU 5684 03:40:14,808 --> 03:40:18,379 BEFORE, NOTING THE 5685 03:40:18,379 --> 03:40:21,081 DIFFERENCE IN SUCCESSFUL 5686 03:40:21,081 --> 03:40:22,283 TRAJECTORIES AND PERFORMANCE 5687 03:40:22,283 --> 03:40:24,485 OF THESE RATS, IN THE THEORY 5688 03:40:24,485 --> 03:40:26,487 RAT CALL GRAPH, THE PROPOSED 5689 03:40:26,487 --> 03:40:27,521 CHANGES HAPPEN OVER TIME AND 5690 03:40:27,521 --> 03:40:28,622 YOU CAN NOTE FROM THE GREEN 5691 03:40:28,622 --> 03:40:30,691 LINE THERE IS A RELATIVELY 5692 03:40:30,691 --> 03:40:32,326 EARLY START OF THAT HYPER 5693 03:40:32,326 --> 03:40:33,694 EXCITABILITY AND OF COURSE 5694 03:40:33,694 --> 03:40:35,763 THE KEY QUESTION IS WHEN 5695 03:40:35,763 --> 03:40:38,199 DOES THIS HYPER EXCITABILITY 5696 03:40:38,199 --> 03:40:38,532 START? 5697 03:40:38,532 --> 03:40:40,067 THERE HAS BEEN EVIDENCE OUT 5698 03:40:40,067 --> 03:40:41,402 THERE SUGGESTING THIS IS NOT 5699 03:40:41,402 --> 03:40:47,575 A CONDITION THAT IS 5700 03:40:47,575 --> 03:40:48,409 SPECIFICALLY MILD IMPAIRMENT 5701 03:40:48,409 --> 03:40:50,578 BUT CAN BE OBSERVED IN ANY 5702 03:40:50,578 --> 03:40:52,146 INDIVIDUALS WHO ARE 5703 03:40:52,146 --> 03:40:53,247 COGNITIVELY NORMAL. 5704 03:40:53,247 --> 03:40:54,915 SO THE QUESTION WOULD ARISE 5705 03:40:54,915 --> 03:40:57,218 CAN WE START WITH THIS 5706 03:40:57,218 --> 03:41:02,256 TREATMENT BEFORE THE ONSET 5707 03:41:02,256 --> 03:41:03,824 AND REDUCE THE 5708 03:41:03,824 --> 03:41:04,258 HYPERACTIVITY? 5709 03:41:04,258 --> 03:41:06,393 SO TO ADDRESS THIS QUESTION, 5710 03:41:06,393 --> 03:41:10,431 WE ENGAGED IN A PILOT STUDY 5711 03:41:10,431 --> 03:41:13,567 WITH UNIVERSITY OF WISCONSIN 5712 03:41:13,567 --> 03:41:15,402 WITH LI THERE, VERY 5713 03:41:15,402 --> 03:41:18,005 INTERESTED IN USING 5714 03:41:18,005 --> 03:41:19,773 COGNITIVE FUNCTIONAL IMAGING 5715 03:41:19,773 --> 03:41:23,043 TO QUANTIFY THE HIPPO CAMP 5716 03:41:23,043 --> 03:41:23,444 PAL NETWORK. 5717 03:41:23,444 --> 03:41:24,011 THROUGH LITERATURE WE 5718 03:41:24,011 --> 03:41:26,280 UNDERSTAND THIS CHANGE IN 5719 03:41:26,280 --> 03:41:29,216 OVER ACTIVITY AND 5720 03:41:29,216 --> 03:41:31,485 EXCITABILITY IN THE 5721 03:41:31,485 --> 03:41:32,886 INHIBITOR VALVES THE 5722 03:41:32,886 --> 03:41:35,823 HIPPOCAMPUS CAN BE OBSERVED 5723 03:41:35,823 --> 03:41:39,326 IN MEASURES THAT SHOW AN 5724 03:41:39,326 --> 03:41:39,994 INCREASED EXCITABILITY WITH 5725 03:41:39,994 --> 03:41:42,363 THE FUNCTION OF THE BRAIN 5726 03:41:42,363 --> 03:41:43,764 ASSOCIATED WITH AGING. 5727 03:41:43,764 --> 03:41:46,667 SO THE INCREASING AGE IS 5728 03:41:46,667 --> 03:41:48,168 ASSOCIATED WITH INCREASED 5729 03:41:48,168 --> 03:41:50,504 FUNCTION CONNECTIVITY OF THE 5730 03:41:50,504 --> 03:41:51,605 HIPPOCAMPUS WITH THE REST OF 5731 03:41:51,605 --> 03:41:52,539 THE BRAIN. 5732 03:41:52,539 --> 03:41:55,743 IN THIS PILOT STUDY, A 5733 03:41:55,743 --> 03:41:57,011 SAMPLE OF 25 COGNITIVELY 5734 03:41:57,011 --> 03:42:00,748 NORMAL OLDER ADULTS WERE 5735 03:42:00,748 --> 03:42:01,749 ENROLLED, FUNCTIONAL 5736 03:42:01,749 --> 03:42:06,887 CONNECTIVE WAS USED TO 5737 03:42:06,887 --> 03:42:13,494 QUANTIFY HIPPOCAMPAL HYPER 5738 03:42:13,494 --> 03:42:14,561 CONNECTIVITY WITH THE REST 5739 03:42:14,561 --> 03:42:16,897 OF THE BRAIN AND AS YOU CAN 5740 03:42:16,897 --> 03:42:21,735 SEE IN THE SAMPLE, AGB101 5741 03:42:21,735 --> 03:42:22,703 LOWERED THE EXCITABILITY IN 5742 03:42:22,703 --> 03:42:23,070 THE BRAIN. 5743 03:42:23,070 --> 03:42:24,104 SO THERE ARE A NUMBER OF 5744 03:42:24,104 --> 03:42:25,572 STEPS WE HAVE TO CONSIDER 5745 03:42:25,572 --> 03:42:27,741 GOING FORWARD IN THIS 5746 03:42:27,741 --> 03:42:28,208 RESEARCH. 5747 03:42:28,208 --> 03:42:29,877 WE'RE CURRENTLY PLANNING A 5748 03:42:29,877 --> 03:42:33,881 PHASE 3 TRIAL OF AGB101 5749 03:42:33,881 --> 03:42:35,716 TESTING THE EFFICACY OF THIS 5750 03:42:35,716 --> 03:42:37,484 TREATMENT IN NONCARRIERS AS 5751 03:42:37,484 --> 03:42:40,421 A SUCCESSFUL TREATMENT FOR 5752 03:42:40,421 --> 03:42:41,989 MCI AND MCS PROGRESSION. 5753 03:42:41,989 --> 03:42:43,991 WE ALSO NEED TO UNDERSTAND 5754 03:42:43,991 --> 03:42:46,593 MORE THAT THE SIGNAL WE'RE 5755 03:42:46,593 --> 03:42:47,695 SEEING IN AGING. 5756 03:42:47,695 --> 03:42:49,496 CAN THIS BE SUCCESSFULLY 5757 03:42:49,496 --> 03:42:50,998 USED IN SLOW PROGRESSION OF 5758 03:42:50,998 --> 03:42:53,934 THOSE ON THE PATH FOR 5759 03:42:53,934 --> 03:42:54,835 ALZHEIMER'S DISEASE BY 5760 03:42:54,835 --> 03:42:57,104 INTERVENING EARLY IN THIS 5761 03:42:57,104 --> 03:42:58,939 TRAJECTORY AND SELECTING 5762 03:42:58,939 --> 03:42:59,840 THESE CASES FOR 5763 03:42:59,840 --> 03:43:01,642 PARTICIPATION AND THUS FOR 5764 03:43:01,642 --> 03:43:02,710 EARLY TREATMENT? 5765 03:43:02,710 --> 03:43:04,178 THE THIRD THING WE NEED TO 5766 03:43:04,178 --> 03:43:06,580 FOCUS ON IS GOING BACK AND 5767 03:43:06,580 --> 03:43:07,948 ESSENTIALLY DOING THE BACK 5768 03:43:07,948 --> 03:43:10,084 TRANSLATION OF THE ANIMAL 5769 03:43:10,084 --> 03:43:15,956 WORK TO UNDERSTAND WHAT THE 5770 03:43:15,956 --> 03:43:17,891 APOE4 IS. 5771 03:43:17,891 --> 03:43:20,761 AND OF COURSE THE ANIMAL 5772 03:43:20,761 --> 03:43:22,529 IMPROVEMENT AND 5773 03:43:22,529 --> 03:43:26,066 UNDERSTANDING BETWEEN THE 5774 03:43:26,066 --> 03:43:27,234 TREATMENT AND APOE4 STATUS 5775 03:43:27,234 --> 03:43:28,502 WHICH CLEARLY IS IMPORTANT 5776 03:43:28,502 --> 03:43:29,837 AS THESE DATA SHOW. 5777 03:43:29,837 --> 03:43:31,038 SO WITH THAT, I WOULD LIKE 5778 03:43:31,038 --> 03:43:33,474 TO THANK THE PEOPLE IN MY 5779 03:43:33,474 --> 03:43:34,875 LAB AND COLLABORATORS MAKING 5780 03:43:34,875 --> 03:43:39,613 THIS WORK POSSIBLE AND I 5781 03:43:39,613 --> 03:43:47,688 WELCOME ANY QUESTIONS. 5782 03:43:47,688 --> 03:43:48,088 [APPLAUSE] 5783 03:43:48,088 --> 03:43:49,456 >> SO OUR SPEAKERS WERE 5784 03:43:49,456 --> 03:44:00,000 ALTER RISK ALL ALTER RISK 5785 03:44:11,178 --> 03:44:11,612 -- AL TERRIFIC. 5786 03:44:11,612 --> 03:44:14,715 SO I WANT TO KIND OF NOTE 5787 03:44:14,715 --> 03:44:17,584 FROM YOU ALL, GO ROUND 5788 03:44:17,584 --> 03:44:20,087 ROBIN, VERY BRIEF, HOW DOES 5789 03:44:20,087 --> 03:44:21,889 TRAJECTORY RELATE IN YOUR 5790 03:44:21,889 --> 03:44:23,791 WORK, HOW DO YOU NOTE OR 5791 03:44:23,791 --> 03:44:24,425 THINK ABOUT IT? 5792 03:44:24,425 --> 03:44:33,066 ANYONE CAN TAKE IT AWAY. 5793 03:44:33,066 --> 03:44:33,767 >> NATHAN? 5794 03:44:33,767 --> 03:44:35,803 >> TO ME TRAJECTORY IS JUST 5795 03:44:35,803 --> 03:44:37,871 THE MAPPING OF HEALTH OR 5796 03:44:37,871 --> 03:44:39,406 MOVEMENT AWAY FROM IT OVER 5797 03:44:39,406 --> 03:44:44,845 TIME AND WHAT WE FOCUS ON 5798 03:44:44,845 --> 03:44:46,847 VERY STRINGENTLY IN THE TWIN 5799 03:44:46,847 --> 03:44:48,115 MODELS ALTHOUGH I DIDN'T 5800 03:44:48,115 --> 03:44:52,019 SHOW IT AND YOU ARE SHOWING 5801 03:44:52,019 --> 03:44:58,525 THE TRAJECTORY TOWARD BRAIN 5802 03:44:58,525 --> 03:45:00,494 HEALTH, ALZHEIMER'S, ALL 5803 03:45:00,494 --> 03:45:01,128 BASED ON STIMULATION. 5804 03:45:01,128 --> 03:45:02,596 >> THIS IS NOT NECESSARILY 5805 03:45:02,596 --> 03:45:04,765 RELEVANT TO THE WORK I 5806 03:45:04,765 --> 03:45:06,600 PRESENTED TODAY BUT I DO A 5807 03:45:06,600 --> 03:45:09,470 LOT OF WORK WITH ADULTS WITH 5808 03:45:09,470 --> 03:45:12,873 ANXIETY AND DEPRESSION WHICH 5809 03:45:12,873 --> 03:45:16,143 IS AN EPISODIC ILLNESS WHERE 5810 03:45:16,143 --> 03:45:18,278 PEOPLE ARE DEPRESSED IN SOME 5811 03:45:18,278 --> 03:45:20,481 TIMES AND NOT OTHERS WHERE 5812 03:45:20,481 --> 03:45:22,182 ANXIETY TENDS TO START EARLY 5813 03:45:22,182 --> 03:45:25,118 IN LIFE AND RISE THROUGH THE 5814 03:45:25,118 --> 03:45:27,221 THRIVE COURSE SO TRAJECTORY 5815 03:45:27,221 --> 03:45:29,223 IS WHEN PEOPLE START OUT 5816 03:45:29,223 --> 03:45:31,425 WITH ANXIETY AND HOW DOES 5817 03:45:31,425 --> 03:45:32,626 THAT AFFECT THEM THROUGHOUT 5818 03:45:32,626 --> 03:45:35,295 LIFE AS OPPOSED TO THOSE WHO 5819 03:45:35,295 --> 03:45:36,430 MIGHT DEVELOP DEPRESSION FOR 5820 03:45:36,430 --> 03:45:39,032 A SHORT TIME AND HAVE A 5821 03:45:39,032 --> 03:45:39,700 POTENTIALLY BETTER OUTCOME. 5822 03:45:39,700 --> 03:45:42,236 >> I THINK IN WHAT OUR DATA 5823 03:45:42,236 --> 03:45:44,004 SHOWS FROM OUR PARTICULAR 5824 03:45:44,004 --> 03:45:46,139 STUDIES FOR CLIP CALL TRIAL, 5825 03:45:46,139 --> 03:45:47,641 WE TAKE ENROLLMENT CRITERIA 5826 03:45:47,641 --> 03:45:48,976 THAT PERSON HAPPENS TO MEET 5827 03:45:48,976 --> 03:45:50,811 AT THAT POINT IN TIME AND 5828 03:45:50,811 --> 03:45:52,980 GET ENROLLED IN A 18-24 5829 03:45:52,980 --> 03:45:55,182 MONTH TRIAL AND YOU CAN 5830 03:45:55,182 --> 03:45:57,551 CLEARLY SEE FROM OUR WORK 5831 03:45:57,551 --> 03:45:59,052 THOSE INDIVIDUALS WERE ON A 5832 03:45:59,052 --> 03:46:01,355 DIFFERENT PATH OR SLOPE THAN 5833 03:46:01,355 --> 03:46:02,356 NONCARRIERS WERE AND I DON'T 5834 03:46:02,356 --> 03:46:03,757 THINK IN CLINICAL TRIALS WE 5835 03:46:03,757 --> 03:46:05,392 KEEP THAT IN MIND ENOUGH. 5836 03:46:05,392 --> 03:46:07,594 WE HAVE THESE ENROLLMENT 5837 03:46:07,594 --> 03:46:08,428 CRITERIA, TRY TO ENROLL AS 5838 03:46:08,428 --> 03:46:09,730 QUICK AS POSSIBLE AND ASSUME 5839 03:46:09,730 --> 03:46:11,665 THAT MEANS WE HAVE A UNIFORM 5840 03:46:11,665 --> 03:46:16,637 SAMPLE BUT CLEARLY WE DON'T. 5841 03:46:16,637 --> 03:46:20,073 >> ONE OF THE THINGS I THINK 5842 03:46:20,073 --> 03:46:23,010 ABOUT TRAJECTORY IS THE 5843 03:46:23,010 --> 03:46:24,578 SEQUENCE OF INTERVENTION 5844 03:46:24,578 --> 03:46:27,047 THROUGH THE GENETIC PHASE, 5845 03:46:27,047 --> 03:46:28,882 HOW THE INTERVENTIONS 5846 03:46:28,882 --> 03:46:30,250 APPLIED AT DIFFERENT TIMES 5847 03:46:30,250 --> 03:46:31,151 DURING THE SEQUENCES CAN 5848 03:46:31,151 --> 03:46:33,487 RESULT IN A DIFFERENT HEALTH 5849 03:46:33,487 --> 03:46:33,954 TRAJECTORY. 5850 03:46:33,954 --> 03:46:35,188 >> WE HAVE LOTS OF FOLKS 5851 03:46:35,188 --> 03:46:39,359 LINED UP AT THE MICROPHONES 5852 03:46:39,359 --> 03:46:44,731 SO WE'LL START OVER THERE. 