1 00:00:06,025 --> 00:00:07,860 >> HUMAN GENOME RESEARCH 2 00:00:07,860 --> 00:00:09,328 INSTITUTE AND STILL AN ACTIVE 3 00:00:09,328 --> 00:00:10,663 PHYSICIAN SCIENTIST IN THE 4 00:00:10,663 --> 00:00:12,732 INTRAMURAL PROGRAM OF NHGRI. 5 00:00:12,732 --> 00:00:14,767 AND IT IS MY ENORMOUS PLEASURE 6 00:00:14,767 --> 00:00:18,471 TO WELCOME YOU TODAY TO THE 7 00:00:18,471 --> 00:00:20,973 TENTH INSTALLMENT IN THE 2024 8 00:00:20,973 --> 00:00:23,843 SEASON OF DEMYSTIFYING MEDICINE, 9 00:00:23,843 --> 00:00:24,677 A COURSE THAT'S BEEN GOING ON 10 00:00:24,677 --> 00:00:26,646 FOR A NUMBER OF YEARS, OVER 20, 11 00:00:26,646 --> 00:00:30,683 I BELIEVE, THAT AIMS TO BRIDGE 12 00:00:30,683 --> 00:00:32,218 THE EXCITING DEVELOPMENTS IN 13 00:00:32,218 --> 00:00:34,086 BIOLOGY AND ENGINEERING WITH 14 00:00:34,086 --> 00:00:34,520 MEDICINE. 15 00:00:34,520 --> 00:00:39,992 AND OF COURSE WE HAVE THE ICONIC 16 00:00:39,992 --> 00:00:42,061 PICTURE OF THE BROOKLYN BRIDGE. 17 00:00:42,061 --> 00:00:42,728 LET'S SEE. 18 00:00:42,728 --> 00:00:43,596 OH, MY GOODNESS. 19 00:00:43,596 --> 00:00:46,232 I WENT TOO FAR FORWARD -- OF THE 20 00:00:46,232 --> 00:00:47,300 BROOKLYN BRIDGE HERE. 21 00:00:47,300 --> 00:00:50,269 IN THE UPPER RIGHT-HAND CORNER. 22 00:00:50,269 --> 00:00:54,006 WHICH IS OF COURSE BRIDGING 23 00:00:54,006 --> 00:00:56,843 MANHATTAN WITH BROOKLYN OF ALL 24 00:00:56,843 --> 00:00:57,743 PLACES OVER THE EAST RIVER, AND 25 00:00:57,743 --> 00:01:00,780 YOU CAN SEE IN THE LEFT-HAND 26 00:01:00,780 --> 00:01:03,216 SIDE OF THE PHOTO THAT THERE ARE 27 00:01:03,216 --> 00:01:04,951 THESE TWO GUYS, ONE OF THEM FROM 28 00:01:04,951 --> 00:01:08,254 MAMANHATTAN, THE OTHER FROM 29 00:01:08,254 --> 00:01:09,455 BROOKLYN, THAT ARE HAVING A VERY 30 00:01:09,455 --> 00:01:11,324 HEATED CONVERSATION ABOUT ONE OF 31 00:01:11,324 --> 00:01:12,959 THE SCIENTIFIC TOPICS OF 32 00:01:12,959 --> 00:01:15,261 INTEREST OF THE DAY BACK IN THE 33 00:01:15,261 --> 00:01:17,663 1870s, AND WE HOPE TO ENGENDER 34 00:01:17,663 --> 00:01:20,299 THAT SAME KIND OF FERVENT 35 00:01:20,299 --> 00:01:24,337 DISCUSSION BETWEEN OUR TWO 36 00:01:24,337 --> 00:01:25,338 PRESENTERS, DR. SONJA SCHOLZ, 37 00:01:25,338 --> 00:01:27,206 AND DR. REBECCA GOTTESMAN, WHO 38 00:01:27,206 --> 00:01:30,576 WILL BE TALKING TO US TODAY 39 00:01:30,576 --> 00:01:34,614 ABOUT DEMENTIA, BOTH THE GENETIC 40 00:01:34,614 --> 00:01:37,550 AND VASCULAR FACTORS 41 00:01:37,550 --> 00:01:38,451 PREDISPOSING TO DEMENTIA. 42 00:01:38,451 --> 00:01:42,855 IN ANY CASE, AND SO WE HOPE WE 43 00:01:42,855 --> 00:01:47,159 WILL HAVE A LIVELY DISCUSSION, A 44 00:01:47,159 --> 00:01:48,527 LIVELY PRESENTATIONS, WE'LL HEAR 45 00:01:48,527 --> 00:01:49,295 THE TWO PRESENTATIONS AND THEN 46 00:01:49,295 --> 00:01:53,132 QUESTION AND ANSWER AT THE END 47 00:01:53,132 --> 00:01:56,102 AND WE'LL GO ON AT LEAST UNTIL 48 00:01:56,102 --> 00:01:57,303 6:00 AND IF THERE'S STILL MORE 49 00:01:57,303 --> 00:01:59,805 QUESTIONS, WE'LL TAKE THEM BY 50 00:01:59,805 --> 00:02:00,473 EMAIL. 51 00:02:00,473 --> 00:02:02,875 WE WANT TO BREAK DOWN THE SILOS 52 00:02:02,875 --> 00:02:05,177 AS YOU SEE IN THE LOWER 53 00:02:05,177 --> 00:02:06,145 RIGHT-HAND CORNER, PERHAPS EVEN 54 00:02:06,145 --> 00:02:09,315 WITH A FEW CORNY JOKES. 55 00:02:09,315 --> 00:02:11,083 SO IN ANY CASE, THIS IS A SERIES 56 00:02:11,083 --> 00:02:15,655 THAT GOES ON FROM JANUARY UNTIL 57 00:02:15,655 --> 00:02:16,956 MAY OF 2024. 58 00:02:16,956 --> 00:02:20,593 YOU CAN WATCH IT AT THE LINK 59 00:02:20,593 --> 00:02:21,794 SHOWN THERE ON THIS FIRST SLIDE 60 00:02:21,794 --> 00:02:26,699 THAT YOU CAN GET CME CREDITS IF 61 00:02:26,699 --> 00:02:30,636 YOU JUST PUT IN THE CODE 52095. 62 00:02:30,636 --> 00:02:31,871 IF YOU HAVE QUESTIONS, YOU CAN 63 00:02:31,871 --> 00:02:33,272 USE THE SEND LIVE FEEDBACK 64 00:02:33,272 --> 00:02:35,374 BUTTON ON THE VIDEOCAST DISPLAY. 65 00:02:35,374 --> 00:02:36,976 ALL OF THE PREVIOUS SESSIONS ARE 66 00:02:36,976 --> 00:02:39,512 ARCHIVED AND THIS ONE WILL BE 67 00:02:39,512 --> 00:02:41,514 TOO, AND IF YOU HAVE QUESTIONS 68 00:02:41,514 --> 00:02:44,850 YOU CAN USE THAT EMAIL ADDRESS 69 00:02:44,850 --> 00:02:45,751 THERE FOR ADDITIONAL 70 00:02:45,751 --> 00:02:47,186 INFORMATION. 71 00:02:47,186 --> 00:02:49,455 THIS SLIDE JUST GIVES YOU MORE 72 00:02:49,455 --> 00:02:51,023 INFORMATION ABOUT CME. 73 00:02:51,023 --> 00:02:52,725 WE WON'T BELABOR IT ACCEPT AGAIN 74 00:02:52,725 --> 00:02:56,128 THE CODE, 52095. 75 00:02:56,128 --> 00:03:00,166 AND JUST IN TERMS OF SPEAKER 76 00:03:00,166 --> 00:03:02,702 DISCLOSURES, SCHOLZ HAS REPORTED 77 00:03:02,702 --> 00:03:06,539 GRANT OR RESEARCH REPORT FROM 78 00:03:06,539 --> 00:03:07,173 CERAVEL THERAPEUTICS. 79 00:03:07,173 --> 00:03:08,507 IN ANY CASE, LET'S GET ON WITH 80 00:03:08,507 --> 00:03:09,041 IT. 81 00:03:09,041 --> 00:03:11,777 SO OUR TALK TODAY, OUR TALKS 82 00:03:11,777 --> 00:03:14,947 TODAY ARE ON COGNITIVE LOSS, 83 00:03:14,947 --> 00:03:18,250 DEMENTIA, AND NEURODEGENERATIVE 84 00:03:18,250 --> 00:03:20,853 DISORDERS. 85 00:03:20,853 --> 00:03:22,822 BOTH THE VASCULAR AND GENETIC 86 00:03:22,822 --> 00:03:24,690 FACTORS THAT PREDISPOSE TO THEM 87 00:03:24,690 --> 00:03:27,560 AND OUR FIRST SPEAKER WHO WILL 88 00:03:27,560 --> 00:03:29,829 BE SPEAKING IN PERSON WILL BE 89 00:03:29,829 --> 00:03:31,263 DR. SONJA SCHOLZ. 90 00:03:31,263 --> 00:03:33,899 AND SHE IS A LASKER CLINICAL 91 00:03:33,899 --> 00:03:36,035 RESEARCH SCHOLAR AND CHIEF OF 92 00:03:36,035 --> 00:03:38,404 THE NEURODEGENERATIVE DISEASES 93 00:03:38,404 --> 00:03:40,606 RESEARCH UNIT AT THE LABORATORY 94 00:03:40,606 --> 00:03:43,142 OF NEUROGENETICS AT THE NATIONAL 95 00:03:43,142 --> 00:03:44,844 INSTITUTE FOR NEUROLOGIC 96 00:03:44,844 --> 00:03:46,812 DISORDERS AND STROKE, THE NINDS. 97 00:03:46,812 --> 00:03:49,115 SHE GOT HER MEDICAL DEGREE FROM 98 00:03:49,115 --> 00:03:57,890 THE MEDICAL UNIVERSITY OF INN 99 00:03:57,890 --> 00:03:59,158 INNSBRUCK IN AUSTRIA, SHE THEN 100 00:03:59,158 --> 00:04:01,093 DID A POSTDOCTORAL FELLOWSHIP AT 101 00:04:01,093 --> 00:04:02,895 THE LABORATORY OF NEUROGENETICS 102 00:04:02,895 --> 00:04:05,731 AT THE NATIONAL AGING INSTITUTE, 103 00:04:05,731 --> 00:04:07,500 WITH ANDY SINGLETON AND JOHN 104 00:04:07,500 --> 00:04:09,468 HARDY, AND DID A NEUROLOGY 105 00:04:09,468 --> 00:04:11,037 RESIDENCY AND CHIEF RESIDENCY AT 106 00:04:11,037 --> 00:04:12,838 JOHNS HOPKINS. 107 00:04:12,838 --> 00:04:14,840 AND SHE IS ALSO THE RECIPIENT OF 108 00:04:14,840 --> 00:04:17,877 THE MCFARLAND TRANSITION TO 109 00:04:17,877 --> 00:04:19,745 INDEPENDENCE AWARD FOR 110 00:04:19,745 --> 00:04:21,614 NEUROLOGIST SCIENTISTS. 111 00:04:21,614 --> 00:04:25,551 HER LABORATORY RESEARCH GROUP 112 00:04:25,551 --> 00:04:29,221 APPLIES GENOMIC TECHNIQUES TO 113 00:04:29,221 --> 00:04:31,590 LEWY BODY DEMENTIA, MULTIPLE 114 00:04:31,590 --> 00:04:36,729 SYSTEM ATROPHY, FRONTOTEMPORAL 115 00:04:36,729 --> 00:04:37,196 DEMENTIA, PROGRESSIVE 116 00:04:37,196 --> 00:04:38,798 SUPRANUCLEAR PALSY AND 117 00:04:38,798 --> 00:04:40,666 CORTICOBASAL DEGENERATION. 118 00:04:40,666 --> 00:04:42,368 UNRAVELING MOLECULAR MECHANISMS 119 00:04:42,368 --> 00:04:43,736 AND IDENTIFYING TARGETS FOR DRUG 120 00:04:43,736 --> 00:04:46,605 DEVELOPMENT. 121 00:04:46,605 --> 00:04:47,673 OUR SECOND SPEAKER IS 122 00:04:47,673 --> 00:04:48,641 DR. REBECCA GOTTESMAN. 123 00:04:48,641 --> 00:04:50,209 SHE WILL BE SPEAKING TO US 124 00:04:50,209 --> 00:04:51,510 REMOTELY TODAY. 125 00:04:51,510 --> 00:04:53,712 AND SHE IS THE CHIEF OF THE 126 00:04:53,712 --> 00:04:56,215 STROKE, COGNITION AND 127 00:04:56,215 --> 00:04:56,882 NEUROEPIDEMIOLOGY SECTION AND 128 00:04:56,882 --> 00:04:59,185 THE STROKE BRANCH OF THE 129 00:04:59,185 --> 00:05:00,486 NATIONAL INSTITUTE OF NEUROLOGIC 130 00:05:00,486 --> 00:05:02,922 DISORDERS AND STROKE, THE NINDS. 131 00:05:02,922 --> 00:05:08,360 SHE GOT HER MD, MAGNA CUM LAUDE, 132 00:05:08,360 --> 00:05:09,128 FROM COLUMBIA UNIVERSITY COLLEGE 133 00:05:09,128 --> 00:05:10,029 OF PHYSICIANS AND SURGEONS. 134 00:05:10,029 --> 00:05:12,998 SHE RECEIVED A PH.D. IN CLINICAL 135 00:05:12,998 --> 00:05:16,268 INVESTIGATION FROM JOHNS HOPKINS 136 00:05:16,268 --> 00:05:16,969 BLOOMBERG SCHOOL OF PUBLIC 137 00:05:16,969 --> 00:05:19,972 HEALTH, DID A NEUROLOGY 138 00:05:19,972 --> 00:05:21,540 RESIDENCY AND VASCULAR NEUROLOGY 139 00:05:21,540 --> 00:05:23,275 FELLOWSHIP AT JOHNS HOPKINS, AND 140 00:05:23,275 --> 00:05:26,345 BEFORE COMING TO THE NIH, WAS A 141 00:05:26,345 --> 00:05:28,080 PROFESSOR OF NEUROLOGY AND 142 00:05:28,080 --> 00:05:30,182 EPIDEMIOLOGY AT JOHNS HOPKINS. 143 00:05:30,182 --> 00:05:32,084 SHE'S AN ELECTED MEMBER OF THE 144 00:05:32,084 --> 00:05:34,086 AMERICAN SOCIETY OF CLINICAL 145 00:05:34,086 --> 00:05:34,753 INVESTIGATION. 146 00:05:34,753 --> 00:05:37,389 AND HER RESEARCH GROUP THROUGH 147 00:05:37,389 --> 00:05:39,258 LARGE EPIDEMIOLOGIC COHORTS, 148 00:05:39,258 --> 00:05:41,994 STUDIES THE ASSOCIATION BETWEEN 149 00:05:41,994 --> 00:05:44,497 VASCULAR RISK FACTORS, 150 00:05:44,497 --> 00:05:45,598 ESPECIALLY IN MID LIFE, AND 151 00:05:45,598 --> 00:05:47,900 COGNITIVE DECLINE AND DEMENTIA. 152 00:05:47,900 --> 00:05:50,836 AND AS A PART OF A LARGE COHORT 153 00:05:50,836 --> 00:05:52,571 STUDY, THEY'RE CURRENTLY 154 00:05:52,571 --> 00:05:54,006 RECRUITING PATIENTS WITH STROKE 155 00:05:54,006 --> 00:05:55,441 ACROSS 30 U.S. SITES, EVALUATING 156 00:05:55,441 --> 00:05:57,943 THE ASSOCIATION BETWEEN STROKE 157 00:05:57,943 --> 00:05:59,245 AND DEMENTIA, AND THEY LOOK AT 158 00:05:59,245 --> 00:06:01,680 RISK FACTORS FOR PROGRESSION OF 159 00:06:01,680 --> 00:06:03,149 AND OUTCOMES RELATED TO CEREBRAL 160 00:06:03,149 --> 00:06:05,951 SMALL VESSEL DISEASE. 161 00:06:05,951 --> 00:06:07,586 WELL, WITH ALL THAT HAVING BEEN 162 00:06:07,586 --> 00:06:10,089 SAID, IT'S TIME TO GET ON WITH 163 00:06:10,089 --> 00:06:15,661 THINGS AND INVITE DR SCHOLZ TO E 164 00:06:15,661 --> 00:06:20,599 UP TO THE PODIUM AND RE GA REGAS 165 00:06:20,599 --> 00:06:23,335 WITH STORIES OF GENETIC FACTORS 166 00:06:23,335 --> 00:06:25,938 THAT PREDISPOSE TO DEMENTIA. 167 00:06:25,938 --> 00:06:35,381 SCHOLZ, TAKE IT AWAY. 168 00:06:35,381 --> 00:06:37,650 >> THANK YOU VERY MUCH FOR THE 169 00:06:37,650 --> 00:06:38,651 KIND INTRODUCTION, AND THANK YOU 170 00:06:38,651 --> 00:06:40,920 FOR HAVING ME TODAY, FOR 171 00:06:40,920 --> 00:06:45,157 ALLOWING ME TO SPEAK ABOUT AN 172 00:06:45,157 --> 00:06:47,526 EXCITING AND EMERGING FIELD, HOW 173 00:06:47,526 --> 00:06:51,230 GENETIC FACTORS AND VASCULAR 174 00:06:51,230 --> 00:06:53,499 FACTORS ARE ACTUALLY PLAYING A 175 00:06:53,499 --> 00:06:55,267 COAL IN COGNITIVE DECLINE AND 176 00:06:55,267 --> 00:06:55,701 DEMENTIA. 177 00:06:55,701 --> 00:06:57,670 BEFORE I GET STARTED HERE ARE MY 178 00:06:57,670 --> 00:06:58,470 DISCLOSURES THAT HAVE ALREADY 179 00:06:58,470 --> 00:07:00,306 BEEN HIGHLIGHTED. 180 00:07:00,306 --> 00:07:02,141 I AM AN INTRAMURAL RESEARCHER 181 00:07:02,141 --> 00:07:03,309 AND RECEIVED SOME INDUSTRY 182 00:07:03,309 --> 00:07:07,546 SUPPORT AND ALSO SERVE ON VEFERL 183 00:07:07,546 --> 00:07:09,348 BOARDS, ADVISORY AND EDITORIAL 184 00:07:09,348 --> 00:07:09,615 BOARDS. 185 00:07:09,615 --> 00:07:10,816 SO THE TOPICS THAT WE'RE GOING 186 00:07:10,816 --> 00:07:16,855 TO COVER TODAY ARE IF FIELDS WE 187 00:07:16,855 --> 00:07:18,791 COLLECTIVELY SUMMARIZE AS 188 00:07:18,791 --> 00:07:19,558 NON-ALZHEIMER'S DEMENTIAS. 189 00:07:19,558 --> 00:07:20,759 I'M GOING TO GO INTO THAT TERM, 190 00:07:20,759 --> 00:07:21,994 WHAT WE SPECIFICALLY MEAN AMINO 191 00:07:21,994 --> 00:07:25,397 BYTHAT AND WE DELIBERATELY CHOSE 192 00:07:25,397 --> 00:07:27,566 THAT BECAUSE WHEN WE TALK ABOUT 193 00:07:27,566 --> 00:07:28,934 DEMENTIA, WE OFTEN FOCUS ON 194 00:07:28,934 --> 00:07:29,735 ALZHEIMER'S DISEASE BUT WE 195 00:07:29,735 --> 00:07:31,070 REALLY WANT TO CONVEY THERE'S A 196 00:07:31,070 --> 00:07:33,239 WHOLE GROUP OF DISEASES THAT ARE 197 00:07:33,239 --> 00:07:33,973 UNDERLYING DEMENTIA SYNDROMES 198 00:07:33,973 --> 00:07:36,575 AND IT'S ACTUALLY BY STUDYING 199 00:07:36,575 --> 00:07:37,843 THE BROADER SPECTRUM WE CAN 200 00:07:37,843 --> 00:07:39,278 REALLY LEARN A LOT ABOUT 201 00:07:39,278 --> 00:07:41,180 NEUROLOGIC DISEASES OF AGING. 202 00:07:41,180 --> 00:07:42,514 SO MY JOB AS THE FIRST SPEAKER 203 00:07:42,514 --> 00:07:44,717 IS TO REALLY FOCUS IN ON THE 204 00:07:44,717 --> 00:07:48,220 NEURODEGENERATIVE FORMS OF 205 00:07:48,220 --> 00:07:52,291 DEMENTIAS INCLUDING LUO BODY AND 206 00:07:52,291 --> 00:07:53,158 FRONTOTEMPORAL DEMENTIA AND I'LL 207 00:07:53,158 --> 00:07:54,560 SHOWCASE A COUPLE EXAMPLES FROM 208 00:07:54,560 --> 00:07:57,830 MY LAB AND HOW WE USE GENOMIC 209 00:07:57,830 --> 00:08:00,366 TOOLS TO PINPOINT DISEASE 210 00:08:00,366 --> 00:08:01,900 MECHANISMS AND CHANGES THAT MAY 211 00:08:01,900 --> 00:08:07,973 BE TRANSLATIONAL BILLY RELEVANTD 212 00:08:07,973 --> 00:08:09,108 IN THE SECOND HALF, 213 00:08:09,108 --> 00:08:10,309 DR. GOTTESMAN IS THEN GOING TO 214 00:08:10,309 --> 00:08:11,844 LOOK AT VASCULAR FACTORS AND 215 00:08:11,844 --> 00:08:14,013 REVIEW WITH US HOW THESE 216 00:08:14,013 --> 00:08:15,014 VASCULAR CONTRIBUTIONS ARE 217 00:08:15,014 --> 00:08:16,882 PLAYING A ROLE IN COGNITIVE 218 00:08:16,882 --> 00:08:17,750 DECLINE AND DEMENTIA. 219 00:08:17,750 --> 00:08:19,918 THEN WE BRING IT ALL TOGETHER 220 00:08:19,918 --> 00:08:21,453 AND REALLY DISCUSS HOW THEY 221 00:08:21,453 --> 00:08:22,788 ACTUALLY LINK TOGETHER, HOW 222 00:08:22,788 --> 00:08:23,989 VASCULAR FACTORS ARE PLAYING AN 223 00:08:23,989 --> 00:08:25,624 IMPORTANT ROLE IN 224 00:08:25,624 --> 00:08:26,425 NEURODEGENERATION, WHAT DOES IT 225 00:08:26,425 --> 00:08:28,661 MEAN MOVING FORWARD. 226 00:08:28,661 --> 00:08:29,895 ALL RIGHT. 227 00:08:29,895 --> 00:08:31,096 LET'S JUST START OUT WITH GIVING 228 00:08:31,096 --> 00:08:32,298 A LITTLE BIT OF BACKGROUND 229 00:08:32,298 --> 00:08:33,499 INFORMATION. 230 00:08:33,499 --> 00:08:35,234 SO IT DOESN'T COME AS A SURPRISE 231 00:08:35,234 --> 00:08:40,072 THAT WE ARE AN AGING SOCIETY. 232 00:08:40,072 --> 00:08:41,707 AS A COMMUNITY, WE'RE ENJOYING 233 00:08:41,707 --> 00:08:44,310 LONGER LIFE EXPECTANCIES DUE TO 234 00:08:44,310 --> 00:08:46,278 JUST DRASTIC CHANGES IN MEDICAL 235 00:08:46,278 --> 00:08:48,814 CARE BUT ALSO PUBLIC HEALTH 236 00:08:48,814 --> 00:08:50,683 MEASURES, AND WHILE THAT IS, OF 237 00:08:50,683 --> 00:08:52,084 COURSE, GREAT NEWS, IT ALSO 238 00:08:52,084 --> 00:08:53,819 COMES WITH ITS OWN CHALLENGES. 239 00:08:53,819 --> 00:08:57,222 SO AS A SOCIETY, WE'LL HAVE TO 240 00:08:57,222 --> 00:08:58,891 ADAPT AS TO HOW WE ARE GOING TO 241 00:08:58,891 --> 00:09:00,292 DELIVER HEALTHCARE FOR AN 242 00:09:00,292 --> 00:09:02,161 INCREASINGLY AGING POPULATION. 243 00:09:02,161 --> 00:09:06,198 SO THESE DEMOGRAPHIC CHANGES 244 00:09:06,198 --> 00:09:08,500 REALLY ARE COMING TO US RATHER 245 00:09:08,500 --> 00:09:09,168 RAPIDLY. 246 00:09:09,168 --> 00:09:12,104 WE ACTUALLY HAVE TO DEAL WITH 247 00:09:12,104 --> 00:09:13,305 AGE-RELATED NEURODEGENERATIVE 248 00:09:13,305 --> 00:09:14,640 DISEASES AND STROKES AT SUCH A 249 00:09:14,640 --> 00:09:15,507 RAPID PACE THAT IT'S REALLY 250 00:09:15,507 --> 00:09:16,675 DIFFICULT FOR US TO JUST KEEP UP 251 00:09:16,675 --> 00:09:18,010 WITH THE PATIENT VOLUME. 252 00:09:18,010 --> 00:09:20,846 SO THE NEUROLOGICAL DISEASES 253 00:09:20,846 --> 00:09:21,880 THAT ARE ASSOCIATED WITH AGING 254 00:09:21,880 --> 00:09:23,582 ARE REALLY A MAJOR CHALLENGE. 255 00:09:23,582 --> 00:09:31,123 SO SHOWN HERE ARE -- OKAY. 256 00:09:31,123 --> 00:09:34,093 SO SHOWN HERE ARE -- I HOPE YOU 257 00:09:34,093 --> 00:09:36,628 CAN HEAR ME. 258 00:09:36,628 --> 00:09:37,830 SO SHOWN HERE ARE THE 259 00:09:37,830 --> 00:09:40,032 NEUROLOGICAL DISEASES ACROSS THE 260 00:09:40,032 --> 00:09:40,499 LIFESPAN. 261 00:09:40,499 --> 00:09:42,201 SO IN EARLY CHILDHOOD, THE 262 00:09:42,201 --> 00:09:44,703 NEUROLOGICAL CONDITIONS WE 263 00:09:44,703 --> 00:09:49,208 MOSTLY DEAL WITH ARE INFECTIOUS 264 00:09:49,208 --> 00:09:50,843 DISEASES, THEN IN ADOLESCENCE, 265 00:09:50,843 --> 00:09:52,611 YOUNG ADULTHOOD IT'S MORE 266 00:09:52,611 --> 00:09:54,012 HEADACHE SYNDROMES, AUTOIMMUNE 267 00:09:54,012 --> 00:09:55,047 CONDITIONS, BUT AS WE ARE 268 00:09:55,047 --> 00:09:58,083 GETTING OLDER, STROKE AND 269 00:09:58,083 --> 00:09:59,051 DEMENTIA SYNDROMES ARE A REAL 270 00:09:59,051 --> 00:10:01,019 CHALLENGE. 271 00:10:01,019 --> 00:10:05,257 AND IT IS NOT SURPRISING THAT 272 00:10:05,257 --> 00:10:06,825 THEY ARE ACTUALLY MAJOR CAUSES 273 00:10:06,825 --> 00:10:08,360 OF DEATH IN THE POPULATION OVER 274 00:10:08,360 --> 00:10:10,095 65, ALSO MAJOR CAUSES OF 275 00:10:10,095 --> 00:10:11,430 DISABILITY, AND THAT'S REALLY 276 00:10:11,430 --> 00:10:12,297 CONCERNING. 277 00:10:12,297 --> 00:10:13,399 AND AS A HEALTHCARE COMMUNITY, 278 00:10:13,399 --> 00:10:15,501 WE ARE REALLY CALLED TO ACTION 279 00:10:15,501 --> 00:10:19,638 TO ACTUALLY TACKLE THIS PROBLEM. 280 00:10:19,638 --> 00:10:23,909 SO HERE ARE SOME IMPORTANT 281 00:10:23,909 --> 00:10:24,443 NUMBERS. 282 00:10:24,443 --> 00:10:26,812 DEMENTIA ON A WORLDWIDE SCALE IS 283 00:10:26,812 --> 00:10:28,814 A MASSIVE PROBLEM, ABOUT 284 00:10:28,814 --> 00:10:30,916 55 MILLION PEOPLE ARE SUFFERING 285 00:10:30,916 --> 00:10:32,818 FROM DEMENTIA, AND ABOUT 286 00:10:32,818 --> 00:10:34,086 7 MILLION OF THOSE ARE JUST IN 287 00:10:34,086 --> 00:10:36,488 THE UNITED STATES. 288 00:10:36,488 --> 00:10:38,457 THIS IS PROJECTED TO GROW VERY 289 00:10:38,457 --> 00:10:40,626 DRAMATICALLY IN THE NEXT FEW 290 00:10:40,626 --> 00:10:45,130 DECADES BECAUSE OF THE 291 00:10:45,130 --> 00:10:46,198 DEMOGRAPHIC CHANGES AND 292 00:10:46,198 --> 00:10:46,932 PARTICULARLY WHAT'S HAPPENING IN 293 00:10:46,932 --> 00:10:48,967 LOW AND MIDDLE INCOME COUNTRIES. 294 00:10:48,967 --> 00:10:52,004 AND THE CURRENT COST IS ABOUT 295 00:10:52,004 --> 00:10:53,338 $1.3 TRILLION ALREADY, BY 2030 296 00:10:53,338 --> 00:10:56,175 IT'S GOING TO BE $2.8 TRILLION, 297 00:10:56,175 --> 00:10:57,242 SO WE'RE GETTING TO A POINT 298 00:10:57,242 --> 00:10:58,811 WHERE IT'S JUST 299 00:10:58,811 --> 00:11:00,979 SOCIOECONOMICALLY NOT VIABLE, 300 00:11:00,979 --> 00:11:02,848 AND THAT'S WHY WE NEED TO 301 00:11:02,848 --> 00:11:03,816 UNDERSTAND THIS DISEASE AND COME 302 00:11:03,816 --> 00:11:07,753 UP WITH TREATMENTS VERY RAPIDLY. 303 00:11:07,753 --> 00:11:10,222 AS I SAID, DEMENTIA SYNDROMES 304 00:11:10,222 --> 00:11:11,490 ARE REALLY IMPORTANT IN THE 305 00:11:11,490 --> 00:11:14,092 AGING POPULATION, AND WHILE 306 00:11:14,092 --> 00:11:14,993 ALZHEIMER'S DISEASE IS THE MOST 307 00:11:14,993 --> 00:11:16,695 COMMON FORM OF DEMENTIA, THERE'S 308 00:11:16,695 --> 00:11:19,531 A WHOLE GROUP OF OTHER DISEASES, 309 00:11:19,531 --> 00:11:21,767 WHICH WE ELECTIVELY DESCRIBE AS 310 00:11:21,767 --> 00:11:25,103 THE NON-ALZHEIMER'S DEMENTIAS, 311 00:11:25,103 --> 00:11:26,705 OR RELATED DEMENTIAS. 312 00:11:26,705 --> 00:11:28,674 THEY INCLUDE VASCULAR DEMENTIA, 313 00:11:28,674 --> 00:11:36,648 WHICH IS THE TO PICK TOPIC OF S 314 00:11:36,648 --> 00:11:37,082 TALK. 315 00:11:37,082 --> 00:11:39,284 WHAT DO WE ACTUALLY MEAN WITH 316 00:11:39,284 --> 00:11:40,919 THIS TERM DEMENTIA? 317 00:11:40,919 --> 00:11:44,189 SO IT'S A CLINICAL TERM, AND IT 318 00:11:44,189 --> 00:11:45,624 BASICALLY IS DEFINED AS HAVING 319 00:11:45,624 --> 00:11:48,126 SIGNIFICANT COGNITIVE DECLINE IN 320 00:11:48,126 --> 00:11:51,463 AT LEAST TWO OR MORE DOMAINS. 321 00:11:51,463 --> 00:11:53,832 IT HAS TO BE SEVERE ENOUGH TO 322 00:11:53,832 --> 00:11:55,367 INTERFERE WITH INDEPENDENCE OF 323 00:11:55,367 --> 00:11:57,102 DAILY LIVING. 324 00:11:57,102 --> 00:11:59,838 SO THOSE ARE ACTIVITIES SUCH AS 325 00:11:59,838 --> 00:12:02,241 BATHING YOURSELF, FEEDING 326 00:12:02,241 --> 00:12:03,242 YOURSELF, MANAGING BASIC 327 00:12:03,242 --> 00:12:03,475 HYGIENE. 328 00:12:03,475 --> 00:12:04,877 SO YOU HAVE TO BE REALLY 329 00:12:04,877 --> 00:12:06,845 IMPAIRED IN ORDER TO QUALIFY FOR 330 00:12:06,845 --> 00:12:08,046 THE CLINICAL DIAGNOSIS OF 331 00:12:08,046 --> 00:12:10,015 DEMENTIA. 332 00:12:10,015 --> 00:12:12,117 WHAT WE MEAN WITH COGNITIVE 333 00:12:12,117 --> 00:12:14,620 DOMAINS ARE HIGHER COGNITIVE 334 00:12:14,620 --> 00:12:17,122 FUNCTIONS SUCH AS BEING ABLE TO 335 00:12:17,122 --> 00:12:18,924 FORM MEMORIES, BEING ABLE TO 336 00:12:18,924 --> 00:12:20,859 ORIENT YOURSELF IN SPACE AND 337 00:12:20,859 --> 00:12:22,594 INTEGRATE VISUAL INFORMATION 338 00:12:22,594 --> 00:12:27,299 INTO MEANINGFUL CONCEPTS, BEING 339 00:12:27,299 --> 00:12:28,934 ABLE TO FORMULATE THOUGHTS, 340 00:12:28,934 --> 00:12:31,236 BEING ABLE TO PAY ATTENTION TO 341 00:12:31,236 --> 00:12:32,771 THOUGHTS, ORGANIZE YOUR 342 00:12:32,771 --> 00:12:33,639 THOUGHTS, EXECUTIVE FUNCTION, 343 00:12:33,639 --> 00:12:37,276 BUT ALSO BEHAVIOR IN THE 344 00:12:37,276 --> 00:12:38,477 GENERATION AND PRODUCTION OF 345 00:12:38,477 --> 00:12:40,979 LANGUAGE AND COMPREHENSION OF 346 00:12:40,979 --> 00:12:42,281 LANGUAGE, ALL HIGHER COGNITIVE 347 00:12:42,281 --> 00:12:42,714 DOMAINS. 348 00:12:42,714 --> 00:12:44,182 AND YOU CAN IMAGINE DEPENDING ON 349 00:12:44,182 --> 00:12:46,618 THE UNDERLYING DISEASE PROCESS, 350 00:12:46,618 --> 00:12:48,220 THERE MAY BE DIFFERENT PATTERNS 351 00:12:48,220 --> 00:12:49,621 OF COGNITIVE IMPAIRMENT THAT WE 352 00:12:49,621 --> 00:12:51,189 CAN SEE. 353 00:12:51,189 --> 00:12:52,491 SO IN ALZHEIMER'S DISEASE, WHICH 354 00:12:52,491 --> 00:12:56,295 IS OUR TEXTBOOK EXAMPLE, IN ITS 355 00:12:56,295 --> 00:12:57,429 MOST DIFFICULT PRESENTATION, YOU 356 00:12:57,429 --> 00:12:58,730 GET IMPAIRMENT OF SHORT TERM 357 00:12:58,730 --> 00:13:00,699 MEMORY, BUT YOU ALSO HAVE 358 00:13:00,699 --> 00:13:03,735 DIFFICULTIES WITH VISUAL 359 00:13:03,735 --> 00:13:04,503 PERCEPTUAL VISUAL SPAISHT 360 00:13:04,503 --> 00:13:05,504 FUNCTION, GETTING LOST IN 361 00:13:05,504 --> 00:13:06,705 FAMILIAR ENVIRONMENTS, HAVING 362 00:13:06,705 --> 00:13:09,007 DIFFICULTIES WITH RECALLING 363 00:13:09,007 --> 00:13:11,276 NAMES, KIND OF TIP OF THE TONGUE 364 00:13:11,276 --> 00:13:12,511 FEELING, THAT'S THE TYPICAL 365 00:13:12,511 --> 00:13:13,078 PRESENTATION OF ALZHEIMER'S 366 00:13:13,078 --> 00:13:16,214 DISEASE. 367 00:13:16,214 --> 00:13:25,624 IIN LILEWY BODY DEMENTIA PATIENS 368 00:13:25,624 --> 00:13:26,858 MANIFEST WITH VISUAL 369 00:13:26,858 --> 00:13:27,793 HALLUCINATIONS THAT ARE VERY 370 00:13:27,793 --> 00:13:29,428 WELL FORMED BUT ALSO EXECUTIVE 371 00:13:29,428 --> 00:13:30,762 FUNCTION PROBLEMS SUCH AS 372 00:13:30,762 --> 00:13:32,831 IMPAIRED WORKING MEMORY, 373 00:13:32,831 --> 00:13:34,533 IMPAIRED INTENTIONAL TASKS THAT 374 00:13:34,533 --> 00:13:36,134 OFTEN CAN FLUCTUATE FROM HOUR TO 375 00:13:36,134 --> 00:13:37,436 HOUR OR FROM DAY TO DAY. 376 00:13:37,436 --> 00:13:39,605 IN ADDITION, THESE PATIENTS ALSO 377 00:13:39,605 --> 00:13:41,740 OFTEN HAVE PARKINSON 378 00:13:41,740 --> 00:13:43,108 DISEASE-LIKE SYMPTOMS, BEING 379 00:13:43,108 --> 00:13:47,145 STIFF, BEING SLOW. 380 00:13:47,145 --> 00:13:48,547 SO IT'S A DIFFERENT PATTERN YOU 381 00:13:48,547 --> 00:13:49,548 CAN RECOGNIZE AND YOU REALLY 382 00:13:49,548 --> 00:13:50,983 LOOK FOR IMPAIRMENTS IN THESE 383 00:13:50,983 --> 00:13:52,184 DOMAINS IN ORDER TO MAKE A 384 00:13:52,184 --> 00:13:52,618 CLINICAL DIAGNOSIS. 385 00:13:52,618 --> 00:13:54,953 AND THE THIRD MAJOR GROUP ARE 386 00:13:54,953 --> 00:13:56,388 THE FRONTOTEMPORAL DEMENTIA 387 00:13:56,388 --> 00:13:56,688 SYNDROMES. 388 00:13:56,688 --> 00:13:59,324 IT'S ACTUALLY A COUPLE OF 389 00:13:59,324 --> 00:14:02,394 DISEASES SUMMARIZED UNDER THAT 390 00:14:02,394 --> 00:14:02,894 UMBRELLA TERM. 391 00:14:02,894 --> 00:14:04,863 THERE ARE DIFFERENT SUBTYPES. 392 00:14:04,863 --> 00:14:07,299 ONE SUBTYPE AFFECTS BEHAVIOR 393 00:14:07,299 --> 00:14:09,267 PREDOMINANTLY, ANOTHER AFFECTS 394 00:14:09,267 --> 00:14:10,168 PREDOMINANTLY LANGUAGE BUT THERE 395 00:14:10,168 --> 00:14:11,236 IS OFTEN A LOT OF OVERLAP. 396 00:14:11,236 --> 00:14:12,571 SO YOU CAN SEE THERE ARE 397 00:14:12,571 --> 00:14:13,872 DIFFERENT PATTERNS JUST IN THE 398 00:14:13,872 --> 00:14:19,311 CLINICAL PRESENTATION. 399 00:14:19,311 --> 00:14:21,246 SO ASIDE FROM HAVING ONGOING 400 00:14:21,246 --> 00:14:21,813 PROGRESSIVE NEUROLOGICAL 401 00:14:21,813 --> 00:14:23,348 DECLINE, THE OTHER MAJOR 402 00:14:23,348 --> 00:14:24,883 HALLMARKER OF NEURODEGENERATION 403 00:14:24,883 --> 00:14:29,054 IS THE DEPOSITION OF SPECIFIC 404 00:14:29,054 --> 00:14:29,321 PROTEINS. 405 00:14:29,321 --> 00:14:30,255 IN ALZHEIMER'S DISEASE, THE 406 00:14:30,255 --> 00:14:32,024 PROTEINS THAT WE FIND DEPOSITED 407 00:14:32,024 --> 00:14:34,393 IN THE BRAINS OF PATIENTS ARE 408 00:14:34,393 --> 00:14:35,827 SO-CALLED BETA AMYLOID IN THE 409 00:14:35,827 --> 00:14:40,766 FORM OF AMYLOID PLAQUES. 410 00:14:40,766 --> 00:14:49,207 AND TAU PROTEIN, TANGLES, TO 411 00:14:49,207 --> 00:14:50,842 ESTABLISH A PATHOLOGICAL 412 00:14:50,842 --> 00:14:52,611 DIAGNOSE. 413 00:14:52,611 --> 00:14:53,812 LEWY BODY DEMENTIA DISEASE WHERE 414 00:14:53,812 --> 00:14:56,314 WE SEE ABNORMAL DEPOSITION OF 415 00:14:56,314 --> 00:14:57,649 MISFOLDED ALPHA SYNUCLEIN 416 00:14:57,649 --> 00:15:01,386 PROTEIN IN THE FORM OF SO-CALLED 417 00:15:01,386 --> 00:15:03,789 LEWY BODIES, HENCE THE DISEASE 418 00:15:03,789 --> 00:15:05,424 NAME. 419 00:15:05,424 --> 00:15:06,024 FRONTOTEMPORAL DEMENTIA ON THE 420 00:15:06,024 --> 00:15:07,626 OTHER HAND IS USUALLY A DISEASE 421 00:15:07,626 --> 00:15:14,066 OF EITHER DEPOSITION OF TDP 422 00:15:14,066 --> 00:15:15,367 TDP-43 PROTEIN OR TAU. 423 00:15:15,367 --> 00:15:20,072 THEALTHOUGH THIS LOOKS NICE AND 424 00:15:20,072 --> 00:15:23,575 CLEAN, THIS SCHEMA IS A VERY 425 00:15:23,575 --> 00:15:24,342 IDEAL WORLD. 426 00:15:24,342 --> 00:15:25,777 IN REALITY, WE HAVE LEARNED THAT 427 00:15:25,777 --> 00:15:30,315 THERE ARE TREMENDOUS OVERLAPS 428 00:15:30,315 --> 00:15:33,618 ACROSS THE DISEASE ENTITIES. 429 00:15:33,618 --> 00:15:37,022 LEWY BODY EMBODIES THAT, WHEN WE 430 00:15:37,022 --> 00:15:39,191 LOOK AT PATIENTS WITH LEWY BODY 431 00:15:39,191 --> 00:15:40,926 DEMENTIA, WE SEE 80% OF PATIENTS 432 00:15:40,926 --> 00:15:42,894 ALSO HAVE SIGNIFICANT 433 00:15:42,894 --> 00:15:43,662 ALZHEIMER'S DISEASE 434 00:15:43,662 --> 00:15:44,262 CO-PATHOLOGY. 435 00:15:44,262 --> 00:15:45,630 IT'S NOT SURPRISING THAT WHEN WE 436 00:15:45,630 --> 00:15:48,266 GO AND LOOK AT THE GENETICS, WE 437 00:15:48,266 --> 00:15:49,501 ACTUALLY SEE A LOT OF OVERLAPS 438 00:15:49,501 --> 00:15:51,236 IN THE GENETIC RISK PROFILES. 439 00:15:51,236 --> 00:15:52,437 AND WHILE IT'S MAKING OUR LIVES 440 00:15:52,437 --> 00:15:53,505 A LITTLE BIT MORE DIFFICULT, 441 00:15:53,505 --> 00:15:55,407 IT'S ACTUALLY GOOD NEWS BECAUSE 442 00:15:55,407 --> 00:15:56,908 IT SUGGESTS THAT A LOT OF THE 443 00:15:56,908 --> 00:15:57,909 INSIGHTS WE GAIN IN ONE FIELD 444 00:15:57,909 --> 00:15:59,411 COULD HAVE IMPLICATIONS IN A 445 00:15:59,411 --> 00:16:01,613 MUCH BROADER SPECTRUM OF 446 00:16:01,613 --> 00:16:02,714 NEURODEGENERATIVE DISEASING. 447 00:16:02,714 --> 00:16:04,449 AND THERE ARE OTHER EXAMPLES. 448 00:16:04,449 --> 00:16:08,420 WE ALSO SEE, FOR EXAMPLE, TDP-4A 449 00:16:08,420 --> 00:16:09,855 SUBSTANTIAL PROPORTION OF 450 00:16:09,855 --> 00:16:11,556 ALZHEIMER'S DISEASE LEWY BODY 451 00:16:11,556 --> 00:16:12,991 DEMENTIA CASES AND VICE VERSA. 452 00:16:12,991 --> 00:16:16,194 SO WE'RE STILL LEARNING HOW TO 453 00:16:16,194 --> 00:16:16,828 BEST APPROACH THAT. 454 00:16:16,828 --> 00:16:18,363 IT'S REALLY A SPECTRUM OF 455 00:16:18,363 --> 00:16:20,766 CONDITIONS THAT WE'RE TRYING TO 456 00:16:20,766 --> 00:16:21,967 STUDY. 457 00:16:21,967 --> 00:16:28,974 HERE'S JUST A VERY FAMOUS STUDY 458 00:16:28,974 --> 00:16:30,342 THAT'S RUN OUT OF RUSH 459 00:16:30,342 --> 00:16:31,810 UNIVERSITY WHERE THEY BASICALLY 460 00:16:31,810 --> 00:16:37,649 LOOKED AT ALZHEIMER'S DISEASE, 461 00:16:37,649 --> 00:16:39,384 WE THINK WE KNOW HOW TO DIAGNOSE 462 00:16:39,384 --> 00:16:40,786 THESE CASES, LOOK AT THE 463 00:16:40,786 --> 00:16:43,421 PATHOLOGY YOU CAN FIND IN THESE 464 00:16:43,421 --> 00:16:46,057 INDIVIDUALS. 465 00:16:46,057 --> 00:16:47,893 ACTUALLY ONLY A SMALL FRACTION 466 00:16:47,893 --> 00:16:49,227 OF THE INDIVIDUALS WITH PROBABLE 467 00:16:49,227 --> 00:16:50,996 ALZHEIMER'S DISEASE ON PATHOLOGY 468 00:16:50,996 --> 00:16:52,831 HAVE PURE ALZHEIMER'S DISEASE 469 00:16:52,831 --> 00:16:53,265 PATHOLOGY CHANGES. 470 00:16:53,265 --> 00:16:54,800 THE VAST MAJORITY ACTUALLY HAVE 471 00:16:54,800 --> 00:16:57,803 ALL SORTS OF CO-PATHOLOGIES. 