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>> DR. IADECOLA: HI.  THIS
IS 

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CONSTANTINO IADECOLA.  CAN I 

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HAVE MY FIRST SLIDE?

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I AM A NEUROLOGIST FROM WEILL 

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CORNELL MEDICAL COLLEGE IN NEW 

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YORK AND HAVE NO DISCLOSURES, 

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AND I AM HONORED TO BE PART OF 

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THIS DISTINGUISHED GROUP, AND 

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PROVIDE SOME INPUT INTO THIS 

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VERY IMPORTANT MEDICAL ISSUES 

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THAT WE ARE FACING. 

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NEXT SLIDE. 

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OKAY SO THIS IS THE  

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RECOMMENDATION WHICH HAVE TO DO 

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WITH THE BASIC MECHANISMS AND 

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THE RECOMMENDATION TO ADVANCE 

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BASIC RESEARCH AND EXPERIMENTAL 

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MODELS ON SINGLE, MULTIPLE 

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INTERACTIVE MECHANISMS DRIVING 

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MIXED PATHOLOGY, INCLUDING 

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COMORBIDITIES ACROSS TEXAS, 

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WITH EMPHASIS ON THE VALIDATION 

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OF HUMAN DATA SET AND 

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IDENTIFICATION OF THERAPEUTIC 

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TARGETS. 

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SO PARTICULARLY WE NEED TO 

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DEVELOP NEW MODELS OF MIXED 

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PATHOLOGY TAKING INTO ACCOUNT 

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THE COURSE OF THE DISEASES, THE 

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INTERACTION OF THE DIFFERENT 

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PATHOLOGIES, CRITICAL 

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CHECKPOINT FOR THE IMPACT OF 

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THESE PATHOLOGIES, AND OVER THE 

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LIFE COURSE THE THERAPEUTIC 

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WINDOWS THAT MAY BE AVAILABLE 

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AND NEEDED. 

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CONSIDER THE IMPACT OF SEX, AGE 

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AND COMORBIDITY, AT THIS POINT 

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DR. KOROSHETZ EMPHASIZE THE 

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IMPORTANCE OF AGING IN THE 

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EMERGENCE OF MIXED PATHOLOGIES. 

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THAT IS GOING TO BE VERY, VERY 

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IMPORTANT ASPECT TO BE 

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CONSIDERED. 

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AND ALSO TO IDENTIFY WHAT ARE 

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THE KEY DRIVERS OF THIS 

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PATHOLOGY. AND WHAT ARE THE 

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ULTIMATE FACTORS. 

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TO THIS UNDERSTANDING OF THIS 

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INTERACTION, WE MAY BE ABLE TO 

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FIGURE OUT NEW THERAPEUTIC 

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INTERVENTION THAT MAY BE 

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EFFECTIVE. 

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AS EMPHASIZED BY DR. ERTEKIN 

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TANER'S REPORT FROM THE 

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NATIONAL ACADEMY REPORT, WE 

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NEED TO HAVE METABOLIC RESEARCH 

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TO APPLY IN THE DIFFERENT 

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MULTIDISCIPLINARY TEAMS 

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NECESSARY TO CRACK THIS VERY 

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COMPLEX PROBLEM OF THIS 

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MULTIPLE PATHOLOGIES. 

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WE NEED AN OPEN ACCESS 

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REPOSITORIES.  THERE ARE A LOT 

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OF EXISTING REPOSITORIES. WE 

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NEED TO ADD HARMONIZATION, AND 

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WE NEED EVERYTHING TO BE EASY 

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TO BE ACCESSIBLE AND SEARCHABLE 

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AN UP ONLINE SO THAT PROTOCOLS 

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CAN BE REPRODUCED, AND METHODS 

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CAN BE ESTABLISHED AND SO ON. 

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AND FINALLY WE NEED TO 

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EMPHASIZE THE PUBLIC PRIVATE 

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PARTNERSHIP AND RAPIDLY REACH A 

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CONSENSUS ABOUT THERAPEUTIC 

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TARGETS AND MODEL INTERVENTIONS 

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SO THIS NEW DISCOVERIES CAN BE 

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RAPIDLY TRANSLATED INTO THE 

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CLINIC. 

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NEXT SLIDE. 

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THERE IS A VERY UNIQUE AND 

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COMPLEX FRAMEWORK IN MULTIPLE 

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DEMENTIAS, HAS TO DO WITH THE 

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IMPACT OF MULTIPLE THERAPIES.  

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AND THIS CAN BE CONSIDERED IN 

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DIFFERENT WAYS. 

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FOR EXAMPLE YOU MAY HAVE A 

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MULTIPLE INDEPENDENT 

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PATHOLOGIST, LIKE 1, 2 AND 3 IN 

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DIFFERENT REGIONS AND EACH ONE 

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LEADING TO CERTAIN ASPECTS OF 

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COGNITIVE IMPAIRMENT.  YOU MAY 

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HAVE DIFFERENT COGNITIVE 

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DOMAINS BEING AFFECTED BY EACH 

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INDEPENDENT PATHOLOGY. 

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ESSENTIALLY THE IMPACT WOULD BE 

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ADDITIVE, ONE TO THE OTHER. 

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NEXT SLIDE. 

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IN THESE SCENARIOS THERE IS A 

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DRIVING PATHOLOGY RESPONSIBLE 

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FOR DOWNSTREAM PATHOLOGIES AS 

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SHOWN HERE. 

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FOR EXAMPLE IN THE DOMINANT 

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ALZHEIMER'S DISEASE YOU HAVE A 

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PATHOLOGY DRIVING -- YOU HAVE A 

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SITUATION WHERE A PATHOLOGY 

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DRIVES THE OTHERS AND THE 

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COGNITIVE IMPAIRMENT-- NEXT 

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00:04:01,742 --> 00:04:08,415
SLIDE -- THE COGNITIVE 

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IMPAIRMENT IS A RESULT OF THIS 

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ADDITIVE PATHOLOGIES THAT MAY 

112
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OCCUR. 

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NEXT SLIDE. 

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ONE OF THE COMPLEXITIES OF THIS 

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ISSUE IS UNDERLINED BY THE FACT 

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THAT THESE PATHOLOGIES MAY BE 

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INTERACTING. SO FOR EXAMPLE 

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(INDISCERNIBLE) MAY LEAD TO 

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(INDISCERNIBLE) PATHOLOGY IN 

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THEM INTERACT RECIPROCALLY, AND 

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AMPLIFYING THE COGNITIVE 

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IMPACT. AND THESE PATHOLOGIES 

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MAY BE LOCATED IN DIFFERENT 

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BRAIN REGIONS AND MAY BE 

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CONNECTED TO PATHWAYS WHICH MAY 

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LEAD TO THE PATHOLOGY 

127
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DEVELOPING IN A DIFFERENT BRAIN 

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REGION. LIKE WE DISCOVERED FOR 

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(INDISCERNIBLE) WHERE THERE IS 

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A SPREAD OF THE PATHOLOGY IN 

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DIFFERENT BRAIN REGIONS. 