5853 03:46:44,731 --> 03:46:45,999 >> THANKS, MITCH HARKINS 5854 03:46:45,999 --> 03:46:50,037 FROM THE AMERICAN HEART 5855 03:46:50,037 --> 03:46:51,071 ASSOCIATION, ANOTHER 5856 03:46:51,071 --> 03:46:52,239 TERRIFIC SESSION, LEARNED A 5857 03:46:52,239 --> 03:46:52,506 LOT. 5858 03:46:52,506 --> 03:46:53,640 I HAVE A COUPLE OF QUESTIONS 5859 03:46:53,640 --> 03:46:55,776 BUT WILL LIMIT MYSELF TO 5860 03:46:55,776 --> 03:46:56,109 TWO. 5861 03:46:56,109 --> 03:47:00,781 THE FIRST SUN IS IN THE 5862 03:47:00,781 --> 03:47:02,182 ACHIEVED MINUTES TRIAL, THE 5863 03:47:02,182 --> 03:47:03,216 ONE OVERALL MESSAGE IS 5864 03:47:03,216 --> 03:47:05,118 EFFECTS MAY BE GREATER IN 5865 03:47:05,118 --> 03:47:07,220 THEME ALREADY EXPERIENCING A 5866 03:47:07,220 --> 03:47:08,689 MORE SIGNIFICANT OUTCOME OF 5867 03:47:08,689 --> 03:47:10,190 DECLINE THAN PEOPLE EARLIER 5868 03:47:10,190 --> 03:47:12,125 IN THE DISEASE COURSE. 5869 03:47:12,125 --> 03:47:15,562 AND I AM JUST WONDERING HOW 5870 03:47:15,562 --> 03:47:16,730 WE RECONCILE WITH WHAT WE 5871 03:47:16,730 --> 03:47:19,266 THINK TO BE THE CASE 5872 03:47:19,266 --> 03:47:20,534 GENERALLY, THE FURTHER ALONG 5873 03:47:20,534 --> 03:47:21,802 YOU ARE THE LESS LIKELY WE 5874 03:47:21,802 --> 03:47:24,371 ARE TO HELP PEOPLE AND IF WE 5875 03:47:24,371 --> 03:47:27,941 WANT TO INTERVENE IN 5876 03:47:27,941 --> 03:47:29,476 ALZHEIMER'S DISEASE AND SLOW 5877 03:47:29,476 --> 03:47:31,144 THEIR DECLINE, WE WANT TO 5878 03:47:31,144 --> 03:47:32,779 START EARLIER IN LIFE. 5879 03:47:32,779 --> 03:47:34,815 WE HAVE HEARD ABOUT HOW 5880 03:47:34,815 --> 03:47:42,823 EARLY IN LIFE INTERVENTIONS 5881 03:47:42,823 --> 03:47:43,557 ARE IMPORTANT. 5882 03:47:43,557 --> 03:47:45,692 SO WHAT IS GOING ON? 5883 03:47:45,692 --> 03:47:47,160 >> I WILL TAKE A STAB AT IT 5884 03:47:47,160 --> 03:47:50,831 AND THAT IS A GREAT 5885 03:47:50,831 --> 03:47:52,265 QUESTION. 5886 03:47:52,265 --> 03:47:55,836 AS SCIENTISTS ARE LIMITED TO 5887 03:47:55,836 --> 03:47:57,804 A 5-YEAR GRANT, YOU ARE 5888 03:47:57,804 --> 03:47:58,872 LIMITED TO FOLLOWING THAT 5889 03:47:58,872 --> 03:48:02,976 FOR A LONGER ACTIVITY. 5890 03:48:02,976 --> 03:48:04,544 AND FOR 10, 20 YEARS, THERE 5891 03:48:04,544 --> 03:48:08,515 IS A PRAGMATIC AS WELL AS 5892 03:48:08,515 --> 03:48:10,083 REALISTIC THING. 5893 03:48:10,083 --> 03:48:13,854 IN THE ACHIEVE TRIAL, WE ARE 5894 03:48:13,854 --> 03:48:16,623 ACTUALLY -- IF YOU PREHOP, 5895 03:48:16,623 --> 03:48:19,559 THE DENOVO CORE WOULD DO 5896 03:48:19,559 --> 03:48:21,294 BETTER BECAUSE THEY ARE MORE 5897 03:48:21,294 --> 03:48:24,531 LIKELY TO RESPOND TO 5898 03:48:24,531 --> 03:48:31,605 INTERVENTION, DOING BETTER 5899 03:48:31,605 --> 03:48:35,375 THAN THE AIRC COHORT. 5900 03:48:35,375 --> 03:48:39,112 THESE ARE SUPER MOTIVATING 5901 03:48:39,112 --> 03:48:39,713 ONES. 5902 03:48:39,713 --> 03:48:41,081 THE AIRC, A LITTLE LESS BUT 5903 03:48:41,081 --> 03:48:43,917 I THINK THAT EFFECT WAS 5904 03:48:43,917 --> 03:48:45,786 TRENCHED BECAUSE THE PRIMARY 5905 03:48:45,786 --> 03:48:47,487 OUTCOMES WAS REDUCING 5906 03:48:47,487 --> 03:48:48,155 COGNITIVE DECLINE. 5907 03:48:48,155 --> 03:48:49,723 SO YOU WANT DETECT THAT 5908 03:48:49,723 --> 03:48:52,526 UNLESS YOU HAVE COGNITIVE 5909 03:48:52,526 --> 03:48:53,827 DECLINE, RIGHT? 5910 03:48:53,827 --> 03:48:56,463 SO I THINK WE'RE ENCOURAGED 5911 03:48:56,463 --> 03:48:58,398 TO ACHIEVE TRIALS WITH A 5912 03:48:58,398 --> 03:49:00,033 POPULATION -- I SHOULDN'T 5913 03:49:00,033 --> 03:49:01,802 SAY INCREASED RISK BUT A 5914 03:49:01,802 --> 03:49:04,438 POPULATION WE SAW IN EFFECT 5915 03:49:04,438 --> 03:49:05,572 THERE, LATE LIFE WITHIN 5916 03:49:05,572 --> 03:49:07,207 THREE YEARS AND THE THING I 5917 03:49:07,207 --> 03:49:09,743 DIDN'T GET TO SHOW OF ALL 5918 03:49:09,743 --> 03:49:11,645 THE EXPLORATORY OUTCOMES, 5919 03:49:11,645 --> 03:49:19,219 VERY PROXIMAL IN COGNITION, 5920 03:49:19,219 --> 03:49:20,987 SOCIAL INTERACTION, 5921 03:49:20,987 --> 03:49:23,056 LONELINESS, YOU SAW CLEAR 5922 03:49:23,056 --> 03:49:26,460 SIGNALS CROSS BOTH COHORTS 5923 03:49:26,460 --> 03:49:29,730 BUT ONLY MANIFEST THIS 5924 03:49:29,730 --> 03:49:31,765 REDUCING THOSE ADULTS WITH A 5925 03:49:31,765 --> 03:49:32,365 COGNITIVE DECLINE. 5926 03:49:32,365 --> 03:49:35,135 SO I THINK YOUR POINT THERE 5927 03:49:35,135 --> 03:49:37,204 IS WELL TAKEN AND IT IS A 5928 03:49:37,204 --> 03:49:39,339 TRADEOFF AS FAR AS THE 5929 03:49:39,339 --> 03:49:41,308 TRIALS WHERE YOU GET A 5930 03:49:41,308 --> 03:49:45,178 POPULATION THAT IS REALLY 5931 03:49:45,178 --> 03:49:51,218 HELPFUL AND EXPERIENCE 5932 03:49:51,218 --> 03:49:53,887 INTERVENTION, THEY MAY GET 5933 03:49:53,887 --> 03:49:55,188 LESS OUTCOME. 5934 03:49:55,188 --> 03:50:01,261 SO SOMETIMES TIME IS HARD TO 5935 03:50:01,261 --> 03:50:02,929 MODEL AND PREDICT COMPLETELY 5936 03:50:02,929 --> 03:50:06,566 BUT I WISH I HAD A BETTER 5937 03:50:06,566 --> 03:50:06,967 ANSWER. 5938 03:50:06,967 --> 03:50:08,301 >> TOO SOON OR TOO LATE IN 5939 03:50:08,301 --> 03:50:10,036 THAT WE WERE STARTING WITH 5940 03:50:10,036 --> 03:50:11,538 THESE PEOPLE WHEN THEY WERE 5941 03:50:11,538 --> 03:50:13,006 OLDER BUT HEALTHIER AND 5942 03:50:13,006 --> 03:50:16,576 STARTING AT A HIGHER 5943 03:50:16,576 --> 03:50:16,943 BASELINE. 5944 03:50:16,943 --> 03:50:22,315 WE DON'T HAVE THE DATA TO 5945 03:50:22,315 --> 03:50:24,151 SAY WHICH IS WHICH BUT WE 5946 03:50:24,151 --> 03:50:28,188 ARE CONTINUING TO FOLLOW SO 5947 03:50:28,188 --> 03:50:30,590 WE WILL SEE. 5948 03:50:30,590 --> 03:50:34,194 >> THIS IS FOR Dr. 5949 03:50:34,194 --> 03:50:37,931 REINHART, THIS IS APPLICABLE 5950 03:50:37,931 --> 03:50:40,433 TO YOUR STUDIES BUT THE 5951 03:50:40,433 --> 03:50:42,135 BRAIN STIMULATION PARADIGM 5952 03:50:42,135 --> 03:50:44,104 AND PERHAPS EFFECTIVE ON 5953 03:50:44,104 --> 03:50:45,806 OLDER AGING PEOPLE, MAYBE 5954 03:50:45,806 --> 03:50:50,243 LOOK FOR EFFECTS ON YOUNGER 5955 03:50:50,243 --> 03:50:51,344 HEALTHY PEOPLE TO 5956 03:50:51,344 --> 03:50:52,312 DEMONSTRATE AN IMPROVEMENT 5957 03:50:52,312 --> 03:50:55,749 BEYOND NORMAL SO NOT JUST 5958 03:50:55,749 --> 03:50:56,983 TALKING ABOUT PREVENTING 5959 03:50:56,983 --> 03:50:58,718 DECLINE BUT MAKING PEOPLE 5960 03:50:58,718 --> 03:51:04,691 SMARTER, SO FORTH, KIND OF A 5961 03:51:04,691 --> 03:51:11,598 NEUROGENIC COS MET TO 5962 03:51:11,598 --> 03:51:12,866 M ETOLOGY AS YOU WILL. 5963 03:51:12,866 --> 03:51:15,402 IT STRUCK ME STRONGLY YOU 5964 03:51:15,402 --> 03:51:17,103 CAN GET A LONG-TERM EFFECT 5965 03:51:17,103 --> 03:51:19,573 WITH A SHORT STIMULATION AND 5966 03:51:19,573 --> 03:51:21,708 THE ACCESS MIGHT BE FOR 5967 03:51:21,708 --> 03:51:23,577 PERFECTLY NORMAL PEOPLE 5968 03:51:23,577 --> 03:51:24,477 SEEKING SOME ADVANTAGE, IS 5969 03:51:24,477 --> 03:51:26,079 THAT SOMETHING YOU WOULD 5970 03:51:26,079 --> 03:51:26,446 CONSIDER? 5971 03:51:26,446 --> 03:51:27,581 >> YEAH, I MEAN ONE 5972 03:51:27,581 --> 03:51:29,282 EXPERIMENT I DIDN'T MENTION 5973 03:51:29,282 --> 03:51:32,152 WAS WE INVITED ALL THE 5974 03:51:32,152 --> 03:51:33,486 HEALTHY YOUNG PEOPLE FROM 5975 03:51:33,486 --> 03:51:37,190 EXPERIMENT 2 BACK IN THE LAB 5976 03:51:37,190 --> 03:51:40,560 AND JUST TESTED THE PEOPLE 5977 03:51:40,560 --> 03:51:42,929 FOR COUPLERS WHO HAD BRAIN, 5978 03:51:42,929 --> 03:51:44,598 YOU KNOW, RHYTHMS THAT 5979 03:51:44,598 --> 03:51:47,834 APPROXIMATED THAT OF THE 60, 5980 03:51:47,834 --> 03:51:49,169 70YEAR ~OLD AND SO THERE WAS 5981 03:51:49,169 --> 03:51:50,637 MORE ROOM FOR IMPROVEMENT 5982 03:51:50,637 --> 03:51:54,441 AND WE WERE ABLE TO APPLY 5983 03:51:54,441 --> 03:51:56,042 STIMULATIONS TO SEE MORE 5984 03:51:56,042 --> 03:51:58,178 BENEFIT IN THAT SUBGROUP BUT 5985 03:51:58,178 --> 03:52:02,549 ACTUALLY MOST OF OUR WORK IS 5986 03:52:02,549 --> 03:52:06,586 IN HEALTHY YOUNG DOUBTS AND 5987 03:52:06,586 --> 03:52:11,157 YOUNG ADULTS AND YOU CAN SEE 5988 03:52:11,157 --> 03:52:15,228 IMPROVEMENT THERE BUT THE 5989 03:52:15,228 --> 03:52:16,997 BIGGEST IMPROVEMENT IS IN 5990 03:52:16,997 --> 03:52:19,232 OLDER ADULTS. 5991 03:52:19,232 --> 03:52:22,669 ACCESS AND EQUITY, I DON'T 5992 03:52:22,669 --> 03:52:25,805 THINK OF THAT A LOT BUT 5993 03:52:25,805 --> 03:52:27,641 MAYBE STARTUP INDUSTRY FOLKS 5994 03:52:27,641 --> 03:52:29,242 TO SPIN-OFF TECHNOLOGIES 5995 03:52:29,242 --> 03:52:30,110 AVAILABLE TO THE PUBLIC AND 5996 03:52:30,110 --> 03:52:34,147 THEY ARE ALREADY OUT THERE. 5997 03:52:34,147 --> 03:52:36,583 THESE ARE DEVICES THAT ARE 5998 03:52:36,583 --> 03:52:39,185 EASY TO MAKE YOUR SELF 5999 03:52:39,185 --> 03:52:41,454 POTENTIALLY, SO THERE ARE 6000 03:52:41,454 --> 03:52:45,558 HOME HOBBYISTS WHO ARE 6001 03:52:45,558 --> 03:52:47,193 DESIGNING DIRECT CURRENT 6002 03:52:47,193 --> 03:52:49,429 STIMULATION TO MY KNOWLEDGE, 6003 03:52:49,429 --> 03:52:51,598 TIN FOIL AND BATTERY AND 6004 03:52:51,598 --> 03:52:53,800 WIRE SO I DON'T RECOMMEND 6005 03:52:53,800 --> 03:52:56,169 THAT BUT WERE THINGS TO 6006 03:52:56,169 --> 03:52:57,437 PROGRESS THROUGH FDA 6007 03:52:57,437 --> 03:53:01,207 APPROVAL THROUGH THE STAGES 6008 03:53:01,207 --> 03:53:02,809 OF CLINICAL TRIALS AND 6009 03:53:02,809 --> 03:53:06,179 BECOME AVAILABLE LIKE P.M.S. 6010 03:53:06,179 --> 03:53:08,081 NOW FOR NDD, HOPEFULLY IT 6011 03:53:08,081 --> 03:53:12,619 WOULD BE AVAILABLE FOR 6012 03:53:12,619 --> 03:53:14,821 EVERYONE. 6013 03:53:14,821 --> 03:53:17,324 PERSONALLY MORE LIKE SALK 6014 03:53:17,324 --> 03:53:19,492 AND THE POLIO VACCINE, LET 6015 03:53:19,492 --> 03:53:21,461 'EM HAVE IT FOR FREE BUT IT 6016 03:53:21,461 --> 03:53:31,705 IS KIND OF BEYOND MY 6017 03:53:31,705 --> 03:53:32,472 BACKGROUND. 