1 00:00:11,440 --> 00:00:13,640 Welcome to the Clinical Center Grand Rounds, 2 00:00:13,640 --> 00:00:17,440 a weekly series of educational lectures for physicians and 3 00:00:17,440 --> 00:00:20,080 health care professionals broadcast from the Clinical 4 00:00:20,080 --> 00:00:23,040 Center at the National Institutes of Health in 5 00:00:23,040 --> 00:00:24,840 Bethesda, MD. 6 00:00:24,840 --> 00:00:28,400 The NIH Clinical Center is the world's largest hospital totally 7 00:00:28,400 --> 00:00:32,080 dedicated to investigational research and leads the global 8 00:00:32,080 --> 00:00:35,040 effort in training today's investigators and discovering 9 00:00:35,040 --> 00:00:37,200 tomorrow's cures. 10 00:00:37,200 --> 00:00:46,920 Learn more by visiting us online at http://clinicalcenter.nih.gov 11 00:00:46,920 --> 00:00:48,720 >>I'M HONORED TO INTRODUCE 12 00:00:48,720 --> 00:00:50,960 OUR SPEAKER DR. REBECCA 13 00:00:50,960 --> 00:00:52,360 GOTTESMAN, THE STROKE BRANCH 14 00:00:52,360 --> 00:00:54,640 CHIEF AND SENIOR INVESTIGATOR OF 15 00:00:54,640 --> 00:01:01,120 THE STROKE COGNITION AND 16 00:01:01,120 --> 00:01:01,880 NEUROEPIDEMIOLOGIC SESSION AT 17 00:01:01,880 --> 00:01:04,040 THE NINDS INTRAMURAL RESEARCH 18 00:01:04,040 --> 00:01:05,400 PROGRAM. 19 00:01:05,400 --> 00:01:06,920 SHE COMPLETED HER DEGREES AT 20 00:01:06,920 --> 00:01:09,880 COLUMBIA UNIVERSITY AND 21 00:01:09,880 --> 00:01:11,880 INTERNSHIP AND NEUROLOGY 22 00:01:11,880 --> 00:01:13,480 RESIDENCY AT JOHNS HOPKINS. 23 00:01:13,480 --> 00:01:15,880 SHE COMPLETED Ph.D. AND 24 00:01:15,880 --> 00:01:16,600 CLINICAL INVESTIGATION AT THE 25 00:01:16,600 --> 00:01:18,400 JOHNS HOPKINS BLOOMBERG SCHOOL 26 00:01:18,400 --> 00:01:20,880 OF PUBLIC HEALTH, ON FACULTY AT 27 00:01:20,880 --> 00:01:21,760 THE JOHNS HOPKINS DEPARTMENT OF 28 00:01:21,760 --> 00:01:22,560 NEUROLOGY AND EPIDEMIOLOGY AS 29 00:01:22,560 --> 00:01:26,520 WELL AS CORE FACULTY MEMBER AT 30 00:01:26,520 --> 00:01:32,400 JOHNS HOPKINS UNTIL 2021 WHEN 31 00:01:32,400 --> 00:01:37,640 SHE JOINED THE NINDS. 32 00:01:37,640 --> 00:01:40,440 RESEARCH IS ON DEMENTIA, 33 00:01:40,440 --> 00:01:42,800 ALZHEIMER'S DISEASE, AS WELL AS 34 00:01:42,800 --> 00:01:47,040 CEREBRAL SMALL VESSEL DISEASE 35 00:01:47,040 --> 00:01:56,000 AND POST STROKE DEMENTIA, USING 36 00:01:56,000 --> 00:01:57,360 NEURAL IMAGING TO EVALUATE 37 00:01:57,360 --> 00:01:58,640 RESEARCH QUESTIONS. 38 00:01:58,640 --> 00:02:03,480 SHE STUDIES DISPARITIES IN 39 00:02:03,480 --> 00:02:04,080 STROKE, DEMENTIA, POST-STROKE 40 00:02:04,080 --> 00:02:05,080 COGNITIVE IMPAIRMENT. 41 00:02:05,080 --> 00:02:06,520 DR. GOTTESMAN IS BOARD CERTIFIED 42 00:02:06,520 --> 00:02:07,640 IN NEUROLOGY AND VASCULAR 43 00:02:07,640 --> 00:02:09,720 NEUROLOGY BY THE AMERICAN BOARD 44 00:02:09,720 --> 00:02:11,240 OF PSYCHIATRY AND NEUROLOGY. 45 00:02:11,240 --> 00:02:12,880 SHE'S A FORMER ASSOCIATE EDITOR 46 00:02:12,880 --> 00:02:18,920 FOR JOURNAL OF NEUROLOGY, 2019 47 00:02:18,920 --> 00:02:19,920 OUTSTANDING STROKE RESEARCH 48 00:02:19,920 --> 00:02:21,120 AWARD AMERICAN HEART 49 00:02:21,120 --> 00:02:23,360 ASSOCIATION, AUTHORED OVER 50 00:02:23,360 --> 00:02:24,640 CO-AUTHORED OVER 350 51 00:02:24,640 --> 00:02:34,200 PUBLICATIONS, MENTORING OVER 40 52 00:02:34,200 --> 00:02:38,040 STUDENTS, RESIDENTS, FELLOWS. 53 00:02:38,040 --> 00:02:40,440 SHE HOLDS NUMEROUS LEADERSHIP 54 00:02:40,440 --> 00:02:41,240 POSITIONS 55 00:02:41,240 --> 00:02:43,200 ELECTED MEMBER OF THE AMERICAN 56 00:02:43,200 --> 00:02:44,560 SOCIETY FOR CLINICAL 57 00:02:44,560 --> 00:02:46,280 INVESTIGATION, MEMBER OF THE 58 00:02:46,280 --> 00:02:48,680 INTRAMURAL CLINICAL NEUROSCIENCE 59 00:02:48,680 --> 00:02:51,160 WORKSHOP PLANNING COMMITTEE, 60 00:02:51,160 --> 00:02:53,520 NINDS HEALTH DISPARITIES 61 00:02:53,520 --> 00:02:55,680 WORKSHOP, NINDS CLINICAL TRIALS 62 00:02:55,680 --> 00:02:56,880 NETWORK EVALUATION WORKING 63 00:02:56,880 --> 00:02:59,880 GROUP, NINDS EXECUTIVE ADVISORY 64 00:02:59,880 --> 00:03:00,200 COMMITTEE. 65 00:03:00,200 --> 00:03:02,800 DR. GOTTESMAN IS CO-CHAIR AND 66 00:03:02,800 --> 00:03:05,880 PANELIST FOR NINDS AMERICAN 67 00:03:05,880 --> 00:03:09,720 NEUROLOGICAL ASSOCIATION 68 00:03:09,720 --> 00:03:11,160 SPONSORED INTERACTIVE WEBINAR 69 00:03:11,160 --> 00:03:12,640 SERIES CREATING A SUCCESSFUL 70 00:03:12,640 --> 00:03:15,200 PROGRAM, BUILDING A DIVERSE AND 71 00:03:15,200 --> 00:03:17,160 INCLUSIVE RESEARCH ENVIRONMENT. 72 00:03:17,160 --> 00:03:19,680 SHE'S ALSO THE ANNUAL PROGRAM 73 00:03:19,680 --> 00:03:22,080 CHAIR FOR AMERICAN NEUROLOGICAL 74 00:03:22,080 --> 00:03:23,400 ASSOCIATION. 75 00:03:23,400 --> 00:03:24,000 TODAY THE TITLE OF THE 76 00:03:24,000 --> 00:03:26,800 PRESENTATION IS "IS 77 00:03:26,800 --> 00:03:30,440 CEREBROVASCULAR VASCULAR DISEASE 78 00:03:30,440 --> 00:03:32,760 EVER SILENT. 79 00:03:32,760 --> 00:03:34,640 JOIN ME IN WELCOMING DR. GOTTESMAN. 80 00:03:34,640 --> 00:03:36,080 THANK YOU FOR THE OPPORTUNITY TO 81 00:03:36,080 --> 00:03:37,160 SPEAK, DELIGHTED TO TALK ABOUT 82 00:03:37,160 --> 00:03:38,920 MY WORK AND THE WORK OF THE MANY 83 00:03:38,920 --> 00:03:40,320 PEOPLE I WORKED WITH OVER THE 84 00:03:40,320 --> 00:03:40,880 YEARS. 85 00:03:40,880 --> 00:03:43,480 THE TITLE OF MY TALK IS TRYING 86 00:03:43,480 --> 00:03:47,800 TO GET AT THIS THIS ISSUE OF 87 00:03:47,800 --> 00:03:48,880 SO-CALLED SILENT CEREBROVASCULAR 88 00:03:48,880 --> 00:03:51,840 DISEASE. 89 00:03:51,840 --> 00:03:52,840 HERE IS MY DISCLOSURES. 90 00:03:52,840 --> 00:03:54,560 I THINK THE DEFINITIONS WILL BE 91 00:03:54,560 --> 00:03:56,360 REALLY IMPORTANT TO MAKE SURE 92 00:03:56,360 --> 00:04:00,840 WE'RE ON THE SAME PAGE, I'LL 93 00:04:00,840 --> 00:04:03,040 APPROACH WHETHER WE SHOULD THINK 94 00:04:03,040 --> 00:04:09,080 OF SMALL VESSEL DISEASE IN LUMP 95 00:04:09,080 --> 00:04:10,560 OR SMALL MANNER AND WHY THEY 96 00:04:10,560 --> 00:04:11,880 AREN'T SO SILENT IN TERMS OF 97 00:04:11,880 --> 00:04:13,760 IMPACT ON STROKE AND POST-STROKE 98 00:04:13,760 --> 00:04:16,280 OUTCOME AND ALSO ON IMPACT ON 99 00:04:16,280 --> 00:04:17,680 COGNITION AND COGNITIVE DECLINE 100 00:04:17,680 --> 00:04:18,360 AND DEMENTIA. 101 00:04:18,360 --> 00:04:19,800 FINALLY WE'LL TOUCH ON 102 00:04:19,800 --> 00:04:22,320 MECHANISMS AND THINK ABOUT SMALL 103 00:04:22,320 --> 00:04:23,600 VESSELS BEYOND THE BRAIN BEFORE 104 00:04:23,600 --> 00:04:25,480 WRAPPING UP WITH FUTURE 105 00:04:25,480 --> 00:04:27,760 DIRECTIONS. 106 00:04:27,760 --> 00:04:29,560 WHEN WE TALK ABOUT SILENCE, 107 00:04:29,560 --> 00:04:30,840 WE'RE TALKING ABOUT A NUMBER OF 108 00:04:30,840 --> 00:04:33,360 CHANGES SEEN IN THE BRAIN OF 109 00:04:33,360 --> 00:04:35,120 INDIVIDUALS THAT IN THEORY ARE 110 00:04:35,120 --> 00:04:37,400 ASYMPTOMATIC, AND I'M SAYING IN 111 00:04:37,400 --> 00:04:38,480 THEORY, OBVIOUSLY I'M PREPARING 112 00:04:38,480 --> 00:04:40,680 YOU FOR THE FACT I DON'T THINK 113 00:04:40,680 --> 00:04:42,640 THESE ARE FULLY ASYMPTOMATIC BUT 114 00:04:42,640 --> 00:04:45,520 THESE ARE IMAGING CHANGES 115 00:04:45,520 --> 00:04:47,160 FREQUENTLY SEEN ON CLINICAL 116 00:04:47,160 --> 00:04:48,880 SCANS OR RESEARCH SCANS, 117 00:04:48,880 --> 00:04:50,000 INCIDENTAL FINDINGS, SO NOT 118 00:04:50,000 --> 00:04:51,560 UNCOMMON IN A CLINICAL READ OF 119 00:04:51,560 --> 00:04:56,240 MRI FOR THERE TO BE A NOTE MADE 120 00:04:56,240 --> 00:05:00,840 OF MICROHEMORRHAGE, WHITE MATTER 121 00:05:00,840 --> 00:05:03,280 HYPERINTENSITIES, INFARCTS NOT 122 00:05:03,280 --> 00:05:05,760 ASSOCIATED WITH STROKE-LIKE 123 00:05:05,760 --> 00:05:08,800 SYMPTOMS, SOFTEN CALL SILENT AND 124 00:05:08,800 --> 00:05:10,880 COVERT CHANGES, A LOT OF 125 00:05:10,880 --> 00:05:13,040 SYNONYMS, BUT THE REALITY IS 126 00:05:13,040 --> 00:05:15,200 THEY ARE OFTEN WHAT IS SUBMERGED 127 00:05:15,200 --> 00:05:16,400 BELOW THE WATER AND CLINICAL 128 00:05:16,400 --> 00:05:18,800 STROKE IS REALLY WHAT WE KNOW OF 129 00:05:18,800 --> 00:05:20,240 MORE CLEARLY HAS CLINICAL 130 00:05:20,240 --> 00:05:20,760 IMPLICATIONS. 131 00:05:20,760 --> 00:05:22,440 I'M GOING TO TALK MORE ABOUT 132 00:05:22,440 --> 00:05:23,920 RISK FACTORS AND PROTECTIVE 133 00:05:23,920 --> 00:05:25,120 FACTORS THROUGHOUT THE TALK BUT 134 00:05:25,120 --> 00:05:30,400 I WANTED TO USE THIS GRAPHIC TO 135 00:05:30,400 --> 00:05:31,520 EMPHASIZE CHANGES LURKING 136 00:05:31,520 --> 00:05:33,920 BENEATH THE WATER, PROBABLY MORE 137 00:05:33,920 --> 00:05:35,320 CLINICALLY APPARENT THAN WE 138 00:05:35,320 --> 00:05:35,560 THINK. 139 00:05:35,560 --> 00:05:36,760 GENERALLY WHEN WE THINK ABOUT 140 00:05:36,760 --> 00:05:39,040 STROKE WE THINK ABOUT STROKE 141 00:05:39,040 --> 00:05:40,120 THAT CAUSES SYMPTOMS AND 142 00:05:40,120 --> 00:05:41,560 INFARCTS THAT DON'T NECESSARILY 143 00:05:41,560 --> 00:05:42,240 CAUSE SYMPTOMS. 144 00:05:42,240 --> 00:05:45,280 SO, THIS SORT OF REWORKING OF 145 00:05:45,280 --> 00:05:47,160 STROKE DEFINITIONS PUBLISHED NOW 146 00:05:47,160 --> 00:05:49,640 TEN YEARS AGO REALLY FOCUSES ON 147 00:05:49,640 --> 00:05:51,200 WHETHER SYMPTOMS OCCUR OR DON'T 148 00:05:51,200 --> 00:05:53,200 TO DETERMINE IF SOMETHING IS A 149 00:05:53,200 --> 00:05:54,160 STROKE, CLINICAL STROKE, OR IF 150 00:05:54,160 --> 00:05:56,680 THERE ARE NO SYMPTOMS IT'S OFTEN 151 00:05:56,680 --> 00:05:59,640 CALLED, AGAIN, A SILENT CEREBRAL 152 00:05:59,640 --> 00:06:00,600 INFARCTION OR CNS INFARCTION. 153 00:06:00,600 --> 00:06:02,480 THIS IS AN EXAMPLE OF SOMETHING 154 00:06:02,480 --> 00:06:03,680 THAT COULD BE SILENT BUT 155 00:06:03,680 --> 00:06:04,880 CERTAINLY COULD HAVE HAD 156 00:06:04,880 --> 00:06:05,400 SYMPTOMS AS WELL. 157 00:06:05,400 --> 00:06:09,960 I DON'T KNOW BY LOOKING AT THE 158 00:06:09,960 --> 00:06:11,040 SCAN, DIFFUSION WEIGHTED MRI 159 00:06:11,040 --> 00:06:14,000 WITH A RIGHT ACUTE INFARCT, 160 00:06:14,000 --> 00:06:15,880 SHOWS BRIGHT LESIONS OR ACUTE 161 00:06:15,880 --> 00:06:17,960 EVENTS THAT OCCUR, WHICH COULD 162 00:06:17,960 --> 00:06:19,800 HAVE HAPPENED INCIDENTALLY IN 163 00:06:19,800 --> 00:06:21,120 SOMEONE AND NOT CAUSED SYMPTOMS 164 00:06:21,120 --> 00:06:24,320 OR MAY HAVE CAUSED SYMPTOMS AND 165 00:06:24,320 --> 00:06:26,080 THAT MIGHT LEAD TO DIFFERENTIAL 166 00:06:26,080 --> 00:06:30,360 BETWEEN STROKES OR SILENT 167 00:06:30,360 --> 00:06:30,880 INFARCTION. 168 00:06:30,880 --> 00:06:32,840 WHAT ARE THESE CHANGES BELOW THE 169 00:06:32,840 --> 00:06:35,960 WATER, THE TYPE OF THE ICEBERG? 170 00:06:35,960 --> 00:06:38,000 ONE VERY COMMON FINDING, AGAIN 171 00:06:38,000 --> 00:06:40,560 AS PEOPLE GET OLDER ALL OF THESE 172 00:06:40,560 --> 00:06:41,640 FINDINGS OCCUR MORE FREQUENTLY, 173 00:06:41,640 --> 00:06:43,960 AND THEY ARE VERY COMMON AS 174 00:06:43,960 --> 00:06:45,920 INCIDENTAL FINDINGS ON MRI 175 00:06:45,920 --> 00:06:46,360 SCANS. 176 00:06:46,360 --> 00:06:48,000 AS MRI TECHNOLOGY IMPROVES, 177 00:06:48,000 --> 00:06:49,880 SEQUENCES IMPROVE, THE FREQUENCY 178 00:06:49,880 --> 00:06:51,800 AND ABILITY TO SEE THESE 179 00:06:51,800 --> 00:06:53,880 SUBCLINICAL OR SILENT LESIONS 180 00:06:53,880 --> 00:06:56,840 GETS EVEN BETTER. 181 00:06:56,840 --> 00:06:59,040 WHITE MATTER HYPER INTENSITY ARE 182 00:06:59,040 --> 00:07:01,240 CHANGES WE SEE FREQUENTLY IN 183 00:07:01,240 --> 00:07:04,400 PEOPLE PARTICULARLY AS THEY AGE. 184 00:07:04,400 --> 00:07:07,000 THE TINY CAVITATIONS HERE 185 00:07:07,000 --> 00:07:12,040 LECUNES MIGHT LOOK LIKE A SMALL 186 00:07:12,040 --> 00:07:14,160 VESSEL LECUNAR INFARCT BUT 187 00:07:14,160 --> 00:07:15,440 DIDN'T NECESSARILY HAVE 188 00:07:15,440 --> 00:07:18,960 SYMPTOMS, EVEN IN LARGE 189 00:07:18,960 --> 00:07:19,800 PERIVASCULAR SPACES, MICROBLEEDS 190 00:07:19,800 --> 00:07:23,320 ARE SMALL HEMORRHAGES THAT 191 00:07:23,320 --> 00:07:24,960 OCCURRED IN THE PAST, NOT 192 00:07:24,960 --> 00:07:26,040 NECESSARILY CAUSING SYMPTOMS. 193 00:07:26,040 --> 00:07:28,160 HERE IS AN EXAMPLE OF A NEW 194 00:07:28,160 --> 00:07:29,880 LOOKING INFARCT ON A SCAN BUT 195 00:07:29,880 --> 00:07:31,200 DIDN'T NECESSARILY CAUSE 196 00:07:31,200 --> 00:07:31,640 SYMPTOMS. 197 00:07:31,640 --> 00:07:32,960 BRAIN ATROPHY CAN EVEN BE A 198 00:07:32,960 --> 00:07:34,600 DOWNSTREAM CHANGE OF SOME OF 199 00:07:34,600 --> 00:07:37,800 THESE OTHER VASCULAR CHANGES, 200 00:07:37,800 --> 00:07:39,080 AND CORTICAL MICROINFARCTS, 201 00:07:39,080 --> 00:07:40,640 THERE'S MORE CONTROVERSY ON WHAT 202 00:07:40,640 --> 00:07:42,720 STRENGTH MAGNET CAN IDENTIFY 203 00:07:42,720 --> 00:07:46,320 THESE ON MRI BUT THESE SMALL 204 00:07:46,320 --> 00:07:47,240 INFARCTS ARE DESCRIBED 205 00:07:47,240 --> 00:07:47,600 PATHOLOGICALLY. 206 00:07:47,600 --> 00:07:51,760 ALL OF THESE GO UP WITH AGE, 207 00:07:51,760 --> 00:07:56,480 HERE IS A GRAPHIC SHOWING 208 00:07:56,480 --> 00:07:57,600 SHOWING LACUNEAR, AND THE 209 00:07:57,600 --> 00:08:01,880 PREVALENCE IN A NUMBER OF COHORT 210 00:08:01,880 --> 00:08:03,200 STUDIES GOES UP, PROBABLY SMALL, 211 00:08:03,200 --> 00:08:06,360 BUT THE TOP OF THE Y-AXIS IS 212 00:08:06,360 --> 00:08:06,520 40%. 