472 00:16:57,803 --> 00:16:59,538 VASCULAR DISEASE ON TOP OR IN 473 00:16:59,538 --> 00:17:02,240 MOST INSTANCES, ALZHEIMER'S 474 00:17:02,240 --> 00:17:03,341 DISEASE PLUS OTHER DEGENERATIVE 475 00:17:03,341 --> 00:17:08,046 CHANGES SUCH AS LEWY BODYs, 476 00:17:08,046 --> 00:17:09,047 TDP-43, VASCULAR DISEASE, SO 477 00:17:09,047 --> 00:17:10,582 THERE'S REALLY TREMENDOUS 478 00:17:10,582 --> 00:17:12,083 OVERLAP ACROSS THESE DISEASES. 479 00:17:12,083 --> 00:17:14,352 SO THAT'S AN IMPORTANT POINT TO 480 00:17:14,352 --> 00:17:15,253 WRAP OUR MINDS AROUND. 481 00:17:15,253 --> 00:17:16,721 THESE DISEASES ARE NOT BLACK AND 482 00:17:16,721 --> 00:17:18,623 WHITE ENTITIES AS WE LIKE TO 483 00:17:18,623 --> 00:17:22,227 PRESENT THEM. 484 00:17:22,227 --> 00:17:23,428 THIS IS WHERE GENETICS CAN 485 00:17:23,428 --> 00:17:24,596 ACTUALLY BE QUITE ELEGANT. 486 00:17:24,596 --> 00:17:25,730 SO WE LOVE COMPLEX DISEASES. 487 00:17:25,730 --> 00:17:28,133 WE HAVE AN ENTIRE FIELD CALLED 488 00:17:28,133 --> 00:17:29,367 COMPLEX GENETICS WHERE WE REALLY 489 00:17:29,367 --> 00:17:31,536 TRY TO TEASE APART HOW MOLECULAR 490 00:17:31,536 --> 00:17:36,474 FACTORS ARE PLAYING A ROLE. 491 00:17:36,474 --> 00:17:38,109 IN DEMENTIA, WE KNOW GENETIC 492 00:17:38,109 --> 00:17:39,110 FACTORS ARE INVOLVED. 493 00:17:39,110 --> 00:17:40,745 IN SOME INSTANCES, WE DO SEE 494 00:17:40,745 --> 00:17:42,480 CLEAR FAMILY HISTORIES. 495 00:17:42,480 --> 00:17:43,915 IT'S USUALLY JUST SMALL 496 00:17:43,915 --> 00:17:45,383 PROPORTION IN ALZHEIMER'S 497 00:17:45,383 --> 00:17:45,617 DISEASE. 498 00:17:45,617 --> 00:17:50,689 IT'S REALLY ABOUT 10% OF 499 00:17:50,689 --> 00:17:51,690 PATIENTS, FRONTOTEMPORAL 500 00:17:51,690 --> 00:17:52,724 DEMENTIA, ABOUT 40% OF PATIENTS 501 00:17:52,724 --> 00:17:54,092 WHO HAVE A CLEAR FAMILY HISTORY. 502 00:17:54,092 --> 00:17:55,627 BUT EVEN IN THOSE APPARENTLY 503 00:17:55,627 --> 00:17:56,828 SPORADIC CASES, ONCE WE START 504 00:17:56,828 --> 00:17:58,697 LOOKING AT GENETIC FACTORS, WE 505 00:17:58,697 --> 00:18:01,233 DO FIND RISK GENES INVOLVED THAT 506 00:18:01,233 --> 00:18:03,068 ARE PREDISPOSING INDIVIDUALS TO 507 00:18:03,068 --> 00:18:04,603 DEVELOP THE DISEASE. 508 00:18:04,603 --> 00:18:08,006 SO I'M GOING TO SHOW YOU SOME 509 00:18:08,006 --> 00:18:09,741 EXAMPLES OF HOW WE HAVE BEEN 510 00:18:09,741 --> 00:18:11,243 LEVERAGING MODERN GENOMIC TOOLS 511 00:18:11,243 --> 00:18:12,477 TO PINPOINT WHERE THE PROBLEMS 512 00:18:12,477 --> 00:18:13,812 ARE, WHERE THE PATHWAYS AND HOW 513 00:18:13,812 --> 00:18:16,748 CAN WE USE TO SHOW THE 514 00:18:16,748 --> 00:18:18,216 RELATIONSHIPS BETWEEN THESE 515 00:18:18,216 --> 00:18:21,586 DISEASE ENTITIES. 516 00:18:21,586 --> 00:18:23,788 SO MY LAB IS REALLY FOCUSING 517 00:18:23,788 --> 00:18:26,024 VERY HEAVILY ON LEWY BODY 518 00:18:26,024 --> 00:18:27,259 DEMENTIA, WHICH IS THE SECOND 519 00:18:27,259 --> 00:18:32,197 MOST COMMON NEURODEGENERATIVE 520 00:18:32,197 --> 00:18:33,865 DEMENTIA TO ALZHEIMER'S DISEASE, 521 00:18:33,865 --> 00:18:35,600 CHARACTERIZED BY A COMPLEX 522 00:18:35,600 --> 00:18:39,871 NEUROPSYCHIATRIC SYNDROME, AND 523 00:18:39,871 --> 00:18:43,909 THESE VERY CLASSICAL LEWY BODIES 524 00:18:43,909 --> 00:18:46,878 MADE UP OF ALPHA SYNUCLEIN 525 00:18:46,878 --> 00:18:47,212 PROTEIN. 526 00:18:47,212 --> 00:18:49,281 ABOUT A THIRD OF ALL PATIENTS 527 00:18:49,281 --> 00:18:51,683 ACTUALLY HAVE A FAMILY HISTORY 528 00:18:51,683 --> 00:18:54,085 OF DEMENTIA OR PARKINSON'S 529 00:18:54,085 --> 00:18:55,620 DISEASE IN FIRST OR 530 00:18:55,620 --> 00:18:56,187 SECOND DEGREE RELATIVES AND 531 00:18:56,187 --> 00:18:58,356 THAT'S REALLY VERY SUSPICIOUS. 532 00:18:58,356 --> 00:19:00,592 LUCKILY, WE LIVE IN THE MODERN 533 00:19:00,592 --> 00:19:00,759 AGE. 534 00:19:00,759 --> 00:19:02,727 WE LIVE IN THE GENOMICS ERA, SO 535 00:19:02,727 --> 00:19:06,231 WHEN I STARTED OFF MY LAB, I 536 00:19:06,231 --> 00:19:10,068 IMMEDIATELY REALLY WENT FOR NEXT 537 00:19:10,068 --> 00:19:10,769 GENERATION SEQUENCING 538 00:19:10,769 --> 00:19:11,736 APPLICATIONS BECAUSE WE CAN NOW 539 00:19:11,736 --> 00:19:14,239 READ THE GENETIC INFORMATION AT 540 00:19:14,239 --> 00:19:15,774 SUCH AN ADVANCED CASE THAT WE 541 00:19:15,774 --> 00:19:19,044 CAN ACTUALLY PINPOINT VARIANTS 542 00:19:19,044 --> 00:19:22,881 IN RECORD TIME. 543 00:19:22,881 --> 00:19:25,116 AND SO I WANT TO JUST REVIEW 544 00:19:25,116 --> 00:19:26,184 WHAT THE KIND OF APPROACHES ARE 545 00:19:26,184 --> 00:19:27,919 THAT WE ARE USING IN GENETICS. 546 00:19:27,919 --> 00:19:35,460 SO IF WE HAVE FAMILIES, WE 547 00:19:35,460 --> 00:19:39,097 TYPICALLY LIKE TO USE SO-CA 548 00:19:39,097 --> 00:19:40,098 SO-CALLED -- WE LOOK FOR 549 00:19:40,098 --> 00:19:41,299 MUTATIONS THAT OCCUR IN THE 550 00:19:41,299 --> 00:19:44,970 FAMILIES AND THAT SEG GREAT WITH 551 00:19:44,970 --> 00:19:45,837 THE DISEASE. 552 00:19:45,837 --> 00:19:46,604 THIS TOOL HAS BEEN SUPER 553 00:19:46,604 --> 00:19:47,706 SUCCESSFUL IN THE PEDIATRIC 554 00:19:47,706 --> 00:19:49,574 COMMUNITY WHERE WE HAVE LOTS OF 555 00:19:49,574 --> 00:19:50,775 FAMILY MEMBERS THAT MAY BE 556 00:19:50,775 --> 00:19:51,876 AFFECTED. 557 00:19:51,876 --> 00:19:54,379 HOWEVER, IN OUR AGED COMMUNITY, 558 00:19:54,379 --> 00:19:56,414 THIS HAS REALLY BEEN DIFFICULT. 559 00:19:56,414 --> 00:19:58,883 WE MAY HAVE FAMILY HISTORIES BUT 560 00:19:58,883 --> 00:20:00,785 WE OFTEN DO NOT HAVE MULTIPLE 561 00:20:00,785 --> 00:20:01,186 GENERATIONS ALIVE. 562 00:20:01,186 --> 00:20:03,722 SO OUR MAIN WORKHORSE, SO TO 563 00:20:03,722 --> 00:20:05,023 SPEAK, ARE ASSOCIATION STUDY 564 00:20:05,023 --> 00:20:05,890 TESTS. 565 00:20:05,890 --> 00:20:07,759 SO ASSOCIATION STUDIES ARE 566 00:20:07,759 --> 00:20:08,760 BASICALLY COMPARING LARGE 567 00:20:08,760 --> 00:20:10,495 COHORTS OF CASES VERSUS 568 00:20:10,495 --> 00:20:12,464 CONTROLS, AND WE CAN BASICALLY 569 00:20:12,464 --> 00:20:15,100 LOOK FOR DIFFERENCES IN THEM, 570 00:20:15,100 --> 00:20:16,968 EITHER AT A GENE LEVEL OR 571 00:20:16,968 --> 00:20:18,069 GENOME-WIDE IDEA MAYBE BECAUSE 572 00:20:18,069 --> 00:20:20,238 THEN WE CAN DO UNBIASED 573 00:20:20,238 --> 00:20:20,772 GENOME-WIDE SCREENING. 574 00:20:20,772 --> 00:20:23,308 SO THIS IS A PLOT THAT WE 575 00:20:23,308 --> 00:20:25,510 GENETICISTS JUST LOVE TO SHOW. 576 00:20:25,510 --> 00:20:29,314 IT'S NAMED AFTER NHGRI 577 00:20:29,314 --> 00:20:31,649 INVESTIGATOR TERRY WHO FIRST 578 00:20:31,649 --> 00:20:32,050 SHOWED THAT. 579 00:20:32,050 --> 00:20:35,453 IT BASICALLY ENCAPSULATES HOW WE 580 00:20:35,453 --> 00:20:37,088 THINK ABOUT A COMPLEX GENETIC 581 00:20:37,088 --> 00:20:38,923 DISEASE SUCH AS A DEMENTIA 582 00:20:38,923 --> 00:20:40,625 SYNDROME WHERE WE HAVE A SMALL 583 00:20:40,625 --> 00:20:41,493 SUBSEGMENT OF THE PATIENT 584 00:20:41,493 --> 00:20:47,832 POPULATION THAT HAS -- WE WANT 585 00:20:47,832 --> 00:20:50,802 TO USE A STATISTICAL TOOL CALLED 586 00:20:50,802 --> 00:20:51,669 LINKAGE ANALYSIS. 587 00:20:51,669 --> 00:20:52,971 HOWEVER, THE MOST PATIENTS THAT 588 00:20:52,971 --> 00:20:55,140 WE SEE, THEY HAVE APPARENTLY 589 00:20:55,140 --> 00:20:56,374 SPORADIC DISEASE, AND FOR THOSE 590 00:20:56,374 --> 00:20:58,143 WE'RE USING A TOOL CALLED GENOME 591 00:20:58,143 --> 00:20:59,444 WIDE ASSOCIATION STUDIES, WHERE 592 00:20:59,444 --> 00:21:01,079 WE TEST MILLIONS OF VARIANTS 593 00:21:01,079 --> 00:21:02,614 ACROSS THE ENTIRE GENOME AND 594 00:21:02,614 --> 00:21:04,349 LOOK FOR SIGNIFICANT DIFFERENCES 595 00:21:04,349 --> 00:21:07,752 IN THE CASES VERSUS CONTROLS. 596 00:21:07,752 --> 00:21:09,621 IN BETWEEN, WE HAVE ANOTHER TEST 597 00:21:09,621 --> 00:21:10,822 THAT WE LIKE TO USE WHICH IS 598 00:21:10,822 --> 00:21:12,690 KIND OF AN IN BETWEEN WHERE WE 599 00:21:12,690 --> 00:21:14,659 HAVE A HYPOTHESIS IN MIND AND WE 600 00:21:14,659 --> 00:21:17,162 CAN LOOK FOR AN ASSOCIATION. 601 00:21:17,162 --> 00:21:20,999 SO FOR EXAMPLE, DO WE SEE 602 00:21:20,999 --> 00:21:23,935 ENRICHMENT OF DAMAGING MUTATIONS 603 00:21:23,935 --> 00:21:25,603 IN A CERTAIN PATHWAY OR IN A 604 00:21:25,603 --> 00:21:26,805 CERTAIN GENE, AND THAT CAN HELP 605 00:21:26,805 --> 00:21:28,440 US SEE IF THERE ARE ACTUAL 606 00:21:28,440 --> 00:21:30,408 DISEASE RELATIONSHIPS. 607 00:21:30,408 --> 00:21:32,410 BUT HAVING THAT SAID, ONCE WE 608 00:21:32,410 --> 00:21:37,515 PINPOINT WHERE A PROBLEM IS, OUR 609 00:21:37,515 --> 00:21:39,584 WORK ISN'T DONE AS GENETICISTS. 610 00:21:39,584 --> 00:21:41,086 SO OVER THE LAST DECADE IN 611 00:21:41,086 --> 00:21:42,320 PARTICULAR, THERE'S A WHOLE NEW 612 00:21:42,320 --> 00:21:44,089 FIELD WHICH HAS EMERGED WHICH IS 613 00:21:44,089 --> 00:21:45,957 CALL WOULD THE FUNCTIONAL 614 00:21:45,957 --> 00:21:47,058 GENOMICS FIELD, WHERE WE 615 00:21:47,058 --> 00:21:48,026 ESSENTIALLY TRY TO ADD 616 00:21:48,026 --> 00:21:49,094 ADDITIONAL LAYERS OF OMIC 617 00:21:49,094 --> 00:21:50,962 INFORMATION ON TOP OF THE 618 00:21:50,962 --> 00:21:53,498 GENOME, SO FOR EXAMPLE, WE HAVE 619 00:21:53,498 --> 00:21:54,599 RISK VARIANTS IN A CERTAIN AREA 620 00:21:54,599 --> 00:21:56,868 OF THE GENOME THAT WE THINK ARE 621 00:21:56,868 --> 00:21:58,303 INVOLVED BUT WE STILL DON'T KNOW 622 00:21:58,303 --> 00:22:00,071 WHICH OF THE MANY VARIANTS IN 623 00:22:00,071 --> 00:22:03,108 THERE ARE ACTUALLY DRIVING THE 624 00:22:03,108 --> 00:22:03,875 DISEASE SUSCEPTIBILITY. 625 00:22:03,875 --> 00:22:05,643 SO BY DOING STATISTICAL TESTS, 626 00:22:05,643 --> 00:22:07,712 WE CAN LOOK AT WHICH TRANSCRIPTS 627 00:22:07,712 --> 00:22:10,415 HAVE CHANGED, WHICH PROTEINS ARE 628 00:22:10,415 --> 00:22:11,549 CHANGED, AND IN A WAY WE'RE 629 00:22:11,549 --> 00:22:15,153 REALLY TRYING TO USE A SYSTEMS 630 00:22:15,153 --> 00:22:17,222 BIOLOGY FRAMEWORK TO PIN POIT .. 631 00:22:17,222 --> 00:22:18,656 WHAT ARE THE VARIANTS, WHAT ARE 632 00:22:18,656 --> 00:22:19,858 THE POSSIBLE MECHANISMS AS TO 633 00:22:19,858 --> 00:22:23,128 HOW IT'S RELATED TO DISEASE. 634 00:22:23,128 --> 00:22:24,229 THIS SOUNDS SOMEWHAT SIMPLIFIED 635 00:22:24,229 --> 00:22:26,865 BUT IT CAN HELP US REALLY WITH 636 00:22:26,865 --> 00:22:27,565 PRIORITIZING WHICH VARIANTS 637 00:22:27,565 --> 00:22:29,033 WE'RE GOING TO TEST IN A MODEL 638 00:22:29,033 --> 00:22:30,368 SYSTEM, WHICH IS WHERE IT GETS 639 00:22:30,368 --> 00:22:33,872 REALLY INVOLVED AND EXPENSIVE. 640 00:22:33,872 --> 00:22:35,940 SO WE ARE USING A COHORT THAT WE 641 00:22:35,940 --> 00:22:36,908 ESTABLISHED OVER THE LAST COUPLE 642 00:22:36,908 --> 00:22:38,676 OF YEARS, AND I'M GOING TO JUST 643 00:22:38,676 --> 00:22:40,445 VERY BRIEFLY HIGHLIGHT WHAT WENT 644 00:22:40,445 --> 00:22:41,746 INTO THIS. 645 00:22:41,746 --> 00:22:43,515 SO WE PERFORMED WHOLE GENOME 646 00:22:43,515 --> 00:22:45,717 SEQUENCING IN ABOUT 2600 LEWY 647 00:22:45,717 --> 00:22:46,551 BODY DEMENTIA CASES FROM ALL 648 00:22:46,551 --> 00:22:48,219 ACROSS EUROPE, ALL ACROSS NORTH 649 00:22:48,219 --> 00:22:49,521 AMERICA, WENT TO ALL SORTS OF 650 00:22:49,521 --> 00:22:51,923 BRAIN BANKS WE COULD POSSIBLY 651 00:22:51,923 --> 00:22:55,760 FIND, AND WE WERE REALLY 652 00:22:55,760 --> 00:22:57,428 EMPHASIZING WELL CHARACTERIZED 653 00:22:57,428 --> 00:22:57,962 CASES. 654 00:22:57,962 --> 00:23:00,732 ABOUT 70% OF THE CASES WERE FROM 655 00:23:00,732 --> 00:23:01,666 PATHOLOGIC CONFIRMED INDIVIDUALS 656 00:23:01,666 --> 00:23:04,102 AND THE REMAINING CASES WERE 657 00:23:04,102 --> 00:23:05,537 CLINICALLY PROBABLE DISEASE 658 00:23:05,537 --> 00:23:06,938 CASES, REALLY CASES WHERE WE 659 00:23:06,938 --> 00:23:08,473 WERE PRETTY SURE THAT'S THEIR 660 00:23:08,473 --> 00:23:09,374 CLINICAL SYNDROME WE'RE TRYING 661 00:23:09,374 --> 00:23:10,108 TO STUDY. 662 00:23:10,108 --> 00:23:12,510 ALL OF THESE INDIVIDUALS WERE 663 00:23:12,510 --> 00:23:15,680 GENOME SEQUENCED USING UNIFORM 664 00:23:15,680 --> 00:23:18,983 PIPELINE AND UNIFORM VARIANT 665 00:23:18,983 --> 00:23:19,984 CULLING, THEN WE WENT TO WORK. 666 00:23:19,984 --> 00:23:21,819 WE PUT OUR GWAS APPROACH TO GOOD 667 00:23:21,819 --> 00:23:23,988 USE HERE. 668 00:23:23,988 --> 00:23:26,724 SO WHEN WE DID THAT, WE 669 00:23:26,724 --> 00:23:27,926 IDENTIFIED THERE WERE FIVE MAJOR 670 00:23:27,926 --> 00:23:29,994 RISK SIGNALS ASSOCIATED WITH 671 00:23:29,994 --> 00:23:31,796 LEWY BODY DEMENTIA 672 00:23:31,796 --> 00:23:32,463 SUSCEPTIBILITY. 673 00:23:32,463 --> 00:23:39,003 SO THESE ARE GBA, SNCA, APOE, 674 00:23:39,003 --> 00:23:40,438 BIN1 AND TMEM175. 675 00:23:40,438 --> 00:23:42,707 THREE OF THOSE HAVE ALREADY BEEN 676 00:23:42,707 --> 00:23:45,143 IMPLICATED BASED ON CANADA GENE 677 00:23:45,143 --> 00:23:46,644 WORK, SO WE WERE REALLY 678 00:23:46,644 --> 00:23:51,683 REASSURED TO SH SEE THEM SHOWINP 679 00:23:51,683 --> 00:23:55,620 HERE. 680 00:23:55,620 --> 00:23:57,488 -- IN PARKINSON DISEASE AND 681 00:23:57,488 --> 00:23:58,556 ALZHEIMER'S DISEASE, AND NOW 682 00:23:58,556 --> 00:24:00,558 WE'RE SEEING THEM SHOWING UP 683 00:24:00,558 --> 00:24:02,860 HERE IN OUR LEWY BODY DEMENTIA 684 00:24:02,860 --> 00:24:05,430 PATIENT POPULATION, WHICH REALLY 685 00:24:05,430 --> 00:24:07,832 SUGGESTS THAT LEWY BODY DEMENTIA 686 00:24:07,832 --> 00:24:08,700 PROBABLY SITS SOMEWHERE ALONG 687 00:24:08,700 --> 00:24:11,202 THE SPECTRUM BETWEEN THESE TWO 688 00:24:11,202 --> 00:24:13,271 DISEASES, AND THE GENETIC 689 00:24:13,271 --> 00:24:14,405 ARCHITECTURES ARE LIKELY TO 690 00:24:14,405 --> 00:24:16,007 OVERLAP. 691 00:24:16,007 --> 00:24:17,108 SO THAT'S JUST A SIMPLIFIED 692 00:24:17,108 --> 00:24:17,342 VIEW. 693 00:24:17,342 --> 00:24:18,643 THIS IS JUST WITHOUT GOING INTO 694 00:24:18,643 --> 00:24:21,279 THE DETAILS. 695 00:24:21,279 --> 00:24:26,317 BUT I MENTIONED ONCE WE HAVE A 696 00:24:26,317 --> 00:24:28,953 SIGNAL IN GWAS, WE CAN DELVE IN 697 00:24:28,953 --> 00:24:29,254 FURTHER. 698 00:24:29,254 --> 00:24:31,489 WE USED A TRANSCRIPTOMICS DATA 699 00:24:31,489 --> 00:24:33,658 AND USED A SO-CALLED 700 00:24:33,658 --> 00:24:34,158 COLOCALIZATION ANALYSIS. 701 00:24:34,158 --> 00:24:36,828 IN DOING SO, WE WERE ABLE TO 702 00:24:36,828 --> 00:24:38,563 REALLY HIGHLIGHT A FUNCTIONAL 703 00:24:38,563 --> 00:24:41,633 VARIANT THAT SEEMS TO BE 704 00:24:41,633 --> 00:24:43,701 AFFECTING THE EXPRESSION OF THIS 705 00:24:43,701 --> 00:24:47,639 PROTEIN OF SNCA THAT ENCODES THE 706 00:24:47,639 --> 00:24:49,307 ALPHA SYNUCLEIN PROTEIN. 707 00:24:49,307 --> 00:24:50,942 SO THE TRANSCRIPT THAT SEEMS TO 708 00:24:50,942 --> 00:24:56,514 REGULATE IT IS CALLED SNCA AS-#. 709 00:24:56,514 --> 00:25:03,087 BAS-1.PARKINSON'S DISEASE, THE N 710 00:25:03,087 --> 00:25:06,257 SIGNAL IS ACTUALLY COMING FROM 711 00:25:06,257 --> 00:25:07,992 AN ENTRONIC SEQUENCE SO THERE'S 712 00:25:07,992 --> 00:25:09,961 A DIFFERENCE ONCE YOU REALLY 713 00:25:09,961 --> 00:25:10,862 START TO ZOOM IN. 714 00:25:10,862 --> 00:25:12,397 BASED ON OUR EVALUATION, WHAT 715 00:25:12,397 --> 00:25:16,534 OUR DATA SUGGESTS IS THAT THE 716 00:25:16,534 --> 00:25:18,136 RISK IS -- ACTUALLY IT'S A 717 00:25:18,136 --> 00:25:19,170 PROTECTIVE ONE, IF YOU HAVE THIS 718 00:25:19,170 --> 00:25:20,371 RISK ALLELE, YOU ACTUALLY 719 00:25:20,371 --> 00:25:23,641 PRODUCE A LITTLE BIT LESS OF 720 00:25:23,641 --> 00:25:25,943 ALPHA SYNUCLEIN PROTEIN THAT'S 721 00:25:25,943 --> 00:25:27,045 PROTECTIVE IN LEWY BODY 722 00:25:27,045 --> 00:25:27,679 DEMENTIA. 723 00:25:27,679 --> 00:25:28,680 THINKING THAT THROUGH, IT ALSO 724 00:25:28,680 --> 00:25:30,415 SUGGESTS THAT BY LOWERING ALPHA 725 00:25:30,415 --> 00:25:32,517 SYNUCLEIN, YOU MAY BE ABLE TO 726 00:25:32,517 --> 00:25:34,485 PROTECT, YOU MAY HAVE A DISEASE 727 00:25:34,485 --> 00:25:35,787 MODIFYING STRATEGY FOR PATIENTS 728 00:25:35,787 --> 00:25:37,422 WITH LEWY BODY DEMENTIA. 729 00:25:37,422 --> 00:25:39,524 SO THAT'S JUST ONE OF THE WAYS 730 00:25:39,524 --> 00:25:44,028 WE ARE TRYING TO COMBINE GENETIC 731 00:25:44,028 --> 00:25:46,764 SIGNALS WITH POSSIBLE FUNCTIONAL 732 00:25:46,764 --> 00:25:48,933 EFFECTS. 733 00:25:48,933 --> 00:25:49,834 NOW LOOKING AT A DIFFERENT 734 00:25:49,834 --> 00:25:51,703 SEGMENT OF THE GENETIC ARCTIC 735 00:25:51,703 --> 00:25:54,205 SURE, WE CAN ALSO LOOK AT 736 00:25:54,205 --> 00:25:57,275 DAMAGING MUTATIONS THAT ARE RARE 737 00:25:57,275 --> 00:25:58,943 BUT THAT ARE ENRICHED IN CERTAIN 738 00:25:58,943 --> 00:26:00,678 GENES, AND SO THE WAY WE DID 739 00:26:00,678 --> 00:26:04,115 THAT IS BY BASICALLY LOOKING ON 740 00:26:04,115 --> 00:26:05,750 GENE-BASED GENE BURDEN TESTS 741 00:26:05,750 --> 00:26:09,153 ACROSS THE ENTIRE GENOME, POWER 742 00:26:09,153 --> 00:26:10,455 IS ALWAYS AN ISSUE BUT IF YOU 743 00:26:10,455 --> 00:26:11,856 HAVE A REALLY COMMON RISK GENE, 744 00:26:11,856 --> 00:26:12,523 YOU SEE SOMETHING. 745 00:26:12,523 --> 00:26:15,259 WE WERE VERY LUCKY TO ACTUALLY 746 00:26:15,259 --> 00:26:18,429 SEE THAT MUTATIONS, MISSENSE 747 00:26:18,429 --> 00:26:19,430 MUTATIONS BUT ALSO LOSS OF 748 00:26:19,430 --> 00:26:21,499 FUNCTION MUTATIONS IN THE GBA 749 00:26:21,499 --> 00:26:23,134 GENE WHICH WE HAD SEEN IN THE 750 00:26:23,134 --> 00:26:26,637 GWAS AS WELL ACTUALLY SHOWING 751 00:26:26,637 --> 00:26:27,839 UP -- IT'S A MAJOR GENE, AND 752 00:26:27,839 --> 00:26:30,908 ONCE YOU SEE THAT, WE REFER TO 753 00:26:30,908 --> 00:26:32,343 IT AS PLEIOMORPHIC. 754 00:26:32,343 --> 00:26:35,179 COMMON VARIANT AND YOU OFTEN 755 00:26:35,179 --> 00:26:36,180 HAVE MORE RARE VARIANTS. 756 00:26:36,180 --> 00:26:38,249 IN TOTAL WHEN WE SUM UP ALL OF 757 00:26:38,249 --> 00:26:40,551 THE RISK ALLELE CARRIERS, WE SEE 758 00:26:40,551 --> 00:26:43,054 IT IN ABOUT 13% OF PATIENTS WITH 759 00:26:43,054 --> 00:26:45,156 LEWY BODY DEMENTIA, AND IT A 760 00:26:45,156 --> 00:26:45,790 MAJOR RISK GENE FOR THIS 761 00:26:45,790 --> 00:26:47,225 DISEASE, A MAJOR TARGET FOR 762 00:26:47,225 --> 00:26:50,161 THERAPY DEVELOPMENTS. 763 00:26:50,161 --> 00:26:52,597 AND SO THIS IS REALLY SOMETHING 764 00:26:52,597 --> 00:26:53,765 THAT'S BEEN QUITE EXCITING AND 765 00:26:53,765 --> 00:26:55,333 WE'RE GOING TO HEAR MORE ABOUT 766 00:26:55,333 --> 00:26:57,735 THIS PARTICULAR GENE AS WE MOVE 767 00:26:57,735 --> 00:27:00,171 FORWARD. 768 00:27:00,171 --> 00:27:01,472 THE OTHER CONCEPT THAT I REALLY 769 00:27:01,472 --> 00:27:02,774 WANTED TO INTRODUCE IS THE 770 00:27:02,774 --> 00:27:05,943 CONCEPT OF POLYGENIC RISK. 771 00:27:05,943 --> 00:27:07,845 SO UNLIKE MENDELIAN DISEASE 772 00:27:07,845 --> 00:27:09,113 WHERE YOU HAVE ONE MAJOR DEFECT 773 00:27:09,113 --> 00:27:12,283 THAT IS CAUSING A DISEASE, 774 00:27:12,283 --> 00:27:13,151 POLYGENIC DISEASE IS MORE 775 00:27:13,151 --> 00:27:15,353 MULTIPLE SMALLER RISK VARIANTS 776 00:27:15,353 --> 00:27:17,855 COMING TOGETHER, PLAYING A ROLE. 777 00:27:17,855 --> 00:27:19,924 WE CAN DO SOME INTERESTING 778 00:27:19,924 --> 00:27:21,025 STATISTIC MODELING BY BASICALLY 779 00:27:21,025 --> 00:27:23,127 HAVING A STATISTICAL TOOL TO SUM 780 00:27:23,127 --> 00:27:26,297 UP THE POLYGENIC RISK, SO YOU 781 00:27:26,297 --> 00:27:28,266 MAY HAVE MULTIPLE DIFFERENT 782 00:27:28,266 --> 00:27:29,700 SMALL RISK VARIANTS, WHICH IS 783 00:27:29,700 --> 00:27:31,002 UNLUCKY ENOUGH, AND IF YOU HAVE 784 00:27:31,002 --> 00:27:34,305 A LOT, IT CAN REALLY AFFECT THE 785 00:27:34,305 --> 00:27:36,607 WAY YOU PRESENT, AFFECT THE AGE 786 00:27:36,607 --> 00:27:38,109 THAT YOU PRESENT, AFFECT THE 787 00:27:38,109 --> 00:27:38,576 SEVERITY. 788 00:27:38,576 --> 00:27:40,645 AND SO WE CAN USE THAT FOR 789 00:27:40,645 --> 00:27:41,512 MULTIPLE DIFFERENT THINGS. 790 00:27:41,512 --> 00:27:43,581 WE CAN USE POLYGENIC RISK SCORES 791 00:27:43,581 --> 00:27:45,783 TO EXAMINE THE RELATIONSHIPS 792 00:27:45,783 --> 00:27:49,253 BETWEEN COMPLEX TRAITS, WE CAN 793 00:27:49,253 --> 00:27:52,323 SUBSTRATIFY PATIENTS BASED ON 794 00:27:52,323 --> 00:27:54,091 HIGH POLYGENIC RISK VERSUS NO 795 00:27:54,091 --> 00:27:57,028 POLYGENIC RI RISKS, AND WE CAN K 796 00:27:57,028 --> 00:27:58,162 AT INTERESTING PHENOTYPE 797 00:27:58,162 --> 00:27:58,563 CORRELATIONS. 798 00:27:58,563 --> 00:28:05,336 SO NOW OUR COHORT, WE COULD 799 00:28:05,336 --> 00:28:06,771 DEMONSTRATE TA TIS PARTICULARLY 800 00:28:06,771 --> 00:28:08,506 THAT THERE'S A REAL GENETIC 801 00:28:08,506 --> 00:28:09,740 OVERLAP BETWEEN LEWY BODY 802 00:28:09,740 --> 00:28:10,341 DEMENTIA, ALZHEIMER'S DISEASE 803 00:28:10,341 --> 00:28:11,809 AND PARKINSON'S DISEASE. 804 00:28:11,809 --> 00:28:14,412 SO BY ESSENTIALLY APPLYING THE 805 00:28:14,412 --> 00:28:15,980 POLYGENIC RISK SCORES THAT WE 806 00:28:15,980 --> 00:28:18,483 HAVE DEVELOPED FOR PARKINSON'S 807 00:28:18,483 --> 00:28:19,784 DISEASE AND ALZHEIMER'S DISEASE 808 00:28:19,784 --> 00:28:21,219 TO OUR LEWY BODY DEMENTIA 809 00:28:21,219 --> 00:28:23,621 POPULATION, WE CAN SEE THEY 810 00:28:23,621 --> 00:28:26,023 ARE -- THEY HAVE A STATISTICALLY 811 00:28:26,023 --> 00:28:27,358 HIGHER RISK AND IT REMAINS HIGH 812 00:28:27,358 --> 00:28:29,093 EVEN WHEN WE REMOVE THE HIGH 813 00:28:29,093 --> 00:28:29,527 RISK VARIANTS. 814 00:28:29,527 --> 00:28:32,263 WE ALSO ARE SEEING ENRICHMENT OF 815 00:28:32,263 --> 00:28:33,598 GENETIC DEFECTS IN CERTAIN 816 00:28:33,598 --> 00:28:34,565 PATHWAYS THAT ARE ALWAYS COMING 817 00:28:34,565 --> 00:28:37,201 UP IN NEURODEGENERATION AND THE 818 00:28:37,201 --> 00:28:41,672 THING THAT'S REALLY EMERGING IS 819 00:28:41,672 --> 00:28:42,874 PATHWAYS THAT ARE IMPORTANT FOR 820 00:28:42,874 --> 00:28:45,843 PROTEIN DEGRADATION, FOR ENDO 821 00:28:45,843 --> 00:28:46,310 LYSOSOMAL TRANSPORT. 822 00:28:46,310 --> 00:28:47,712 SO AGAIN AND AGAIN, IT 823 00:28:47,712 --> 00:28:48,813 HIGHLIGHTS PATHWAYS REALLY 824 00:28:48,813 --> 00:28:50,081 RELEVANT FOR THERAPY DEVELOPMENT 825 00:28:50,081 --> 00:28:52,850 ACROSS THE WHOLE GAMUT OF 826 00:28:52,850 --> 00:28:57,121 NEURODEGENERATIVE DISEASES. 827 00:28:57,121 --> 00:28:58,489 NOW I WANT TO SWITCH GEARS A 828 00:28:58,489 --> 00:28:59,223 LITTLE BIT. 829 00:28:59,223 --> 00:29:00,591 SO EVERYTHING THAT I HAVE TOLD 830 00:29:00,591 --> 00:29:02,960 YOU SO FAR HAS REALLY BEEN 831 00:29:02,960 --> 00:29:06,664 FOCUSED ON SMALL GENETIC 832 00:29:06,664 --> 00:29:07,565 CHANGES, SINGLE LETTER CHANGES 833 00:29:07,565 --> 00:29:08,199 IN THE GENOME. 834 00:29:08,199 --> 00:29:09,600 BUT THERE ARE ACTUALLY A LOT OF 835 00:29:09,600 --> 00:29:10,768 OTHER CHANGES THAT CAN HAPPEN IN 836 00:29:10,768 --> 00:29:13,004 THE GENETIC CODE. 837 00:29:13,004 --> 00:29:16,274 AND LARGER CHANGES ARE SO CALLED 838 00:29:16,274 --> 00:29:17,041 STRUCTURAL VARIANTS WHERE YOU 839 00:29:17,041 --> 00:29:18,910 HAVE EITHER AN ENTIRE ADDITIONAL 840 00:29:18,910 --> 00:29:19,911 TRUNK OR SOMETHING IS MISSING OR 841 00:29:19,911 --> 00:29:24,649 SOMETHING IS INVERTED, AND 842 00:29:24,649 --> 00:29:25,650 INTERESTINGLY ACTUALLY, THESE 843 00:29:25,650 --> 00:29:28,953 CHUNKS OR STRUCTURAL VARIANTS 844 00:29:28,953 --> 00:29:30,121 ARE ACTUALLY AN IMPORTANT SOURCE 845 00:29:30,121 --> 00:29:30,888 IN OUR EVOLUTION. 846 00:29:30,888 --> 00:29:32,089 AND WE DON'T UNDERSTAND THEM 847 00:29:32,089 --> 00:29:33,090 QUITE AS WELL, IT'S VERY 848 00:29:33,090 --> 00:29:35,159 DIFFICULT TO STUDY THEM AND TO 849 00:29:35,159 --> 00:29:37,261 MAP THEM SYSTEMATICALLY, BUT WE 850 00:29:37,261 --> 00:29:38,796 HAVE GOOD REASON TO SUSPECT THAT 851 00:29:38,796 --> 00:29:40,231 THEY COULD PLAY AN IMPORTANT 852 00:29:40,231 --> 00:29:43,601 ROLE IN LEWY BODY DEMENTIA BASED 853 00:29:43,601 --> 00:29:46,671 ON RARE FAMILIES WHERE WE HAVE 854 00:29:46,671 --> 00:29:49,106 SEEN HAVING EXTRA COPIES FOR 855 00:29:49,106 --> 00:29:57,748 EXAMPLE OF THE SCNA GENE, GBA 856 00:29:57,748 --> 00:29:58,516 RECOMBINATION ARE RARE CAUSE OF 857 00:29:58,516 --> 00:29:58,849 IT. 858 00:29:58,849 --> 00:30:00,585 SO WE HAVE GENOME SEQUENCE DATA, 859 00:30:00,585 --> 00:30:02,320 WE WERE ABLE TO USE MODERN 860 00:30:02,320 --> 00:30:04,288 COMPUTATIONAL TOOLS TO 861 00:30:04,288 --> 00:30:05,623 ESSENTIALLY PREDICT STRUCTURAL 862 00:30:05,623 --> 00:30:06,724 VARIANTS ACROSS THE ENTIRE 863 00:30:06,724 --> 00:30:09,126 GENOME, AND THEN INSTEAD OF 864 00:30:09,126 --> 00:30:13,130 SINGLE KNEW CLEE T NUCLEOTIDE CD 865 00:30:13,130 --> 00:30:14,365 STRUCTURAL TESTING AGAIN. 866 00:30:14,365 --> 00:30:16,233 ONE OF THE VERY FIRST ONES IN 867 00:30:16,233 --> 00:30:18,302 THE WORLD TO REALLY USE A GENOME 868 00:30:18,302 --> 00:30:19,604 WIDE STRUCTURAL VARIANT 869 00:30:19,604 --> 00:30:21,272 ASSOCIATION STUDY. 870 00:30:21,272 --> 00:30:23,574 SO EVERY DOT ON THIS MAN TA TAN 871 00:30:23,574 --> 00:30:26,877 MANHATTANPLOT IS ACTUALLY A STRL 872 00:30:26,877 --> 00:30:27,945 VARIANT. 873 00:30:27,945 --> 00:30:29,213 LO AND BEHOLD WHEN WE DID THIS 874 00:30:29,213 --> 00:30:30,848 ANALYSIS, WE SAW ANOTHER RISK 875 00:30:30,848 --> 00:30:32,383 GENE POP UP THAT WE DIDN'T SEE 876 00:30:32,383 --> 00:30:33,951 USING THE SINGLE VARIANT 877 00:30:33,951 --> 00:30:35,920 ANALYSIS, WHICH WAS A DELETION 878 00:30:35,920 --> 00:30:37,121 POLYMORPHISM THAT IS ACTUALLY 879 00:30:37,121 --> 00:30:39,323 QUITE PREVALENT IN THE LEWY BODY 880 00:30:39,323 --> 00:30:40,291 DEMENTIA POPULATION. 881 00:30:40,291 --> 00:30:44,562 IT HAS A SIGNIFICANT RISK. 882 00:30:44,562 --> 00:30:46,864 ABOUT 1.4. 883 00:30:46,864 --> 00:30:48,599 AND WE WERE ABLE TO REPLICATE 884 00:30:48,599 --> 00:30:50,868 IT, VALIDATE IT USING LONG-READ 885 00:30:50,868 --> 00:30:51,369 SEQUENCING. 886 00:30:51,369 --> 00:30:54,105 IT'S PRESENT IN ABOUT 8% OF 887 00:30:54,105 --> 00:30:55,840 CASES. 888 00:30:55,840 --> 00:30:57,041 WE WERE IMMEDIATELY EXCITE TODAY 889 00:30:57,041 --> 00:30:59,010 FIND THAT BECAUSE IT ACTUALLY IS 890 00:30:59,010 --> 00:31:00,978 A GENE THAT HAS BEEN IMPLICATED 891 00:31:00,978 --> 00:31:01,512 PREVIOUSLY IN ALZHEIMER'S 892 00:31:01,512 --> 00:31:04,148 DISEASE, AND SO THIS IS A GWAS 893 00:31:04,148 --> 00:31:06,350 STUDY THAT INDICATED THIS 894 00:31:06,350 --> 00:31:08,319 PARTICULAR LOCUS BEFORE, IT 895 00:31:08,319 --> 00:31:09,520 DIDN'T QUITE REACH SIGNIFICANCE 896 00:31:09,520 --> 00:31:10,955 BUT IT REALLY WAS ONE OF THE 897 00:31:10,955 --> 00:31:13,658 SUGGESTED LOCI. 898 00:31:13,658 --> 00:31:14,659 AND THERE'S ALREADY BEEN SOME 899 00:31:14,659 --> 00:31:18,596 WORK ON THIS PARTICULAR GENE. 900 00:31:18,596 --> 00:31:25,136 IT'S A TWO PORT CHANNEL, 901 00:31:25,136 --> 00:31:27,471 ENDOLYSOSOMAL CHANNEL, 902 00:31:27,471 --> 00:31:30,975 INHIBITION COULD ACTUALLY 903 00:31:30,975 --> 00:31:32,276 AMELIORATE PATHOLOGY, SO IT 904 00:31:32,276 --> 00:31:35,680 REALLY HAS AN IMPACT SO IT'S AN 905 00:31:35,680 --> 00:31:37,415 INTERESTING TARGET FOR LEWY BODY 906 00:31:37,415 --> 00:31:37,815 DEMENTIA. 907 00:31:37,815 --> 00:31:41,485 NOW THAT WE KNOW THAT 908 00:31:41,485 --> 00:31:42,553 TPCN1 SEEMS TO BE PLAYING A ROLE 909 00:31:42,553 --> 00:31:43,654 IN ALZHEIMER'S DISEASE AND LEWY 910 00:31:43,654 --> 00:31:44,755 BODY DEMENTIA, WE DID A LITTLE 911 00:31:44,755 --> 00:31:46,290 BIT MORE WORK SO WE BASICALLY 912 00:31:46,290 --> 00:31:49,760 ZOOMED IN ON THE ASSOCIATION 913 00:31:49,760 --> 00:31:51,595 SIGNALS THAT EXIST IN 914 00:31:51,595 --> 00:31:53,731 ALZHEIMER'S DISEASE GWAS STUDIES 915 00:31:53,731 --> 00:31:55,232 VERSUS LEWY BODY DEMENTIA GWAS 916 00:31:55,232 --> 00:31:57,101 STUDIES AND LO AND BEHOLD, WE DO 917 00:31:57,101 --> 00:31:57,768 SEE A VERY STRONG CORRELATION, 918 00:31:57,768 --> 00:31:59,537 IT REALLY SEEMS TO BE THE SAME 919 00:31:59,537 --> 00:32:00,938 RISK GENES THAT SEEMS TO BE 920 00:32:00,938 --> 00:32:02,707 SHARED BETWEEN THOSE TWO 921 00:32:02,707 --> 00:32:05,443 DEMENTIA SYNDROMES. 922 00:32:05,443 --> 00:32:07,078 HOWEVER, WE DO NOT SEE SUCH A 923 00:32:07,078 --> 00:32:07,845 RELATIONSHIP WITH PARKINSON'S 924 00:32:07,845 --> 00:32:09,146 DISEASE, SO IT REALLY SEEMS TO 925 00:32:09,146 --> 00:32:10,581 BE ONE THAT'S MORE ASSOCIATED 926 00:32:10,581 --> 00:32:12,183 WITH ALZHEIMER'S AND LEWY BODY 927 00:32:12,183 --> 00:32:14,218 DEMENTIA PATHOLOGIES. 928 00:32:14,218 --> 00:32:15,419 ALL RIGHT. 929 00:32:15,419 --> 00:32:17,388 SO ONE OF THE THEMES THAT ARE 930 00:32:17,388 --> 00:32:18,689 CLEARLY EMERGING IS THIS TEAM 931 00:32:18,689 --> 00:32:20,658 THAT YOU CAN HAVE A RISK GENE 932 00:32:20,658 --> 00:32:22,760 AND IT CAN BE INVOLVED IN A 933 00:32:22,760 --> 00:32:24,295 WHOLE HOST OF DIFFERENT 934 00:32:24,295 --> 00:32:25,730 DISEASES, AND SO THE TECHNICAL 935 00:32:25,730 --> 00:32:33,504 TERM FOR THAT IS GENETIC 936 00:32:33,504 --> 00:32:34,138 PLEIOTROPY. 937 00:32:34,138 --> 00:32:35,139 IT'S GOOD NEWS IN A WAY BECAUSE 938 00:32:35,139 --> 00:32:36,774 IT INDICATES THERE IS SHARED 939 00:32:36,774 --> 00:32:37,775 BIOLOGY IN THE BACKGROUND, AND 940 00:32:37,775 --> 00:32:39,076 THAT BIOLOGY IS SOMETHING THAT 941 00:32:39,076 --> 00:32:41,045 WE CAN WORK WITH IN OUR MODEL 942 00:32:41,045 --> 00:32:43,347 SYSTEM AND IN OUR DRUG SCREENS. 943 00:32:43,347 --> 00:32:44,882 AND SO THERE ARE MULTIPLE 944 00:32:44,882 --> 00:32:45,983 EXAMPLES NOW IN LEWY BODY 945 00:32:45,983 --> 00:32:47,184 DEMENTIA WHERE WE HAVE SEEN 946 00:32:47,184 --> 00:32:49,386 THAT, BUT ALSO BEYOND THAT. 947 00:32:49,386 --> 00:32:52,356 AND I JUST WANT TO HIGHLIGHT ONE 948 00:32:52,356 --> 00:32:54,892 OTHER SUCCESS STORY ALONG THOSE 949 00:32:54,892 --> 00:32:57,928 LINES WHICH IS WHERE WE HAVE 950 00:32:57,928 --> 00:33:05,069 LOOKED AT MUTATIONS IN A KNOWN 951 00:33:05,069 --> 00:33:07,338 NEURODEGENERATIVE DISEASE. 