6018 03:53:32,472 --> 03:53:34,140 >> SO THE VALIDITY AND 6019 03:53:34,140 --> 03:53:35,875 SENSITIVITY OF COGNITIVE 6020 03:53:35,875 --> 03:53:38,244 MEASURES BEING MEASURED IN 6021 03:53:38,244 --> 03:53:40,580 THESE STUDIES, WE'RE USING 6022 03:53:40,580 --> 03:53:42,382 DIFFERENT COGS OF MEASURES, 6023 03:53:42,382 --> 03:53:44,484 SOME HAVE A PRACTICED EFFECT 6024 03:53:44,484 --> 03:53:48,088 MEANING THEY ARE LESS 6025 03:53:48,088 --> 03:53:49,689 PREDICTABLE IN EVERY DAY 6026 03:53:49,689 --> 03:53:51,858 EXPERIENCES AND IN OTHER 6027 03:53:51,858 --> 03:53:53,093 CASES, EVERY DAY EXPERIENCES 6028 03:53:53,093 --> 03:53:55,095 MAY BE CHANGING BUT WE ARE 6029 03:53:55,095 --> 03:53:56,796 NOT MEASURING THEM WELL SO I 6030 03:53:56,796 --> 03:53:58,732 AM CURIOUS YOUR THOUGHTS 6031 03:53:58,732 --> 03:54:03,837 AROUND THIS ISSUE AND WHAT 6032 03:54:03,837 --> 03:54:05,338 MIGHT NEED TO ADDRESS IT. 6033 03:54:05,338 --> 03:54:08,308 >> SO IN THE FIRST STUDY WE 6034 03:54:08,308 --> 03:54:11,277 DID NOT FIND EFFECTS ON 6035 03:54:11,277 --> 03:54:12,545 COGNITIVE CONTROL OR 6036 03:54:12,545 --> 03:54:13,880 FUNCTION AND WE THOUGHT THAT 6037 03:54:13,880 --> 03:54:15,582 WAS BECAUSE IT WAS MORE PEN 6038 03:54:15,582 --> 03:54:18,518 AND PAPER AND COMPUTER BASED 6039 03:54:18,518 --> 03:54:20,153 CONTROLS MIGHT BE MORE 6040 03:54:20,153 --> 03:54:21,554 SENSITIVE BUT I DON'T THINK 6041 03:54:21,554 --> 03:54:24,190 NECESSARILY THINK THAT IS 6042 03:54:24,190 --> 03:54:24,491 TRUE. 6043 03:54:24,491 --> 03:54:26,259 SOME OF WHAT I AM MORE 6044 03:54:26,259 --> 03:54:28,928 INTERESTED IN IN THE FUTURE 6045 03:54:28,928 --> 03:54:32,699 MAY BE A MORE COGNITIVE 6046 03:54:32,699 --> 03:54:33,400 AUDITORY ASSESSMENT, THINGS 6047 03:54:33,400 --> 03:54:36,569 THAT COME UP ON YOUR PHONE 6048 03:54:36,569 --> 03:54:38,738 THAT YOU CAN PARTICIPATE IN 6049 03:54:38,738 --> 03:54:40,206 AND MAKE MEASURES MORE 6050 03:54:40,206 --> 03:54:44,978 SENSITIVE BUT WE DIDN'T DO 6051 03:54:44,978 --> 03:54:45,311 THAT. 6052 03:54:45,311 --> 03:54:46,246 >> OTHER PEOPLE HAVE VIEWS 6053 03:54:46,246 --> 03:54:52,619 ON THE SAME QUESTION? 6054 03:54:52,619 --> 03:54:53,553 OTHER OPINIONS? 6055 03:54:53,553 --> 03:54:55,955 >> I CAN JUST WRAP IT UP 6056 03:54:55,955 --> 03:54:57,857 FROM A CLINICAL TRIAL 6057 03:54:57,857 --> 03:54:58,558 PERSPECTIVE. 6058 03:54:58,558 --> 03:54:59,492 I AGREE MORE WORK NEEDS TO 6059 03:54:59,492 --> 03:55:03,096 BE DONE BUT IT IS VERY 6060 03:55:03,096 --> 03:55:06,566 DIFFICULT TO DO THAT, RIGHT? 6061 03:55:06,566 --> 03:55:08,902 IF YOU DO GET RESULTS IN 6062 03:55:08,902 --> 03:55:11,271 CLINICAL TRIALS FOR OLDER 6063 03:55:11,271 --> 03:55:12,205 ADULTS, THERE ARE OTHER 6064 03:55:12,205 --> 03:55:14,707 RESULTS OUT THERE SO 6065 03:55:14,707 --> 03:55:16,409 CHANGING SOMETHING IS VERY 6066 03:55:16,409 --> 03:55:17,010 DIFFICULT. 6067 03:55:17,010 --> 03:55:18,945 WHERE YOU NEED LONGER 6068 03:55:18,945 --> 03:55:21,081 CLINICAL TRIALS, YOU NEED A 6069 03:55:21,081 --> 03:55:22,015 PROGRESSION RELIABLE OVER 6070 03:55:22,015 --> 03:55:23,683 TIME AND THAT IS VERY 6071 03:55:23,683 --> 03:55:24,417 DIFFICULT TO VALIDATE 6072 03:55:24,417 --> 03:55:27,587 BECAUSE YOU NEED TO DO 6073 03:55:27,587 --> 03:55:28,588 LONG-TERM STUDIES TO 6074 03:55:28,588 --> 03:55:29,923 GENERATE ALL THAT DATA. 6075 03:55:29,923 --> 03:55:32,859 WE NEED MORE WORK IN THESE 6076 03:55:32,859 --> 03:55:34,027 AREAS BUT THEY ARE DIFFICULT 6077 03:55:34,027 --> 03:55:42,735 PROBLEMS TO SOLVE SOMETIMES. 6078 03:55:42,735 --> 03:55:43,436 >> HI, STAN GOLDMAN, 6079 03:55:43,436 --> 03:55:48,108 QUESTION I HAVE FOR JULIE, 6080 03:55:48,108 --> 03:55:50,076 YOUR PRESENTATION REALLY 6081 03:55:50,076 --> 03:55:51,277 IMPRESSIVE AND AMBITIOUS. 6082 03:55:51,277 --> 03:55:55,315 THE THING THAT STOOD OUT FOR 6083 03:55:55,315 --> 03:55:57,984 ME IS THIS STUDY WITH 6084 03:55:57,984 --> 03:55:59,652 HEALTH, EDUCATION, IMPROVING 6085 03:55:59,652 --> 03:56:04,757 SLEEP, DIET AND WEIGHT, THAT 6086 03:56:04,757 --> 03:56:13,800 TO ME USING THE ENGAGEMENT 6087 03:56:13,800 --> 03:56:14,601 OF PHYSIOLOGICAL ASSESSMENT, 6088 03:56:14,601 --> 03:56:17,403 IF YOU HAD TOLD ME YOU WERE 6089 03:56:17,403 --> 03:56:18,671 GOING TO DO THOSE 6090 03:56:18,671 --> 03:56:22,275 INTERVENTIONS, I WOULD NOT 6091 03:56:22,275 --> 03:56:22,809 BE SURPRISED. 6092 03:56:22,809 --> 03:56:27,147 DID YOU MEASURE CHANGES IN 6093 03:56:27,147 --> 03:56:30,550 PHYSIOLOGICAL MEASURES WITH 6094 03:56:30,550 --> 03:56:32,652 THE DD02 IN THE ASSESSMENT 6095 03:56:32,652 --> 03:56:34,287 GROUP AS THE CONTROL GROUP? 6096 03:56:34,287 --> 03:56:35,955 >> WE DID AND DIDN'T FIND 6097 03:56:35,955 --> 03:56:38,057 THEM AND WE WERE PRETTY 6098 03:56:38,057 --> 03:56:39,726 CAREFUL ABOUT DRAWING A 6099 03:56:39,726 --> 03:56:40,393 BALANCE BETWEEN PEOPLE 6100 03:56:40,393 --> 03:56:44,097 SAYING I WANT TO EXERCISE 6101 03:56:44,097 --> 03:56:46,900 MORE AND MAYBE MAY HAVE BEEN 6102 03:56:46,900 --> 03:56:47,901 WALKING MORE VERSUS OUR 6103 03:56:47,901 --> 03:56:51,671 FOLKS IN THE TRIAL WHO IN 6104 03:56:51,671 --> 03:56:52,539 OUR CASE HAD MEMBERSHIP AT 6105 03:56:52,539 --> 03:56:54,440 THE Y IN ST. LOUIS, ACCESS 6106 03:56:54,440 --> 03:56:56,576 TO A GYM THAT WAS RESEARCH 6107 03:56:56,576 --> 03:56:57,210 ORIENTED. 6108 03:56:57,210 --> 03:56:58,978 SO I TRULY DON'T THINK THEY 6109 03:56:58,978 --> 03:57:00,880 WERE GETTING, EVEN THE FOLKS 6110 03:57:00,880 --> 03:57:02,081 WHO WANTED TO EXERCISE MORE, 6111 03:57:02,081 --> 03:57:04,017 I DON'T THINK THEY WERE 6112 03:57:04,017 --> 03:57:06,119 GETTING THE SAME AMOUNT OF 6113 03:57:06,119 --> 03:57:07,353 EXERCISE IN THE HEALTH 6114 03:57:07,353 --> 03:57:08,821 EDUCATION GROUP BUT THE 6115 03:57:08,821 --> 03:57:09,889 CHALLENGE WITH BEHAVIORAL 6116 03:57:09,889 --> 03:57:13,092 TRIALS, YOU NEED TO GET 6117 03:57:13,092 --> 03:57:14,427 INTERVENTIONS THAT ARE 6118 03:57:14,427 --> 03:57:15,361 COMPARABLY CRITICAL AND 6119 03:57:15,361 --> 03:57:17,730 EARLIER IN OUR STUDY WE HAD 6120 03:57:17,730 --> 03:57:20,333 LOOKED TO SEE THE HEALTH 6121 03:57:20,333 --> 03:57:21,668 EDUCATION AND MBR WERE 6122 03:57:21,668 --> 03:57:22,035 CREDIBLE. 6123 03:57:22,035 --> 03:57:23,770 SO IF YOU HAVE SOMEONE 6124 03:57:23,770 --> 03:57:25,138 COMING IN SAYING I HAVE THE 6125 03:57:25,138 --> 03:57:27,006 CONTROL OR THIS WON'T HELP, 6126 03:57:27,006 --> 03:57:28,575 LIKELY IT WON'T. 6127 03:57:28,575 --> 03:57:30,743 SO HOW DO YOU FIND SOMETHING 6128 03:57:30,743 --> 03:57:32,312 EQUALLY BELIEVABLE BUT 6129 03:57:32,312 --> 03:57:34,414 INERT, SO TO SPEAK. 6130 03:57:34,414 --> 03:57:36,015 AND IN RECRUITING, YOU ARE 6131 03:57:36,015 --> 03:57:37,917 ABLE TO OFFER SOMETHING TO 6132 03:57:37,917 --> 03:57:38,284 EVERYONE. 6133 03:57:38,284 --> 03:57:40,520 THESE CLASSES WERE CLEARLY A 6134 03:57:40,520 --> 03:57:44,457 VALUE TO PEOPLE AND PEOPLE 6135 03:57:44,457 --> 03:57:45,358 ENJOYED THEM AND GOT 6136 03:57:45,358 --> 03:57:47,126 SOMETHING OUT OF THEM. 6137 03:57:47,126 --> 03:57:48,795 BUT CROSS BENEFITS, I AGREE 6138 03:57:48,795 --> 03:57:51,497 WITH YOU NOT A LOT OF PEOPLE 6139 03:57:51,497 --> 03:57:53,666 WHO WERE USING EXERCISE WERE 6140 03:57:53,666 --> 03:57:55,268 DOING DIFFERENT KINDS OF 6141 03:57:55,268 --> 03:57:57,370 THINGS, SETTING GOALS AND 6142 03:57:57,370 --> 03:57:59,505 NOT TO THE INTENSITY LEVEL 6143 03:57:59,505 --> 03:58:01,808 WE WERE BRINGING THEM ALONG 6144 03:58:01,808 --> 03:58:03,276 WITH OUR INTERVENTION. 6145 03:58:03,276 --> 03:58:06,913 >> DID YOU SAY YOU DID -- 6146 03:58:06,913 --> 03:58:07,380 [INDISCERNIBLE] 6147 03:58:07,380 --> 03:58:09,048 [ OFF MIC ] 6148 03:58:09,048 --> 03:58:09,916 >> YEAH, WE DID. 6149 03:58:09,916 --> 03:58:10,383 >> DAVID? 6150 03:58:10,383 --> 03:58:11,751 >> I WANT TO MAKE ONE FOLLOW 6151 03:58:11,751 --> 03:58:12,318 UP POINT THERE. 6152 03:58:12,318 --> 03:58:15,154 WHEN WE WERE BUILDING THE 6153 03:58:15,154 --> 03:58:16,889 DIGITAL TWIN MODELS I WAS 6154 03:58:16,889 --> 03:58:17,991 TALKING ABOUT, ONE OF THE 6155 03:58:17,991 --> 03:58:19,859 THINGS YOU GET INTO IS THERE 6156 03:58:19,859 --> 03:58:21,661 IS AN EXPECTATION THAT 6157 03:58:21,661 --> 03:58:22,729 EXERCISE WOULD HAVE A HUGE 6158 03:58:22,729 --> 03:58:23,930 EFFECT BECAUSE OF THE 6159 03:58:23,930 --> 03:58:25,064 IMPORTANCE OF PROFUSION OF 6160 03:58:25,064 --> 03:58:26,566 OXYGEN IN THE BRAIN. 6161 03:58:26,566 --> 03:58:28,101 THE MOST DETAILED STUDY OF 6162 03:58:28,101 --> 03:58:30,770 THIS, ONE OF THE THINGS THAT 6163 03:58:30,770 --> 03:58:31,638 COULD HAPPEN IS EXERCISE 6164 03:58:31,638 --> 03:58:33,906 COULD CHANGE THE SLOPE OF 6165 03:58:33,906 --> 03:58:37,243 THE TRAJECTORY IN AGING FOR 6166 03:58:37,243 --> 03:58:38,278 HOW QUICKLY OXYGENATION GOES 6167 03:58:38,278 --> 03:58:40,113 DOWN IN THE BRAIN BUT THE 6168 03:58:40,113 --> 03:58:42,782 MOST CAREFUL STUDY OF THAT 6169 03:58:42,782 --> 03:58:44,917 ACTUALLY DID NOT CHANGE THE 6170 03:58:44,917 --> 03:58:48,221 SLOPE BUT WAS AN OFFSET THAT 6171 03:58:48,221 --> 03:58:50,156 DELAYED THE ONSET BUT THE 6172 03:58:50,156 --> 03:58:52,091 SHOWN WAS THE SAME AFTER 6173 03:58:52,091 --> 03:58:52,392 THAT. 6174 03:58:52,392 --> 03:58:54,427 SO ONE OF THE BIG SURPRISES 6175 03:58:54,427 --> 03:58:56,796 OF THE MODEL IS WHEN WE 6176 03:58:56,796 --> 03:58:58,097 SIMULATED THE DETAILED DATA 6177 03:58:58,097 --> 03:58:59,932 THAT WAS AVAILABLE, IT 6178 03:58:59,932 --> 03:59:00,867 PREDICTED EXERCISE WOULD 6179 03:59:00,867 --> 03:59:03,269 HAVE A VERY MODEST EFFECT 6180 03:59:03,269 --> 03:59:05,438 AND VERY SURPRISING TO ME 6181 03:59:05,438 --> 03:59:07,140 AND I HATED THAT OUTCOME 6182 03:59:07,140 --> 03:59:08,441 WITH THE TEAM BUT JUST 6183 03:59:08,441 --> 03:59:09,342 SOMETHING THAT MIGHT BE 6184 03:59:09,342 --> 03:59:11,177 INTERESTING TO LOOK AT, THAT 6185 03:59:11,177 --> 03:59:14,147 IS KIND OF WHEN WE LOOKED AT 6186 03:59:14,147 --> 03:59:18,251 THE WHOLE THING, WHAT CAME 6187 03:59:18,251 --> 03:59:18,518 OUT. 6188 03:59:18,518 --> 03:59:19,952 >> THOSE MODELS LOOKING AT 6189 03:59:19,952 --> 03:59:22,622 THE CHANGE IN PLASTICITY AND 6190 03:59:22,622 --> 03:59:24,190 EXERCISE DON'T HAVE ANYTHING 6191 03:59:24,190 --> 03:59:26,826 TO DO WITH OXYGENATION. 6192 03:59:26,826 --> 03:59:32,231 OKLAHOMA GENUINE 6193 03:59:32,231 --> 03:59:36,369 OXYGENATION OF THE BRAIN IS 6194 03:59:36,369 --> 03:59:39,138 REALLY PRETTY CONSTANT AND 6195 03:59:39,138 --> 03:59:40,606 EXERCISE DOESN'T CHANGE MUCH 6196 03:59:40,606 --> 03:59:41,674 OF THAT. 6197 03:59:41,674 --> 03:59:44,177 IT IS JUST THE FOLK IDEA OF 6198 03:59:44,177 --> 03:59:45,311 GETTING MORE OXYGEN TO THE 6199 03:59:45,311 --> 03:59:47,480 BRAIN THAT IS BENEFICIAL. 6200 03:59:47,480 --> 03:59:49,882 >> YES, WE JUST TAKE THE 6201 03:59:49,882 --> 03:59:53,152 EXACT MEASURES THAT ARE 6202 03:59:53,152 --> 03:59:53,953 DONE. 6203 03:59:53,953 --> 03:59:57,657 >> SO MY QUESTION IS FOR 6204 03:59:57,657 --> 03:59:58,191 DOCTOR LIN. 6205 03:59:58,191 --> 04:00:02,128 I AM REALLY GLAD YOU ARE 6206 04:00:02,128 --> 04:00:04,097 HERE BECAUSE THE T TRIALS 6207 04:00:04,097 --> 04:00:05,965 HAVE FUNDAMENTALLY CHANGED 6208 04:00:05,965 --> 04:00:07,233 WHAT I THINK ARE POSSIBLE 6209 04:00:07,233 --> 04:00:08,601 ABOUT TRIALS TO IMPROVE 6210 04:00:08,601 --> 04:00:08,968 COGNITION. 