213 00:08:06,520 --> 00:08:08,520 SO SOME ESTIMATES HERE AS PEOPLE 214 00:08:08,520 --> 00:08:10,040 GET TO AGE 90, OVER A THIRD OF 215 00:08:10,040 --> 00:08:13,800 PEOPLE MAY HAVE SOME OF THESE 216 00:08:13,800 --> 00:08:16,320 LACUNAR INFARCT, AND WHITE 217 00:08:16,320 --> 00:08:26,840 MATTER HYPERINTENSITIES EVEN 218 00:08:27,240 --> 00:08:28,840 MORE COMMON. 219 00:08:28,840 --> 00:08:30,680 WE CATEGORIZE THESE INTO SMALL 220 00:08:30,680 --> 00:08:31,640 VESSEL DISEASE. 221 00:08:31,640 --> 00:08:33,560 WHEN YOU IDENTIFY ON MRI, YOU 222 00:08:33,560 --> 00:08:35,000 DON'T KNOW WHAT THE ETIOLOGY 223 00:08:35,000 --> 00:08:35,160 WAS. 224 00:08:35,160 --> 00:08:37,600 SO WHEN WE THINK ABOUT ACUTE 225 00:08:37,600 --> 00:08:39,880 STROKE SOMEONE COMES IN WITH 226 00:08:39,880 --> 00:08:41,000 SYMPTOMS, WE SCAN THEM, SEE 227 00:08:41,000 --> 00:08:43,560 ACUTE CHANGES ON THIS DIFFUSION 228 00:08:43,560 --> 00:08:45,920 MRI, DWI MRI. 229 00:08:45,920 --> 00:08:48,240 WE CAN USE OUR INTUITION ABOUT 230 00:08:48,240 --> 00:08:50,200 WHAT THE INFARCTS LOOK LIKE BUT 231 00:08:50,200 --> 00:08:52,280 IMPORTANTLY WE DO OTHER STUDIES 232 00:08:52,280 --> 00:09:01,160 TO HELP US EVALUATE PROBABLE 233 00:09:01,160 --> 00:09:05,200 ETIOLOGY, WE MIGHT SEE THE 234 00:09:05,200 --> 00:09:08,560 LECUNAR AS WELL AS HYPERTENSION 235 00:09:08,560 --> 00:09:09,680 DIABETES, DETERMINING ETIOLOGY 236 00:09:09,680 --> 00:09:12,840 BETTER FOR ACUTE STROKES WITH 237 00:09:12,840 --> 00:09:14,920 SEVERAL CLASSIFICATION SYSTEMS. 238 00:09:14,920 --> 00:09:19,000 THE COMBINATION OF IMAGING PLUS 239 00:09:19,000 --> 00:09:22,280 THE WORKUP. 240 00:09:22,280 --> 00:09:23,600 SILENT CHANGES, INCIDENTAL 241 00:09:23,600 --> 00:09:26,560 FINDINGS ON MRI, WE DON'T KNOW 242 00:09:26,560 --> 00:09:27,640 WHAT UNDERLYING ETIOLOGY WAS AND 243 00:09:27,640 --> 00:09:29,400 TEND TO GROUP THESE TOGETHER AS 244 00:09:29,400 --> 00:09:30,720 FORMS OF SMALL VESSEL DISEASE 245 00:09:30,720 --> 00:09:31,920 BASED ON WHERE THEY ARE, WHAT WE 246 00:09:31,920 --> 00:09:33,400 KNOW THEY ARE ASSOCIATED WITH 247 00:09:33,400 --> 00:09:34,560 BUT THE REALITY IS WE DON'T 248 00:09:34,560 --> 00:09:37,400 REALLY KNOW FOR SURE WHAT THE 249 00:09:37,400 --> 00:09:38,800 UNDERLYING ETIOLOGY IS. 250 00:09:38,800 --> 00:09:44,480 IT'S PLAUSIBLE THAT A CARDIO 251 00:09:44,480 --> 00:09:47,360 EMBOLIC STROKE CAN LEAVE 252 00:09:47,360 --> 00:09:48,520 APPEARANCE LIKE SMALLER LECUNAR 253 00:09:48,520 --> 00:09:49,280 STROKE OVER TIME. 254 00:09:49,280 --> 00:09:50,920 I WANT TO MAKE THAT CAVEAT 255 00:09:50,920 --> 00:09:52,600 BECAUSE I'M GOING TO MAKE 256 00:09:52,600 --> 00:09:54,120 ASSUMPTIONS THAT WE THINK WHEN 257 00:09:54,120 --> 00:09:55,960 WE SEE THESE CHRONIC CHANGES ON 258 00:09:55,960 --> 00:09:57,320 MRI THAT WE CAN GUESS SOME MIGHT 259 00:09:57,320 --> 00:09:59,280 BE FORMS OF SMALL VESSEL DISEASE 260 00:09:59,280 --> 00:10:00,680 BUT WE DON'T ABSOLUTELY KNOW 261 00:10:00,680 --> 00:10:03,960 THAT FOR SURE FOR THESE KINDS OF 262 00:10:03,960 --> 00:10:04,720 CHANGES. 263 00:10:04,720 --> 00:10:06,280 SO, CLASSIFYING SMALL VESSEL 264 00:10:06,280 --> 00:10:07,240 DISEASE SUBTYPES IS SOMETHING 265 00:10:07,240 --> 00:10:08,600 THERE'S MORE OF AN EMPHASIS ON 266 00:10:08,600 --> 00:10:10,640 IN THE LAST TEN YEARS. 267 00:10:10,640 --> 00:10:12,280 SO THIS STRIVE CONSORTIUM WAS A 268 00:10:12,280 --> 00:10:15,360 GROUP IN 2013 THAT PUBLISHED AN 269 00:10:15,360 --> 00:10:18,840 IMPORTANT PAPER, DEFINING FORMS 270 00:10:18,840 --> 00:10:20,480 OF CEREBRAL SMALL VESSEL 271 00:10:20,480 --> 00:10:23,040 DISEASE, WHICH OF THESE WE THINK 272 00:10:23,040 --> 00:10:26,080 ARE INDICATIVE OF DISEASE OF THE 273 00:10:26,080 --> 00:10:26,880 ARTERIAL SMALLER BLOOD VESSELS 274 00:10:26,880 --> 00:10:28,040 IN THE BRAIN. 275 00:10:28,040 --> 00:10:29,800 JUST LAST WEEK THEY RELEASED AN 276 00:10:29,800 --> 00:10:32,720 UPDATE TO THE STRIVE CONSORTIUM, 277 00:10:32,720 --> 00:10:34,280 STRIVE 2, AGAIN FOCUSING ON THE 278 00:10:34,280 --> 00:10:37,000 SAME LESIONS, THESE ARE THINGS 279 00:10:37,000 --> 00:10:37,960 I'VE SHOWN, RECENT SUBCORTICAL 280 00:10:37,960 --> 00:10:40,400 INFARCT IN A LOCATION THAT MIGHT 281 00:10:40,400 --> 00:10:44,440 BE SEEN FOR A LECUNE OR THAT 282 00:10:44,440 --> 00:10:49,280 CAUSED SYMPTOMS, AND WHITE 283 00:10:49,280 --> 00:10:53,440 MATTER HYPERINTENSITIES ENLARGE 284 00:10:53,440 --> 00:10:55,640 THE SPACE. 285 00:10:55,640 --> 00:10:57,080 IN THIS STRIVE-2 UPDATE I MAKE A 286 00:10:57,080 --> 00:10:58,680 POINT OF SAYING THAT THERE ARE 287 00:10:58,680 --> 00:11:03,720 DIFFERENCES WHEN WE SEE THESE AS 288 00:11:03,720 --> 00:11:06,280 SYMPTOMATIC VERSUS SILENT OR 289 00:11:06,280 --> 00:11:07,680 COVERT EVENTS, MAKING STATEMENTS 290 00:11:07,680 --> 00:11:09,120 DESCRIBING WHAT GENERALLY LEADS 291 00:11:09,120 --> 00:11:11,320 TO SOMETHING TO CAUSE SYMPTOMS 292 00:11:11,320 --> 00:11:13,160 VERSUS WHAT DOESN'T, BUT THESE 293 00:11:13,160 --> 00:11:16,200 ARE NOT UNIFORM RULES. 294 00:11:16,200 --> 00:11:17,080 CERTAINLY SOMEONE COULD HAVE 295 00:11:17,080 --> 00:11:19,280 VERY SMALL INFARCT THAT CAUSES 296 00:11:19,280 --> 00:11:20,920 SYMPTOMS, DEPENDING ON WHERE IT 297 00:11:20,920 --> 00:11:22,440 IS, OR SLIGHTLY BIGGER ONE THAT 298 00:11:22,440 --> 00:11:24,720 DOESN'T CAUSE SYMPTOMS. 299 00:11:24,720 --> 00:11:27,160 IN GENERAL, THEIR POINT IS THAT 300 00:11:27,160 --> 00:11:30,760 INFARCTS THAT OCCUR OUTSIDE THE 301 00:11:30,760 --> 00:11:33,200 PRIMARY MOTOR TRACKS OR SENSORY 302 00:11:33,200 --> 00:11:36,120 TRACKS MAY MORE LIKELY BE 303 00:11:36,120 --> 00:11:37,480 SYMPTOMATIC AND VICE VERSA FOR 304 00:11:37,480 --> 00:11:40,320 THE IMPORTANT REGIONS N STRIVE-2 305 00:11:40,320 --> 00:11:44,160 THEY DIFFERENTIATE BETWEEN ACUTE 306 00:11:44,160 --> 00:11:45,200 VERSUS CHRONIC, EMPHASIZING HOW 307 00:11:45,200 --> 00:11:46,360 THINGS LOOK DIFFERENT AT THE 308 00:11:46,360 --> 00:11:48,640 TIME, AND YOU MAY BE ABLE TO 309 00:11:48,640 --> 00:11:50,200 MORE CONFIDENTLY SAY WHAT IS 310 00:11:50,200 --> 00:11:52,040 ACUTE AND WHAT THE ETIOLOGY IS 311 00:11:52,040 --> 00:11:55,880 AS OPPOSED TO MORE CHRONIC SMALL 312 00:11:55,880 --> 00:11:57,280 VESSEL CHANGES ON SCANS THAT ARE 313 00:11:57,280 --> 00:11:58,160 INCIDENTAL FINDINGS. 314 00:11:58,160 --> 00:11:59,920 SO NOW THAT I'M DESCRIBING 315 00:11:59,920 --> 00:12:03,520 DIFFERENT TYPES OF SMALL VESSEL 316 00:12:03,520 --> 00:12:05,720 DISEASE AND GIVEN CAVEATS 317 00:12:05,720 --> 00:12:06,640 ACUTELY VERSUS CHRONICALLY MAY 318 00:12:06,640 --> 00:12:08,480 MAKE A DIFFERENT IN THE 319 00:12:08,480 --> 00:12:11,320 CONFIDENCE OF ETIOLOGY, IN 320 00:12:11,320 --> 00:12:12,160 ADDITION THAT THERE ARE 321 00:12:12,160 --> 00:12:15,160 DIFFERENT FORMS OF SMALL VESSEL 322 00:12:15,160 --> 00:12:17,200 DISEASE, AND WE SEE THEM AGAIN 323 00:12:17,200 --> 00:12:19,640 IN A LOT OF THESE SCANS BUT SOME 324 00:12:19,640 --> 00:12:21,600 OCCUR MORE FREQUENTLY THAN 325 00:12:21,600 --> 00:12:22,480 OTHERS. 326 00:12:22,480 --> 00:12:24,000 ONE IMPORTANT CONSIDERATION 327 00:12:24,000 --> 00:12:25,840 SHOULD WE CATEGORIZE ALL THESE 328 00:12:25,840 --> 00:12:26,960 FORMS TOGETHER OR REALLY SHOULD 329 00:12:26,960 --> 00:12:28,840 WE THINK OF THEM AS DISTINCT 330 00:12:28,840 --> 00:12:29,080 ENTITIES? 331 00:12:29,080 --> 00:12:30,440 AND THE REASON IT MIGHT BE 332 00:12:30,440 --> 00:12:31,640 IMPORTANT TO CONSIDER THEM 333 00:12:31,640 --> 00:12:32,760 TOGETHER IS BECAUSE IT MIGHT 334 00:12:32,760 --> 00:12:34,960 HELP US UNDERSTAND MORE ABOUT 335 00:12:34,960 --> 00:12:36,920 THEIR ETIOLOGY AND IMPORTANTLY 336 00:12:36,920 --> 00:12:38,120 THEIR OUTCOME AND ULTIMATELY IF 337 00:12:38,120 --> 00:12:41,920 THERE'S A WAY TO PREVENT THESE. 338 00:12:41,920 --> 00:12:44,040 THIS IS A VENN DIAGRAM FAR FROM 339 00:12:44,040 --> 00:12:45,040 COMPREHENSIVE BUT WHICH GIVES A 340 00:12:45,040 --> 00:12:47,680 SENSE OF HOW MUCH OVERLAP THERE 341 00:12:47,680 --> 00:12:49,760 IS IN SHARED RISK FACTORS. 342 00:12:49,760 --> 00:12:52,320 STROKE IS ONE END OF THE 343 00:12:52,320 --> 00:12:53,680 SPECTRUM, WE HAVE A GOOD SENSE 344 00:12:53,680 --> 00:12:55,400 OF WHAT THAT LOOKS LIKE, EVEN 345 00:12:55,400 --> 00:12:58,600 THOUGH THERE'S MANY TYPES OF 346 00:12:58,600 --> 00:12:58,960 STROKE. 347 00:12:58,960 --> 00:13:02,640 SILENT LACUNES OR SMALL VESSEL 348 00:13:02,640 --> 00:13:05,200 TYPE CHANGES, LECUNAR INFARCTS 349 00:13:05,200 --> 00:13:05,840 PRESUMABLY SILENT OR SUBCLINICAL 350 00:13:05,840 --> 00:13:08,080 AT THE TIME. 351 00:13:08,080 --> 00:13:08,680 MICROBLEEDS, HEMORRHAGES THAT 352 00:13:08,680 --> 00:13:09,880 DIDN'T NECESSARILY CAUSE 353 00:13:09,880 --> 00:13:12,520 SYMPTOMS. 354 00:13:12,520 --> 00:13:14,160 AND WHITE MATTER 355 00:13:14,160 --> 00:13:16,480 HYPERINTENSITIES. 356 00:13:16,480 --> 00:13:22,480 THERE'S SO MUCH OVERLAP IN RISK 357 00:13:22,480 --> 00:13:23,040 FACTORS. 358 00:13:23,040 --> 00:13:26,320 HYPERTENSION IS A RISK FACTOR. 359 00:13:26,320 --> 00:13:29,040 SOME RISK FACTORS NOT IN CERTAIN 360 00:13:29,040 --> 00:13:30,240 OVERLAP BECAUSE THEY HAVEN'T 361 00:13:30,240 --> 00:13:31,800 BEEN STUDIED OR BECAUSE THOSE 362 00:13:31,800 --> 00:13:33,200 OUTCOMES ARE LESS FREQUENT AND 363 00:13:33,200 --> 00:13:34,640 HARDER TO STUDY BUT REALLY WANT 364 00:13:34,640 --> 00:13:35,840 TO MAKE THE POINT IF WE'RE 365 00:13:35,840 --> 00:13:38,080 TRYING TO DECIDE IF WE SHOULD 366 00:13:38,080 --> 00:13:40,320 LUMP OR SPLIT THESE SMALL VESSEL 367 00:13:40,320 --> 00:13:41,280 DISEASE TYPES IT'S USEFUL TO 368 00:13:41,280 --> 00:13:43,480 THINK HOW THEY HAVE SHARED RISK 369 00:13:43,480 --> 00:13:45,040 FACTORS, AGAIN IT MAY BE 370 00:13:45,040 --> 00:13:46,080 INFORMATIVE TO STUDY THEM 371 00:13:46,080 --> 00:13:47,760 TOGETHER IF THEY HAVE VERY 372 00:13:47,760 --> 00:13:48,960 SIMILAR RISK FACTORS FOR PEOPLE 373 00:13:48,960 --> 00:13:50,400 THAT GET ONE TYPE VERSUS 374 00:13:50,400 --> 00:13:50,720 ANOTHER. 375 00:13:50,720 --> 00:13:53,760 IN ADDITION TO THE RISK FACTORS 376 00:13:53,760 --> 00:13:54,560 BEING SIMILAR, 377 00:13:54,560 --> 00:13:55,960 HISTOPATHOLOGICALLY WE SEE MANY 378 00:13:55,960 --> 00:13:56,960 SIMILARITIES BETWEEN THESE 379 00:13:56,960 --> 00:13:58,560 DIFFERENT TYPES OF SMALL VESSEL 380 00:13:58,560 --> 00:14:00,160 DISEASE CHANGES. 381 00:14:00,160 --> 00:14:04,000 SO WHITE MATTER HYPERINTENSITIES 382 00:14:04,000 --> 00:14:05,960 AND SILENT LECUNAR INFARCTS ARE 383 00:14:05,960 --> 00:14:09,440 ARTERIAL CHANGES WE SEE ON 384 00:14:09,440 --> 00:14:12,960 PATHOLOGY FURTHER EVIDENCE THEY 385 00:14:12,960 --> 00:14:14,040 MIGHT GO TOGETHER. 386 00:14:14,040 --> 00:14:16,240 PEOPLE WITH LECUNAR STROKES ARE 387 00:14:16,240 --> 00:14:17,080 MORE ENLARGED PERIVASCULAR 388 00:14:17,080 --> 00:14:20,920 SPACES AND MORE WHITE MATTER 389 00:14:20,920 --> 00:14:23,680 HYPERINTENSITIES, IN ADDITION 390 00:14:23,680 --> 00:14:27,640 PEOPLE WHO HAVE LACUNES, ALMOST 391 00:14:27,640 --> 00:14:31,560 HALF ALSO HAVE MICROHEMORRHAGES. 392 00:14:31,560 --> 00:14:33,960 MONOGENIC DISORDERS, ALL OF 393 00:14:33,960 --> 00:14:36,000 THESE ARE DESCRIBED TOGETHER, 394 00:14:36,000 --> 00:14:37,200 SUCH AS CADASIL. 395 00:14:37,200 --> 00:14:40,840 IN ADDITION, WE'LL TALK MORE 396 00:14:40,840 --> 00:14:42,240 ABOUT THIS LATER, OUTCOMES TEND 397 00:14:42,240 --> 00:14:44,360 TO BE SIMILAR WITH STROKE AND 398 00:14:44,360 --> 00:14:45,880 SMALL VESSEL DISEASE TYPES. 399 00:14:45,880 --> 00:14:47,720 SO WE KNOW YOU HAVE MICROBLEEDS, 400 00:14:47,720 --> 00:14:50,240 MIGHT HAVE THE SAME EFFECT ON 401 00:14:50,240 --> 00:14:53,200 OUTCOME AS IF YOU HAD WHITE 402 00:14:53,200 --> 00:14:54,640 MATTER INTENSITIES OR SOME 403 00:14:54,640 --> 00:14:54,960 COMBINATION. 404 00:14:54,960 --> 00:14:56,600 THERE'S MORE TO BE DONE IN THIS 405 00:14:56,600 --> 00:14:58,040 AREA, THERE'S SOME EVIDENCE 406 00:14:58,040 --> 00:14:59,240 PREVENTION EFFORTS HAVE WORKED 407 00:14:59,240 --> 00:15:03,280 IN A SIMILAR WAY TO REDUCE 408 00:15:03,280 --> 00:15:04,680 PROGRESSION OF SEVERAL FORMS OF 409 00:15:04,680 --> 00:15:06,000 SMALL VESSEL DISEASE, THE MOST 410 00:15:06,000 --> 00:15:08,520 EVIDENCE IS FOR STROKE AND WHITE 411 00:15:08,520 --> 00:15:16,760 MATTER HYPERINTENSITIES WITH 412 00:15:16,760 --> 00:15:19,040 BLOOD PRESSURE CONTROL, 413 00:15:19,040 --> 00:15:20,720 SPRINT-MIND RANDOMIZED PEOPLE TO 414 00:15:20,720 --> 00:15:22,240 MORE PROGRESSIVE BLOOD PRESSURE 415 00:15:22,240 --> 00:15:23,320 CONTROL, STOPPED EARLY FOR 416 00:15:23,320 --> 00:15:24,400 CARDIOVASCULAR BENEFIT AS MANY 417 00:15:24,400 --> 00:15:26,920 OF YOU KNOW AND DIDN'T REACH 418 00:15:26,920 --> 00:15:29,000 PRIMARY OUTCOME REDUCING 419 00:15:29,000 --> 00:15:32,520 DEMENTIA, THE PRIMARY GOAL OF 420 00:15:32,520 --> 00:15:33,760 SPRINT-MIND, BUT SHOWED 421 00:15:33,760 --> 00:15:36,360 REDUCTION IN MCI IN MORE 422 00:15:36,360 --> 00:15:37,640 AGGRESSIVE BLOOD PRESSURE 423 00:15:37,640 --> 00:15:39,760 CONTROL GROUP BUT EVIDENCE IT 424 00:15:39,760 --> 00:15:43,400 REDUCES CARDIOVASCULAR DISEASE, 425 00:15:43,400 --> 00:15:48,200 THE MORE AGGRESSIVE BLOOD 426 00:15:48,200 --> 00:15:48,880 PRESSURE CONTROL. 