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SO CLEARLY WE NEED TO 

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UNDERSTAND ALL OF THESE 

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INTERACTIONS TO REALLY COME UP 

135
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WITH EFFECTIVE SOLUTIONS. 

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NEXT SLIDE. 

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WHAT WE REALLY NEED -- NEXT -- 

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WOULD BE TO AGAIN DEVELOP 

139
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MODELS THAT REFLECT THE 

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COMPLEXITY OF THIS MULTI 

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DEMENTIA, WE MAY REFLECT THE 

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COMPLICITY OF DIFFERENT 

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PATHOLOGIES, AGAIN THE ROLE OF 

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SEX AND COMORBIDITY IS GOING TO 

145
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BE CRITICAL, IDENTIFYING 

146
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HUMAN-BASED METHODS SUCH AS IP 

147
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CELLS AND ORGANOIDS AND SOMEONE 

148
00:05:36,703 --> 00:05:40,374
THAT MAY LEAD TO A BETTER 

149
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TRANSLATION INTO THE HUMAN. 

150
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AND DEVELOP DATA REPOSITORIES 

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IN AN OPEN AND EASILY 

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ACCESSIBLE, AND MOVE TOWARDS 

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TRANSLATION.

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BECAUSE ONE OF THE KEY ELEMENTS 

155
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IS GOING TO BE TO DETERMINE 

156
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WHAT IS THE PATHOLOGY THAT IS 

157
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MOST PREVAILING FOR AFFECTING 

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THE KIND OF IMPACT OF THE 

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PATHOLOGY?

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SOME OF THIS MIGHT BE BASED 

161
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STANDARDS; SOME MAY BE MORE 

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DIRECTED TOWARDS THE COGNITIVE 

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IMPAIRMENT. 

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I AM DONE I THINK, AHEAD OF 

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TIME.

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>> THANK YOU. 

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>> DR. FARDO: THANK YOU
DR. 

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IADECOLA. I AM DAVID FARDO, 

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BIOSTATISTICIAN AND STATISTICAL 

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GENETICIST FROM THE UNIVERSITY 

171
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OF KENTUCKY. I AM HAPPY TO 

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PRESENT THIS ON BEHALF OF THE 

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NINDS WORKING GROUP AND THE 

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SPECTRUM FROM BASIC 

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TRANSLATIONAL AND CLINICAL 

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RESEARCH AND DATA 

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STANDARDIZATION, HARMONIZATION, 

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AND INTEGRATION. I HAVE NO 

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DISCLOSURES. 

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NEXT SLIDE. 

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00:06:49,176 --> 00:06:52,145
THIS DATA RECOMMENDATION IS 

182
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SUPPORTING MULTIPLE ETIOLOGY 

183
00:07:00,254 --> 00:07:00,821
DEMENTIAS  FAIRLY BROAD IN 

184
00:07:00,821 --> 00:07:01,388
SCOPE INTENDED TO SUPPORT A 

185
00:07:01,388 --> 00:07:02,022
BROAD SPECTRUM OF RESEARCH WITH 

186
00:07:02,022 --> 00:07:02,489
TARGETED EFFORTS TO 

187
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STANDARDIZE, HARMONIZE, AND 

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INTEGRATE MULTIPLE ETIOLOGY 

189
00:07:09,529 --> 00:07:10,097
DATA FROM NEW AND EXISTING 

190
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MODALITIES INCLUDING THAT FROM 

191
00:07:10,731 --> 00:07:11,331
NOVEL CLINICAL AND BIOMARKER 

192
00:07:11,331 --> 00:07:12,599
COLLECTION APPROACHES. 

193
00:07:12,599 --> 00:07:13,166
SPECIFICALLY WE ARE ENDORSING 

194
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THE DEVELOPMENT OF DIGITAL 

195
00:07:13,734 --> 00:07:18,272
IMAGING, AND AI DRIVEN 

196
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APPROACHES TO HARMONIZE DATA 

197
00:07:19,006 --> 00:07:21,975
SETS ACROSS THE STATE 

198
00:07:21,975 --> 00:07:22,442
PLATFORMS, AS WELL AS 

199
00:07:22,442 --> 00:07:24,411
OPEN-SOURCE PLATFORMS FOR 

200
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STORAGE, ANALYSIS, 

201
00:07:28,348 --> 00:07:28,982
VISUALIZATION, AND INTEGRATION 

202
00:07:28,982 --> 00:07:33,687
OF BOTH EXISTING AND NEW DATA 

203
00:07:33,687 --> 00:07:34,254
WITH HARMONIZED AND IDEALLY 

204
00:07:34,254 --> 00:07:34,788
CONSENSUS OF STANDARDIZED 

205
00:07:34,788 --> 00:07:37,090
CONVENTIONS OF NED. 

206
00:07:37,090 --> 00:07:39,159
AND EMPHASIZE EFFORTS FOR DRUG 

207
00:07:39,159 --> 00:07:40,060
DEVELOPMENT REPURPOSING AND 

208
00:07:40,060 --> 00:07:40,694
SHARED ANALYTICAL PRACTICES AND 

209
00:07:40,694 --> 00:07:43,130
COMMON NED CODING TO PROMOTE 

210
00:07:43,130 --> 00:07:45,365
HARMONIZED INTEGRATION ACROSS 

211
00:07:45,365 --> 00:07:48,769
EMRS IN MULTIGROUP EFFORTS. 

212
00:07:48,769 --> 00:07:49,303
WE ALSO RECOMMEND TO CREATE 

213
00:07:49,303 --> 00:07:52,406
CONSENSUS QUALITY METRICS TO 

214
00:07:52,406 --> 00:07:53,040
SUPPORT DATA INTEGRATION ACROSS 

215
00:07:53,040 --> 00:07:57,077
BIOMARKER PLATFORMS AND COHORTS 

216
00:07:57,077 --> 00:07:58,545
FOR CROSS STUDY COMPARISON AND 

217
00:07:58,545 --> 00:07:59,212
AGGREGATION, AS WELL AS 

218
00:07:59,212 --> 00:07:59,780
COOPERATION AMONG DATABASE 

219
00:07:59,780 --> 00:08:02,816
GROUP SO THAT NED-SPECIFIC DATA 

220
00:08:02,816 --> 00:08:04,885
CAN BE MOST PROBABLY, 

221
00:08:04,885 --> 00:08:06,653
RESPONSIBLY AND SAFELY BE 

222
00:08:06,653 --> 00:08:07,254
INTERCHANGED, AGGREGATED AND 

223
00:08:07,254 --> 00:08:17,431
COMPARED. 