6211 04:00:08,968 --> 04:00:11,738 THE FIRST THING IS REALLY 6212 04:00:11,738 --> 04:00:13,172 JUST A COMMENT. 6213 04:00:13,172 --> 04:00:15,274 YOU DESCRIBED THAT THE 6214 04:00:15,274 --> 04:00:18,077 ERRANT COHORT IS A RANDOM 6215 04:00:18,077 --> 04:00:20,246 POPULATION SAMPLE BUT THEY 6216 04:00:20,246 --> 04:00:22,115 WERE RANDOM IN 1987 WHEN 6217 04:00:22,115 --> 04:00:22,949 THEY WERE RECRUITED. 6218 04:00:22,949 --> 04:00:24,650 WHAT THEY WERE WHEN YOU 6219 04:00:24,650 --> 04:00:25,818 STARTED YOUR TRIAL IS 6220 04:00:25,818 --> 04:00:27,320 SOMETHING THAT, YOU KNOW, IS 6221 04:00:27,320 --> 04:00:29,455 BASED ON A RANDOM SAMPLE 6222 04:00:29,455 --> 04:00:30,723 FROM THOSE CITIES BUT IT IS 6223 04:00:30,723 --> 04:00:31,257 NOT NOW. 6224 04:00:31,257 --> 04:00:33,726 SO THAT IS JUST A COMMENT, I 6225 04:00:33,726 --> 04:00:36,028 THINK, JUST FOR ACCURACY. 6226 04:00:36,028 --> 04:00:37,997 THE OTHER PART IS I WILL BE 6227 04:00:37,997 --> 04:00:39,632 HONEST WITH EVERYBODY, I 6228 04:00:39,632 --> 04:00:40,400 REALLY DON'T UNDERSTAND, 6229 04:00:40,400 --> 04:00:42,835 HAVING A HARD TIME 6230 04:00:42,835 --> 04:00:44,504 UNDERSTANDING THIS ISSUE 6231 04:00:44,504 --> 04:00:47,673 WITH PRACTICE EFFECTS VERSUS 6232 04:00:47,673 --> 04:00:48,741 THE POPULATION DECLINE MORE. 6233 04:00:48,741 --> 04:00:51,144 SO I UNDERSTAND WHAT YOU ARE 6234 04:00:51,144 --> 04:00:54,080 SAYING THAT A COHORT WAS 6235 04:00:54,080 --> 04:00:55,214 TESTED OVER SEVERAL TIMES 6236 04:00:55,214 --> 04:00:57,283 AND AS A RESULT, THE TESTS 6237 04:00:57,283 --> 04:01:01,487 THAT WERE USED IN THE TRIAL 6238 04:01:01,487 --> 04:01:02,288 WERE NOT PARTICULARLY NOVEL 6239 04:01:02,288 --> 04:01:03,790 FOR THEM SO YOU DIDN'T 6240 04:01:03,790 --> 04:01:04,857 NECESSARILY SEE THAT BUMP 6241 04:01:04,857 --> 04:01:05,158 UP. 6242 04:01:05,158 --> 04:01:06,793 BUT I AM WONDERING IF YOU 6243 04:01:06,793 --> 04:01:09,529 CAN SAY MORE ABOUT THE 6244 04:01:09,529 --> 04:01:10,329 TRAJECTORIES WITHIN EACH 6245 04:01:10,329 --> 04:01:12,665 GROUP, IF YOU TOOK A LOOK AT 6246 04:01:12,665 --> 04:01:14,066 THAT, AND HELP US UNDERSTAND 6247 04:01:14,066 --> 04:01:16,269 HOW MUCH OF THIS IS PRACTICE 6248 04:01:16,269 --> 04:01:17,937 EFFECT OR HOW MUCH OF THIS 6249 04:01:17,937 --> 04:01:19,105 IS THE VERY IMPORTANT 6250 04:01:19,105 --> 04:01:20,606 CONCLUSION YOU CAME TO WHICH 6251 04:01:20,606 --> 04:01:22,408 IS THAT PEOPLE WHO ARE 6252 04:01:22,408 --> 04:01:25,111 ESSENTIALLY AT HIGHER RISK 6253 04:01:25,111 --> 04:01:26,345 FOR COGNITIVE DECLINE ARE 6254 04:01:26,345 --> 04:01:28,514 THE ONES WHERE WE SHOULD BE 6255 04:01:28,514 --> 04:01:29,749 FOCUSING OUR TRIALS. 6256 04:01:29,749 --> 04:01:31,417 AND THEN I HAVE ONE MORE 6257 04:01:31,417 --> 04:01:33,419 THING WHICH I HAD TO LOOK AT 6258 04:01:33,419 --> 04:01:34,554 MY PHONE TO REMEMBER BECAUSE 6259 04:01:34,554 --> 04:01:36,422 I AM GETTING SO EXCITED. 6260 04:01:36,422 --> 04:01:39,125 I AM VAN ROLLING HERE 6261 04:01:39,125 --> 04:01:41,194 BECAUSE I HAVE BEEN TALKING 6262 04:01:41,194 --> 04:01:43,162 ABOUT YOUR TRIALS A VERY 6263 04:01:43,162 --> 04:01:43,529 LONG TIME. 6264 04:01:43,529 --> 04:01:45,565 AT THE END AND IN YOUR 6265 04:01:45,565 --> 04:01:47,366 ANSWER TO MITCH, YOU 6266 04:01:47,366 --> 04:01:50,903 MENTIONED THE REAL MOVERS 6267 04:01:50,903 --> 04:01:53,406 WHICH WERE SOCIAL ISOLATION, 6268 04:01:53,406 --> 04:01:54,474 DECLINE AND WELL-BEING 6269 04:01:54,474 --> 04:01:55,975 INCREASE TO PEOPLE 6270 04:01:55,975 --> 04:01:57,343 RANDOMIZED TO THE HEARING 6271 04:01:57,343 --> 04:01:57,610 AID. 6272 04:01:57,610 --> 04:02:00,313 IS IT POSSIBLE EFFECTS OF 6273 04:02:00,313 --> 04:02:03,616 HEAR AIDS WERE INDIRECT 6274 04:02:03,616 --> 04:02:06,552 THROUGH THOSE 6275 04:02:06,552 --> 04:02:07,253 SOCIAL/WELL-BEING MECHANISMS 6276 04:02:07,253 --> 04:02:09,722 AND NOT THROUGH, YOU KNOW, 6277 04:02:09,722 --> 04:02:15,027 HEARING IN AND OF ITSELF? 6278 04:02:15,027 --> 04:02:20,299 >> THANK YOU SO MUCH MUCH 6279 04:02:20,299 --> 04:02:21,133 FOR THOSE PHENOMENAL 6280 04:02:21,133 --> 04:02:26,472 QUESTIONS AND I COMPLETELY 6281 04:02:26,472 --> 04:02:26,772 AGREE. 6282 04:02:26,772 --> 04:02:27,807 THEY REPRESENT ONE POINT IN 6283 04:02:27,807 --> 04:02:31,944 A CERTAIN DAY AND ARE 6284 04:02:31,944 --> 04:02:34,046 SURVIVORS OF THAT. 6285 04:02:34,046 --> 04:02:36,449 BUT THE NEW COHORTS ARE 6286 04:02:36,449 --> 04:02:39,318 SURVIVORS OF THE CURRENT 6287 04:02:39,318 --> 04:02:39,585 DAY. 6288 04:02:39,585 --> 04:02:40,853 SO TRAJECTORY, THE PRACTICE 6289 04:02:40,853 --> 04:02:43,155 TEST, THIS IS REALLY 6290 04:02:43,155 --> 04:02:43,556 INTERESTING. 6291 04:02:43,556 --> 04:02:44,790 THE DATA THAT I SHOWED YOU 6292 04:02:44,790 --> 04:02:47,960 WHICH IS WHAT WE PUT IN THE 6293 04:02:47,960 --> 04:02:50,329 LANCET TRIAL IS ALL 6294 04:02:50,329 --> 04:02:52,064 PREDICATED ON BASELINE AND 6295 04:02:52,064 --> 04:02:54,267 YEAR 3 AND NOT ANY 6296 04:02:54,267 --> 04:02:56,903 INTERVENING DATA WHICH IS 6297 04:02:56,903 --> 04:03:00,439 NOT WHAT WE INTENDED TO DO. 6298 04:03:00,439 --> 04:03:03,876 WE INTENDED TO DO A 6299 04:03:03,876 --> 04:03:05,378 TRAJECTORY USING YEAR 1 AND 6300 04:03:05,378 --> 04:03:07,647 YEAR 2 DATA BUT THE REASON 6301 04:03:07,647 --> 04:03:09,615 WE HAD TO THROW THAT OUT, 6302 04:03:09,615 --> 04:03:11,350 SOME WAS IN PERSON, SOME ON 6303 04:03:11,350 --> 04:03:14,153 THE PHONE AND THAT IS VERY 6304 04:03:14,153 --> 04:03:16,188 DIFFERENT. 6305 04:03:16,188 --> 04:03:17,423 WE TRIED RENORMALIZING IT, 6306 04:03:17,423 --> 04:03:20,359 BUT IN THE END IT WAS 6307 04:03:20,359 --> 04:03:23,663 DECIDED BY THE DMSB TO ONLY 6308 04:03:23,663 --> 04:03:26,299 BASE IT ON YEAR 3 TO GET A 6309 04:03:26,299 --> 04:03:29,035 CLEAN ANALYSIS AND WE KNOW 6310 04:03:29,035 --> 04:03:29,936 WHAT WE GOT. 6311 04:03:29,936 --> 04:03:32,805 BUT WHAT WE PLAN FOR, IN THE 6312 04:03:32,805 --> 04:03:40,746 SUBANALYSIS IF WE HAD NOT 6313 04:03:40,746 --> 04:03:42,148 MISSED THAT TO A PERSON, 6314 04:03:42,148 --> 04:03:43,983 COULD YOU SEE A BUMP-UP ON 6315 04:03:43,983 --> 04:03:46,052 THE EFFECTS OF THAT. 6316 04:03:46,052 --> 04:03:49,388 ON THE LONG LAUNDRY LIST OF 6317 04:03:49,388 --> 04:03:50,556 EFFECTS, YOU LOOK AT THE 6318 04:03:50,556 --> 04:03:54,594 PEOPLE WHO HAD YEAR 1 IN 6319 04:03:54,594 --> 04:03:56,162 PERSON, AND DUE IN FACT TO 6320 04:03:56,162 --> 04:03:59,565 SEE MORE OF A PRACTICE SET 6321 04:03:59,565 --> 04:04:03,402 AMONG THE DENOVOS VERSUS THE 6322 04:04:03,402 --> 04:04:08,507 AIRC AND I WOULD THINK WE 6323 04:04:08,507 --> 04:04:09,609 WOULD SEE LESS. 6324 04:04:09,609 --> 04:04:12,445 SO THAT IS IN THE TEST, WE 6325 04:04:12,445 --> 04:04:15,615 JUST HAVEN'T GOT TEN AROUND 6326 04:04:15,615 --> 04:04:18,484 TO IT SO THAT IS WHY WE 6327 04:04:18,484 --> 04:04:21,821 BASED IT ON YEAR 3 TO GET A 6328 04:04:21,821 --> 04:04:22,755 CLEAR STUDY OF IT. 6329 04:04:22,755 --> 04:04:26,125 BUT I THINK WE CAN GO BACK 6330 04:04:26,125 --> 04:04:28,527 TO STUDY YEAR 1 AND 2 DATA. 6331 04:04:28,527 --> 04:04:34,533 SO THE OTHER PART OF YOUR 6332 04:04:34,533 --> 04:04:40,239 QUESTION, GOING TO COGNITIVE 6333 04:04:40,239 --> 04:04:41,474 ON INSTRUCTION, SOCIAL 6334 04:04:41,474 --> 04:04:42,975 ISOLATION, I DON'T THINK IT 6335 04:04:42,975 --> 04:04:43,643 WOULD BE JUST ONE, I THINK 6336 04:04:43,643 --> 04:04:45,678 IT WOULD BE A COMBINATION OF 6337 04:04:45,678 --> 04:04:46,746 ALL THREE. 6338 04:04:46,746 --> 04:04:52,451 AND LOOKING AT THE MRI DATA 6339 04:04:52,451 --> 04:04:54,086 FUNDED BY AH GRAHAM, WE 6340 04:04:54,086 --> 04:04:56,889 DIDN'T THINK WE WOULD SEE 6341 04:04:56,889 --> 04:05:00,426 ANYTHING BUT WE SAW IT AS A 6342 04:05:00,426 --> 04:05:01,027 SIGNAL. 6343 04:05:01,027 --> 04:05:05,998 MAYBE THERE WAS THINNING OF 6344 04:05:05,998 --> 04:05:11,804 THE CORTICAL NETWORK BUT YOU 6345 04:05:11,804 --> 04:05:13,105 ARE EITHER SEEING 6346 04:05:13,105 --> 04:05:15,041 IMPROVEMENT WITH YOUR 6347 04:05:15,041 --> 04:05:20,312 INTERVENTION OR RELATIVELY 6348 04:05:20,312 --> 04:05:21,213 REDUCED DECLINES. 6349 04:05:21,213 --> 04:05:29,088 SO ANOTHER THING IN THE LIST 6350 04:05:29,088 --> 04:05:29,955 OF ANALYSIS,. 6351 04:05:29,955 --> 04:05:30,423 [INDISCERNIBLE] 6352 04:05:30,423 --> 04:05:32,124 INSTEAD OF LOOKING AT 6353 04:05:32,124 --> 04:05:33,392 MEDIATION MODELING, WE JUST 6354 04:05:33,392 --> 04:05:35,561 HAVEN'T GOT AROUND TO IT BUT 6355 04:05:35,561 --> 04:05:35,895 WE WILL. 6356 04:05:35,895 --> 04:05:39,365 >> ISN'T IT POSSIBLE THAT 6357 04:05:39,365 --> 04:05:42,835 THE BRAIN IMAGING FINDINGS, 6358 04:05:42,835 --> 04:05:43,836 CORTICO FITNESS FINDINGS 6359 04:05:43,836 --> 04:05:45,304 COULD ALSO BE EXPLAINED BY 6360 04:05:45,304 --> 04:05:48,607 THE IMPROVEMENT IN SOCIAL 6361 04:05:48,607 --> 04:05:50,042 INTERACTION AND WELL-BEING? 6362 04:05:50,042 --> 04:05:51,677 >> YEAH -- NO, ABSOLUTELY. 6363 04:05:51,677 --> 04:05:53,212 THE ONLY THING THERE THAT 6364 04:05:53,212 --> 04:05:58,451 WAS INTERESTING AND I WILL 6365 04:05:58,451 --> 04:06:00,286 SAY IT CAN BE A STRONG PART 6366 04:06:00,286 --> 04:06:03,122 OF THE ANALYSIS, ONE OF THE 6367 04:06:03,122 --> 04:06:13,632 STRONGEST SIGNALS IS THE 6368 04:06:16,669 --> 04:06:21,774 CORTICO METALIS WHICH IS THE 6369 04:06:21,774 --> 04:06:22,475 BASE OF LANGUAGE. 6370 04:06:22,475 --> 04:06:25,244 SO IN TERMS OF ACCELERATED 6371 04:06:25,244 --> 04:06:30,950 HEARING LOSS, THAT IS IN THE 6372 04:06:30,950 --> 04:06:32,985 FRONT AL TEMPORAL NODE. 6373 04:06:32,985 --> 04:06:34,954 AND AGAIN, HAND WAVING MIGHT 6374 04:06:34,954 --> 04:06:38,357 MAKE SENSE BUT HEARING 6375 04:06:38,357 --> 04:06:41,727 INTERVENTION IS NOT 6376 04:06:41,727 --> 04:06:42,661 REVERSING HEARING LOSS. 6377 04:06:42,661 --> 04:06:46,265 IN A WAY IT IS AN UNDER 6378 04:06:46,265 --> 04:06:48,934 REGENT, NOT THE AREAS THAT 6379 04:06:48,934 --> 04:06:52,371 CAN BE AFFECTED BY AUDITORY 6380 04:06:52,371 --> 04:06:56,509 DEGENERATION BUT IT IS IN 6381 04:06:56,509 --> 04:06:57,810 EARLY DAYS OF FURTHER AND 6382 04:06:57,810 --> 04:06:59,044 ANALYSIS ALL STILL ON THE 6383 04:06:59,044 --> 04:07:00,279 TABLE AND WE'LL GET AROUND 6384 04:07:00,279 --> 04:07:05,284 TO IT. 6385 04:07:05,284 --> 04:07:07,753 THANK YOU. 6386 04:07:07,753 --> 04:07:12,925 BACK. 6387 04:07:12,925 --> 04:07:14,126 >> CAN YOU HEAR ME? 6388 04:07:14,126 --> 04:07:16,462 I HAVE TWO QUICK QUESTIONS. 