427 00:15:48,880 --> 00:15:50,440 AND THEN AS I SAID I WOULD GET 428 00:15:50,440 --> 00:15:52,520 BACK TO THERE IS SOME EVIDENCE 429 00:15:52,520 --> 00:15:55,720 OF SHARED GENETIC RISK, SO HERE 430 00:15:55,720 --> 00:15:57,360 IS ONE EXAMPLE. 431 00:15:57,360 --> 00:15:59,560 FOX F2 AS PART OF A 432 00:15:59,560 --> 00:16:05,120 META-ANALYSIS I WAS PART OF, 433 00:16:05,120 --> 00:16:06,400 GWAS, CHROMOSOME 6, ASSOCIATED 434 00:16:06,400 --> 00:16:09,360 WITH CLINICAL STROKE AND BURDEN 435 00:16:09,360 --> 00:16:11,680 OF WHITE MATTER 436 00:16:11,680 --> 00:16:12,240 HYPERINTENSITIES, ADDITIONAL 437 00:16:12,240 --> 00:16:13,640 STUDIES FOUND WHEN DELETED TO BE 438 00:16:13,640 --> 00:16:16,200 ASSOCIATED WITH MORE WHITE 439 00:16:16,200 --> 00:16:16,960 MATTER HYPERINTENSITIES BUT 440 00:16:16,960 --> 00:16:22,000 KNOCKOUT MICE ARE MORE 441 00:16:22,000 --> 00:16:23,160 MICROHEMORRHAGE, THESE 442 00:16:23,160 --> 00:16:24,840 PHENOTYPES, GLIOSIS, INFARCTION, 443 00:16:24,840 --> 00:16:26,480 IN ZEBRAFISH MUTANTS DECREASED 444 00:16:26,480 --> 00:16:29,520 PARASITE COVERAGE AND SMOOTH 445 00:16:29,520 --> 00:16:32,080 MUSCLE CELL COVERAGE. 446 00:16:32,080 --> 00:16:33,480 FOXF 2 IS ASSOCIATED WITH 447 00:16:33,480 --> 00:16:35,680 LECUNAR STROKE AND WHITE MATTER 448 00:16:35,680 --> 00:16:37,880 HYPERINTENSITIES IN A SEPARATE 449 00:16:37,880 --> 00:16:39,920 GWAS, ONE EXAMPLE LUMPING MIGHT 450 00:16:39,920 --> 00:16:41,360 BE HELPFUL WITH SHARED GENETIC 451 00:16:41,360 --> 00:16:41,560 RISK. 452 00:16:41,560 --> 00:16:43,000 FURTHERMORE THERE ARE A NUMBER 453 00:16:43,000 --> 00:16:44,960 OF IMPORTANT RISK VARIANTS 454 00:16:44,960 --> 00:16:47,480 IDENTIFIED WITH MULTIPLE SMALL 455 00:16:47,480 --> 00:16:48,160 VESSEL DISEASE PHENOTYPES, AND 456 00:16:48,160 --> 00:16:51,880 THIS IS SORT OF SIMILAR TO MY 457 00:16:51,880 --> 00:16:55,840 RISK FACTOR VENN DIAGRAM WHITE 458 00:16:55,840 --> 00:16:56,360 MATTER HYPERINTENSITIES, 459 00:16:56,360 --> 00:16:58,040 INFARCTS, THESE ARE MEASURES OF 460 00:16:58,040 --> 00:17:00,240 WHITE MATTER INTEGRITY FROM 461 00:17:00,240 --> 00:17:01,320 DIFFUSION TENSOR IMAGING, 462 00:17:01,320 --> 00:17:03,360 INDICATORS OF SMALL VESSEL 463 00:17:03,360 --> 00:17:06,320 DISEASE, IN THE WHITE MATTER, 464 00:17:06,320 --> 00:17:07,440 MICROBLEEDS, HEMORRHAGE, SMALL 465 00:17:07,440 --> 00:17:09,760 VESSEL STROKE, YOU SEE A LOT OF 466 00:17:09,760 --> 00:17:11,520 OVERLAP WITH GENETIC RISK. 467 00:17:11,520 --> 00:17:13,560 SO, I HOPE I PERSUADED YOU IT'S 468 00:17:13,560 --> 00:17:17,080 REASONABLE TO LUMP THESE THINGS 469 00:17:17,080 --> 00:17:18,160 TOGETHER, THERE ARE SUBTLE 470 00:17:18,160 --> 00:17:19,040 DIFFERENCES BUT IF WE'RE TRYING 471 00:17:19,040 --> 00:17:20,680 TO UNDERSTAND WHAT THEY MEAN FOR 472 00:17:20,680 --> 00:17:22,000 OUTCOME AND HOW TO PREVENT THEM 473 00:17:22,000 --> 00:17:24,600 IT'S USEFUL TO THINK OF THEM AS 474 00:17:24,600 --> 00:17:27,040 A COMPOSITE ENTITY OF SMALL 475 00:17:27,040 --> 00:17:28,560 VESSEL DISEASE PHENOTYPES. 476 00:17:28,560 --> 00:17:30,000 TO TELL YOU MORE ABOUT WHY I 477 00:17:30,000 --> 00:17:31,080 THINK THESE CHANGES ARE NOT SO 478 00:17:31,080 --> 00:17:33,800 SILENT I WANT TO GIVE BACKGROUND 479 00:17:33,800 --> 00:17:36,680 FOR THE STUDY WHERE THIS WORK 480 00:17:36,680 --> 00:17:40,120 HAS BEEN DONE, THE 481 00:17:40,120 --> 00:17:41,800 ATHEROSCLEROSIS COHORT STUDY, 482 00:17:41,800 --> 00:17:43,760 16,000 PEOPLE RECRUITED IN 483 00:17:43,760 --> 00:17:45,400 1980s, FOLLOWED INITIALLY WITH 484 00:17:45,400 --> 00:17:52,760 VISITS EVERY FEW YEARS, A BIGGER 485 00:17:52,760 --> 00:17:55,240 GAP BEFORE THE FIFTH IN-PERSON 486 00:17:55,240 --> 00:17:57,880 VISIT, NOW AT TENTH IN-PERSON 487 00:17:57,880 --> 00:17:59,800 VISIT, HALF IN PERSON, SHIFTED 488 00:17:59,800 --> 00:18:03,560 TO A VIRTUAL SETTING. 489 00:18:03,560 --> 00:18:08,640 THEY WERE MIDDLE AGE WHEN THEY 490 00:18:08,640 --> 00:18:14,200 STARTED, NOW 8 0-100, FROM FOUR 491 00:18:14,200 --> 00:18:15,640 U.S. COMMUNITIES. 492 00:18:15,640 --> 00:18:17,840 EARLY VISITS WE ASSESSED 493 00:18:17,840 --> 00:18:19,480 COGNITION AT MULTIPLE VISITS AS 494 00:18:19,480 --> 00:18:25,520 WELL AS SUBSET HAVING BRAIN MRI 495 00:18:25,520 --> 00:18:27,320 OR AMYLOID PET SCANS. 496 00:18:27,320 --> 00:18:29,480 STUDY WAS DESIGNED TO LOOK AT 497 00:18:29,480 --> 00:18:31,680 NATURAL HISTORY OF 498 00:18:31,680 --> 00:18:33,880 ATHEROSCLEROSIS AND RISK 499 00:18:33,880 --> 00:18:35,960 FACTORS, DETAILED VASCULAR RISK 500 00:18:35,960 --> 00:18:38,040 FACTOR AND MICROVASCULAR AND 501 00:18:38,040 --> 00:18:39,160 MACROVASCULAR MARKER INFORMATION 502 00:18:39,160 --> 00:18:40,440 THROUGHOUT THE COHORT FOLLOW-UP. 503 00:18:40,440 --> 00:18:46,640 IN ADDITION TO THESE IN-PERSON 504 00:18:46,640 --> 00:18:50,840 VISITS THERE'S NOW SEMI ANNUAL 505 00:18:50,840 --> 00:18:52,480 PHONE CALLS, ONGOING 506 00:18:52,480 --> 00:18:54,760 SURVEILLANCE OF STROKE, 507 00:18:54,760 --> 00:18:57,520 DEMENTIA, OTHER IMPORTANT 508 00:18:57,520 --> 00:18:59,080 OUTCOMES. 509 00:18:59,080 --> 00:19:01,000 GLEN WYNDHAM, UNIVERSITY OF 510 00:19:01,000 --> 00:19:04,560 MISSISSIPPI, LOOKED AT THE ARIC 511 00:19:04,560 --> 00:19:06,480 COHORT, IMPACT ON STROKE AND 512 00:19:06,480 --> 00:19:06,840 MORTALITY. 513 00:19:06,840 --> 00:19:10,320 PEOPLE WHO CEMENTED TO HAVE 514 00:19:10,320 --> 00:19:12,440 SIGH -- SEEMED TO HAVE SILENT 515 00:19:12,440 --> 00:19:14,160 INFARCTS, INCIDENTAL FINDINGS ON 516 00:19:14,160 --> 00:19:15,880 A RESEARCH MRI SCAN. 517 00:19:15,880 --> 00:19:19,600 SHE FOUND PEOPLE WHO HAD MORE 518 00:19:19,600 --> 00:19:22,160 LACUNES AND MULTIPLE TYPES OF 519 00:19:22,160 --> 00:19:24,680 LACUNES, SMALLER VERSUS BIGGER, 520 00:19:24,680 --> 00:19:31,560 WHICH MAY REFLECT ENLARGED 521 00:19:31,560 --> 00:19:35,080 PERIVASCULAR SPACE ARE GREATER 522 00:19:35,080 --> 00:19:38,480 RISK OF POST-STROKE MORTALITY, 523 00:19:38,480 --> 00:19:39,600 MORE WHITE MATTER 524 00:19:39,600 --> 00:19:41,040 HYPERINTENSITIES AND LACUNES WAS 525 00:19:41,040 --> 00:19:43,000 ASSOCIATED WITH INCREASED RISK 526 00:19:43,000 --> 00:19:48,320 OF STROKE AND STROKE-RELATED 527 00:19:48,320 --> 00:19:48,600 MORTALITY. 528 00:19:48,600 --> 00:19:50,200 PROGRESSION WAS LOOKED AT, TO 529 00:19:50,200 --> 00:19:51,840 UNDERSTAND IF YOU HAVE THEM BUT 530 00:19:51,840 --> 00:19:53,920 THEY CONTINUE TO PROGRESS OVER A 531 00:19:53,920 --> 00:19:56,120 PERIOD OF TIME IS THAT WORSE FOR 532 00:19:56,120 --> 00:19:56,520 OUTCOME? 533 00:19:56,520 --> 00:19:57,800 THE ANSWER IS YES. 534 00:19:57,800 --> 00:20:03,360 PEOPLE WITH MORE INCIDENT 535 00:20:03,360 --> 00:20:04,240 LACUNES 536 00:20:04,240 --> 00:20:06,880 EITHER NON AND DEVELOPED SOME OR 537 00:20:06,880 --> 00:20:08,200 SOME AND DEVELOPED MORE, THIS IS 538 00:20:08,200 --> 00:20:10,240 OVER A 10-YEAR PERIOD OF TIME, 539 00:20:10,240 --> 00:20:12,320 HIGHER RISK OF STROKE IN THE 540 00:20:12,320 --> 00:20:13,560 SUBSEQUENT 12 YEARS. 541 00:20:13,560 --> 00:20:14,760 AGAIN, THESE FINDINGS ARE BAD 542 00:20:14,760 --> 00:20:16,520 FOR RISK OF STROKE AND, AGAIN, 543 00:20:16,520 --> 00:20:18,440 IT'S PROBABLY THIS ISSUE OF IT 544 00:20:18,440 --> 00:20:20,240 BEING TIP OF THE ICEBERG IS 545 00:20:20,240 --> 00:20:21,760 STROKE, WE KNOW THESE ARE 546 00:20:21,760 --> 00:20:22,640 LURKING UNDER THE WATER, 547 00:20:22,640 --> 00:20:24,280 INDICATING YOU'RE AT RISK FOR 548 00:20:24,280 --> 00:20:25,600 HAVING A CLINICAL STROKE. 549 00:20:25,600 --> 00:20:27,120 IF YOU HAVE MORE PROGRESSION 550 00:20:27,120 --> 00:20:28,440 RISK MAY BE GREATER. 551 00:20:28,440 --> 00:20:31,320 WE KNOW PEOPLE WHO HAVE STROKE 552 00:20:31,320 --> 00:20:34,360 BUT AT THE TIME HAVE WORSE SMALL 553 00:20:34,360 --> 00:20:39,600 VESSEL DISEASE, AND WE KNOW MORE 554 00:20:39,600 --> 00:20:42,680 FOR WHITE MATTER 555 00:20:42,680 --> 00:20:43,200 HYPERINTENSITIES, LECUNAR 556 00:20:43,200 --> 00:20:44,520 STROKES, YOU CAN COUNT THEM, 557 00:20:44,520 --> 00:20:48,040 HARDER TO LOOK AT THE WHOLE 558 00:20:48,040 --> 00:20:50,360 SPECTRUM OF SEVERITY OF LECUNAR 559 00:20:50,360 --> 00:20:51,880 STROKES OR MICROCLEATS THAN 560 00:20:51,880 --> 00:20:52,880 WHITE MATTER INTENSITIES WHICH 561 00:20:52,880 --> 00:20:54,520 WE CAN MEASURE AND QUANTIFY. 562 00:20:54,520 --> 00:20:58,440 PEOPLE WHO HAVE STROKE CAN GET 563 00:20:58,440 --> 00:21:00,080 tPA, DO WORSE AFTER STROKE IF 564 00:21:00,080 --> 00:21:01,520 THEY HAD WHITE MATTER 565 00:21:01,520 --> 00:21:02,840 HYPERINTENSITIES TO BEGIN WITH. 566 00:21:02,840 --> 00:21:07,760 IF YOU HAVE A HEMORRHAGE AND 567 00:21:07,760 --> 00:21:08,760 MORE WHITE MATTER 568 00:21:08,760 --> 00:21:10,560 HYPERINTENSITIES, WORSE OUTCOME, 569 00:21:10,560 --> 00:21:11,880 MORE GROWTH OF HEMORRHAGE. 570 00:21:11,880 --> 00:21:15,720 FUNCTIONAL STATUS IS WORSE FOR 571 00:21:15,720 --> 00:21:18,920 PEOPLE WITH MORE WHITE MATTER 572 00:21:18,920 --> 00:21:20,080 HYPERINTENSITY, OUT OF 573 00:21:20,080 --> 00:21:25,360 PROPORTION, THEY DO WORSE AFTER 574 00:21:25,360 --> 00:21:26,200 STROKE. 575 00:21:26,200 --> 00:21:31,480 IN ADDITION, LOOKING AT 576 00:21:31,480 --> 00:21:34,560 HEMISPATIAL NEGLECT, THOSE 577 00:21:34,560 --> 00:21:36,440 PEOPLE INDEPENDENT OF STROKE 578 00:21:36,440 --> 00:21:39,600 SIZE HAD WORSE NEGLECT WITH 579 00:21:39,600 --> 00:21:41,440 WHITE MATTER HYPERINTENSITIES. 580 00:21:41,440 --> 00:21:44,160 A FELLOW AT JOHNS HOPKINS LOOKED 581 00:21:44,160 --> 00:21:47,600 AT COLLATERAL FLOW AND FOUND 582 00:21:47,600 --> 00:21:50,400 PEOPLE WITH WHITE MATTER 583 00:21:50,400 --> 00:21:50,960 HYPERINTENSITIES DEVELOPED 584 00:21:50,960 --> 00:21:52,600 COLLATERALS, VERY IMPORTANT FOR 585 00:21:52,600 --> 00:21:54,600 POST-STROKE OUTCOME, ABILITY TO 586 00:21:54,600 --> 00:21:55,880 RECOVER FROM LARGE VESSEL 587 00:21:55,880 --> 00:21:56,440 OCCLUSION. 588 00:21:56,440 --> 00:21:57,760 IN ADDITION, GAIT IS SOMETHING 589 00:21:57,760 --> 00:21:59,840 THAT'S VERY IMPORTANT AND 590 00:21:59,840 --> 00:22:02,800 AFFECTED BY SMALL VESSEL 591 00:22:02,800 --> 00:22:03,880 DISEASE, STROKE RECURRENCE, 592 00:22:03,880 --> 00:22:04,720 MORTALITY, KEVIN SULLIVAN AT 593 00:22:04,720 --> 00:22:05,280 UNIVERSITY OF MISSISSIPPI 594 00:22:05,280 --> 00:22:07,520 MEDICAL CENTER LOOKED AT THIS IN 595 00:22:07,520 --> 00:22:08,480 THE ARIC COHORT. 596 00:22:08,480 --> 00:22:11,320 PEOPLE WITH MORE WHITE MATTER 597 00:22:11,320 --> 00:22:12,200 HYPERINTENSITY WITH LARGER 598 00:22:12,200 --> 00:22:16,040 INCREASE WITH LARGER VOLUME OF 599 00:22:16,040 --> 00:22:19,080 WHITE MATTER HYPERINTENSITIES 600 00:22:19,080 --> 00:22:21,080 HAD SLOWER GAIT SPEED AND 601 00:22:21,080 --> 00:22:22,920 DECLINED MORE RAPIDLY OVER TIME, 602 00:22:22,920 --> 00:22:25,320 IMPORTANT FOR OUTCOMES. 603 00:22:25,320 --> 00:22:29,240 INDIRECTLY WHITE MATTER 604 00:22:29,240 --> 00:22:30,600 HYPERINTENSITIES AFFECTING GAIT 605 00:22:30,600 --> 00:22:31,640 COULD AFFECT RISK, PARTICULARLY 606 00:22:31,640 --> 00:22:33,520 IN OLDER PEOPLE. 607 00:22:33,520 --> 00:22:34,840 STROKE PATIENTS HAVE WORSE GAIT 608 00:22:34,840 --> 00:22:37,680 WITH A LOT OF SMALL VESSEL 609 00:22:37,680 --> 00:22:38,320 DISEASE, IN GENERAL FUNCTIONAL 610 00:22:38,320 --> 00:22:39,320 OUTCOME BEYOND JUST GAIT APPEARS 611 00:22:39,320 --> 00:22:42,520 TO BE WORSE IN PEOPLE WITH MORE 612 00:22:42,520 --> 00:22:46,240 WHITE MATTER HYPERINTENSITIES, 613 00:22:46,240 --> 00:22:48,240 INDEPENDENT MUCH UNDERLYING RISK 614 00:22:48,240 --> 00:22:48,640 FACTORS. 615 00:22:48,640 --> 00:22:51,320 WHITE MATTER HYPERINTENSITIES 616 00:22:51,320 --> 00:22:53,360 BECAUSE THEY ARE SO COMMON ARE 617 00:22:53,360 --> 00:22:55,040 PROBABLY RELEVANT IN OTHER 618 00:22:55,040 --> 00:22:55,800 NEUROLOGIC DISEASE AS WELL. 619 00:22:55,800 --> 00:23:00,520 EVEN IF THEY ARE NOT DIRECTLY 620 00:23:00,520 --> 00:23:01,920 MECHANISTICALLY PLAYING A ROLE 621 00:23:01,920 --> 00:23:03,800 THEIR PRESENCE MAY WORSEN 622 00:23:03,800 --> 00:23:05,840 OUTCOME RELATED TO THAT DISEASE. 623 00:23:05,840 --> 00:23:09,280 PARKINSON'S PATIENTS WHO ALSO 624 00:23:09,280 --> 00:23:13,720 HAVE SMALL VESSEL DISEASE DO 625 00:23:13,720 --> 00:23:14,440 WORSE. 626 00:23:14,440 --> 00:23:15,520 I'LL EMPHASIZE THESE CHANGES ARE 627 00:23:15,520 --> 00:23:17,800 SO COMMON AS PEOPLE GET OLDER 628 00:23:17,800 --> 00:23:19,000 IT'S INEVITABLE A FAIRLY LARGE 629 00:23:19,000 --> 00:23:20,760 PROPORTION OF PATIENTS WITH A 630 00:23:20,760 --> 00:23:21,600 DISEASE LIKE PARKINSON'S ARE 631 00:23:21,600 --> 00:23:23,800 GOING TO HAVE SMALL VESSEL 632 00:23:23,800 --> 00:23:24,240 DISEASE. 