952 00:33:07,338 --> 00:33:10,441 THE REASON FOR THAT WAS BECAUSE 953 00:33:10,441 --> 00:33:12,476 MANY PATIENTS WITH MUTATIONS IN 954 00:33:12,476 --> 00:33:13,811 THAT GENE ACTUALLY HAVE LEWY 955 00:33:13,811 --> 00:33:17,214 BODY PATHOLOGY IN ADDITION TO 956 00:33:17,214 --> 00:33:18,415 FRONTOTEMPORAL DEMENTIA 957 00:33:18,415 --> 00:33:21,018 PATHOLOGY, THE TDP43 PATHOLOGY. 958 00:33:21,018 --> 00:33:23,320 SO WE HAD HYPOTHESIZED MAYBE 959 00:33:23,320 --> 00:33:25,189 THERE IS AN ACTUAL RELATIONSHIP. 960 00:33:25,189 --> 00:33:27,725 LO AND BEHOLD ONCE WE LOOKED, WE 961 00:33:27,725 --> 00:33:29,593 SAW NOTES OF KNOWN DISEASE 962 00:33:29,593 --> 00:33:31,228 CAUSING MUTATIONS ENRICHED IN 963 00:33:31,228 --> 00:33:33,631 OUR LEWY BODY DEMENTIA PATIENT 964 00:33:33,631 --> 00:33:34,832 POPULATION, ALTHOUGH THEY ARE 965 00:33:34,832 --> 00:33:39,203 RARE, THEY DO EXIST, AND WE DO 966 00:33:39,203 --> 00:33:40,771 SEE GENUINE COPATHOLOGY, SO WE 967 00:33:40,771 --> 00:33:44,041 SEE THE SINGLE -- PATHOLOGY WE 968 00:33:44,041 --> 00:33:45,009 ASSOCIATE WITH LEWY BODY 969 00:33:45,009 --> 00:33:50,414 DEMENTIA BUT WE ALSO SEE TD 970 00:33:50,414 --> 00:33:52,249 TDP43 PATHOLOGY, WHERE IT'S BEEN 971 00:33:52,249 --> 00:33:53,117 ORIGINALLY DESCRIBED. 972 00:33:53,117 --> 00:33:54,752 CLINICALLY THESE CASES REALLY 973 00:33:54,752 --> 00:33:56,086 CAN HAVE EITHER WAY, THEY CAN 974 00:33:56,086 --> 00:33:59,223 PRESENT WITH MORE FRONTOTEMPORAL 975 00:33:59,223 --> 00:34:00,124 DEMENTIA-LIKE PRESENTATIONS OR 976 00:34:00,124 --> 00:34:01,992 AS IN OUR CASE WHAT REALLY LOOKS 977 00:34:01,992 --> 00:34:05,930 LIKE CLASSICAL CLINICAL DEMENTIA 978 00:34:05,930 --> 00:34:07,898 WITH LEWY BODIES. 979 00:34:07,898 --> 00:34:09,433 WHAT THAT MEANS IS THAT IT'S 980 00:34:09,433 --> 00:34:10,434 IMPORTANT TO RECOGNIZE THESE 981 00:34:10,434 --> 00:34:11,635 CASES BECAUSE INCREASINGLY WE 982 00:34:11,635 --> 00:34:13,037 CAN USE GENETIC INFORMATION IN 983 00:34:13,037 --> 00:34:14,939 THE CLINICAL SETTING, WE CAN 984 00:34:14,939 --> 00:34:17,308 IDENTIFY THESE PATIENTS, AND CAN 985 00:34:17,308 --> 00:34:19,510 FUNNEL THEM INTO GENE THERAPY 986 00:34:19,510 --> 00:34:21,612 TRIALS AND OTHER TARGETED 987 00:34:21,612 --> 00:34:23,013 THERAPEUTIC INTERVENTIONS, SO 988 00:34:23,013 --> 00:34:24,114 FOR THOSE CASES IT'S REALLY 989 00:34:24,114 --> 00:34:26,617 IMPORTANT TO RECOGNIZE THEM. 990 00:34:26,617 --> 00:34:33,324 AND ACTUALLY TARGETED CLINICAL 991 00:34:33,324 --> 00:34:36,160 TRIALS THAT ARE ACTUALLY ONGOING 992 00:34:36,160 --> 00:34:37,027 SO INTERESTING TO KNOW. 993 00:34:37,027 --> 00:34:38,896 SO THAT REALLY BRINGS ME TO THE 994 00:34:38,896 --> 00:34:41,632 LAST SECTION OF MY PRESENTATION, 995 00:34:41,632 --> 00:34:44,268 WHICH IS, YOU KNOW, IT'S NICE 996 00:34:44,268 --> 00:34:45,269 ACADEMIC EXERCISE THAT WE'RE 997 00:34:45,269 --> 00:34:46,804 DOING HERE, BUT WHAT DOES IT 998 00:34:46,804 --> 00:34:50,074 ACTUALLY MEAN FOR THE PATIENTS? 999 00:34:50,074 --> 00:34:51,942 SO THERE ARE SOME VERY IMMEDIATE 1000 00:34:51,942 --> 00:34:53,911 IMPLICATIONS FOR THE CLINICAL 1001 00:34:53,911 --> 00:34:55,880 PRACTICE, SO ONE IS THAT WE 1002 00:34:55,880 --> 00:34:57,548 INCREASINGLY ACTUALLY OFFER 1003 00:34:57,548 --> 00:34:59,183 GENETIC COUNSELING, GENETIC 1004 00:34:59,183 --> 00:35:00,918 TESTING IN OUR DEMENTIA 1005 00:35:00,918 --> 00:35:01,685 POPULATION. 1006 00:35:01,685 --> 00:35:03,020 BUT THAT REALLY HAS CHANGED OVER 1007 00:35:03,020 --> 00:35:04,321 THE LAST 10 YEARS. 1008 00:35:04,321 --> 00:35:07,725 AND YOU KNOW, WE CAN OFFER THAT 1009 00:35:07,725 --> 00:35:10,127 NOT JUST TO PATIENTS WITH CLEAR 1010 00:35:10,127 --> 00:35:11,662 FAMILY HISTORY BUT ALSO 1011 00:35:11,662 --> 00:35:13,297 APPARENTLY SPORADIC CASES. 1012 00:35:13,297 --> 00:35:14,431 REASON WHY IT IS HELPFUL IS 1013 00:35:14,431 --> 00:35:15,833 BECAUSE IT CAN HELP US WITH 1014 00:35:15,833 --> 00:35:17,368 ESTABLISHING THE MOLECULAR 1015 00:35:17,368 --> 00:35:20,304 DIAGNOSIS WHEN WE'VE IDENTIFIED 1016 00:35:20,304 --> 00:35:21,605 MAINTAINING DISEASE, BUT IT CAN 1017 00:35:21,605 --> 00:35:23,707 ALSO REALLY REFINE OUR ABILITY 1018 00:35:23,707 --> 00:35:25,442 TO COUNSEL AND TO STUDY AND 1019 00:35:25,442 --> 00:35:26,877 FOLLOW THESE PATIENTS AND GET 1020 00:35:26,877 --> 00:35:28,412 THEM INTO THE RIGHT KIND OF 1021 00:35:28,412 --> 00:35:29,813 CLINICAL TRIALS THAT ARE 1022 00:35:29,813 --> 00:35:31,382 BECOMING MUCH, MUCH MORE PRECISE 1023 00:35:31,382 --> 00:35:34,451 AND MUCH, MUCH MORE FOCUSED ON 1024 00:35:34,451 --> 00:35:36,620 CERTAIN MOLECULAR SUBTYPES. 1025 00:35:36,620 --> 00:35:38,489 AND THERE'S GOOD REASON TO BE 1026 00:35:38,489 --> 00:35:41,225 HOPEFUL AND TO HAVE THE CLASS IS 1027 00:35:41,225 --> 00:35:42,526 HALF FULL KIND OF ATTITUDE. 1028 00:35:42,526 --> 00:35:44,762 SO GENOMICS HAS REALLY BEEN 1029 00:35:44,762 --> 00:35:45,596 REVOLUTIONIZING THE DRUG 1030 00:35:45,596 --> 00:35:47,264 DEVELOPMENT PI PIPELINE. 1031 00:35:47,264 --> 00:35:49,867 THERE'S BEEN MULTIPLE SUCCESS 1032 00:35:49,867 --> 00:35:52,403 STORIES. 1033 00:35:52,403 --> 00:35:53,604 INTERNAL MEDICINE AND 1034 00:35:53,604 --> 00:35:54,371 NEUROLOGISTS WE STILL HAVE TO 1035 00:35:54,371 --> 00:35:55,372 CATCH UP AS WE'RE MAPPING OUT 1036 00:35:55,372 --> 00:35:58,309 THE GENETIC ARCHITECTURE FOR 1037 00:35:58,309 --> 00:35:59,643 MANY OF THE DISEASES. 1038 00:35:59,643 --> 00:36:05,582 SO IN 2021, ABOUT A THIRD OF 1039 00:36:05,582 --> 00:36:07,084 APPROVED DRUGS HAVE HAD GENETIC 1040 00:36:07,084 --> 00:36:08,185 SUPPORT AND IT'S GOING UP 1041 00:36:08,185 --> 00:36:10,054 BECAUSE WE'RE STARTING TO HAVE A 1042 00:36:10,054 --> 00:36:11,689 REAL ANCHOR AS TO HOW WE MODEL 1043 00:36:11,689 --> 00:36:13,123 THE DISEASES AND HOW WE 1044 00:36:13,123 --> 00:36:14,091 UNDERSTAND DISEASES AND 1045 00:36:14,091 --> 00:36:15,292 ULTIMATELY HOW WE TARGET THE 1046 00:36:15,292 --> 00:36:16,393 DEEDS, AND THAT'S REALLY WHERE 1047 00:36:16,393 --> 00:36:19,797 WE'RE TRYING TO GO. 1048 00:36:19,797 --> 00:36:21,165 I'M GOING TO SHOW YOU ONE STUDY 1049 00:36:21,165 --> 00:36:25,703 WHERE WE HAVE IMPLICATED 1050 00:36:25,703 --> 00:36:27,137 INTERESTING DRUGS FOR LEWY BODY 1051 00:36:27,137 --> 00:36:28,539 DEMENTIA SPECIFICALLY, AND HOW 1052 00:36:28,539 --> 00:36:31,308 WE CAN LEVERAGE GENOMIC DATA TO 1053 00:36:31,308 --> 00:36:32,710 REALLY PROVIDE MOLECULAR 1054 00:36:32,710 --> 00:36:33,043 SUPPORT. 1055 00:36:33,043 --> 00:36:36,113 SO THIS IS A STUDY THAT ONE OF 1056 00:36:36,113 --> 00:36:38,649 MY PANDEMIC EXERCISES WITH 1057 00:36:38,649 --> 00:36:42,686 DR. RUTH PFEIFFER FROM NCI THAT 1058 00:36:42,686 --> 00:36:47,725 REALLY LOOKED AT THE U.S. 1059 00:36:47,725 --> 00:36:49,259 MEDICARE CLAIMS DATABASE, A 1060 00:36:49,259 --> 00:36:50,461 HEALTHCARE DATABASE FOR 1061 00:36:50,461 --> 00:36:51,762 INDIVIDUALS OF THE AGE OF 65 OR 1062 00:36:51,762 --> 00:36:52,997 ABOVE. 1063 00:36:52,997 --> 00:36:56,166 AND BASED ON THAT, WE WERE ABLE 1064 00:36:56,166 --> 00:36:58,769 TO QUERY WHICH ARE PATIENTS WHO 1065 00:36:58,769 --> 00:37:00,871 HAVE LEWY BODY DEMENTIA AND WHO 1066 00:37:00,871 --> 00:37:02,840 ARE NEUROLOGICALLY HEALTHY 1067 00:37:02,840 --> 00:37:04,141 CONTROLS, SO YOU CAN REALLY PULL 1068 00:37:04,141 --> 00:37:05,809 THEM OUT. 1069 00:37:05,809 --> 00:37:07,378 AND THEN WHAT WE DID WAS WE 1070 00:37:07,378 --> 00:37:09,213 LOOKED AT THOSE THAT HAD LEWY 1071 00:37:09,213 --> 00:37:11,648 BODY DEMENTIA AND REVIEWED WHAT 1072 00:37:11,648 --> 00:37:14,184 WAS THE DRUG PRESCRIPTION 1073 00:37:14,184 --> 00:37:15,386 PATTERN THREE YEARS BEFORE THEY 1074 00:37:15,386 --> 00:37:15,919 MANIFESTED WITH DISEASE. 1075 00:37:15,919 --> 00:37:18,122 AND WE WANT TO GO INTO THE 1076 00:37:18,122 --> 00:37:19,356 PRODROMAL PHASE OF THE DISEASE 1077 00:37:19,356 --> 00:37:21,225 WHERE WE REALLY WANT TO 1078 00:37:21,225 --> 00:37:21,892 POTENTIALLY HELP THE PATIENT, WE 1079 00:37:21,892 --> 00:37:24,028 WANT TO KNOW WHAT'S POTENTIALLY 1080 00:37:24,028 --> 00:37:26,030 PROTECTED. 1081 00:37:26,030 --> 00:37:28,999 AND SO WHAT WE WERE QUITE 1082 00:37:28,999 --> 00:37:30,034 ASTONISHED TO FIND WAS THAT ANY 1083 00:37:30,034 --> 00:37:32,403 OF THE CARDIOVASCULAR DISEASE 1084 00:37:32,403 --> 00:37:33,470 MANAGEMENT DRUG CLASSES WAS 1085 00:37:33,470 --> 00:37:37,107 COMING UP AS PROTECTIVE AND THAT 1086 00:37:37,107 --> 00:37:38,976 REALLY HIGHLIGHTS THE OVERALL 1087 00:37:38,976 --> 00:37:40,978 THEME OF OUR TALK TODAY, THE 1088 00:37:40,978 --> 00:37:42,146 VASCULAR RISK FACTOR IS REALLY 1089 00:37:42,146 --> 00:37:43,680 IMPORTANT IN NEURODEGENERATION, 1090 00:37:43,680 --> 00:37:44,681 SO WE NEED TO PAY ATTENTION TO 1091 00:37:44,681 --> 00:37:45,182 IT. 1092 00:37:45,182 --> 00:37:46,984 BUT THAT WAS ONLY THE 1093 00:37:46,984 --> 00:37:49,086 EPIDEMIOLOGICAL PART OF THE 1094 00:37:49,086 --> 00:37:49,520 STUDY. 1095 00:37:49,520 --> 00:37:53,891 SO THEN ONCE WE SAW THAT, WE HAD 1096 00:37:53,891 --> 00:38:01,031 PROVE SEISHYPOTHESIZED -- BETWEN 1097 00:38:01,031 --> 00:38:02,666 CARDIOVASCULAR DISEASES AND LEWY 1098 00:38:02,666 --> 00:38:05,169 BODY DEMENTIA, WE KNOW THEIR 1099 00:38:05,169 --> 00:38:06,937 GENETIC ARCHITECTURE, THE RISK 1100 00:38:06,937 --> 00:38:11,775 SCORE FOR HYPERTENSION, WE CAN 1101 00:38:11,775 --> 00:38:13,210 ACTUALLY LOOK AT GENETIC 1102 00:38:13,210 --> 00:38:13,544 CORRELATIONS. 1103 00:38:13,544 --> 00:38:15,312 WHEN WE DID THAT, LO AND BEHOLD 1104 00:38:15,312 --> 00:38:17,848 WE FOUND SIGNIFICANT GENETIC 1105 00:38:17,848 --> 00:38:19,716 CORRELATIONS BETWEEN CARD JOE 1106 00:38:19,716 --> 00:38:21,351 VASCULAR DISEASE GENETIC 1107 00:38:21,351 --> 00:38:22,453 ARCHITECTURE AND LEWY BODY 1108 00:38:22,453 --> 00:38:22,820 DEMENTIA. 1109 00:38:22,820 --> 00:38:25,055 AND IN DOING SO CALLED 1110 00:38:25,055 --> 00:38:26,156 CONDITIONAL ANALYSIS, WE COULD 1111 00:38:26,156 --> 00:38:26,824 REALLY MODEL THAT IF YOU HAVE 1112 00:38:26,824 --> 00:38:28,459 ONE OF THOSE CARDIOVASCULAR 1113 00:38:28,459 --> 00:38:30,661 DISEASE RISK FACTORS, YOU REALLY 1114 00:38:30,661 --> 00:38:32,429 HAVE A HIGHER RISK OF LEWY BODY 1115 00:38:32,429 --> 00:38:35,165 DEMENTIA, AND THAT REALLY 1116 00:38:35,165 --> 00:38:36,500 SUGGESTS WE NEED TO BE PAYING 1117 00:38:36,500 --> 00:38:37,701 CLOSE ATTENTION TO THESE RISK 1118 00:38:37,701 --> 00:38:39,903 FACTORS IN THE MANAGEMENT OF OUR 1119 00:38:39,903 --> 00:38:41,371 PATIENTS AS THEY COULD BE REALLY 1120 00:38:41,371 --> 00:38:44,074 DISEASE MODIFYING. 1121 00:38:44,074 --> 00:38:45,676 I'M CERTAINLY NOT THE FIRST ONE 1122 00:38:45,676 --> 00:38:46,176 TO IMPLICATE THAT. 1123 00:38:46,176 --> 00:38:47,945 THERE'S REALLY AN EMERGING BODY 1124 00:38:47,945 --> 00:38:49,680 OF LITERATURE THAT SUGGESTS THAT 1125 00:38:49,680 --> 00:38:51,348 THESE VASCULAR RISK FACTORS ARE 1126 00:38:51,348 --> 00:38:53,083 REALLY DRIVING NEURODEGENERATION 1127 00:38:53,083 --> 00:38:55,519 ON A BIG SCALE, SO ACROSS THE 1128 00:38:55,519 --> 00:38:59,022 DEGENERATIVE DISEASES, DIABETES 1129 00:38:59,022 --> 00:39:01,091 MELLITUS INCREASES YOUR RISK FOR 1130 00:39:01,091 --> 00:39:03,060 NEURODEGENERATION AND IT SEGUES 1131 00:39:03,060 --> 00:39:04,628 QUITE NICELY INTO REBECCA'S 1132 00:39:04,628 --> 00:39:06,063 TALK, WHERE WE CAN REALLY REVIEW 1133 00:39:06,063 --> 00:39:07,898 HOW EXACTLY THAT INTERPLAY MAY 1134 00:39:07,898 --> 00:39:10,200 BE TAKING PLACE. 1135 00:39:10,200 --> 00:39:14,505 AND THE REAL CAUSAL 1136 00:39:14,505 --> 00:39:15,572 RELATIONSHIPS, THESE ARE 1137 00:39:15,572 --> 00:39:16,807 MODIFIABLE RISK FACTORS SO WE 1138 00:39:16,807 --> 00:39:17,808 CAN DO SOMETHING ABOUT THAT. 1139 00:39:17,808 --> 00:39:20,010 WE DON'T ALWAYS HAVE TO WAIT FOR 1140 00:39:20,010 --> 00:39:22,179 GENE THERAPY, ADDRESSING 1141 00:39:22,179 --> 00:39:23,814 VASCULAR RISK FACTORS IN 1142 00:39:23,814 --> 00:39:24,481 NEURODEGENERATION IS REALLY 1143 00:39:24,481 --> 00:39:26,116 IMPORTANT. 1144 00:39:26,116 --> 00:39:27,317 SO WHERE THE OVERALL FIELD IS 1145 00:39:27,317 --> 00:39:28,652 GOING WITH THE GENOMIC 1146 00:39:28,652 --> 00:39:29,887 INFORMATION IS THAT, YES, WE'RE 1147 00:39:29,887 --> 00:39:31,522 LEARNING MORE ABOUT THE 1148 00:39:31,522 --> 00:39:34,024 UNDERLYING MOLECULAR MECHANISM 1149 00:39:34,024 --> 00:39:36,226 THAT ARE INVOLVED IN UNDERLYING 1150 00:39:36,226 --> 00:39:38,195 MOLECULAR PATHWAYS AND WE CAN 1151 00:39:38,195 --> 00:39:38,795 PINPOINT CERTAIN INTEREST IN 1152 00:39:38,795 --> 00:39:40,831 THOSE THAT ARE AFFECTED NOT JUST 1153 00:39:40,831 --> 00:39:42,166 IN OUR DISEASE OF INTEREST BUT 1154 00:39:42,166 --> 00:39:43,133 ACROSS THE BROADER SPECTRUM THAT 1155 00:39:43,133 --> 00:39:46,103 HELPS US PR PRIORITIZE WHICH DRS 1156 00:39:46,103 --> 00:39:47,771 TO PUT INTO THE PIPELINE, WHICH 1157 00:39:47,771 --> 00:39:50,073 DRUGS WE SHOULD ACTUALLY BRING 1158 00:39:50,073 --> 00:39:51,808 FORTH FOR CLINICAL TRIALS. 1159 00:39:51,808 --> 00:39:53,110 ULTIMATELY REALLY THE GENETICS 1160 00:39:53,110 --> 00:39:55,479 IS THE DRIVING ENGINE BEHIND 1161 00:39:55,479 --> 00:39:57,748 WHAT WE KNOW AS POSITION -- 1162 00:39:57,748 --> 00:39:59,416 WHERE WE TRY TO REALLY BRING IN 1163 00:39:59,416 --> 00:40:00,817 THE RIGHT KIND OF TREATMENT FOR 1164 00:40:00,817 --> 00:40:02,152 THE RIGHT PATIENT, THE RIGHT 1165 00:40:02,152 --> 00:40:03,687 POINT OF TIME, AND THAT'S REALLY 1166 00:40:03,687 --> 00:40:05,889 WHAT THE GOAL IS. 1167 00:40:05,889 --> 00:40:07,424 SO THE KEY MESSAGES IN THE FIRST 1168 00:40:07,424 --> 00:40:09,960 HALF OF THE TALK WAS I WANTED TO 1169 00:40:09,960 --> 00:40:11,395 REALLY HIGHLIGHT THAT THERE ARE 1170 00:40:11,395 --> 00:40:12,396 RAPID ADVANCES IN OUR 1171 00:40:12,396 --> 00:40:17,734 UNDERSTANDING OF SO CALLED 1172 00:40:17,734 --> 00:40:18,635 NON-ALZHEIMER'S DEMENTIAS AND 1173 00:40:18,635 --> 00:40:20,070 REAL INTRICATE RELATIONSHIPS 1174 00:40:20,070 --> 00:40:22,839 BETWEEN VASCULAR RISK AND 1175 00:40:22,839 --> 00:40:23,807 NEURODEGENERATION. 1176 00:40:23,807 --> 00:40:26,777 WE'RE INCREASING USER MOLECULAR 1177 00:40:26,777 --> 00:40:27,911 INSIGHTS TO DEVELOP NEW 1178 00:40:27,911 --> 00:40:29,012 THERAPIES AND HOPEFULLY BRING A 1179 00:40:29,012 --> 00:40:30,881 CURE FOR THE DEMENTIA EPIDEMIC 1180 00:40:30,881 --> 00:40:31,748 THAT WE'RE DEALING WITH RIGHT 1181 00:40:31,748 --> 00:40:32,349 NOW. 1182 00:40:32,349 --> 00:40:34,551 SO WITH THAT, I WANT TO 1183 00:40:34,551 --> 00:40:35,886 HIGHLIGHT, THIS IS ALL TEAM 1184 00:40:35,886 --> 00:40:37,955 SCIENCE THAT I'M SHOWING YOU 1185 00:40:37,955 --> 00:40:40,157 HERE, SO NONE OF THAT IS MY 1186 00:40:40,157 --> 00:40:42,226 WORK, IT IS ALL OUR WORK AND WE 1187 00:40:42,226 --> 00:40:44,061 HAVE A FABULOUS NEUROSCIENCE 1188 00:40:44,061 --> 00:40:45,195 COMMUNITY HERE AND WE HAVE LODZ 1189 00:40:45,195 --> 00:40:46,863 OF GREAT SUPPORTERS AND 1190 00:40:46,863 --> 00:40:48,832 COLLABORATORS, SO I'M VERY 1191 00:40:48,832 --> 00:40:49,833 GRATEFUL ALSO TO UR A PATIENT'S 1192 00:40:49,833 --> 00:40:53,237 AND FAMILIES FOR WORKING WITH US 1193 00:40:53,237 --> 00:40:54,304 AND NEVER GIVING UP HOPE. 1194 00:40:54,304 --> 00:40:55,672 SO WITH THAT, I'M GOING TO STOP 1195 00:40:55,672 --> 00:40:57,407 HERE AND HAND OVER THE PODIUM TO 1196 00:40:57,407 --> 00:41:05,215 REBECCA FOR HER TALK. 1197 00:41:05,215 --> 00:41:06,183 >> WONDERFUL. 1198 00:41:06,183 --> 00:41:08,919 THANK YOU SO MUCH, SONJA, FOR AN 1199 00:41:08,919 --> 00:41:09,586 ABSOLUTELY WONDERFUL TALK. 1200 00:41:09,586 --> 00:41:11,021 THANK YOU FOR HAVING ME. 1201 00:41:11,021 --> 00:41:12,022 I'M SO SORRY THAT I'M NOT THERE 1202 00:41:12,022 --> 00:41:13,991 IN PERSON. 1203 00:41:13,991 --> 00:41:18,161 TO INTERACT WITH EVERYONE. 1204 00:41:18,161 --> 00:41:19,263 ABOUT I'M REALLY LOOKING FORWARD 1205 00:41:19,263 --> 00:41:20,330 TO CONTINUED DISCUSSION AT THE 1206 00:41:20,330 --> 00:41:24,368 END OF MY TALK. 1207 00:41:24,368 --> 00:41:27,738 SO AS SONJA BEAUTIFULLY OUTLI 1208 00:41:27,738 --> 00:41:28,405 OUTLINED, I'M GOING TO TALK 1209 00:41:28,405 --> 00:41:29,873 ABOUT THE VASCULAR CONTRIBUTIONS 1210 00:41:29,873 --> 00:41:31,608 TO DEMENTIA BROADLY AND TO 1211 00:41:31,608 --> 00:41:32,276 NEURODEGENERATION. 1212 00:41:32,276 --> 00:41:34,711 AND I'M REALLY -- THANK YOU, 1213 00:41:34,711 --> 00:41:36,113 SONJA, FOR GOING OVER SOME 1214 00:41:36,113 --> 00:41:37,347 REALLY IMPORTANT EVIDENCE BOTH 1215 00:41:37,347 --> 00:41:38,649 FROM YOUR OWN WORK BUT ALSO IN 1216 00:41:38,649 --> 00:41:40,317 THE CONTEXT OF HOW WE THINK 1217 00:41:40,317 --> 00:41:44,054 ABOUT DEMENTIA MORE BROADLY. 1218 00:41:44,054 --> 00:41:45,555 HERE ARE MY OWN DISCLOSURES 1219 00:41:45,555 --> 00:41:47,224 FUNDED BY THE INTRAMURAL 1220 00:41:47,224 --> 00:41:47,991 RESEARCH PROGRAM AT NINDS. 1221 00:41:47,991 --> 00:41:49,192 SO YOU'VE HEARD THIS MESSAGE 1222 00:41:49,192 --> 00:41:52,462 ALREADY AND I DON'T WANT TO 1223 00:41:52,462 --> 00:41:54,231 DWELL ON IT TOO MUCH BUT REALLY, 1224 00:41:54,231 --> 00:41:55,432 WE KNOW THAT AS THE POPULATION 1225 00:41:55,432 --> 00:41:57,868 AGES, THE EPIDEMIC OF DEMENTIA 1226 00:41:57,868 --> 00:41:58,969 BROADLY IS A GROWING THREAT IN 1227 00:41:58,969 --> 00:42:00,704 THE COMING DECADES. 1228 00:42:00,704 --> 00:42:04,675 POTASSBOTH IN HIGH-INCOME COUNTS 1229 00:42:04,675 --> 00:42:06,443 AND EVEN MORE SO IN ID EL INCOME 1230 00:42:06,443 --> 00:42:07,644 COUNTRIES AS YOU CAN SEE IN THIS 1231 00:42:07,644 --> 00:42:08,312 GRAPHIC. 1232 00:42:08,312 --> 00:42:09,513 AS YOU'VE HEARD, ALZHEIMER'S 1233 00:42:09,513 --> 00:42:12,916 DISEASE IS THE LEADING CAUSE OF 1234 00:42:12,916 --> 00:42:13,483 DEMENTIA. 1235 00:42:13,483 --> 00:42:14,685 ALTHOUGH THERE ARE SOME 1236 00:42:14,685 --> 00:42:15,419 TREATMENTS AVAILABLE AND OTHERS 1237 00:42:15,419 --> 00:42:17,554 IN THE WORKS, GENERALLY EFFECT 1238 00:42:17,554 --> 00:42:18,855 SIZES HAVE BEEN MODEST OR DRUGS 1239 00:42:18,855 --> 00:42:20,190 HAVE BEEN INEFFECTIVE WHERE IT'S 1240 00:42:20,190 --> 00:42:21,391 NOT CLEAR THAT THEY MODIFY THE 1241 00:42:21,391 --> 00:42:23,360 PATH OF DISEASE IN GENERAL. 1242 00:42:23,360 --> 00:42:26,997 SO THIS IS WHY THINKING WITH 1243 00:42:26,997 --> 00:42:28,799 VASCULAR RISK AND VASCULAR 1244 00:42:28,799 --> 00:42:31,068 CONTRIBUTIONS IS REALLY 1245 00:42:31,068 --> 00:42:35,639 APPEALING. 1246 00:42:35,639 --> 00:42:37,407 I WANT TO TELL YOU A LITTLE BIT 1247 00:42:37,407 --> 00:42:38,241 ABOUT VASCULAR DEMENTIA. 1248 00:42:38,241 --> 00:42:41,178 SO IN THEORY, THE IDEA OF 1249 00:42:41,178 --> 00:42:42,512 VASCULAR DEMENTIA, HI WISCONSIN 1250 00:42:42,512 --> 00:42:44,181 HAS ALSO BEEN CALLED 1251 00:42:44,181 --> 00:42:46,049 MULTI-INFARCT DEMENTIA, 1252 00:42:46,049 --> 00:42:49,853 SOMETIMES BINSWANGERS TO REFER 1253 00:42:49,853 --> 00:42:53,056 TO SUBCORTICAL VASCULAR 1254 00:42:53,056 --> 00:42:55,058 DEMENTIA, OR CADASIL, THESE ARE 1255 00:42:55,058 --> 00:42:56,727 ALL DIFFERENT TYPES OF VASCULAR 1256 00:42:56,727 --> 00:42:57,127 DEMENTIA. 1257 00:42:57,127 --> 00:43:01,198 IN GENERAL, THE CLASSICALLY 1258 00:43:01,198 --> 00:43:03,600 DEFINED IS RAPID ONSET, STEP 1259 00:43:03,600 --> 00:43:05,569 WISE PROGRESSION OF SYMPTOMS, 1260 00:43:05,569 --> 00:43:06,336 SOMETIMES AFTER A STROKE BUT 1261 00:43:06,336 --> 00:43:08,672 OFTEN NOT. 1262 00:43:08,672 --> 00:43:11,208 ANTITHE NINDS-AIREN CRITERIA 1263 00:43:11,208 --> 00:43:13,076 ESTABLISHED IN 1993 REQUIRE THE 1264 00:43:13,076 --> 00:43:15,412 PRESENCE OF THOSE COMPONENTS, SO 1265 00:43:15,412 --> 00:43:17,914 SOME FORM OF SCREEN ROW VASCULAR 1266 00:43:17,914 --> 00:43:18,915 DISEASE, WHETHER A STROKE OR 1267 00:43:18,915 --> 00:43:23,186 FINDINGS ON NEUROIMAGING, 1268 00:43:23,186 --> 00:43:24,187 DEMENTIA, AND THEN RELATIONSHIP 1269 00:43:24,187 --> 00:43:25,255 BETWEEN THE TWO THAT APPEARS TO 1270 00:43:25,255 --> 00:43:25,689 LINK THEM. 1271 00:43:25,689 --> 00:43:27,891 SO THE DIAGNOSIS IN GENERAL 1272 00:43:27,891 --> 00:43:29,459 REQUIRES BOTH THE COGNITIVE 1273 00:43:29,459 --> 00:43:30,961 DISORDER AND THEN EITHER STROKE 1274 00:43:30,961 --> 00:43:33,397 OR EVIDENCE OF INFARCT OR 1275 00:43:33,397 --> 00:43:34,831 STROKE-LIKE FINDINGS ON IMAGING. 1276 00:43:34,831 --> 00:43:36,366 HERE'S AN EXAMPLE, THIS IS AN 1277 00:43:36,366 --> 00:43:38,435 MRI WITH A LARGE STROKE, HERE'S 1278 00:43:38,435 --> 00:43:41,338 EVIDENCE OF BRIGHT MATTER 1279 00:43:41,338 --> 00:43:41,905 HYPERINTENSITIES, WHICH ARE 1280 00:43:41,905 --> 00:43:43,173 OFTEN SEEN IN PEOPLE WITH 1281 00:43:43,173 --> 00:43:43,974 LONG-STANDING HYPERTENSION. 1282 00:43:43,974 --> 00:43:44,941 WE'LL TALK A LITTLE BIT ABOUT 1283 00:43:44,941 --> 00:43:45,742 THAT LATER. 1284 00:43:45,742 --> 00:43:47,177 YOU HEARD A BIT ABOUT THE 1285 00:43:47,177 --> 00:43:48,812 DOMAINS, THE COGNITIVE DOMAINS 1286 00:43:48,812 --> 00:43:50,580 OF THE MOST COMMONLY AFFECTED, 1287 00:43:50,580 --> 00:43:52,015 PEOPLE WITH ALZHEIMER'S DISEASE 1288 00:43:52,015 --> 00:43:53,550 AS WELL AS OTHER NON-AD 1289 00:43:53,550 --> 00:43:55,285 DEMENTIAS FOR VASCULAR DEMENTIA, 1290 00:43:55,285 --> 00:43:56,953 THE CLASSIC SET OF DOMAINS THAT 1291 00:43:56,953 --> 00:43:58,288 ARE AFFECTED ARE EXECUTIVE 1292 00:43:58,288 --> 00:44:00,123 FUNCTION AND ATTENTION. 1293 00:44:00,123 --> 00:44:02,759 MEMORY MAY NOT BE AS AFFECTED 1294 00:44:02,759 --> 00:44:03,860 WHICH MEANS SOMETIMES THIS IS 1295 00:44:03,860 --> 00:44:05,162 DIAGNOSED AT A LATER STAGE IN 1296 00:44:05,162 --> 00:44:05,862 THE DISEASE. 1297 00:44:05,862 --> 00:44:08,265 AND CLINICALLY, WE THINK ABOUT 1298 00:44:08,265 --> 00:44:09,499 VASCULAR DEMENTIA AS THE SECOND 1299 00:44:09,499 --> 00:44:11,034 LEADING CAUSE OF DEMENTIA, 1300 00:44:11,034 --> 00:44:12,335 ACCOUNTING FOR THAT 20% OF DMEP 1301 00:44:12,335 --> 00:44:15,372 DEMENTIA CASES AND THE ESTIMATES 1302 00:44:15,372 --> 00:44:17,407 ARE CERTAINLY A LOT LOWER FOR 1303 00:44:17,407 --> 00:44:18,308 WHAT WE SEE FOR ALZHEIMER'S 1304 00:44:18,308 --> 00:44:18,542 DISEASE. 1305 00:44:18,542 --> 00:44:20,977 THE PROBLEM IS, PURE VASCULAR 1306 00:44:20,977 --> 00:44:23,447 DEMENTIA REALLY FITTING THESE 1307 00:44:23,447 --> 00:44:24,548 CRITERIA AND BY THESE 1308 00:44:24,548 --> 00:44:26,049 DEFINITIONS IS RELATIVELY RARE. 1309 00:44:26,049 --> 00:44:27,184 THIS IS FOR THE SAME REASONS 1310 00:44:27,184 --> 00:44:28,285 THAT SONJA JUST OUTLINED THAT 1311 00:44:28,285 --> 00:44:30,020 I'M GOING TO GET INTO IN A LOT 1312 00:44:30,020 --> 00:44:30,587 MORE DETAIL. 1313 00:44:30,587 --> 00:44:32,122 SO IN GENERAL WHEN WE THINK 1314 00:44:32,122 --> 00:44:33,156 ABOUT VASCULAR DEMENTIA, THERE'S 1315 00:44:33,156 --> 00:44:34,524 BEEN A SHIFT TO NOT THINK ABOUT 1316 00:44:34,524 --> 00:44:36,092 THIS PURE ENTITY THAT OCCURS 1317 00:44:36,092 --> 00:44:39,563 AFTER A STROKE OR IN EVIDENCE OF 1318 00:44:39,563 --> 00:44:41,131 THESE IMAGING MARKERS AND HAS 1319 00:44:41,131 --> 00:44:43,433 THE STEP WISE PROGRESSION BUT 1320 00:44:43,433 --> 00:44:44,634 WHAT WE CALL VASCULAR 1321 00:44:44,634 --> 00:44:45,635 CONTRIBUTIONS TO COGNITIVE 1322 00:44:45,635 --> 00:44:46,837 IMPAIRMENT AND DEMENTIA. 1323 00:44:46,837 --> 00:44:50,006 SO HERE'S A NICE BEAUTIFUL 1324 00:44:50,006 --> 00:44:53,677 GRAPHIC FROM ROB CORRIVEAU HAS 1325 00:44:53,677 --> 00:44:55,545 PUBLISHED AND USES A LOT WHEN I 1326 00:44:55,545 --> 00:44:57,714 DISCUSSES THIS CONCEPT OF A 1327 00:44:57,714 --> 00:44:59,149 VCID, WHICH ALLOWS US TO HAVE A 1328 00:44:59,149 --> 00:45:00,116 BROADER SET OF TERMS THAT REFER 1329 00:45:00,116 --> 00:45:02,018 TO THE MANY DIFFERENT WAYS THAT 1330 00:45:02,018 --> 00:45:02,886 VASCULAR RISK AND VASCULAR 1331 00:45:02,886 --> 00:45:06,289 HEALTH CAN AFFECT COGNITIVE 1332 00:45:06,289 --> 00:45:08,859 COMEN SLA AND BRAIN HEALTH IN 1333 00:45:08,859 --> 00:45:09,192 GENERAL. 1334 00:45:09,192 --> 00:45:10,594 AS YOU CAN SEE THERE'S A LONG 1335 00:45:10,594 --> 00:45:11,695 LIST OF POSSIBLE WAYS AND 1336 00:45:11,695 --> 00:45:13,163 POSSIBLE SUBSETS OF VASCULAR 1337 00:45:13,163 --> 00:45:15,398 CONTRIBUTIONS TO DEMENTIA, 1338 00:45:15,398 --> 00:45:17,634 RANGING FROM STROKE ITSELF TO 1339 00:45:17,634 --> 00:45:19,002 MICRO INFARCTS AND SMALL VESSEL 1340 00:45:19,002 --> 00:45:20,203 DISEASE AND OTHER CHANGES IN 1341 00:45:20,203 --> 00:45:20,871 BETWEEN. 1342 00:45:20,871 --> 00:45:25,909 INCLUDING THINGS LIKE CEREBRAL 1343 00:45:25,909 --> 00:45:28,545 AMYLOID ANGIOPATHY, FORMING 1344 00:45:28,545 --> 00:45:29,913 PLAQUES AND PAREN MA IN 1345 00:45:29,913 --> 00:45:31,448 ALZHEIMER'S DISEASE, IN THIS 1346 00:45:31,448 --> 00:45:32,782 CASE YOU GET FILLED UP IN THE 1347 00:45:32,782 --> 00:45:34,818 BLOOD VESSEL WALL, THAT'S 1348 00:45:34,818 --> 00:45:36,353 ANOTHER FORM OF VASCULAR 1349 00:45:36,353 --> 00:45:37,387 CONTRIBUTIONS TO DEMENTIA. 1350 00:45:37,387 --> 00:45:38,788 HERE'S SOME EXAMPLES OF WAYS IN 1351 00:45:38,788 --> 00:45:41,758 WHICH VASCULAR DISEASE AND 1352 00:45:41,758 --> 00:45:43,093 ADVERSE VASCULAR HEALTH CAN 1353 00:45:43,093 --> 00:45:46,096 AFFECT COGNITIVE HEALTH AND 1354 00:45:46,096 --> 00:45:46,396 DEMENTIA. 1355 00:45:46,396 --> 00:45:49,032 THIS IS A WORKSHOP WHERE WE 1356 00:45:49,032 --> 00:45:50,333 PUBLISHED THE FINDINGS AFTER A 1357 00:45:50,333 --> 00:45:51,868 GROUP OF EXPERT GOT TOGETHER AND 1358 00:45:51,868 --> 00:45:53,103 THOUGHT ABOUT ALL OF THE 1359 00:45:53,103 --> 00:45:55,071 POTENTIAL MECHANISMS BY WHICH 1360 00:45:55,071 --> 00:45:56,706 VASCULAR RISK MIGHT AFFECT THE 1361 00:45:56,706 --> 00:45:58,475 BRAIN AND NEURONAL HEALTH, AND 1362 00:45:58,475 --> 00:46:00,143 HEALTH OF THE NEUROVASCULAR 1363 00:46:00,143 --> 00:46:00,677 UNIT. 1364 00:46:00,677 --> 00:46:02,312 AND CERTAINLY THERE'S FURTHER 1365 00:46:02,312 --> 00:46:03,847 WORK ON THESE MECHANISMS, I'LL 1366 00:46:03,847 --> 00:46:05,315 TALK A LITTLE WITH THEM SHORTLY 1367 00:46:05,315 --> 00:46:07,484 BUT I MOSTLY WANT TO FOCUS ON 1368 00:46:07,484 --> 00:46:09,019 THE EPIDEMIOLOGY OF WHAT WE KNOW 1369 00:46:09,019 --> 00:46:10,186 ABOUT VASCULAR CONTRIBUTIONS TO 1370 00:46:10,186 --> 00:46:10,687 DEMENTIA. 1371 00:46:10,687 --> 00:46:12,756 OKAY, I TOLD YOU I WOULD SHARE 1372 00:46:12,756 --> 00:46:13,523 ANOTHER PIE CHART. 1373 00:46:13,523 --> 00:46:15,959 HERE IS ANOTHER PIE CHART, AND 1374 00:46:15,959 --> 00:46:17,494 THESE ARE DATA FROM THE SAME 1375 00:46:17,494 --> 00:46:19,796 STUDY BUT BY JULIE SCHNEIDER 1376 00:46:19,796 --> 00:46:20,797 THAT SONJA PRESENTED EARLIER. 1377 00:46:20,797 --> 00:46:22,232 THIS HAS SHOWN YOU AGAIN, AMONG 1378 00:46:22,232 --> 00:46:24,534 PEOPLE WITH A CLINICAL DIAGNOSIS 1379 00:46:24,534 --> 00:46:26,336 PREMORTEM OF PROBABLE AD, OR 1380 00:46:26,336 --> 00:46:28,738 MILD COGNITIVE IMPAIRMENT OR 1381 00:46:28,738 --> 00:46:29,806 MCI, A PRECURSOR OFTEN TO. 1382 00:46:29,806 --> 00:46:32,042 A D, BUT A LESS THAN HALF AND 1383 00:46:32,042 --> 00:46:33,810 HER GRAPH IS MORE UPDATED 1384 00:46:33,810 --> 00:46:35,478 INCLUDES NEWER PATHOLOGIES SUCH 1385 00:46:35,478 --> 00:46:37,914 AT LATE THAT WE DIDN'T KNOW 1386 00:46:37,914 --> 00:46:39,215 ABOUT IN SOME OF THESE EARLIER 1387 00:46:39,215 --> 00:46:40,984 STUDIES, THAT PURE AD ITSELF, 1388 00:46:40,984 --> 00:46:42,419 EVEN IN SOMEONE WHO'S FELT 1389 00:46:42,419 --> 00:46:45,055 CLINICALLY TO HAVE PURE AD IS 1390 00:46:45,055 --> 00:46:46,690 RELATIVELY UNCOMMON, THAT IS NOT 1391 00:46:46,690 --> 00:46:47,657 ACCOUNTING FOR MOST CASES. 1392 00:46:47,657 --> 00:46:49,793 YOU CAN SEE HERE, THIS IS THESE 1393 00:46:49,793 --> 00:46:53,630 DIFFERENT PIE PIECES THAT ARE 1394 00:46:53,630 --> 00:46:55,498 ACCOUNTING FOR I BEING INFARCT, 1395 00:46:55,498 --> 00:46:59,502 LB BEING LUO B LEWY BODY, MANY E 1396 00:46:59,502 --> 00:47:01,504 FOUND TO HAVE THESE OVERLAPPING 1397 00:47:01,504 --> 00:47:02,038 PATHOLOGIES. 1398 00:47:02,038 --> 00:47:03,573 IN GENERAL, PATIENTS AT A 1399 00:47:03,573 --> 00:47:04,674 CERTAIN COGNITIVE LEVEL BEFORE 1400 00:47:04,674 --> 00:47:06,009 DEATH, THOSE WHO HAVE MORE 1401 00:47:06,009 --> 00:47:07,644 VASCULAR CHANGES IN THE BRAIN 1402 00:47:07,644 --> 00:47:09,279 HAVE FEWER ALZHEIMER'S DISEASE 1403 00:47:09,279 --> 00:47:10,513 CHANGES TO GET TO THAT 1404 00:47:10,513 --> 00:47:11,381 EQUIVALENT COGNITIVE LEVEL AND 1405 00:47:11,381 --> 00:47:13,683 IN GENERAL, WE JUST VERY 1406 00:47:13,683 --> 00:47:15,018 FREQUENTLY SEE THESE VASCULAR 1407 00:47:15,018 --> 00:47:15,919 CHANGES IN THE BRAIN OF PEOPLE 1408 00:47:15,919 --> 00:47:19,089 WHO DIE OF ALZHEIMER'S DISEASE. 1409 00:47:19,089 --> 00:47:20,624 AND OF NEURODEGENERATIVE 1410 00:47:20,624 --> 00:47:21,191 DISEASES IN GENERAL. 1411 00:47:21,191 --> 00:47:22,292 SO REALLY THINKING ABOUT HOW 1412 00:47:22,292 --> 00:47:24,928 THESE PATHOLOGIES OVERLAP IS 1413 00:47:24,928 --> 00:47:28,531 IMPORTANT. 