6389 04:07:16,462 --> 04:07:18,531 ONE REGARDING THE AG 6390 04:07:18,531 --> 04:07:20,132 BIOMARKERS FOR EXAMPLE YOU 6391 04:07:20,132 --> 04:07:21,600 TALKED ABOUT, THE HIGHER 6392 04:07:21,600 --> 04:07:24,937 LEVEL IN THE CONTEXT OF 6393 04:07:24,937 --> 04:07:25,805 COMORBIDITY, ARE YOU 6394 04:07:25,805 --> 04:07:28,340 SUGGESTING THAT IT IS 6395 04:07:28,340 --> 04:07:30,409 ABILITY TO ACTUAL PRODUCTION 6396 04:07:30,409 --> 04:07:34,079 SEEMS TO BE DIFFERENT BUT 6397 04:07:34,079 --> 04:07:35,514 MAYBE ALSO CONTRIBUTING TO 6398 04:07:35,514 --> 04:07:36,515 THE QUESTION OF CLEARANCE 6399 04:07:36,515 --> 04:07:39,518 AND I AM HAVING A HARD TIME 6400 04:07:39,518 --> 04:07:42,788 HAVING THAT CONCLUSION 6401 04:07:42,788 --> 04:07:44,423 WITHOUT OTHER ANOMALY 6402 04:07:44,423 --> 04:07:45,057 BIOMARKERS AS CONTROL. 6403 04:07:45,057 --> 04:07:47,526 SO THAT IS ONE THING IN 6404 04:07:47,526 --> 04:07:49,562 TERMS OF THINKING. 6405 04:07:49,562 --> 04:07:52,765 AND THEN THE SECOND QUESTION 6406 04:07:52,765 --> 04:07:56,468 IS THE GREAT SHROUD WE'RE 6407 04:07:56,468 --> 04:08:02,241 PRESENTING AND TO COME UP TO 6408 04:08:02,241 --> 04:08:11,851 WHAT YOU WERE SAYING, THE 6409 04:08:11,851 --> 04:08:12,885 POPULATION IN JACKSON,. 6410 04:08:12,885 --> 04:08:13,552 [INDISCERNIBLE] 6411 04:08:13,552 --> 04:08:17,923 IN THE NEW COHORT, DID YOU 6412 04:08:17,923 --> 04:08:19,525 STRATIFY -- I MIGHT HAVE 6413 04:08:19,525 --> 04:08:20,826 MISSED THAT WHEN YOU 6414 04:08:20,826 --> 04:08:26,966 PRESENTED, DID YOU STRATIFY 6415 04:08:26,966 --> 04:08:30,636 IN TERMS OF ENROLLMENT IN 6416 04:08:30,636 --> 04:08:31,103 THE NEW COHORT? 6417 04:08:31,103 --> 04:08:35,908 THAT IS SORT OF MY FIRST 6418 04:08:35,908 --> 04:08:37,009 QUESTION, ALLEVIATING 6419 04:08:37,009 --> 04:08:38,677 POSSIBLY THE IMBALANCE AND 6420 04:08:38,677 --> 04:08:45,317 THEN PERHAPS TRY TO ANALYZE 6421 04:08:45,317 --> 04:08:52,157 BY SITE AND FOLLOWING UP ON 6422 04:08:52,157 --> 04:08:53,259 JENNIFER'S QUESTION, YOU 6423 04:08:53,259 --> 04:08:55,027 WOULD KNOW THE OBJECT OF 6424 04:08:55,027 --> 04:08:57,296 HEARING LOSS BECAUSE YOU 6425 04:08:57,296 --> 04:08:58,998 WOULD HAVE PREVIOUS 6426 04:08:58,998 --> 04:08:59,431 INFORMATION. 6427 04:08:59,431 --> 04:09:00,966 SO HOW DID PEOPLE GET THERE 6428 04:09:00,966 --> 04:09:07,273 AND THEN THE LAST ONE, IN 6429 04:09:07,273 --> 04:09:08,641 ONE SENTENCE, AND SOMETHING 6430 04:09:08,641 --> 04:09:10,843 I AM ABOUT TO SAY, THE 6431 04:09:10,843 --> 04:09:12,511 BEAUTIFUL WORD PRESENTED BY 6432 04:09:12,511 --> 04:09:13,879 THE TRIAL WHICH WAS THERE 6433 04:09:13,879 --> 04:09:14,380 WAS NO RESULT. 6434 04:09:14,380 --> 04:09:16,582 IT IS NOT A NEGATIVE TRIAL, 6435 04:09:16,582 --> 04:09:19,318 YOU KNOW, IT IS THE RESULT. 6436 04:09:19,318 --> 04:09:21,287 YOU KNOW THAT BUT I AM JUST 6437 04:09:21,287 --> 04:09:24,757 SAYING TO ADD VALUE TO 6438 04:09:24,757 --> 04:09:26,091 ACTUALLY IDENTIFY 6439 04:09:26,091 --> 04:09:27,993 SUBPOPULATIONS THAT ARE 6440 04:09:27,993 --> 04:09:38,404 ACTUALLY JUST LIKE 6441 04:09:38,771 --> 04:09:39,338 UNDERESTIMATING YOUR WORTH. 6442 04:09:39,338 --> 04:09:40,272 >> SORRY, I LOST THE 6443 04:09:40,272 --> 04:09:40,839 QUESTION. 6444 04:09:40,839 --> 04:09:42,241 I WILL ANSWER VERY BRIEFLY 6445 04:09:42,241 --> 04:09:45,744 AND MAYBE YOU CAN TALK TO ME 6446 04:09:45,744 --> 04:09:47,112 AFTER. 6447 04:09:47,112 --> 04:09:52,318 THE ERIC COHORT CONCLUDED30 6448 04:09:52,318 --> 04:09:54,853 YEARS AGO, 60,000 PEOPLE, 6449 04:09:54,853 --> 04:09:58,824 AND HUNDRED PERCENT BLACK 6450 04:09:58,824 --> 04:10:00,259 AMERICANS. 6451 04:10:00,259 --> 04:10:02,761 OTHER SITES PRIMARILY WHITE 6452 04:10:02,761 --> 04:10:08,500 DEPENDING ON THE LOCATION. 6453 04:10:08,500 --> 04:10:10,436 SO THE BREAKDOWN OF RACE IN 6454 04:10:10,436 --> 04:10:12,071 THE ERIC IS DIFFERENT 6455 04:10:12,071 --> 04:10:15,908 BECAUSE OF THAT ORIGINAL 6456 04:10:15,908 --> 04:10:17,009 DESIGN. 6457 04:10:17,009 --> 04:10:18,544 THE DENOVOS WERE RECRUITED 6458 04:10:18,544 --> 04:10:21,080 IN THE SAME EXACT FOUR 6459 04:10:21,080 --> 04:10:22,614 COMMUNITIES BUT NOT NEARLY 6460 04:10:22,614 --> 04:10:33,125 SEEING THE SAME DEGREE OF 6461 04:10:34,193 --> 04:10:35,794 RACIAL SPREAD. 6462 04:10:35,794 --> 04:10:38,263 SO THE ANSWER REALLY 6463 04:10:38,263 --> 04:10:39,898 QUICKLY, WE DO SUBANALYSIS 6464 04:10:39,898 --> 04:10:41,500 BY SITE, RACE, EDUCATION, 6465 04:10:41,500 --> 04:10:42,935 THINGS LIKE THAT, WE DIDN'T 6466 04:10:42,935 --> 04:10:44,236 REALLY SEE ANYTHING YET. 6467 04:10:44,236 --> 04:10:47,406 I MEAN THERE WAS NO SMOKING 6468 04:10:47,406 --> 04:10:49,608 GUN PER SE. 6469 04:10:49,608 --> 04:10:56,882 EVERY TIME YOU STRATIFY A 6470 04:10:56,882 --> 04:10:58,550 LITTLE BIT, THERE ARE STRONG 6471 04:10:58,550 --> 04:11:00,252 SIGNALS WHEN YOU GET TO 6472 04:11:00,252 --> 04:11:01,053 ANALYSIS. 6473 04:11:01,053 --> 04:11:04,757 THE ONE WE THOUGHT WE SAW 6474 04:11:04,757 --> 04:11:11,563 WAS PEOPLE WITH A MILD TO 6475 04:11:11,563 --> 04:11:13,365 MODERATE HEARING LOSS, WE 6476 04:11:13,365 --> 04:11:15,801 WEREN'T SEEING ANY TRENDS 6477 04:11:15,801 --> 04:11:16,735 THERE. 6478 04:11:16,735 --> 04:11:18,470 WE HAVEN'T PUBLISHED THAT 6479 04:11:18,470 --> 04:11:20,172 YET BUT THE PRO NERVE 6480 04:11:20,172 --> 04:11:23,208 READOUT YOU ARE NOT SEEING 6481 04:11:23,208 --> 04:11:26,545 ANY BIG DIFFERENCES BY SEX, 6482 04:11:26,545 --> 04:11:28,380 LEVEL HEARING, EDUCATION, 6483 04:11:28,380 --> 04:11:29,314 THINGS LIKE THAT. 6484 04:11:29,314 --> 04:11:32,951 ACTUALLY I DON'T KNOW IF WE 6485 04:11:32,951 --> 04:11:34,453 HAVE IN-STUDY SITES BUT YOUR 6486 04:11:34,453 --> 04:11:36,455 SAMPLE SIZE GETS MORE AND 6487 04:11:36,455 --> 04:11:37,856 MORE RESTRICTED AS YOU DO 6488 04:11:37,856 --> 04:11:40,025 THAT BUT HAPPY TO CHAT 6489 04:11:40,025 --> 04:11:40,759 AFTERWARDS. 6490 04:11:40,759 --> 04:11:41,827 >> I HAVE A QUESTION FOR 6491 04:11:41,827 --> 04:11:43,028 EVERY SINGLE ONE OF YOU BUT 6492 04:11:43,028 --> 04:11:45,931 I WILL ASK THE ONE QUESTION 6493 04:11:45,931 --> 04:11:47,266 THAT ENCOMPASSES MOST OF YOU 6494 04:11:47,266 --> 04:11:49,234 AND I AM ASKING BECAUSE I 6495 04:11:49,234 --> 04:11:50,736 HAVE NEVER DONE HUMAN 6496 04:11:50,736 --> 04:11:51,670 STUDIES BEFORE AND I AM 6497 04:11:51,670 --> 04:11:54,840 ABOUT TO DO A SURVEY OF 6498 04:11:54,840 --> 04:11:57,810 SLEEP IN SOUTH L.A. AND I 6499 04:11:57,810 --> 04:11:59,445 DEFINITELY AM AFRAID I WILL 6500 04:11:59,445 --> 04:12:00,446 BE WASTING MY TIME BECAUSE 6501 04:12:00,446 --> 04:12:02,414 THE ONLY ONES WHO WILL 6502 04:12:02,414 --> 04:12:04,883 VOLUNTEER FOR MY STUDY WILL 6503 04:12:04,883 --> 04:12:06,285 BE THE AFFLUENT ONES WHO 6504 04:12:06,285 --> 04:12:08,287 HAVE THE TIME, YOU KNOW, AND 6505 04:12:08,287 --> 04:12:10,689 I WILL NOT GET A SURVEY OF 6506 04:12:10,689 --> 04:12:11,857 SLEEP IN SOUTH L.A. 6507 04:12:11,857 --> 04:12:15,227 SO HOW CAN YOU DO BETTER AT 6508 04:12:15,227 --> 04:12:17,062 REALLY ACTUALLY SAMPLING THE 6509 04:12:17,062 --> 04:12:19,498 POPULATION SO THAT WE GET 6510 04:12:19,498 --> 04:12:21,934 PEOPLE WHO, YOU KNOW, REALLY 6511 04:12:21,934 --> 04:12:23,969 MIGHT BENEFIT FROM THE 6512 04:12:23,969 --> 04:12:24,803 INTERVENTION, PEOPLE 6513 04:12:24,803 --> 04:12:27,072 MIGHT -- I FEEL LIKE WE'RE 6514 04:12:27,072 --> 04:12:29,241 GOING TO WASTE MILLIONS OF 6515 04:12:29,241 --> 04:12:30,843 DOLLARS AND YEARS OF TIME IF 6516 04:12:30,843 --> 04:12:32,878 WE DON'T GET THE RIGHT 6517 04:12:32,878 --> 04:12:33,312 POPULATION. 6518 04:12:33,312 --> 04:12:34,847 I AM ASKING ALL OF YOU IN 6519 04:12:34,847 --> 04:12:37,749 THE ROOM HOW CAN WE DO 6520 04:12:37,749 --> 04:12:38,250 BETTER? 6521 04:12:38,250 --> 04:12:41,920 WE KNOW A LOT OF THE 6522 04:12:41,920 --> 04:12:43,755 PROBLEMS WITH COMMUNITY 6523 04:12:43,755 --> 04:12:45,891 ENGAGEMENT IN CERTAIN 6524 04:12:45,891 --> 04:12:47,626 POPULATIONS, PEOPLE DON'T 6525 04:12:47,626 --> 04:12:48,961 COME FORWARD BECAUSE THEY 6526 04:12:48,961 --> 04:12:50,929 DON'T TRUST US AND PERHAPS 6527 04:12:50,929 --> 04:12:52,965 SHOULDN'T OR PERHAPS THEY 6528 04:12:52,965 --> 04:12:54,466 SHOULD, THEY DON'T 6529 04:12:54,466 --> 04:12:55,501 COMMUNICATE, WE DON'T TELL 6530 04:12:55,501 --> 04:12:57,102 THEM THE RESULTS OF THE 6531 04:12:57,102 --> 04:12:58,604 STUDY, DON'T GIVE THEM 6532 04:12:58,604 --> 04:13:00,205 ANYTHING BACK EXCEPT MAYBE A 6533 04:13:00,205 --> 04:13:00,873 GIFT CARD AND THEY DON'T 6534 04:13:00,873 --> 04:13:02,774 HAVE THE TIME TO ENGAGE. 6535 04:13:02,774 --> 04:13:09,748 HOW DO WE DO BETTER? 6536 04:13:09,748 --> 04:13:10,115 ANYBODY? 6537 04:13:10,115 --> 04:13:12,618 >> YOU ARE ASKING SOMEONE 6538 04:13:12,618 --> 04:13:15,687 WHO WISHES THEY HAD DONE 6539 04:13:15,687 --> 04:13:16,021 THAT. 6540 04:13:16,021 --> 04:13:18,690 AND WE TRIED TO DO SOME OF 6541 04:13:18,690 --> 04:13:21,393 THIS, RECRUITING THROUGH 6542 04:13:21,393 --> 04:13:22,694 ORGANIZATIONS OF TRUSTED 6543 04:13:22,694 --> 04:13:26,465 GATEKEEPERS FOR EXAMPLE, SO 6544 04:13:26,465 --> 04:13:27,299 RELIGIOUS MINISTERS, PASTORS 6545 04:13:27,299 --> 04:13:28,967 KIND OF AT THE BEGINNING OF 6546 04:13:28,967 --> 04:13:30,035 YOUR PLANNING STAGES AND 6547 04:13:30,035 --> 04:13:31,737 THEN YOU MIGHT HAVE BETTER 6548 04:13:31,737 --> 04:13:34,373 LUCK IN KIND OF BEING, YOU 6549 04:13:34,373 --> 04:13:36,475 KNOW, SEEN AS A SAFE AND 6550 04:13:36,475 --> 04:13:38,277 TRUSTED SOURCE OF 6551 04:13:38,277 --> 04:13:38,677 ASSISTANCE. 6552 04:13:38,677 --> 04:13:39,711 WE PRESENTED AT A LOT OF 6553 04:13:39,711 --> 04:13:42,981 HEALTH FAIRS AND SOME OF 6554 04:13:42,981 --> 04:13:44,850 THOSE WERE TARGETING 6555 04:13:44,850 --> 04:13:45,751 SPECIFIC POPULATIONS. 6556 04:13:45,751 --> 04:13:46,952 I THINK YOU KNOW THIS MEANS 6557 04:13:46,952 --> 04:13:49,521 YOU ARE NOT GOING TO GET A 6558 04:13:49,521 --> 04:13:50,556 RANDOM SAMPLE BUT I THINK 6559 04:13:50,556 --> 04:13:53,525 ASKING PEOPLE TO REFER THEIR 6560 04:13:53,525 --> 04:13:57,462 FRIENDS AND NEIGHBORS, YOU 6561 04:13:57,462 --> 04:13:59,665 KNOW, SORT OF GETTING 6562 04:13:59,665 --> 04:14:00,899 COMPLETELY RANDOM WHICH YOU 6563 04:14:00,899 --> 04:14:02,968 ARE NOT GOING TO GET FOR AN 6564 04:14:02,968 --> 04:14:03,569 INTERVIEW. 