224
00:08:17,698 --> 00:08:18,131
FINALLY, WE RECOMMEND 

225
00:08:18,131 --> 00:08:18,699
SUPPORTING BY REPOSITORIES 

226
00:08:18,699 --> 00:08:19,232
ACROSS ORGANIZATION TABS 

227
00:08:19,232 --> 00:08:19,766
INCLUDING PUBLIC/PRIVATE 

228
00:08:19,766 --> 00:08:20,367
PARTNERSHIPS TO ACHIEVE THIS 

229
00:08:20,367 --> 00:08:20,901
RESEARCH SUPPORT. 

230
00:08:20,901 --> 00:08:22,602
NEXT SLIDE. 

231
00:08:22,602 --> 00:08:31,345
THIS RECOMMENDATION IS 

232
00:08:31,345 --> 00:08:31,945
MOTIVATED BY THE FOUNDATIONAL 

233
00:08:31,945 --> 00:08:32,579
ROLE THAT QUALITY DATA PLAYS IN 

234
00:08:32,579 --> 00:08:33,146
MULTIPLE ETIOLOGY DEMENTIA 

235
00:08:33,146 --> 00:08:33,747
RESEARCH AND WE HAVE TO HAVE 

236
00:08:33,747 --> 00:08:34,381
COMMON DEFINITIONS AND 

237
00:08:34,381 --> 00:08:40,754
NOMENCLATURE REGARDING THIS.  

238
00:08:40,754 --> 00:08:41,254
RECOMMENDING EFFORTS TO 

239
00:08:41,254 --> 00:08:41,755
MAXIMIZE UTILITY IMPACT 

240
00:08:41,755 --> 00:08:42,823
PREVIOUSLY COLLECTED DATA TO 

241
00:08:42,823 --> 00:08:44,524
HONOR BOTH FINANCIAL AND HUMAN 

242
00:08:44,524 --> 00:08:45,125
INVESTMENTS INCLUDING THAT OF 

243
00:08:45,125 --> 00:08:48,528
OUR COMMITTED AND PASSIONATE 

244
00:08:48,528 --> 00:08:50,897
RESEARCH VOLUNTEERS, BY 

245
00:08:50,897 --> 00:08:51,498
INTEGRATING EXISTING AND NEW 

246
00:08:51,498 --> 00:08:52,666
SOURCES OF DATA IN THE MOST 

247
00:08:52,666 --> 00:08:56,036
EVER BE RESPONSIBLE AND 

248
00:08:56,036 --> 00:08:56,636
EFFICIENT WAY POSSIBLE WE CAN 

249
00:08:56,636 --> 00:08:57,270
MAXIMIZE STATISTICAL POWER AND 

250
00:08:57,270 --> 00:08:58,972
OUR ABILITY TO MAKE 

251
00:08:58,972 --> 00:08:59,473
STATISTICALLY RIGOROUS 

252
00:08:59,473 --> 00:09:00,273
INFERENCES AND ADVANCES IN OUR 

253
00:09:00,273 --> 00:09:05,512
UNDERSTANDING OF NED. 

254
00:09:05,512 --> 00:09:06,113
ADDITIONALLY WITH A BACKDROP OF 

255
00:09:06,113 --> 00:09:06,613
STRONG DATA PROTECTIONS 

256
00:09:06,613 --> 00:09:09,082
ESPECIALLY FOR HUMAN SUBJECTS 

257
00:09:09,082 --> 00:09:09,683
DATA, WE CAN DEMOCRATIZE AND 

258
00:09:09,683 --> 00:09:11,118
DATA ACCESS FOR QUALIFIED 

259
00:09:11,118 --> 00:09:13,186
RESEARCHERS, THUS PROVIDING 

260
00:09:13,186 --> 00:09:13,653
OPPORTUNITY FOR MORE 

261
00:09:13,653 --> 00:09:14,154
INVESTIGATION AND MORE 

262
00:09:14,154 --> 00:09:14,654
ADVANCED. 

263
00:09:14,654 --> 00:09:20,327
NEXT SLIDE. 

264
00:09:20,327 --> 00:09:20,894
THIS IS THE DEPICTION OF DATA 

265
00:09:20,894 --> 00:09:24,331
COLLECTION AND PROCESSING FOR 

266
00:09:24,331 --> 00:09:24,998
DIGITAL HISTOPATHOLOGY, GOING 

267
00:09:24,998 --> 00:09:27,801
FROM RESEARCH VOLUNTEERS' 

268
00:09:27,801 --> 00:09:29,469
DONATIONS OF THE RANGE THROUGH 

269
00:09:29,469 --> 00:09:30,036
AUTOPSY, THROUGH STAGES OF 

270
00:09:30,036 --> 00:09:33,106
PREPARATION AND ANALYSIS. 

271
00:09:33,106 --> 00:09:36,843
WE RECOMMEND EFFORTS FOR OPEN 

272
00:09:36,843 --> 00:09:37,344
SOURCE DIGITAL IMAGING, 

273
00:09:37,344 --> 00:09:37,911
FOCUSING ON THE ABILITY TO 

274
00:09:37,911 --> 00:09:40,347
RECOGNIZE DIFFERENCES IN 

275
00:09:40,347 --> 00:09:40,914
APPROACHES HERE DEPICTED BY 

276
00:09:40,914 --> 00:09:42,449
SINGLE NOTES, AND SUBSEQUENTLY 

277
00:09:42,449 --> 00:09:43,083
HARMONIZED ACROSS THEM WITH THE 

278
00:09:43,083 --> 00:09:45,819
GOAL OF SHARING AND INTEGRATING 

279
00:09:45,819 --> 00:09:47,721
ACROSS COHORTS AND PLATFORMS. 

280
00:09:47,721 --> 00:09:48,321
AND THEN DISSEMINATING TO 

281
00:09:48,321 --> 00:09:49,189
INVESTIGATORS AS ROUNDLY AS 

282
00:09:49,189 --> 00:09:50,290
POSSIBLE. 

283
00:09:50,290 --> 00:09:55,462
NEXT SLIDE. 