633 00:23:24,240 --> 00:23:25,360 SO THINKING ABOUT PREVENTING 634 00:23:25,360 --> 00:23:27,440 THESE AND THEIR PROGRESSION IS 635 00:23:27,440 --> 00:23:29,520 RELEVANT FOR ALL TYPES OF 636 00:23:29,520 --> 00:23:31,800 OUTCOMES RELATED TO NEUROLOGIC 637 00:23:31,800 --> 00:23:32,480 DISEASE. 638 00:23:32,480 --> 00:23:33,320 IN ADDITION, PEOPLE WITH 639 00:23:33,320 --> 00:23:36,280 TRAUMATIC BRAIN INJURY WITH MORE 640 00:23:36,280 --> 00:23:37,280 SMALL VESSEL DISEASE APPEAR TO 641 00:23:37,280 --> 00:23:39,040 DO WORSE THAN THOSE WHO DIDN'T 642 00:23:39,040 --> 00:23:39,640 HAVE SMALL VESSEL DISEASE TO 643 00:23:39,640 --> 00:23:42,200 BEGIN WITH. 644 00:23:42,200 --> 00:23:43,720 IT'S ASSOCIATED WITH MORE 645 00:23:43,720 --> 00:23:45,600 FRAILTY, AGAIN THIS ISSUE OF 646 00:23:45,600 --> 00:23:48,240 WORSE GAIT, WORSE RISK OF 647 00:23:48,240 --> 00:23:52,720 FALLING, MORE FRAILTY IN 648 00:23:52,720 --> 00:23:58,080 GENERAL. 649 00:23:58,080 --> 00:24:00,720 EMILY JOHNSON AT HOPKINS SHOWED 650 00:24:00,720 --> 00:24:07,840 INCREASED RISK OF LATE-ONSET 651 00:24:07,840 --> 00:24:08,080 EPILEPSY. 652 00:24:08,080 --> 00:24:08,840 IT MIGHT ACTUALLY INFLUENCE THE 653 00:24:08,840 --> 00:24:10,360 DEVELOPMENT OF THE DISEASE 654 00:24:10,360 --> 00:24:20,920 ITSELF, IN THIS CASE LATE-ONSET 655 00:24:22,800 --> 00:24:23,480 EPILEPSY. 656 00:24:23,480 --> 00:24:24,720 WHAT ABOUT COGNITION? 657 00:24:24,720 --> 00:24:27,960 SO, THESE ARE DATA FROM THE 658 00:24:27,960 --> 00:24:29,400 ROTTERDAM STUDY SHOWING CLEARLY 659 00:24:29,400 --> 00:24:31,480 AND CONSISTENTLY NO MATTER WHICH 660 00:24:31,480 --> 00:24:33,560 TYPE OF THESE SMALL VESSELS YOU 661 00:24:33,560 --> 00:24:35,080 LOOK AT, I'VE ARGUED WE SHOULD 662 00:24:35,080 --> 00:24:37,480 THINK OF THEM LUMPED TOGETHER, 663 00:24:37,480 --> 00:24:38,720 THAT COGNITION IS WORSE, THIS IS 664 00:24:38,720 --> 00:24:43,840 ANNUAL CHANGE ON A COGNITIVE 665 00:24:43,840 --> 00:24:47,320 INDEX IN ROTTERDAM. 666 00:24:47,320 --> 00:24:51,280 MORE WHITE MATTER, GREATER 667 00:24:51,280 --> 00:24:53,680 DECLINE, DEPENDING ON 668 00:24:53,680 --> 00:24:55,760 PERIVENTRICULAR OR SUBCORTICAL. 669 00:24:55,760 --> 00:24:58,160 SIMILAR PATTERN FOR BRAIN 670 00:24:58,160 --> 00:24:59,040 INFARCTS, SO-CALLED SILENT 671 00:24:59,040 --> 00:25:01,640 VERSUS THOSE WHO DON'T, HAVE 672 00:25:01,640 --> 00:25:03,520 WORSE COGNITIVE SCORES. 673 00:25:03,520 --> 00:25:05,080 MICROBLEEDS ARE ASSOCIATED WITH 674 00:25:05,080 --> 00:25:06,800 WORSE COGNITION WHEN DEFINED IN 675 00:25:06,800 --> 00:25:08,360 A BINARY WAY AS WELL. 676 00:25:08,360 --> 00:25:09,880 STROKE AS WELL, AGAIN THIS TALK 677 00:25:09,880 --> 00:25:11,080 IS FOCUSING ON SMALL VESSEL 678 00:25:11,080 --> 00:25:15,120 DISEASE BUT IF WE THINK ALONG 679 00:25:15,120 --> 00:25:17,520 THE SPECTRUM, STROKE AS THE MOST 680 00:25:17,520 --> 00:25:20,160 CLINICALLY OBVIOUS FORM OF THESE 681 00:25:20,160 --> 00:25:21,720 SMALL VESSEL DISEASE TYPES, WE 682 00:25:21,720 --> 00:25:23,800 KNOW SMALL VESSEL DISEASE TYPES 683 00:25:23,800 --> 00:25:25,440 ARE ALSO ASSOCIATED WITH RISK OF 684 00:25:25,440 --> 00:25:26,960 STROKE, IT'S IMPORTANT TO THINK 685 00:25:26,960 --> 00:25:28,720 ABOUT WHAT STROKE DOES FOR 686 00:25:28,720 --> 00:25:29,920 COGNITION. 687 00:25:29,920 --> 00:25:37,360 HERE IS DATA FROM THE LEVINE-LED 688 00:25:37,360 --> 00:25:38,880 REGARDS STUDY, AFTER THE TIME OF 689 00:25:38,880 --> 00:25:40,600 STROKE WE SEE DECLINE IN 690 00:25:40,600 --> 00:25:42,160 PEOPLE'S COGNITION AND CONTINUES 691 00:25:42,160 --> 00:25:44,800 TO DECLINE OVER TIME SO THIS IS 692 00:25:44,800 --> 00:25:46,760 LOOKING AT LONGITUDINAL REPEATED 693 00:25:46,760 --> 00:25:48,960 COGNITIVE MEASURES ASSOCIATED 694 00:25:48,960 --> 00:25:53,840 WITH STROKE OF ALL TYPES. 695 00:25:53,840 --> 00:25:59,080 GLEN WYNDHAM LOOKED AT COGNITION 696 00:25:59,080 --> 00:26:01,840 WITH INFARCTS AS WELL AS WHITE 697 00:26:01,840 --> 00:26:05,320 MATTER HYPERINTENSITIES AND SHE 698 00:26:05,320 --> 00:26:07,200 FOUND PEOPLE WHO HAD THE CHANGES 699 00:26:07,200 --> 00:26:09,960 SMALL OR LARGE INFARCTS HAD MORE 700 00:26:09,960 --> 00:26:11,360 COGNITIVE DECLINE THAN NORMAL 701 00:26:11,360 --> 00:26:12,200 POPULATION BUT MOST IMPORTANTLY 702 00:26:12,200 --> 00:26:17,680 IF YOU HAD BOTH YOU HAD STEEPER 703 00:26:17,680 --> 00:26:19,200 DECLINE OVER TIME ON COGNITION 704 00:26:19,200 --> 00:26:21,960 OVER 20 YEARS. 705 00:26:21,960 --> 00:26:22,640 AND WHITE MATTER 706 00:26:22,640 --> 00:26:23,840 HYPERINTENSITIES, THE MORE YOU 707 00:26:23,840 --> 00:26:26,680 HAVE, THE GREATER YOUR COGNITIVE 708 00:26:26,680 --> 00:26:28,200 DECLINE OVER TWO DECADES. 709 00:26:28,200 --> 00:26:29,280 WHAT ABOUT DEMENTIA? 710 00:26:29,280 --> 00:26:35,720 I MENTIONED IN ARIC REPEATED 711 00:26:35,720 --> 00:26:36,840 COGNITIVE MEASURES OVER TIME, 712 00:26:36,840 --> 00:26:39,920 TENDS TO BE LESS CONFOUNDED 713 00:26:39,920 --> 00:26:42,200 OUTCOME THAN LOOKING AT 714 00:26:42,200 --> 00:26:42,880 CROSS-SECTIONAL COGNITIVE 715 00:26:42,880 --> 00:26:44,160 PERFORMANCE OR EVEN DEMENTIA. 716 00:26:44,160 --> 00:26:45,480 DEMENTIA IS MORE UNDERSTANDABLE 717 00:26:45,480 --> 00:26:46,760 TO THE POPULATION AND CERTAINLY 718 00:26:46,760 --> 00:26:48,880 IF WE'RE THINKING ABOUT 719 00:26:48,880 --> 00:26:50,400 IMPORTANT TARGETS FOR 720 00:26:50,400 --> 00:26:51,520 PREVENTION, IMPORTANT PUBLIC 721 00:26:51,520 --> 00:26:53,040 HEALTH MESSAGES ABOUT WHY TO 722 00:26:53,040 --> 00:26:54,600 SCREEN FOR RISK FACTORS, ET 723 00:26:54,600 --> 00:26:55,800 CETERA, IT'S IMPORTANT TO THINK 724 00:26:55,800 --> 00:26:58,400 ABOUT THE IMPACT ON DEMENTIA. 725 00:26:58,400 --> 00:26:59,680 HERE ALSO IN ROTTERDAM WE SEE 726 00:26:59,680 --> 00:27:02,560 HAVING ANY OF THESE CHANGES, 727 00:27:02,560 --> 00:27:04,960 SILENT INFARCTS, WHITE MATTER 728 00:27:04,960 --> 00:27:06,280 HYPERINTENSITIESES ASSOCIATED 729 00:27:06,280 --> 00:27:08,360 WITH INCREASED DEMENTIA, NOT AS 730 00:27:08,360 --> 00:27:12,640 UP FOR SUBCORTICAL CHANGES BUT 731 00:27:12,640 --> 00:27:13,400 PERIVENTRICULAR, AFTER 732 00:27:13,400 --> 00:27:14,720 ADJUSTMENT FOR MRI MEASURES THIS 733 00:27:14,720 --> 00:27:15,720 IS SIGNIFICANCE, INCREASED RISK 734 00:27:15,720 --> 00:27:20,880 OF DEMENTIA, WE SEE THAT FOR 735 00:27:20,880 --> 00:27:21,840 JUST WHITE MATTER 736 00:27:21,840 --> 00:27:23,280 HYPERINTENSITIES IN GENERAL, AND 737 00:27:23,280 --> 00:27:26,120 SIMILAR FOR MICROBLEEDS. 738 00:27:26,120 --> 00:27:27,280 AGAIN, MICROHEMORRHAGES 739 00:27:27,280 --> 00:27:29,760 ASSOCIATED WITH INCREASED RISK 740 00:27:29,760 --> 00:27:30,600 OF DEMENTIA. 741 00:27:30,600 --> 00:27:34,000 SULLIVAN LOOKED AT THIS IN ARIC 742 00:27:34,000 --> 00:27:35,240 AND INFARCTS LATER IN LIFE. 743 00:27:35,240 --> 00:27:39,360 WE TALK ABOUT IMPORTANCE OF 744 00:27:39,360 --> 00:27:41,240 MID-LIFE, RISK FACTORS FOR 745 00:27:41,240 --> 00:27:42,880 COGNITIVE DECLINE AND IMAGING 746 00:27:42,880 --> 00:27:43,120 FACTORS. 747 00:27:43,120 --> 00:27:44,880 I'LL TOUCH ON THAT LATER BUT HE 748 00:27:44,880 --> 00:27:46,840 WANTED TO UNDERSTAND A BIT MORE 749 00:27:46,840 --> 00:27:48,920 ABOUT HOW MRI PRESENCE OF THESE 750 00:27:48,920 --> 00:27:51,320 INFARCTS WHICH WE DON'T HAVE IN 751 00:27:51,320 --> 00:27:52,160 MID-LIFE ON PARTICIPANTS BECAUSE 752 00:27:52,160 --> 00:27:54,800 MRI WAS NOT AVAILABLE WHEN THE 753 00:27:54,800 --> 00:27:56,160 STUDY WAS STARTED, BUT 754 00:27:56,160 --> 00:27:57,680 ASSOCIATED WITH RISK OF DEMENTIA 755 00:27:57,680 --> 00:27:58,640 IN SUBSEQUENT YEARS AND FOUND 756 00:27:58,640 --> 00:28:01,040 WHEN YOU THINK ABOUT THESE 757 00:28:01,040 --> 00:28:01,720 SMALLER VERSUS LARGER 758 00:28:01,720 --> 00:28:03,680 INFARCTION, A LITTLE BIT OF 759 00:28:03,680 --> 00:28:05,400 INRISK WITH BOTH BUT REALLY THIS 760 00:28:05,400 --> 00:28:07,280 BIG JUMP IN THE HAZARD IF YOU 761 00:28:07,280 --> 00:28:09,600 HAD TWO TYPES OF SMALL VESSEL 762 00:28:09,600 --> 00:28:11,240 DISEASE, HIGHER RISK OF DEMENTIA 763 00:28:11,240 --> 00:28:15,160 OVER TIME AFTER THAT IMAGING WAS 764 00:28:15,160 --> 00:28:15,360 DONE. 765 00:28:15,360 --> 00:28:16,600 SO, WHAT ABOUT STROKE? 766 00:28:16,600 --> 00:28:18,760 WHEN WE TALK ABOUT THESE TYPES 767 00:28:18,760 --> 00:28:21,080 WE WANT TO THINK ABOUT STROKE, 768 00:28:21,080 --> 00:28:22,360 GIVEN HOW RELATED THEY ARE TO 769 00:28:22,360 --> 00:28:26,200 EACH OTHER, HOW THEY ARE 770 00:28:26,200 --> 00:28:30,600 ASSOCIATED WITH EACH OTHER, 771 00:28:30,600 --> 00:28:33,360 SYLVIA CATONE LED THIS PAPER, 772 00:28:33,360 --> 00:28:35,080 HOW STROKE RECURRENCE AND 773 00:28:35,080 --> 00:28:36,400 SEVERITY WAS ASSOCIATED WITH 774 00:28:36,400 --> 00:28:36,640 DEMENTIA. 775 00:28:36,640 --> 00:28:37,480 SHE FOUND THAT COMPARED TO 776 00:28:37,480 --> 00:28:39,240 PEOPLE WHO NEVER HAD A STROKE 777 00:28:39,240 --> 00:28:42,080 DURING FOLLOW-UP AND YOU CAN SEE 778 00:28:42,080 --> 00:28:44,480 40 YEARS WORTH OF FOLLOW-UP 779 00:28:44,480 --> 00:28:46,480 BASICALLY, THAT PEOPLE WHO HAD 780 00:28:46,480 --> 00:28:49,120 AT LEAST ONE STROKE WITH GREATER 781 00:28:49,120 --> 00:28:50,600 SEVERITY SCORE, NIH STROKE SCALE 782 00:28:50,600 --> 00:28:54,000 IS A WAY TO MEASURE STROKE 783 00:28:54,000 --> 00:28:59,160 SEVERITY, MORE SEVERE STROKES 784 00:28:59,160 --> 00:29:01,160 HAD GREATER HAD MORE DEMENTIA, 785 00:29:01,160 --> 00:29:02,360 AND BOTH WERE GREATER THAN 786 00:29:02,360 --> 00:29:03,440 PEOPLE WITH NO STROKES. 787 00:29:03,440 --> 00:29:05,840 IF YOU LOOKED AT STROKE 788 00:29:05,840 --> 00:29:07,920 RECURRENCE IN COMBINATION WITH 789 00:29:07,920 --> 00:29:10,240 SEVERITY PEOPLE WHO HAD AT LEAST 790 00:29:10,240 --> 00:29:12,960 TWO STROKES HAD GREATER RISK OF 791 00:29:12,960 --> 00:29:14,720 DEMENTIA, PARTICULARLY IF ONE OF 792 00:29:14,720 --> 00:29:17,040 THE STROKES WAS AT LEAST SEVERE 793 00:29:17,040 --> 00:29:17,480 STROKE. 794 00:29:17,480 --> 00:29:19,000 EVEN IF YOU HAD TWO STROKES AND 795 00:29:19,000 --> 00:29:24,240 THEY WERE MILD YOUR RISK IS 796 00:29:24,240 --> 00:29:26,120 SIMILAR, BUT TWO STROKES WITH 797 00:29:26,120 --> 00:29:27,640 ONE MODERATE TO SEVERE RISK OF 798 00:29:27,640 --> 00:29:38,320 DEMENTIA WENT WAY UP AS YOU CAN 799 00:29:38,320 --> 00:29:38,800 SEE HERE. 800 00:29:38,800 --> 00:29:42,440 GOMEZ, BEFORE I MET HER WAS A 801 00:29:42,440 --> 00:29:43,720 POSTBAC HERE AT NIH, NOW A 802 00:29:43,720 --> 00:29:45,360 MEDICAL STUDENT AT JOHNS 803 00:29:45,360 --> 00:29:49,080 HOPKINS, LOOKED AT SPECIFIC 804 00:29:49,080 --> 00:29:50,880 SYNDROME, THIS IS AN ENTITY 805 00:29:50,880 --> 00:29:54,240 DESCRIBED AS SIMILAR TO MCI BUT 806 00:29:54,240 --> 00:29:58,080 HAS A DISTRICT SET OF FEATURES, 807 00:29:58,080 --> 00:29:59,480 PREDOMINANTLY GAIT INVOLVEMENT, 808 00:29:59,480 --> 00:30:01,880 SLOW GAIT AND SUBJECTIVE 809 00:30:01,880 --> 00:30:02,560 COGNITIVE DECLINE. 810 00:30:02,560 --> 00:30:03,960 PEOPLE WHO HAVE MCR HAVE HIGHER 811 00:30:03,960 --> 00:30:05,280 RISK OF DEMENTIA. 812 00:30:05,280 --> 00:30:08,120 MAY START WITH GAIT DISTURBANCE 813 00:30:08,120 --> 00:30:09,000 AND SUBJECTIVE COMPLAINTS BUT 814 00:30:09,000 --> 00:30:14,520 SHE DEFINED THIS IN THE ARIC 815 00:30:14,520 --> 00:30:16,040 COHORT USING STANDARDIZED 816 00:30:16,040 --> 00:30:16,280 CRITERIA. 817 00:30:16,280 --> 00:30:17,320 WHITE MATTER HYPERINTENSITIESES 818 00:30:17,320 --> 00:30:20,040 IN THE PARTICIPANTS WAS 819 00:30:20,040 --> 00:30:26,080 ASSOCIATED WITH MCI AND MCR BUT 820 00:30:26,080 --> 00:30:26,840 PARTICULARLY MCR. 821 00:30:26,840 --> 00:30:28,120 WE KNOW HOW IMPORTANT IT IS FOR 822 00:30:28,120 --> 00:30:29,840 GAIT, A PARTICULAR PART OF THE 823 00:30:29,840 --> 00:30:31,160 DIAGNOSIS OF MCR. 824 00:30:31,160 --> 00:30:34,880 YOU CAN SEE REALLY BOTH WHITE 825 00:30:34,880 --> 00:30:36,200 MATTER HYPERINTENSITIES VOLUME 826 00:30:36,200 --> 00:30:41,800 BEING MORE IMPORTANT FOR MCR 827 00:30:41,800 --> 00:30:43,840 THAN MCI, IMPORTANT AS WE THINK 828 00:30:43,840 --> 00:30:46,160 ABOUT THE CLINICAL SYNDROME THAT 829 00:30:46,160 --> 00:30:49,640 GOES ALONG WITH WHITE MATTER 830 00:30:49,640 --> 00:30:50,520 HYPERINTENSITIES MAY LOOK 831 00:30:50,520 --> 00:30:52,840 SLIGHTLY DIFFERENT THAN OTHER 832 00:30:52,840 --> 00:30:54,280 CLASSIC PATHWAYS WE'RE USED TO 833 00:30:54,280 --> 00:30:55,480 SEEING BUT REALLY THERE'S 834 00:30:55,480 --> 00:30:57,640 PROBABLY A LOT OF OVERLAP IN 835 00:30:57,640 --> 00:30:59,680 DIFFERENT OUTCOMES IN THESE 836 00:30:59,680 --> 00:31:00,480 PATIENTS. 837 00:31:00,480 --> 00:31:02,480 SO WHAT ABOUT MECHANISMS? 