6565 04:14:03,569 --> 04:14:04,870 BUT YOU SAID A SURVEY SO YOU 6566 04:14:04,870 --> 04:14:07,172 MIGHT WANT A LITTLE MORE 6567 04:14:07,172 --> 04:14:07,539 RANDOM -- 6568 04:14:07,539 --> 04:14:09,474 >> YEAH, EVEN IF YOU DO 6569 04:14:09,474 --> 04:14:12,277 PHONE CALLS, THE ONLY PEOPLE 6570 04:14:12,277 --> 04:14:13,045 ANSWERING THEIR PHONES ARE 6571 04:14:13,045 --> 04:14:15,681 THE ONES THAT ARE HOME AND 6572 04:14:15,681 --> 04:14:16,148 DON'T HAVE JOBS. 6573 04:14:16,148 --> 04:14:17,583 AND TO BUILD THOSE 6574 04:14:17,583 --> 04:14:19,318 COMMUNITIES TO TRUST 6575 04:14:19,318 --> 04:14:20,219 PARTNERSHIPS TAKES YEARS AND 6576 04:14:20,219 --> 04:14:21,954 I AM SURE THESE CHURCH 6577 04:14:21,954 --> 04:14:23,889 LEADERS ARE GETTING LOTS AND 6578 04:14:23,889 --> 04:14:25,991 LOTS OF REQUESTS NOW SO I 6579 04:14:25,991 --> 04:14:26,458 JUST -- 6580 04:14:26,458 --> 04:14:27,893 >> ACTUALLY IN SOME WAYS, 6581 04:14:27,893 --> 04:14:29,461 YOU ACTUALLY ANSWERED YOUR 6582 04:14:29,461 --> 04:14:30,896 OWN QUESTION SAYING HERE IS 6583 04:14:30,896 --> 04:14:33,298 ALL THE STUFF WE DO, DO THE 6584 04:14:33,298 --> 04:14:38,670 APPS OF -- OPPOSITE OF ALL 6585 04:14:38,670 --> 04:14:40,439 OF THAT BECAUSE CLEARLY IT 6586 04:14:40,439 --> 04:14:41,873 HAS NOT WORKED. 6587 04:14:41,873 --> 04:14:43,075 WE HAD ONE LAST YEAR -- YOU 6588 04:14:43,075 --> 04:14:45,577 WANT TO WEIGH IN ON THIS? 6589 04:14:45,577 --> 04:14:48,447 OKAY, FINE, I AM CHANNELING 6590 04:14:48,447 --> 04:14:49,748 Dr. MANLY HERE BUT I THINK 6591 04:14:49,748 --> 04:14:52,184 IT DOES TAKE A VERY 6592 04:14:52,184 --> 04:14:53,418 CAREFULLY THOUGHT-OUT 6593 04:14:53,418 --> 04:14:54,186 APPROACH AND PARTNERSHIP 6594 04:14:54,186 --> 04:14:55,287 WITH THE COMMUNITY SO 6595 04:14:55,287 --> 04:14:57,022 ORGANIZATION IS PART OF IT 6596 04:14:57,022 --> 04:14:58,991 BUT JUST LISTENING, SPENDING 6597 04:14:58,991 --> 04:15:00,025 TIME, NOT ASKING FOR 6598 04:15:00,025 --> 04:15:01,260 ANYTHING AND TRYING TO 6599 04:15:01,260 --> 04:15:02,094 UNDERSTAND THE CHALLENGES 6600 04:15:02,094 --> 04:15:03,028 AND WHAT THEY ARE GOING 6601 04:15:03,028 --> 04:15:05,264 THROUGH AND THEN TRYING TO 6602 04:15:05,264 --> 04:15:06,565 BUILD THEM AS PARTNERS. 6603 04:15:06,565 --> 04:15:07,699 >> FROM THE LISTENING 6604 04:15:07,699 --> 04:15:09,968 STANDPOINT, I ALSO FEAR THE 6605 04:15:09,968 --> 04:15:14,139 QUESTIONS I WILL ASK WITH MY 6606 04:15:14,139 --> 04:15:17,242 ECOLOGICAL MOMENTARY 6607 04:15:17,242 --> 04:15:19,711 ASSESSMENT AREN'T THE ONES 6608 04:15:19,711 --> 04:15:21,446 THAT ARE RELEVANT. 6609 04:15:21,446 --> 04:15:23,181 I MEAN THEY ARE VERY 6610 04:15:23,181 --> 04:15:25,484 LIMITED, DOING ONE TO 6611 04:15:25,484 --> 04:15:27,286 THREE-MINUTE SAMPLES PER DAY 6612 04:15:27,286 --> 04:15:28,520 BUT MAYBE I NEED TO LISTEN 6613 04:15:28,520 --> 04:15:30,122 TO THE COMMUNITY TO SEE WHAT 6614 04:15:30,122 --> 04:15:31,089 THE RIGHT QUESTIONS ARE 6615 04:15:31,089 --> 04:15:32,591 BEFORE I FILL OUT THIS 6616 04:15:32,591 --> 04:15:35,627 SURVEY OR GIVE THEM A FREE 6617 04:15:35,627 --> 04:15:37,129 FORM AREA SO THEY CAN TELL 6618 04:15:37,129 --> 04:15:42,634 ME WHAT IS THE PROBLEM 6619 04:15:42,634 --> 04:15:49,941 SATURDAY INSTEAD OF 6620 04:15:49,941 --> 04:15:52,778 ASSUMING THE ANSWER. 6621 04:15:52,778 --> 04:15:54,746 >> OKAY, JAN ICE WILL HELP 6622 04:15:54,746 --> 04:15:55,347 ANSWER YOUR QUESTION. 6623 04:15:55,347 --> 04:15:56,381 >> I THINK FIRST OF ALL 6624 04:15:56,381 --> 04:15:57,749 THERE ARE PEOPLE IN THE 6625 04:15:57,749 --> 04:15:59,851 WORLD WHO HAVE EXPERTISE IN 6626 04:15:59,851 --> 04:16:00,952 THIS TYPE OF THING AND I 6627 04:16:00,952 --> 04:16:03,188 WOULD URGE YOU TO PARTNER 6628 04:16:03,188 --> 04:16:04,956 WITH THEM IN A MEANINGFUL 6629 04:16:04,956 --> 04:16:07,526 WAY BECAUSE THEY HAVE HAD 6630 04:16:07,526 --> 04:16:10,095 SUCCESS AND THEY HAVE TRUST 6631 04:16:10,095 --> 04:16:12,264 AND THEY KNOW THE SCIENCE OF 6632 04:16:12,264 --> 04:16:14,099 INCLUSION TO WHAT YOU ARE 6633 04:16:14,099 --> 04:16:15,100 TALKING ABOUT. 6634 04:16:15,100 --> 04:16:18,303 AND WHAT THEY ARE GOING TO 6635 04:16:18,303 --> 04:16:21,173 DO IS COMMUNITY ENGAGED 6636 04:16:21,173 --> 04:16:22,240 METHODS SO THAT THOSE 6637 04:16:22,240 --> 04:16:23,942 QUESTIONS THAT YOU HAVE, YOU 6638 04:16:23,942 --> 04:16:26,144 KNOW, IF I WERE TO ASK YOU 6639 04:16:26,144 --> 04:16:28,113 THESE QUESTIONS ABOUT SLEEP, 6640 04:16:28,113 --> 04:16:29,548 HOW WOULD THAT COME ACROSS 6641 04:16:29,548 --> 04:16:30,282 TO YOU? 6642 04:16:30,282 --> 04:16:33,685 YOU KNOW, THAT SORT OF 6643 04:16:33,685 --> 04:16:34,653 COGNITIVE INTERVIEWING TYPE 6644 04:16:34,653 --> 04:16:36,621 OF THING COULD GIVE ONE 6645 04:16:36,621 --> 04:16:37,389 APPROACH. 6646 04:16:37,389 --> 04:16:38,423 YOU COULD PARTNER WITH A 6647 04:16:38,423 --> 04:16:39,925 COMMUNITY TO COME UP WITH 6648 04:16:39,925 --> 04:16:41,426 THE QUESTIONS, PEOPLE WHO DO 6649 04:16:41,426 --> 04:16:41,860 THAT AS WELL. 6650 04:16:41,860 --> 04:16:43,962 THERE ARE A LOT OF OPTIONS 6651 04:16:43,962 --> 04:16:46,431 BUT THEY ARE GENERALLY, YOU 6652 04:16:46,431 --> 04:16:49,167 KNOW, AND IT TAKES A LOT OF 6653 04:16:49,167 --> 04:16:50,102 RESOURCES, IT DOES TAKE TIME 6654 04:16:50,102 --> 04:16:52,704 BUT IT IS TIME AND RESOURCES 6655 04:16:52,704 --> 04:16:54,573 THAT SHOULD BE BUILT INTO 6656 04:16:54,573 --> 04:16:58,410 ANY STUDIES, THAT IS WHAT WE 6657 04:16:58,410 --> 04:17:00,846 SHOULD BE EXPECTING FROM 6658 04:17:00,846 --> 04:17:02,748 THOSE SEEKING COMMUNITY 6659 04:17:02,748 --> 04:17:04,483 PARTICIPATION AND 6660 04:17:04,483 --> 04:17:04,916 REPRESENTATIVE 6661 04:17:04,916 --> 04:17:05,350 PARTICIPATION. 6662 04:17:05,350 --> 04:17:08,253 SO THAT'S JUST A START. 6663 04:17:08,253 --> 04:17:09,921 >> I WOULD MAYBE ADD ONE 6664 04:17:09,921 --> 04:17:11,189 MORE THING, VERY BRIEFLY AND 6665 04:17:11,189 --> 04:17:13,225 I DON'T WANT TO TAKE UP TOO 6666 04:17:13,225 --> 04:17:14,826 MUCH SPACE HERE BUT ONE OF 6667 04:17:14,826 --> 04:17:16,294 THE PROBLEMS WE DEAL WITH IS 6668 04:17:16,294 --> 04:17:17,796 STRUCTURE IN THE WAY OUR 6669 04:17:17,796 --> 04:17:18,964 GRANTS AND PROJECTS ARE 6670 04:17:18,964 --> 04:17:20,465 DESIGNED, RIGHT? 6671 04:17:20,465 --> 04:17:23,335 SO WE DESIGN OUR RESEARCH 6672 04:17:23,335 --> 04:17:25,203 QUESTIONS AND THINK THOSE 6673 04:17:25,203 --> 04:17:26,405 ARE THE MOST IMPORTANT AND 6674 04:17:26,405 --> 04:17:28,473 THEN SAY WE ARE GOING TO GO 6675 04:17:28,473 --> 04:17:31,343 COLLECT THE DATA BUT WE'RE 6676 04:17:31,343 --> 04:17:32,210 MISSING CODESIGNING THE 6677 04:17:32,210 --> 04:17:33,945 RESEARCH QUESTIONS WITH THE 6678 04:17:33,945 --> 04:17:36,181 COMMUNITY, ASKING THE RIGHT 6679 04:17:36,181 --> 04:17:37,516 QUESTIONS, BEING INFORMED 6680 04:17:37,516 --> 04:17:39,551 WITH THIS THEY HAVE SO SAY 6681 04:17:39,551 --> 04:17:43,155 BUT THAT IS WHAT WE LEARN AS 6682 04:17:43,155 --> 04:17:45,757 WELL AND WE DON'T DO ENOUGH 6683 04:17:45,757 --> 04:17:47,826 OF THAT. 6684 04:17:47,826 --> 04:17:50,028 >> EVEN JUST TO ADMIT IT IN 6685 04:17:50,028 --> 04:17:51,396 THE CV -- 6686 04:17:51,396 --> 04:17:53,698 >> RIGHT, BUT ALSO JOIN THE 6687 04:17:53,698 --> 04:17:58,003 CHAT, GO HAVE A CUP OF 6688 04:17:58,003 --> 04:17:58,703 COFFEE. 6689 04:17:58,703 --> 04:18:01,206 >> SO I WANT TO ASK Dr. 6690 04:18:01,206 --> 04:18:02,841 LIN OR OPEN TO ANYBODY ON 6691 04:18:02,841 --> 04:18:12,617 THE PANEL, GIVEN THE 6692 04:18:12,617 --> 04:18:14,786 90 PERCENT RETENTION ON THE 6693 04:18:14,786 --> 04:18:18,557 LONG-TERM STUDY AND WHY WAS 6694 04:18:18,557 --> 04:18:19,391 IT SO SUCCESSFUL? 6695 04:18:19,391 --> 04:18:22,427 >> THE STAFF OVER 30 YEARS, 6696 04:18:22,427 --> 04:18:24,029 A PHENOMENAL GROUP OF 6697 04:18:24,029 --> 04:18:24,963 PROFESSIONALS AND WHAT I 6698 04:18:24,963 --> 04:18:28,233 MEAN BY THAT IS THEY 6699 04:18:28,233 --> 04:18:28,867 MAINTAINED THAT THROUGHOUT 6700 04:18:28,867 --> 04:18:31,803 30 YEARS WHICH WAS REALLY A 6701 04:18:31,803 --> 04:18:35,006 LOT OF TLC AND HAND HOLDING. 6702 04:18:35,006 --> 04:18:40,479 WE SENT THEM BIRTHDAY CARDS, 6703 04:18:40,479 --> 04:18:43,215 PICKED THEM UP IF WE NEEDED 6704 04:18:43,215 --> 04:18:45,217 TO, SO THAT WAS IMPORTANT. 6705 04:18:45,217 --> 04:18:47,752 THE OTHER THING IS YOU ARE 6706 04:18:47,752 --> 04:18:50,255 ALWAYS GETTING SOMETHING, 6707 04:18:50,255 --> 04:18:52,424 EITHER THE CURE INTERVENTION 6708 04:18:52,424 --> 04:18:55,293 OR REALLY THE REAL PROGRAM, 6709 04:18:55,293 --> 04:18:56,661 ONE-ON-ONE HAND HOLDING WITH 6710 04:18:56,661 --> 04:19:01,299 A NURSE OR HEALTH EDUCATOR. 6711 04:19:01,299 --> 04:19:02,501 USUALLY A NURSE. 6712 04:19:02,501 --> 04:19:04,870 SO EVERYBODY GOT SOMETHING 6713 04:19:04,870 --> 04:19:05,770 SO THERE REALLY WAS 6714 04:19:05,770 --> 04:19:07,572 SOMETHING IN IT FOR THEM AND 6715 04:19:07,572 --> 04:19:08,840 THEN SAID AFTER THREE YEARS, 6716 04:19:08,840 --> 04:19:10,141 YOU GET THE OTHER 6717 04:19:10,141 --> 04:19:10,942 INTERVENTION AS WELL. 6718 04:19:10,942 --> 04:19:13,879 SO I THINK IT IS A 6719 04:19:13,879 --> 04:19:15,814 COMBINATION OF SITE DESIGN, 6720 04:19:15,814 --> 04:19:16,882 COMBINATIONS WERE APPEALING 6721 04:19:16,882 --> 04:19:18,216 TO PEOPLE, RIGHT, AND THEN A 6722 04:19:18,216 --> 04:19:21,953 CREDIT TO THE STUDY STAFF 6723 04:19:21,953 --> 04:19:24,289 THERE FOR MANY YEARS WITH A 6724 04:19:24,289 --> 04:19:29,394 HIGH GROUP OF OF 6725 04:19:29,394 --> 04:19:30,962 PROFESSIONALS TO TREAT THE 6726 04:19:30,962 --> 04:19:33,431 PARTICIPANTS HOW THEY WANT 6727 04:19:33,431 --> 04:19:34,099 TO BE TREATED. 6728 04:19:34,099 --> 04:19:35,901 REALLY A LOT OF LITTLE 6729 04:19:35,901 --> 04:19:39,704 THINGS THAT MATTER THERE. 6730 04:19:39,704 --> 04:19:42,707 >> HI, I AM A SENIOR AT -- 6731 04:19:42,707 --> 04:19:43,775 [INDISCERNIBLE] 6732 04:19:43,775 --> 04:19:47,312 AND MY QUESTION IS ABOUT THE 6733 04:19:47,312 --> 04:19:48,113 MCI TRIAL. 6734 04:19:48,113 --> 04:19:50,849 IT IS VERY INFORMATIVE ABOUT 6735 04:19:50,849 --> 04:19:55,020 THE STRATIFICATION OF APOE4 6736 04:19:55,020 --> 04:19:55,387 CARRIERS. 