1414 00:47:28,531 --> 00:47:29,699 VCID CAN TAKE A LOT OF DIFFERENT 1415 00:47:29,699 --> 00:47:31,635 FORMS AND VASCULAR DEMENTIA 1416 00:47:31,635 --> 00:47:33,837 ALTHOUGH IN A PURE FORM IS 1417 00:47:33,837 --> 00:47:35,639 RELATIVELY RARE, THIS IDEA OF 1418 00:47:35,639 --> 00:47:37,073 VCID MORE BROADLY IS NOT SO RARE 1419 00:47:37,073 --> 00:47:38,041 BUT IT'S GOING TO LOOK DIFFERENT 1420 00:47:38,041 --> 00:47:38,708 IN DIFFERENT PEOPLE. 1421 00:47:38,708 --> 00:47:41,945 SO HERE'S ALITTLE MORE DATA 1422 00:47:41,945 --> 00:47:44,881 WHERE I JUST SHARED SOME OF THE 1423 00:47:44,881 --> 00:47:45,315 INITIAL DATA. 1424 00:47:45,315 --> 00:47:49,152 WE HAVE 2,000 INDIVIDUALS WITH 1425 00:47:49,152 --> 00:47:49,853 POSTMORTEM EXAMS. 1426 00:47:49,853 --> 00:47:51,054 OVER HALF HAD SOME TYPE OF MIXED 1427 00:47:51,054 --> 00:47:55,125 THAT POLG,THAT POLG, AND A FIFTE 1428 00:47:55,125 --> 00:47:57,994 THOUGHT TO HAVE 1429 00:47:57,994 --> 00:47:59,195 NEURODEGENERATION HAD PURE 1430 00:47:59,195 --> 00:48:00,764 VASCULAR PATHOLOGY WITHOUT 1431 00:48:00,764 --> 00:48:02,532 NEURODEGENERATION, ANOTHER 1432 00:48:02,532 --> 00:48:04,100 QUARTER HAD NEURODEGENERATION 1433 00:48:04,100 --> 00:48:05,268 WITHOUT VASCULAR CHANGES AND WE 1434 00:48:05,268 --> 00:48:07,270 VERY FREQUENTLY SAW INFARCTS AS 1435 00:48:07,270 --> 00:48:08,705 WELL AS MICRO INFARCTS AS WELL. 1436 00:48:08,705 --> 00:48:11,207 THIS WAS INDEPENDENT OF CLINICAL 1437 00:48:11,207 --> 00:48:11,775 HISTORY OF STROKE. 1438 00:48:11,775 --> 00:48:12,909 SO THERE'S A LOT OF DIFFERENT 1439 00:48:12,909 --> 00:48:13,910 FORMS THIS CAN TAKE DID YOU WE 1440 00:48:13,910 --> 00:48:15,345 KNOW IN GENERAL THE MORE 1441 00:48:15,345 --> 00:48:16,312 VASCULAR DISEASE YOU HAVE, THE 1442 00:48:16,312 --> 00:48:17,347 WORSE YOUR COGNITION IS, AND 1443 00:48:17,347 --> 00:48:19,949 THIS IS SOMETHING THAT THEY SAW 1444 00:48:19,949 --> 00:48:20,283 CONSISTENTLY. 1445 00:48:20,283 --> 00:48:22,218 I WANT TO TALK A LITTLE BIT MORE 1446 00:48:22,218 --> 00:48:24,621 ABOUT ONE POTENTIAL FORM OF VCID 1447 00:48:24,621 --> 00:48:27,557 BEFORE I TALK ABOUT THE EVIDENCE 1448 00:48:27,557 --> 00:48:29,325 LINKING VASCULAR RISK WITH 1449 00:48:29,325 --> 00:48:30,126 DEMENTIA BECAUSE WE'RE GOING TO 1450 00:48:30,126 --> 00:48:34,631 TALK A LITTLE ABOUT NEUROIMAGING 1451 00:48:34,631 --> 00:48:37,701 AAS A WAY TO LINK THEM WITH 1452 00:48:37,701 --> 00:48:38,201 DEMENTIA AND ALZHEIMER'S 1453 00:48:38,201 --> 00:48:38,935 DISEASE. 1454 00:48:38,935 --> 00:48:40,136 SO CEREBRAL SMALL VESSEL DISEASE 1455 00:48:40,136 --> 00:48:42,338 IS ONE FORM OF VCID AND OFTEN A 1456 00:48:42,338 --> 00:48:43,139 COMMON ONE THAT WE THINK OF WHEN 1457 00:48:43,139 --> 00:48:45,775 WE'RE TALKING ABOUT VASCULAR 1458 00:48:45,775 --> 00:48:46,876 CONTRIBUTIONS TO DEMENTIA AND 1459 00:48:46,876 --> 00:48:47,644 COGNITIVE IMPAIRMENT. 1460 00:48:47,644 --> 00:48:48,945 THE STRIVE CONSORTIUM PUBLISHED 1461 00:48:48,945 --> 00:48:50,313 A SET OF CRITERIA BY WHICH WE 1462 00:48:50,313 --> 00:48:51,948 SHOULD BE THINKING ABOUT SMALL 1463 00:48:51,948 --> 00:48:53,850 VESSEL DISEASE BUT IN GENERAL, 1464 00:48:53,850 --> 00:48:56,419 THESE FINDINGS ARE SILENT 1465 00:48:56,419 --> 00:48:58,788 INFARCTS AND LARGE PERIVASCULAR 1466 00:48:58,788 --> 00:49:01,658 SPACES, THOSE WHITE MATTER 1467 00:49:01,658 --> 00:49:03,093 HYPERINTENSITIES SHOWN ON 1468 00:49:03,093 --> 00:49:08,798 EARLIER MRI SCAN, CEREBRAL 1469 00:49:08,798 --> 00:49:09,399 MICROBLEEDS, NEURODEGENERATIVE 1470 00:49:09,399 --> 00:49:11,234 PRPROCESSES. 1471 00:49:11,234 --> 00:49:13,002 THIS WAS VERY INFORMATIVE AND 1472 00:49:13,002 --> 00:49:14,404 USEFUL IN HELPING MAKE SURE 1473 00:49:14,404 --> 00:49:15,905 WE'RE SPEAKING THE SAME LANGUAGE 1474 00:49:15,905 --> 00:49:17,006 IN THE FIELD AND REALLY THINK 1475 00:49:17,006 --> 00:49:20,376 ABOUT ARE THESE POTENTIAL 1476 00:49:20,376 --> 00:49:21,544 BIOMARKERS IN WHAT'S HAPPENING 1477 00:49:21,544 --> 00:49:22,712 IN VCID CASES. 1478 00:49:22,712 --> 00:49:24,147 SO I SAID I'D SHARE A LITTLE 1479 00:49:24,147 --> 00:49:26,216 MORE ABOUT MECHANISMS LINKING 1480 00:49:26,216 --> 00:49:27,884 VASCULAR RISK WITH AD AND SONJA 1481 00:49:27,884 --> 00:49:29,552 DID A BEAUTIFUL JOB TALKING 1482 00:49:29,552 --> 00:49:31,087 ABOUT GENETIC OVERLAPS AND WHY A 1483 00:49:31,087 --> 00:49:33,289 LOT OF THESE CONDITIONS -- 1484 00:49:33,289 --> 00:49:34,858 GENETICS MAY BE AN INCREDIBLY 1485 00:49:34,858 --> 00:49:36,593 VALUABLE WAY TO UNDERSTAND HOW 1486 00:49:36,593 --> 00:49:38,361 MECHANISMS MAY TIE THESE 1487 00:49:38,361 --> 00:49:39,596 DIFFERENT PATHOLOGIES TOGETHER, 1488 00:49:39,596 --> 00:49:41,097 BUT THERE'S ALSO GREAT EVIDENCE 1489 00:49:41,097 --> 00:49:43,833 LOOKING PURELY AT VASCULAR RISK 1490 00:49:43,833 --> 00:49:44,634 AND ALZHEIMER'S DISEASE 1491 00:49:44,634 --> 00:49:45,435 SPECIFICALLY, PARTICULARLY FOR 1492 00:49:45,435 --> 00:49:46,970 HYPERTENSION, WHICH IS A VERY 1493 00:49:46,970 --> 00:49:48,838 IMPORTANT RISK FACTOR THAT WE'LL 1494 00:49:48,838 --> 00:49:49,806 TALK ABOUT SHORTLY. 1495 00:49:49,806 --> 00:49:55,245 SO HERE'S A SUMMARY GRAPH AND A 1496 00:49:55,245 --> 00:49:57,113 PAPER FROM SEVERAL YEARS AGO BUT 1497 00:49:57,113 --> 00:49:58,081 THERE'S A FEW DIFFERENT 1498 00:49:58,081 --> 00:49:59,616 MECHANISMS THAT HAVE BEEN 1499 00:49:59,616 --> 00:50:00,216 HYPOTHESIZED. 1500 00:50:00,216 --> 00:50:03,052 CERTAINLY WE KNOW VASCULAR RISK 1501 00:50:03,052 --> 00:50:05,889 FACTORS OVER TIME CAN ALTER 1502 00:50:05,889 --> 00:50:07,690 CEREBRAL BLOOD FLOW WHICH CAN 1503 00:50:07,690 --> 00:50:10,426 LEAD TO REDUCTION OF WHITE 1504 00:50:10,426 --> 00:50:10,994 MATTER OF THE BRAIN. 1505 00:50:10,994 --> 00:50:12,829 WE CERTAINLY KNOW THE BLOOD 1506 00:50:12,829 --> 00:50:13,930 BRAIN BARRIER MAY NOT FUNCTION 1507 00:50:13,930 --> 00:50:15,298 AS WELL AND THE NEUROVASCULAR 1508 00:50:15,298 --> 00:50:17,133 UNIT ITSELF MAY BE IMPAIRED IN 1509 00:50:17,133 --> 00:50:21,237 THE PRESENCE OF VA VASCULAR RISK 1510 00:50:21,237 --> 00:50:24,307 FACTORS WHICH IN TURN CAN LEAD 1511 00:50:24,307 --> 00:50:26,276 TO AMYLOID PRODUCTION, IMPORTANT 1512 00:50:26,276 --> 00:50:27,143 PLAYER IN THE DEVELOPMENT OF 1513 00:50:27,143 --> 00:50:28,178 ALZHEIMER'S DISEASE, AND THAT IN 1514 00:50:28,178 --> 00:50:33,817 TURN CAN LEAD TO WORSE VASCULAR 1515 00:50:33,817 --> 00:50:36,820 HEALTH AND CEREBRAL BLOOD FLOW. 1516 00:50:36,820 --> 00:50:40,256 THE LIMB LYMPHATIC SIM TEM WHIS 1517 00:50:40,256 --> 00:50:42,892 FELT TO DRAIN TOXINS INCLUDING 1518 00:50:42,892 --> 00:50:45,328 POTENTIALLY TOXIC PROTEINS LIKE 1519 00:50:45,328 --> 00:50:46,629 AMYLOID BETA, IN THE PRESENCE OF 1520 00:50:46,629 --> 00:50:48,464 VASCULAR DISEASE, THE LYMPHATIC 1521 00:50:48,464 --> 00:50:49,599 SYSTEM MAY NOT FUNCTION AS WELL, 1522 00:50:49,599 --> 00:50:52,302 SO THIS IS ONE OTHER MECHANISM 1523 00:50:52,302 --> 00:50:54,337 BY WHICH VASCULAR DISEASE, 1524 00:50:54,337 --> 00:50:56,573 CHRONIC CONDITIONS LIKE 1525 00:50:56,573 --> 00:50:58,575 HYPERTENSION, CAN LEAD TO 1526 00:50:58,575 --> 00:50:59,375 ALZHEIMER'S MORE BROADLY. 1527 00:50:59,375 --> 00:51:01,311 ONE OTHER REALLY IMPORTANT AREA 1528 00:51:01,311 --> 00:51:03,313 IN MY OPINION AS TO WHY WE NEED 1529 00:51:03,313 --> 00:51:05,014 TO THINK ABOUT VASCULAR HEALTH, 1530 00:51:05,014 --> 00:51:06,549 THESE ARE RISK FACTORS WE KNOW 1531 00:51:06,549 --> 00:51:09,752 HOW TO TREAT, THEY'RE A PRO 1532 00:51:09,752 --> 00:51:10,520 TENSIONALLY MODIFIABLE WAY TO 1533 00:51:10,520 --> 00:51:12,322 ALTER THE RISK OF ALZHEIMER'S 1534 00:51:12,322 --> 00:51:13,489 DISEASE AND THAT'S REALLY WHAT 1535 00:51:13,489 --> 00:51:14,991 I'M GOING TO TALK ABOUT MORE 1536 00:51:14,991 --> 00:51:16,392 DETAIL BUT I ALSO WANT TO TALK 1537 00:51:16,392 --> 00:51:18,294 ABOUT IN GENERAL ALZHEIMER'S 1538 00:51:18,294 --> 00:51:19,529 DISEASE HAS THIS VERY LONG 1539 00:51:19,529 --> 00:51:19,996 PRE-CLINICAL PERIOD. 1540 00:51:19,996 --> 00:51:22,198 SO YOU CAN SEE HERE IN WHAT'S 1541 00:51:22,198 --> 00:51:24,200 CALLED THE JACK CURVE THAT CLIFF 1542 00:51:24,200 --> 00:51:26,369 JACK PUBLISHED ON, THAT IN 1543 00:51:26,369 --> 00:51:27,503 GENERAL, COGNITION STARTS TO BE 1544 00:51:27,503 --> 00:51:28,705 AFFECTED RELATIVELY LATE IN THE 1545 00:51:28,705 --> 00:51:29,939 COURSE OF ALZHEIMER'S DISEASE. 1546 00:51:29,939 --> 00:51:31,674 SO THIS IS SHOWING YOU THE 1547 00:51:31,674 --> 00:51:33,610 COGNITIVE CHANGES, BUT ALL 1548 00:51:33,610 --> 00:51:35,111 BIOMARKER CHANGES THAT OCCUR IN 1549 00:51:35,111 --> 00:51:37,847 PROBABLY THE DECADES PRECEDING 1550 00:51:37,847 --> 00:51:38,848 COGNITIVE CHANGE. 1551 00:51:38,848 --> 00:51:40,750 SO PART OF THE REASON THAT MANY 1552 00:51:40,750 --> 00:51:42,151 ALZHEIMER'S TREATMENTS TO DATE 1553 00:51:42,151 --> 00:51:43,920 HAVE NOT BEEN EFFECTIVE, NOT AS 1554 00:51:43,920 --> 00:51:45,288 EFFECTIVE AS THEY MIGHT, IS 1555 00:51:45,288 --> 00:51:46,122 BECAUSE THEY MIGHT BE STARTING 1556 00:51:46,122 --> 00:51:47,490 WHEN PEOPLE ARE TOO FAR ALONG 1557 00:51:47,490 --> 00:51:47,924 THAT PROCESS. 1558 00:51:47,924 --> 00:51:49,926 SO IF THE DISEASE HAS ALREADY 1559 00:51:49,926 --> 00:51:52,128 STARTED, LEADING TO ALL THESE 1560 00:51:52,128 --> 00:51:53,429 ALTERATIONS IN VARIOUS 1561 00:51:53,429 --> 00:51:55,365 BIOMARKERS AND ALTERATIONS IN 1562 00:51:55,365 --> 00:51:57,200 AMYLOID AND TAU, IT MAY BE 1563 00:51:57,200 --> 00:51:59,302 REALLY TOO LATE TO CHANGE THE 1564 00:51:59,302 --> 00:52:00,403 COURSE OF THE DISEASE. 1565 00:52:00,403 --> 00:52:01,404 VASCULAR RISK IS ESPECIALLY 1566 00:52:01,404 --> 00:52:02,505 APPEALING BECAUSE INCREASING 1567 00:52:02,505 --> 00:52:03,840 EVIDENCE SUGGESTS THAT VASCULAR 1568 00:52:03,840 --> 00:52:05,942 RISK FACTORS ARE MOST STRONGLY 1569 00:52:05,942 --> 00:52:07,577 ASSOCIATED WITH DEMENTIA AND 1570 00:52:07,577 --> 00:52:08,578 POSSIBLY ALZHEIMER'S 1571 00:52:08,578 --> 00:52:09,045 SPECIFICALLY. 1572 00:52:09,045 --> 00:52:09,979 IF YOU LOOK AT THEM FROM MID 1573 00:52:09,979 --> 00:52:12,015 LIFE OR PROBABLY EVEN EARLIER, 1574 00:52:12,015 --> 00:52:13,216 ALTHOUGH THERE'S NOT AT MANY 1575 00:52:13,216 --> 00:52:14,284 STUDIES LOOKING EARLIER IN LIFE. 1576 00:52:14,284 --> 00:52:16,319 IN OTHER WORDS, VASCULAR HEALTH 1577 00:52:16,319 --> 00:52:18,521 AT A YOUNGER AGE APPEARS TO BE 1578 00:52:18,521 --> 00:52:19,289 MOST ASSOCIATED WITH YOUR BRAIN 1579 00:52:19,289 --> 00:52:20,590 HEALTH WHEN YOU'RE OLDER, AND 1580 00:52:20,590 --> 00:52:24,160 IT'S BEEN HYPOTHESIZED IN THIS 1581 00:52:24,160 --> 00:52:25,662 PARTICULAR MODIFICATION JACK 1582 00:52:25,662 --> 00:52:26,996 CURVE THAT VASCULAR 1583 00:52:26,996 --> 00:52:27,764 DYSREGULATION, I'M SURE YOU 1584 00:52:27,764 --> 00:52:28,898 CAN'T SEE ALL THESE SEPARATE 1585 00:52:28,898 --> 00:52:30,533 LINES BUT TAKE MY WORD THAT THIS 1586 00:52:30,533 --> 00:52:33,069 FIRST LINE HERE, THIS BROWNISH 1587 00:52:33,069 --> 00:52:36,639 LINE IS VASCULAR DYSREGULATION. 1588 00:52:36,639 --> 00:52:39,342 IT'S BEEN HIGH POT SIZED THAT 1589 00:52:39,342 --> 00:52:40,209 THAT MIGHT BE THE FIRST 1590 00:52:40,209 --> 00:52:42,779 CONDITION THAT OCCURS LEADING TO 1591 00:52:42,779 --> 00:52:44,080 OTHER PROTEIN ALTERATIONS AND 1592 00:52:44,080 --> 00:52:45,048 ULTIMATELY COGNITIVE CHANGE. 1593 00:52:45,048 --> 00:52:46,749 SO HAVING A MODIFIABLE RISK 1594 00:52:46,749 --> 00:52:48,518 FACTOR IS INCREDIBLY APPEALING. 1595 00:52:48,518 --> 00:52:49,619 HAVING ONE THAT YOU CAN 1596 00:52:49,619 --> 00:52:50,787 POTENTIALLY ALTER THE COURSE OF 1597 00:52:50,787 --> 00:52:52,422 DISEASE OR AT LEAST ALTER THE 1598 00:52:52,422 --> 00:52:54,057 COURSE OF THE PHENOTYPE OF THE 1599 00:52:54,057 --> 00:52:55,458 DISEASE AT AN EARLY ENOUGH STAGE 1600 00:52:55,458 --> 00:52:57,160 IS ESPECIALLY APPEALING. 1601 00:52:57,160 --> 00:52:59,028 SO I'M GOING TO SHARE SOME DATA 1602 00:52:59,028 --> 00:53:00,463 THAT I'VE BEEN A PART OF LOOKING 1603 00:53:00,463 --> 00:53:02,398 AT THE EPIDEMIOLOGIC EVIDENCE 1604 00:53:02,398 --> 00:53:03,900 LINKING VASCULAR RISK TO 1605 00:53:03,900 --> 00:53:05,668 COGNITIVE DECLINE IN DEMENTIA. 1606 00:53:05,668 --> 00:53:07,136 I JUST WANT TO SORT OF EXPAND 1607 00:53:07,136 --> 00:53:10,106 UPON THAT LAST POINT THAT I MA 1608 00:53:10,106 --> 00:53:10,640 MADE. 1609 00:53:10,640 --> 00:53:11,941 WE KNOW THAT VASCULAR RISK 1610 00:53:11,941 --> 00:53:13,443 FACTORS ARE MORE COMMON IN 1611 00:53:13,443 --> 00:53:14,310 INDIVIDUALS WITH DEMENTIA AND 1612 00:53:14,310 --> 00:53:14,744 ALZHEIMER'S DISEASE. 1613 00:53:14,744 --> 00:53:16,079 WHAT WE DON'T KNOW AND WHAT I 1614 00:53:16,079 --> 00:53:17,714 REALLY HAVE BEEN TRYING TO 1615 00:53:17,714 --> 00:53:19,182 UNDERSTAND AS MUCH AS IS 1616 00:53:19,182 --> 00:53:22,885 POSSIBLE IN THE OBSERVATIONAL 1617 00:53:22,885 --> 00:53:24,520 STUDIES IS WHETHER IT'S SIMPLY A 1618 00:53:24,520 --> 00:53:27,023 MATTER OF VASCULAR RISK IS VERY 1619 00:53:27,023 --> 00:53:28,658 COMMON, NEURO DEGENERATION SUCH 1620 00:53:28,658 --> 00:53:30,059 AS WE SEE IN ALZHEIMER'S DISEASE 1621 00:53:30,059 --> 00:53:31,060 IS VERY COMMON AND PEOPLE WHO 1622 00:53:31,060 --> 00:53:32,996 HAVE BOTH MAY BE MORE LIKELY TO 1623 00:53:32,996 --> 00:53:34,564 PASS A THRESHOLD OF COGNITIVE 1624 00:53:34,564 --> 00:53:36,699 PERFORMANCE WHERE THEY LOOK LIKE 1625 00:53:36,699 --> 00:53:38,267 THEY HAVE DEMENTIA AND ARE 1626 00:53:38,267 --> 00:53:39,802 CLINICALLY DIAGNOSED WITH 1627 00:53:39,802 --> 00:53:41,738 DEMENTIA, SO IS IT SIMPLY TWO 1628 00:53:41,738 --> 00:53:43,473 DIFFERENT PROCESSES THAT IN 1629 00:53:43,473 --> 00:53:44,240 COMBINATION MAKES SOMEONE MORE 1630 00:53:44,240 --> 00:53:45,541 LIKELY TO BE DIAGNOSED WITH 1631 00:53:45,541 --> 00:53:49,045 DEMENTIA OR IS THERE SOME DIRECT 1632 00:53:49,045 --> 00:53:52,982 MECHANISTIC LINK, AND SIMILARLY, 1633 00:53:52,982 --> 00:53:54,951 DOES IT ALTER THE PATHOGENESIS 1634 00:53:54,951 --> 00:53:56,886 OF THESE OTHER NON-AD DEMENTIAS 1635 00:53:56,886 --> 00:53:59,255 SUCH AS WHAT SONJA TALKED ABOUT. 1636 00:53:59,255 --> 00:54:00,490 SO TO TRY TO UNDERSTAND A LITTLE 1637 00:54:00,490 --> 00:54:02,225 BIT ABOUT THAT, WE CONDUCTED 1638 00:54:02,225 --> 00:54:03,159 SEVERAL STUDIES THAT I'M GOING 1639 00:54:03,159 --> 00:54:09,132 TO SHARE WITH YOU FROM THE ARIC 1640 00:54:09,132 --> 00:54:11,100 COHORT, NEARLY 16,000 1641 00:54:11,100 --> 00:54:12,335 INDIVIDUALS FROM FOUR U.S. 1642 00:54:12,335 --> 00:54:14,370 COMMUNITIES AS YOU CAN SEE HERE. 1643 00:54:14,370 --> 00:54:16,272 THEY WERE RECRUITED STARTING IN 1644 00:54:16,272 --> 00:54:20,777 MIDDLE AGE, 45 TO 64 IN THE LATE 1645 00:54:20,777 --> 00:54:21,110 1980s. 1646 00:54:21,110 --> 00:54:22,311 THEY'VE BEEN FOLLOWED NOW FOR 1647 00:54:22,311 --> 00:54:24,013 SEVERAL DECADES, ABOUT 35 YEARS 1648 00:54:24,013 --> 00:54:24,914 NOW. 1649 00:54:24,914 --> 00:54:26,983 THIS GRAPHIC STOPS AT VISIT 1650 00:54:26,983 --> 00:54:28,951 7 BUT WE'RE ACTUALLY JUST 1651 00:54:28,951 --> 00:54:30,987 STARTED YESTERDAY, I BELIEVE, 1652 00:54:30,987 --> 00:54:33,723 VISIT 11, WHICH WAS REALLY 1653 00:54:33,723 --> 00:54:33,990 EXCITING. 1654 00:54:33,990 --> 00:54:35,591 I'M MOSTLY SHARING DATA FROM 1655 00:54:35,591 --> 00:54:36,826 VISIT 7, BUT WE'RE CONTINUING TO 1656 00:54:36,826 --> 00:54:37,260 SEE PEOPLE. 1657 00:54:37,260 --> 00:54:39,028 BUT I WANT TO EMPHASIZE A FEW 1658 00:54:39,028 --> 00:54:39,595 THINGS. 1659 00:54:39,595 --> 00:54:41,497 FIRST OF ALL, THE AGE RANGE OF 1660 00:54:41,497 --> 00:54:43,599 THE COHORT, SO MIDDLE AGED WHEN 1661 00:54:43,599 --> 00:54:45,234 WE FIRST SAW THEM, NOW THEY'RE 1662 00:54:45,234 --> 00:54:46,602 80 TO 100. 1663 00:54:46,602 --> 00:54:48,471 AND CERTAINLY THE RATES OF 1664 00:54:48,471 --> 00:54:49,772 DEMENTIA ARE GOING UP AS 1665 00:54:49,772 --> 00:54:51,107 EXPECTED. 1666 00:54:51,107 --> 00:54:52,341 SIMILARLY ATTRITION DUE TO DEATH 1667 00:54:52,341 --> 00:54:54,243 AND OTHER DISEASES HAS GONE UP 1668 00:54:54,243 --> 00:54:54,977 AS WELL. 1669 00:54:54,977 --> 00:54:56,612 THEY WERE A POPULATION-BASED 1670 00:54:56,612 --> 00:54:58,081 COHORT SO NOT RECRUITED ON THE 1671 00:54:58,081 --> 00:55:00,349 BASIS OF HAVING EXISTENCE 1672 00:55:00,349 --> 00:55:01,017 VASCULAR OR OTHER DISEASE. 1673 00:55:01,017 --> 00:55:02,885 THEY'VE BEEN FOLLOWED FOR 1674 00:55:02,885 --> 00:55:03,553 COGNITIVE PERFORMANCE STARTING 1675 00:55:03,553 --> 00:55:05,755 AT AN EARLY VISIT REPEATED OVER 1676 00:55:05,755 --> 00:55:06,055 TIME. 1677 00:55:06,055 --> 00:55:10,159 AT THE FIFTH ARIC VISIT, WE 1678 00:55:10,159 --> 00:55:11,461 EXPANDED THE NEUROCOGNITIVE 1679 00:55:11,461 --> 00:55:17,166 BATTERY INCLUDED -- SO WE HAVE 1680 00:55:17,166 --> 00:55:19,502 EXPERT ADJUDICATION OF MILD 1681 00:55:19,502 --> 00:55:21,471 COGNITIVE IMPAIRMENT OF DEMENTIA 1682 00:55:21,471 --> 00:55:23,005 AND SUBSEQUENT VISITS INCLUDING 1683 00:55:23,005 --> 00:55:25,174 THE ONGOING ONES. 1684 00:55:25,174 --> 00:55:27,110 BRAIN MRI WAS ON A SUBSET OF 1685 00:55:27,110 --> 00:55:31,047 INDIVIDUALS AND THEN FLORBETAPIR 1686 00:55:31,047 --> 00:55:33,516 PET THAT BINDS TO AMYLOID IN THE 1687 00:55:33,516 --> 00:55:35,284 BRAIN WAS PERFORMED IN 346 1688 00:55:35,284 --> 00:55:36,786 PEOPLE FROM THREE OF THESE SITES 1689 00:55:36,786 --> 00:55:41,557 WHO WHO DID NOT HAVE DEMENTIA. 1690 00:55:41,557 --> 00:55:43,326 SO I'M GOING TO TALK A BIT ABOUT 1691 00:55:43,326 --> 00:55:44,660 SOME OF THESE DATA IN THE 1692 00:55:44,660 --> 00:55:45,928 CONTEXT OF THE COGNITIVE 1693 00:55:45,928 --> 00:55:46,195 RESULTS. 1694 00:55:46,195 --> 00:55:48,131 I'M GOING TO SHARE SOME DATA ON 1695 00:55:48,131 --> 00:55:49,665 COGNITIVE CHANGE AS WELL AS 1696 00:55:49,665 --> 00:55:51,200 INCIDENT DEMENTIA, SO WE HAVE 1697 00:55:51,200 --> 00:55:52,969 DEMENTIA CASES CLASSIFIED 1698 00:55:52,969 --> 00:55:55,972 BECAUSE WE SAW THEM IN DETAIL, 1699 00:55:55,972 --> 00:55:58,274 WE DID -- TALKED TO THEIR FAMILY 1700 00:55:58,274 --> 00:56:02,178 MEMBERS AND THE EXPERT 1701 00:56:02,178 --> 00:56:03,813 COMMUNITY -- WE HAVE PEOPLE THAT 1702 00:56:03,813 --> 00:56:06,782 WERE NOT ABLE TO COME IN, PHONE 1703 00:56:06,782 --> 00:56:08,084 INTERVIEWS WITH FAMILY MEMBERS 1704 00:56:08,084 --> 00:56:11,087 FOR PEOPLE WHO WERE DECEASED, 1705 00:56:11,087 --> 00:56:12,722 AND THEN FINALLY USE SOME 1706 00:56:12,722 --> 00:56:13,923 HOSPITALIZATION CODES TO MAKE 1707 00:56:13,923 --> 00:56:16,526 SURE WE HAD AS COMPLETE A SET OF 1708 00:56:16,526 --> 00:56:18,161 DATA ON DEMENTIA INCIDENTS AND 1709 00:56:18,161 --> 00:56:20,296 WE HAD ONGOING SURVEILLANCE IN 1710 00:56:20,296 --> 00:56:21,264 THE COHORT AS WELL. 1711 00:56:21,264 --> 00:56:23,466 THE LAST SORT OF PATHOLOGIC 1712 00:56:23,466 --> 00:56:25,368 POINT I WANT TO MAKE IS WHEN I 1713 00:56:25,368 --> 00:56:26,869 SHARE RESULTS WITH YOU, WE 1714 00:56:26,869 --> 00:56:28,704 CONSIDER ADRITION AND DROPOUT AS 1715 00:56:28,704 --> 00:56:29,505 REALLY IMPORTANT IN THINKING 1716 00:56:29,505 --> 00:56:34,777 ABOUT ASSOCIATIONS TBEEN BETWEEN 1717 00:56:34,777 --> 00:56:35,978 VASCULAR RISK AND DEMENTIA AND 1718 00:56:35,978 --> 00:56:36,445 COGNITIVE CHANGE. 1719 00:56:36,445 --> 00:56:37,513 THE REASON WHY IS PEOPLE WHO 1720 00:56:37,513 --> 00:56:39,348 HAVE A GREAT DEAL OF VASCULAR 1721 00:56:39,348 --> 00:56:40,416 RISK ESPECIALLY IN MIDDLE AGE 1722 00:56:40,416 --> 00:56:41,717 ARE THOSE WHO ARE LEAST LIKELY 1723 00:56:41,717 --> 00:56:44,120 TO MAKE TO A LATER VISIT DECADES 1724 00:56:44,120 --> 00:56:48,524 LATER TO ASSESS THEIR COGNITION. 1725 00:56:48,524 --> 00:56:50,159 SIMILARLY PEOPLE -- ARE THE 1726 00:56:50,159 --> 00:56:51,861 LEAST LIKELY AND COME IN FOR A 1727 00:56:51,861 --> 00:56:53,596 VISIT ASSESSING OF THEIR OWN 1728 00:56:53,596 --> 00:56:54,030 COGNITIVE FUNCTION. 1729 00:56:54,030 --> 00:56:55,798 SO IF WE IGNORE THOSE PEOPLE 1730 00:56:55,798 --> 00:56:57,099 THAT ARE LEAST LIKELY TO BE 1731 00:56:57,099 --> 00:56:59,268 FOLLOWED FOR THAT LONG PERIOD OF 1732 00:56:59,268 --> 00:57:01,237 TIME, VASCULAR DISEASE WHEN THEY 1733 00:57:01,237 --> 00:57:03,072 WERE YOUNGER, WE'LL HAVE AN 1734 00:57:03,072 --> 00:57:03,706 UNDERESTIMATION OF THE 1735 00:57:03,706 --> 00:57:04,574 ASSOCIATIONS IF WE'RE NOT SEEING 1736 00:57:04,574 --> 00:57:06,342 THE MOST AT-RISK PEOPLE. 1737 00:57:06,342 --> 00:57:07,810 SO STATISTICALLY, THERE'S WAYS 1738 00:57:07,810 --> 00:57:09,812 WE CAN UPWEIGHT THE PEOPLE WE 1739 00:57:09,812 --> 00:57:11,647 THINK ARE LEAST LIKELY TO MAKE 1740 00:57:11,647 --> 00:57:12,748 TO SUBSEQUENT VISITS. 1741 00:57:12,748 --> 00:57:14,217 SO I'LL SHOW YOU ONE EXAMPLE AS 1742 00:57:14,217 --> 00:57:15,885 TO HOW THAT ALTERS OUR RESULTS 1743 00:57:15,885 --> 00:57:16,986 AND IT'S IMPORTANT TO THINK 1744 00:57:16,986 --> 00:57:18,854 ABOUT IN ANY LONGITUDINAL STUDY 1745 00:57:18,854 --> 00:57:19,889 OF THIS TYPE. 1746 00:57:19,889 --> 00:57:22,758 SO HERE'S SOME OF OUR EVIDENCE. 1747 00:57:22,758 --> 00:57:26,562 ANDREA SCHNEIDER HERE AND -- DID 1748 00:57:26,562 --> 00:57:29,265 THE ANALYSES, SONJA ALREADY 1749 00:57:29,265 --> 00:57:30,733 MENTIONED THAT THERE'S BEEN A 1750 00:57:30,733 --> 00:57:31,934 GROWING BODY OF LITERATURE 1751 00:57:31,934 --> 00:57:33,536 LINKING THESE RISK FACTORS WITH 1752 00:57:33,536 --> 00:57:35,404 COGNITIVE CHANGE AND I WANT TO 1753 00:57:35,404 --> 00:57:36,372 EMPHASIZE HERE THAT THIS IS 1754 00:57:36,372 --> 00:57:37,707 REALLY OUR WAY OF LOOKING AT 1755 00:57:37,707 --> 00:57:39,075 THESE RISK FACTORS BUT ALSO 1756 00:57:39,075 --> 00:57:40,276 LOOKING IN PARTICULAR AT THE 1757 00:57:40,276 --> 00:57:41,510 IMPORTANCE OF MID LIFE FOR 1758 00:57:41,510 --> 00:57:45,014 REASONS I MENTIONED EARLIER. 1759 00:57:45,014 --> 00:57:46,482 IT'S A MODIFIABLE WINDOW, WE 1760 00:57:46,482 --> 00:57:49,151 THINK IT'S PROBABLY AN IMPORTANT 1761 00:57:49,151 --> 00:57:50,953 WINDOW FOR RELATIONSHIP TO LATE 1762 00:57:50,953 --> 00:57:52,221 LIFE BRAIN HEALTH, AND WE HAVE 1763 00:57:52,221 --> 00:57:53,756 FURTHER SUPPORT THESE 1764 00:57:53,756 --> 00:57:55,191 RELATIONSHIPS ARE QUITE A BIT 1765 00:57:55,191 --> 00:57:56,592 STRONGER WHEN YOU LOOK AT SOME 1766 00:57:56,592 --> 00:57:58,094 OF THE RISK FACTORS. 1767 00:57:58,094 --> 00:58:02,565 SO HYPERTHE HYPERTENSION HERE, D 1768 00:58:02,565 --> 00:58:05,034 BE CONSIDERED STAGE TWO 1769 00:58:05,034 --> 00:58:07,270 HYPERTENSION NOW, WAS -- IN MID 1770 00:58:07,270 --> 00:58:09,105 LIFE WAS ASSOCIATED WITH STEEPER 1771 00:58:09,105 --> 00:58:10,840 COGNITIVE DECLINE OVER THE NEXT 1772 00:58:10,840 --> 00:58:12,008 20 YEARS INDEPENDENT OF OTHER 1773 00:58:12,008 --> 00:58:15,745 RISK FACTORS AND DEMOGRAPHICS. 1774 00:58:15,745 --> 00:58:17,613 BUT LATE LIFE HYPERTENSION WAS 1775 00:58:17,613 --> 00:58:19,415 NOT ASSOCIATED WITH PRECEDING 1776 00:58:19,415 --> 00:58:20,716 YEARS, ABOUT 20 YEARS WORTH OF 1777 00:58:20,716 --> 00:58:21,250 COGNITIVE CHANGE. 1778 00:58:21,250 --> 00:58:23,686 YOU CAN JUST SEE HERE SORT OF 1779 00:58:23,686 --> 00:58:25,087 CONTINUOUS BLOOD PRESSURE 1780 00:58:25,087 --> 00:58:25,955 MEASUREMENTS AND STEEPER AMOUNTS 1781 00:58:25,955 --> 00:58:29,325 OF COGNITIVE DECLINE. 1782 00:58:29,325 --> 00:58:32,395 ANDREA LOOKED AT HEMOGLOBIN A1C 1783 00:58:32,395 --> 00:58:34,563 LEVELS, THIS IS YOUR X AXIS, 1784 00:58:34,563 --> 00:58:37,066 AMONG NON-DIABETICS, AND FOUND 1785 00:58:37,066 --> 00:58:38,934 WE HAVE STEEPER COGNITIVE 1786 00:58:38,934 --> 00:58:40,636 DECLINE, SO THIS IS MORE CHANGE 1787 00:58:40,636 --> 00:58:42,071 OVER 20 YEARS BEYOND WHAT'S 1788 00:58:42,071 --> 00:58:44,240 EXPECTED WITH AGE. 1789 00:58:44,240 --> 00:58:45,875 STEEPER COGNITIVE DECLINE OVER 1790 00:58:45,875 --> 00:58:48,044 20 YEARS WITH INCREASING 1791 00:58:48,044 --> 00:58:51,647 HEMOGLOBIN A1C EVEN IN THE 1792 00:58:51,647 --> 00:58:52,748 NON-DIABETIC RANGE. 1793 00:58:52,748 --> 00:58:53,883 ESTIMATES SHOW WHAT HAPPENS WHEN 1794 00:58:53,883 --> 00:58:54,884 YOU ACCOUNT FOR THAT ADRITION 1795 00:58:54,884 --> 00:58:56,652 THAT I MENTIONED. 1796 00:58:56,652 --> 00:58:59,588 SO HERE'S ON THE FAR RIGHT HERE, 1797 00:58:59,588 --> 00:59:01,090 THE HIGHER UP DOT SHOWS WHAT 1798 00:59:01,090 --> 00:59:02,091 HAPPENS IF YOU DON'T ACCOUNT FOR 1799 00:59:02,091 --> 00:59:04,460 ATTRITION AND YOU JUST MEASURE 1800 00:59:04,460 --> 00:59:05,594 ASSOCIATIONS IN THOSE PEOPLE WHO 1801 00:59:05,594 --> 00:59:08,030 DID HAVE FOLLOW-UP OVER TIME. 1802 00:59:08,030 --> 00:59:09,365 AND WHEN YOU ACCOUNT FOR THAT 1803 00:59:09,365 --> 00:59:13,803 ADRITATTRITION AND UPWEIGHT THOE 1804 00:59:13,803 --> 00:59:15,671 PEOPLE YOU'RE LEAST LIKELY TO 1805 00:59:15,671 --> 00:59:17,873 STAY IN THE STUDY BECAUSE OF 1806 00:59:17,873 --> 00:59:21,177 THEIR POORLY CONTROLLED DIABETES 1807 00:59:21,177 --> 00:59:22,878 IN LATE LIFE, YOU SEE GREATER 1808 00:59:22,878 --> 00:59:24,280 AMOUNTS OF COGNITIVE DECLINE 1809 00:59:24,280 --> 00:59:24,947 EXPECTED. 1810 00:59:24,947 --> 00:59:26,816 LIPIDS, WE SEE SOME RELATIONSHIP 1811 00:59:26,816 --> 00:59:29,485 BUT IT'S LESS STRONG AND 1812 00:59:29,485 --> 00:59:35,558 HYPERTENSION AND DIABETES. 1813 00:59:35,558 --> 00:59:37,827 HERE YOU CAN SEE HERE THE TOTAL 1814 00:59:37,827 --> 00:59:40,229 CHOLESTEROL LEVELS AS THEY WERE 1815 00:59:40,229 --> 00:59:43,165 HIGHER IN MID LIFE, AGAIN, 1816 00:59:43,165 --> 00:59:44,367 ASSOCIATED WITH STEEPER 1817 00:59:44,367 --> 00:59:45,134 COGNITIVE DECLINE OVER 20 YEARS. 1818 00:59:45,134 --> 00:59:46,936 THE ESTIMATE IS NOT AS LARGE AS 1819 00:59:46,936 --> 00:59:48,137 WE SEE FROM HYPERTENSION, WHICH 1820 00:59:48,137 --> 00:59:50,373 IS HERE FOR REFERENCE. 1821 00:59:50,373 --> 00:59:51,774 CERTAINLY NOT AS HIGH AS WHAT WE 1822 00:59:51,774 --> 00:59:54,810 SEE FOR HAVING AN APOE4 ALLELE 1823 00:59:54,810 --> 00:59:56,879 WHICH, AGAIN, HERE FOR 1824 00:59:56,879 --> 00:59:58,080 REFERENCE, KNOWN AS THE MOST 1825 00:59:58,080 --> 00:59:59,482 IMPORTANT GENETIC RISK FACTOR 1826 00:59:59,482 --> 01:00:01,350 FOR ALZHEIMER'S DISEASE. 1827 01:00:01,350 --> 01:00:04,186 AFIB, ANOTHER IMPORTANT VASCULAR 1828 01:00:04,186 --> 01:00:05,287 RISK FACTOR HIGHLY ASSOCIATED 1829 01:00:05,287 --> 01:00:06,922 WITH RISK OF STROKE. 1830 01:00:06,922 --> 01:00:08,758 IN THIS PARTICULAR STUDY, 1831 01:00:08,758 --> 01:00:10,626 ANOTHER LARGE EPIDEMIOLOGIC 1832 01:00:10,626 --> 01:00:12,027 COHORT SHOWING THAT THE 1833 01:00:12,027 --> 01:00:14,296 DIAGNOSIS AND INCIDENCE OF 1834 01:00:14,296 --> 01:00:15,197 ATRIAL FIBRILLATION IS 1835 01:00:15,197 --> 01:00:16,499 ASSOCIATED WITH A STEEPER 1836 01:00:16,499 --> 01:00:17,967 DECLINE IN COGNITION. 1837 01:00:17,967 --> 01:00:21,504 HERE IS SORT OF AN EXPECTED 1838 01:00:21,504 --> 01:00:22,805 AGE-EXPECTED DECLINE, STEEPER 1839 01:00:22,805 --> 01:00:24,507 DECLINE IN COGNITION AFTER 1840 01:00:24,507 --> 01:00:26,442 DIAGNOSIS OF AFIB, INDEPENDENT 1841 01:00:26,442 --> 01:00:26,876 OF CLINICAL STROKE. 1842 01:00:26,876 --> 01:00:28,477 SO THIS IS NOT COUNTING PEOPLE 1843 01:00:28,477 --> 01:00:30,713 WHO HAD A STROKE FROM THEIR AFIB 1844 01:00:30,713 --> 01:00:32,515 AND THAT'S WHY THEY DECLINED, 1845 01:00:32,515 --> 01:00:35,751 BUT RATHER HAD COGNITIVE CHANGE 1846 01:00:35,751 --> 01:00:36,786 REGARDLESS OF THAT KIND OF A 1847 01:00:36,786 --> 01:00:38,254 STROKE. 1848 01:00:38,254 --> 01:00:39,021 WHAT ABOUT DEMENTIA? 1849 01:00:39,021 --> 01:00:39,855 SO I MENTIONED THAT IT'S 1850 01:00:39,855 --> 01:00:40,890 IMPORTANT TO THINK NOT ONLY 1851 01:00:40,890 --> 01:00:43,893 ABOUT COGNITIVE CHANGE BUT 1852 01:00:43,893 --> 01:00:45,594 INCIDENT DEMENTIA FOR TREATMENT 1853 01:00:45,594 --> 01:00:49,031 FOLLOWING AN ARIC COHORT. 1854 01:00:49,031 --> 01:00:51,000 THESE ARE ALSO LOOKING FROM THE 1855 01:00:51,000 --> 01:00:53,068 ARIC STUDY WHERE WE LOOKED TET 1856 01:00:53,068 --> 01:00:55,237 ENTIRE COHORT AND LOOKED AT 1857 01:00:55,237 --> 01:00:57,006 ASSOCIATION WITH INCIDENT 1858 01:00:57,006 --> 01:00:58,707 DEMENTIA OVER 25-YEAR FOLLOW-UP. 1859 01:00:58,707 --> 01:01:00,042 THESE ARE ADJUSTED FOR EACH 1860 01:01:00,042 --> 01:01:01,877 OTHER AS WELL AS BASIC 1861 01:01:01,877 --> 01:01:04,613 DEMOGRAPHICS AND APOE STATUS. 1862 01:01:04,613 --> 01:01:06,148 BASICALLY WE FOUND AS EXPECTED 1863 01:01:06,148 --> 01:01:07,416 SOME OF THESE RISK FACTORS AND 1864 01:01:07,416 --> 01:01:09,185 VERY STRONG RELATIONSHIPS WITH 1865 01:01:09,185 --> 01:01:11,620 INCIDENT DEMENTIA. 1866 01:01:11,620 --> 01:01:13,656 SMOKING, 40% INCREASED HAZARD 1867 01:01:13,656 --> 01:01:14,990 OVER THESE YEARS. 1868 01:01:14,990 --> 01:01:16,459 DIABETES, THIS IS A HUGE EFFECT 1869 01:01:16,459 --> 01:01:19,061 SIZE IN MY OPINION. 1870 01:01:19,061 --> 01:01:26,469 NEARLY DOUBLING THE RI RISK. 1871 01:01:26,469 --> 01:01:27,970 DIABETES IS SOMETHING WE CAN 1872 01:01:27,970 --> 01:01:29,738 POTENTIALLY DO SOMETHING ABOUT, 1873 01:01:29,738 --> 01:01:30,372 TREAT AND PREVENT. 1874 01:01:30,372 --> 01:01:32,675 THIS IS REALLY IMPORTANT AS WE 1875 01:01:32,675 --> 01:01:33,876 THINK ABOUT PUBLIC HEALTH 1876 01:01:33,876 --> 01:01:35,711 MESSAGING. 