284
00:09:55,462 --> 00:09:56,463
THESE RESULTS ARE FROM AN 

285
00:09:56,463 --> 00:10:00,901
EXAMPLE HARMONIZATION FOR 

286
00:10:00,901 --> 00:10:02,969
MULTI-ETIOLOGY DEMENTIAS FOR 

287
00:10:02,969 --> 00:10:03,603
NEURO- PATHOLOGICAL EVALUATIONS 

288
00:10:03,603 --> 00:10:04,204
AND SO THE FIGURE ON THE LEFT 

289
00:10:04,204 --> 00:10:09,976
SHOWS THE EXTENT TO WHICH THE 

290
00:10:09,976 --> 00:10:12,546
PROTEINOPTHYS LIKE DR. CARLSSON 

291
00:10:12,546 --> 00:10:17,884
DISPLAYED EARLIER OF TAO, -- 

292
00:10:17,884 --> 00:10:24,324
AND TDP 43 FROM PARTICIPANTS IN 

293
00:10:24,324 --> 00:10:24,858
SEVERAL COHORTS EACH ROW 

294
00:10:24,858 --> 00:10:27,994
REPRESENTS A PATTERN OF 

295
00:10:27,994 --> 00:10:28,562
MISCODED PROTEINS WITH RED 

296
00:10:28,562 --> 00:10:29,162
INDICATOR PRESENCE AND GREY 

297
00:10:29,162 --> 00:10:31,164
ABSENT. 

298
00:10:31,164 --> 00:10:31,765
IN THE STATE OF THE FIRST ROAD 

299
00:10:31,765 --> 00:10:40,340
INDICATES THAT THAT 384 OF THE 

300
00:10:40,340 --> 00:10:50,817
-- BRAIN HAD AUTOPSIES. THE 

301
00:10:52,118 --> 00:10:52,619
MAJORITY OF BRAINS EXHIBIT 

302
00:10:52,619 --> 00:10:54,821
MULTIPLE PROTEIN OPATHIES 

303
00:10:54,821 --> 00:10:55,455
SHOWING   THE AGE EXCEPTION OF 

304
00:10:55,455 --> 00:10:56,056
INDIVIDUALS AND THIS POINTED 

305
00:10:56,056 --> 00:10:56,656
MULTIPLE TIMES ON THE SUMMIT 

306
00:10:56,656 --> 00:10:57,290
AND UNDERWRITE THE CORRELATION 

307
00:10:57,290 --> 00:11:01,094
BETWEEN THOSE FOUR MISS FOLDER 

308
00:11:01,094 --> 00:11:01,695
PROTEINS AN ADDITIONAL NEURO- 

309
00:11:01,695 --> 00:11:04,130
PATHOLOGIC AND PHENOTYPES, AND 

310
00:11:04,130 --> 00:11:04,698
THIS SHOWS INTERRELATEDNESS 

311
00:11:04,698 --> 00:11:09,703
BETWEEN DISTINCT PHENOTYPES, 

312
00:11:09,703 --> 00:11:10,337
AND IT ECHOES THE IMPORTANCE OF 

313
00:11:10,337 --> 00:11:10,937
IDENTIFYING SPECIFIC DISEASE 

314
00:11:10,937 --> 00:11:11,538
SUBTYPES THAT CAN BE TARGETED 

315
00:11:11,538 --> 00:11:12,072
THERAPEUTICALLY. 

316
00:11:12,072 --> 00:11:17,077
NEXT SLIDE. 

317
00:11:17,077 --> 00:11:21,181
THIS FINAL SLIDE, HIGHLIGHT TO 

318
00:11:21,181 --> 00:11:24,584
EXISTING AND RELATED EFFORTS 

319
00:11:24,584 --> 00:11:25,118
FOR RELATING DATA ACROSS 

320
00:11:25,118 --> 00:11:28,421
STUDIES AND DATA TYPES AND WE 

321
00:11:28,421 --> 00:11:28,955
ADVOCATE FOR THE EXPLICIT 

322
00:11:28,955 --> 00:11:33,059
INCORPORATION OF NED. 

323
00:11:33,059 --> 00:11:36,830
THE ALZHEIMER'S DISEASE 

324
00:11:36,830 --> 00:11:37,397
SEQUENCE PROJECT PHENOTYPE 

325
00:11:37,397 --> 00:11:39,399
HARMONIZATION PROJECT BRINGS 

326
00:11:39,399 --> 00:11:39,966
TOGETHER DATA FROM MULTIPLE 

327
00:11:39,966 --> 00:11:41,501
MODALITIES INCLUDING 

328
00:11:41,501 --> 00:11:44,004
LONGITUDINAL, COGNITIVE EXAMS, 

329
00:11:44,004 --> 00:11:44,604
IMAGING BIOMARKERS AND 

330
00:11:44,604 --> 00:11:45,338
NEUROPATHOLOGY.

331
00:11:45,338 --> 00:11:53,313
AND ON THE RIGHT -- AGGREGATES 

332
00:11:53,313 --> 00:11:55,181
GENETIC AND RELATED PHENOTYPIC 

333
00:11:55,181 --> 00:11:55,749
DATA FROM MANY STUDIES AND 

334
00:11:55,749 --> 00:11:56,383
MAKES THESE DATA AVAILABLE FOR 

335
00:11:56,383 --> 00:11:57,584
QUALIFIED INVESTIGATORS. 

336
00:11:57,584 --> 00:11:59,553
SIMILAR EFFORT SPECIFIC TO 

337
00:11:59,553 --> 00:12:01,888
MULTI-ETIOLOGY DEMENTIA AND 

338
00:12:01,888 --> 00:12:02,355
OTHER FOCUS GROUPS IS 

339
00:12:02,355 --> 00:12:04,391
RECOMMENDED IN THE SUMMIT IN 

340
00:12:04,391 --> 00:12:06,793
THE REPORT, NEEDED TO 

341
00:12:06,793 --> 00:12:07,394
EFFICIENTLY ADVANCE DRUG AND 

342
00:12:07,394 --> 00:12:09,429
CLINICAL TRIAL DEVELOPMENT AND 

343
00:12:09,429 --> 00:12:16,736
PRECISION MEDICINE. THANK YOU. 

344
00:12:16,736 --> 00:12:22,409
I WOULD NOT TURN IT OVER TO DR. 

345
00:12:22,409 --> 00:12:24,744
CAITLIN LATIMER. 

346
00:12:24,744 --> 00:12:28,648
>> THANK YOU SO MUCH MY
NAME IS 

347
00:12:28,648 --> 00:12:33,587
CAITLIN LATIMER, A PATHOLOGIST 

348
00:12:33,587 --> 00:12:36,022
AND ASSISTANT PROFESSOR AT THE 

349
00:12:36,022 --> 00:12:36,556
UNIVERSITY OF WASHINGTON 

350
00:12:36,556 --> 00:12:37,057
SEATTLE. APPRECIATE THE 

351
00:12:37,057 --> 00:12:37,691
PRIVILEGE TO CONTRIBUTE TO THIS 

352
00:12:37,691 --> 00:12:38,258
WORKGROUP. I'M GOING TO BE 

353
00:12:38,258 --> 00:12:40,327
TALKING ABOUT RECOMMENDATION 4, 

354
00:12:40,327 --> 00:12:45,732
BUILDING A MULTIPLE ETIOLOGY 

355
00:12:45,732 --> 00:12:46,333
DEMENTIA COMPETENT WORKFORCE. 