6737 04:19:55,387 --> 04:19:59,224 I WONDER IF THERE IS ANY 6738 04:19:59,224 --> 04:20:02,460 QUANTIFICATION OF THE 6739 04:20:02,460 --> 04:20:04,930 HIPPOCAMPUS FLUIDITY IN THIS 6740 04:20:04,930 --> 04:20:09,134 SYSTEM, LIKE THE ETIOLOGY OR 6741 04:20:09,134 --> 04:20:11,736 MRI AND WOULD IT BE THE CASE 6742 04:20:11,736 --> 04:20:14,906 THAT IF YOU STRATIFY WITH 6743 04:20:14,906 --> 04:20:17,309 INDIVIDUALS WHO HAVE HYPER 6744 04:20:17,309 --> 04:20:19,177 EXCITEMENT VERSUS THOSE WHO 6745 04:20:19,177 --> 04:20:20,946 DON'T OR PEOPLE AT THE 6746 04:20:20,946 --> 04:20:22,681 HIGHER EXTREME OF IT OR 6747 04:20:22,681 --> 04:20:24,749 AGAIN THE LOWER EXTREME OF 6748 04:20:24,749 --> 04:20:27,085 IT, WOULD THAT BE BEN 6749 04:20:27,085 --> 04:20:37,629 EFFICIENT TO BENEFICIAL FOR 6750 04:20:38,563 --> 04:20:40,599 PEOPLE INVOLVED WITH THAT. 6751 04:20:40,599 --> 04:20:43,468 >> VERY DIFFICULT TO OBTAIN 6752 04:20:43,468 --> 04:20:45,103 A FUNCTIONAL MRI AND 6753 04:20:45,103 --> 04:20:50,642 PARTICULARLY THE TYPE OF MRI 6754 04:20:50,642 --> 04:20:56,681 TO LOCALIZE THE HIPPO 6755 04:20:56,681 --> 04:21:01,152 CAMPAL, VERY DIFFICULT TO DO 6756 04:21:01,152 --> 04:21:01,953 AT SITES. 6757 04:21:01,953 --> 04:21:03,989 ALSO THE CHASE WAS MADE NOT 6758 04:21:03,989 --> 04:21:05,390 TO COLLECT THAT. 6759 04:21:05,390 --> 04:21:07,325 WE DID COLLECT PARTICULAR 6760 04:21:07,325 --> 04:21:10,528 DATA ON THE SET OF 6761 04:21:10,528 --> 04:21:12,764 PARTICIPANTS WHO CAN SO AT 6762 04:21:12,764 --> 04:21:14,933 JOHNS HOPKINS BUT THERE IS 6763 04:21:14,933 --> 04:21:17,135 NOT ENOUGH SUBJECT TO DO 6764 04:21:17,135 --> 04:21:21,373 THERE TO DO THE BREAKDOWN, 6765 04:21:21,373 --> 04:21:23,308 PLANNED VERSUS NOT PLANNED. 6766 04:21:23,308 --> 04:21:25,410 SO GOING BACK TO THE 6767 04:21:25,410 --> 04:21:26,344 HISTORICAL DATA, TRYING TO 6768 04:21:26,344 --> 04:21:27,846 UNDERSTAND WHAT THE SOURCE 6769 04:21:27,846 --> 04:21:29,381 OF THOSE DIFFERENCES MIGHT 6770 04:21:29,381 --> 04:21:30,048 BE. 6771 04:21:30,048 --> 04:21:31,549 SO IN ANSWER TO YOUR 6772 04:21:31,549 --> 04:21:35,053 QUESTION, CAN YOU LOOK AT 6773 04:21:35,053 --> 04:21:37,088 THE EXCITABILITY, THESE ARE 6774 04:21:37,088 --> 04:21:38,023 MEASURES OBTAINED AT THE 6775 04:21:38,023 --> 04:21:39,758 GROUP LEVEL AND VERY SMALL 6776 04:21:39,758 --> 04:21:42,394 SIGNALS YOU GET AT THE GROUP 6777 04:21:42,394 --> 04:21:44,696 LEVEL AND UNFORTUNATELY NOT 6778 04:21:44,696 --> 04:21:46,831 POSSIBLE AS IDENTIFYING THE 6779 04:21:46,831 --> 04:21:48,900 SUBJECT AS HAVING HIPPO 6780 04:21:48,900 --> 04:21:50,869 CAMPAL ACTIVITY OR NOT 6781 04:21:50,869 --> 04:21:51,436 HAVING THAT ACTIVITY. 6782 04:21:51,436 --> 04:21:53,138 BECAUSE THERE IS NO 6783 04:21:53,138 --> 04:21:55,306 THRESHOLD TO COMPARE THAT, 6784 04:21:55,306 --> 04:21:56,808 NO THRESHOLD TO SAY THIS 6785 04:21:56,808 --> 04:21:58,643 PERSON IS POSITIVE OR 6786 04:21:58,643 --> 04:21:59,077 NEGATIVE. 6787 04:21:59,077 --> 04:22:00,545 SO I AM GOING TO SOLVE THAT 6788 04:22:00,545 --> 04:22:02,180 PROBLEM AND THAT IS 6789 04:22:02,180 --> 04:22:04,115 SOMETHING WE WILL FOCUS 6790 04:22:04,115 --> 04:22:04,749 GOING FORWARD. 6791 04:22:04,749 --> 04:22:06,451 >> ONLY GOT A COUPLE OF 6792 04:22:06,451 --> 04:22:09,621 MINUTES LEFT, THIS IS THE 6793 04:22:09,621 --> 04:22:12,257 BONUS ROUND SO WE WILL GO 6794 04:22:12,257 --> 04:22:18,296 WITH QUICK QUESTIONS, QUICK 6795 04:22:18,296 --> 04:22:19,230 ANSWERS. 6796 04:22:19,230 --> 04:22:21,232 >> FOR SOMEONE WHO SAID 6797 04:22:21,232 --> 04:22:23,268 OXYGENATION DOES NOT HAVE 6798 04:22:23,268 --> 04:22:27,806 IMPACT ON, EXERCISE, YOU 6799 04:22:27,806 --> 04:22:29,874 CAN PUT IN ALL THE OXYGEN IN 6800 04:22:29,874 --> 04:22:32,277 THE WORLD AND THE BRAIN 6801 04:22:32,277 --> 04:22:34,112 COULDN'T CARELESS. 6802 04:22:34,112 --> 04:22:38,149 JULIE YOU MAY HAVE FOUND 6803 04:22:38,149 --> 04:22:39,084 75 PERCENT ADHERENCE BUT 6804 04:22:39,084 --> 04:22:41,219 DON'T DO ANYTHING ABOUT THE 6805 04:22:41,219 --> 04:22:43,755 QUALITY OF THE EXERCISE 6806 04:22:43,755 --> 04:22:46,257 BECAUSE IF YOU DON'T QUALIFY 6807 04:22:46,257 --> 04:22:48,393 THE EXERCISE, YOU DON'T GET 6808 04:22:48,393 --> 04:22:49,594 A TREATMENT EFFECT. 6809 04:22:49,594 --> 04:22:51,196 >> THAT'S TRUE EX ISN'T WE 6810 04:22:51,196 --> 04:22:54,966 DID IDENTIFY PEOPLE WHO 6811 04:22:54,966 --> 04:23:00,839 IMPROVED THEIR STRENGTH AND 6812 04:23:00,839 --> 04:23:02,707 WHAT THEY WERE DOING. 6813 04:23:02,707 --> 04:23:05,276 >> SOME OF THE STUDIES WE 6814 04:23:05,276 --> 04:23:08,713 HAVE DONE, WE FOUND INCREASE 6815 04:23:08,713 --> 04:23:12,784 IN BO2 MAX BUT NOTHING ELSE. 6816 04:23:12,784 --> 04:23:14,285 >> WITH RESPECT TO FITNESS, 6817 04:23:14,285 --> 04:23:16,087 CURIOUS IN THE CONTROL 6818 04:23:16,087 --> 04:23:20,492 GROUP, WAS IT ASSESSED THEIR 6819 04:23:20,492 --> 04:23:21,693 MINDFULNESS BEFORE, A AND 6820 04:23:21,693 --> 04:23:23,762 ALSO HOW DID THEY LIVE THEIR 6821 04:23:23,762 --> 04:23:26,931 LIFE, THEIR LIFE STYLE, WHAT 6822 04:23:26,931 --> 04:23:27,966 KIND OF STRESSORS DID THEY 6823 04:23:27,966 --> 04:23:29,467 HAVE IN THEIR LIFE? 6824 04:23:29,467 --> 04:23:31,503 I WOULD BE CURIOUS TO KNOW 6825 04:23:31,503 --> 04:23:37,909 COMPARED TO THE OTHER 6826 04:23:37,909 --> 04:23:41,412 STRESSORS WITH THE GROUP IN 6827 04:23:41,412 --> 04:23:43,948 THEIR LIFE. 6828 04:23:43,948 --> 04:23:45,483 >> SO LOOKING AT THIS ACROSS 6829 04:23:45,483 --> 04:23:47,786 ALL PARTICIPANTS, IN TERMS 6830 04:23:47,786 --> 04:23:49,587 OF STRESSORS, WE DID NOT 6831 04:23:49,587 --> 04:23:51,389 ASSESS FOR LIFE STRESSORS 6832 04:23:51,389 --> 04:23:53,925 WHICH I THINK IS A GAP IN 6833 04:23:53,925 --> 04:23:56,394 THE DATA WE COLLECTED AND IN 6834 04:23:56,394 --> 04:23:58,229 TERMS OF THEIR OVERALL 6835 04:23:58,229 --> 04:23:59,063 LIFESTYLE, THERE WAS A 6836 04:23:59,063 --> 04:24:00,999 SUGGESTION TO LOOK AT DIET 6837 04:24:00,999 --> 04:24:02,867 AND SOME OTHER FACTORS BUT 6838 04:24:02,867 --> 04:24:04,302 AGAIN, WE WERE ALREADY KIND 6839 04:24:04,302 --> 04:24:06,805 OF COLLECTING A LOT OF DATA 6840 04:24:06,805 --> 04:24:08,540 FROM FOLKS SO THAT WAS ONE 6841 04:24:08,540 --> 04:24:10,441 OF THE THINGS WE DID NOT DO. 6842 04:24:10,441 --> 04:24:12,310 IN THE EXTENSION WHICH HAS 6843 04:24:12,310 --> 04:24:12,944 GONE THROUGH THE PANDEMIC, 6844 04:24:12,944 --> 04:24:16,514 WE HAVE BEEN ASKING ABOUT 6845 04:24:16,514 --> 04:24:18,349 STRESSORS SO LOOKING AT 6846 04:24:18,349 --> 04:24:19,818 SOCIAL ISOLATION AND 6847 04:24:19,818 --> 04:24:22,187 LONELINESS AND SOME OF THAT 6848 04:24:22,187 --> 04:24:26,157 AS WELL SO THE IMPACT ON 6849 04:24:26,157 --> 04:24:27,025 STRESS AND COGNITIVE 6850 04:24:27,025 --> 04:24:30,028 FUNCTION BUT IN THE FIRST 6851 04:24:30,028 --> 04:24:32,030 PHASE, UNFORTUNATELY NO. 6852 04:24:32,030 --> 04:24:35,099 >> AND MINDFULNESS BEFORE 6853 04:24:35,099 --> 04:24:36,134 AND AFTER? 6854 04:24:36,134 --> 04:24:36,668 >> CAMS, YEAH. 6855 04:24:36,668 --> 04:24:38,269 >> I AM GETTING THE SIGNAL 6856 04:24:38,269 --> 04:24:40,371 WE HAVE TO SHUT IT OFF HERE 6857 04:24:40,371 --> 04:24:42,173 BUT THIS WAS A GREAT 6858 04:24:42,173 --> 04:24:43,241 DISCUSSION, LET'S THANK OUR 6859 04:24:43,241 --> 04:24:45,677 SPEAKERS ONE MORE TIME. 6860 04:24:45,677 --> 04:24:46,044 [APPLAUSE] 6861 04:24:46,044 --> 04:24:56,554 >> AND MOLLY, YOU ARE UP. 6862 04:25:28,820 --> 04:25:30,321 >> SO WE'RE AT THE END OF 6863 04:25:30,321 --> 04:25:33,625 THE MEETING AND, YOU KNOW, I 6864 04:25:33,625 --> 04:25:36,160 ALWAYS LIKE TO SEE A GAUGE 6865 04:25:36,160 --> 04:25:41,132 AT A LEVEL OF SUCCESS IN 6866 04:25:41,132 --> 04:25:42,367 TERMS OF HOW MANY IDEAS WE 6867 04:25:42,367 --> 04:25:43,668 HAVE SEEN THAT ARE GOING TO 6868 04:25:43,668 --> 04:25:46,337 BE TURNED IN OR HAVE BEEN 6869 04:25:46,337 --> 04:25:47,605 TURNED INTO ACTION OR 6870 04:25:47,605 --> 04:25:48,072 RESEARCH. 6871 04:25:48,072 --> 04:25:50,575 AND THEY BE TAKING THOSE 6872 04:25:50,575 --> 04:25:51,409 ACTIONS INTO IMPLEMENTATION. 6873 04:25:51,409 --> 04:25:52,744 SO OVER THE PAST COUPLE OF 6874 04:25:52,744 --> 04:25:55,914 DAYS, I HAVE HEARD A LOT OF 6875 04:25:55,914 --> 04:25:57,582 ENCOURAGING TALKS THAT WE 6876 04:25:57,582 --> 04:25:58,616 ARE MOVING IN THE RIGHT 6877 04:25:58,616 --> 04:26:00,752 DIRECTION AND THE KIND OF 6878 04:26:00,752 --> 04:26:03,087 DIRECTIONS WE WANT TO MOVE 6879 04:26:03,087 --> 04:26:07,358 IN TO BEGIN TO REALLY SORT 6880 04:26:07,358 --> 04:26:08,860 OF PIERCE THE ENVELOPE AND 6881 04:26:08,860 --> 04:26:12,330 MOVE FORWARD IN A VERY 6882 04:26:12,330 --> 04:26:13,631 POSITIVE AND DIFFERENT WAY. 6883 04:26:13,631 --> 04:26:15,900 IN A DIFFERENT WAY. 6884 04:26:15,900 --> 04:26:17,168 AND INSTEAD OF DOING WHAT WE 6885 04:26:17,168 --> 04:26:20,605 HAVE BEEN DOING BUT TO 6886 04:26:20,605 --> 04:26:25,109 IMPROVE AND TRY ON NEW 6887 04:26:25,109 --> 04:26:28,012 OPPORTUNITIES, NEW 6888 04:26:28,012 --> 04:26:29,414 APPROACHES, NEW TECHNOLOGY 6889 04:26:29,414 --> 04:26:30,415 TO RELAY FURTHER OUR 6890 04:26:30,415 --> 04:26:30,848 KNOWLEDGE. 6891 04:26:30,848 --> 04:26:33,818 SO I WOULD LIKE TO RECOGNIZE 6892 04:26:33,818 --> 04:26:35,820 AGAIN THE SPEAKERS, THEIR 6893 04:26:35,820 --> 04:26:36,587 EFFORTS AND CONTRIBUTIONS 6894 04:26:36,587 --> 04:26:40,024 HAVE BEEN EVEN MORE 6895 04:26:40,024 --> 04:26:42,393 EXTENSIVE THAN THE SHARING 6896 04:26:42,393 --> 04:26:43,428 THE RESEARCH FUNDS OVER THE 6897 04:26:43,428 --> 04:26:44,562 LAST COUPLE OF DAYS. 6898 04:26:44,562 --> 04:26:47,632 THEY HAVE BEEN WORKING WITH 6899 04:26:47,632 --> 04:26:51,035 NIH STAFF FOR WEEKS, MONTHS 6900 04:26:51,035 --> 04:26:51,869 REGARDING DISCUSSION, 6901 04:26:51,869 --> 04:26:53,037 DEVELOPMENT OF CONTENT AND 6902 04:26:53,037 --> 04:26:54,806 CONSIDERATION OF GAPS AND 6903 04:26:54,806 --> 04:26:56,140 OPPORTUNITIES IN THE 6904 04:26:56,140 --> 04:26:57,208 SCIENTIFIC SPACE, EFFORTS 6905 04:26:57,208 --> 04:26:58,810 FOR WHICH THEY HAVE 6906 04:26:58,810 --> 04:27:00,912 GENEROUSLY GIVEN THEIR TIME 6907 04:27:00,912 --> 04:27:03,915 AND INSIGHTS SO ONE MORE 6908 04:27:03,915 --> 04:27:11,856 ROUND OF APPLAUSE FOR OUR 6909 04:27:11,856 --> 04:27:12,590 SPEAKERS. 