1877 01:01:35,711 --> 01:01:37,012 HYPERTENSION, INCREASED RISK, WE 1878 01:01:37,012 --> 01:01:38,848 ALSO SAW AN INCREASED RISK OF 1879 01:01:38,848 --> 01:01:40,049 WHAT WAS THEN CALLED 1880 01:01:40,049 --> 01:01:41,584 PRE-HYPERTENSION IS NOW CALLED 1881 01:01:41,584 --> 01:01:42,985 STAGE I HYPERTENSION ASSOCIATED 1882 01:01:42,985 --> 01:01:45,387 WITH INCREASED DEMENTIA RISK. 1883 01:01:45,387 --> 01:01:47,089 INTERESTINGLY IN THAT STUDY, WE 1884 01:01:47,089 --> 01:01:50,059 DID SEE INCREASED DEMENTIA WITH 1885 01:01:50,059 --> 01:01:52,027 OBESITY AND TOTAL CHOLESTEROL 1886 01:01:52,027 --> 01:01:54,597 BUT OTHERS SUPPORTED THOSE RISK 1887 01:01:54,597 --> 01:01:54,864 FACTORS. 1888 01:01:54,864 --> 01:01:55,831 THE OTHER THING TO CONSIDER IS 1889 01:01:55,831 --> 01:01:57,366 NOT JUST VASCULAR HEALTH IN MID 1890 01:01:57,366 --> 01:01:59,134 LIFE, BUT HOW IT CHANGES OVER 1891 01:01:59,134 --> 01:02:00,002 THE LIFE COURSE. 1892 01:02:00,002 --> 01:02:02,605 SO MID LIFE IS CERTAINLY WHAT WE 1893 01:02:02,605 --> 01:02:04,039 THINK IS VERY IMPORTANT IN 1894 01:02:04,039 --> 01:02:04,707 UNDERSTANDING LATE LIFE BRAIN 1895 01:02:04,707 --> 01:02:05,641 HEALTH RISKS. 1896 01:02:05,641 --> 01:02:08,277 BUT THINGS CHANGE OVER THE LIFE 1897 01:02:08,277 --> 01:02:19,388 COURSE, SOMETIMES DEUM TO A, SOT 1898 01:02:20,523 --> 01:02:23,859 BLOOD PRESSURE TRAJECTORIES OVER 1899 01:02:23,859 --> 01:02:25,928 THE LIFE COURSE FROM MID LIFE TO 1900 01:02:25,928 --> 01:02:27,897 LATE LIFE AND INCIDENT DEMENTIA. 1901 01:02:27,897 --> 01:02:29,064 AFTER PHTHALATE LIFE 1902 01:02:29,064 --> 01:02:29,565 MEASUREMENT. 1903 01:02:29,565 --> 01:02:31,500 WHAT WE FOUND, SO WE EXPECTED TO 1904 01:02:31,500 --> 01:02:33,402 SEE HYPERTENSION CONSISTENTLY 1905 01:02:33,402 --> 01:02:36,138 THROUGHOUT THE LIFE COURSE TO BE 1906 01:02:36,138 --> 01:02:40,509 ASSOCIATED WITH IN INCIDENT 1907 01:02:40,509 --> 01:02:41,043 DEMENTIA. 1908 01:02:41,043 --> 01:02:42,978 BUT WE ALSO FOUND HYPERTENSION 1909 01:02:42,978 --> 01:02:44,213 FOLLOWED BY HYPOTENSION, SO 1910 01:02:44,213 --> 01:02:46,682 PEOPLE WITH HIGH BLOOD PRESSURE 1911 01:02:46,682 --> 01:02:49,752 IN MID LIFE BUT LOW BLOOD 1912 01:02:49,752 --> 01:02:50,486 PRESSURE IN LATE LIFE. 1913 01:02:50,486 --> 01:02:52,121 IF ANYTHING, THIS IS THE TOP 1914 01:02:52,121 --> 01:02:53,322 LINE HERE THAT RISK HAVE EVEN 1915 01:02:53,322 --> 01:02:55,457 BEEN A LITTLE HIGHER THAN THE 1916 01:02:55,457 --> 01:02:56,292 HYPERTENSIVE GROUP. 1917 01:02:56,292 --> 01:02:59,461 SO HYPERTENSION FOLLOWED BY 1918 01:02:59,461 --> 01:03:01,664 HYPOTENSION DID APPEAR TO BE A 1919 01:03:01,664 --> 01:03:03,132 HARMFUL PATTERN IN THIS 1920 01:03:03,132 --> 01:03:04,366 OBSERVATIONAL DATA. 1921 01:03:04,366 --> 01:03:05,467 IT'S ESPECIALLY THE CASE FOR 1922 01:03:05,467 --> 01:03:06,969 PEOPLE WHO WERE YOUNGER AT THE 1923 01:03:06,969 --> 01:03:08,370 START OF FOLLOW-UP, WHICH MEANS 1924 01:03:08,370 --> 01:03:10,005 THEY WERE PROBABLY CLOSER TO MID 1925 01:03:10,005 --> 01:03:11,106 LIFE, FURTHER EMPHASIZING THE 1926 01:03:11,106 --> 01:03:12,841 IMPORTANCE OF THESE EARLIER LIFE 1927 01:03:12,841 --> 01:03:17,446 MEASURES. 1928 01:03:17,446 --> 01:03:19,515 OTHER IMPORTANT VASCULAR RISK 1929 01:03:19,515 --> 01:03:21,250 FACTORS. 1930 01:03:21,250 --> 01:03:24,520 MICHELLE 1931 01:03:24,520 --> 01:03:28,857 [OH LOOKED AT ATRIAL CARD 1932 01:03:28,857 --> 01:03:39,234 CACARDIOPATHY. 1933 01:03:39,234 --> 01:03:40,536 REALLY SHE WANTED TO UNDERSTAND 1934 01:03:40,536 --> 01:03:44,540 HOW ATRIAL CARD YOP THEE 1935 01:03:44,540 --> 01:03:46,742 DIAGNOSED BY ECHO DATA AS WELL 1936 01:03:46,742 --> 01:03:48,377 AS BIOMARKER DATA WAS ASSOCIATED 1937 01:03:48,377 --> 01:03:50,679 WITH INCIDENT DEMENTIA, AND 1938 01:03:50,679 --> 01:03:51,747 ACTUALLY FOUND IT WAS. 1939 01:03:51,747 --> 01:03:53,415 SO INDIVIDUALS WHO WERE 1940 01:03:53,415 --> 01:03:54,516 DEMENTIA-FREE AT ECHO BASELINE 1941 01:03:54,516 --> 01:03:57,219 AT THAT VISIT 5 WHEN WE WERE IN 1942 01:03:57,219 --> 01:03:59,221 OLDER AGE, HAD MORE INCIDENT 1943 01:03:59,221 --> 01:04:03,626 DEMENTIA IF THEY HAD ATRIAL 1944 01:04:03,626 --> 01:04:08,664 CARDIOPATHY. 1945 01:04:08,664 --> 01:04:09,832 WENDY WANG LOOKED AT THIS WITH 1946 01:04:09,832 --> 01:04:11,467 OTHER ECHO MEASURES AND 1947 01:04:11,467 --> 01:04:13,969 SIMILARLY FOUND MEASURES OF POOR 1948 01:04:13,969 --> 01:04:15,237 LEFT ATRIAL FUNCTION AND SIZE 1949 01:04:15,237 --> 01:04:16,472 WERE ASSOCIATED WITH DEMENTIA AS 1950 01:04:16,472 --> 01:04:17,206 WELL. 1951 01:04:17,206 --> 01:04:18,507 SO FURTHER INDICATIONS THAT 1952 01:04:18,507 --> 01:04:21,910 VASCULAR RISK, THESE WERE BOTH 1953 01:04:21,910 --> 01:04:24,613 INDEPENDENT OF UNDERLYING 1954 01:04:24,613 --> 01:04:26,815 DIABETES, HYPERTENSION, ET 1955 01:04:26,815 --> 01:04:28,083 CETERA, WHEN WE'RE THINKING 1956 01:04:28,083 --> 01:04:29,518 ABOUT VASCULAR CONTRIBUTIONS TO 1957 01:04:29,518 --> 01:04:29,985 DEMENTIA. 1958 01:04:29,985 --> 01:04:30,819 WHAT ABOUT STROKE? 1959 01:04:30,819 --> 01:04:32,821 SO CERTAINLY I'VE BEEN 1960 01:04:32,821 --> 01:04:33,656 HIGHLIGHTING VASCULAR RISK 1961 01:04:33,656 --> 01:04:35,424 FACTORS THAT ARE ALSO WELL-KNOWN 1962 01:04:35,424 --> 01:04:37,059 RISK FACTORS FOR STROKE OF THE 1963 01:04:37,059 --> 01:04:38,827 I'M A STROKE NEUROLOGIST SO 1964 01:04:38,827 --> 01:04:39,561 CERTAINLY I THINK ABOUT STROKE 1965 01:04:39,561 --> 01:04:40,729 AND HOW TO TREAT PEOPLE WITH 1966 01:04:40,729 --> 01:04:42,197 STROKE, I THINK ABOUT THE LONG 1967 01:04:42,197 --> 01:04:42,931 TERM CONSEQUENCES OF STROKE AS 1968 01:04:42,931 --> 01:04:46,502 WELL. 1969 01:04:46,502 --> 01:04:52,274 SO SILVIA KOTON SHOWED INCIDENT 1970 01:04:52,274 --> 01:04:52,975 STROKE WAS ASSOCIATED WITH 1971 01:04:52,975 --> 01:04:56,345 HIGHER RISK OF DEMENTIA BUT 1972 01:04:56,345 --> 01:04:57,780 WASN'T SURPRISING BUT NEVER 1973 01:04:57,780 --> 01:04:59,682 SHOWN IN THIS LONGITUDAL SETTING 1974 01:04:59,682 --> 01:05:00,916 BEFORE BUT SHE ALSO LOOKED AT 1975 01:05:00,916 --> 01:05:03,452 STROKE SEVERITY. 1976 01:05:03,452 --> 01:05:04,953 WE SEPARATE PEOPLE BY THIS BLACK 1977 01:05:04,953 --> 01:05:06,922 LINE LOOKING AT DEMENTIA-FREE 1978 01:05:06,922 --> 01:05:07,890 SURVIVAL, THE BLACK LINE IS 1979 01:05:07,890 --> 01:05:10,793 PEOPLE WHO NEVER HAD A STROKE. 1980 01:05:10,793 --> 01:05:13,896 WE ADJUDICATE OVER THE ENTIRE 1981 01:05:13,896 --> 01:05:16,732 STUDY FOLLOW-UP IN ARIC. 1982 01:05:16,732 --> 01:05:18,133 PEOPLE WHO HAD ONE STROKE BUT 1983 01:05:18,133 --> 01:05:19,568 WHAT I RECALL A MILD MODERATE 1984 01:05:19,568 --> 01:05:21,070 STROKE USING WHAT'S CALLED THE 1985 01:05:21,070 --> 01:05:23,939 NIH STROKE SCALE AND PEOPLE WHO 1986 01:05:23,939 --> 01:05:25,274 HAD ONE STROKE BUT IT WAS 1987 01:05:25,274 --> 01:05:26,375 MODERATE TO SEVERE. 1988 01:05:26,375 --> 01:05:28,110 YOU CAN CLEARLY SEE SEPARATION, 1989 01:05:28,110 --> 01:05:29,712 NOT JUST EARLY ON BUT OVER 1990 01:05:29,712 --> 01:05:31,547 CONTINUED FOLLOW-UP. 1991 01:05:31,547 --> 01:05:32,948 SIMILARLY, NOT ONLY ARE MORE 1992 01:05:32,948 --> 01:05:34,283 SEVERE STROKES POTENTIALLY WORSE 1993 01:05:34,283 --> 01:05:37,653 FOR YOUR RISK OF DEMENTIA, BUT 1994 01:05:37,653 --> 01:05:38,754 CURRENT STROKES APPEAR TO BE. 1995 01:05:38,754 --> 01:05:40,556 SO HERE SHE LOOKED AT PEOPLE WHO 1996 01:05:40,556 --> 01:05:42,124 HAD SORT OF ONE STROKE OR 1997 01:05:42,124 --> 01:05:42,991 MULTIPLE STROKES DEPENDING ON 1998 01:05:42,991 --> 01:05:46,495 THE SEVERITY AND REALLY THE 1999 01:05:46,495 --> 01:05:48,397 WORST WERE PEOPLE WHO HAD TWO OR 2000 01:05:48,397 --> 01:05:49,465 MORE STROKES WHICH AT LEAST ONE 2001 01:05:49,465 --> 01:05:50,866 OF THEM WAS IN THE MODERATE TO 2002 01:05:50,866 --> 01:05:51,500 SEVERE RANGE. 2003 01:05:51,500 --> 01:05:52,835 THIS IS A REALLY BIG INCREASE IN 2004 01:05:52,835 --> 01:05:53,135 HAZARD. 2005 01:05:53,135 --> 01:05:54,837 THIS IS INDEPENDENT OF ADJUSTING 2006 01:05:54,837 --> 01:05:59,241 FOR OTHER TIME BEARING 2007 01:05:59,241 --> 01:06:00,442 COVARIATES INCLUDING UNDERLYING 2008 01:06:00,442 --> 01:06:03,245 FACTORS FOR STROKE RISK ITSELF 2009 01:06:03,245 --> 01:06:04,947 SO THIS IS NOT █JUST TELLING US 2010 01:06:04,947 --> 01:06:06,615 MULTIPLE PEOPLE HAVING MULTIPLE 2011 01:06:06,615 --> 01:06:07,649 STROKES ALTHOUGH I THINK THAT IS 2012 01:06:07,649 --> 01:06:09,852 SOME OF WHAT WE'RE SEEING HERE, 2013 01:06:09,852 --> 01:06:11,787 BUT WE STILL SEE THIS VERY LARGE 2014 01:06:11,787 --> 01:06:15,824 INCREASE IN DEMENTIA RATES. 2015 01:06:15,824 --> 01:06:17,259 SO HOW DO WE THINK ABOUT 2016 01:06:17,259 --> 01:06:20,662 MECHANISM LINKING? 2017 01:06:20,662 --> 01:06:21,764 CERTAINLY THERE'S A FEW MAJOR 2018 01:06:21,764 --> 01:06:22,831 THINGS THAT I THINK ABOUT WHEN 2019 01:06:22,831 --> 01:06:24,700 I'M THINKING FROM AN 2020 01:06:24,700 --> 01:06:25,901 EPIDEMIOLOGIC STANDPOINT HOW CAN 2021 01:06:25,901 --> 01:06:27,436 I LINK THESE TOGETHER. 2022 01:06:27,436 --> 01:06:29,538 SO ONE IS THAT VASCULAR RISK 2023 01:06:29,538 --> 01:06:30,472 FACTORS CAN LEAD TO STROKE. 2024 01:06:30,472 --> 01:06:32,741 THAT'S A CLINICAL VASCULAR EVENT 2025 01:06:32,741 --> 01:06:36,578 THAT CAN LEAD TO COGNITIVE 2026 01:06:36,578 --> 01:06:38,647 FINDING OF DEMENTIA. 2027 01:06:38,647 --> 01:06:41,250 I SHOWED YOU THE STRIVE 2028 01:06:41,250 --> 01:06:42,384 CONSORTIUM, DEFINITIONS OF SMALL 2029 01:06:42,384 --> 01:06:43,018 VESSEL DISEASE. 2030 01:06:43,018 --> 01:06:45,888 THOSE ARE SOME FORMS OF SILENT 2031 01:06:45,888 --> 01:06:46,822 VASCULAR IMPACT ON THE BRAIN. 2032 01:06:46,822 --> 01:06:48,390 THAT'S POSSIBLE THAT THAT'S THE 2033 01:06:48,390 --> 01:06:49,358 MECHANISTIC LINK BETWEEN 2034 01:06:49,358 --> 01:06:52,127 VASCULAR RISK AND COGNITIVE 2035 01:06:52,127 --> 01:06:53,128 DEMENTIA. 2036 01:06:53,128 --> 01:06:55,230 IT'S ALSO POSSIBLE THAT VASCULAR 2037 01:06:55,230 --> 01:06:57,633 RISK LEADS TO OTHER BRAIN 2038 01:06:57,633 --> 01:06:59,301 STRUCTURAL CHANGES, SO BRAIN 2039 01:06:59,301 --> 01:07:00,035 ATROPHY, FOR EXAMPLE. 2040 01:07:00,035 --> 01:07:01,670 AND THEN FINALLY, THERE'S A 2041 01:07:01,670 --> 01:07:03,305 POSSIBILITY THAT VASCULAR RISK 2042 01:07:03,305 --> 01:07:05,941 MIGHT DIRECTLY LEAD TO 2043 01:07:05,941 --> 01:07:08,911 ALTERATIONS IN ALZHEIMER'S 2044 01:07:08,911 --> 01:07:10,179 DISEASE NEUROPATHOLOGY AND THAT 2045 01:07:10,179 --> 01:07:13,248 IN TURN COULD -- AT THE 2046 01:07:13,248 --> 01:07:14,650 BEGINNING, IS THAT YOU HAVE TWO 2047 01:07:14,650 --> 01:07:16,618 COMMON PROCESSES WHICH ARE BOTH 2048 01:07:16,618 --> 01:07:20,222 IN TURN INCREASING YOUR RISK OF 2049 01:07:20,222 --> 01:07:23,425 A DIAGNOSIS AS DEMENTIA OR IT 2050 01:07:23,425 --> 01:07:25,527 MIGHT LEAD TO PATHOLOGIC 2051 01:07:25,527 --> 01:07:25,928 CHANGES. 2052 01:07:25,928 --> 01:07:27,429 SO HERE'S A SCHEMATIC SORT OF 2053 01:07:27,429 --> 01:07:28,664 THINKING ABOUT HOW WE TIE THESE 2054 01:07:28,664 --> 01:07:30,933 THINGS FOGHT. 2055 01:07:30,933 --> 01:07:31,600 TOGETHER. 2056 01:07:31,600 --> 01:07:33,001 THERE'S A LOT OF IMPORTANT RISK 2057 01:07:33,001 --> 01:07:33,869 FACTORS LISTED HERE. 2058 01:07:33,869 --> 01:07:35,404 WE KNOW THEY'RE ASSOCIATED WITH 2059 01:07:35,404 --> 01:07:36,605 DIFFERENT FORMS OF CEREBRAL 2060 01:07:36,605 --> 01:07:38,574 SMALL VESSEL DISEASE AND AGAIN 2061 01:07:38,574 --> 01:07:40,609 SOME OF THESE ARE SILENT 2062 01:07:40,609 --> 01:07:41,276 VASCULAR CHANGES IN THE BRAIN. 2063 01:07:41,276 --> 01:07:46,348 AND I COULD PUT SILENT IN COATS 2064 01:07:46,348 --> 01:07:48,250 BECAUSE THEY'RE VERY -- WITH 2065 01:07:48,250 --> 01:07:50,219 GATE DISTUR BABSS, INCREASED 2066 01:07:50,219 --> 01:07:52,087 RISK OF STROKE, ET CETERA, AND 2067 01:07:52,087 --> 01:07:53,155 LOOKING AT THESE OTHER 2068 01:07:53,155 --> 01:07:55,224 MECHANISMS THAT COULD TIE THESE 2069 01:07:55,224 --> 01:07:56,892 SMALL VESSEL DISEASE CHANGES AS 2070 01:07:56,892 --> 01:07:59,795 WELL AS THE RISK FACTORS TO 2071 01:07:59,795 --> 01:08:04,733 COGNITIVE DECLINE AND DEMENTIA. 2072 01:08:04,733 --> 01:08:06,034 SO LOOKING AT PART OF THE 2073 01:08:06,034 --> 01:08:07,135 RELATIONSHIP BETWEEN VASCULAR 2074 01:08:07,135 --> 01:08:08,904 RISK, SMALL VESSELS AND 2075 01:08:08,904 --> 01:08:10,305 COGNITIVE DECLINE BY 2076 01:08:10,305 --> 01:08:11,173 SPECIFICALLY FOCUSING ON THE 2077 01:08:11,173 --> 01:08:12,808 SMALL VESSEL DISEASE MARKERS. 2078 01:08:12,808 --> 01:08:15,244 AND WHAT SHE FOUND IS THAT IN 2079 01:08:15,244 --> 01:08:20,549 ARIC, PEOPLE WHO HAD MORE SILENT 2080 01:08:20,549 --> 01:08:21,416 CEREBROVASCULAR CHANGES AND 2081 01:08:21,416 --> 01:08:23,952 INFARCT IN THE BRAIN, AGAIN, NOT 2082 01:08:23,952 --> 01:08:26,989 CLINICAL STROKES BUT STROKE-LIED 2083 01:08:26,989 --> 01:08:27,422 CHANGES. 2084 01:08:27,422 --> 01:08:28,523 PEOPLE WHO HAD MORE OF THOSE 2085 01:08:28,523 --> 01:08:29,725 CHANGES AND YOU HAD BOTH OF 2086 01:08:29,725 --> 01:08:31,493 THOSE DIFFERENT TYPES OF CHANGES 2087 01:08:31,493 --> 01:08:32,861 HAD STEEPER COGNITIVE DECLINE 2088 01:08:32,861 --> 01:08:38,033 OVER 20 YEARS. 2089 01:08:38,033 --> 01:08:41,203 THIS WAS LOOKED AT IN OTHER 2090 01:08:41,203 --> 01:08:42,104 VASCULAR RISK FACTORS. 2091 01:08:42,104 --> 01:08:43,805 BLOOD PRESSURE, OTHER VASCULAR 2092 01:08:43,805 --> 01:08:45,107 RISK FACTORS WERE NOT ONLY 2093 01:08:45,107 --> 01:08:47,109 ASSOCIATED WITH MORE WHITE 2094 01:08:47,109 --> 01:08:48,944 MATTER HYPERINTENSITIES AS WELL 2095 01:08:48,944 --> 01:08:50,579 AS PROGRESSION, BUT ALSO A 2096 01:08:50,579 --> 01:08:52,114 DIFFUSION TENSOR IMAGING MEASURE 2097 01:08:52,114 --> 01:08:53,949 OF POOR WHITE MATTER INTEGRITY. 2098 01:08:53,949 --> 01:08:55,918 SO THIS IS FELT TO REALLY 2099 01:08:55,918 --> 01:08:59,855 CAPTURE SORT OF PREWHITE MATTER 2100 01:08:59,855 --> 01:09:00,522 HYPERINTENSITY IN THE PRAIN AND 2101 01:09:00,522 --> 01:09:02,024 TELLS US ABOUT AN EVEN EARLIER 2102 01:09:02,024 --> 01:09:05,093 STAGE IF YOU'RE TRYING TO 2103 01:09:05,093 --> 01:09:06,295 MECHANISTICALLY LINK WITH 2104 01:09:06,295 --> 01:09:06,728 VASCULAR CHANGES. 2105 01:09:06,728 --> 01:09:09,464 IN ADDITION, MELINDA ALSO LOOKED 2106 01:09:09,464 --> 01:09:10,766 AT THIS PATTERN OF HYPERTENSION 2107 01:09:10,766 --> 01:09:13,602 IN MID LIFE TO HYPOTENSION IN 2108 01:09:13,602 --> 01:09:15,237 LATE LIFE AND HOW IT RELATED TO 2109 01:09:15,237 --> 01:09:17,572 IMAGING MARKERS AND FOUND THOSE 2110 01:09:17,572 --> 01:09:18,540 PEOPLE HAD CERTAIN REGIONS IN 2111 01:09:18,540 --> 01:09:19,808 THE BRAIN THAT WERE SMALLER. 2112 01:09:19,808 --> 01:09:22,144 I MENTIONED ATROPHY, ALTERATIONS 2113 01:09:22,144 --> 01:09:24,012 IN BRAIN STRUCTURE, COULD BE ONE 2114 01:09:24,012 --> 01:09:29,851 ADDITIONAL WAY THAT -- PHYSICAL 2115 01:09:29,851 --> 01:09:30,852 ACTIVITY IN PARTICULAR AND ALSO 2116 01:09:30,852 --> 01:09:31,954 FOUND SOME ASSOCIATIONS WITH 2117 01:09:31,954 --> 01:09:33,288 SMALLER BRAIN VOLUMES, 2118 01:09:33,288 --> 01:09:34,456 ESPECIALLY IN THOSE REGIONS OF 2119 01:09:34,456 --> 01:09:35,757 THE PLAIN BRAIN THAT ARE 2120 01:09:35,757 --> 01:09:36,425 TYPICALLY INVOLVED IN 2121 01:09:36,425 --> 01:09:39,594 ALZHEIMER'S DISEASE. 2122 01:09:39,594 --> 01:09:40,896 SO WE TOOK THIS ONE STEP FURTHER 2123 01:09:40,896 --> 01:09:42,864 TO REALLY EP US UNDERSTAND HOW 2124 01:09:42,864 --> 01:09:44,933 MUCH OF A VASCULAR IMPACT 2125 01:09:44,933 --> 01:09:47,002 COGNITIVE DECLINE MIGHT BE 2126 01:09:47,002 --> 01:09:48,704 THROUGH SMALL VESSEL DISEASE AND 2127 01:09:48,704 --> 01:09:51,273 HOW MUCH MIGHT BE THROUGH BRAIN 2128 01:09:51,273 --> 01:09:52,441 ALTERATIONS AND STRUCTURE, SO 2129 01:09:52,441 --> 01:09:56,411 FOR INSTANCE, ATROPHY. 2130 01:09:56,411 --> 01:09:58,146 HE BASICALLY HYPOTHESIZED THAT 2131 01:09:58,146 --> 01:10:00,782 WHITE MATTER HYPERINTENSITIES, 2132 01:10:00,782 --> 01:10:02,317 INFARCTS WHICH ARE STROKE-LIKE 2133 01:10:02,317 --> 01:10:03,719 CHANGES BUT DIDN'T ACTUALLY 2134 01:10:03,719 --> 01:10:04,486 CAUSE STROKE SYMPTOMS AT THE 2135 01:10:04,486 --> 01:10:07,122 TIME, WERE SO SUITED WITH 2136 01:10:07,122 --> 01:10:08,957 COGNITIVE FUNCTION THAT WE 2137 01:10:08,957 --> 01:10:11,393 THOUGHT THAT RELATIONSHIP MIGHT 2138 01:10:11,393 --> 01:10:13,228 BE VALIDATED WILL, SO IN OTHER 2139 01:10:13,228 --> 01:10:15,530 WORDS WHEN WE SEE SMALLER BRAIN 2140 01:10:15,530 --> 01:10:18,166 VOLUMES IN A PATIENT, IS IT 2141 01:10:18,166 --> 01:10:19,501 BECAUSE THEY HAD A PRIOR 2142 01:10:19,501 --> 01:10:19,968 VASCULAR EVENT? 2143 01:10:19,968 --> 01:10:21,336 IN OTHER WORDS, WHEN WE SEE 2144 01:10:21,336 --> 01:10:22,204 VASCULAR RISK FACTOR 2145 01:10:22,204 --> 01:10:24,206 ASSOCIATIONS WITH ATROPHY, IS 2146 01:10:24,206 --> 01:10:25,607 THIS SIMPLY SAYING THERE WAS AT 2147 01:10:25,607 --> 01:10:26,608 SOME POINT A SMALL VESSEL 2148 01:10:26,608 --> 01:10:27,976 DISEASE MECHANISM LINKING THEM, 2149 01:10:27,976 --> 01:10:30,178 WE JUST CAN'T SEE THAT LATER 2150 01:10:30,178 --> 01:10:30,746 TIME POINT. 2151 01:10:30,746 --> 01:10:32,781 BASICALLY WHAT WE FOUND IS YES, 2152 01:10:32,781 --> 01:10:35,017 VASCULAR -- THE CEREBROVASCULAR 2153 01:10:35,017 --> 01:10:38,020 CHANGES IN THE BRAIN ARE 2154 01:10:38,020 --> 01:10:39,354 ASSOCIATED WITH WORSE COGNITION, 2155 01:10:39,354 --> 01:10:41,623 THIS DOMAIN POWER I TALKED ABOUT 2156 01:10:41,623 --> 01:10:42,924 EARLIER BUT AT LEAST PART OF 2157 01:10:42,924 --> 01:10:46,428 THAT RELATIONSHIP WAS -- SO 2158 01:10:46,428 --> 01:10:47,963 AGAIN, IMPLICATING VOLUME LOSS 2159 01:10:47,963 --> 01:10:49,498 AND LEASE TO PARTIALLY EXPLAIN 2160 01:10:49,498 --> 01:10:53,535 SOME OF THE MECHANISTIC LINK 2161 01:10:53,535 --> 01:10:54,436 BETWEEN CEREBROVASCULAR CHANGES 2162 01:10:54,436 --> 01:10:56,038 IN THE BRAIN THEMSELVES HIGHLY 2163 01:10:56,038 --> 01:10:57,039 ASSOCIATED WITH VAST LAR RISK 2164 01:10:57,039 --> 01:10:58,507 AND COGNITIVE PERFORMANCE. 2165 01:10:58,507 --> 01:11:00,008 AND THEN TO ANSWER THAT LAST 2166 01:11:00,008 --> 01:11:03,979 SORT OF MECHANISTIC QUESTION, I 2167 01:11:03,979 --> 01:11:05,280 HYPOTHESIZED THAT VASCULAR RISK 2168 01:11:05,280 --> 01:11:06,481 FACTORS COULD HAVE SOME DIRECT 2169 01:11:06,481 --> 01:11:07,816 IMPACT ON ALZHEIMER'S 2170 01:11:07,816 --> 01:11:08,183 NEUROPATHOLOGY. 2171 01:11:08,183 --> 01:11:10,752 SO I WANT TO MAKE A BRIEF ASIDE 2172 01:11:10,752 --> 01:11:12,521 BEFORE I SHARE THESE DATA WITH 2173 01:11:12,521 --> 01:11:14,256 YOU, I BY NO MEANS AM SUGGESTING 2174 01:11:14,256 --> 01:11:15,991 THAT AMYLOID DEPOSITION IS 2175 01:11:15,991 --> 01:11:17,726 SYNONYMOUS WITH ALZHEIMER'S 2176 01:11:17,726 --> 01:11:18,627 DISEASE. 2177 01:11:18,627 --> 01:11:19,594 CERTAINLY WE KNOW THAT AMYLOID 2178 01:11:19,594 --> 01:11:21,363 AND TAU ARE BOTH INCREDIBLY 2179 01:11:21,363 --> 01:11:23,265 IMPORTANT IN THE PATHOGENESIS OF 2180 01:11:23,265 --> 01:11:26,601 AD AND LEADING HYPOTHESES POINT 2181 01:11:26,601 --> 01:11:28,770 TO AMYLOID AS A MAJOR PLAYER AND 2182 01:11:28,770 --> 01:11:32,741 TO DATE CERTAINLY THAT'S BEEN 2183 01:11:32,741 --> 01:11:34,810 THE -- AND AT THE TIME, THE 2184 01:11:34,810 --> 01:11:38,847 DEVELOPMENT OF THE STUDY, IT WAS 2185 01:11:38,847 --> 01:11:40,715 THE AVAILABLE PET ISOTOPE WE 2186 01:11:40,715 --> 01:11:42,350 COULD LOCK AT AND REALLY LOOK AT 2187 01:11:42,350 --> 01:11:43,885 IN LIVING PEOPLE THAT WOULD HELP 2188 01:11:43,885 --> 01:11:45,520 US TO UNDERSTAND IN AN 2189 01:11:45,520 --> 01:11:47,355 OBSERVATIONAL STUDY SETTING THE 2190 01:11:47,355 --> 01:11:49,257 DIFFERENCE BETWEEN VASCULAR RISK 2191 01:11:49,257 --> 01:11:54,129 AND AN OPPENHEI -- THESE ARE ALE 2192 01:11:54,129 --> 01:11:56,531 WITHOUT DEMENTIA BY DESIGN FROM 2193 01:11:56,531 --> 01:11:58,166 THREE OF THE ARIC SITES. 2194 01:11:58,166 --> 01:11:59,501 SO WE LOOKED AT VASCULAR RISK 2195 01:11:59,501 --> 01:12:00,402 FACTORS IN MID LIFE AS WELL AS 2196 01:12:00,402 --> 01:12:01,770 IN LATER LIFE AND REALLY AGAIN 2197 01:12:01,770 --> 01:12:04,539 HERE THE QUESTION IS WAS THERE A 2198 01:12:04,539 --> 01:12:06,708 DIRECT LINK WITH PEOPLE THAT ARE 2199 01:12:06,708 --> 01:12:08,343 NOT DEMENTED IN THIS POPULATION 2200 01:12:08,343 --> 01:12:09,644 BETWEEN VASCULAR RISK AND 2201 01:12:09,644 --> 01:12:10,512 AMYLOID DEPOSITION. 2202 01:12:10,512 --> 01:12:11,947 AND IN GENERAL, WHEN WE LOOKED 2203 01:12:11,947 --> 01:12:13,682 AT MID LIFE RISK FACTORS, THE 2204 01:12:13,682 --> 01:12:15,350 GENERAL THEME WAS NO. 2205 01:12:15,350 --> 01:12:17,953 BUT WE DID SEE AN ASSOCIATION 2206 01:12:17,953 --> 01:12:21,123 BETWEEN MID LIFE RISK FACTORS 2207 01:12:21,123 --> 01:12:23,191 AND AMYLOID DEPOSITION IN LATER 2208 01:12:23,191 --> 01:12:24,426 LIFE ABOUT 20 YEARS LATER. 2209 01:12:24,426 --> 01:12:28,763 THERE WAS ONE EXCEPTION, OBES 2210 01:12:28,763 --> 01:12:30,632 OBESITY -- OTHER RISK FACTORS 2211 01:12:30,632 --> 01:12:31,500 INDEPENDENTLY WHEN WE LOOKED AT 2212 01:12:31,500 --> 01:12:32,968 EACH OF THEM SEPARATELY ADJUSTED 2213 01:12:32,968 --> 01:12:34,769 FOR EACH OTHER, ADJUSTED FOR 2214 01:12:34,769 --> 01:12:35,570 DEMOGRAPHICS, WERE NOT 2215 01:12:35,570 --> 01:12:36,972 ASSOCIATED WITH ELEVATED 2216 01:12:36,972 --> 01:12:38,173 AMYLOID. 2217 01:12:38,173 --> 01:12:40,242 SIMILARLY WHEN WE LOOK AT LATE 2218 01:12:40,242 --> 01:12:42,210 LIFE VASCULAR RISK FACTOR STATUS 2219 01:12:42,210 --> 01:12:43,512 WE DID NOT SEE ASSOCIATIONS FOR 2220 01:12:43,512 --> 01:12:46,381 ANY OF THEM WITH CONCURRENT 2221 01:12:46,381 --> 01:12:46,815 AMYLOID DEPOSITION. 2222 01:12:46,815 --> 01:12:48,550 SO INDIVIDUAL RISK FACTORS WITH 2223 01:12:48,550 --> 01:12:50,519 THE EXCEPTION OF BMI DID NOT 2224 01:12:50,519 --> 01:12:55,657 APPEAR IMPORTANT IN SUBS SUBSEQT 2225 01:12:55,657 --> 01:12:56,458 AMYLOID DEFINITION. 2226 01:12:56,458 --> 01:12:57,893 HOWEVER WHEN WE THOUGHT ABOUT 2227 01:12:57,893 --> 01:12:58,994 VASCULAR BURDEN IN A DIFFERENT 2228 01:12:58,994 --> 01:13:00,629 WAY WE SAW A SLIGHTLY DIFFERENT 2229 01:13:00,629 --> 01:13:02,464 STORY, AND THIS IS IMPORTANT AND 2230 01:13:02,464 --> 01:13:04,432 IN MY OPINION JUSTIFIABLE 2231 01:13:04,432 --> 01:13:06,735 BECAUSE MOST OF THESE VASCULAR 2232 01:13:06,735 --> 01:13:10,872 RISK FACTORS DON'T ACT BY 2233 01:13:10,872 --> 01:13:13,275 THEMSELVES, JUST LIKE THESE 2234 01:13:13,275 --> 01:13:13,909 UNDERLYING PATHOLOGIES DON'T ACT 2235 01:13:13,909 --> 01:13:14,709 BY THEMSELVES. 2236 01:13:14,709 --> 01:13:15,477 CERTAINLY PEOPLE WITH 2237 01:13:15,477 --> 01:13:16,678 HYPERTENSION MIGHT HAVE ANOTHER 2238 01:13:16,678 --> 01:13:17,579 RISK FACTOR AND SO ON. 2239 01:13:17,579 --> 01:13:19,414 SO WE DID A TALLEY OF HOW MANY 2240 01:13:19,414 --> 01:13:21,483 RISK FACTORS OUT OF THE SET OF 2241 01:13:21,483 --> 01:13:21,683 FIVE. 2242 01:13:21,683 --> 01:13:22,717 SO HIGH BLOOD PRESSURE, 2243 01:13:22,717 --> 01:13:23,919 DIABETES, OBESITY, HIGH 2244 01:13:23,919 --> 01:13:25,086 CHOLESTEROL AND SMOKING. 2245 01:13:25,086 --> 01:13:27,055 WE TALLEYED HOW MANY OF THOSE 2246 01:13:27,055 --> 01:13:28,490 PEOPLE HAD IN MID LIFE AND 2247 01:13:28,490 --> 01:13:31,226 LOOKED FOR ASSOCIATIONS WITH 2248 01:13:31,226 --> 01:13:32,460 AMYLOID IN LATER LIFE. 2249 01:13:32,460 --> 01:13:33,762 WHAT WE FOUND, IF YOU LOOKED AT 2250 01:13:33,762 --> 01:13:36,498 THE EARLIEST VISIT, THE CLOSEST 2251 01:13:36,498 --> 01:13:38,266 WE HAVE IN THIS COHORT, PEOPLE 2252 01:13:38,266 --> 01:13:40,769 WHO HAD ONE VASCULAR RISK FACTOR 2253 01:13:40,769 --> 01:13:42,204 IN MID LIFE AS COMPARED TO THOSE 2254 01:13:42,204 --> 01:13:43,939 WHO HAD NONE HAD NEARLY A 2255 01:13:43,939 --> 01:13:45,607 DOUBLING OF ODDS OF AMYLOID IN 2256 01:13:45,607 --> 01:13:46,942 THEIR BRAIN IN LATER LIFE AND IF 2257 01:13:46,942 --> 01:13:48,443 YOU HAD TWO OR MORE RISK 2258 01:13:48,443 --> 01:13:51,413 FACTORS, YOU HAD NEARLY A 2259 01:13:51,413 --> 01:13:54,482 TRIPLING OF ODDS OF AMYLOID IN 2260 01:13:54,482 --> 01:13:57,652 LATER LIFE ALONG WITH OTHER 2261 01:13:57,652 --> 01:13:58,420 DEMOGRAPHIC FACTORS. 2262 01:13:58,420 --> 01:14:01,823 AS YOU GET CLOSER TO -- VISIT 2263 01:14:01,823 --> 01:14:02,724 5 HERE, THAT ASSOCIATION GETS 2264 01:14:02,724 --> 01:14:03,158 WEAKER. 2265 01:14:03,158 --> 01:14:04,559 SO AGAIN, FURTHER EVIDENCE THAT 2266 01:14:04,559 --> 01:14:08,063 MID LIFE IS ESPECIALLY IMPORTANT 2267 01:14:08,063 --> 01:14:09,731 FOR ASSOCIATION WITH LATER LIFE 2268 01:14:09,731 --> 01:14:11,032 PATHOLOGIES, IN THIS CASE 2269 01:14:11,032 --> 01:14:12,434 AMYLOID DEPOSITION, AND 2270 01:14:12,434 --> 01:14:13,635 SOMETHING RESEMBLING A 2271 01:14:13,635 --> 01:14:15,270 DOSE-RESPONSE RELATIONSHIP 2272 01:14:15,270 --> 01:14:18,039 BETWEEN EXTENT OF VASCULAR RISK 2273 01:14:18,039 --> 01:14:19,908 IN LATE LIFE. 2274 01:14:19,908 --> 01:14:21,376 I ALSO WANT TO POINT OUT 2275 01:14:21,376 --> 01:14:22,310 SOMETHING WHICH IS IN MY OPINION 2276 01:14:22,310 --> 01:14:25,614 VERY RELEVANT TO SONJA'S TALK IN 2277 01:14:25,614 --> 01:14:27,782 THINKING ABOUT NOT JUST GENETIC 2278 01:14:27,782 --> 01:14:28,883 PATHOLOGIES OR CONTRIBUTIONS AND 2279 01:14:28,883 --> 01:14:30,085 VASCULAR CONTRIBUTIONS IN 2280 01:14:30,085 --> 01:14:31,820 ISOLATION, BUT HOW THEY PLAY A 2281 01:14:31,820 --> 01:14:32,387 ROLE TOGETHER. 2282 01:14:32,387 --> 01:14:34,356 SO IN THIS PARTICULAR STUDY, WE 2283 01:14:34,356 --> 01:14:37,292 LOOKED AT PEOPLE WHO HAD A HIGH 2284 01:14:37,292 --> 01:14:38,393 VASCULAR RISK AND WERE CARRIERS 2285 01:14:38,393 --> 01:14:43,999 OF AT LEAST ONE APOE 4 ALLELE, 2286 01:14:43,999 --> 01:14:46,034 THEIR RISK FOR AMYLOID WENT UP. 2287 01:14:46,034 --> 01:14:47,702 SO NINE FOLD INCREASED ODDS OF 2288 01:14:47,702 --> 01:14:49,571 HAVING ELEVATED AMYLOID IF UR 2289 01:14:49,571 --> 01:14:51,473 WERE AN E4 CARRIER AND HAD TWO 2290 01:14:51,473 --> 01:14:53,541 OR MORE VASCULAR RISK FACTORS IN 2291 01:14:53,541 --> 01:14:54,709 MID LIFE, AND IF YOU LOOK DOWN 2292 01:14:54,709 --> 01:14:56,811 HERE IN THE BOTTOM CORNER, 2293 01:14:56,811 --> 01:14:58,546 HYPERTENSION IF YOU LOOKED AT 2294 01:14:58,546 --> 01:14:59,347 SYSTOLIC BLOOD PRESSURE 2295 01:14:59,347 --> 01:15:00,515 CONTINUOUSLY, IT LOOKS AS THOUGH 2296 01:15:00,515 --> 01:15:02,751 THE RELATIONSHIP BETWEEN MID 2297 01:15:02,751 --> 01:15:04,586 LIFE BLOOD PRESSURE AND LATER 2298 01:15:04,586 --> 01:15:08,990 LIFE AMYLOID DEPOSITION IS 2299 01:15:08,990 --> 01:15:11,393 NON-EXISTNON-EXISTENT IF YOU ONN 2300 01:15:11,393 --> 01:15:13,094 PEOPLE WITHOUT E FOR ALLELE BUT 2301 01:15:13,094 --> 01:15:15,163 IF YOU LOOK IN CARRIERS, IT 2302 01:15:15,163 --> 01:15:15,997 SUGGESTS THERE'S RELATIONSHIP 2303 01:15:15,997 --> 01:15:16,564 TWEENL THE TWO. 2304 01:15:16,564 --> 01:15:17,799 SO THIS IN MY OPINION IS 2305 01:15:17,799 --> 01:15:19,868 EVIDENCE THERE'S SOME TWO-BIT 2306 01:15:19,868 --> 01:15:20,869 PROCESS POTENTIALLY GOING ON HEE 2307 01:15:20,869 --> 01:15:24,139 AND AGAIN WE NEED TO THINK ABOUT 2308 01:15:24,139 --> 01:15:26,408 WHO IS AT HIGHEST RISK BUT ALSO 2309 01:15:26,408 --> 01:15:28,109 HOW MANY DIFFERENT ANGLES DO WE 2310 01:15:28,109 --> 01:15:29,377 NEED TO APPROACH THIS DISEASE IF 2311 01:15:29,377 --> 01:15:31,246 WE'RE UNDERSTANDING INTERACTIONS 2312 01:15:31,246 --> 01:15:32,781 BETWEEN VASCULAR RISK AND 2313 01:15:32,781 --> 01:15:34,949 GENETIC RISK AS WELL. 2314 01:15:34,949 --> 01:15:37,152 FURTHER EVIDENCE, KENAN WALKER 2315 01:15:37,152 --> 01:15:39,688 LOOKED AT THIS FOR WHITE MATTER 2316 01:15:39,688 --> 01:15:40,622 HYPERINTENSITIES AND AMYLOID 2317 01:15:40,622 --> 01:15:41,323 DEPOSITION. 2318 01:15:41,323 --> 01:15:43,058 I MENTIONED AS A FORM OF SMALL 2319 01:15:43,058 --> 01:15:44,292 VESSEL DISEASE ARE HIGHLY 2320 01:15:44,292 --> 01:15:45,727 ASSOCIATED WITH VASCULAR RISK 2321 01:15:45,727 --> 01:15:46,161 FACTORS. 2322 01:15:46,161 --> 01:15:48,463 WE LOOKED A AT THEM CONCURRENT 2323 01:15:48,463 --> 01:15:49,331 WITH AMYLOID DEPOSITION AND 2324 01:15:49,331 --> 01:15:52,967 FOUND THAT IN GENERAL, AMYLOID 2325 01:15:52,967 --> 01:15:54,035 DEPOSITION WAS ELEVATED IN 2326 01:15:54,035 --> 01:15:56,404 PEOPLE WHO HAD MORE WHITEWATER 2327 01:15:56,404 --> 01:15:57,238 HYPERINTENSITIES HELPING US TO 2328 01:15:57,238 --> 01:15:58,573 TRY TO UNDERSTAND THE 2329 01:15:58,573 --> 01:16:00,108 MECHANISTIC LINK HERE IN THIS 2330 01:16:00,108 --> 01:16:02,310 NON-DEMENTED COHORT AND IF 2331 01:16:02,310 --> 01:16:03,812 ANYTHING, THE ASSOCIATION IS 2332 01:16:03,812 --> 01:16:05,046 STRONGER IN BLACK THAN WHITE 2333 01:16:05,046 --> 01:16:08,083 PARTICIPANTS. 2334 01:16:08,083 --> 01:16:09,617 SO WHAT ABOUT THIS MODIFIABLE 2335 01:16:09,617 --> 01:16:09,851 RISK? 2336 01:16:09,851 --> 01:16:11,486 SO I HOPE THAT I'VE MADE A CASE 2337 01:16:11,486 --> 01:16:12,787 THAT VASCULAR RISK FACTORS ARE 2338 01:16:12,787 --> 01:16:14,089 ASSOCIATED WITH COGNITIVE 2339 01:16:14,089 --> 01:16:14,923 DECLINE AND DEMENTIA. 