838 00:31:02,480 --> 00:31:04,520 TO TOUCH ON MECHANISM, I WANT TO 839 00:31:04,520 --> 00:31:07,040 PROVIDE CAVEAT I'M AN 840 00:31:07,040 --> 00:31:08,920 EPIDEMIOLOGIST, I'M NOT A BENCH 841 00:31:08,920 --> 00:31:10,200 RESEARCHER AND THERE'S LOTS OF 842 00:31:10,200 --> 00:31:12,000 PEOPLE DOING REALLY EXCITING 843 00:31:12,000 --> 00:31:13,600 WORK IN THIS AREA. 844 00:31:13,600 --> 00:31:18,080 I THINK THAT THIS IS REALLY 845 00:31:18,080 --> 00:31:20,600 EXCITING TO UNDERSTAND WHY THESE 846 00:31:20,600 --> 00:31:23,440 STROKES AND SMALL VESSEL DISEASE 847 00:31:23,440 --> 00:31:24,560 SUBTYPES MAY GROUP TOGETHER, 848 00:31:24,560 --> 00:31:26,440 THINKING ABOUT IMPACT ON 849 00:31:26,440 --> 00:31:28,160 COGNITION AND STROKE RISK. 850 00:31:28,160 --> 00:31:30,320 SO ONE POSSIBILITY IS THAT SMALL 851 00:31:30,320 --> 00:31:32,440 VESSEL DISEASE AS I TOLD YOU IS 852 00:31:32,440 --> 00:31:33,920 ASSOCIATED WITH HIGHER RISK OF 853 00:31:33,920 --> 00:31:36,040 STROKE AND MAY JUST BE THESE 854 00:31:36,040 --> 00:31:37,480 PATIENTS WITH SMALL VESSEL 855 00:31:37,480 --> 00:31:38,320 DISEASE HAVE MORE STROKE, THE 856 00:31:38,320 --> 00:31:39,640 STROKE IS CAUSING THE PROBLEMS 857 00:31:39,640 --> 00:31:42,520 AND LEADS TO A MORE TYPICAL 858 00:31:42,520 --> 00:31:43,600 VASCULAR DEMENTIA PICTURE, BUT 859 00:31:43,600 --> 00:31:47,160 THE PROBLEM IS WE LOOK AT THESE 860 00:31:47,160 --> 00:31:47,840 RELATIONSHIPS AND FIND THEY ARE 861 00:31:47,840 --> 00:31:50,160 STILL THERE EVEN IN PEOPLE WHO 862 00:31:50,160 --> 00:31:52,120 DON'T HAVE CLINICAL STROKE 863 00:31:52,120 --> 00:31:52,800 EVENTS. 864 00:31:52,800 --> 00:31:54,960 IN ADDITION, WE RARELY SEE 865 00:31:54,960 --> 00:32:04,040 REALLY A PERIVASCULAR DEMENTIA. 866 00:32:04,040 --> 00:32:07,960 SOME SITUATIONS WE SEE ONE PURE 867 00:32:07,960 --> 00:32:11,880 NEUROPATHIC ENTITY BUT IN MOST 868 00:32:11,880 --> 00:32:13,480 WE SEE MIXED PATHOLOGY. 869 00:32:13,480 --> 00:32:15,200 IT'S NOT LIKELY TO FULLY EXPLAIN 870 00:32:15,200 --> 00:32:16,760 THE RELATIONSHIPS HERE. 871 00:32:16,760 --> 00:32:18,160 IT'S POSSIBLE, I MENTIONED BRAIN 872 00:32:18,160 --> 00:32:19,800 ATROPHY WAS A DOWNSTREAM MARKER 873 00:32:19,800 --> 00:32:21,280 OF SMALL VESSEL DISEASE. 874 00:32:21,280 --> 00:32:22,640 IT'S POSSIBLE THAT SMALL VESSEL 875 00:32:22,640 --> 00:32:24,840 DISEASE LEADS TO BRAIN ATROPHY, 876 00:32:24,840 --> 00:32:26,600 THAT BRAIN ATROPHY CAN LEAD TO 877 00:32:26,600 --> 00:32:28,240 DECREASE IN FUNCTION OVER TIME, 878 00:32:28,240 --> 00:32:29,880 THAT MAY CONTRIBUTE, I'LL SHOW 879 00:32:29,880 --> 00:32:32,640 YOU EVIDENCE FOR THAT, OR 880 00:32:32,640 --> 00:32:34,960 PERHAPS CONTRIBUTES DIRECTLY 881 00:32:34,960 --> 00:32:36,440 PERHAPS TO ALZHEIMER'S-TIME 882 00:32:36,440 --> 00:32:36,760 CHANGES. 883 00:32:36,760 --> 00:32:38,640 WE SEE MIXED PATHOLOGY, IS IT 884 00:32:38,640 --> 00:32:39,480 POSSIBLE SMALL VESSEL DISEASE 885 00:32:39,480 --> 00:32:42,320 MIGHT EVEN BE DIRECTLY 886 00:32:42,320 --> 00:32:44,200 CONTRIBUTING TO ALZHEIMER'S 887 00:32:44,200 --> 00:32:47,360 PATHOLOGY AND THAT'S WHY MIXED 888 00:32:47,360 --> 00:32:48,360 PATHOLOGY IS COMMON? 889 00:32:48,360 --> 00:32:51,320 IT MAY DUE THIS THROUGH 890 00:32:51,320 --> 00:32:53,360 INCORRECT ROUTES LEADING TO 891 00:32:53,360 --> 00:33:02,560 DECREASED BLOOD-BRAIN BARRIER 892 00:33:02,560 --> 00:33:03,640 FUNCTION, NEUROINFLAMMATION. 893 00:33:03,640 --> 00:33:05,240 I SHOWED COMMON RISK FACTORS, IS 894 00:33:05,240 --> 00:33:09,480 IT A MARKER OF THE UNDERLYING 895 00:33:09,480 --> 00:33:14,600 RISK FACTOR CONTRIBUTING TO 896 00:33:14,600 --> 00:33:15,600 DEMENTIA, MAYBE ALZHEIMER'S 897 00:33:15,600 --> 00:33:16,920 NEUROPATHOLOGY, OR AS OPPOSED TO 898 00:33:16,920 --> 00:33:20,320 BEING A PRIMARY DRIVER OF SOME 899 00:33:20,320 --> 00:33:20,520 CHANGES. 900 00:33:20,520 --> 00:33:21,800 SO, I MENTIONED THE IMPORTANCE 901 00:33:21,800 --> 00:33:23,160 OF THESE SHARED RISK FACTORS 902 00:33:23,160 --> 00:33:24,920 BECAUSE WE THINK THEY MAY HAVE 903 00:33:24,920 --> 00:33:26,960 DIRECT LINKS NOT ONLY TO STROKE 904 00:33:26,960 --> 00:33:28,440 BUT ALSO TO DEMENTIA. 905 00:33:28,440 --> 00:33:30,280 WE KNOW A LOT OF DIFFERENT 906 00:33:30,280 --> 00:33:31,200 IMPORTANT RISK FACTORS ARE 907 00:33:31,200 --> 00:33:34,120 ASSOCIATED WITH A LOT OF THESE 908 00:33:34,120 --> 00:33:41,360 SMALL VESSEL DISEASE SUBTYPES. 909 00:33:41,360 --> 00:33:45,280 HERE IS ACCUSE LACUNAR, WHITE 910 00:33:45,280 --> 00:33:46,680 MATTER HYPERINTENSITIES, ALL 911 00:33:46,680 --> 00:33:47,760 ASSOCIATED WITH IMAGING CHANGES. 912 00:33:47,760 --> 00:33:49,880 WE KNOW PEOPLE WHO HAVE IMAGING 913 00:33:49,880 --> 00:33:54,120 CHANGES ARE MORE LIKELY TO HAVE 914 00:33:54,120 --> 00:33:56,680 ACUTE STROKE, THEY MAY HAVE 915 00:33:56,680 --> 00:34:00,760 ATROPHY, AND THEY MAY HAVE 916 00:34:00,760 --> 00:34:01,720 CHANGES RELATED TO 917 00:34:01,720 --> 00:34:02,480 ALZHEIMER'S-SPECIFIC BIOMARKERS. 918 00:34:02,480 --> 00:34:04,880 I WANT TO GIVE YOU EVIDENCE FOR 919 00:34:04,880 --> 00:34:05,880 THESE DASHED LINES. 920 00:34:05,880 --> 00:34:08,080 WE ALSO KNOW NOT ONLY DO ALL OF 921 00:34:08,080 --> 00:34:10,600 THESE CHANGES CONTRIBUTE TO 922 00:34:10,600 --> 00:34:12,920 DEMENTIA RISK, AMYLOID 923 00:34:12,920 --> 00:34:14,560 CERTAINLY, ALTHOUGH NOT 924 00:34:14,560 --> 00:34:19,680 NECESSARILY THE ONLY PATHWAY OR 925 00:34:19,680 --> 00:34:21,120 LEADING HYPOTHESIS IT'S A MAJOR 926 00:34:21,120 --> 00:34:23,480 PLAYER, I WASN'T GOING TO GET TO 927 00:34:23,480 --> 00:34:25,160 THAT, I WANT TO MAKE SURE YOU 928 00:34:25,160 --> 00:34:27,520 UNDERSTAND I'M NOT DISCUSSING 929 00:34:27,520 --> 00:34:28,560 AMYLOID AS SYNONYMOUS WITH 930 00:34:28,560 --> 00:34:29,360 ALZHEIMER'S DISEASE BUT AN 931 00:34:29,360 --> 00:34:30,120 IMPORTANT PLAYER IN THE 932 00:34:30,120 --> 00:34:32,080 DEVELOPMENT OF ALZHEIMER'S, THE 933 00:34:32,080 --> 00:34:35,240 LEADING CAUSE OF DEMENTIA. 934 00:34:35,240 --> 00:34:37,000 ATROPHY IS ASSOCIATED WITH 935 00:34:37,000 --> 00:34:39,200 DEMENTIA, STROKE IS ASSOCIATED 936 00:34:39,200 --> 00:34:39,520 WITH DEMENTIA. 937 00:34:39,520 --> 00:34:40,680 MANY RISK FACTORS ARE ASSOCIATED 938 00:34:40,680 --> 00:34:41,920 WITH DEMENTIA AS WELL. 939 00:34:41,920 --> 00:34:44,880 I'LL TOUCH ON THAT BRIEFLY. 940 00:34:44,880 --> 00:34:46,520 SO, HERE YOU SEE A LOT OF THESE 941 00:34:46,520 --> 00:34:47,160 RISK FACTORS. 942 00:34:47,160 --> 00:34:50,480 I WANT TO POINT OUT HERE 943 00:34:50,480 --> 00:34:52,080 EMPHASIZING MID-LIFE RISK 944 00:34:52,080 --> 00:34:52,520 FACTORS. 945 00:34:52,520 --> 00:34:54,600 IN ARIC, I'M NOT GETTING INTO 946 00:34:54,600 --> 00:34:56,560 THAT LITERATURE HERE, BUT WE'VE 947 00:34:56,560 --> 00:34:58,120 SHOWN CONSISTENTLY THAT 948 00:34:58,120 --> 00:34:58,720 RELATIONSHIPS ARE STRONGER AND 949 00:34:58,720 --> 00:34:59,960 THIS IS SHOWN IN OTHER STUDIES 950 00:34:59,960 --> 00:35:02,360 AS WELL, IF YOU LOOK AT THEM, 951 00:35:02,360 --> 00:35:03,520 RISK FACTORS FOR MID-LIFE AS 952 00:35:03,520 --> 00:35:04,800 OPPOSED TO LATER LIFE. 953 00:35:04,800 --> 00:35:07,200 IT MAY BE IT TAKES DECADES FOR 954 00:35:07,200 --> 00:35:10,400 HYPERTENSION TO HAVE AN IMPACT 955 00:35:10,400 --> 00:35:11,320 ON COGNITION, FOR EXAMPLE, OY 956 00:35:11,320 --> 00:35:13,120 THERE MATE BE A CRITICAL WINDOW 957 00:35:13,120 --> 00:35:18,160 DURING WHICH YOU HAVE TO BE 958 00:35:18,160 --> 00:35:20,320 EXPOSED TO HYPERTENSION OR A 959 00:35:20,320 --> 00:35:20,720 COMBINATION. 960 00:35:20,720 --> 00:35:22,520 LATE IN LIFE IT'S LESS 961 00:35:22,520 --> 00:35:23,400 INDICATIVE, HYPERTENSION IN 962 00:35:23,400 --> 00:35:25,240 MID-LIFE IS A STRONG RISK FACTOR 963 00:35:25,240 --> 00:35:26,880 FOR FUTURE RISK OF DEMENTIA. 964 00:35:26,880 --> 00:35:29,520 YOU CAN SEE FOR A LOT OF RISK 965 00:35:29,520 --> 00:35:32,120 FACTORS, THERE'S BEEN GOOD 966 00:35:32,120 --> 00:35:33,320 EVIDENCE SHOWING ASSOCIATIONS 967 00:35:33,320 --> 00:35:35,000 WITH SMALL VESSEL DISEASE, 968 00:35:35,000 --> 00:35:36,640 STROKE, DEMENTIA AS WELL. 969 00:35:36,640 --> 00:35:38,160 BUT MORE QUESTIONABLE EVIDENCE 970 00:35:38,160 --> 00:35:39,760 ABOUT RELATIONSHIPS WITH THESE 971 00:35:39,760 --> 00:35:45,600 POTENTIAL MECHANISTIC LINKS. 972 00:35:45,600 --> 00:35:47,080 SOME ASSOCIATED WITH ATROPHY, 973 00:35:47,080 --> 00:35:51,400 SOME WITH AMYLOID. 974 00:35:51,400 --> 00:35:53,240 THREE PLUSES MEANS GOOD STRONG 975 00:35:53,240 --> 00:35:54,440 DATA, SOME IS CLINICAL TRIAL 976 00:35:54,440 --> 00:35:55,680 DATA, AS WE GET TO THE NEGATIVE 977 00:35:55,680 --> 00:35:59,680 IT MEANS THERE MIGHT BE EVEN 978 00:35:59,680 --> 00:36:01,320 DATA SUGGESTING LACK OF 979 00:36:01,320 --> 00:36:03,000 RELATIONSHIP BETWEEN THESE TWO 980 00:36:03,000 --> 00:36:03,840 THINGS, WHEREVER THE NEGATIVE 981 00:36:03,840 --> 00:36:05,880 HAPPENS TO BE, FOR INSTANCE 982 00:36:05,880 --> 00:36:07,160 MID-LIFE PHYSICAL INACTIVITY IS 983 00:36:07,160 --> 00:36:09,480 NOT ASSOCIATED WITH AMYLOID IN 984 00:36:09,480 --> 00:36:14,320 THE ARIC STUDIES, IN BETWEEN ARE 985 00:36:14,320 --> 00:36:15,720 DIFFERENT LEVELS OF EVIDENCE. 986 00:36:15,720 --> 00:36:16,440 THERE'S OVERLAP BETWEEN THESE 987 00:36:16,440 --> 00:36:20,200 AND AS WE THINK ABOUT POTENTIAL 988 00:36:20,200 --> 00:36:25,000 MECHANISTIC LINKS WITH 989 00:36:25,000 --> 00:36:27,400 UNANSWERED QUESTIONS. 990 00:36:27,400 --> 00:36:29,360 ATROPHY IS ONE POTENTIAL LINK. 991 00:36:29,360 --> 00:36:31,320 WE EVALUATED WHETHER PEOPLE WHO 992 00:36:31,320 --> 00:36:32,760 WILL WHITE MATTER 993 00:36:32,760 --> 00:36:34,640 HYPERINTENSITIESES AND INFARCT, 994 00:36:34,640 --> 00:36:36,120 ASSOCIATED WITH SMALL VESSEL 995 00:36:36,120 --> 00:36:37,800 DISEASE, RELATIONSHIP BETWEEN 996 00:36:37,800 --> 00:36:40,400 THOSE CHANGES AND COGNITION, 997 00:36:40,400 --> 00:36:42,280 WHETHER MEDIATED THROUGH VOLUME 998 00:36:42,280 --> 00:36:44,560 LOSS, LOOKED AT BRAIN VOLUME AND 999 00:36:44,560 --> 00:36:45,880 FOUND THAT PART OF THE 1000 00:36:45,880 --> 00:36:48,080 RELATIONSHIP WAS MEDIATED 1001 00:36:48,080 --> 00:36:52,800 THROUGH VOLUME LOSS, SO WE SAW 1002 00:36:52,800 --> 00:36:53,800 STRONG RELATIONSHIP ATTENUATED 1003 00:36:53,800 --> 00:36:55,240 WHEN INCLUDING BRAIN VOLUME BUT 1004 00:36:55,240 --> 00:36:56,640 NOT FULLY EXPLAINED BY VOLUME 1005 00:36:56,640 --> 00:36:59,440 LOSS TO LINK SMALL VESSEL 1006 00:36:59,440 --> 00:37:01,000 DISEASE AND COGNITION. 1007 00:37:01,000 --> 00:37:03,200 WHAT ABOUT ALZHEIMER'S DISEASE 1008 00:37:03,200 --> 00:37:03,560 NEUROPATHOLOGY? 1009 00:37:03,560 --> 00:37:11,120 SO IN THIS WORK LED BY WALKER, 1010 00:37:11,120 --> 00:37:12,360 NOW TENURE TRACK INVESTIGATOR AT 1011 00:37:12,360 --> 00:37:15,120 NIA, WE LOOKED AT AMYLOID PET. 1012 00:37:15,120 --> 00:37:19,920 I MENTIONED WE HAD A STUDY 1013 00:37:19,920 --> 00:37:22,120 LOOKING WITHIN A SUBSET FROM 1014 00:37:22,120 --> 00:37:23,560 THREE ARIC SITES. 1015 00:37:23,560 --> 00:37:25,160 YOU CAN SEE HERE HE FOUND THAT 1016 00:37:25,160 --> 00:37:29,240 PEOPLE WHO HAD MORE WHITE MATTER 1017 00:37:29,240 --> 00:37:29,640 HYPERINTENSITIES, 1018 00:37:29,640 --> 00:37:31,640 CROSS-SECTIONAL, HAD MORE BRAIN 1019 00:37:31,640 --> 00:37:33,040 AMYLOID INDEPENDENT OF 1020 00:37:33,040 --> 00:37:33,600 UNDERLYING VASCULAR RISK 1021 00:37:33,600 --> 00:37:36,320 FACTORS, WASN'T JUST A MARKER OF 1022 00:37:36,320 --> 00:37:37,520 HYPERTENSION, FOR EXAMPLE. 1023 00:37:37,520 --> 00:37:38,440 THE SUGGESTION THIS RELATIONSHIP 1024 00:37:38,440 --> 00:37:44,440 MIGHT BE STRONGER IN BLACK 1025 00:37:44,440 --> 00:37:44,880 PARTICIPANTS. 1026 00:37:44,880 --> 00:37:48,160 DEREK, A POSTBAC IN MY LAB NOW, 1027 00:37:48,160 --> 00:37:49,720 LOOKED WITH CEREBRAL MICROBLEEDS 1028 00:37:49,720 --> 00:37:52,120 IN THIS PAPER UNDER REVISION. 1029 00:37:52,120 --> 00:37:53,640 HE FOUND -- HE WAS TRYING TO 1030 00:37:53,640 --> 00:37:57,080 UNDERSTAND WHETHER DIFFERENT 1031 00:37:57,080 --> 00:37:59,400 PATTERNS OF MICROBLEEDS, SO I 1032 00:37:59,400 --> 00:38:01,120 SHOW WHERE THEY WERE 1033 00:38:01,120 --> 00:38:04,280 SUBCORTICAL, WHEN PEOPLE ARE 1034 00:38:04,280 --> 00:38:07,800 MORE CORTICAL MICRO BLEEDS THERE 1035 00:38:07,800 --> 00:38:09,760 ARE A MARKER, DEEPER BLEEDS ARE 1036 00:38:09,760 --> 00:38:11,640 A MARKER OF SMALL VESSEL 1037 00:38:11,640 --> 00:38:11,880 DISEASE. 1038 00:38:11,880 --> 00:38:13,280 WHAT HAPPENS WHEN YOU HAVE BOTH 1039 00:38:13,280 --> 00:38:15,120 BECAUSE WE SEE THAT FREQUENTLY 1040 00:38:15,120 --> 00:38:17,520 IN PEOPLE, IN THE 1041 00:38:17,520 --> 00:38:18,640 POPULATION-BASED STUDIES CAN WE 1042 00:38:18,640 --> 00:38:21,360 UNDERSTAND HOW THE PATTERN OF 1043 00:38:21,360 --> 00:38:22,800 MICROBLEEDS MIGHT BE RELATED TO 1044 00:38:22,800 --> 00:38:23,600 AMYLOID DEPOSITION? 1045 00:38:23,600 --> 00:38:26,400 HE FOUND THAT THE MIXED PATTERN 1046 00:38:26,400 --> 00:38:29,160 OF DEEP AND LOW BAR WAS NOT 1047 00:38:29,160 --> 00:38:30,720 ASSOCIATED WITH AMYLOID. 1048 00:38:30,720 --> 00:38:32,360 AND HAVING DEEP MICROBLEEDS 1049 00:38:32,360 --> 00:38:33,400 ALONE, SMALL VESSEL DISEASE 1050 00:38:33,400 --> 00:38:35,960 TYPE, IN THIS CASE NOT 1051 00:38:35,960 --> 00:38:41,200 ASSOCIATED WITH AMYLOID. 