6910 04:27:12,590 --> 04:27:13,157 [APPLAUSE] 6911 04:27:13,157 --> 04:27:14,692 THOSE WE DON'T SEE BUT WHO 6912 04:27:14,692 --> 04:27:19,197 ALLOW US TO SEE AND HEAR 6913 04:27:19,197 --> 04:27:21,766 EVERYTHING, MY DEEP THANKS 6914 04:27:21,766 --> 04:27:26,771 GOES TO NIH MANAGEMENT THAT 6915 04:27:26,771 --> 04:27:28,239 THEY HAVE TAKEN, DAISY CHAIN 6916 04:27:28,239 --> 04:27:32,944 OVER ON THE SIDE OF THE 6917 04:27:32,944 --> 04:27:37,515 RAIN, THE BETHESDA MARRIOTT 6918 04:27:37,515 --> 04:27:41,953 HOTEL, DAVID LOPEZ, NIA 6919 04:27:41,953 --> 04:27:44,322 PERSON WHO HAS BEEN WORKING 6920 04:27:44,322 --> 04:27:46,924 OVER THE LAST SEVERAL WEEKS 6921 04:27:46,924 --> 04:27:49,894 AND RALPH, AN INSTANT WAVE 6922 04:27:49,894 --> 04:27:52,096 OF CALM AND CONFIDENCE THAT 6923 04:27:52,096 --> 04:27:53,631 SWEEPS OVER ME SO THANK YOU 6924 04:27:53,631 --> 04:27:55,633 VERY MUCH TO THOSE WHO 6925 04:27:55,633 --> 04:28:01,773 HELPED US SEE AND HEAR THE 6926 04:28:01,773 --> 04:28:03,341 CONFERENCE. 6927 04:28:03,341 --> 04:28:03,708 [APPLAUSE] 6928 04:28:03,708 --> 04:28:05,376 >> FOR NIH, WE HAVE WORKED 6929 04:28:05,376 --> 04:28:07,311 CLOSELY A NUMBER OF WEEKS 6930 04:28:07,311 --> 04:28:11,449 AND MONTHS WITH MATT SLADER, 6931 04:28:11,449 --> 04:28:13,284 WHO IS CORPORATE FOUNDATION 6932 04:28:13,284 --> 04:28:14,419 RELATIONS AND APPRECIATE HIS 6933 04:28:14,419 --> 04:28:15,586 GUIDANCE AND DIRECTION 6934 04:28:15,586 --> 04:28:16,554 THROUGHOUT THE SUMMIT. 6935 04:28:16,554 --> 04:28:19,524 AND THEN OF COURSE THERE IS 6936 04:28:19,524 --> 04:28:22,293 THE EVENT STAFF WHO HAVE 6937 04:28:22,293 --> 04:28:23,494 COORDINATED ALL THE 6938 04:28:23,494 --> 04:28:25,563 LOGISTICS TO BRING US HERE 6939 04:28:25,563 --> 04:28:29,167 THE LAST FEW DAYS, INCLUDING 6940 04:28:29,167 --> 04:28:32,737 MIRA PATEL, MEETING AND 6941 04:28:32,737 --> 04:28:34,305 EVENTS. 6942 04:28:34,305 --> 04:28:36,007 MATHIA HICKS, JASMINE 6943 04:28:36,007 --> 04:28:37,141 BUCHANAN AND THE PRIMARY 6944 04:28:37,141 --> 04:28:38,776 MOVER, I ASKED THE STAFF FOR 6945 04:28:38,776 --> 04:28:41,112 HER TO COME IN THE ROOM BUT 6946 04:28:41,112 --> 04:28:42,814 DON'T KNOW IF SHE IS, THERE 6947 04:28:42,814 --> 04:28:45,683 SHE IS, FOR ALL SUMMIT 6948 04:28:45,683 --> 04:28:56,194 RELATED LOGISTICS, ASHLEY 6949 04:28:56,794 --> 04:28:57,995 SOMERVAL, A MEETING OF THIS 6950 04:28:57,995 --> 04:29:01,232 SCALE TAKES A LOT OF THINGS 6951 04:29:01,232 --> 04:29:03,801 TO HAPPEN AND SO WANT TO 6952 04:29:03,801 --> 04:29:04,735 EXPRESS OUR THANKS. 6953 04:29:04,735 --> 04:29:05,670 NOT PRESENT, YOU HAVEN'T 6954 04:29:05,670 --> 04:29:07,738 SEEN THEM BUT THEY DID A LOT 6955 04:29:07,738 --> 04:29:09,140 FOR WORKING UP TO THIS DAY. 6956 04:29:09,140 --> 04:29:11,175 I STILL WANT TO RECOGNIZE 6957 04:29:11,175 --> 04:29:13,311 FROM NIA FROM OUR OFFICE OF 6958 04:29:13,311 --> 04:29:17,048 COMMUNICATIONS AND PUBLIC 6959 04:29:17,048 --> 04:29:20,251 LIAISON, JORDAN BRODERICK 6960 04:29:20,251 --> 04:29:23,187 AND KELLY OHAVER WHO HELPED 6961 04:29:23,187 --> 04:29:24,055 ADVERTISE THIS MEETING 6962 04:29:24,055 --> 04:29:26,524 THROUGH THE WEBSITE AND 6963 04:29:26,524 --> 04:29:27,425 OUTER COMMUNICATIONS DISSEM 6964 04:29:27,425 --> 04:29:28,793 NATIONS EFFORTS. 6965 04:29:28,793 --> 04:29:29,894 AND THEN SPECIAL THANKS TO 6966 04:29:29,894 --> 04:29:32,830 THE MEMBERS OF THE SUMMIT 6967 04:29:32,830 --> 04:29:34,098 ORGANIZING COMMITTEE WHO 6968 04:29:34,098 --> 04:29:35,366 ALSO SERVED AS SESSION 6969 04:29:35,366 --> 04:29:38,202 CHAIRS IF YOU DON'T NOTICE 6970 04:29:38,202 --> 04:29:38,503 THAT. 6971 04:29:38,503 --> 04:29:41,539 THEIR CONTRIBUTIONS HAVE 6972 04:29:41,539 --> 04:29:44,208 BEEN ENORMOUS AND THEY 6973 04:29:44,208 --> 04:29:48,212 EXTENDED THEIR TIME AND 6974 04:29:48,212 --> 04:29:49,714 EXPERTISE OVER THE LAST 6975 04:29:49,714 --> 04:29:53,317 SEVERAL MONTHS AND THEN 6976 04:29:53,317 --> 04:29:57,655 LATER TODAY, THE EXECUTIVE 6977 04:29:57,655 --> 04:29:58,422 SESSION. 6978 04:29:58,422 --> 04:30:05,229 SO THANK YOU. 6979 04:30:05,229 --> 04:30:05,696 [APPLAUSE] 6980 04:30:05,696 --> 04:30:08,933 AND THEN THERE IS THE NIA 6981 04:30:08,933 --> 04:30:10,635 FOLKS, LAURA, SO I WANT TO 6982 04:30:10,635 --> 04:30:13,271 THANK Dr. JOHN KING AND 6983 04:30:13,271 --> 04:30:14,405 Dr. HERALD FROM THE 6984 04:30:14,405 --> 04:30:17,208 DIVISION OF BEHAVIORAL AND 6985 04:30:17,208 --> 04:30:19,777 SOCIAL RESEARCH, Dr. 6986 04:30:19,777 --> 04:30:21,379 FRANKOWSKI FROM THE DIVISION 6987 04:30:21,379 --> 04:30:22,280 OF NEURAL SCIENCE. 6988 04:30:22,280 --> 04:30:24,549 THEY ROSE TO THE OCCASION 6989 04:30:24,549 --> 04:30:26,317 MORE TIMES THAN YOU WOULD 6990 04:30:26,317 --> 04:30:30,721 CARE TO COUNT TO MAKE THIS 6991 04:30:30,721 --> 04:30:31,522 COHESIVE, EXCITING, BLEEDING 6992 04:30:31,522 --> 04:30:33,591 EDGE SO I WILL ASK THEM TO 6993 04:30:33,591 --> 04:30:36,928 RISE ONE MORE TIME SO WE CAN 6994 04:30:36,928 --> 04:30:38,062 RECOGNIZE THEIR CENTRAL 6995 04:30:38,062 --> 04:30:39,997 ROLE. 6996 04:30:39,997 --> 04:30:43,801 JOHN AND AARON AND DAVE, IF 6997 04:30:43,801 --> 04:30:46,070 YOU COULD STAND? 6998 04:30:46,070 --> 04:30:46,437 [APPLAUSE] 6999 04:30:46,437 --> 04:30:49,207 AND I AM GOING TO TAKE A 7000 04:30:49,207 --> 04:30:52,376 MOMENT TO INDIVIDUALLY 7001 04:30:52,376 --> 04:30:53,678 RECOGNIZE DAVE FRANKOWSKI 7002 04:30:53,678 --> 04:30:55,680 WHO CHEERFULLY AND 7003 04:30:55,680 --> 04:30:56,280 CONSISTENTLY OFFERED HIS 7004 04:30:56,280 --> 04:30:58,916 SKILLS AND TIME TO EVERY 7005 04:30:58,916 --> 04:31:00,818 ASPECT OF THE THE PLANNING 7006 04:31:00,818 --> 04:31:04,522 AND EXECUTION. 7007 04:31:04,522 --> 04:31:05,389 THANKS, DAVE. 7008 04:31:05,389 --> 04:31:06,524 [APPLAUSE] 7009 04:31:06,524 --> 04:31:07,758 BUT MOST IMPORTANTLY, OUR 7010 04:31:07,758 --> 04:31:09,794 THANKS GOES TO THE 7011 04:31:09,794 --> 04:31:11,095 McKNIGHT BRAIN RESEARCH 7012 04:31:11,095 --> 04:31:13,965 FOUNDATION BOARD OF TRUSTEES 7013 04:31:13,965 --> 04:31:14,999 FOR HAVING THE 7014 04:31:14,999 --> 04:31:18,236 DETERMINATION, COMMITMENT 7015 04:31:18,236 --> 04:31:19,604 AND VISION TO PRIORITIZE 7016 04:31:19,604 --> 04:31:20,004 THIS. 7017 04:31:20,004 --> 04:31:21,439 THIS MARKS THE FOURTH TIME 7018 04:31:21,439 --> 04:31:23,774 THE FOUNDATION HAS MADE IT 7019 04:31:23,774 --> 04:31:25,376 POSSIBLE TO CONVENE THIS 7020 04:31:25,376 --> 04:31:27,645 IMPORTANT MEETING. 7021 04:31:27,645 --> 04:31:28,579 ANGELICA, EXECUTIVE DIRECTOR 7022 04:31:28,579 --> 04:31:30,114 FOR THE FOUNDATION WORKED 7023 04:31:30,114 --> 04:31:31,882 CLOSELY WITH THE SUMMIT 7024 04:31:31,882 --> 04:31:33,651 PLANNING COMMITTEE OVER THE 7025 04:31:33,651 --> 04:31:36,988 PAST SEVERAL MONTHS SPECIAL 7026 04:31:36,988 --> 04:31:38,923 PROVIDED VALUABLE INPUT AND 7027 04:31:38,923 --> 04:31:40,057 RESOURCES. 7028 04:31:40,057 --> 04:31:46,564 DURING THE PLANNING PHASE, 7029 04:31:46,564 --> 04:31:50,334 MET WITH US MULTIPLE TIMES 7030 04:31:50,334 --> 04:31:53,704 AND ALL HERE TODAY BECAUSE 7031 04:31:53,704 --> 04:31:57,074 OF THE McKNIGHT BRAIN 7032 04:31:57,074 --> 04:31:58,075 RESEARCH FOUNDATION. 7033 04:31:58,075 --> 04:31:58,442 [APPLAUSE] 7034 04:31:58,442 --> 04:32:01,145 AND NOW I WILL TURN IT OVER 7035 04:32:01,145 --> 04:32:01,812 TO YOU. 7036 04:32:01,812 --> 04:32:03,748 >> THANK YOU ALL VERY MUCH. 7037 04:32:03,748 --> 04:32:05,149 NOT ONLY FOR STICKING IT OUT 7038 04:32:05,149 --> 04:32:06,717 TO THE END BUT BEING HERE IN 7039 04:32:06,717 --> 04:32:08,653 THE FIRST PLACE. 7040 04:32:08,653 --> 04:32:09,720 AMAZED THE DISTANCES PEOPLE 7041 04:32:09,720 --> 04:32:11,589 HAVE TRAVELED AND TAKING 7042 04:32:11,589 --> 04:32:12,757 TIME OUT OF YOUR SCHEDULES 7043 04:32:12,757 --> 04:32:17,795 NOT ONLY TO BE HERE BUT 7044 04:32:17,795 --> 04:32:19,463 PARTICULARLY THE ORGANIZING 7045 04:32:19,463 --> 04:32:20,631 COMMITTEE, GIVING US 7046 04:32:20,631 --> 04:32:21,966 WONDERFUL IDEAS THAT ARE NEW 7047 04:32:21,966 --> 04:32:24,201 TO ME SO I THANK YOU FOR 7048 04:32:24,201 --> 04:32:24,502 THAT. 7049 04:32:24,502 --> 04:32:27,104 LET'S SEE, WE WANT TO HAVE A 7050 04:32:27,104 --> 04:32:28,306 FEW PUBLIC RELATIONS 7051 04:32:28,306 --> 04:32:28,939 COMMENTS HERE, TAKE A 7052 04:32:28,939 --> 04:32:31,475 PICTURE OF THAT IF YOU WANT, 7053 04:32:31,475 --> 04:32:34,245 OF THE NEW BRAIN WORKS SITE 7054 04:32:34,245 --> 04:32:35,680 THAT GOES LIVE TOMORROW AND 7055 04:32:35,680 --> 04:32:37,815 WANTING US TO BE A OUTREACH 7056 04:32:37,815 --> 04:32:40,451 SO SHARE THAT WITH FRIENDS, 7057 04:32:40,451 --> 04:32:41,719 FAMILY, PATIENTS AND THEN 7058 04:32:41,719 --> 04:32:42,953 ALSO ON OUR WEBSITE WHILE 7059 04:32:42,953 --> 04:32:44,889 YOU ARE THERE, WE HAVE 7060 04:32:44,889 --> 04:32:46,424 SEVERAL PARTNERSHIPS WHERE 7061 04:32:46,424 --> 04:32:47,758 THERE ARE FUNDING 7062 04:32:47,758 --> 04:32:49,560 OPPORTUNITIES SO I KNOW THAT 7063 04:32:49,560 --> 04:32:51,395 PEAKS THE INTEREST FOR FOLKS 7064 04:32:51,395 --> 04:32:53,197 DOING RESEARCH TO BE SURE TO 7065 04:32:53,197 --> 04:32:55,032 CHECK THAT OUT AS WELL. 7066 04:32:55,032 --> 04:32:59,070 AND THEN AT THE END I WOULD 7067 04:32:59,070 --> 04:33:01,005 JUST THANK YOU ALL FOR THE 7068 04:33:01,005 --> 04:33:01,472 GREAT RESEARCH. 7069 04:33:01,472 --> 04:33:03,341 I WOULD KIND OF ASK FOR A 7070 04:33:03,341 --> 04:33:04,475 LITTLE TWIST BECAUSE WE ARE 7071 04:33:04,475 --> 04:33:05,976 LOOKING FOR HOW CAN WE MAKE 7072 04:33:05,976 --> 04:33:07,611 A DIFFERENCE SO THEN THE 7073 04:33:07,611 --> 04:33:09,580 QUESTION ALWAYS IS HOW CAN 7074 04:33:09,580 --> 04:33:11,882 WE APPLY THIS CLINICALLY IN 7075 04:33:11,882 --> 04:33:13,617 HUMANS, TO MAKE A 7076 04:33:13,617 --> 04:33:14,985 DIFFERENCE, HELP US 7077 04:33:14,985 --> 04:33:15,820 SUCCESSFULLY AGE WELL. 7078 04:33:15,820 --> 04:33:17,621 AND SO AS LONG AS WE HAVE 7079 04:33:17,621 --> 04:33:19,890 THAT LENSE THROUGH WHICH 7080 04:33:19,890 --> 04:33:21,525 WE'RE VIEWING EVERYTHING, I 7081 04:33:21,525 --> 04:33:25,096 THINK THE WORK MAKES AN EVEN 7082 04:33:25,096 --> 04:33:25,763 GREATER SIGNIFICANCE. 7083 04:33:25,763 --> 04:33:28,833 SO THANK YOU ALL AGAIN AND 7084 04:33:28,833 --> 04:33:37,074 THAT'S IT. 7085 04:33:37,074 --> 04:33:37,842 [APPLAUSE] 7086 04:33:37,842 --> 04:33:40,244 >> AND THAT CONCLUDES THE 7087 04:33:40,244 --> 04:33:41,045 MEETING. 7088 04:33:41,045 --> 04:33:42,780 SAFE TRAVELS HOME, EVERYONE. 7089 04:33:42,780 --> 04:33:43,280 THANKS AGAIN. 7090 04:33:43,280 --> 04:33:53,691 [ END OF SESSION ]