2340 01:16:14,923 --> 01:16:16,291 I HOPE THAT I'VE CONVINCED YOU 2341 01:16:16,291 --> 01:16:18,159 THAT THERE'S SOME EVIDENCE 2342 01:16:18,159 --> 01:16:19,894 MECHANISTICALLY LINKING THESE 2343 01:16:19,894 --> 01:16:20,261 TOGETHER. 2344 01:16:20,261 --> 01:16:22,197 AND THAT WE REALLY NEED TO THINK 2345 01:16:22,197 --> 01:16:23,098 ABOUT MULTIPLE PROCESSES WHEN 2346 01:16:23,098 --> 01:16:25,367 WE'RE TRYING TO UNDERSTAND 2347 01:16:25,367 --> 01:16:26,901 COGNITIVE FINDING IN PATIENTS. 2348 01:16:26,901 --> 01:16:29,104 THE LANCET COMMISSION REALLY DID 2349 01:16:29,104 --> 01:16:33,908 A WONDERFUL JOB IN MY OPINION, 2350 01:16:33,908 --> 01:16:35,210 TRYING TO ESTIMATE HOW MUCH 2351 01:16:35,210 --> 01:16:36,444 DEMENTIA RISK WAS POTENTIALLY 2352 01:16:36,444 --> 01:16:36,978 MODIFIABLE. 2353 01:16:36,978 --> 01:16:37,779 YOU CAN SEE HERE THIS GRAPHIC 2354 01:16:37,779 --> 01:16:39,080 THIS PUBLISHED, THIS IS THE 2355 01:16:39,080 --> 01:16:41,616 UPDATE IN 2020, BEAUTIFULLY 2356 01:16:41,616 --> 01:16:43,318 THINKS ABOUT MODIFIABLE RISK 2357 01:16:43,318 --> 01:16:44,319 OVER THE LIFE COURSE. 2358 01:16:44,319 --> 01:16:47,622 SO HERE THEY EMPHASIZE IN EARLY 2359 01:16:47,622 --> 01:16:48,590 LIFELESS EDUCATION IS AN 2360 01:16:48,590 --> 01:16:51,760 IMPORTANT RISK FACTOR, AND IN 2361 01:16:51,760 --> 01:16:54,496 THESE CIRCLES THEY SHOW THE 2362 01:16:54,496 --> 01:16:59,300 PERCENT DEMENTIA CASES THAT THEY 2363 01:16:59,300 --> 01:17:00,301 THINK ARE MODIFIABLE 2364 01:17:00,301 --> 01:17:01,302 CONTRIBUTING TO THAT RISK 2365 01:17:01,302 --> 01:17:02,170 FACTOR. 2366 01:17:02,170 --> 01:17:03,938 SO CERTAINLY IF WE SEE 2367 01:17:03,938 --> 01:17:05,340 HYPERTENSION IN MID LIFE, 2368 01:17:05,340 --> 01:17:06,875 DIABETES IS HERE, I WOULD ARGUE 2369 01:17:06,875 --> 01:17:08,076 IT'S ALSO IMPORTANT IN MID LIFE. 2370 01:17:08,076 --> 01:17:09,611 I'M NOT GOING TO SPEND TIME 2371 01:17:09,611 --> 01:17:10,779 TALKING ABOUT REALLY IMPORTANT 2372 01:17:10,779 --> 01:17:12,280 RISK FACTORS SUCH AS HEARING 2373 01:17:12,280 --> 01:17:13,381 LOSS, SOCIAL ISOLATION I'LL TALK 2374 01:17:13,381 --> 01:17:14,916 ABOUT VERY BRIEFLY, BUT REALLY 2375 01:17:14,916 --> 01:17:16,351 THIS IS I THINK AN IMPORTANT WAY 2376 01:17:16,351 --> 01:17:20,388 TO THINK ABOUT MODIFIABLE RISK. 2377 01:17:20,388 --> 01:17:24,125 MARK LEE AT UNIVERSITY OF 2378 01:17:24,125 --> 01:17:29,197 MINNESOTA LOOKED AT RISK FACTORS 2379 01:17:29,197 --> 01:17:31,466 IDENTIFIED -- ESTIMATED THAT 2380 01:17:31,466 --> 01:17:33,168 ABOUT 41% OF CASES OF DEMENTIA 2381 01:17:33,168 --> 01:17:36,070 IN THE U.S. ARE ATTRIT UTABLE TO 2382 01:17:36,070 --> 01:17:37,572 THESE 12 MODIFIABLE RISK 2383 01:17:37,572 --> 01:17:37,906 FACTORS. 2384 01:17:37,906 --> 01:17:40,141 THE STRONGEST ATTRIBUTABLE RISKS 2385 01:17:40,141 --> 01:17:41,609 WERE FOR HYPERTENSION, OBESITY 2386 01:17:41,609 --> 01:17:43,545 AND PHYSICAL INACTIVITY. 2387 01:17:43,545 --> 01:17:44,412 AND REALISTICALLY WE KNOW WE 2388 01:17:44,412 --> 01:17:46,481 CAN'T MAKE THESE RISK FACTORS GO 2389 01:17:46,481 --> 01:17:47,215 AWAY COMPLETELY. 2390 01:17:47,215 --> 01:17:48,783 BUT THE ESTIMATE WAS THAT IF WE 2391 01:17:48,783 --> 01:17:50,885 COULD REDUCE EACH OF THEM BY 2392 01:17:50,885 --> 01:17:52,720 15%, THAT WE COULD REDUCE 2393 01:17:52,720 --> 01:17:54,255 DEMENTIA RATES BY ABOUT 7%. 2394 01:17:54,255 --> 01:17:55,857 I DO WANT TO MAKE AN IMPORTANT 2395 01:17:55,857 --> 01:17:57,325 POINT, THE POPULATION 2396 01:17:57,325 --> 01:17:59,794 ATTRIBUTABLE RISK OF 41% IS 2397 01:17:59,794 --> 01:18:01,563 HIGHER IF WE LOOK AT MINORITIZED 2398 01:18:01,563 --> 01:18:02,397 POPULATIONS. 2399 01:18:02,397 --> 01:18:04,933 SO 46% FOR BLACK AMERICANS, 47% 2400 01:18:04,933 --> 01:18:08,269 FOR LATINX AMERICANS. 2401 01:18:08,269 --> 01:18:11,339 SO THESE REALLY IMPORTANT 2402 01:18:11,339 --> 01:18:12,740 MODIFIABLE RISK FACTORS BROADLY 2403 01:18:12,740 --> 01:18:13,775 BUT ALSO UNDERSTANDING SOME OF 2404 01:18:13,775 --> 01:18:15,477 THE DISPARITIES ASSOCIATED WITH 2405 01:18:15,477 --> 01:18:16,544 DISEASES SUCH AS DEMENTIA. 2406 01:18:16,544 --> 01:18:17,645 SO WHAT ABOUT THE ACTUAL 2407 01:18:17,645 --> 01:18:18,746 EVIDENCE THAT TREATING THESE 2408 01:18:18,746 --> 01:18:20,048 RISK FACTORS MIGHT MAKE A 2409 01:18:20,048 --> 01:18:20,381 DIFFERENCE? 2410 01:18:20,381 --> 01:18:22,550 SO I'VE SHARED OBSERVATIONAL 2411 01:18:22,550 --> 01:18:25,286 EPIDEMIOLOGIC DATA, AND IN 2412 01:18:25,286 --> 01:18:26,154 GENERAL, THERE AREN'T A HUGE 2413 01:18:26,154 --> 01:18:27,489 AMOUNT OF DATA THAT SHOW US THAT 2414 01:18:27,489 --> 01:18:29,891 ACTUALLY TREATING THESE RISK 2415 01:18:29,891 --> 01:18:32,327 FACTORS REDUCES RISK AND LEADS 2416 01:18:32,327 --> 01:18:34,062 TO LESS COGNITIVE DECLINE AND 2417 01:18:34,062 --> 01:18:35,463 DEMENTIA. 2418 01:18:35,463 --> 01:18:38,233 THE SPRINT STUDY WAS ONE STUDY 2419 01:18:38,233 --> 01:18:40,201 THAT SORT OF CAME CLOSE TO 2420 01:18:40,201 --> 01:18:43,071 SHOWING A POSITIVE IMPACT OF AN 2421 01:18:43,071 --> 01:18:43,571 INTERVENTION. 2422 01:18:43,571 --> 01:18:45,273 SO SPRINT WAS A TRIAL LOOKING AT 2423 01:18:45,273 --> 01:18:46,574 BLOOD PRESSURE CONTROL, STANDARD 2424 01:18:46,574 --> 01:18:48,843 BLOOD PRESSURE CONTROL VERSUS 2425 01:18:48,843 --> 01:18:49,511 MORE INTENSIVE BLOOD PRESSURE 2426 01:18:49,511 --> 01:18:52,046 CONTROL TO BRING SYSTOLICS BELOW 2427 01:18:52,046 --> 01:18:52,213 120. 2428 01:18:52,213 --> 01:18:54,315 THE STUDY WAS DESIGNED TO LOOK 2429 01:18:54,315 --> 01:18:55,517 AT CARDIOVASCULAR END POINTS AND 2430 01:18:55,517 --> 01:18:57,652 THEY DID AN AMAZING JOB AT 2431 01:18:57,652 --> 01:18:59,888 ACHIEVING A GREAT DELTA BETWEEN 2432 01:18:59,888 --> 01:19:01,456 THEIR TWO BLOOD PRESSURE GROUPS. 2433 01:19:01,456 --> 01:19:03,091 THE STUDY WAS STOPPED EARLY FOR 2434 01:19:03,091 --> 01:19:06,261 AN OVERWHELMING CARDIOVASCULAR 2435 01:19:06,261 --> 01:19:07,896 BENEFIT BUT THE SECOND STUDY, 2436 01:19:07,896 --> 01:19:08,596 SPRINT-MIND, WAS THEREFORE NOT 2437 01:19:08,596 --> 01:19:10,098 ABLE TO ACCRUE AS MUCH TIME AS 2438 01:19:10,098 --> 01:19:12,500 MIGHT HAVE BEEN INITIALLY 2439 01:19:12,500 --> 01:19:13,501 PLANNED. 2440 01:19:13,501 --> 01:19:14,469 SPRINT-MIND WAS DESIGNED TO LOOK 2441 01:19:14,469 --> 01:19:16,004 AT DIFFERENCES IN DEMENTIA RATE 2442 01:19:16,004 --> 01:19:16,905 AND ALTHOUGH THERE'S A 2443 01:19:16,905 --> 01:19:17,906 SUGGESTION OF A DIFFERENCE HERE, 2444 01:19:17,906 --> 01:19:19,641 THEY DID NOT ACHIEVE THEIR 2445 01:19:19,641 --> 01:19:21,943 PRIMARY OUT COME SHOWING LESS 2446 01:19:21,943 --> 01:19:23,912 DEMENTIA IN PEOPLE WITH THE MORE 2447 01:19:23,912 --> 01:19:24,779 INTENSIVE BLOOD PRESSURE CONTROL 2448 01:19:24,779 --> 01:19:25,980 VERSUS PEOPLE WITH THE MORE 2449 01:19:25,980 --> 01:19:28,182 STANDARD BLOOD PRESSURE CONTROL. 2450 01:19:28,182 --> 01:19:31,286 THEY DID SHOW LESS MCI AND LESS 2451 01:19:31,286 --> 01:19:34,122 COMPOSITE MCI AND DEMENTIA WITH 2452 01:19:34,122 --> 01:19:35,089 SORT OF CONSISTENT EFFECT SIZES 2453 01:19:35,089 --> 01:19:37,492 HERE, YOU CAN SEE THE CURVE 2454 01:19:37,492 --> 01:19:38,593 SEPARATING, BUT IN GENERAL, THIS 2455 01:19:38,593 --> 01:19:40,361 IS A RELATIVELY SHORT PERIOD OF 2456 01:19:40,361 --> 01:19:42,096 FOLLOW-UP. 2457 01:19:42,096 --> 01:19:43,765 WHICH IS REALLY AN IMPORTANT 2458 01:19:43,765 --> 01:19:45,300 THING TO THINK IN MIND. 2459 01:19:45,300 --> 01:19:46,701 I'VE SHARED WITH YOU I THINK MID 2460 01:19:46,701 --> 01:19:48,336 LIFE IS ESPECIALLY IMPORTANT IN 2461 01:19:48,336 --> 01:19:49,571 UNDERSTANDING RISK OF SUBSEQUENT 2462 01:19:49,571 --> 01:19:51,139 COGNITIVE DECLINE, AND DEMENTIA, 2463 01:19:51,139 --> 01:19:52,840 AND THIS IS A STUDY OF PEOPLE 2464 01:19:52,840 --> 01:19:54,809 GENERALLY IN OLDER AGE THAT 2465 01:19:54,809 --> 01:19:55,944 FOLLOWED THEM FOR FOUR YEARS, 2466 01:19:55,944 --> 01:19:57,345 IT'S LESS LIKELY THAT WE'RE 2467 01:19:57,345 --> 01:20:00,848 GOING TO SEE A BENEFIT OF 2468 01:20:00,848 --> 01:20:01,516 INTENSIVE BLOOD PRESSURE CONTROL 2469 01:20:01,516 --> 01:20:02,283 OVER THAT PERIOD OF TIME OF WHAT 2470 01:20:02,283 --> 01:20:03,384 ABOUT OTHER MODIFICATIONS OF 2471 01:20:03,384 --> 01:20:06,220 RISK OF DEMENTIA? 2472 01:20:06,220 --> 01:20:10,158 SO THE ASPREE TRIAL LOOKED AT 2473 01:20:10,158 --> 01:20:12,060 THE ROLE OF ASPIRIN, NOT PEOPLE 2474 01:20:12,060 --> 01:20:13,361 WITH PRIOR STROKE OR 2475 01:20:13,361 --> 01:20:14,596 CARDIOVASCULAR DISEASE AND 2476 01:20:14,596 --> 01:20:16,931 LOOKED AT IMPACT OF ASPIRIN USE 2477 01:20:16,931 --> 01:20:22,036 IN THAT SETTING, THESE CURVES 2478 01:20:22,036 --> 01:20:23,137 LOOK COMPLETELY SUPERIMPOSED AND 2479 01:20:23,137 --> 01:20:26,608 THEY BASICALLY ARE STATIS 2480 01:20:26,608 --> 01:20:26,941 STATISTICALLY. 2481 01:20:26,941 --> 01:20:27,976 IN GENERAL THAT'S A GENERALLY 2482 01:20:27,976 --> 01:20:28,743 LOWER RISK POPULATION. 2483 01:20:28,743 --> 01:20:31,713 BUT STILL, NOT EVIDENCE THAT 2484 01:20:31,713 --> 01:20:33,348 TREATING OR PREVENTING STROKE 2485 01:20:33,348 --> 01:20:35,216 WHICH IS A WAY THAT WE THINK 2486 01:20:35,216 --> 01:20:36,851 ABOUT RISK FACTORS AND 2487 01:20:36,851 --> 01:20:37,585 MODIFIABLE RISK IS ACTUALLY 2488 01:20:37,585 --> 01:20:39,087 GOING TO HAVE IMPACT ON 2489 01:20:39,087 --> 01:20:40,188 PREVENTING DEMENTIA. 2490 01:20:40,188 --> 01:20:42,390 THE MULTIMODAL, THERE'VE BEEN A 2491 01:20:42,390 --> 01:20:43,691 SERIES OF MULTIMODAL TRIALS THAT 2492 01:20:43,691 --> 01:20:44,993 APPEAR TO BE A LITTLE BIT MORE 2493 01:20:44,993 --> 01:20:46,327 PROMISING. 2494 01:20:46,327 --> 01:20:48,830 SO THE FINGER TRIAL WAS A STUDY 2495 01:20:48,830 --> 01:20:50,264 THAT RANDOMIZED PEOPLE TO A 2496 01:20:50,264 --> 01:20:51,232 TWO-YEAR MULTIDOMAIN 2497 01:20:51,232 --> 01:20:51,933 INTERVENTION WHICH WAS A 2498 01:20:51,933 --> 01:20:53,434 COMPOSITE OF VAST LAR RISK 2499 01:20:53,434 --> 01:20:54,669 FACTOR CONTROL MONITORING, 2500 01:20:54,669 --> 01:20:57,939 CLOCKTIVE TRAINING, DIET AND 2501 01:20:57,939 --> 01:20:59,841 EXERCISE, AND VERSUS A SORT OF 2502 01:20:59,841 --> 01:21:00,708 STANDARD CONTROL GROUP THAT 2503 01:21:00,708 --> 01:21:02,944 STILL HAD FOLLOW-UP VISITS. 2504 01:21:02,944 --> 01:21:05,146 OVER TWO YEARS THEY SAW LESS 2505 01:21:05,146 --> 01:21:06,114 COGNITIVE CHANGE IN THE 2506 01:21:06,114 --> 01:21:06,914 INTERVENTION GROUP AS COMPARED 2507 01:21:06,914 --> 01:21:09,417 TO THE CONTROL, AND THIS IS 2508 01:21:09,417 --> 01:21:10,752 REALLY BEEN EXPANDED INTO A 2509 01:21:10,752 --> 01:21:11,719 SERIES OF STUDIES. 2510 01:21:11,719 --> 01:21:13,121 IN THE U.S. THERE'S ONE CALLED 2511 01:21:13,121 --> 01:21:15,790 U.S. POINTER, THEY'RE ALL FINGER 2512 01:21:15,790 --> 01:21:17,325 THEMES, WORLDWIDE FINGERS IS THE 2513 01:21:17,325 --> 01:21:18,192 INTERNATIONAL CONSORTIUM OF ALL 2514 01:21:18,192 --> 01:21:21,062 OF THESE DIFFERENT TRIALS. 2515 01:21:21,062 --> 01:21:22,296 WHAT I THINK IS THE REALLY COOL 2516 01:21:22,296 --> 01:21:23,731 THING ABOUT ALL OF THESE STUDIES 2517 01:21:23,731 --> 01:21:25,500 IS EACH COMPONENT OF WORLDWIDE 2518 01:21:25,500 --> 01:21:28,870 FINGERS IS ADAPTING THE CONCEPT 2519 01:21:28,870 --> 01:21:30,638 OF A MULTIMODAL INTERVENTION TO 2520 01:21:30,638 --> 01:21:31,639 A CULTURALLY APPROPRIATE 2521 01:21:31,639 --> 01:21:35,043 SETTING, SO FOR EXAMPLE, FINGER 2522 01:21:35,043 --> 01:21:37,111 WAS IN FINLAND AND THE DIETARY 2523 01:21:37,111 --> 01:21:40,348 INTERVENTIONS WERE VERY 2524 01:21:40,348 --> 01:21:41,816 HERRING-BASED AND DIETARY SORT 2525 01:21:41,816 --> 01:21:44,619 OF MO MODIFICATIONS THAT WOULDNT 2526 01:21:44,619 --> 01:21:45,520 NECESSARILY TRANSLATE AS WELL TO 2527 01:21:45,520 --> 01:21:46,721 A DIFFERENT CULTURE, SO REALLY 2528 01:21:46,721 --> 01:21:48,990 THERE'S BEEN AN EMPHASIS ON 2529 01:21:48,990 --> 01:21:50,358 THINKING ABOUT HOW TO ADAPT THIS 2530 01:21:50,358 --> 01:21:52,760 TO MAKE A MEANINGFUL MULTIDOMAIN 2531 01:21:52,760 --> 01:21:54,195 INTERVENTION THAT CAN BE TESTED 2532 01:21:54,195 --> 01:21:55,229 IN DIFFERENT CULTURES AND ALL 2533 01:21:55,229 --> 01:21:57,165 OVER THE WORLD. 2534 01:21:57,165 --> 01:21:58,900 SO WHY IS IT THAT WE'RE SEEING 2535 01:21:58,900 --> 01:22:01,235 PRETTY STRONG EVIDENCE FROM THE 2536 01:22:01,235 --> 01:22:04,105 EPIDEMIOLOGY SIDE BUT NOT SEEING 2537 01:22:04,105 --> 01:22:05,006 SUCCESSFUL INTERVENTIONS FOR 2538 01:22:05,006 --> 01:22:05,406 BRAIN HEALTH. 2539 01:22:05,406 --> 01:22:06,274 SO ONE IS WHAT I ALREADY 2540 01:22:06,274 --> 01:22:06,941 MENTIONED. 2541 01:22:06,941 --> 01:22:08,042 MOST TRIALS ARE SIMPLY NOT LONG 2542 01:22:08,042 --> 01:22:10,344 ENOUGH TO REALLY GET AT THIS 2543 01:22:10,344 --> 01:22:13,848 LIFE COURSE RISK FACTORS ON 2544 01:22:13,848 --> 01:22:15,383 COGNITIVE DECLINE AND DEMENTIA. 2545 01:22:15,383 --> 01:22:16,718 SO REALISTICALLY NO ONE IS GOING 2546 01:22:16,718 --> 01:22:18,686 TO FUND A 30-YEAR TRIAL LOOKING 2547 01:22:18,686 --> 01:22:19,987 AT SOME INTERVENTION OVER THAT 2548 01:22:19,987 --> 01:22:21,556 TIME PERIOD TO SEE IF IT AFFECTS 2549 01:22:21,556 --> 01:22:23,191 COGNITIVE DECLINE AND DEMENTIA. 2550 01:22:23,191 --> 01:22:25,159 IN ADDITION, PEOPLE CAN BE 2551 01:22:25,159 --> 01:22:26,360 OUTLIERS, SO IT'S POSSIBLE THAT 2552 01:22:26,360 --> 01:22:27,929 A POPULATION BASED APPROACH 2553 01:22:27,929 --> 01:22:29,464 DOESN'T REALLY APPLY WHEN YOU'RE 2554 01:22:29,464 --> 01:22:31,099 THINKING ABOUT INDIVIDUALS, AND 2555 01:22:31,099 --> 01:22:33,101 THEN IT MAY BE THAT VASCULAR 2556 01:22:33,101 --> 01:22:34,502 HEALTH HAS DIFFERENT IMPACTS IN 2557 01:22:34,502 --> 01:22:34,936 DIFFERENT PEOPLE. 2558 01:22:34,936 --> 01:22:36,571 AND I JUST WANT TO SPEND THE 2559 01:22:36,571 --> 01:22:37,338 LAST COUPLE MINUTES OF MY PART 2560 01:22:37,338 --> 01:22:39,874 OF THE TALK TOUCHING ON A FEW 2561 01:22:39,874 --> 01:22:40,341 DIFFERENT IMPORTANT 2562 01:22:40,341 --> 01:22:40,708 CONSIDERATIONS. 2563 01:22:40,708 --> 01:22:42,944 SO THERE MAY BE OTHER FACTORS 2564 01:22:42,944 --> 01:22:44,045 THAT REALLY ARE IMPORTANT FOR 2565 01:22:44,045 --> 01:22:45,813 BRAIN HEALTH THAT WE'RE NOT 2566 01:22:45,813 --> 01:22:46,681 THINKING ABOUT WHEN WE'RE 2567 01:22:46,681 --> 01:22:48,249 THINKING ABOUT HOWL TO ADAPT 2568 01:22:48,249 --> 01:22:49,650 THESE OBSERVATIONAL DATA TO A 2569 01:22:49,650 --> 01:22:51,185 TRIAL SETTING OR TO AN 2570 01:22:51,185 --> 01:22:52,386 INTERVENTIONAL SETTING. 2571 01:22:52,386 --> 01:22:54,188 SO ONE IS A CONCEPT OF COGNITIVE 2572 01:22:54,188 --> 01:22:55,423 RESERVE WHICH I'M GOING TO 2573 01:22:55,423 --> 01:22:56,257 DEFINE IN A MOMENT. 2574 01:22:56,257 --> 01:22:57,358 ANOTHER IS IN GENERAL HOW WE 2575 01:22:57,358 --> 01:22:58,826 THINK ABOUT HEALTH PROMOTING 2576 01:22:58,826 --> 01:22:59,794 LIFESTYLE FACTORS AND THAT TIES 2577 01:22:59,794 --> 01:23:01,329 IN WITH COGNITIVE RESERVE, AND 2578 01:23:01,329 --> 01:23:02,764 THEN BRIEFLY I WANT TO WRAP UP 2579 01:23:02,764 --> 01:23:04,432 TALKING ABOUT INTERACTIONS WITH 2580 01:23:04,432 --> 01:23:06,067 GENETICS AND OTHER PATHOLOGIES 2581 01:23:06,067 --> 01:23:07,635 CERTAINLY TO TRY TO TIE BACK IN 2582 01:23:07,635 --> 01:23:10,571 WITH SONJA'S BEAUTIFUL TALK. 2583 01:23:10,571 --> 01:23:11,973 SO KILOGRAMTIVE RESERVE IS THE 2584 01:23:11,973 --> 01:23:13,241 IDEA THAT SOMEONE'S COGNITIVE 2585 01:23:13,241 --> 01:23:15,176 FUNCTION IS BETTER THAN EXPECTED 2586 01:23:15,176 --> 01:23:17,478 DESPITE UNDERLYING BRAIN 2587 01:23:17,478 --> 01:23:18,346 PATHOLOGY. 2588 01:23:18,346 --> 01:23:19,247 SO WE KNOW THAT THIS HAS BEEN 2589 01:23:19,247 --> 01:23:22,116 SHOWN IN MULTIPLE STUDIES, DAVID 2590 01:23:22,116 --> 01:23:23,551 BENNETT PUBLISHED THESE DATA 2591 01:23:23,551 --> 01:23:25,820 AGAIN FROM THE RELIGIOUS ORDER 2592 01:23:25,820 --> 01:23:27,288 STUDY SET OF PATHOLOGY DATA THAT 2593 01:23:27,288 --> 01:23:30,691 I SHARED THE DATA EARLIER, BUT 2594 01:23:30,691 --> 01:23:31,993 IN GENERAL WE EXPECT SOMEONE TO 2595 01:23:31,993 --> 01:23:33,361 BE AT A CERTAIN LEVEL BUT SOME 2596 01:23:33,361 --> 01:23:34,796 FACTOR MAKES THEM PERFORM BETTER 2597 01:23:34,796 --> 01:23:35,997 THAN EXPECTED. 2598 01:23:35,997 --> 01:23:38,166 SO EDUCATION IS THE CLASSIC 2599 01:23:38,166 --> 01:23:39,300 EXAMPLE OF THE FORM OF COGNITIVE 2600 01:23:39,300 --> 01:23:41,169 RESERVE THAT WE WOULD EXPECT BY 2601 01:23:41,169 --> 01:23:42,470 SOMEONE'S PATHOLOGY IN THEIR 2602 01:23:42,470 --> 01:23:44,005 BRAIN THAT THEIR PERFORMANCE 2603 01:23:44,005 --> 01:23:46,240 WOULD BE AT A CERTAIN LEVEL, 2604 01:23:46,240 --> 01:23:47,308 PEOPLE OF HIGHER EDUCATION 2605 01:23:47,308 --> 01:23:48,643 APPEAR TO PERFORM AT A HIGHER 2606 01:23:48,643 --> 01:23:50,077 LEVEL THAN EXPECTED. 2607 01:23:50,077 --> 01:23:52,046 SO WE KNOW THAT EARLY LIFE EVEN 2608 01:23:52,046 --> 01:23:53,281 BEFORE THAT MID LIFE PERIOD THAT 2609 01:23:53,281 --> 01:23:55,483 I TALKED ABOUT, THERE'S GOOD 2610 01:23:55,483 --> 01:23:56,918 EVIDENCE THAT COGNITIVE RESERVE, 2611 01:23:56,918 --> 01:23:58,553 THINGS THAT HAPPEN TO 2612 01:23:58,553 --> 01:24:00,288 INDIVIDUALS IN EARLY LIFE MAY BE 2613 01:24:00,288 --> 01:24:01,823 VERY IMPORTANT IN GIVING THEM 2614 01:24:01,823 --> 01:24:03,825 THAT RESERVE AND THAT RESILIENCE 2615 01:24:03,825 --> 01:24:04,692 TO NEUROPATHOLOGY. 2616 01:24:04,692 --> 01:24:06,994 SO HERE IS EVIDENCE BETTER 2617 01:24:06,994 --> 01:24:08,129 CHILDHOOD GRADES ASSOCIATED WITH 2618 01:24:08,129 --> 01:24:09,764 LOWER RISK OF DEMENTIA. 2619 01:24:09,764 --> 01:24:12,066 THE EPIDEMIOLOGISTS IN THE 2620 01:24:12,066 --> 01:24:13,267 AUDIENCE SAY THAT COULD BE 2621 01:24:13,267 --> 01:24:14,936 MASSIVELY CONFOUNDED BY SO MANY 2622 01:24:14,936 --> 01:24:16,137 DIFFERENT FACTORS AND CERTAINLY 2623 01:24:16,137 --> 01:24:17,238 THAT'S GOING TO BE THE CASE FOR 2624 01:24:17,238 --> 01:24:19,473 A LOT OF THESE WHICH MAKES THESE 2625 01:24:19,473 --> 01:24:21,209 SORT OF HARD TO STUDY. 2626 01:24:21,209 --> 01:24:22,543 HIGHER CHILDHOOD IQ ASSOCIATED 2627 01:24:22,543 --> 01:24:24,312 WITH LOWER DEMENTIA RATES. 2628 01:24:24,312 --> 01:24:26,113 TEENAGERS WITH MORE PHYSICAL 2629 01:24:26,113 --> 01:24:28,049 ACTIVITY SO LIFESTYLE PROMOTING 2630 01:24:28,049 --> 01:24:28,816 BEHAVIORS ASSOCIATED WITH 2631 01:24:28,816 --> 01:24:31,352 DELAYED COGNITIVE DECLINE IN 2632 01:24:31,352 --> 01:24:32,787 MULTIPLE STUDIES, AND THEN THE 2633 01:24:32,787 --> 01:24:35,790 FAMOUS NUN STUDY, LINGUISTIC 2634 01:24:35,790 --> 01:24:37,225 COMPLEXITY, WHICH WAS -- SO A 2635 01:24:37,225 --> 01:24:38,860 SERIES OF NUNS, THEIR DIARIES 2636 01:24:38,860 --> 01:24:41,295 WERE REVIEWED FOR THE LINGUISTIC 2637 01:24:41,295 --> 01:24:42,930 COMPLEXITY AND THOSE WHO HAD 2638 01:24:42,930 --> 01:24:44,031 LESS LINGUISTIC COMPLEXITY IN 2639 01:24:44,031 --> 01:24:45,099 THESE DIARIES THAT THEY KEPT 2640 01:24:45,099 --> 01:24:47,401 WHEN THEY WERE IN THEIR EARLY 2641 01:24:47,401 --> 01:24:49,470 20s HAD A MORE LATE LIFE 2642 01:24:49,470 --> 01:24:51,405 ALZHEIMER'S DISEASE. 2643 01:24:51,405 --> 01:24:52,406 SO EVIDENCE THAT THINGS THAT 2644 01:24:52,406 --> 01:24:55,243 PEOPLE DO EARLY ON AND THEIR 2645 01:24:55,243 --> 01:24:57,245 ABILITY TO SORT OF INTERACT 2646 01:24:57,245 --> 01:24:58,546 EARLY ON MAY BE REALLY IMPORTANT 2647 01:24:58,546 --> 01:25:00,181 FOR HOW THEY PERFORM LATER OVER 2648 01:25:00,181 --> 01:25:05,319 TIME. 2649 01:25:05,319 --> 01:25:06,988 I WANT TO BRIEFLY MENTION AN 2650 01:25:06,988 --> 01:25:12,693 ONGOING STUDY, RENEE LOOKED 2651 01:25:12,693 --> 01:25:13,494 SPECIFICALLY AT SOCIAL 2652 01:25:13,494 --> 01:25:14,929 ENGAGEMENT IN THE ARIC COHORT. 2653 01:25:14,929 --> 01:25:16,564 SO WE HAVE MEASURES OF SOCIAL 2654 01:25:16,564 --> 01:25:18,666 ISOLATION AND SOCIAL SUPPORT IN 2655 01:25:18,666 --> 01:25:20,434 ARIC AND SHE'S COME UP WITH A 2656 01:25:20,434 --> 01:25:21,535 COMPOSITE SOCIAL ENGAGEMENT 2657 01:25:21,535 --> 01:25:22,937 MEASURE IN MID LIFE AND LOOKING 2658 01:25:22,937 --> 01:25:24,872 AT RELATIONSHIPS WITH INCIDENT 2659 01:25:24,872 --> 01:25:25,706 DEMENTIA OVER TIME, AND IN 2660 01:25:25,706 --> 01:25:27,875 GENERAL, YOU CAN SEE HERE PEOPLE 2661 01:25:27,875 --> 01:25:29,310 WHO HAVE STRONG SOCIAL 2662 01:25:29,310 --> 01:25:30,878 ENGAGEMENT VERSUS POOR SOCIAL 2663 01:25:30,878 --> 01:25:34,615 ENGAGEMENT WHERE THIS IS NEN 2664 01:25:34,615 --> 01:25:36,250 DEMENTIA-FREE SURVIVAL, THOSE 2665 01:25:36,250 --> 01:25:37,351 WITH STRONG SOCIAL ENGAGEMENT DO 2666 01:25:37,351 --> 01:25:38,653 BETTER THAN THOSE WHO HAD POOR 2667 01:25:38,653 --> 01:25:39,654 SOCIAL ENGAGEMENT. 2668 01:25:39,654 --> 01:25:41,022 AND HERE ARE THE HAZARDS FOR 2669 01:25:41,022 --> 01:25:42,356 STRONG SOCIAL RELATIONSHIPS AS 2670 01:25:42,356 --> 01:25:43,557 COMPARED TO POOR VERSUS AVERAGE. 2671 01:25:43,557 --> 01:25:45,760 SO AGAIN, SORT OF A 2672 01:25:45,760 --> 01:25:46,294 DOSE-RESPONSE KIND OF 2673 01:25:46,294 --> 01:25:47,295 RELATIONSHIP POINTING TO THE 2674 01:25:47,295 --> 01:25:48,496 IMPORTANCE OF THIS OTHER 2675 01:25:48,496 --> 01:25:49,697 POTENTIAL FORM OF COGNITIVE 2676 01:25:49,697 --> 01:25:50,031 RESERVE. 2677 01:25:50,031 --> 01:25:52,233 AND THIS IS INDEPENDENT OF 2678 01:25:52,233 --> 01:25:55,102 GENETICS, NOT MODIFIED BY JE NE 2679 01:25:55,102 --> 01:26:01,242 AT THE RICK IGENETIC RISK EITHE. 2680 01:26:01,242 --> 01:26:03,077 PEOPLE WITH JOBS WITH HIGHER 2681 01:26:03,077 --> 01:26:03,644 INFORMATION PROCESSING ARE 2682 01:26:03,644 --> 01:26:04,645 ASSOCIATED WITH LOWER DEMENTIA 2683 01:26:04,645 --> 01:26:05,212 RATES OVER TIME. 2684 01:26:05,212 --> 01:26:06,347 I MENTIONED THAT EDUCATION IS 2685 01:26:06,347 --> 01:26:07,615 ONE OF THE MOST COMMON ONES, BUT 2686 01:26:07,615 --> 01:26:09,050 I THINK WE NEED TO THINK ABOUT 2687 01:26:09,050 --> 01:26:10,818 THESE FACTORS IN ADDITION TO 2688 01:26:10,818 --> 01:26:11,886 THESE ADDITIONAL PATHOLOGIES 2689 01:26:11,886 --> 01:26:15,256 THAT WE SEE WHICH ARE OFTEN 2690 01:26:15,256 --> 01:26:16,624 OVERLAID. 2691 01:26:16,624 --> 01:26:21,562 SO WHAT ABOUT HOW GENETIC RISK 2692 01:26:21,562 --> 01:26:22,096 TIES IN. 2693 01:26:22,096 --> 01:26:23,497 I WANT TO BRING IT BACK TO WHAT 2694 01:26:23,497 --> 01:26:24,999 SONJA TALKED ABOUT A BIT. 2695 01:26:24,999 --> 01:26:26,834 SO HERE'S A STUDY IN THE UK 2696 01:26:26,834 --> 01:26:29,370 BIOBANK WHICH CATEGORIZED BOTH A 2697 01:26:29,370 --> 01:26:31,105 POLYGENIC RISK, SO USING A 2698 01:26:31,105 --> 01:26:33,074 CLASSIC DEMENTIA POLYGENIC RISK 2699 01:26:33,074 --> 01:26:34,575 SCORE AS HAS BEEN DESCRIBED FOR 2700 01:26:34,575 --> 01:26:35,209 ALZHEIMER'S DISEASE, AS WELL AS 2701 01:26:35,209 --> 01:26:36,510 WHAT THEY CALL THE POLYSOCIAL 2702 01:26:36,510 --> 01:26:38,045 RISK, SO AGAIN, THIS IS GETTING 2703 01:26:38,045 --> 01:26:40,047 AT FACTORS LIKE I JUST TALKED 2704 01:26:40,047 --> 01:26:42,450 ABOUT, SOCIAL ISOLATION, 2705 01:26:42,450 --> 01:26:45,619 EDUCATION, AND HERE THEY SORT OF 2706 01:26:45,619 --> 01:26:46,921 CAPTURED PEOPLE WITH BOTH HIGH 2707 01:26:46,921 --> 01:26:49,290 RISK AND LOW RISK, BUT THEY 2708 01:26:49,290 --> 01:26:50,057 FOUND IN GENERAL THAT EVEN IF 2709 01:26:50,057 --> 01:26:53,094 YOU HAVE A HIGH GENETIC RISK, SO 2710 01:26:53,094 --> 01:26:54,295 YOUR POLYGENIC RISK SCORE WAS 2711 01:26:54,295 --> 01:26:56,364 ELEVATED SO YOU HAD A HIGH 2712 01:26:56,364 --> 01:26:57,231 GENETIC RISK TO ALZHEIMER'S 2713 01:26:57,231 --> 01:26:58,199 DISEASE AND HERE THEY HAVE WHAT 2714 01:26:58,199 --> 01:27:01,369 THEY CLASSIFY AS ALL CAUSE 2715 01:27:01,369 --> 01:27:02,803 DEMENTIA ALZHEIMER'S DISEASE AND 2716 01:27:02,803 --> 01:27:03,804 VASCULAR DEMENTIA, AND AGAIN I 2717 01:27:03,804 --> 01:27:07,008 WOULD ARGUE THAT MEAN MANY OF E 2718 01:27:07,008 --> 01:27:09,210 CASES ARE MIXED PATHOLOGY BUT IF 2719 01:27:09,210 --> 01:27:11,979 YOU'RE AT THE HIGHEST GENETIC 2720 01:27:11,979 --> 01:27:13,314 RISK, YOUR SOCIAL RISK IS LOWER, 2721 01:27:13,314 --> 01:27:14,715 THAT REDUCED YOUR RISK OF 2722 01:27:14,715 --> 01:27:16,617 DEMENTIA. 2723 01:27:16,617 --> 01:27:18,085 SO OBSERVATIONAL DATA OBVIOUSLY 2724 01:27:18,085 --> 01:27:21,322 BUT IT SUGGESTS IF YOUR GENETIC 2725 01:27:21,322 --> 01:27:29,430 RRISK IS HIGH -- ADRIENNE TIN DD 2726 01:27:29,430 --> 01:27:30,998 THIS WORK AT UNIVERSITY OF 2727 01:27:30,998 --> 01:27:32,533 MISSISSIPPI MEDICAL CENTER AND 2728 01:27:32,533 --> 01:27:34,602 LOOKED AT THE LIFE SIMPLE SEVEN 2729 01:27:34,602 --> 01:27:34,935 SCORE. 2730 01:27:34,935 --> 01:27:36,637 THIS IS A MEASURE THAT THE 2731 01:27:36,637 --> 01:27:37,171 AMERICAN HEART ASSOCIATION 2732 01:27:37,171 --> 01:27:39,140 DESCRIBED WHICH WAS A MEASURE OF 2733 01:27:39,140 --> 01:27:40,641 OPTIMAL IDEAL CARDIOVASCULAR 2734 01:27:40,641 --> 01:27:41,008 HEALTH. 2735 01:27:41,008 --> 01:27:44,545 THEY'VE SINCE UPDATED TO THE -- 2736 01:27:44,545 --> 01:27:47,381 THERE'S EIGHT COMPONENTS NOW, 2737 01:27:47,381 --> 01:27:50,684 BUT THE LIFE SIMPLE SEVEN 2738 01:27:50,684 --> 01:27:53,120 CAPTURED -- A HIGHER SCORE IS 2739 01:27:53,120 --> 01:27:54,021 BETTER CARDIOVASCULAR HEALTH AND 2740 01:27:54,021 --> 01:27:55,189 BASICALLY SHE FOUND A SIMILAR 2741 01:27:55,189 --> 01:27:57,992 RESULT, WHICH IS THAT LOOKING AT 2742 01:27:57,992 --> 01:27:59,193 A POLYGENIC RISK SCORE IN BOTH 2743 01:27:59,193 --> 01:28:00,828 BLACK AND WHITE ADULTS, THAT 2744 01:28:00,828 --> 01:28:02,263 EVEN IN PEOPLE WITH A HIGH 2745 01:28:02,263 --> 01:28:04,799 GENETIC RISK, THAT HAVING IDEAL 2746 01:28:04,799 --> 01:28:05,900 CARDIOVASCULAR HEALTH REDUCED 2747 01:28:05,900 --> 01:28:07,735 YOUR RISK OF DEMENTIA. 2748 01:28:07,735 --> 01:28:10,438 SO HERE IS SORT OF TOP GENETIC 2749 01:28:10,438 --> 01:28:12,206 RISK HERE, THE HIGHEST QUINTILE 2750 01:28:12,206 --> 01:28:14,141 HERE, TOP GENETIC RISK, YOU CAN 2751 01:28:14,141 --> 01:28:17,278 SEE THAT HAVING HIGH LIFE SIMPLE 2752 01:28:17,278 --> 01:28:20,448 SEVEN HAD A REDUCTION IN -- I'M 2753 01:28:20,448 --> 01:28:21,782 SORRY, THIS IS THE HIGHEST 2754 01:28:21,782 --> 01:28:23,551 GENETIC RISK SCORE IN ALL 2755 01:28:23,551 --> 01:28:25,052 GENETIC STRATA HAVING A HIGHER 2756 01:28:25,052 --> 01:28:26,387 LIFE SIMPLE SEVEN WAS ASSOCIATED 2757 01:28:26,387 --> 01:28:28,556 WITH REDUCED RISK OF INCIDENT 2758 01:28:28,556 --> 01:28:32,660 DEMENTIA. 2759 01:28:32,660 --> 01:28:33,994 NAD, OTHER PATHOLOGIES ARE 2760 01:28:33,994 --> 01:28:34,862 OBVIOUSLY GOING TO PLAY A ROLE. 2761 01:28:34,862 --> 01:28:36,530 WE TALKED ABOUT THE OVERLAP 2762 01:28:36,530 --> 01:28:37,498 BETWEEN ALZHEIMER'S DISEASE AND 2763 01:28:37,498 --> 01:28:38,365 VASCULAR HEALTH AND CERTAINLY 2764 01:28:38,365 --> 01:28:39,700 BETWEEN ALZHEIMER'S DISEASE, 2765 01:28:39,700 --> 01:28:40,701 VASCULAR HEALTH AND LEWY BODY 2766 01:28:40,701 --> 01:28:42,336 DEMENTIA AND OTHER 2767 01:28:42,336 --> 01:28:43,637 NEURODEGENERATIVE CONDITIONS. 2768 01:28:43,637 --> 01:28:45,339 IN THIS STUDY, WE WANTED TO 2769 01:28:45,339 --> 01:28:46,440 UNDERSTAND HOW DIFFERENT 2770 01:28:46,440 --> 01:28:47,641 PATHOLOGIES MIGHT ACTUALLY 2771 01:28:47,641 --> 01:28:49,276 CONTRIBUTE TO DEMENTIA. 2772 01:28:49,276 --> 01:28:51,312 I MENTIONED EARLIER THAT I 2773 01:28:51,312 --> 01:28:54,048 THOUGHT THAT HAVING BOTH 2774 01:28:54,048 --> 01:28:57,017 VASCULAR DISEASE AND ALZHEIMER'S 2775 01:28:57,017 --> 01:28:58,552 NEUROPATHOLOGY MOST LIKELY MIGHT 2776 01:28:58,552 --> 01:29:00,020 INCREASE YOUR RISK OF DEMENTIA 2777 01:29:00,020 --> 01:29:01,455 BUT THERE MIGHT BE SOME DIRECT 2778 01:29:01,455 --> 01:29:02,957 LINK BETWEEN THEM AS WELL AS 2779 01:29:02,957 --> 01:29:04,825 SUGGESTED BY OUR ARIC PET DATA, 2780 01:29:04,825 --> 01:29:07,128 BUT IN THIS STUDY WE LOOKED AT 2781 01:29:07,128 --> 01:29:08,229 ASSOCIATIONS BETWEEN VASCULAR 2782 01:29:08,229 --> 01:29:10,931 RISK AS WELL AS WHITE MATTER 2783 01:29:10,931 --> 01:29:12,333 HYPERINTENSITIES AND LATER LIFE 2784 01:29:12,333 --> 01:29:14,101 MEASURE THAT MIGHT LINK VASCULAR 2785 01:29:14,101 --> 01:29:15,503 RISK WITH DEMENTIA AND AMYLOID 2786 01:29:15,503 --> 01:29:17,771 AND BASICALLY FOUND THAT 2787 01:29:17,771 --> 01:29:20,174 HYPERTENSION AND AMYLOID EACH 2788 01:29:20,174 --> 01:29:21,142 INDEPENDENTLY WERE ASSOCIATED 2789 01:29:21,142 --> 01:29:22,743 WITH INCIDENT DEMENTIA RISK 2790 01:29:22,743 --> 01:29:24,678 MEASURED AFTER THE POINT OF THE 2791 01:29:24,678 --> 01:29:26,247 PET SCAN, AND ACTUALLY THEY BOTH 2792 01:29:26,247 --> 01:29:27,548 HAD A VERY LARGE RISK, AND THIS 2793 01:29:27,548 --> 01:29:29,483 IS LOOKING AT MID LIFE VASCULAR 2794 01:29:29,483 --> 01:29:31,352 RISK FACTOR, SO HYPERTENSION IN 2795 01:29:31,352 --> 01:29:33,154 MID LIFE WAS ASSOCIATED WITH 2796 01:29:33,154 --> 01:29:35,422 MORE THAN A DOUBLING INDEPENDENT 2797 01:29:35,422 --> 01:29:36,423 OF AMYLOID, INDEPENDENT OF 2798 01:29:36,423 --> 01:29:39,393 DEMOGRAPHICS AND OTHER RISK 2799 01:29:39,393 --> 01:29:41,295 FACTORS, AFTER VISIT FIVE AND 2800 01:29:41,295 --> 01:29:43,063 THIS IS ALSO INDEPENDENT OF APOE 2801 01:29:43,063 --> 01:29:45,499 I'LL ADD, BUT THESE DID NOT 2802 01:29:45,499 --> 01:29:48,369 INTERACT ON A MULTIPLICATIVE 2803 01:29:48,369 --> 01:29:48,702 SCALE. 