356
00:12:46,333 --> 00:12:47,100
AND I HAVE NOTHING TO DISCLOSE. 

357
00:12:47,100 --> 00:12:48,668
NEXT SLIDE. 

358
00:12:48,668 --> 00:12:55,075
THE FIRST THREE RECOGNITIONS 

359
00:12:55,075 --> 00:12:55,709
ARE REALLY FOCUSED ON DISCOVERY 

360
00:12:55,709 --> 00:12:56,343
AND ADVANCEMENT AND DIAGNOSTIC 

361
00:12:56,343 --> 00:13:04,184
AND THERAPEUTIC STRATEGIES FOR 

362
00:13:04,184 --> 00:13:04,784
NEDTHIS COMMISSION EMPHASIZES 

363
00:13:04,784 --> 00:13:05,418
THE NEED TO DEVELOP A WORKFORCE 

364
00:13:05,418 --> 00:13:06,686
THAT UNDERSTANDS AND RECOGNIZES 

365
00:13:06,686 --> 00:13:07,621
THE CONCEPT OF MULTIPLE 

366
00:13:07,621 --> 00:13:09,723
ETIOLOGY DEMENTIA, TO IMPROVE 

367
00:13:09,723 --> 00:13:13,193
HOW WE STUDY, DIAGNOSE AND 

368
00:13:13,193 --> 00:13:13,760
MANAGE INDIVIDUAL MULTIPLE 

369
00:13:13,760 --> 00:13:18,365
DEGENERATIVE PATHOLOGIES. 

370
00:13:18,365 --> 00:13:18,965
TO ACCOMPLISH THIS WE UNDERLINE 

371
00:13:18,965 --> 00:13:22,202
SEVERAL KEY POINTS EMPHASIZE. 

372
00:13:22,202 --> 00:13:22,769
THE DEVELOPER WORKFORCE WE 

373
00:13:22,769 --> 00:13:23,370
REALLY NEED TRAINING PROGRAMS 

374
00:13:23,370 --> 00:13:23,870
THAT INTEGRATE MULTIPLE 

375
00:13:23,870 --> 00:13:27,774
ETIOLOGY DEMENTIA PRINCIPLES 

376
00:13:27,774 --> 00:13:28,408
AND THIS INCLUDES BASIC SCIENCE 

377
00:13:28,408 --> 00:13:31,344
RESEARCHERS, CLINICIANS, 

378
00:13:31,344 --> 00:13:31,945
CLINICAL CORNERS AND WE NEED 

379
00:13:31,945 --> 00:13:36,883
EVERYONE INVOLVED IN DEMENTIA 

380
00:13:36,883 --> 00:13:37,484
RESEARCH AND CARE TEAM EFFORT 

381
00:13:37,484 --> 00:13:40,320
AND WE NEED TO INVEST IN 

382
00:13:40,320 --> 00:13:40,954
IMPLEMENTATION SCIENCE RESEARCH 

383
00:13:40,954 --> 00:13:41,521
TO REACH A BROADER SWATH OF 

384
00:13:41,521 --> 00:13:43,356
INVESTIGATORS AND CLINICIANS 

385
00:13:43,356 --> 00:13:44,557
WHO ARE ENCOUNTERING 

386
00:13:44,557 --> 00:13:45,225
INDIVIDUALS WITH MULTIPLE 

387
00:13:45,225 --> 00:13:45,825
ETIOLOGY DEMENTIA ON A DAILY 

388
00:13:45,825 --> 00:13:49,129
BASIS. 

389
00:13:49,129 --> 00:13:52,932
THE IMPLEMENTATION OF SCIENCE 

390
00:13:52,932 --> 00:13:53,566
CAN IN TURN HELP INFORM HOW TO 

391
00:13:53,566 --> 00:13:54,167
INTEGRATE PRACTICAL TRAINING 

392
00:13:54,167 --> 00:13:54,668
METHODS BACK INTO THOSE 

393
00:13:54,668 --> 00:13:55,168
TRAINING PROGRAMS, TO 

394
00:13:55,168 --> 00:13:58,271
FACILITATE THE ADOPTION OF MED 

395
00:13:58,271 --> 00:13:59,506
CONCEPTS. AND ENSURE THAT NEW 

396
00:13:59,506 --> 00:14:04,210
AND EVOLVING MED TOOLS ARE 

397
00:14:04,210 --> 00:14:04,811
INTEGRATED IN RESEARCH STUDY 

398
00:14:04,811 --> 00:14:05,445
DESIGN, AND PATIENT MANAGEMENT 

399
00:14:05,445 --> 00:14:05,979
APPROACHES. 

400
00:14:05,979 --> 00:14:10,417
AND FINALLY, PROMOTING 

401
00:14:10,417 --> 00:14:12,652
EDUCATION ON THE USE OF NOVEL 

402
00:14:12,652 --> 00:14:13,186
DIAGNOSTIC TOOLS TO MORE 

403
00:14:13,186 --> 00:14:14,988
EFFECTIVELY AND EFFICIENTLY 

404
00:14:14,988 --> 00:14:20,794
IDENTIFY MULTIPLE ETIOLOGY 

405
00:14:20,794 --> 00:14:21,428
DEMENTIA, AND COMMUNICATE THOSE 

406
00:14:21,428 --> 00:14:21,995
FINDINGS WITH PATIENTS AND 

407
00:14:21,995 --> 00:14:22,495
THEIR FAMILIES. 

408
00:14:22,495 --> 00:14:24,397
NEXT SLIDE. 

409
00:14:24,397 --> 00:14:24,964
CURRENTLY THERE ARE MULTIPLE 

410
00:14:24,964 --> 00:14:27,133
CHALLENGES FACING THE DEMENTIA 

411
00:14:27,133 --> 00:14:28,568
WORKFORCE. 

412
00:14:28,568 --> 00:14:33,239
THESE REALLY BEGIN WITH 

413
00:14:33,239 --> 00:14:33,840
AWARENESS. AS WE HEARD TODAY 

414
00:14:33,840 --> 00:14:36,342
ALTHOUGH THE NEUROPATHOLOGY HAS 

415
00:14:36,342 --> 00:14:36,976
SHOWN IS THAT MULTIPLE ETIOLOGY 

416
00:14:36,976 --> 00:14:38,878
DEMENTIA IS A RULE NOT THE 

417
00:14:38,878 --> 00:14:39,446
EXCEPTION, ON A DAILY BASIS 

418
00:14:39,446 --> 00:14:40,513
MOST INDIVIDUALS ARE STILL PUT 

419
00:14:40,513 --> 00:14:42,649
INTO EIGHT SINGULAR DIAGNOSTIC 

420
00:14:42,649 --> 00:14:47,187
BUCKET. THAT IS THE ATTEMPT. 