1052 00:38:41,200 --> 00:38:50,600 ELEVATED AMYLOID CONSISTENT WITH 1053 00:38:50,600 --> 00:38:51,920 ANGIOOPATHY, IT COULD BE 1054 00:38:51,920 --> 00:38:52,760 QUIESCENT BUT REPRESENTS A 1055 00:38:52,760 --> 00:38:54,240 DIFFERENT ENTITY HERE. 1056 00:38:54,240 --> 00:38:57,080 THIS DIDN'T SUPPORT LIKE THE 1057 00:38:57,080 --> 00:38:58,240 WHITE MATTER HYPERINTENSITIES 1058 00:38:58,240 --> 00:39:00,240 STUDY, SMALL VESSEL DISEASE 1059 00:39:00,240 --> 00:39:03,400 MARKER ASSOCIATED WITH AMYLOID 1060 00:39:03,400 --> 00:39:05,120 IN DEEP PATTERN, MORE CONSISTENT 1061 00:39:05,120 --> 00:39:06,800 WITH SMALL VESSEL DISEASE. 1062 00:39:06,800 --> 00:39:09,640 THERE'S SOME OTHER EVIDENCE THAT 1063 00:39:09,640 --> 00:39:11,040 AD-SPECIFIC BIOMARKERS HAVE BEEN 1064 00:39:11,040 --> 00:39:15,680 ASSOCIATED WITH SMALL VESSEL 1065 00:39:15,680 --> 00:39:15,880 DISEASE. 1066 00:39:15,880 --> 00:39:20,160 SO TREM-2 RELATED TO WHITE 1067 00:39:20,160 --> 00:39:24,720 MATTER HYPERINTENSITY, THIS IS 1068 00:39:24,720 --> 00:39:28,720 AN IMPORTANT EVIDENCE OF 1069 00:39:28,720 --> 00:39:29,720 MICROGLIAL ACTIVATION. 1070 00:39:29,720 --> 00:39:31,120 IN ADDITION WE HAVE INDICATION, 1071 00:39:31,120 --> 00:39:33,960 THIS IS REALLY AN EXCITING TIME 1072 00:39:33,960 --> 00:39:37,520 FOR THIS FIELD, WE HAVE REALLY 1073 00:39:37,520 --> 00:39:39,640 GOOD PLASMA BIOMARKERS OF 1074 00:39:39,640 --> 00:39:44,280 ALZHEIMER'S DISEASE CHANGES, AND 1075 00:39:44,280 --> 00:39:46,920 SO P-TAU 181 AND 17 WERE 1076 00:39:46,920 --> 00:39:48,240 ASSOCIATED WITH HIGHER WHITE 1077 00:39:48,240 --> 00:39:50,080 MATTER HYPERINTENSITIES BUT 1078 00:39:50,080 --> 00:39:51,800 DIDN'T FIND CONSISTENT 1079 00:39:51,800 --> 00:39:54,480 RELATIONSHIPS WITH TAU PET AND 1080 00:39:54,480 --> 00:40:01,200 WHITE MATTER HYPERINTENSITIES. 1081 00:40:01,200 --> 00:40:02,200 FURTHER INDICATION THAT THERE 1082 00:40:02,200 --> 00:40:05,840 MIGHT BE A LINK BETWEEN SMALL 1083 00:40:05,840 --> 00:40:07,680 VESSEL DISEASE AND AD-SPECIFIC 1084 00:40:07,680 --> 00:40:08,280 BIOMARKERS, REALLY IMPORTANT 1085 00:40:08,280 --> 00:40:10,000 CONSIDERATION AS YOU THINK ABOUT 1086 00:40:10,000 --> 00:40:11,520 THESE AND THINK ABOUT THE ROLE 1087 00:40:11,520 --> 00:40:16,120 SMALL VESSEL DISEASE MAY PLAY IN 1088 00:40:16,120 --> 00:40:21,360 A.D. PATHOGENESIS THINKING ABOUT 1089 00:40:21,360 --> 00:40:22,920 UNDERLYING RISK FACTORS AND 1090 00:40:22,920 --> 00:40:24,880 WHETHER CONFOUNDERS ARE 1091 00:40:24,880 --> 00:40:26,680 ADDRESSED. 1092 00:40:26,680 --> 00:40:31,760 ANOTHER IMPORTANT QUESTION, HOW 1093 00:40:31,760 --> 00:40:33,640 IT CONTRIBUTES TO DEMENTIA, WE 1094 00:40:33,640 --> 00:40:36,800 DID HERE IN THE COHORT LOOKED AT 1095 00:40:36,800 --> 00:40:38,320 RELATIVE CONTRIBUTIONS EVER 1096 00:40:38,320 --> 00:40:39,560 WHITE MATTER HYPERINTENSITIES 1097 00:40:39,560 --> 00:40:43,160 AND AMYLOID ON DEMENTIA RISK. 1098 00:40:43,160 --> 00:40:45,680 SO IN THE SUBSTUDY THESE ARE 1099 00:40:45,680 --> 00:40:48,440 PEOPLE JUST WITHOUT DEMENTIA WE 1100 00:40:48,440 --> 00:40:50,520 FOUND THAT WHITE MATTER 1101 00:40:50,520 --> 00:40:51,920 HYPERINTENSITIES AND AMYLOID 1102 00:40:51,920 --> 00:40:53,600 MEASURED THE UPTAKE VALUE RATIO 1103 00:40:53,600 --> 00:40:54,440 WERE BOTH INDEPENDENTLY 1104 00:40:54,440 --> 00:40:55,880 ASSOCIATED WITH RISK OF 1105 00:40:55,880 --> 00:40:56,280 DEMENTIA. 1106 00:40:56,280 --> 00:40:57,280 THEY DID NOT INTERACT WITH EACH 1107 00:40:57,280 --> 00:41:03,640 OTHER MEANING IF YOU HAD HIGH 1108 00:41:03,640 --> 00:41:04,520 AMYLOID AND WHITE MATTER 1109 00:41:04,520 --> 00:41:06,280 HYPERINTENSITIES THERE WAS NO 1110 00:41:06,280 --> 00:41:07,240 INCREASED RISK OF DEMENTIA 1111 00:41:07,240 --> 00:41:10,400 INDIAN 1112 00:41:10,400 --> 00:41:16,920 INDEPENDENT OF RISK FACTORS. 1113 00:41:16,920 --> 00:41:20,400 HOWEVER, THE RELATIONSHIP WITH 1114 00:41:20,400 --> 00:41:21,040 WHITE MATTER HYPERINTENSITIESES 1115 00:41:21,040 --> 00:41:23,600 WENT AWAY, THINKING ABOUT HOW 1116 00:41:23,600 --> 00:41:26,320 SMALL VESSEL DISEASE MIGHT BE 1117 00:41:26,320 --> 00:41:27,080 ASSOCIATED WITH 1118 00:41:27,080 --> 00:41:27,840 ALZHEIMER'S-SPECIFIC MARKERS, WE 1119 00:41:27,840 --> 00:41:30,120 NEED TO THINK ABOUT UNDERLYING 1120 00:41:30,120 --> 00:41:30,880 POTENTIAL CONFOUNDERS, MOST 1121 00:41:30,880 --> 00:41:32,000 STUDIES DON'T HAVE ABILITY TO 1122 00:41:32,000 --> 00:41:36,360 LOOK OVER DECADES TO UNDERSTAND 1123 00:41:36,360 --> 00:41:37,120 WHAT UNDERLYING VASCULAR RISK 1124 00:41:37,120 --> 00:41:38,760 MIGHT HAVE CONTRIBUTED BUT IT'S 1125 00:41:38,760 --> 00:41:40,520 IMPORTANT IN UNDERSTANDING 1126 00:41:40,520 --> 00:41:41,080 WHETHER WHITE MATTER 1127 00:41:41,080 --> 00:41:42,360 HYPERINTENSITIES NO MATTER WHAT 1128 00:41:42,360 --> 00:41:45,120 ROLE THEY PLAY IF CAUSAL OR JUST 1129 00:41:45,120 --> 00:41:47,400 ASSOCIATIVE THAT THEY MAY BE A 1130 00:41:47,400 --> 00:41:49,280 MARKER OF OTHER UNDERLYING RISK. 1131 00:41:49,280 --> 00:41:51,800 AGAIN, DIDN'T HAVE EVIDENCE OF 1132 00:41:51,800 --> 00:41:53,200 INTERACTION BETWEEN THE RISK 1133 00:41:53,200 --> 00:41:54,640 FACTORS AND AMYLOID ON THE RISK 1134 00:41:54,640 --> 00:41:55,960 OF DEMENTIA. 1135 00:41:55,960 --> 00:41:58,680 YOU CAN SEE THE NUMBERS ARE NOT 1136 00:41:58,680 --> 00:42:02,200 SO BIG, THIS LAST LINE HERE, 1137 00:42:02,200 --> 00:42:04,600 SMALLEST -- LOWEST LINE WHICH 1138 00:42:04,600 --> 00:42:05,600 MEANS THE LEAST DEMENTIA-FREE 1139 00:42:05,600 --> 00:42:06,760 SURVIVAL OR MOST DEMENTIA IS 1140 00:42:06,760 --> 00:42:08,400 INDIVIDUALS WHO HAD HIGH BLOOD 1141 00:42:08,400 --> 00:42:10,920 PRESSURE AND HAD HIGH AMYLOID 1142 00:42:10,920 --> 00:42:12,920 LEVEL, AGAIN SUGGESTING THAT 1143 00:42:12,920 --> 00:42:14,920 PERHAPS THERE MAY BE SOME 1144 00:42:14,920 --> 00:42:16,160 SYNERGISTIC EFFECT WE'RE NOT 1145 00:42:16,160 --> 00:42:19,160 ABLE TO CAPTURE WITH INADEQUATE 1146 00:42:19,160 --> 00:42:19,360 POWER. 1147 00:42:19,360 --> 00:42:22,080 THERE'S SOME EVIDENCE IN THE 1148 00:42:22,080 --> 00:42:25,240 WORK BY LOOKING AT SYNERGISTIC 1149 00:42:25,240 --> 00:42:29,760 INFLUENCE OF VASCULAR RISK AND 1150 00:42:29,760 --> 00:42:31,840 AMYLOID-BETA ON COGNITIVE 1151 00:42:31,840 --> 00:42:32,640 DECLINE, SUGGESTING PARTLY 1152 00:42:32,640 --> 00:42:36,440 RELATED THROUGH TAU, IF YOU HAVE 1153 00:42:36,440 --> 00:42:37,560 HIGH AMYLOID YOU'RE GOING TO 1154 00:42:37,560 --> 00:42:39,480 LOOK DIFFERENT IN TERMS OF TAU 1155 00:42:39,480 --> 00:42:40,560 LEVELS, FOR EXAMPLE, THAN 1156 00:42:40,560 --> 00:42:43,320 SOMEONE WHO DOESN'T HAVE THOSE 1157 00:42:43,320 --> 00:42:44,640 HIGH AMYLOID-BETA LEVELS AS 1158 00:42:44,640 --> 00:42:45,160 WELL. 1159 00:42:45,160 --> 00:42:47,480 SO AGAIN THE JURY IS VERY MUCH 1160 00:42:47,480 --> 00:42:47,640 OUT. 1161 00:42:47,640 --> 00:42:50,560 WE THINK THAT THERE ARE 1162 00:42:50,560 --> 00:42:51,200 IMPORTANT INTERRELATIONSHIPS 1163 00:42:51,200 --> 00:42:52,160 BETWEEN THESE. 1164 00:42:52,160 --> 00:42:53,800 THE DIFFICULTY IS MEASURES THESE 1165 00:42:53,800 --> 00:42:55,240 DIFFERENT A.D.-SPECIFIC 1166 00:42:55,240 --> 00:42:56,680 BIOMARKERS, MEASURING FORMS OF 1167 00:42:56,680 --> 00:42:58,440 SMALL VESSEL DISEASE, 1168 00:42:58,440 --> 00:42:59,840 UNDERSTANDING ABOUT THE 1169 00:42:59,840 --> 00:43:00,600 UNDERLYING LONG-TERM VASCULAR 1170 00:43:00,600 --> 00:43:03,800 RISK THAT COULD BE CONFOUNDING 1171 00:43:03,800 --> 00:43:04,640 SOME RELATIONSHIPS. 1172 00:43:04,640 --> 00:43:06,040 WHAT ABOUT SMALL VESSEL DISEASE 1173 00:43:06,040 --> 00:43:08,840 BEYOND THE BRAIN? 1174 00:43:08,840 --> 00:43:11,040 SO, CERTAINLY I SUSPECT THAT 1175 00:43:11,040 --> 00:43:12,200 MANY PEOPLE WHO ATTEND THIS TALK 1176 00:43:12,200 --> 00:43:14,200 AND WHO WORK IN THE CLINICAL 1177 00:43:14,200 --> 00:43:16,920 CENTER ARE STUDYING SOME FORM OF 1178 00:43:16,920 --> 00:43:17,520 SMALL VESSEL DISEASE ELSEWHERE 1179 00:43:17,520 --> 00:43:18,480 IN THE BODY. 1180 00:43:18,480 --> 00:43:19,680 I'M NOT TOUCHING ON MOST OF 1181 00:43:19,680 --> 00:43:21,200 THOSE OTHER FORMS OF SMALL 1182 00:43:21,200 --> 00:43:22,760 VESSEL DISEASE BUT I WANT TO 1183 00:43:22,760 --> 00:43:25,360 TALK ABOUT THE RETINA BECAUSE 1184 00:43:25,360 --> 00:43:27,240 IT'S THE MOST RELEVANT AND 1185 00:43:27,240 --> 00:43:28,200 HIGHLY LINKED WITH THESE 1186 00:43:28,200 --> 00:43:32,040 CEREBRAL FORMS OF SMALL VESSEL 1187 00:43:32,040 --> 00:43:36,520 DISEASE. 1188 00:43:36,520 --> 00:43:40,040 MICROVASCULAR CHANGES IN THE 1189 00:43:40,040 --> 00:43:43,520 RETINA OCCUR AFTER VASCULAR RISK 1190 00:43:43,520 --> 00:43:44,760 FACTOR EVALUATION, AND SOMETIME 1191 00:43:44,760 --> 00:43:45,840 BEFORE COGNITIVE DECLINE. 1192 00:43:45,840 --> 00:43:47,800 IT'S POSSIBLE THIS COULD MEDIATE 1193 00:43:47,800 --> 00:43:48,720 SOME OF THOSE OBSERVED 1194 00:43:48,720 --> 00:43:50,200 ASSOCIATIONS THAT WE COULD 1195 00:43:50,200 --> 00:43:51,640 UNDERSTAND MORE ABOUT HOW 1196 00:43:51,640 --> 00:43:52,600 VASCULAR RISK AFFECTS DEMENTIA 1197 00:43:52,600 --> 00:43:54,280 BUT THINKING ABOUT HOW THE 1198 00:43:54,280 --> 00:43:56,440 RETINA IS AFFECTED AS WELL. 1199 00:43:56,440 --> 00:44:00,360 IT COULD BE A MARKER FOR DISEASE 1200 00:44:00,360 --> 00:44:01,360 PRESENCE OR DISEASE PROGRESSION, 1201 00:44:01,360 --> 00:44:05,440 CERTAINLY EASY ISSUE -- EASIER 1202 00:44:05,440 --> 00:44:07,840 TO LOOK IN THE EYE THAN GET AN 1203 00:44:07,840 --> 00:44:09,040 MRI AND CHEAPER. 1204 00:44:09,040 --> 00:44:09,840 POTENTIALLY A USEFUL SURROGATE 1205 00:44:09,840 --> 00:44:11,720 FOR CLINICAL TRIALS OR MAYBE 1206 00:44:11,720 --> 00:44:13,600 EVEN HAVE A ROLE IN ENROLLMENT 1207 00:44:13,600 --> 00:44:14,880 OF CLINICAL TRIALS. 1208 00:44:14,880 --> 00:44:19,440 SO, WE KNOW IT CO-OCCURS WITH 1209 00:44:19,440 --> 00:44:20,080 MICROVASCULAR DISEASE MARKERS IN 1210 00:44:20,080 --> 00:44:21,440 THE BRAIN. 1211 00:44:21,440 --> 00:44:24,160 WE KNOW THERE'S COMMON GENETIC 1212 00:44:24,160 --> 00:44:26,120 RISK FACTORS, IN GENERAL AS WELL 1213 00:44:26,120 --> 00:44:28,760 AS RELATIONSHIP WITH COGNITION 1214 00:44:28,760 --> 00:44:31,360 AND RELATED OUTCOMES. 1215 00:44:31,360 --> 00:44:33,560 WE HAVE RETINAL IMAGING FROM 1216 00:44:33,560 --> 00:44:35,360 EARLIER VISITS AND MORE RECENT 1217 00:44:35,360 --> 00:44:37,600 VISITS, JUST TO SHOW IN THIS 1218 00:44:37,600 --> 00:44:40,160 EARLIER WORK MORE RETINAL 1219 00:44:40,160 --> 00:44:42,080 MICROVASCULAR DISEASE VISIT 3 1220 00:44:42,080 --> 00:44:43,080 ASSOCIATED CROSS-SECTIONALLY 1221 00:44:43,080 --> 00:44:48,240 WITH MORE WHITE MATTER 1222 00:44:48,240 --> 00:44:49,680 HYPERINTENSITIES, TOM HANFF 1223 00:44:49,680 --> 00:44:53,280 WORKED WITH ME, NOW AT PENN AT A 1224 00:44:53,280 --> 00:44:53,920 CARDIOLOGIST, WAS STUDYING 1225 00:44:53,920 --> 00:44:56,320 IMPORTANCE OF PROGRESSION OF 1226 00:44:56,320 --> 00:44:58,400 RETINAL MICROVASCULAR DISEASE, 1227 00:44:58,400 --> 00:45:01,920 I'M SORRY, PROGRESSION OF SMALL 1228 00:45:01,920 --> 00:45:03,360 VESSEL DISEASE PREDICTED BY 1229 00:45:03,360 --> 00:45:08,920 RETINAL DISEASE, IF YOU HAD MORE 1230 00:45:08,920 --> 00:45:10,000 RETINAL DISEASE IT PROGRESSED 1231 00:45:10,000 --> 00:45:10,440 MORE. 1232 00:45:10,440 --> 00:45:11,400 I'VE TOLD YOU PROGRESSION OF 1233 00:45:11,400 --> 00:45:13,960 CHANGES IS AN IMPORTANT RISK 1234 00:45:13,960 --> 00:45:16,240 FACTOR FOR WORSE OUTCOME 1235 00:45:16,240 --> 00:45:17,240 INCLUDING RECURRENT STROKE. 1236 00:45:17,240 --> 00:45:19,080 IN ADDITION WE KNOW IT'S 1237 00:45:19,080 --> 00:45:20,280 ASSOCIATED WITH COGNITION SO 1238 00:45:20,280 --> 00:45:24,680 PEOPLE WHO ARE ABNORMAL RETINAL 1239 00:45:24,680 --> 00:45:25,280 MICROVASCULATURE SIMILAR TO 1240 00:45:25,280 --> 00:45:32,440 OTHER CHANGES IN THE BRAIN HAVE 1241 00:45:32,440 --> 00:45:34,520 MORE COGNITIVE DECLINE. 1242 00:45:34,520 --> 00:45:35,640 PEOPLE WITH RETINOPATHY HAD MORE 1243 00:45:35,640 --> 00:45:37,600 DECLINE OVER TEN YEARS IN 1244 00:45:37,600 --> 00:45:38,800 COGNITION THAN PEOPLE WITHOUT, 1245 00:45:38,800 --> 00:45:41,560 WE SEE LESSER EFFECT SIZES FOR 1246 00:45:41,560 --> 00:45:41,960 OTHER MARKERS. 1247 00:45:41,960 --> 00:45:45,720 A LOT OF THESE ARE NOT PREVALENT 1248 00:45:45,720 --> 00:45:47,240 IN THIS POPULATION RECRUITED AS 1249 00:45:47,240 --> 00:45:48,440 A COMMUNITY-BASED COHORT BUT WE 1250 00:45:48,440 --> 00:45:51,320 DO SEE THIS CLEAR RELATIONSHIP. 1251 00:45:51,320 --> 00:45:53,720 JENNIFER DEAL AT HOPKINS LOOKED 1252 00:45:53,720 --> 00:45:55,680 AT LONGER FOLLOW-UP, TWO 1253 00:45:55,680 --> 00:46:00,520 DECADES, PEOPLE WHO HAD MORE 1254 00:46:00,520 --> 00:46:01,400 RETINOPATHY, MODERATE/SEVERE 1255 00:46:01,400 --> 00:46:03,480 VERSUS NONE IN ADJUSTED MODELS 1256 00:46:03,480 --> 00:46:04,880 HAD MORE COGNITIVE DECLINE OVER 1257 00:46:04,880 --> 00:46:05,640 TWO DECADES. 