2804 01:29:48,702 --> 01:29:49,904 EACH WAS ASSOCIATED WITH A I 2805 01:29:49,904 --> 01:29:52,873 HAOER RISK OF DEMENTIA BUT NOT 2806 01:29:52,873 --> 01:29:54,241 AS INCREASED AS WE THOUGHT IT 2807 01:29:54,241 --> 01:29:55,576 MIGHT BE IN THE PRESENCE OF 2808 01:29:55,576 --> 01:29:56,777 THESE TWO PATHOLOGIES TOGETHER. 2809 01:29:56,777 --> 01:29:58,479 SO I WANT TO BRING THESE POINTS 2810 01:29:58,479 --> 01:29:58,746 TOGETHER. 2811 01:29:58,746 --> 01:30:00,881 I THINK AS WE THINK ABOUT 2812 01:30:00,881 --> 01:30:02,383 GENETICS, AS WE THINK ABOUT 2813 01:30:02,383 --> 01:30:05,419 UNDERLYING PROCESSES LEADING TO 2814 01:30:05,419 --> 01:30:06,153 NEURODEGENERATION AND AS WE 2815 01:30:06,153 --> 01:30:08,822 THINK ABOUT CARDIOVASCULAR RISK, 2816 01:30:08,822 --> 01:30:10,291 THIS IS GOING TO IDENTIFY MORE 2817 01:30:10,291 --> 01:30:12,927 PEOPLE WHO ARE PROBABLY AT HIGH 2818 01:30:12,927 --> 01:30:13,627 RISK. 2819 01:30:13,627 --> 01:30:14,595 SONJA MAILED THE POINT THAT ONE 2820 01:30:14,595 --> 01:30:16,263 ADVANTAGE OF HAVING DISEASES 2821 01:30:16,263 --> 01:30:18,999 WITH MIXED PATHOLOGIES AND 2822 01:30:18,999 --> 01:30:20,201 OVERLAPPING MECHANISMS, WE CAN 2823 01:30:20,201 --> 01:30:21,969 TAKE WHAT WE LEARN FROM ONE AND 2824 01:30:21,969 --> 01:30:23,070 APPLY TO THE OTHERS. 2825 01:30:23,070 --> 01:30:26,874 I WOULD ALSO ARGUE THAT THERE'S 2826 01:30:26,874 --> 01:30:28,108 A POTENTIAL DANGER IF WE SPEND A 2827 01:30:28,108 --> 01:30:29,877 LOT OF TIME LEARNING HOW TO 2828 01:30:29,877 --> 01:30:31,378 TREAT ONE UNDERLYING PATHOLOGY 2829 01:30:31,378 --> 01:30:32,813 OR ONE NEURODEGENERATIVE PROCESS 2830 01:30:32,813 --> 01:30:33,948 AND IGNORE THE OTHER COMPONENTS 2831 01:30:33,948 --> 01:30:35,382 SUCH AS VASCULAR RISK AND WE'RE 2832 01:30:35,382 --> 01:30:37,284 NOT GOING TO REALLY SOLVE THE 2833 01:30:37,284 --> 01:30:37,685 PROBLEM ENTIRELY. 2834 01:30:37,685 --> 01:30:38,919 SO I THINK IT'S REALLY IMPORTANT 2835 01:30:38,919 --> 01:30:41,222 TO THINK ABOUT WAYS THAT WE CAN 2836 01:30:41,222 --> 01:30:43,157 MODIFY RISK FROM SEVERAL 2837 01:30:43,157 --> 01:30:44,325 DIFFERENT ANGLES, AND THIS 2838 01:30:44,325 --> 01:30:45,726 REALLY NICE REVIEW SORT OF MAKES 2839 01:30:45,726 --> 01:30:46,527 THIS POINT, THAT THERE'S PEOPLE 2840 01:30:46,527 --> 01:30:49,530 WHO MIGHT BE PARTICULARLY HIGH 2841 01:30:49,530 --> 01:30:51,899 RISK THAT ARE AT A GENETIC RISK 2842 01:30:51,899 --> 01:30:54,134 BUT PARTICULARLY IN COMBINATION 2843 01:30:54,134 --> 01:30:55,469 WITH CARDIOVASCULAR RISK, YOU 2844 01:30:55,469 --> 01:30:57,805 REALLY HAVE TO THINK ABOUT WHO 2845 01:30:57,805 --> 01:30:59,106 WE MIGHT TARGET PREVENTION 2846 01:30:59,106 --> 01:30:59,907 STRATEGIES. 2847 01:30:59,907 --> 01:31:01,275 SO IN CONCLUSION, MOST DEMENTIAS 2848 01:31:01,275 --> 01:31:03,978 ARE DUE TO MIXED PATHOLOGY. 2849 01:31:03,978 --> 01:31:05,746 VASCULAR RISK FACTORS ARE IN MY 2850 01:31:05,746 --> 01:31:07,414 OPINION A REALLY IMPORTANT 2851 01:31:07,414 --> 01:31:09,183 MODIFIABLE TARGET TO DEMENTIA 2852 01:31:09,183 --> 01:31:11,352 PREVENTION DESPITE THE LACK OF 2853 01:31:11,352 --> 01:31:13,187 CONSISTENT RESULTS IN ACTUAL 2854 01:31:13,187 --> 01:31:14,188 CLINICAL TRIALS, MUCH DUE TO THE 2855 01:31:14,188 --> 01:31:15,189 IMPORTANCE OF MID LIFE AND 2856 01:31:15,189 --> 01:31:17,291 LOOKING AT THE WHOLE LIFE 2857 01:31:17,291 --> 01:31:18,325 PERSON, UNDERSTANDING THE 2858 01:31:18,325 --> 01:31:22,096 COMBINATION OF VASCULAR RISK. 2859 01:31:22,096 --> 01:31:23,464 MECHANISTICALLY, THE 2860 01:31:23,464 --> 01:31:24,798 EPIDEMIOLOGIC DATA SUGGESTS 2861 01:31:24,798 --> 01:31:26,700 THATTALITY RAIGS IN BRAIN SUCK 2862 01:31:26,700 --> 01:31:30,237 TREUR FUNCTION AND MAYBE EVEN 2863 01:31:30,237 --> 01:31:32,406 AMYLOID PRODUCTION -- AND THEN 2864 01:31:32,406 --> 01:31:34,074 IN ADDITION, THIS POINT ABOUT 2865 01:31:34,074 --> 01:31:36,844 GENETIC RISK MIGHT FURTHER 2866 01:31:36,844 --> 01:31:37,444 INCREASE -- CERTAIN LE WE KNOW 2867 01:31:37,444 --> 01:31:38,812 THE GENETIC RISK IS GOING TO 2868 01:31:38,812 --> 01:31:41,348 CONTRIBUTE TO RISK FOR DEMENTIA, 2869 01:31:41,348 --> 01:31:43,117 BUT IT MAY BE THAT THERE'S A 2870 01:31:43,117 --> 01:31:44,451 COMBINATION OF VASCULAR AND 2871 01:31:44,451 --> 01:31:45,119 GENETIC COMPONENTS WE NEED TO 2872 01:31:45,119 --> 01:31:46,320 THINK ABOUT AND ALSO AS WELL AS 2873 01:31:46,320 --> 01:31:48,289 THINKING ABOUT THINGS LIKE WHAT 2874 01:31:48,289 --> 01:31:49,456 CONTRIBUTES TO COGNITIVE RESERVE 2875 01:31:49,456 --> 01:31:51,158 AND SOCIAL FACTORS AS THESE ALL 2876 01:31:51,158 --> 01:31:52,793 CLEARLY HAVE AN INTERPLAY. 2877 01:31:52,793 --> 01:31:54,194 IN GENERAL, THIS LAST POINT IS 2878 01:31:54,194 --> 01:31:55,062 THE POINT THAT I JUST MADE, 2879 01:31:55,062 --> 01:31:56,330 WHICH IS AS WE CONTINUE TO THINK 2880 01:31:56,330 --> 01:31:58,332 ABOUT TREATMENT OPTIONS, AND 2881 01:31:58,332 --> 01:31:59,700 CERTAINLY THERE'S A FOCUS ON 2882 01:31:59,700 --> 01:32:01,735 TREATMENT OPTIONS FOR AD, WE 2883 01:32:01,735 --> 01:32:04,071 CAN'T IGNORE THESE OTHER 2884 01:32:04,071 --> 01:32:06,907 ASPECTS, BECAUSE MOST 2885 01:32:06,907 --> 01:32:07,941 PATHOLOGIES, MOST DEMENTIAS ARE 2886 01:32:07,941 --> 01:32:09,009 MIXED AND TREATING ONE PART OF 2887 01:32:09,009 --> 01:32:10,344 IT IS NOT GOING TO TREAT THE 2888 01:32:10,344 --> 01:32:11,578 WHOLE PROBLEM, NOR IS IT GOING 2889 01:32:11,578 --> 01:32:13,781 TO TREAT EVERYONE WHO HAS A 2890 01:32:13,781 --> 01:32:14,214 DEMENTING DISORDER. 2891 01:32:14,214 --> 01:32:15,916 WE ALSO NEED TO THINK ABOUT 2892 01:32:15,916 --> 01:32:17,685 MODIFYING NOT ONLY VASCULAR RISK 2893 01:32:17,685 --> 01:32:19,787 BUT ALSO WAYS TO AUGMENT 2894 01:32:19,787 --> 01:32:22,122 COGNITIVE RESERVE IN DIVERSE 2895 01:32:22,122 --> 01:32:22,589 POPULATIONS. 2896 01:32:22,589 --> 01:32:24,425 HERE'S MY ACKNOWLEDGMENTS. 2897 01:32:24,425 --> 01:32:26,060 MY WORK IS ABSOLUTELY VERY MUCH 2898 01:32:26,060 --> 01:32:28,395 TEAM SCIENCE, AS IS SONJA'S, AND 2899 01:32:28,395 --> 01:32:29,897 I'VE HAD SOME ABSOLUTELY 2900 01:32:29,897 --> 01:32:30,564 WONDERFUL COLLEAGUES THAT I'VE 2901 01:32:30,564 --> 01:32:31,365 HAD THE OPPORTUNITY TO WORK WITH 2902 01:32:31,365 --> 01:32:33,367 OVER TIME, CERTAINLY 2903 01:32:33,367 --> 01:32:34,735 ACKNOWLEDGING THE ARIC 2904 01:32:34,735 --> 01:32:35,569 PARTICIPANTS AND STAFF AND MY 2905 01:32:35,569 --> 01:32:37,271 FUNDING WITH THE INTRAMURAL 2906 01:32:37,271 --> 01:32:38,339 RESEARCH PROGRAM AT NINDS. 2907 01:32:38,339 --> 01:32:40,474 HERE WE ARE IN VARIOUS FORMS, 2908 01:32:40,474 --> 01:32:43,711 AND WITH THAT, I WILL STOP, AND 2909 01:32:43,711 --> 01:32:45,412 I'M HAPPY -- LOOKING FORWARD TO 2910 01:32:45,412 --> 01:32:46,347 THE DISCUSSION THAT SONJA AND A 2911 01:32:46,347 --> 01:32:47,848 I CAN HAVE WITH THE REST OF YOU. 2912 01:32:47,848 --> 01:32:57,524 SO THANK YOU VERY MUCH. 2913 01:32:57,524 --> 01:32:57,991 >> ALL RIGHT. 2914 01:32:57,991 --> 01:33:00,060 WELL, I CAN ONLY SAY, HOLY 2915 01:33:00,060 --> 01:33:01,895 MACKEREL, THAT WAS REALLY 2916 01:33:01,895 --> 01:33:02,596 SOMETHING. 2917 01:33:02,596 --> 01:33:09,737 THE ONE-TWO PUNCH OF DRS. SCHOLZ 2918 01:33:09,737 --> 01:33:10,337 AND GOTTESMAN. 2919 01:33:10,337 --> 01:33:12,039 THAT WAS FASCINATING AND 2920 01:33:12,039 --> 01:33:12,539 INCREDIBLY STIMULATING. 2921 01:33:12,539 --> 01:33:15,242 WE HAVE LOTS AND LOTS OF 2922 01:33:15,242 --> 01:33:16,977 QUESTIONS FROM THE ONLINE 2923 01:33:16,977 --> 01:33:17,811 AUDIENCE. 2924 01:33:17,811 --> 01:33:20,614 SO ONE OF THEM THAT CAME UP THAT 2925 01:33:20,614 --> 01:33:22,683 I DON'T THINK WAS COVERED BY 2926 01:33:22,683 --> 01:33:25,586 EITHER OF OUR TWO SPEAKERS IS 2927 01:33:25,586 --> 01:33:26,787 THE -- AND MAYBE IT'S BECAUSE 2928 01:33:26,787 --> 01:33:28,922 THERE ISN'T ANYTHING, BUT IS THE 2929 01:33:28,922 --> 01:33:30,624 ROLE OF GENDER. 2930 01:33:30,624 --> 01:33:33,660 AND WHETHER THERE ARE ANY 2931 01:33:33,660 --> 01:33:34,294 DIFFERENCES BETWEEN MEN AND 2932 01:33:34,294 --> 01:33:39,900 WOMEN IN TERMS OF THEIR RISK OF 2933 01:33:39,900 --> 01:33:41,034 DEMENTIA, AND FOR THAT MATTER, 2934 01:33:41,034 --> 01:33:42,870 ARE THERE ANY DIFFERENCES IN 2935 01:33:42,870 --> 01:33:47,474 TERMS OF INTERVENTIONS THAT ONE 2936 01:33:47,474 --> 01:33:49,009 MIGHT CONSIDER BETWEEN MEN AND 2937 01:33:49,009 --> 01:33:51,345 WOMEN? 2938 01:33:51,345 --> 01:33:53,647 >> I CAN GET STARTED AND THEN 2939 01:33:53,647 --> 01:33:54,081 REBECCA CAN ADD ON. 2940 01:33:54,081 --> 01:33:57,184 SO YES, WE ARE ACTUALLY -- SEE 2941 01:33:57,184 --> 01:33:59,420 DIFFERENCES IN BOTH SEX AND 2942 01:33:59,420 --> 01:34:00,788 GENDER, AND IT'S SOMETIMES 2943 01:34:00,788 --> 01:34:02,623 REALLY HARD TO DISENTANGLE THE 2944 01:34:02,623 --> 01:34:04,825 TWO OF THEM. 2945 01:34:04,825 --> 01:34:06,527 BUT SO FOR EXAMPLE IN OUR LEWY 2946 01:34:06,527 --> 01:34:09,596 BODY DEMENTIA CASES, IN WOMEN 2947 01:34:09,596 --> 01:34:11,965 IT'S MUCH MORE COMMON TO HAVE 2948 01:34:11,965 --> 01:34:12,833 MULTIPLE PROTEINOPATHY. 2949 01:34:12,833 --> 01:34:15,202 SO IT VERY UNUSUAL TO SEE A PURE 2950 01:34:15,202 --> 01:34:16,837 LEWY BODY DEMENTIA PRESENTATION. 2951 01:34:16,837 --> 01:34:18,372 WOMEN ALSO TEND TO BE A LITTLE 2952 01:34:18,372 --> 01:34:21,875 BIT OLDER COMPARED TO MOST MEN. 2953 01:34:21,875 --> 01:34:23,977 AND WE'VE DONE A LITTLE BIT OF 2954 01:34:23,977 --> 01:34:26,413 RESEARCH ALREADY LOOKING AT SEX 2955 01:34:26,413 --> 01:34:27,481 CHROMOSOME DIFFERENCES, AND WE 2956 01:34:27,481 --> 01:34:30,350 WERE ABLE TO ACTUALLY SHOW THAT 2957 01:34:30,350 --> 01:34:33,921 WOMEN ALSO HAVE THE APOE4 RISK 2958 01:34:33,921 --> 01:34:35,756 ALLELE, THEY ARE AT HIGHER RISK 2959 01:34:35,756 --> 01:34:37,157 FOR DEVELOPING LEWY BODY 2960 01:34:37,157 --> 01:34:40,294 DEMENTIA IF THEY HAVE A CERTAIN 2961 01:34:40,294 --> 01:34:42,596 RISK VARYING K PATHWAY WHICH IS 2962 01:34:42,596 --> 01:34:43,997 INVOLVED IN LOTS OF DIFFERENT 2963 01:34:43,997 --> 01:34:45,132 SIGNALING PATHWAYS THAT HAVE 2964 01:34:45,132 --> 01:34:46,600 ALREADY BEEN IMPLICATED IN 2965 01:34:46,600 --> 01:34:47,367 ALZHEIMER'S DISEASE, AND WE'RE 2966 01:34:47,367 --> 01:34:49,002 STARTING TO JUST SCRAPE THE 2967 01:34:49,002 --> 01:34:49,470 SURFACE OF THAT. 2968 01:34:49,470 --> 01:34:52,573 WE ALSO ARE SEEING DIFFERENCES 2969 01:34:52,573 --> 01:34:53,640 IN THE OVERALL PREVALENCE OF 2970 01:34:53,640 --> 01:34:55,676 ALZHEIMER'S DISEASE BEING MUCH 2971 01:34:55,676 --> 01:34:58,512 MORE WOMEN-CENTRIC. 2972 01:34:58,512 --> 01:35:02,049 LEWY BODY SEEMS TO BE MORE MALE 2973 01:35:02,049 --> 01:35:02,716 CENTRIC, MALE-FOCUSED BUT 2974 01:35:02,716 --> 01:35:03,450 THERE'S ALSO JUST DIFFERENCES IN 2975 01:35:03,450 --> 01:35:05,919 THE WAYS THE DISEASE MAY 2976 01:35:05,919 --> 01:35:06,487 MANIFEST. 2977 01:35:06,487 --> 01:35:07,488 SO THERE'S A LITTLE BIT WE HAVE 2978 01:35:07,488 --> 01:35:12,092 TO BE CAUTIOUS THAT MULTIPLE 2979 01:35:12,092 --> 01:35:13,894 CASES HAVE BEEN REPORTED WHERE 2980 01:35:13,894 --> 01:35:15,028 WOMEN HAVEN'T BEEN DIAGNOSED 2981 01:35:15,028 --> 01:35:15,996 APPROPRIATELY BECAUSE OF THE 2982 01:35:15,996 --> 01:35:17,965 CO-PATHOLOGY, THEY MAY NOT QUITE 2983 01:35:17,965 --> 01:35:19,800 PRESENT THIS CLASSICALLY AS LEWY 2984 01:35:19,800 --> 01:35:21,168 BODY DEMENTIA, SO SOMETIMES IT'S 2985 01:35:21,168 --> 01:35:22,603 JUST THE CLINICAL PRESENTATION 2986 01:35:22,603 --> 01:35:26,440 MAY NOT ALWAYS BE AT CLEAR-CUT. 2987 01:35:26,440 --> 01:35:27,641 SO DEFINITELY THERE'S MORE AND 2988 01:35:27,641 --> 01:35:30,344 MORE LITERATURE EMERGING AROUND 2989 01:35:30,344 --> 01:35:32,079 DIFFERENCES BUT I THINK WE'VE 2990 01:35:32,079 --> 01:35:34,181 JUST STARTED, AT THE MOMENT OUR 2991 01:35:34,181 --> 01:35:35,582 TREATMENT APPROACHES ARE PRETTY 2992 01:35:35,582 --> 01:35:39,019 MUCH THE SAME FOR MEN AND WOMEN 2993 01:35:39,019 --> 01:35:40,087 BUT IT'S A POSSIBILITY THAT SOME 2994 01:35:40,087 --> 01:35:43,524 OF THE GENETIC MODIFIERS THAT 2995 01:35:43,524 --> 01:35:44,892 WE'RE DEVELOPING MAY BECOME MORE 2996 01:35:44,892 --> 01:35:46,860 DEFINED AND MAY REALLY PINPOINT 2997 01:35:46,860 --> 01:35:49,329 TO TREATMENTS IN MALES VERSUS 2998 01:35:49,329 --> 01:35:50,464 FEMALES. 2999 01:35:50,464 --> 01:35:51,298 MAYBE REBECCA, IF YOU WANT TO 3000 01:35:51,298 --> 01:35:53,133 ADD SOMETHING FROM THE 3001 01:35:53,133 --> 01:35:53,767 EPIDEMIOLOGY SIDE AS WELL. 3002 01:35:53,767 --> 01:35:56,436 >> SURE. 3003 01:35:56,436 --> 01:35:57,804 THOSE ARE CERTAINLY REALLY 3004 01:35:57,804 --> 01:35:58,805 INTERESTING DATA THAT YOU HAVE, 3005 01:35:58,805 --> 01:35:59,006 SONJA. 3006 01:35:59,006 --> 01:36:00,974 I THINK FROM THE VASCULAR WORLD, 3007 01:36:00,974 --> 01:36:02,910 THE TRICKY PART IS THAT WOME% 3008 01:36:02,910 --> 01:36:05,212 TEND TO BE TREATED DIFFERENTLY 3009 01:36:05,212 --> 01:36:07,514 FOR VASCULAR DISEASE THAN ARE 3010 01:36:07,514 --> 01:36:09,483 MEN. 3011 01:36:09,483 --> 01:36:10,751 SO STROKE BEING ONE EXAMPLE. 3012 01:36:10,751 --> 01:36:14,254 IN GENERAL, WOMEN TEND TO 3013 01:36:14,254 --> 01:36:15,622 OUTSURVIVE THEIR SPOUSES SO 3014 01:36:15,622 --> 01:36:16,757 GENERALLY, YES, THEY'RE OLDER 3015 01:36:16,757 --> 01:36:18,025 WHEN THEY'RE PRESENTING WITH 3016 01:36:18,025 --> 01:36:18,792 STROKE, FOR EXAMPLE, THEY'RE 3017 01:36:18,792 --> 01:36:20,294 MORE LIKELY TO BE LIVING ALONE 3018 01:36:20,294 --> 01:36:21,328 AND TO GET TO THE HOSPITAL 3019 01:36:21,328 --> 01:36:22,596 LATER, SO FOR THAT PLUS A 3020 01:36:22,596 --> 01:36:24,731 VARIETY OF REASONS, THEY'RE LESS 3021 01:36:24,731 --> 01:36:27,301 LIKELY TO GET INTERVENTIONS LIKE 3022 01:36:27,301 --> 01:36:29,102 TPA, THROMBECTOMY. 3023 01:36:29,102 --> 01:36:31,138 THEY'RE LESS LIKELY TO BE GIVEN 3024 01:36:31,138 --> 01:36:32,906 THE SAME SECONDARY PREVENTION 3025 01:36:32,906 --> 01:36:35,008 TREATMENTS ACTUALLY, AND THEY'RE 3026 01:36:35,008 --> 01:36:36,343 LESS LIKELY TO HAVE SORT OF THE 3027 01:36:36,343 --> 01:36:39,746 SAME DEGREE OF REHABILITATION 3028 01:36:39,746 --> 01:36:40,948 POST-STROKE THAN MIGHT MEN SO 3029 01:36:40,948 --> 01:36:41,949 THAT'S CERTAINLY GOING TO 3030 01:36:41,949 --> 01:36:43,717 CONFOUND HOW YOU LOOK AT SEX 3031 01:36:43,717 --> 01:36:45,118 DIFFERENCES IN LONG TERM 3032 01:36:45,118 --> 01:36:46,353 OUTCOMES INCLUDING COGNITIVE 3033 01:36:46,353 --> 01:36:48,822 OUTCOMES. 3034 01:36:48,822 --> 01:36:50,791 THERE ARE DATA IN GENERAL THAT 3035 01:36:50,791 --> 01:36:53,727 WOMEN TEND TO HAVE HIGHER RATES 3036 01:36:53,727 --> 01:36:55,295 OF DEMENTIA, BUT THE DATA ARE A 3037 01:36:55,295 --> 01:36:57,164 LITTLE BIT INCONSISTENT WITH 3038 01:36:57,164 --> 01:36:58,599 SOME OF THESE OTHER POTENTIAL 3039 01:36:58,599 --> 01:36:59,366 MECHANISMS, AND I THINK WE'RE 3040 01:36:59,366 --> 01:37:00,968 NOT YET AT THE POINT WHERE WE 3041 01:37:00,968 --> 01:37:01,969 COULD SAY ANYTHING ABOUT 3042 01:37:01,969 --> 01:37:05,138 DIFFERENCES IN TREATMENT, BUT AS 3043 01:37:05,138 --> 01:37:08,609 WE LEARN MORE AND UNDERSTAND THE 3044 01:37:08,609 --> 01:37:10,010 IMPORTANCE OF, FOR INSTANCE, HOW 3045 01:37:10,010 --> 01:37:10,777 COGNITIVE RESERVE MIGHT BE 3046 01:37:10,777 --> 01:37:12,079 DIFFERENT IN MEN VERSUS WOMEN, 3047 01:37:12,079 --> 01:37:13,280 THIS IS SOMETHING WE SHOULD 3048 01:37:13,280 --> 01:37:15,282 CONTINUE TO THINK ABOUT. 3049 01:37:15,282 --> 01:37:20,253 IT'S A GREAT QUESTION. 3050 01:37:20,253 --> 01:37:23,290 >> IS THERE ANY ROLE FOR DE NOVO 3051 01:37:23,290 --> 01:37:26,793 MUTATIONS AND GENETIC -- IN THE 3052 01:37:26,793 --> 01:37:29,496 BRAIN IN THESE NEURODEGENERATIVE 3053 01:37:29,496 --> 01:37:29,763 DISORDERS? 3054 01:37:29,763 --> 01:37:33,634 >> YEAH, I MEAN, THE STUDIES 3055 01:37:33,634 --> 01:37:35,002 LOOKING AT THAT SPECIFICALLY ARE 3056 01:37:35,002 --> 01:37:36,670 VERY LIMITED. 3057 01:37:36,670 --> 01:37:38,305 BUT THAT'S -- THERE IS A REAL 3058 01:37:38,305 --> 01:37:41,341 CONCERN THAT SOME OF THOSE 3059 01:37:41,341 --> 01:37:42,509 APPARENTLY SPORADIC CASES COULD 3060 01:37:42,509 --> 01:37:45,212 BE DUE TO ACQUIRED MUTATIONS, 3061 01:37:45,212 --> 01:37:46,313 MOSAICISM. 3062 01:37:46,313 --> 01:37:47,381 I DON'T THINK WE HAVE ALL THE 3063 01:37:47,381 --> 01:37:49,983 ANSWERS AS OF YET, BUT IT IS A 3064 01:37:49,983 --> 01:37:50,984 POSSIBILITY THAT THAT'S WHAT'S 3065 01:37:50,984 --> 01:37:54,354 GOING ON IN SOME OF THOSE 3066 01:37:54,354 --> 01:37:55,989 INDIVIDUALS. 3067 01:37:55,989 --> 01:37:56,723 >> OKAY. 3068 01:37:56,723 --> 01:37:57,724 ONE OF THE OTHER QUESTIONS 3069 01:37:57,724 --> 01:38:01,428 THAT'S COME UP IS JUST HEARING 3070 01:38:01,428 --> 01:38:03,930 ABOUT THE OVERLAP IN TERMS OF 3071 01:38:03,930 --> 01:38:05,999 ETIOLOGIC FACTORS AMONGST THE 3072 01:38:05,999 --> 01:38:09,269 DIFFERENT DEMENTIAS. 3073 01:38:09,269 --> 01:38:10,937 WHETHER, IN FACT, ONE MIGHT 3074 01:38:10,937 --> 01:38:12,539 CONSIDER AT LEAST AT SOME POINT, 3075 01:38:12,539 --> 01:38:14,474 NOT QUITE YET BUT AT SOME POINT, 3076 01:38:14,474 --> 01:38:17,878 ADOPTING A DIFFERENT TAXONOMY OF 3077 01:38:17,878 --> 01:38:22,315 THE DEMENTIAS RATHER THAN USING 3078 01:38:22,315 --> 01:38:25,819 TERMS LIKE LEWY BODY AND 3079 01:38:25,819 --> 01:38:27,654 FRONTOTEMPORAL AND ALZHEIMER'S 3080 01:38:27,654 --> 01:38:29,089 DEMENTIAS THAT MAYBE IT WOULD BE 3081 01:38:29,089 --> 01:38:31,024 BETTER TO ORGANIZE THESE IN 3082 01:38:31,024 --> 01:38:34,494 TERMS OF GENETIC RISK FACTORS OR 3083 01:38:34,494 --> 01:38:37,130 SOME OTHER MOLECULAR 3084 01:38:37,130 --> 01:38:38,265 DESIGNATIONS. 3085 01:38:38,265 --> 01:38:40,567 >> I THINK THAT'S A GREAT POINT. 3086 01:38:40,567 --> 01:38:44,438 THERE IS CERTAINLY DEVELOPMENTS 3087 01:38:44,438 --> 01:38:45,505 IN THAT SPACE WHERE WE'RE TRYING 3088 01:38:45,505 --> 01:38:48,875 TO USE BIOMARKER-DRIVEN 3089 01:38:48,875 --> 01:38:49,543 DIAGNOSTICS. 3090 01:38:49,543 --> 01:38:52,045 SO FOR EXAMPLE, JUST VERY 3091 01:38:52,045 --> 01:38:55,382 RECENTLY, A NEW BIOMARKER DRIVEN 3092 01:38:55,382 --> 01:38:56,450 DIAGNOSTICS HAVE ACTUALLY BEEN 3093 01:38:56,450 --> 01:38:57,684 PROPOSED FOR BOTH PARKINSON'S 3094 01:38:57,684 --> 01:39:00,387 DISEASE AND LEWY BODY DEMENTIA 3095 01:39:00,387 --> 01:39:04,524 COMBINED, THE NEURONAL A 3096 01:39:04,524 --> 01:39:05,826 SYNUCLEIN SYSTEM, WHICH HAS ITS 3097 01:39:05,826 --> 01:39:07,494 PROS AND CONS BUT IT'S REALLY 3098 01:39:07,494 --> 01:39:08,995 GOING KIND OF DOWN THAT ROUTE 3099 01:39:08,995 --> 01:39:10,897 OF, YOU KNOW, TRYING TO PINPOINT 3100 01:39:10,897 --> 01:39:12,799 WHAT IS THE UNDERLYING 3101 01:39:12,799 --> 01:39:14,434 PROTEINOPATHY BASED ON A 3102 01:39:14,434 --> 01:39:15,502 BIOMARKER AND THEN TARGET THOSE 3103 01:39:15,502 --> 01:39:16,636 PAICIALTS. 3104 01:39:16,636 --> 01:39:18,572 IT'S ALREADY BEING SOMEWHAT 3105 01:39:18,572 --> 01:39:19,306 SUCCESSFUL IN ALZHEIMER'S 3106 01:39:19,306 --> 01:39:20,307 DISEASE, WHERE WE HAVE BEEN 3107 01:39:20,307 --> 01:39:21,608 USING BIOMARKERS VERY 3108 01:39:21,608 --> 01:39:23,443 SUCCESSFULLY, WE CAN MEASURE 3109 01:39:23,443 --> 01:39:26,146 AMYLOID, WE CAN MEASURE TAU IN 3110 01:39:26,146 --> 01:39:27,914 CSF BUT NOW WE ALSO HAVE REALLY 3111 01:39:27,914 --> 01:39:30,851 GREAT PLASMA BIOMARKERS BECOMING 3112 01:39:30,851 --> 01:39:36,089 AVAILABLE AND FOR SYNUCLEIN AS 3113 01:39:36,089 --> 01:39:37,824 WELL, IT'S JUST FOR SOME OF THE 3114 01:39:37,824 --> 01:39:39,760 PROTEINOPATHIES WE DON'T HAVE 3115 01:39:39,760 --> 01:39:40,761 APPROPRIATE BIOMARKERS, WE 3116 01:39:40,761 --> 01:39:42,529 CANNOT DISTINGUISH THE DIFFERENT 3117 01:39:42,529 --> 01:39:43,697 TAUOPATHIES IN THE LIVING 3118 01:39:43,697 --> 01:39:45,298 PATIENT, WE CAN'T REALLY PICK 3119 01:39:45,298 --> 01:39:48,268 OUT TDP-43 PATHOLOGY BASED ON 3120 01:39:48,268 --> 01:39:49,469 THE BIOMARKER. 3121 01:39:49,469 --> 01:39:51,772 THERE'S REAL RESEARCH GOING ON 3122 01:39:51,772 --> 01:39:53,273 AND THAT MAY CHANGE BUT AT THE 3123 01:39:53,273 --> 01:39:56,009 MOMENT WHAT WE HAVE IS A LOT OF 3124 01:39:56,009 --> 01:40:00,981 ANS LANCILLARY TESTS, CLINICAL 3125 01:40:00,981 --> 01:40:02,849 SYNDROMES, ET CETERA, AND MAYBE 3126 01:40:02,849 --> 01:40:04,885 SOME GENETIC DATA THAT PINPOINTS 3127 01:40:04,885 --> 01:40:06,319 CERTAIN FAMILIAL FORMS, AND 3128 01:40:06,319 --> 01:40:08,054 THAT'S WHERE WE ARE, BUT IT 3129 01:40:08,054 --> 01:40:09,790 COULD CHANGE AS WE REALLY ARE 3130 01:40:09,790 --> 01:40:11,958 GETTING BETTER WITH BIOMARKERS. 3131 01:40:11,958 --> 01:40:13,593 >> AND I'LL JUST ADD THAT 3132 01:40:13,593 --> 01:40:15,262 CERTAINLY IN -- SORRY, GO AHEAD. 3133 01:40:15,262 --> 01:40:18,632 >> GO AHEAD, PLEASE. 3134 01:40:18,632 --> 01:40:19,466 >> 3135 01:40:19,466 --> 01:40:21,101 >> IN THE ALZHEIMER'S WORLD, 3136 01:40:21,101 --> 01:40:22,369 CERTAINLY THERE'S BEEN THIS MOVE 3137 01:40:22,369 --> 01:40:23,804 TO USING BIOMARKERS AS THE WAY 3138 01:40:23,804 --> 01:40:25,138 TO DEFINE WHAT'S HAPPENING, SO 3139 01:40:25,138 --> 01:40:27,307 THE ATN FRAMEWORK IS THIS IDEA 3140 01:40:27,307 --> 01:40:30,977 WHERE PEOPLE ARE IDENTIFIED BY 3141 01:40:30,977 --> 01:40:32,746 AMYLOID TAU AND 3142 01:40:32,746 --> 01:40:33,380 NEURODEGENERATION AND PRESENCE 3143 01:40:33,380 --> 01:40:34,848 OR ABSENCE AND THESE REPRESENT 3144 01:40:34,848 --> 01:40:35,682 SLIGHTLY DIFFERENT THINGS. 3145 01:40:35,682 --> 01:40:37,417 THERE'S BEEN A PUSH TO ADD V FOR 3146 01:40:37,417 --> 01:40:39,553 VASCULAR TO THAT FRAMEWORK, BUT 3147 01:40:39,553 --> 01:40:41,888 AS I POINTED OUT, THERE'S A LOT 3148 01:40:41,888 --> 01:40:44,157 OF DIFFERENT FORMS THAT VASCULAR 3149 01:40:44,157 --> 01:40:44,825 CONTRIBUTIONS CAN TAKE AND 3150 01:40:44,825 --> 01:40:46,026 THAT'S ACTUALLY WHY THERE'S BEEN 3151 01:40:46,026 --> 01:40:50,697 A MOVE AWAY FROM THE NAME 3152 01:40:50,697 --> 01:40:51,798 VASCULAR DEMENTIA AND MORE TO 3153 01:40:51,798 --> 01:40:52,999 THIS CONCEPT OF VASCULAR 3154 01:40:52,999 --> 01:40:54,100 CONTRIBUTIONS TO COGNITIVE 3155 01:40:54,100 --> 01:40:55,635 IMPAIRMENT AND DEMENTIA BECAUSE 3156 01:40:55,635 --> 01:40:57,137 IT'S A CONTRIBUTION BECAUSE OF 3157 01:40:57,137 --> 01:40:58,572 SO MUCH MIXED PATHOLOGY. 3158 01:40:58,572 --> 01:40:59,739 BUT I THINK YOU'RE ABSOLUTELY 3159 01:40:59,739 --> 01:41:03,577 RIGHT, THE OLD TERMINOLOGY IS 3160 01:41:03,577 --> 01:41:04,744 DANGEROUS IN SOME WAYS THAT WE 3161 01:41:04,744 --> 01:41:05,846 FORGET WE NEED TO THINK ABOUT 3162 01:41:05,846 --> 01:41:06,947 THE OVERLAP BETWEEN THESE 3163 01:41:06,947 --> 01:41:10,717 PATHOLOGIES. 3164 01:41:10,717 --> 01:41:12,118 >> ALL RIGHT. 3165 01:41:12,118 --> 01:41:12,519 WELL, THANK YOU. 3166 01:41:12,519 --> 01:41:13,854 WE HAVE A QUESTION THAT CAME IN 3167 01:41:13,854 --> 01:41:15,722 OVER THE WIRE. 3168 01:41:15,722 --> 01:41:19,860 CAN YOU COMMENT ON INFECTIOUS 3169 01:41:19,860 --> 01:41:21,161 PROCESSES THAT MIGHT CONTRIBUTE 3170 01:41:21,161 --> 01:41:22,162 TO DEMENTIA? 3171 01:41:22,162 --> 01:41:23,363 THE RECENT COVID-19 PANDEMIC 3172 01:41:23,363 --> 01:41:27,100 COMES TO MIND RIGHT AWAY. 3173 01:41:27,100 --> 01:41:28,802 >> SO THERE WERE A COUPLE OF BIG 3174 01:41:28,802 --> 01:41:30,103 PAPERS THAT CAME ALONG RECENTLY 3175 01:41:30,103 --> 01:41:31,304 SHOWING EVIDENCE OF COGNITIVE 3176 01:41:31,304 --> 01:41:33,707 DECLINE IN PEOPLE WHO HAD COVID. 3177 01:41:33,707 --> 01:41:35,008 THERE WERE A COUPLE EUROPEAN 3178 01:41:35,008 --> 01:41:36,543 STUDIES THAT WERE JUST PUBLISHED 3179 01:41:36,543 --> 01:41:38,411 RECENTLY. 3180 01:41:38,411 --> 01:41:39,479 ARIC IS PART OF A LARGE 3181 01:41:39,479 --> 01:41:41,648 CONSORTIUM OF OTHER COHORTS 3182 01:41:41,648 --> 01:41:43,083 CALLED C4R WHICH ARE TRYING TO 3183 01:41:43,083 --> 01:41:46,419 COLLECT DATA ON COVID -- FRANKLY 3184 01:41:46,419 --> 01:41:48,488 EARLY IN THE PANDEMIC WHEN THIS 3185 01:41:48,488 --> 01:41:52,225 EFFORT WAS STARTED, I DON'T 3186 01:41:52,225 --> 01:41:53,727 THINK ANYONE HAD A SENSE OF HOW 3187 01:41:53,727 --> 01:41:55,362 HIGHLY PREVALENT EXPOSURE TO 3188 01:41:55,362 --> 01:41:58,531 COVID AND PO POSITIVITY AT SOME 3189 01:41:58,531 --> 01:41:59,165 POINT OVER THE COURSE WERE GOING 3190 01:41:59,165 --> 01:42:01,568 TO BE IN THIS POPULATION. 3191 01:42:01,568 --> 01:42:03,069 BUT THAT'S GOING TO PROVIDE SOME 3192 01:42:03,069 --> 01:42:05,705 DATA DOWN THE ROAD. 3193 01:42:05,705 --> 01:42:07,207 WE KNOW IN GENERAL THERE'S 3194 01:42:07,207 --> 01:42:09,609 STUDIES THAT SUGGEST POST 3195 01:42:09,609 --> 01:42:11,044 INFECTIOUS PEOPLE OF HIGH RISK 3196 01:42:11,044 --> 01:42:11,912 OF STROKE AND I'VE ALREADY 3197 01:42:11,912 --> 01:42:14,414 MENTIONED THAT THAT'S CERTAINLY 3198 01:42:14,414 --> 01:42:15,482 ATTRIBUTED TO SUBSEQUENT RISK 3199 01:42:15,482 --> 01:42:16,016 FOR DEMENTIA. 3200 01:42:16,016 --> 01:42:17,350 WE KNOW THAT THERE'S EVIDENCE 3201 01:42:17,350 --> 01:42:20,253 FOR INCREASED SYSTEMIC 3202 01:42:20,253 --> 01:42:20,921 INFLAMMATION. 3203 01:42:20,921 --> 01:42:22,555 WHETHER THAT'S DUE TO RECURRENT 3204 01:42:22,555 --> 01:42:23,857 INFECTION OR SINGLE ACUTE 3205 01:42:23,857 --> 01:42:25,258 INFECTION, WE DON'T UNDERSTAND, 3206 01:42:25,258 --> 01:42:27,661 IS ASSOCIATED WITH A LOT OF 3207 01:42:27,661 --> 01:42:28,862 THESE COGNITIVE CHANGE MARKERS 3208 01:42:28,862 --> 01:42:31,564 AS WELL AS IMAGING MARKERS. 3209 01:42:31,564 --> 01:42:33,333 SO CERTAINLY THERE'S A LOT OF 3210 01:42:33,333 --> 01:42:37,170 EXCITING WORK IN THIS AREA. 3211 01:42:37,170 --> 01:42:38,338 AND THERE ARE LINKS. 3212 01:42:38,338 --> 01:42:40,140 IT'S HARD TO STUDY OBVIOUSLY IF 3213 01:42:40,140 --> 01:42:41,141 SOMEONE HAS AN INFECTION, 3214 01:42:41,141 --> 01:42:42,275 THEY'RE TREATED IN A CERTAIN 3215 01:42:42,275 --> 01:42:45,612 WAY, IT'S HARD TO KNOW WHICH 3216 01:42:45,612 --> 01:42:47,714 ASPECT OF IT MIGHT BE LEADING TO 3217 01:42:47,714 --> 01:42:49,482 RISK IN AN EPIDEMIOLOGIC SETTING 3218 01:42:49,482 --> 01:42:50,850 BUT WE'RE GOING TO LEARN A LOT 3219 01:42:50,850 --> 01:42:53,053 MORE ABOUT HOW COVID FITS IN, 3220 01:42:53,053 --> 01:42:54,120 WHAT LONG COVID LOOKS LIKE, HOW 3221 01:42:54,120 --> 01:42:55,422 THAT PATHOLOGY OVERLAPS WITH 3222 01:42:55,422 --> 01:42:56,856 THESE OTHER PATHOLOGIES, BUT I 3223 01:42:56,856 --> 01:42:59,893 DO WANT TO ADD THAT IF WE'RE 3224 01:42:59,893 --> 01:43:01,895 THINKING ABOUT THE EFFECTS OF 3225 01:43:01,895 --> 01:43:03,263 THE PANDEMIC RECENTLY, THERE'S 3226 01:43:03,263 --> 01:43:04,798 AN ADDITIONAL MAJOR ALTERATION 3227 01:43:04,798 --> 01:43:07,000 IN HEALTH WHICH IS SOCIAL 3228 01:43:07,000 --> 01:43:09,402 ISOLATION, WHICH RESULTED FROM 3229 01:43:09,402 --> 01:43:13,340 IN MANY PEOPLE WHO WERE ISOLATED 3230 01:43:13,340 --> 01:43:15,542 BECAUSE OF REDUCING INFECTION 3231 01:43:15,542 --> 01:43:17,043 RISK, THAT ALSO WE KNOW IS 3232 01:43:17,043 --> 01:43:18,144 ASSOCIATED WITH SOME ADVERSE 3233 01:43:18,144 --> 01:43:19,245 BRAIN HEALTH EFFECTS. 3234 01:43:19,245 --> 01:43:20,647 SO IT'S REALLY TRICKY TO 3235 01:43:20,647 --> 01:43:21,581 SEPARATE OUT THE DIFFERENT 3236 01:43:21,581 --> 01:43:26,419 COMPONENTS HERE. 3237 01:43:26,419 --> 01:43:28,855 >> FASCINATING TALK. 3238 01:43:28,855 --> 01:43:30,957 HAVE YOU LOOKED AT METFORMIN 3239 01:43:30,957 --> 01:43:33,360 WITH DEMENTIA? 3240 01:43:33,360 --> 01:43:35,095 HAVE YOU TAKEN A LOOK AT THE 3241 01:43:35,095 --> 01:43:37,130 ACTION OF METFORMIN? 3242 01:43:37,130 --> 01:43:40,800 >> METFORMIN. 3243 01:43:40,800 --> 01:43:43,003 WELL, METFORMIN IS A VERY 3244 01:43:43,003 --> 01:43:43,737 INTERESTING COMPOUND. 3245 01:43:43,737 --> 01:43:45,872 YOU KNOW, IT'S A DIABETES DRUG, 3246 01:43:45,872 --> 01:43:49,976 BUT IT'S ALSO A DRUG THAT HAS 3247 01:43:49,976 --> 01:43:51,611 BEEN -- AT LEAST THERE'S A GOOD 3248 01:43:51,611 --> 01:43:54,214 BODY OF LITERATURE IN ANIMALS SO 3249 01:43:54,214 --> 01:43:56,082 IT CAN EXPAND LIFE EXPECTANCY. 3250 01:43:56,082 --> 01:43:57,951 SO THERE'S A REALLY INTERESTING 3251 01:43:57,951 --> 01:44:01,521 LINK THAT IT COULD HAVE A LOT OF 3252 01:44:01,521 --> 01:44:03,590 POSITIVE METABOLIC EFFECTS. 3253 01:44:03,590 --> 01:44:05,325 AND SO WE HAVEN'T REALLY STUDIED 3254 01:44:05,325 --> 01:44:10,096 IT OURSELVES DIRECTLY WITH 3255 01:44:10,096 --> 01:44:11,998 DEMENTIA, BUT I WONDER IF 3256 01:44:11,998 --> 01:44:13,600 REBECCA HAS ANY ADDITIONAL DATA 3257 01:44:13,600 --> 01:44:15,368 FROM THE EPIDEMIOLOGY FIELD 3258 01:44:15,368 --> 01:44:21,708 ABOUT METFORMIN SPECIFICALLY AS 3259 01:44:21,708 --> 01:44:23,209 A TREATMENT FOR DEMENTIA. 3260 01:44:23,209 --> 01:44:25,311 >> SO BROADLY, CLINICAL TRIALS 3261 01:44:25,311 --> 01:44:26,413 LOOKING AT DIABETES TREATMENT 3262 01:44:26,413 --> 01:44:31,851 MORE BROADLY SUCH AS ACORMIND 3263 01:44:31,851 --> 01:44:33,520 DID NOT SHOW REDUCTION IN 3264 01:44:33,520 --> 01:44:33,887 DEMENTIA RATES. 3265 01:44:33,887 --> 01:44:35,722 THIS IS CONSISTENT WITH THESE 3266 01:44:35,722 --> 01:44:39,092 PATTERNS OF MOST OBSERVATIONAL 3267 01:44:39,092 --> 01:44:40,360 DATA -- EVEN THOUGH WE SEE 3268 01:44:40,360 --> 01:44:41,161 STRONG RELATIONSHIPS WITH 3269 01:44:41,161 --> 01:44:42,896 DIABETES CERTAINLY. 