421
00:14:47,187 --> 00:14:47,787
 AND INCREASED AWARENESS OF THE 

422
00:14:47,787 --> 00:14:48,822
PERVASIVENESS OF MULTIPLE 

423
00:14:48,822 --> 00:14:56,329
ETIOLOGY DEMENTIA AND ITS 

424
00:14:56,329 --> 00:14:56,896
POTENTIAL FOR DIAGNOSIS AND 

425
00:14:56,896 --> 00:14:57,497
IMPACT , INPATIENT MANAGEMENT 

426
00:14:57,497 --> 00:15:03,670
AS NEEDED BUT HAVING ACCESS TO 

427
00:15:03,670 --> 00:15:04,304
EDUCATION AND HOW TO USE NOVEL 

428
00:15:04,304 --> 00:15:04,871
TESTS FOR MULTIPLE ETIOLOGY 

429
00:15:04,871 --> 00:15:08,007
EFFECTIVELY. 

430
00:15:08,007 --> 00:15:08,608
AND THIS CAN LEAD TO DELAYED 

431
00:15:08,608 --> 00:15:15,648
DIAGNOSIS AND POOR MITIGATION 

432
00:15:15,648 --> 00:15:16,282
OR PERCEIVED POOR COMMUNICATION 

433
00:15:16,282 --> 00:15:16,850
WITH PATIENTS AND FAMILIES 

434
00:15:16,850 --> 00:15:17,417
WHICH LEADS TO FRUSTRATING 

435
00:15:17,417 --> 00:15:21,888
ABOUT SIDES. 

436
00:15:21,888 --> 00:15:22,422
AND UNDER BASIC SCIENCE AND 

437
00:15:22,422 --> 00:15:22,856
CLINICAL TRIAL SITE 

438
00:15:22,856 --> 00:15:23,490
INVESTIGATORS NEED TO BE AWARE 

439
00:15:23,490 --> 00:15:24,090
OF THE POTENTIAL COMPOUNDS ON 

440
00:15:24,090 --> 00:15:28,762
MULTIPLE IDEOLOGY DEMENTIA. 

441
00:15:28,762 --> 00:15:33,266
FOR EXAMPLE IF YOU HAVE 

442
00:15:33,266 --> 00:15:35,468
MULTIPLE PATHOLOGY TRIALS, THE 

443
00:15:35,468 --> 00:15:36,069
TRIAL MAY FAIL BECAUSE IT HAS 

444
00:15:36,069 --> 00:15:36,669
NOTHING TO DO WITH EFFECTIVE 

445
00:15:36,669 --> 00:15:37,437
TREATMENT AGAINST ALZHEIMER'S. 

446
00:15:37,437 --> 00:15:39,005
NEXT SLIDE. 

447
00:15:39,005 --> 00:15:43,042
THIS RECOMMENDATION AIMS TO 

448
00:15:43,042 --> 00:15:43,676
ADDRESS THESE CHALLENGES IN TWO 

449
00:15:43,676 --> 00:15:46,112
MAIN WAYS. 

450
00:15:46,112 --> 00:15:46,713
THE FIRST IS PROMOTING TRAINING 

451
00:15:46,713 --> 00:15:51,651
PROGRAMS THAT PROVIDE CLINICAL 

452
00:15:51,651 --> 00:15:52,118
TRIAL INVESTIGATORS, 

453
00:15:52,118 --> 00:15:52,752
TRANSLATIONAL RESEARCHERS, AND 

454
00:15:52,752 --> 00:15:53,319
BASIC SCIENTISTS WITH SKILL 

455
00:15:53,319 --> 00:15:55,188
SETS TO INTEGRATE MULTIPLE 

456
00:15:55,188 --> 00:15:55,789
ETIOLOGY DEMENTIA PRINCIPLES 

457
00:15:55,789 --> 00:16:00,293
INTO RESEARCH STUDY DESIGN. 

458
00:16:00,293 --> 00:16:00,894
AND SO AGAIN THINKING ABOUT THE 

459
00:16:00,894 --> 00:16:01,494
UNDERLYING PATHOLOGIES OF THE 

460
00:16:01,494 --> 00:16:04,030
STUDY POPULATION, WHETHER THAT 

461
00:16:04,030 --> 00:16:04,631
IS IN CLINICAL TRIAL DESIGN, 

462
00:16:04,631 --> 00:16:09,702
TRANSLATIONAL STUDIES, OR BASIC 

463
00:16:09,702 --> 00:16:10,770
SCIENCE TO ENSURE THAT MODELS 

464
00:16:10,770 --> 00:16:12,872
OF MULTIPLE PATHOLOGIES ARE 

465
00:16:12,872 --> 00:16:14,374
INCORPORATED RATHER THAN 

466
00:16:14,374 --> 00:16:15,008
INDIVIDUAL PATHOLOGIES FOR 

467
00:16:15,008 --> 00:16:17,644
STUDY. 

468
00:16:17,644 --> 00:16:19,579
ALSO THE NEURAL PATHOLOGICAL 

469
00:16:19,579 --> 00:16:24,017
FOR CHARACTERIZATION, ENSURING 

470
00:16:24,017 --> 00:16:24,684
THE PATHOLOGISTS ARE PERFORMING 

471
00:16:24,684 --> 00:16:25,185
COMPLETE ASSESSMENT AND 

472
00:16:25,185 --> 00:16:25,785
DOCUMENTING AND COMMUNICATING 

473
00:16:25,785 --> 00:16:30,857
THE PRESENT MULTIPLE ETIOLOGIES 

474
00:16:30,857 --> 00:16:31,357
TO INFORM THE USE OF BY 

475
00:16:31,357 --> 00:16:31,958
SPECIMENS FROM BIOLOGICALLY 

476
00:16:31,958 --> 00:16:41,968
DIVERSE PARTICIPANTS. 

477
00:16:41,968 --> 00:16:42,435
FOR EXAMPLE OFTEN FIELD 

478
00:16:42,435 --> 00:16:43,336
REQUESTS FOR BY SPECIMENS FROM 

479
00:16:43,336 --> 00:16:43,937
DONORS AND THE REQUESTED THAT 

480
00:16:43,937 --> 00:16:46,639
HAVE ALZHEIMER'S OR DON'T HAVE 

481
00:16:46,639 --> 00:16:47,140
IT AND WHEN I MEET WITH 

482
00:16:47,140 --> 00:16:47,674
INVESTORS AND ASKED WHAT 

483
00:16:47,674 --> 00:16:48,208
PATHOLOGIES THAT WANT TO 

484
00:16:48,208 --> 00:16:48,842
INCLUDE OR EXCLUDE, THE CONCEPT 

485
00:16:48,842 --> 00:16:51,044
OF MULTIPLE ETIOLOGY DOESN'T 

486
00:16:51,044 --> 00:16:58,418
EVEN ENTER THE PICTURE. 