1258 00:46:05,640 --> 00:46:06,920 FURTHER EVIDENCE THIS MIGHT BE 1259 00:46:06,920 --> 00:46:09,040 AN IMPORTANT MARKER OF OUTCOME 1260 00:46:09,040 --> 00:46:10,160 AND IMPORTANT MARKER OF 1261 00:46:10,160 --> 00:46:11,200 CONCURRENT SMALL VESSEL DISEASE 1262 00:46:11,200 --> 00:46:13,520 AND MIGHT BE USEFUL TO THINK IF 1263 00:46:13,520 --> 00:46:15,920 WE'RE TRYING TO STUDY MECHANISMS 1264 00:46:15,920 --> 00:46:19,440 IN SMALL VESSEL DISEASE, ROLE ON 1265 00:46:19,440 --> 00:46:19,920 COGNITION. 1266 00:46:19,920 --> 00:46:22,840 A POSTDOCTORAL FELLOW WITH ME 1267 00:46:22,840 --> 00:46:24,520 HERE AT NINDS IS LOOKING AT THIS 1268 00:46:24,520 --> 00:46:27,200 AND HAS A PAPER UNDER REVIEW 1269 00:46:27,200 --> 00:46:28,880 LOOKING AT AMYLOID PET AND 1270 00:46:28,880 --> 00:46:30,160 RELATIONSHIP WITH RETINAL 1271 00:46:30,160 --> 00:46:30,560 DISEASE. 1272 00:46:30,560 --> 00:46:34,080 IF WE KNOW IT'S ASSOCIATED WITH 1273 00:46:34,080 --> 00:46:37,280 COGNITION WHAT MIGHT THE 1274 00:46:37,280 --> 00:46:38,520 MECHANISM BE? 1275 00:46:38,520 --> 00:46:40,000 HE EVALUATED PEOPLE WITHOUT 1276 00:46:40,000 --> 00:46:41,960 DEMENTIA FROM THREE ARIC SITES, 1277 00:46:41,960 --> 00:46:43,280 LOOKING AT RELATIONSHIPS BETWEEN 1278 00:46:43,280 --> 00:46:44,920 EARLIER, SO CLOSER TO MID-LIFE 1279 00:46:44,920 --> 00:46:47,120 RETINAL DISEASE AS WELL AS LATER 1280 00:46:47,120 --> 00:46:49,840 LIFE RETINAL DISEASE, AND LOOKED 1281 00:46:49,840 --> 00:46:50,920 AT POSITIVE AMYLOID SCANS, YES 1282 00:46:50,920 --> 00:46:51,800 OR NO. 1283 00:46:51,800 --> 00:46:53,800 HERE TO SHOW THERE'S NOT THAT 1284 00:46:53,800 --> 00:46:54,720 MANY PEOPLE WITH RETINOPATHY, 1285 00:46:54,720 --> 00:46:57,520 THAT MADE IT INTO THE MUCH LATER 1286 00:46:57,520 --> 00:46:58,400 STUDY OF NON-DEMENTED 1287 00:46:58,400 --> 00:47:00,920 INDIVIDUALS, SO CERTAINLY THE 1288 00:47:00,920 --> 00:47:10,760 PEOPLE THAT HAD MORE RHETT 1289 00:47:10,760 --> 00:47:14,080 INOPATHY HAD MORE DIABETES, 1290 00:47:14,080 --> 00:47:14,920 SMALL NUMBERS. 1291 00:47:14,920 --> 00:47:18,440 20+ YEARS LATER DIABETES IN THIS 1292 00:47:18,440 --> 00:47:20,600 VISIT 3, LATE MID-LIFE, MUCH 1293 00:47:20,600 --> 00:47:23,600 LESS PREVALENT NOW 10 OF THE 11 1294 00:47:23,600 --> 00:47:25,080 PEOPLE WITH RETINOPATHY AT VISIT 1295 00:47:25,080 --> 00:47:28,960 5, WHEN WE DID THE PET SCAN, HAD 1296 00:47:28,960 --> 00:47:30,040 RETINOPATHY, HAD DIABETES WITH 1297 00:47:30,040 --> 00:47:32,440 HIGH RATES OF HYPERTENSION AS 1298 00:47:32,440 --> 00:47:32,880 WELL. 1299 00:47:32,880 --> 00:47:34,080 BASICALLY HE FOUND RELATIONSHIPS 1300 00:47:34,080 --> 00:47:37,680 WERE NULL, SO PEOPLE WHO HAD 1301 00:47:37,680 --> 00:47:40,520 RETINAL SIGNS, MID-LIFE AND LATE 1302 00:47:40,520 --> 00:47:42,640 LIFE, VERY SMALL NUMBERS, HAD 1303 00:47:42,640 --> 00:47:44,800 ASSOCIATIONS WITH ELEVATED BRAIN 1304 00:47:44,800 --> 00:47:47,440 AMYLOID, I'M SORRY, PEOPLE WHO 1305 00:47:47,440 --> 00:47:49,080 HAD -- WE DID NOT FIND EVIDENCE 1306 00:47:49,080 --> 00:47:51,040 OF RETINAL DISEASE IN MID-LIFE 1307 00:47:51,040 --> 00:47:52,560 OR LATE LIFE BEING ASSOCIATED 1308 00:47:52,560 --> 00:47:57,200 WITH BRAIN AMYLOID BUT IT MAY 1309 00:47:57,200 --> 00:47:59,600 LOOK PROTECTIVE, MEANING IF HAD 1310 00:47:59,600 --> 00:48:07,160 YOU RETINOPATHY LESS LIKELY TO 1311 00:48:07,160 --> 00:48:08,120 HAVE BRAIN AMYLOID. 1312 00:48:08,120 --> 00:48:09,760 THEY WERE A ROBUST GROUP. 1313 00:48:09,760 --> 00:48:12,320 NO EVIDENCE HERE THAT RETINAL 1314 00:48:12,320 --> 00:48:14,080 SIGNS WERE ASSOCIATED WITH 1315 00:48:14,080 --> 00:48:16,360 AMYLOID, EITHER 1316 00:48:16,360 --> 00:48:22,840 CROSS-SECTIONALLY OR LOOKING 1317 00:48:22,840 --> 00:48:23,760 CROSS-TEMPORALLY OVER TIME. 1318 00:48:23,760 --> 00:48:26,280 I WANT TO TOUCH A GAPS AND TALK 1319 00:48:26,280 --> 00:48:27,360 ABOUT TREATMENT AND PREVENTION 1320 00:48:27,360 --> 00:48:29,000 BECAUSE THIS IS REALLY AN 1321 00:48:29,000 --> 00:48:30,760 IMPORTANT AND EXCITING PART OF 1322 00:48:30,760 --> 00:48:31,280 THIS. 1323 00:48:31,280 --> 00:48:34,680 CERTAINLY IN THE FIELD WE NEED 1324 00:48:34,680 --> 00:48:35,440 CLEAR DEFINITIONS, DIAGNOSTIC 1325 00:48:35,440 --> 00:48:39,040 CRITERIA, WHEN WE THINK ABOUT 1326 00:48:39,040 --> 00:48:42,240 HYPERTENSIVE SMALL VESSEL 1327 00:48:42,240 --> 00:48:44,520 DISEASE IT'S HARD TO DEFINE FOR 1328 00:48:44,520 --> 00:48:45,520 RESEARCH OR CLINICAL CARE. 1329 00:48:45,520 --> 00:48:47,360 THERE'S MORE TO BE DONE, 1330 00:48:47,360 --> 00:48:49,680 MECHANISMS OF SMALL VESSEL 1331 00:48:49,680 --> 00:48:50,600 DISEASE, COGNITION, DEMENTIA. 1332 00:48:50,600 --> 00:48:51,960 REALLY WHAT DOES THIS MEAN FOR 1333 00:48:51,960 --> 00:48:53,320 OPPORTUNITIES FOR TREATMENT AND 1334 00:48:53,320 --> 00:48:53,600 PREVENTION? 1335 00:48:53,600 --> 00:48:55,840 I'LL COME BACK TO THAT IN A 1336 00:48:55,840 --> 00:48:56,080 SECOND. 1337 00:48:56,080 --> 00:48:57,000 AND ARE THERE OPPORTUNITIES TO 1338 00:48:57,000 --> 00:48:59,680 USE SOME OF THESE SURROGATE END 1339 00:48:59,680 --> 00:49:01,400 POINTS IN CLINICAL TRIALS FOR 1340 00:49:01,400 --> 00:49:02,080 ENROLLMENT OR OUTCOME? 1341 00:49:02,080 --> 00:49:04,280 AND THIS IS A REALLY TRICKY AREA 1342 00:49:04,280 --> 00:49:05,920 WHEN YOU'RE DESIGNING A TRIAL 1343 00:49:05,920 --> 00:49:06,680 BASED ON STROKE, EVERYONE KNOW 1344 00:49:06,680 --> 00:49:07,880 WHAT IS A STROKE IS. 1345 00:49:07,880 --> 00:49:12,400 YOU CAN SAY HOW TO ENROLL 1346 00:49:12,400 --> 00:49:14,560 SOMEONE WITH A STROKE, BUT 1347 00:49:14,560 --> 00:49:15,560 SURROGATE ENDPOINT HAS LESS 1348 00:49:15,560 --> 00:49:16,760 MEANING FOR THE PUBLIC, ALSO WE 1349 00:49:16,760 --> 00:49:19,720 NEED TO MAKE SURE WE HAVE 1350 00:49:19,720 --> 00:49:20,920 HOMOGENOUS METHODS FOR DEFINING 1351 00:49:20,920 --> 00:49:24,680 SOME OF THESE THINGS. 1352 00:49:24,680 --> 00:49:26,200 TREATMENT AND PREVENTION, THE 1353 00:49:26,200 --> 00:49:27,160 LONG AND SHORT, WE DON'T KNOW 1354 00:49:27,160 --> 00:49:30,240 WHAT TO DO WHEN WE SEE THESE 1355 00:49:30,240 --> 00:49:30,520 PATIENTS. 1356 00:49:30,520 --> 00:49:32,520 PEOPLE WITH SMALL VESSEL DISEASE 1357 00:49:32,520 --> 00:49:35,040 ARE FOUND ALL THE TIME 1358 00:49:35,040 --> 00:49:35,720 INCIDENTALLY. 1359 00:49:35,720 --> 00:49:39,840 WE DID A SURVEY OF NEUROLOGISTS, 1360 00:49:39,840 --> 00:49:44,360 GOT 136 RESPONDENTS, HERE IS A 1361 00:49:44,360 --> 00:49:46,640 PATIENT A LOT OF WHITE MATTER 1362 00:49:46,640 --> 00:49:47,800 HYPERINTENSITIES HERE. 1363 00:49:47,800 --> 00:49:51,280 SHE HAD SOME SYMPTOMS, NO 1364 00:49:51,280 --> 00:49:52,680 CLINICAL STROKE THOUGH. 1365 00:49:52,680 --> 00:49:53,880 HOW WOULD YOU TREAT HER? 1366 00:49:53,880 --> 00:49:55,520 THERE WAS SO MUCH VARIETY IN 1367 00:49:55,520 --> 00:49:56,520 WHAT PEOPLE SAID. 1368 00:49:56,520 --> 00:49:58,520 SOME PEOPLE SAID THIS IS PRIMARY 1369 00:49:58,520 --> 00:49:59,920 PREVENTION, THEY HAVEN'T HAD AN 1370 00:49:59,920 --> 00:50:01,240 EVENT, HAVEN'T HAD A STROKE, 1371 00:50:01,240 --> 00:50:03,320 THEREFORE WE NEED TO THINK AS 1372 00:50:03,320 --> 00:50:04,160 PRIMARY PREVENTION. 1373 00:50:04,160 --> 00:50:07,920 A QUARTER SAID WE SEE THIS MUCH 1374 00:50:07,920 --> 00:50:09,200 WHITE MATTER HYPERINTENSITY, 1375 00:50:09,200 --> 00:50:10,200 COMPARABLE TO HAVING HAD A 1376 00:50:10,200 --> 00:50:13,480 STROKE SO THINK OF SECONDARY 1377 00:50:13,480 --> 00:50:14,880 PREVENTION, IMPORTANT BECAUSE 1378 00:50:14,880 --> 00:50:18,040 DIFFERENT TREATMENT AND 1379 00:50:18,040 --> 00:50:19,280 DIFFERENT THERAPIES ARE 1380 00:50:19,280 --> 00:50:21,440 DIFFERENT EVIDENCE FOR PRIMARY 1381 00:50:21,440 --> 00:50:22,320 VERSUS SECONDARY PREVENTION. 1382 00:50:22,320 --> 00:50:24,520 HALF SAID THEY MIGHT USE 1383 00:50:24,520 --> 00:50:24,760 ASPIRIN. 1384 00:50:24,760 --> 00:50:32,760 A THIRD HAD NO IDEA. 1385 00:50:32,760 --> 00:50:36,520 22% SAID WON'T USE ASPIRIN, AND 1386 00:50:36,520 --> 00:50:36,960 STATIN. 1387 00:50:36,960 --> 00:50:39,760 JUST YESTERDAY THIS WAS 1388 00:50:39,760 --> 00:50:41,560 PUBLISHED ONLINE, PRO/CON 1389 00:50:41,560 --> 00:50:43,520 CONTROVERSY IN STROKE ARTICLE, 1390 00:50:43,520 --> 00:50:47,800 LOOKING AT ANTIPLATELET THERAPY 1391 00:50:47,800 --> 00:50:51,880 OR NOT FOR ASYMPTOMATIC LACUNAR, 1392 00:50:51,880 --> 00:50:55,240 SHOULD WE PUT THOSE PEOPLE ON 1393 00:50:55,240 --> 00:50:56,880 ASPIRIN, FOR EXAMPLE? 1394 00:50:56,880 --> 00:50:58,200 PROMINENT PEOPLE SAID YES, AND 1395 00:50:58,200 --> 00:51:00,480 NO, AND WE DON'T HAVE A 1396 00:51:00,480 --> 00:51:03,800 CONSISTENT MESSAGE OR CONSISTENT 1397 00:51:03,800 --> 00:51:04,160 RECOMMENDATION. 1398 00:51:04,160 --> 00:51:07,280 AS WE THINK ABOUT PRIMARY AND 1399 00:51:07,280 --> 00:51:08,120 SECONDARY PREVENTION, THERE ARE 1400 00:51:08,120 --> 00:51:09,480 DIFFERENT QUESTIONS, IF YOU'RE 1401 00:51:09,480 --> 00:51:11,440 TRYING TO PREVENT A STROKE, WE 1402 00:51:11,440 --> 00:51:12,440 KNOW THAT'S PRIMARY PREVENTION. 1403 00:51:12,440 --> 00:51:15,040 IF HAVE YOU SMALL VESSEL DISEASE 1404 00:51:15,040 --> 00:51:17,000 AND YOU'RE TRYING TO PREVENT 1405 00:51:17,000 --> 00:51:17,680 PROGRESSION OF SMALL VESSEL 1406 00:51:17,680 --> 00:51:20,200 DISEASE OR THE STROKE OR TRYING 1407 00:51:20,200 --> 00:51:21,960 TO PREVENT COGNITIVE DECLINE 1408 00:51:21,960 --> 00:51:23,480 IT'S UNCERTAIN, PART OF WHAT 1409 00:51:23,480 --> 00:51:24,600 MAKES IT CONFUSING ABOUT 1410 00:51:24,600 --> 00:51:24,920 TREATMENT. 1411 00:51:24,920 --> 00:51:26,440 YOU CAN SEE HERE, AGAIN, NOT 1412 00:51:26,440 --> 00:51:28,320 VERY CLEAR DATA ABOUT WHAT TO DO 1413 00:51:28,320 --> 00:51:29,960 DEPENDING WHAT YOU'RE TRYING TO 1414 00:51:29,960 --> 00:51:30,200 PREVENT. 1415 00:51:30,200 --> 00:51:32,160 REALITY IS YOU'RE TRYING TO 1416 00:51:32,160 --> 00:51:33,480 PREVENT MULTIPLE THINGS. 1417 00:51:33,480 --> 00:51:35,760 BUT WE REALLY HAVE SOME 1418 00:51:35,760 --> 00:51:36,960 INCONSISTENT EVIDENCE WHICH 1419 00:51:36,960 --> 00:51:42,360 MAKES THIS MURKY AND CONFUSE C. 1420 00:51:42,360 --> 00:51:43,560 WE NEED BETTER STUDIES. 1421 00:51:43,560 --> 00:51:45,360 SMALL VESSEL DISEASE IS VERY 1422 00:51:45,360 --> 00:51:46,920 COMMON, PARTICULARLY CERTAIN 1423 00:51:46,920 --> 00:51:48,560 FORMS LIKE WHITE MATTER 1424 00:51:48,560 --> 00:51:49,440 HYPERINTENSITIES, AND EVEN 1425 00:51:49,440 --> 00:51:50,560 THOUGH IT'S CLASSICALLY REFERRED 1426 00:51:50,560 --> 00:51:53,400 TO AS SILENT OR COVERT OR 1427 00:51:53,400 --> 00:51:57,440 ASYMPTOMATIC, OR INCIDENTAL, IT 1428 00:51:57,440 --> 00:51:59,600 CLEARLY HAS CONSEQUENCES AND ITS 1429 00:51:59,600 --> 00:52:00,680 PRESENCE AND PROGRESSION CAN 1430 00:52:00,680 --> 00:52:01,880 HAVE GREAT IMPACTS ON PEOPLE. 1431 00:52:01,880 --> 00:52:12,280 WHEN WE THINK ABOUT THESE 1432 00:52:12,280 --> 00:52:13,600 SUBTYPE, IT'S USEFUL TO THINK 1433 00:52:13,600 --> 00:52:16,160 ABOUT LUMPING THEM BECAUSE OF 1434 00:52:16,160 --> 00:52:17,760 SHARED OUTCOMES, MAKING 1435 00:52:17,760 --> 00:52:18,640 RECOMMENDATIONS FOR TREATMENT, 1436 00:52:18,640 --> 00:52:20,800 PROGNOSIS AND THINKING ABOUT 1437 00:52:20,800 --> 00:52:21,240 CAUSE. 1438 00:52:21,240 --> 00:52:23,240 THERE ARE MULTIPLE POTENTIAL 1439 00:52:23,240 --> 00:52:24,600 MECHANISMS, SOME I'VE DISCUSSED 1440 00:52:24,600 --> 00:52:26,960 AS TO HOW SMALL VESSEL DISEASE 1441 00:52:26,960 --> 00:52:35,480 AND STROKE COULD ACT ON DEMENTIA 1442 00:52:35,480 --> 00:52:38,040 INCLUDING ATROPHY, AMYLOID 1443 00:52:38,040 --> 00:52:46,760 DEPOSITION, WE DON'T SEE CLEAR 1444 00:52:46,760 --> 00:52:47,480 EVIDENCE OF MULTI-PLICATIVE 1445 00:52:47,480 --> 00:52:50,280 INDICATIONS IN OUR WORK. 1446 00:52:50,280 --> 00:52:51,920 THERE'S SO MUCH UNCERTAINTY. 1447 00:52:51,920 --> 00:52:54,120 WE SEE THESE INCIDENTAL FINDINGS 1448 00:52:54,120 --> 00:52:59,480 ALL THE TIME, AND WHEN PRESENTED 1449 00:52:59,480 --> 00:53:02,240 CLINICALLY IT'S UNCLEAR. 1450 00:53:02,240 --> 00:53:04,640 IF YOU ARE LOOKING FOR EXCUSE TO 1451 00:53:04,640 --> 00:53:06,360 START MEDICATION WE CAN USE 1452 00:53:06,360 --> 00:53:07,800 SMALL VESSEL DISEASE BUT WE 1453 00:53:07,800 --> 00:53:09,760 DON'T KNOW BEST GUIDANCE. 1454 00:53:09,760 --> 00:53:10,880 FUTURE DIRECTION, I'LL CONTINUE 1455 00:53:10,880 --> 00:53:13,360 TO UNDERSTAND MORE ABOUT SMALL 1456 00:53:13,360 --> 00:53:14,480 VESSEL DISEASE, BETTER 1457 00:53:14,480 --> 00:53:16,440 UNDERSTAND HOW TO PHENOTYPE AND 1458 00:53:16,440 --> 00:53:17,520 UNDERSTAND MORE ABOUT WHO 1459 00:53:17,520 --> 00:53:18,840 PROGRESSES AND WHY, AND 1460 00:53:18,840 --> 00:53:20,800 ULTIMATELY HOW WE CAN MAYBE 1461 00:53:20,800 --> 00:53:22,120 PREVENT THAT PROGRESSION. 1462 00:53:22,120 --> 00:53:23,960 ALSO UNDERSTANDING HOW SMALL 1463 00:53:23,960 --> 00:53:25,760 VESSEL DISEASE AFFECTS EARLY 1464 00:53:25,760 --> 00:53:27,320 STROKE RECOVERY AND OUTCOME. 