3270 01:44:42,896 --> 01:44:44,164 SOME -- I CERTAINLY AM FAMILIAR 3271 01:44:44,164 --> 01:44:45,298 WITH SOME STUDIES THAT HAVE 3272 01:44:45,298 --> 01:44:47,500 LOOKED AT METFORMIN AND SHOWN 3273 01:44:47,500 --> 01:44:51,738 REDUCED ASSOCIATIONS WITH 3274 01:44:51,738 --> 01:44:53,173 DEMENTIA. 3275 01:44:53,173 --> 01:44:54,607 THREASES A BIG CONCERN ABOUT 3276 01:44:54,607 --> 01:44:57,343 CONFOUNDING BY INDICATION, THESE 3277 01:44:57,343 --> 01:44:58,511 STUDIES OF PEOPLE ON MEDICATIONS 3278 01:44:58,511 --> 01:44:59,546 ARE VERY DIFFERENT FROM PEOPLE 3279 01:44:59,546 --> 01:44:59,846 WHO AREN'T. 3280 01:44:59,846 --> 01:45:03,416 SO YOU HAVE TO BE -- I HATE TO 3281 01:45:03,416 --> 01:45:05,251 SOUND LIKE A SKEPTIC ABOUT 3282 01:45:05,251 --> 01:45:06,953 EVERYTHING THAT'S NOT SORT OF 3283 01:45:06,953 --> 01:45:11,458 CLEARLY ADJUSTED AND IT'S 3284 01:45:11,458 --> 01:45:12,258 CONFOUNDING AS AN ADDRESS BUT 3285 01:45:12,258 --> 01:45:14,227 IT'S NOT CLEAR TO ME THAT 3286 01:45:14,227 --> 01:45:16,563 EVIDENCE ARE CLEARLY POINTING TO 3287 01:45:16,563 --> 01:45:19,566 MEMETFORMIN IN REDUCING DEMENTIA 3288 01:45:19,566 --> 01:45:21,201 RISK BUT I SUSPECT THIS IS ALSO 3289 01:45:21,201 --> 01:45:22,502 AN EXAMPLE WHERE IT MAY BE A 3290 01:45:22,502 --> 01:45:23,670 LONGER EFFECT AND CERTAINLY 3291 01:45:23,670 --> 01:45:24,904 DOING IN A SHORT PERIOD OF TIME 3292 01:45:24,904 --> 01:45:26,673 MAY NOT BE ENOUGH TO ACTUALLY 3293 01:45:26,673 --> 01:45:28,274 SHOW A CHANGE IN COGNITIVE 3294 01:45:28,274 --> 01:45:29,008 OUTCOMES. 3295 01:45:29,008 --> 01:45:32,011 BUT THAT'S AN EXAMPLE WHERE 3296 01:45:32,011 --> 01:45:33,046 UNDERSTANDING THE MECHANISTIC 3297 01:45:33,046 --> 01:45:35,014 LINKS IN IMAGING MAY GIVE US A 3298 01:45:35,014 --> 01:45:36,082 SURROGATE END POINT THAT WE CAN 3299 01:45:36,082 --> 01:45:38,051 USE TO UNDERSTAND IF THERE'S A 3300 01:45:38,051 --> 01:45:39,319 POSSIBILITY OF POTENTIAL 3301 01:45:39,319 --> 01:45:40,687 INTERVENTIONS FOR LONGER TERM 3302 01:45:40,687 --> 01:45:44,624 OUTCOMES. 3303 01:45:44,624 --> 01:45:45,592 >> WELL, THANK YOU. 3304 01:45:45,592 --> 01:45:46,726 SO WE HAVE SEVERAL QUESTIONS 3305 01:45:46,726 --> 01:45:50,230 THAT HAVE COME IN OVER THE WIRE. 3306 01:45:50,230 --> 01:45:52,232 WHAT COULD BE THE NEXT STUDIES 3307 01:45:52,232 --> 01:45:54,734 DONE TO TARGET MISSING 3308 01:45:54,734 --> 01:45:57,070 UNDERSTANDING BETWEEN COGNITIVE 3309 01:45:57,070 --> 01:46:05,712 DECLINE AND MID LIFE LIFESTYLES? 3310 01:46:05,712 --> 01:46:07,013 SO I THINK I'M GOING TO BUILD ON 3311 01:46:07,013 --> 01:46:08,081 THAT LAST COMMENT THAT I MADE 3312 01:46:08,081 --> 01:46:09,415 WHICH IS THAT WE ARE NOT -- I 3313 01:46:09,415 --> 01:46:10,650 DON'T THINK ANYONE IS EVER GOING 3314 01:46:10,650 --> 01:46:15,288 TO DO THE TRIAL THAT IS LEADING 3315 01:46:15,288 --> 01:46:17,757 TO INTERVENTIONS IN MID LIFE 3316 01:46:17,757 --> 01:46:18,858 VASCULAR RISK FACTORS AND 3317 01:46:18,858 --> 01:46:19,959 FOLLOWS THEM FOR 30 YEARS 3318 01:46:19,959 --> 01:46:20,927 BECAUSE THAT'S NOT PRACTICAL. 3319 01:46:20,927 --> 01:46:24,731 I THINK THE KEY IS FINDING 3320 01:46:24,731 --> 01:46:25,798 BIOMARKERS THAT ARE REASONABLE 3321 01:46:25,798 --> 01:46:26,799 SURROGATE END POINTS AND THERE 3322 01:46:26,799 --> 01:46:28,968 IS A STUDY CALLED MARK VCID 3323 01:46:28,968 --> 01:46:30,937 WHICH IS AN STRAL MURAL 3324 01:46:30,937 --> 01:46:31,804 NINDS-FUNDED STUDY WHICH IS 3325 01:46:31,804 --> 01:46:34,541 TRYING TO DO EXACTLY THAT. 3326 01:46:34,541 --> 01:46:36,176 IDENTIFY BIOMARKERS FOR VASCULAR 3327 01:46:36,176 --> 01:46:38,478 CONTRIBUTIONS TO DEMENTIA SO 3328 01:46:38,478 --> 01:46:39,646 THAT POTENTIALLY AMONG OTHER 3329 01:46:39,646 --> 01:46:40,246 THINGS, THEY COULD BE PLUGGED 3330 01:46:40,246 --> 01:46:42,382 INTO A TRIAL SETTING SO THAT 3331 01:46:42,382 --> 01:46:43,616 INTERVENTIONS COULD HAPPEN IN 3332 01:46:43,616 --> 01:46:45,185 MID LIFE AND IF WE SEE A 3333 01:46:45,185 --> 01:46:46,819 SURROGATE END POINT THAT'S 3334 01:46:46,819 --> 01:46:47,887 MODIFIED, THAT MIGHT ACTUALLY 3335 01:46:47,887 --> 01:46:50,323 POINT TO THAT AS BEING A 3336 01:46:50,323 --> 01:46:52,058 VALUABLE INTERVENTION LONGER 3337 01:46:52,058 --> 01:46:52,625 TERM. 3338 01:46:52,625 --> 01:46:56,062 I THINK THE OTHER CONSIDERATION 3339 01:46:56,062 --> 01:46:57,497 IS -- SO IN THE ALZHEIMER'S 3340 01:46:57,497 --> 01:46:59,899 COMMUNITY IN GENERAL, TRIALS 3341 01:46:59,899 --> 01:47:02,068 DON'T ENROLL PEOPLE WITH 3342 01:47:02,068 --> 01:47:02,669 VASCULAR DISEASE BECAUSE THEY 3343 01:47:02,669 --> 01:47:04,270 WANT TO SEE THE PURE EFFECT OF 3344 01:47:04,270 --> 01:47:05,238 POTENTIAL TREATMENT. 3345 01:47:05,238 --> 01:47:07,273 I UNDERSTAND THAT, IN LEWY BODY 3346 01:47:07,273 --> 01:47:08,374 DEMENTIA, I SUSPECT THAT YOU 3347 01:47:08,374 --> 01:47:09,676 DON'T WANT TO ENROLL PEOPLE WHO 3348 01:47:09,676 --> 01:47:11,277 HAVE A LOT OF MIXED PATHOLOGY AS 3349 01:47:11,277 --> 01:47:13,513 A SORT OF PROOF OF CONCEPT. 3350 01:47:13,513 --> 01:47:17,450 IN THE VASCULAR WORLDS, WE DON'T 3351 01:47:17,450 --> 01:47:18,418 NECESSARILY PAY ATTENTION TO THE 3352 01:47:18,418 --> 01:47:20,119 OTHER PATHOLOGIES EITHER AND I 3353 01:47:20,119 --> 01:47:21,221 THINK THE MORE WE UNDERSTAND 3354 01:47:21,221 --> 01:47:22,956 ABOUT WHO WE'RE RECRUITING INTO 3355 01:47:22,956 --> 01:47:23,856 STUDIES, THE MORE WE'LL 3356 01:47:23,856 --> 01:47:25,024 UNDERSTAND WHY WE MIGHT SEE AN 3357 01:47:25,024 --> 01:47:26,359 EFFECT OR WHY WE DON'T. 3358 01:47:26,359 --> 01:47:27,660 SO I THINK THINKING ABOUT THESE 3359 01:47:27,660 --> 01:47:30,563 MIXED POPULATIONS COULD BE 3360 01:47:30,563 --> 01:47:32,999 EXCITING, THINKING ABOUT 3361 01:47:32,999 --> 01:47:33,866 MULTIMODAL INTERVENTIONS THAT 3362 01:47:33,866 --> 01:47:35,969 EVEN EXTEND TO AD-SPECIFIC 3363 01:47:35,969 --> 01:47:38,338 TREATMENTS AS WE START TO 3364 01:47:38,338 --> 01:47:39,339 DEVELOP THOSE COULD BE PRETTY 3365 01:47:39,339 --> 01:47:40,173 EXCITING. 3366 01:47:40,173 --> 01:47:41,741 BUT I THINK FOR THE TIME BEING, 3367 01:47:41,741 --> 01:47:44,444 FINDING WHAT'S A GOOD SURROGATE 3368 01:47:44,444 --> 01:47:46,546 END POINT THAT WE'RE WILLING TO 3369 01:47:46,546 --> 01:47:50,283 TRUST WE THINK ACTUALLY 3370 01:47:50,283 --> 01:47:52,185 REPRESENTS AN IMPORTANT PATHWAY 3371 01:47:52,185 --> 01:47:54,654 ON HOW THESE RISK FACTORS MIGHT 3372 01:47:54,654 --> 01:47:58,358 BRING LATER LIFE BRAIN HEALTH. 3373 01:47:58,358 --> 01:47:59,559 GENOMICS MIGHT -- IN SORT OF 3374 01:47:59,559 --> 01:48:00,260 DETERMINING WHO ARE THE PEOPLE 3375 01:48:00,260 --> 01:48:03,029 AT HIGHEST RISK WHO WE SHOULD 3376 01:48:03,029 --> 01:48:03,296 STUDY. 3377 01:48:03,296 --> 01:48:06,332 >> IDEALLY WE WANT TO HAVE A 3378 01:48:06,332 --> 01:48:07,734 ELECTRONIC HEALTHCARE DATABASE 3379 01:48:07,734 --> 01:48:10,870 FROM BIRTH ALL THE WAY UP TO 3380 01:48:10,870 --> 01:48:13,740 DEATH, SO NOT JUST -- WE HAD 3381 01:48:13,740 --> 01:48:15,508 MEDICARE WHICH STARTS AT 65 SO 3382 01:48:15,508 --> 01:48:16,676 IDEALLY YOU MAY HAVE TO GO TO 3383 01:48:16,676 --> 01:48:18,111 OTHER COUNTRIES, EUROPEAN 3384 01:48:18,111 --> 01:48:19,178 COUNTRIES WHERE THEY REALLY HAVE 3385 01:48:19,178 --> 01:48:21,047 KIND OF A SOCIALIZED KIND OF 3386 01:48:21,047 --> 01:48:23,683 HEALTHCARE SYSTEM WHERE WE CAN 3387 01:48:23,683 --> 01:48:27,287 LOOK AT THESE RISK FACTORS ON A 3388 01:48:27,287 --> 01:48:29,022 LONGITUDAL SCALE. 3389 01:48:29,022 --> 01:48:30,356 SO EPIDEMIOLOGICAL STUDIES ARE 3390 01:48:30,356 --> 01:48:32,492 STILL VERY RELEVANT IN THIS 3391 01:48:32,492 --> 01:48:33,793 CONTEXT BUT IT'S HARD TO PIECE 3392 01:48:33,793 --> 01:48:35,328 THE CIRCUMSTANTIAL EVIDENCE ALL 3393 01:48:35,328 --> 01:48:36,562 TOGETHER BECAUSE NOT EVERYBODY 3394 01:48:36,562 --> 01:48:38,164 WILL BE ABLE TO DO ALL THESE 3395 01:48:38,164 --> 01:48:39,932 LONG TERM CLINICAL TRIALS OVER 3396 01:48:39,932 --> 01:48:41,067 DECADES BUT EVIDENCE THAT'S 3397 01:48:41,067 --> 01:48:42,568 EMERGING IS STILL QUITE 3398 01:48:42,568 --> 01:48:43,536 COMPELLING THAT IT'S REALLY 3399 01:48:43,536 --> 01:48:44,637 IMPORTANT TO TAKE CARE OF YOUR 3400 01:48:44,637 --> 01:48:46,706 VASCULAR HEALTH, BE ACTIVE AND 3401 01:48:46,706 --> 01:48:47,073 HEALTHY. 3402 01:48:47,073 --> 01:48:48,441 ALL THE THINGS WE WERE TOLD BY 3403 01:48:48,441 --> 01:48:51,010 OUR MOTHERS. 3404 01:48:51,010 --> 01:48:52,378 >> ANOTHER THING I GUESS WE'VE 3405 01:48:52,378 --> 01:48:55,882 BEEN TOLD BY OUR MOTHERS AND 3406 01:48:55,882 --> 01:48:57,150 PERHAPS JUST TO OBSERVE THROUGH 3407 01:48:57,150 --> 01:48:59,485 LIFE IS THE QUESTION OF THE ROLE 3408 01:48:59,485 --> 01:49:02,655 OF SLEEP IN THE DEVELOPMENT OF 3409 01:49:02,655 --> 01:49:03,489 COGNITIVE IMPAIRMENT. 3410 01:49:03,489 --> 01:49:06,359 ARE THERE ANY DATA WITH REGARD 3411 01:49:06,359 --> 01:49:09,962 TO AVERAGE AMOUNTS OF SLEEP OR 3412 01:49:09,962 --> 01:49:13,132 OCCUPATIONS THAT LEAD TO SLEEP 3413 01:49:13,132 --> 01:49:14,667 DEPRIVATION AND RISK OF 3414 01:49:14,667 --> 01:49:19,806 COGNITIVE DECLINE OR DEMENTIA? 3415 01:49:19,806 --> 01:49:21,107 >> WE BOTH HAVE SOMETHING TO SAY 3416 01:49:21,107 --> 01:49:21,441 ABOUT THIS. 3417 01:49:21,441 --> 01:49:22,909 DO YOU WANT TO TALK ABOUT IN THE 3418 01:49:22,909 --> 01:49:27,113 CONTEXT -- I HAVE A LOT TO SAY. 3419 01:49:27,113 --> 01:49:31,150 >> I'LL LEAVE THE -- BUT YES, 3420 01:49:31,150 --> 01:49:32,518 SLEEP DISRUPTION IS A VERY 3421 01:49:32,518 --> 01:49:34,620 COMMON FEATURE OF MOST 3422 01:49:34,620 --> 01:49:35,922 NEURODEGENERATIVE DISEASES, AND 3423 01:49:35,922 --> 01:49:37,256 YOU KNOW, IT IS AN IMPORTANT 3424 01:49:37,256 --> 01:49:38,991 THING THAT WE REALLY ADDRESS IN 3425 01:49:38,991 --> 01:49:40,860 THE CLINIC, PAYING ATTENTION TO 3426 01:49:40,860 --> 01:49:43,363 SLEEP DYSFUNCTION AND TRYING TO 3427 01:49:43,363 --> 01:49:45,331 REALLY TREAT THE PATIENTS, AND 3428 01:49:45,331 --> 01:49:46,299 REALLY COUNSEL PATIENTS ABOUT 3429 01:49:46,299 --> 01:49:48,167 SLEEP HYGIENE. 3430 01:49:48,167 --> 01:49:49,569 BECAUSE IF YOU DO NOT SLEEP 3431 01:49:49,569 --> 01:49:51,204 WELL, YOU CANNOT THINK WELL. 3432 01:49:51,204 --> 01:49:53,172 SO NOBODY DOES THAT. 3433 01:49:53,172 --> 01:49:55,808 SO IT'S A CRUCIAL METABOLIC 3434 01:49:55,808 --> 01:49:57,443 STATE THAT WE REALLY NEED TO BE 3435 01:49:57,443 --> 01:50:00,313 ABLE TO TEACH OUR PATIENTS WHAT 3436 01:50:00,313 --> 01:50:03,349 IS GOOD SLEEP HYGIENE. 3437 01:50:03,349 --> 01:50:05,084 BUT THEN THE QUESTION ALSO IS 3438 01:50:05,084 --> 01:50:06,419 WHAT IS CHICKEN VERSUS EGG. 3439 01:50:06,419 --> 01:50:08,554 I MEAN, IN SOME INSTANCES, IF 3440 01:50:08,554 --> 01:50:10,223 YOU HAVE A LOT OF SLEEP 3441 01:50:10,223 --> 01:50:11,991 DISRUPTION, INDEPENDENTLY TO 3442 01:50:11,991 --> 01:50:13,626 WHICH DOES THAT DRIVE THE 3443 01:50:13,626 --> 01:50:14,927 UNDERLYING DISEASE PATHOGENESIS. 3444 01:50:14,927 --> 01:50:16,929 SO MAYBE THE EPIDEMIOLOGY CAN 3445 01:50:16,929 --> 01:50:18,631 GIVE YOU A FEW MORE QUEUES, SO 3446 01:50:18,631 --> 01:50:19,899 REBECCA, WHAT DO YOU THINK? 3447 01:50:19,899 --> 01:50:23,436 >> SO THIS WAS NOT A PLANT BUT 3448 01:50:23,436 --> 01:50:25,638 I'LL POINT OUT THAT I WAS THE 3449 01:50:25,638 --> 01:50:26,773 LEAD AUTHOR ON A SCIENTIFIC 3450 01:50:26,773 --> 01:50:27,740 STATEMENT FROM THE AMERICAN 3451 01:50:27,740 --> 01:50:28,508 HEART ASSOCIATION JUST PUBLISHED 3452 01:50:28,508 --> 01:50:31,077 IN JANUARY ON SLEEP AND SLEEP 3453 01:50:31,077 --> 01:50:34,046 DISORDER AND BROAT BREATHING ANN 3454 01:50:34,046 --> 01:50:36,115 HEALTH WHERE A GROUP OF EXPERTS 3455 01:50:36,115 --> 01:50:37,417 REALLY SORT OF DESCRIBES BOTH 3456 01:50:37,417 --> 01:50:39,719 THE ANIMAL DATA POINTING TO THE 3457 01:50:39,719 --> 01:50:44,323 IMPORTANCE OF SLEEP QUALITY AND 3458 01:50:44,323 --> 01:50:46,292 QUANTITY AND THE DANGER OF SLEEP 3459 01:50:46,292 --> 01:50:47,126 DISORDER AND BREATHING ON BRAIN 3460 01:50:47,126 --> 01:50:47,560 HEALTH. 3461 01:50:47,560 --> 01:50:49,462 SO THERE'S EVIDENCE FROM 3462 01:50:49,462 --> 01:50:50,530 EPIDEMIOLOGIC DATA THAT TOO 3463 01:50:50,530 --> 01:50:51,531 LITTLE SLEEP IS ASSOCIATED WITH 3464 01:50:51,531 --> 01:50:54,567 A HIGHER RISK OF DEMENTIA, BUT 3465 01:50:54,567 --> 01:50:56,202 THIS LAST POINT AND ALSO THAT 3466 01:50:56,202 --> 01:50:57,437 SLEEP DISORDERED BREATHING IS 3467 01:50:57,437 --> 01:50:58,905 ASSOCIATED WITH A HIGHER RISK OF 3468 01:50:58,905 --> 01:50:59,906 DEMENTIA. 3469 01:50:59,906 --> 01:51:01,641 THE BIGGEST ISSUE IS THIS 3470 01:51:01,641 --> 01:51:03,409 CHICKEN OF EGG, THIS IDEA OF 3471 01:51:03,409 --> 01:51:04,510 REVERSE CAUSATION, WHICH IS THAT 3472 01:51:04,510 --> 01:51:08,080 WE KNOW THAT DEMENTIA ITSELF CAN 3473 01:51:08,080 --> 01:51:09,449 LEAD TO ALTERATIONS IN SLEEP. 3474 01:51:09,449 --> 01:51:11,851 WE KNOW THERE'S EVIDENCE FOR AN 3475 01:51:11,851 --> 01:51:13,419 ASSOCIATION BETWEEN SLEEP 3476 01:51:13,419 --> 01:51:14,821 DISTURBANCES AND SUBSEQUENT 3477 01:51:14,821 --> 01:51:16,422 COGNITIVE DECLINE. 3478 01:51:16,422 --> 01:51:18,191 IN THE ARIC COHORT, WE ACTUALLY 3479 01:51:18,191 --> 01:51:21,127 HAVE A SUBSTUDY WHICH I LED WHEN 3480 01:51:21,127 --> 01:51:27,200 I WAS AT HOPKINS CALLED THE ARIC 3481 01:51:27,200 --> 01:51:34,240 PET SLEEP STUDY, THEY HAVE MID 3482 01:51:34,240 --> 01:51:34,874 LIFE POLYSOMOGRAPHY AS WELL AS 3483 01:51:34,874 --> 01:51:35,675 SLEEP QUESTIONNAIRES SO THAT 3484 01:51:35,675 --> 01:51:37,310 WE'RE ACTUALLY ABLE TO SEPARATE 3485 01:51:37,310 --> 01:51:39,612 IN TIME THE SLEEP DISTURBANCES 3486 01:51:39,612 --> 01:51:40,913 AS WELL AS LATER LIFE BRAIN 3487 01:51:40,913 --> 01:51:42,682 AMYLOID AND INCIDENT DEMENTIA. 3488 01:51:42,682 --> 01:51:45,818 SO SLEEP IS THE NEW LIFE -- WHAT 3489 01:51:45,818 --> 01:51:48,788 WAS LIFE SIMPLE 7 AND IS NOW 3490 01:51:48,788 --> 01:51:49,856 LIFE ESSENTIAL 8, THE EIGHTH 3491 01:51:49,856 --> 01:51:51,424 COMPONENT IS SLEEP IS THAT THE 3492 01:51:51,424 --> 01:51:51,958 AMERICAN HEART ASSOCIATION 3493 01:51:51,958 --> 01:51:52,158 ADDED. 3494 01:51:52,158 --> 01:51:53,459 SO IT'S UNDOUBTEDLY IMPORTANT, 3495 01:51:53,459 --> 01:51:54,994 IT'S IMPORTANT FOR STROKE RISK. 3496 01:51:54,994 --> 01:51:58,498 WE KNOW THAT AFTER STROKE, SLEEP 3497 01:51:58,498 --> 01:52:00,466 DISTURBANCES CAN LEAD TO WORSE 3498 01:52:00,466 --> 01:52:01,701 RECOVERY AS WELL AS SORT OF 3499 01:52:01,701 --> 01:52:04,837 WORSE REHAB POTENTIAL, SO IT'S 3500 01:52:04,837 --> 01:52:05,938 INCREDIBLY IMPORTANT AND IT 3501 01:52:05,938 --> 01:52:08,040 APPEARS TO BE SOMEWHAT 3502 01:52:08,040 --> 01:52:09,442 INDEPENDENT OF THESE VASCULAR 3503 01:52:09,442 --> 01:52:10,209 RISK FACTORS. 3504 01:52:10,209 --> 01:52:11,844 THE OTHER REALLY IMPORTANT WAY 3505 01:52:11,844 --> 01:52:13,279 THAT SLEEP IS IMPORTANT IS 3506 01:52:13,279 --> 01:52:15,147 THROUGH THIS IDEA OF THE 3507 01:52:15,147 --> 01:52:15,615 LYMPHATIC SYSTEM. 3508 01:52:15,615 --> 01:52:17,550 SO I MENTIONED EARLY ON WHEN I 3509 01:52:17,550 --> 01:52:20,186 WAS DISCUSSING POSSIBLE BIOLOGIC 3510 01:52:20,186 --> 01:52:22,121 MECHANISMS THAT THE LYMPHATIC 3511 01:52:22,121 --> 01:52:23,890 SYSTEM HAS THIS GENERAL CONCEPT 3512 01:52:23,890 --> 01:52:25,091 OF CLEARING TOXINS FROM THE 3513 01:52:25,091 --> 01:52:27,260 BRAIN SUCH AS AMYLOID BETA, AND 3514 01:52:27,260 --> 01:52:28,361 WE THINK THAT THAT HAPPENS 3515 01:52:28,361 --> 01:52:30,162 DURING SLOW WAVE SLEEP WHICH IS 3516 01:52:30,162 --> 01:52:31,531 ONE OF THE STAGES OF SLEEP AND 3517 01:52:31,531 --> 01:52:33,232 IN GENERAL, IF YOU HAVE ANYTHING 3518 01:52:33,232 --> 01:52:36,168 THAT LEADS TO LESS EFFICIENT OR 3519 01:52:36,168 --> 01:52:37,570 LESS SLOW WAVE SLEEP IT'S 3520 01:52:37,570 --> 01:52:38,771 POSSIBLE YOUR LYMPHATIC FUNCTION 3521 01:52:38,771 --> 01:52:40,640 WILL BE WORSE, THUS LEADING TO 3522 01:52:40,640 --> 01:52:42,942 POTENTIAL BUILDUP OF THESE 3523 01:52:42,942 --> 01:52:43,476 PROTEINS. 3524 01:52:43,476 --> 01:52:44,911 SO THANK YOU FOR ASKING ABOUT 3525 01:52:44,911 --> 01:52:45,111 SLEEP. 3526 01:52:45,111 --> 01:52:46,679 I DO WANT TO SAY, I THINK WIN IS 3527 01:52:46,679 --> 01:52:48,614 TRYING TO ASK A QUESTION ON ZOOM 3528 01:52:48,614 --> 01:52:50,049 AND I DON'T KNOW IF THAT'S -- I 3529 01:52:50,049 --> 01:52:51,717 JUST WANT TO MAKE SURE THAT -- 3530 01:52:51,717 --> 01:52:54,453 >> YES, LET'S HAVE WIN POSE HIS 3531 01:52:54,453 --> 01:52:56,088 QUESTION. 3532 01:52:56,088 --> 01:52:56,389 WIN? 3533 01:52:56,389 --> 01:53:01,327 >> SO MANY YEARS AGO, THE TOWN 3534 01:53:01,327 --> 01:53:05,364 OF FRAMINGHAM WAS SUBJECT TO 3535 01:53:05,364 --> 01:53:07,900 TOTAL DATA RECALL, AND THAT WAS 3536 01:53:07,900 --> 01:53:09,769 FOLLOWED UP UNTIL THE LAST I 3537 01:53:09,769 --> 01:53:12,805 HEARD MAYBE ABOUT 15 YEARS AGO. 3538 01:53:12,805 --> 01:53:16,976 SO QUESTION. 3539 01:53:16,976 --> 01:53:19,145 DATA FROM THE FRAMINGHAM STUDY 3540 01:53:19,145 --> 01:53:21,147 ACTUALLY WELL DONE AND OVER A 3541 01:53:21,147 --> 01:53:22,882 PERIOD OF TIME, ARE THEY 3542 01:53:22,882 --> 01:53:24,183 ACCESSIBLE AND ARE THEY 3543 01:53:24,183 --> 01:53:25,418 VALUABLE, AND AS A SUBSET TO 3544 01:53:25,418 --> 01:53:27,153 THAT, ONE READS ABOUT THE 3545 01:53:27,153 --> 01:53:29,689 RELATIONSHIP BETWEEN ZIP CODES 3546 01:53:29,689 --> 01:53:31,791 AND VARIOUS DEGENERATIVE 3547 01:53:31,791 --> 01:53:33,626 DISEASES OF METABOLISM, ET 3548 01:53:33,626 --> 01:53:34,927 CETERA, ET CETERA. 3549 01:53:34,927 --> 01:53:37,363 IS THERE A RELATIONSHIP TWEENL 3550 01:53:37,363 --> 01:53:40,533 ZIP CODES AND DEMENTIA? 3551 01:53:40,533 --> 01:53:43,469 >> SO I THINK I'LL TA TAKE A FIT 3552 01:53:43,469 --> 01:53:44,236 STAB AT THAT. 3553 01:53:44,236 --> 01:53:45,404 CERTAINLY THE FRAMINGHAM DATA 3554 01:53:45,404 --> 01:53:45,972 ARE WONDERFUL. 3555 01:53:45,972 --> 01:53:47,707 WE HAVE A LOT OF CONSORTIA WHERE 3556 01:53:47,707 --> 01:53:51,410 WE PULL DATA BETWEEN ARIC AND 3557 01:53:51,410 --> 01:53:52,078 FRAMINGHAM. 3558 01:53:52,078 --> 01:53:53,813 FRAMINGHAM IS NOT AN INCREDIBLY 3559 01:53:53,813 --> 01:53:55,414 DIVERSE COHORT AND THAT'S REALLY 3560 01:53:55,414 --> 01:53:56,582 IN MY OPINION THE MAJOR 3561 01:53:56,582 --> 01:53:59,118 POTENTIAL WEAKNESS. 3562 01:53:59,118 --> 01:54:00,620 BUT WE'VE LEARNED A TREMENDOUS 3563 01:54:00,620 --> 01:54:01,487 AMOUNT AND WE CONTINUE TO DO SO 3564 01:54:01,487 --> 01:54:04,690 FROM THE FRAMINGHAM STUDY. 3565 01:54:04,690 --> 01:54:06,125 AND THERE ARE FRIENDS THAT ARE 3566 01:54:06,125 --> 01:54:07,727 HEAVILY INVOLVED IN IT, THE DATA 3567 01:54:07,727 --> 01:54:09,929 ARE REALLY VALUABLE, BUT I 3568 01:54:09,929 --> 01:54:11,430 ACTUALLY THINK YOUR SECOND 3569 01:54:11,430 --> 01:54:12,064 QUESTION HIGHLY RELATES TO THAT 3570 01:54:12,064 --> 01:54:12,431 ISSUE. 3571 01:54:12,431 --> 01:54:14,300 SO FRAMINGHAM IS A VALUABLE 3572 01:54:14,300 --> 01:54:16,335 STUDY IN A NOT DIVERSE COHORT IN 3573 01:54:16,335 --> 01:54:17,470 ONE ZIP CODE BASICALLY OR IN ONE 3574 01:54:17,470 --> 01:54:19,672 PART OF THE WORLD. 3575 01:54:19,672 --> 01:54:21,374 SO AMY KIND AT UNIVERSITY OF 3576 01:54:21,374 --> 01:54:22,174 WISCONSIN DEVELOPED SOMETHING 3577 01:54:22,174 --> 01:54:23,609 CALLED THE AREA DEPRIVATION 3578 01:54:23,609 --> 01:54:25,878 INDEX, WHICH IS A WAY TO USE 3579 01:54:25,878 --> 01:54:27,346 YOUR -- WHERE YOU LIVE, 3580 01:54:27,346 --> 01:54:28,848 BASICALLY YOUR ZIP CODE, TO 3581 01:54:28,848 --> 01:54:30,950 DETERMINE THE LEVEL OF 3582 01:54:30,950 --> 01:54:33,152 NEIGHBORHOOD DEPRIVATION BASED 3583 01:54:33,152 --> 01:54:34,220 ON SOCIOECONOMIC STATUS OF 3584 01:54:34,220 --> 01:54:35,888 PEOPLE THAT LIVE THERE, WHAT'S 3585 01:54:35,888 --> 01:54:39,058 AVAILABLE TO THE COMMUNITY, ET 3586 01:54:39,058 --> 01:54:39,925 CETERA. 3587 01:54:39,925 --> 01:54:41,560 THERE'S PRETTY GOOD COMPELLING 3588 01:54:41,560 --> 01:54:43,429 EVIDENCE THAT ADI, THIS AREA 3589 01:54:43,429 --> 01:54:44,930 DEPRIVATION INDEX, IS ASSOCIATED 3590 01:54:44,930 --> 01:54:46,298 WITH BRAIN HEALTH INCLUDING 3591 01:54:46,298 --> 01:54:47,933 DEMENTIA AND COGNITIVE DECLINE, 3592 01:54:47,933 --> 01:54:50,336 SO CERTAINLY THERE'S A LOT OF 3593 01:54:50,336 --> 01:54:51,103 FACTORS AT PLAY. 3594 01:54:51,103 --> 01:54:53,072 WE KNOW THAT EDUCATION TENDS TO 3595 01:54:53,072 --> 01:54:56,876 BE LOWER IN AREAS WITH A WORSE 3596 01:54:56,876 --> 01:54:57,877 AREA DEPRIVATION INDEX. 3597 01:54:57,877 --> 01:54:58,944 IS IT BECAUSE OF EDUCATION, IS 3598 01:54:58,944 --> 01:55:01,447 IT BECAUSE OF FINANCIAL ASPECTS. 3599 01:55:01,447 --> 01:55:03,315 WE'RE TRYING TO UNDERSTAND HOW 3600 01:55:03,315 --> 01:55:05,851 MUCH DISPARITIES THAT WE SEE IN 3601 01:55:05,851 --> 01:55:07,286 THIS COUNTRY IN DEMENTIA RATES 3602 01:55:07,286 --> 01:55:09,155 AND IN STROKE RATES AS WELL, HOW 3603 01:55:09,155 --> 01:55:10,656 MUCH OF THAT IS EXPLAINED BY 3604 01:55:10,656 --> 01:55:12,058 THESE NEIGHBORHOOD LEVEL FACTORS 3605 01:55:12,058 --> 01:55:13,626 WHICH WE KNOW ALTER IN 3606 01:55:13,626 --> 01:55:15,227 COMBINATION WITH THINGS LIKE IN 3607 01:55:15,227 --> 01:55:16,228 GENESIS STE MIBG RACISM WE'RE 3608 01:55:16,228 --> 01:55:18,230 GOING TO ALTER ACCESS TO 3609 01:55:18,230 --> 01:55:20,833 HEALTHCARE AND LIKELIHOOD OF 3610 01:55:20,833 --> 01:55:22,168 GETTING YOUR RISK FACTORS AS 3611 01:55:22,168 --> 01:55:23,035 WELL CONTROLLED, ET CETERA, 3612 01:55:23,035 --> 01:55:25,805 WHICH IN TURN CAN AFFECT BIOL 3613 01:55:25,805 --> 01:55:26,038 BIOLOGY. 3614 01:55:26,038 --> 01:55:27,606 SO CERTAINLY THINKING ABOUT 3615 01:55:27,606 --> 01:55:28,741 WHERE PEOPLE COME FROM AND WHERE 3616 01:55:28,741 --> 01:55:31,477 THEY LIVE IS, I THINK, A REALLY 3617 01:55:31,477 --> 01:55:32,578 IMPORTANT WAY WHEN WE THINK 3618 01:55:32,578 --> 01:55:35,414 ABOUT THIS OTHER ASPECT OF 3619 01:55:35,414 --> 01:55:36,182 COGNITIVE RESERVE AND SOCIAL 3620 01:55:36,182 --> 01:55:37,383 FACTORS AND HOW THEY MAY 3621 01:55:37,383 --> 01:55:39,051 INTERPLAY AND HOW WE CAN 3622 01:55:39,051 --> 01:55:40,219 POTENTIALLY REDUCE RISK OF 3623 01:55:40,219 --> 01:55:41,987 DEMENTIA NOT JUST BY ACTING ON 3624 01:55:41,987 --> 01:55:43,789 GENETIC FACTORS AND BIOLOGIC 3625 01:55:43,789 --> 01:55:44,857 FACTORS, BUT ALSO SOME OF THESE 3626 01:55:44,857 --> 01:55:45,825 SOCIAL FACTORS AS WELL. 3627 01:55:45,825 --> 01:55:47,026 SO THANKS FOR ASKING ABOUT 3628 01:55:47,026 --> 01:55:50,796 THOSE. 3629 01:55:50,796 --> 01:55:52,198 >> WELL, WE'RE GETTING CLOSE TO 3630 01:55:52,198 --> 01:55:53,733 THE END, BUT MAYBE JUST THINKING 3631 01:55:53,733 --> 01:56:00,973 A LITTLE BIT IN TERMS OF THE 3632 01:56:00,973 --> 01:56:02,808 NETHER ZONE BETWEEN NORMAL 3633 01:56:02,808 --> 01:56:04,143 EXPERIENCE AND DEMENTIA, 3634 01:56:04,143 --> 01:56:10,116 QUESTION COMES UP OF FO FORGETTG 3635 01:56:10,116 --> 01:56:11,150 NAMES AND THE FACT THAT THAT'S 3636 01:56:11,150 --> 01:56:12,885 SOMETHING THAT SEEMS TO HAPPEN 3637 01:56:12,885 --> 01:56:14,286 AS LIFE PROGRESSES. 3638 01:56:14,286 --> 01:56:18,691 IS THERE ANY REASON WHY THAT IN 3639 01:56:18,691 --> 01:56:20,993 PARTICULAR IS AN AREA OF LOSS, 3640 01:56:20,993 --> 01:56:23,729 OR IS IT JUST THAT THAT'S 3641 01:56:23,729 --> 01:56:25,798 EMBARRASSING AND SO IT NOTICED 3642 01:56:25,798 --> 01:56:27,066 FIRST? 3643 01:56:27,066 --> 01:56:28,901 >> I THINK IT'S CERTAINLY TO 3644 01:56:28,901 --> 01:56:32,171 SOME EXTENT BECAUSE IT'S A 3645 01:56:32,171 --> 01:56:36,442 NOTABLE IMPAIRMENT. 3646 01:56:36,442 --> 01:56:38,077 WHEN WE LOOK AT COGNITIVE 3647 01:56:38,077 --> 01:56:39,044 PERFORMANCE OVER THE LIFESPAN, 3648 01:56:39,044 --> 01:56:41,680 WE DO SEE, YOU KNOW, SLIGHT 3649 01:56:41,680 --> 01:56:46,819 DROPS IN MULTIPLE DOMAINS. 3650 01:56:46,819 --> 01:56:49,555 BUT IN GENERAL, WHILE NAMING IS 3651 01:56:49,555 --> 01:56:51,757 SOMETHING THAT MANY PEOPLE 3652 01:56:51,757 --> 01:56:55,694 EXPERIENCE, IN GENERAL IT IS 3653 01:56:55,694 --> 01:56:57,229 SOMETHING THAT CAN BE PRESERVED 3654 01:56:57,229 --> 01:56:58,197 VERY LATE IN LIFESPAN. 3655 01:56:58,197 --> 01:57:00,966 SO LANGUAGE ABILITY, YOU'RE 3656 01:57:00,966 --> 01:57:02,802 STILL ABLE TO BUILD THAT, AND I 3657 01:57:02,802 --> 01:57:04,670 THINK IT JUST HIGHLIGHTS THE 3658 01:57:04,670 --> 01:57:05,638 EVOLUTIONARY IMPORTANCE OF 3659 01:57:05,638 --> 01:57:08,040 LANGUAGE FUNCTION, SO IF YOU 3660 01:57:08,040 --> 01:57:08,841 EXPERIENCE MILD DIFFICULTY, UR 3661 01:57:08,841 --> 01:57:10,643 MAY JUST FEEL MORE IMPAIRED 3662 01:57:10,643 --> 01:57:12,444 BECAUSE SOCIALLY WE ARE SO 3663 01:57:12,444 --> 01:57:14,180 DEPENDENT ON THIS PARTICULAR 3664 01:57:14,180 --> 01:57:14,413 DOMAIN. 3665 01:57:14,413 --> 01:57:17,449 BUT A LITTLE BIT OF LOSS IS PART 3666 01:57:17,449 --> 01:57:21,120 OF THE NORMAL AIMING PROCESS. A. 3667 01:57:21,120 --> 01:57:22,555 >> DR. GOTTESMAN, DO YOU HAVE 3668 01:57:22,555 --> 01:57:23,422 ANYTHING TO ADD TO THAT? 3669 01:57:23,422 --> 01:57:24,857 >> SONJA, I NOTICED THAT YOU 3670 01:57:24,857 --> 01:57:26,492 MENTIONED EARLY ON THAT OFTEN A 3671 01:57:26,492 --> 01:57:27,393 PRESENTING SYMPTOM OF 3672 01:57:27,393 --> 01:57:28,794 ALZHEIMER'S DISEASE WAS 3673 01:57:28,794 --> 01:57:30,095 FORGETTING NAMES AND I WAS 3674 01:57:30,095 --> 01:57:30,996 WORRIED HOW MANY PEOPLE WERE 3675 01:57:30,996 --> 01:57:34,500 PANICKING THAT YOU JUST -- SO WE 3676 01:57:34,500 --> 01:57:36,035 KNOW WITH AGING, IT IS 3677 01:57:36,035 --> 01:57:37,303 INCREDIBLY COMMON AND IT ONE OF 3678 01:57:37,303 --> 01:57:39,004 THE MOST COMMON COMPLAINTS THAT 3679 01:57:39,004 --> 01:57:41,273 PEOPLE HAVE WHO DO NOT GO ON TO 3680 01:57:41,273 --> 01:57:42,942 PROGRESS TO ANY OF THESE 3681 01:57:42,942 --> 01:57:44,510 DISORDERS. 3682 01:57:44,510 --> 01:57:46,078 BUT I DON'T -- I MEAN, I THINK 3683 01:57:46,078 --> 01:57:47,947 IT'S A GREAT QUESTION, WHAT IS 3684 01:57:47,947 --> 01:57:50,149 IT ABOUT THE STRUCTURE OF THE 3685 01:57:50,149 --> 01:57:51,016 BRAIN AND WHAT HAPPENS WITH AGE 3686 01:57:51,016 --> 01:57:54,887 AS TO WHY NAMING IS AFFECTED 3687 01:57:54,887 --> 01:57:56,055 BECAUSE AS SONJA POINTS OUT, 3688 01:57:56,055 --> 01:57:57,790 IT'S NOT AFFECTED -- LANGUAGE IS 3689 01:57:57,790 --> 01:57:59,925 NOT USUALLY AFFECTED SO EARLY IN 3690 01:57:59,925 --> 01:58:00,559 THESE OTHER CONDITIONS. 3691 01:58:00,559 --> 01:58:01,760 BUT I DON'T THINK WE KNOW MORE 3692 01:58:01,760 --> 01:58:03,295 AS TO WHY SPECIFICALLY, AND I 3693 01:58:03,295 --> 01:58:05,798 THINK THAT PROPOSED IDEA OF IT'S 3694 01:58:05,798 --> 01:58:06,999 JUST MORE NOTICEABLE MAKES AS 3695 01:58:06,999 --> 01:58:08,534 MUCH SENSE AS ANY OTHER 3696 01:58:08,534 --> 01:58:11,637 EXPLANATION THAT WE HAVE. 3697 01:58:11,637 --> 01:58:12,638 >> ALL RIGHT. 3698 01:58:12,638 --> 01:58:15,574 WELL, I THINK THAT, YOU KNOW, 3699 01:58:15,574 --> 01:58:17,209 ALL GOOD THINGS MUST COME TO AN 3700 01:58:17,209 --> 01:58:19,511 END, AND THIS IS ANOTHER EXAMPLE 3701 01:58:19,511 --> 01:58:20,279 OF THAT. 3702 01:58:20,279 --> 01:58:22,815 JUST TO REPEAT THE CME CODE FOR 3703 01:58:22,815 --> 01:58:25,451 THOSE WHO WANT TO GET CONTINUING 3704 01:58:25,451 --> 01:58:28,721 MEDICAL EDUCATION CREDIT, IT IS 3705 01:58:28,721 --> 01:58:33,893 52095. 3706 01:58:33,893 --> 01:58:35,294 AND I THINK THAT AT THIS POINT, 3707 01:58:35,294 --> 01:58:37,296 WE WILL HAVE TO CALL THINGS TO A 3708 01:58:37,296 --> 01:58:37,730 CLOSE. 3709 01:58:37,730 --> 01:58:39,498 THANK THE SPEAKERS VERY, VERY 3710 01:58:39,498 --> 01:58:43,969 MUCH FOR A WONDERFUL 3711 01:58:43,969 --> 01:58:45,304 PRESENTATIONS AND WONDERFUL 3712 01:58:45,304 --> 01:58:47,940 DISCUSSION AFTERWARDS, AND WE 3713 01:58:47,940 --> 01:58:49,675 LOOK FORWARD TO THE NEXT SESSION 3714 01:58:49,675 --> 01:58:50,910 OF DEMYSTIFYING MEDICINE, WHICH 3715 01:58:50,910 --> 01:58:52,111 IF YOU CAN BELIEVE IT IS GOING 3716 01:58:52,111 --> 01:58:56,415 TO BE OVER IN LIPSETT AUDITORIU. 3717 01:58:56,415 --> 01:58:57,483 AND WE'RE GOING TO BE OVER THERE 3718 01:58:57,483 --> 01:58:58,751 FOR THE SECOND HALF OF THE 3719 01:58:58,751 --> 01:58:59,585 SEASON. 3720 01:58:59,585 --> 01:59:01,353 DR. ARIAS AND I HAVE A BET GOING 3721 01:59:01,353 --> 01:59:02,655 AS TO HOW MANY PEOPLE ARE GOING 3722 01:59:02,655 --> 01:59:05,724 TO SHOW UP AT LIPSETT AS OPPOSED 3723 01:59:05,724 --> 01:59:06,825 TO BUILDING 50. 3724 01:59:06,825 --> 01:59:08,360 AND I WON'T TELL YOU WHO'S 3725 01:59:08,360 --> 01:59:09,561 BETTING ON WHAT. 3726 01:59:09,561 --> 01:59:12,631 BUT ANYWAY, I HOPE TO SEE ALL OF 3727 01:59:12,631 --> 01:59:15,901 YOU OVER IN LIPSETT NEXT 3728 01:59:15,901 --> 01:59:17,636 TUESDAY, AND WITH THAT, THANK 3729 01:59:17,636 --> 01:59:19,405 YOU AGAIN TO OUR SPEAKERS AND TO 3730 01:59:19,405 --> 01:59:22,241 ALL OF OUR PARTICIPANTS, AND A 3731 01:59:22,241 --> 01:59:25,477 GOOD EVENING TO EVERYONE. 3732 01:59:25,477 --> 01:59:35,654 >> BRAVO!