487
00:16:58,418 --> 00:16:59,018
 AND SO FINALLY INFORMATICS TO 

488
00:16:59,018 --> 00:16:59,652
LEVERAGE THE COMPLEX COVERT AND 

489
00:16:59,652 --> 00:17:00,253
MODELING APPROACHES TO BETTER 

490
00:17:00,253 --> 00:17:00,854
UNDERSTAND HOW THEY RELATE TO 

491
00:17:00,854 --> 00:17:01,454
ONE ANOTHER AND THE CLINICAL 

492
00:17:01,454 --> 00:17:01,921
PRESENTATION. 

493
00:17:01,921 --> 00:17:08,928
NEXT SLIDE. 

494
00:17:08,928 --> 00:17:09,529
THE OTHER CLINICAL EMPHASIS IS 

495
00:17:09,529 --> 00:17:10,463
IMPLEMENTATION OF SCIENCE. IN 

496
00:17:10,463 --> 00:17:12,966
ORDER TO BUILD A MULTIPLE 

497
00:17:12,966 --> 00:17:15,902
ETIOLOGY-COMPETENT WORKFORCE WE 

498
00:17:15,902 --> 00:17:16,469
NEED TO UNDERSTAND WHAT THE 

499
00:17:16,469 --> 00:17:17,103
CHALLENGES ARE FOR IMPLEMENTING 

500
00:17:17,103 --> 00:17:19,239
NOVEL TESTS, AND APPROPRIATELY 

501
00:17:19,239 --> 00:17:21,774
INTERPRETING, AND USING THOSE 

502
00:17:21,774 --> 00:17:25,411
RESULTS. 

503
00:17:25,411 --> 00:17:28,348
WE ALSO NEED TO UNDERSTAND WHAT 

504
00:17:28,348 --> 00:17:29,115
THE MOST EFFECTIVE APPROACHES 

505
00:17:29,115 --> 00:17:29,749
ARE, TAKING INTO ACCOUNT THE 

506
00:17:29,749 --> 00:17:30,316
SETTING AND THE EDUCATIONAL 

507
00:17:30,316 --> 00:17:31,751
GOALS. 

508
00:17:31,751 --> 00:17:34,153
AND FINALLY LEARN HOW TO 

509
00:17:34,153 --> 00:17:34,721
INCREASE THE REACH OF THESE 

510
00:17:34,721 --> 00:17:36,489
EFFORTS TO GENERATE BROADER 

511
00:17:36,489 --> 00:17:37,891
ENGAGEMENT BOTH ON THE RESEARCH 

512
00:17:37,891 --> 00:17:39,559
AND CLINICAL SIDE. 

513
00:17:39,559 --> 00:17:43,930
>> TWO MINUTES. 

514
00:17:43,930 --> 00:17:44,464
>> ULTIMATELY THESE
EFFORTS 

515
00:17:44,464 --> 00:17:45,064
WILL ADDRESS THOSE CHALLENGES 

516
00:17:45,064 --> 00:17:48,401
CURRENTLY FACING THE DEMENTIA 

517
00:17:48,401 --> 00:17:49,035
WORKFORCE AND WILL BE ASSESSED 

518
00:17:49,035 --> 00:17:54,474
BASED ON OUTCOMES RELATED TO 

519
00:17:54,474 --> 00:17:55,074
BOTH THE PATIENTS AS WELL AS 

520
00:17:55,074 --> 00:18:00,713
CLINICIANS AND RESEARCHERS. 

521
00:18:00,713 --> 00:18:01,247
 SHORTER TIME TO DIAGNOSIS, 

522
00:18:01,247 --> 00:18:04,717
IMPROVED COMMUNICATION WITH 

523
00:18:04,717 --> 00:18:05,251
PATIENTS AND FAMILIES AND 

524
00:18:05,251 --> 00:18:05,785
ULTIMATELY BETTER PATIENT 

525
00:18:05,785 --> 00:18:06,419
EDUCATION AND SUPPORT. 

526
00:18:06,419 --> 00:18:07,153
THAT IS ALL I HAVE. 

527
00:18:07,153 --> 00:18:17,297
THANK YOU. 

528
00:18:19,032 --> 00:18:19,632
>> THANK YOU SO MUCH
APPRECIATE 

529
00:18:19,632 --> 00:18:20,166
ALL THE MEMBERS FOR THEIR 

530
00:18:20,166 --> 00:18:21,301
CONTRIBUTIONS AND TO DR. 

531
00:18:21,301 --> 00:18:27,707
LATIMER, DR. FARDO AND DR. 

532
00:18:27,707 --> 00:18:30,076
IADECOLA FOR THE PRESENTATIONS. 

533
00:18:30,076 --> 00:18:34,280
>> THANK YOU. THE FIRST
Q&A 

534
00:18:34,280 --> 00:18:41,020
SESSION FOR THE SESSIONS TODAY, 

535
00:18:41,020 --> 00:18:41,621
I WANT TO ENCOURAGE EVERYONE 

536
00:18:41,621 --> 00:18:43,089
WHO IS ON THE COMMITTEE TO GO 

537
00:18:43,089 --> 00:18:47,093
AHEAD AND TURN ON YOUR CAMERAS, 

538
00:18:47,093 --> 00:18:51,564
SO WE CAN SEE WHO ALL IS HERE. 

539
00:18:51,564 --> 00:18:52,131
FOR ANYONE ON THE COMMITTEE 

540
00:18:52,131 --> 00:18:52,765
SHOULD HAVE THE ABILITY TO USE 

541
00:18:52,765 --> 00:18:53,333
YOUR MICROPHONE AND CAMERA 

542
00:18:53,333 --> 00:18:57,837
UNDER YOUR CONTROL. THANK YOU. 

543
00:18:57,837 --> 00:18:58,404
>> FIRST BEFORE WE BEGIN
OUR 

544
00:18:58,404 --> 00:18:59,038
DISCUSSION, AS WAS DONE 

545
00:18:59,038 --> 00:19:01,240
YESTERDAY, WE WANT TO WELCOME 

546
00:19:01,240 --> 00:19:02,208
TWO OF OUR COMMITTEE MEMBERS. 