1465 00:53:27,320 --> 00:53:29,880 IN ADDITION WE THINK OF THE 1466 00:53:29,880 --> 00:53:31,200 CONCEPT OF COGNITIVE RESERVE, 1467 00:53:31,200 --> 00:53:35,240 THIS IDEA THERE ARE FACTORS THAT 1468 00:53:35,240 --> 00:53:36,680 MAKE YOU MORE RESISTANT TO 1469 00:53:36,680 --> 00:53:37,440 PATHOLOGIC CHANGES IN YOUR 1470 00:53:37,440 --> 00:53:37,640 BRAIN. 1471 00:53:37,640 --> 00:53:39,280 WE THINK OF THIS IN ALZHEIMER'S 1472 00:53:39,280 --> 00:53:41,040 DISEASE, WHERE WE KNOW PEOPLE 1473 00:53:41,040 --> 00:53:45,680 CAN HAVE A LOT OF PATHOLOGY ON 1474 00:53:45,680 --> 00:53:48,480 AUTOPSY, BUT COGNITIVELY NORMAL. 1475 00:53:48,480 --> 00:53:49,480 COGNITIVE RESEARCH, WHETHER 1476 00:53:49,480 --> 00:53:50,560 EDUCATION OR OTHER FACTORS, 1477 00:53:50,560 --> 00:53:51,680 PROTECTED YOU FROM THAT 1478 00:53:51,680 --> 00:53:52,520 PATHOLOGY, FROM HAVING THE 1479 00:53:52,520 --> 00:53:54,080 COGNITION YOU MIGHT BE EXPECTED 1480 00:53:54,080 --> 00:53:54,320 TO HAVE. 1481 00:53:54,320 --> 00:53:57,160 I THINK IT'S IMPORTANT TO THINK 1482 00:53:57,160 --> 00:53:58,760 OF THIS FOR SMALL VESSEL 1483 00:53:58,760 --> 00:54:03,200 DISEASE, HOW DOES IT AFFECT YOUR 1484 00:54:03,200 --> 00:54:04,360 COGNITIVE PERFORMANCE, IT MAY 1485 00:54:04,360 --> 00:54:07,080 DIFFER BECAUSE OF RESERVE 1486 00:54:07,080 --> 00:54:08,960 FACTORS, WE ARE EVALUATING, 1487 00:54:08,960 --> 00:54:10,600 UNDERSTANDING HOW IT PLAYS A 1488 00:54:10,600 --> 00:54:14,000 ROLE IN A.D. PATHOLOGY, TARGETS 1489 00:54:14,000 --> 00:54:14,640 FOR PREVENTION, TREATMENT, 1490 00:54:14,640 --> 00:54:16,880 BECAUSE THIS IS LIKELY TO HAVE 1491 00:54:16,880 --> 00:54:20,680 LARGE IMPACTS ON A POPULATION 1492 00:54:20,680 --> 00:54:22,040 SCALE. 1493 00:54:22,040 --> 00:54:24,000 BRIEFLY, MY LAST SUBSTANTIVE 1494 00:54:24,000 --> 00:54:26,080 SLIDE, THE DISCOVERY COHORT IS 1495 00:54:26,080 --> 00:54:27,600 REALLY GOING TO FOCUS ON -- IT'S 1496 00:54:27,600 --> 00:54:29,880 A STUDY OF INDIVIDUALS WITH 1497 00:54:29,880 --> 00:54:31,080 STROKE BEING RECRUITED FROM 30 1498 00:54:31,080 --> 00:54:32,400 SITES ACROSS THE COUNTRY AND 1499 00:54:32,400 --> 00:54:33,720 UNDERSTAND THE RELATIONSHIP 1500 00:54:33,720 --> 00:54:35,560 BETWEEN STROKE AND POST-STROKE 1501 00:54:35,560 --> 00:54:37,440 OUTCOMES IN A DISPARITIES 1502 00:54:37,440 --> 00:54:38,840 POPULATION OR DISPARITIES 1503 00:54:38,840 --> 00:54:40,600 POPULATIONS BUT FOCUSING ALSO ON 1504 00:54:40,600 --> 00:54:41,800 HOW SMALL VESSEL DISEASE AFFECTS 1505 00:54:41,800 --> 00:54:44,040 YOUR ABILITY TO RECOVER FROM A 1506 00:54:44,040 --> 00:54:46,960 COGNITIVE STANDPOINT AFTER 1507 00:54:46,960 --> 00:54:47,440 STROKE. 1508 00:54:47,440 --> 00:54:53,880 DISCOVERY IS LED BY CO-P.I.s 1509 00:54:53,880 --> 00:55:00,520 AT MASS GENERAL, A LARGE STUDY 1510 00:55:00,520 --> 00:55:03,160 FROM 30 SITES, TO STUDY 1511 00:55:03,160 --> 00:55:04,720 POST-STROKE COGNITION AND FOCUS 1512 00:55:04,720 --> 00:55:06,120 ON DIVERSE POPULATIONS TO 1513 00:55:06,120 --> 00:55:07,960 UNDERSTAND DISPARITIES IN THIS 1514 00:55:07,960 --> 00:55:08,840 AREA. 1515 00:55:08,840 --> 00:55:11,480 THAT'S ONGOING, CLOSE TO 2,000 1516 00:55:11,480 --> 00:55:13,360 PEOPLE IN RECRUITMENT, STILL 1517 00:55:13,360 --> 00:55:14,000 EARLY DAYS. 1518 00:55:14,000 --> 00:55:16,520 FINALLY I'D LIKE TO ACKNOWLEDGE 1519 00:55:16,520 --> 00:55:17,160 MANY TREMENDOUS COLLABORATORS, 1520 00:55:17,160 --> 00:55:19,240 ALL OF THIS WORK IS VERY MUCH A 1521 00:55:19,240 --> 00:55:19,560 TEAM SPORT. 1522 00:55:19,560 --> 00:55:21,280 AND SO HERE IS MANY OF THE 1523 00:55:21,280 --> 00:55:23,440 PEOPLE INVOLVED IN A LOT OF WORK 1524 00:55:23,440 --> 00:55:24,400 I DESCRIBED, PRIOR FUNDING 1525 00:55:24,400 --> 00:55:31,440 SOURCES AS WELL AS FUNDING FOR 1526 00:55:31,440 --> 00:55:34,600 ARIC IN PARTICULAR, AND HERE WE 1527 00:55:34,600 --> 00:55:36,360 ARE MEETING IN ZOOM TIMES AS 1528 00:55:36,360 --> 00:55:38,760 WELL AS A COUPLE WEEKS AGO ON 1529 00:55:38,760 --> 00:55:40,680 THE SOUTH LAWN OF BUILDING 10, 1530 00:55:40,680 --> 00:55:43,280 AND THIS IS THE STROKE BRANCH, 1531 00:55:43,280 --> 00:55:46,440 AND THIS IS THE GROUP OF ARIC 1532 00:55:46,440 --> 00:55:47,360 INVESTIGATORS YEARS ALLEY. 1533 00:55:47,360 --> 00:55:49,760 WITH THAT I'LL STOP AND TAKE 1534 00:55:49,760 --> 00:55:50,040 QUESTIONS. 1535 00:55:50,040 --> 00:55:53,360 THANK YOU VERY MUCH. 1536 00:55:53,360 --> 00:55:55,560 >>THANK YOU FOR SHARING YOUR 1537 00:55:55,560 --> 00:55:57,200 WORK AND YOUR DEEP INSIGHTS INTO 1538 00:55:57,200 --> 00:56:00,680 THE PRESENCE OF THESE SO-CALLED 1539 00:56:00,680 --> 00:56:03,960 SILENT LESIONS OF SMALL VESSEL 1540 00:56:03,960 --> 00:56:06,280 DISEASE, ESPECIALLY MARKERS OF 1541 00:56:06,280 --> 00:56:07,600 DECLINE IN COGNITION AND 1542 00:56:07,600 --> 00:56:07,880 DEMENTIA. 1543 00:56:07,880 --> 00:56:12,520 WE DO HAVE A COUPLE QUESTIONS. 1544 00:56:12,520 --> 00:56:17,360 FIRST OF ALL, WHY DOES HIGH 1545 00:56:17,360 --> 00:56:18,320 CHOLESTEROL PROTECT AGAINST 1546 00:56:18,320 --> 00:56:18,600 DEMENTIA? 1547 00:56:18,600 --> 00:56:19,960 >>SO, THE CHOLESTEROL ISSUE IS 1548 00:56:19,960 --> 00:56:20,960 VERY TRICKY. 1549 00:56:20,960 --> 00:56:23,160 WE HAVE EVIDENCE THAT HIGH 1550 00:56:23,160 --> 00:56:24,240 CHOLESTEROL IS ASSOCIATED WITH 1551 00:56:24,240 --> 00:56:25,440 DEMENTIA RISK, IT'S NOT NEARLY 1552 00:56:25,440 --> 00:56:28,720 AS STRONG OF A RISK FACTOR AS IS 1553 00:56:28,720 --> 00:56:29,680 HYPERTENSION, FOR EXAMPLE, IN 1554 00:56:29,680 --> 00:56:30,600 GENERAL CHOLESTEROL APPEARS TO 1555 00:56:30,600 --> 00:56:32,880 BE MORE IMPORTANT FOR THE HEART 1556 00:56:32,880 --> 00:56:34,760 AND BLOOD PRESSURE APPEARS TO BE 1557 00:56:34,760 --> 00:56:36,480 MORE IMPORTANT FOR THE BRAIN. 1558 00:56:36,480 --> 00:56:38,120 THERE IS SOME EVIDENCE GOING 1559 00:56:38,120 --> 00:56:39,880 BOTH WAYS THAT STATINS, FOR 1560 00:56:39,880 --> 00:56:41,640 EXAMPLE, ARE ASSOCIATED WITH 1561 00:56:41,640 --> 00:56:43,240 LOWER DEMENTIA RATES. 1562 00:56:43,240 --> 00:56:45,240 BUT ALSO SOME EVIDENCE THAT IT 1563 00:56:45,240 --> 00:56:46,720 CAUSES SOME COGNITIVE PROBLEMS 1564 00:56:46,720 --> 00:56:49,080 AS WELL. 1565 00:56:49,080 --> 00:56:50,720 I THINK IN GENERAL OBVIOUSLY IF 1566 00:56:50,720 --> 00:56:51,720 YOU THINK ABOUT MEDICATION USE, 1567 00:56:51,720 --> 00:56:54,000 YOU HAVE TO WORRY ABOUT THE 1568 00:56:54,000 --> 00:56:56,440 HEALTHY USER EFFECT PEOPLE WHO 1569 00:56:56,440 --> 00:56:58,120 TAKE MEDICATIONS ARE DIFFERENT 1570 00:56:58,120 --> 00:56:58,840 IN OBSERVATIONAL STUDIES THAN 1571 00:56:58,840 --> 00:56:59,600 THOSE WHO DON'T. 1572 00:56:59,600 --> 00:57:01,640 IT'S HARD TO KNOW WHAT TO THINK 1573 00:57:01,640 --> 00:57:03,000 OF THE STATIN EVIDENCE. 1574 00:57:03,000 --> 00:57:05,280 WE SEE HIGHER LEVELS OF MID-LIFE 1575 00:57:05,280 --> 00:57:06,600 CHOLESTEROL ARE ASSOCIATED WITH 1576 00:57:06,600 --> 00:57:07,880 GREATER RISK OF COGNITIVE 1577 00:57:07,880 --> 00:57:09,320 DECLINE BUT IT'S VERY SMALL 1578 00:57:09,320 --> 00:57:10,080 AMOUNT OF DECLINE. 1579 00:57:10,080 --> 00:57:13,600 IT'S NOT A VERY LARGE EFFECT. 1580 00:57:13,600 --> 00:57:14,480 AND, AGAIN, CHOLESTEROL APPEARS 1581 00:57:14,480 --> 00:57:17,400 TO BE LESS IMPORTANT IN GENERAL 1582 00:57:17,400 --> 00:57:20,680 THAN RISK FACTORS LIKE HIGH 1583 00:57:20,680 --> 00:57:21,840 BLOOD PRESSURE. 1584 00:57:21,840 --> 00:57:21,960 s. 1585 00:57:21,960 --> 00:57:23,760 >>THANK YOU VERY MUCH. 1586 00:57:23,760 --> 00:57:24,760 ANOTHER QUESTION HERE. 1587 00:57:24,760 --> 00:57:26,520 IT SAYS, THANK YOU FOR SHARING 1588 00:57:26,520 --> 00:57:28,920 THE EFFECT OF THE LACK OF 1589 00:57:28,920 --> 00:57:30,320 EQUIPOISE IN MANAGEMENT OF THESE 1590 00:57:30,320 --> 00:57:32,280 FINDINGS OF SMALL VESSEL 1591 00:57:32,280 --> 00:57:33,840 DISEASE, BUT DO YOU YOURSELF 1592 00:57:33,840 --> 00:57:36,040 HAVE ANY RECOMMENDATIONS ON HOW 1593 00:57:36,040 --> 00:57:38,520 THESE PATIENTS COULD OR SHOULD 1594 00:57:38,520 --> 00:57:39,040 BE MANAGED? 1595 00:57:39,040 --> 00:57:40,120 >>YEAH, SO I CERTAINLY THINK 1596 00:57:40,120 --> 00:57:41,480 ABOUT BLOOD PRESSURE AS THE 1597 00:57:41,480 --> 00:57:43,800 FIRST THING WHEN I SEE SOMEONE 1598 00:57:43,800 --> 00:57:45,520 WITH A SCAN, WITH SMALL VESSEL 1599 00:57:45,520 --> 00:57:45,960 DECEMBER. 1600 00:57:45,960 --> 00:57:46,600 WE KNOW BLOOD PRESSURE CONTROL 1601 00:57:46,600 --> 00:57:48,920 IS GOING TO BE IMPORTANT FOR 1602 00:57:48,920 --> 00:57:50,160 MULTIPLE REASONS. 1603 00:57:50,160 --> 00:57:52,480 I PERSONALLY DON'T TREAT PEOPLE 1604 00:57:52,480 --> 00:57:55,520 WITH ASPIRIN AT THIS POINT IN 1605 00:57:55,520 --> 00:57:56,280 TIME OR ANOTHER ANTIPLATELET 1606 00:57:56,280 --> 00:57:57,800 BASED ON HAVING THAT KIND OF 1607 00:57:57,800 --> 00:57:58,040 SCAN. 1608 00:57:58,040 --> 00:58:02,840 WE KNOW FROM RECENT STUDIES 1609 00:58:02,840 --> 00:58:06,640 PRIMARY PREVENTION ASPIRIN 1610 00:58:06,640 --> 00:58:07,760 DOESN'T HAVE A CLEAR ROLE. 1611 00:58:07,760 --> 00:58:09,640 I THINK ABOUT RISK FACTORS THIS 1612 00:58:09,640 --> 00:58:11,360 MIGHT BE ALERTING ME TO. 1613 00:58:11,360 --> 00:58:15,000 WHEN I SEE THAT SCAN I LOOK HARD 1614 00:58:15,000 --> 00:58:16,320 FOR HIGH BLOOD PRESSURE. 1615 00:58:16,320 --> 00:58:18,040 IF IT'S NOT THERE, THAT'S RARE 1616 00:58:18,040 --> 00:58:19,800 AND MAKES ME WONDER WHAT ELSE IS 1617 00:58:19,800 --> 00:58:21,200 GOING ON IN THIS PERSON BECAUSE 1618 00:58:21,200 --> 00:58:23,200 THAT'S USUALLY SUCH A BIG PART 1619 00:58:23,200 --> 00:58:26,160 OF THE AMOUNT OF CHANGE WE SEE 1620 00:58:26,160 --> 00:58:29,000 IN WHITE MATTER 1621 00:58:29,000 --> 00:58:29,720 HYPERINTENSITIES, A LOT IS 1622 00:58:29,720 --> 00:58:31,080 DRIVEN BY HIGH BLOOD PRESSURE. 1623 00:58:31,080 --> 00:58:32,800 I USE THIS AS INDICATOR I SHOULD 1624 00:58:32,800 --> 00:58:34,360 DO SOMETHING ABOUT RISK FACTORS 1625 00:58:34,360 --> 00:58:38,200 AND WOULD RECOMMEND TREATMENT OF 1626 00:58:38,200 --> 00:58:39,080 THOSE RISK FACTORS BUT 1627 00:58:39,080 --> 00:58:43,560 PERSONALLY I DON'T TREAT WITH 1628 00:58:43,560 --> 00:58:45,080 ASPIRIN OR ANTIPLATELETS BECAUSE 1629 00:58:45,080 --> 00:58:49,040 I DON'T THINK AWAY EVIDENCE, 1630 00:58:49,040 --> 00:58:50,760 NEED FOR EQUIPOISE AND MORE 1631 00:58:50,760 --> 00:58:51,120 CLINICAL TRIALS. 1632 00:58:51,120 --> 00:58:52,440 >>ANOTHER QUESTION, ARE THERE 1633 00:58:52,440 --> 00:58:54,080 RISK FACTORS OR BIOMARKERS THAT 1634 00:58:54,080 --> 00:58:56,040 COULD BE IDENTIFIED IN YOUNGER 1635 00:58:56,040 --> 00:58:57,920 ADULTS THAT MAY PRECEDE OR EVEN 1636 00:58:57,920 --> 00:59:01,760 BE PREDICTIVE MUCH SMALL VESSEL 1637 00:59:01,760 --> 00:59:03,800 DISEASE FOUND IN OLDER COHORTS 1638 00:59:03,800 --> 00:59:04,200 AND POPULATION? 1639 00:59:04,200 --> 00:59:06,560 >>YES, THIS IS AN IMPORTANT 1640 00:59:06,560 --> 00:59:12,520 AREA THAT WE NEED TO DO MORE 1641 00:59:12,520 --> 00:59:14,040 RESEARCH, I DON'T THINK MID-LIFE 1642 00:59:14,040 --> 00:59:19,840 IS IMAGINE -- MAGICAL. 1643 00:59:19,840 --> 00:59:20,640 THERE'S COHORTS LIKE CARDIA, 1644 00:59:20,640 --> 00:59:26,760 WHICH STARTS ELLER, -- EARLIERI 1645 00:59:26,760 --> 00:59:28,600 WOULD LOVE TO LINK PEDIATRIC 1646 00:59:28,600 --> 00:59:30,680 WITH OLDER, MY SUSPICION IS 1647 00:59:30,680 --> 00:59:31,960 HIGHER RATES OF DIABETES, 1648 00:59:31,960 --> 00:59:32,760 HYPERTENSION IN ADOLESCENTS WILL 1649 00:59:32,760 --> 00:59:34,080 BE A BIG PROBLEM DECADES DOWN 1650 00:59:34,080 --> 00:59:35,840 THE ROAD IN TERMS OF SMALL 1651 00:59:35,840 --> 00:59:37,400 VESSEL DISEASE AND DEMENTIA. 1652 00:59:37,400 --> 00:59:39,920 SO, I WOULD SAY PROBABLY THE 1653 00:59:39,920 --> 00:59:41,760 MOST IMPORTANT THING IS 1654 00:59:41,760 --> 00:59:42,640 SCREENING BLOOD PRESSURE, AND 1655 00:59:42,640 --> 00:59:44,400 THAT'S GOING TO BE IMPORTANT FOR 1656 00:59:44,400 --> 00:59:46,440 SMALL VESSEL DISEASE AS WELL AS 1657 00:59:46,440 --> 00:59:47,880 FOR -- IT'S ASSOCIATED WITH RISK 1658 00:59:47,880 --> 00:59:50,840 OF DEMENTIA AS WELL AND THINGS 1659 00:59:50,840 --> 00:59:53,960 LIKE NOT SMOKING, OTHER VASCULAR 1660 00:59:53,960 --> 00:59:58,160 HEALTH, BUT IF IN TERMS OF 1661 00:59:58,160 --> 00:59:58,920 BIOMARKERS BLOOD PRESSURE 1662 00:59:58,920 --> 01:00:00,360 SCREENING AND MANAGEMENT IS 1663 01:00:00,360 --> 01:00:03,640 WOULDN'T MOST IMPORTANT EARLY 1664 01:00:03,640 --> 01:00:03,880 MARKERS. 1665 01:00:03,880 --> 01:00:06,320 >>THAT TAKES US UP TO THE 1666 01:00:06,320 --> 01:00:06,880 HOUR. 1667 01:00:06,880 --> 01:00:08,040 DR. GOTTESMAN, THANK YOU VERY 1668 01:00:08,040 --> 01:00:09,800 MUCH FOR SHARING YOUR WORK AND 1669 01:00:09,800 --> 01:00:11,000 YOUR BRILLIANT PRESENTATION. 1670 01:00:11,000 --> 01:00:12,000 WE MUCH APPRECIATE IT. 1671 01:00:12,000 --> 01:00:13,960 AND TO THE NIH COMMUNITY, THANK 1672 01:00:13,960 --> 01:00:14,960 YOU FOR JOINING THIS AFTERNOON 1673 01:00:14,960 --> 01:00:16,680 AND HAVE A GOOD DAY. 1674 01:00:16,680 --> 01:00:17,840 THANK YOU VERY MUCH. 1675 01:00:17,840 --> 00:00:00,000 >>THANKS SO MUCH.