547
00:19:02,208 --> 00:19:08,014
MR. AND MS. KAREN AND LARRY 

548
00:19:08,014 --> 00:19:12,018
SQUIRES (PHONETIC), 

549
00:19:12,018 --> 00:19:12,518
PARTICIPANTS WITH LIVED 

550
00:19:12,518 --> 00:19:13,152
EXPERIENCE WHO HAVE SHAPED THE 

551
00:19:13,152 --> 00:19:16,923
RECOGNITIONS OF OUR COMMITTEE. 

552
00:19:16,923 --> 00:19:17,523
I WILL TURN IT OVER TO KAREN 

553
00:19:17,523 --> 00:19:18,358
AND LARRY TO SHARE THEIR 

554
00:19:18,358 --> 00:19:18,958
EXPERIENCE. WELCOME AND THANK 

555
00:19:18,958 --> 00:19:19,993
YOU. 

556
00:19:19,993 --> 00:19:29,836
>> THANK YOU. 

557
00:19:29,836 --> 00:19:33,606
I HAVE A FEW COMMENTS. PLEASE 

558
00:19:33,606 --> 00:19:34,207
IF YOU HAVE WRITTEN THEM DOWN 

559
00:19:34,207 --> 00:19:36,542
BECAUSE I STRUGGLE WITH WORD 

560
00:19:36,542 --> 00:19:37,110
FINDING AND I DON'T WANT TO 

561
00:19:37,110 --> 00:19:38,511
MISS ANYTHING THAT IS 

562
00:19:38,511 --> 00:19:39,212
IMPORTANT, OR THAT I FEEL IS 

563
00:19:39,212 --> 00:19:42,482
IMPORTANT. 

564
00:19:42,482 --> 00:19:43,082
FIRST I WOULD LIKE TO THANK OUR 

565
00:19:43,082 --> 00:19:44,350
FELLOW MEMBERS OF THE COMMITTEE 

566
00:19:44,350 --> 00:19:48,654
FOR ALLOWING US TO PROVIDE 

567
00:19:48,654 --> 00:19:49,288
INPUT, AND CERTAINLY MAKING US 

568
00:19:49,288 --> 00:19:51,924
FEEL WELCOME. THANK YOU. 

569
00:19:51,924 --> 00:19:57,330
I HAD A 3-4 YEAR PATH TO MY 

570
00:19:57,330 --> 00:19:57,897
PROBABLE DIAGNOSIS THAT WAS 

571
00:19:57,897 --> 00:20:01,801
FILLED WITH MORE OBSTACLES THAN 

572
00:20:01,801 --> 00:20:07,974
ONE WOULD EXPECT, AND ANXIETY. 

573
00:20:07,974 --> 00:20:08,474
IT WAS DIFFICULT TO FIND 

574
00:20:08,474 --> 00:20:14,180
CLINICIANS WE FELT WERE 

575
00:20:14,180 --> 00:20:16,416
KNOWLEDGEABLE AND BECAUSE OF MY 

576
00:20:16,416 --> 00:20:21,054
ATYPICAL PRESENTATION. WE WORRY 

577
00:20:21,054 --> 00:20:24,323
FOR THOSE WE JUST DON'T KNOW 

578
00:20:24,323 --> 00:20:25,224
JUST HOW TO ADVOCATE FOR 

579
00:20:25,224 --> 00:20:27,293
THEMSELVES. AND I WAS LUCKY TO 

580
00:20:27,293 --> 00:20:27,927
HAVE KAREN WHO DID A WONDERFUL 

581
00:20:27,927 --> 00:20:31,097
JOB TO ADVOCATE AND RESEARCH. 

582
00:20:31,097 --> 00:20:31,697
KNOWING SOMETHING IS WRONG WITH 

583
00:20:31,697 --> 00:20:36,002
YOUR BRAIN, AND NOT HAVING 

584
00:20:36,002 --> 00:20:36,702
ANSWERS CREATES A TREMENDOUS 

585
00:20:36,702 --> 00:20:39,505
AMOUNT OF FEAR AND ANXIETY IN 

586
00:20:39,505 --> 00:20:43,309
YOUR LIFE.  AND SIMPLY HAVING A 

587
00:20:43,309 --> 00:20:48,514
DIAGNOSIS OR A PROBABLE 

588
00:20:48,514 --> 00:20:49,082
DIAGNOSIS, RELIEVES SOME OF 

589
00:20:49,082 --> 00:20:52,418
THAT ISSUE.  THAT IS PRETTY 

590
00:20:52,418 --> 00:20:53,886
MUCH IT FOR ME. 

591
00:20:53,886 --> 00:21:00,059
THANK YOU. 

592
00:21:00,059 --> 00:21:00,660
>> HE WOULD KEEP TALKING.
I AM 

593
00:21:00,660 --> 00:21:03,529
CUTTING YOU OFF.

594
00:21:03,529 --> 00:21:04,130
WE TALKED ABOUT THIS. WE CANNOT 

595
00:21:04,130 --> 00:21:06,032
COME UP WITH ANY OTHER MEDICAL 

596
00:21:06,032 --> 00:21:07,033
ISSUES WHERE YOUR DOCTOR SAYS 

597
00:21:07,033 --> 00:21:08,401
TO YOU, ALWAYS THINK YOU 

598
00:21:08,401 --> 00:21:10,636
PROBABLY HAVE THIS.

599
00:21:10,636 --> 00:21:12,705
SO, YOUR WORK IS REALLY 

600
00:21:12,705 --> 00:21:15,808
CRITICALLY IMPORTANT TO BOTH 

601
00:21:15,808 --> 00:21:21,914
DEMENTIA PATIENTS AND THEIR 

602
00:21:21,914 --> 00:21:22,515
FAMILIES. WE JUST ASK THAT AS 

603
00:21:22,515 --> 00:21:26,452
YOU MOVE FORWARD WITH RESEARCH, 

604
00:21:26,452 --> 00:21:27,053
THAT YOU ALWAYS KEEP A CLEAR 

605
00:21:27,053 --> 00:21:28,588
VISION OF THE IMPACT YOUR 

606
00:21:28,588 --> 00:21:29,188
RESEARCH IS GOING TO HAVE ON 

607
00:21:29,188 --> 00:21:38,164
THOSE PATIENTS. 

608
00:21:38,164 --> 00:21:38,664
WILL IT EASE THE TIME AND 

609
00:21:38,664 --> 00:21:40,566
ACCURACY OF THE DIAGNOSIS?

610
00:21:40,566 --> 00:21:43,169
WOULD REVERSE THE SITUATION?

611
00:21:43,169 --> 00:21:44,003
HAVING RELIABLE BIOMARKERS 

612
00:21:44,003 --> 00:21:47,173
INDICATE THE PRESENCE OF 

613
00:21:47,173 --> 00:21:47,807
MULTIPLE ETIOLOGY IS CRITICAL. 

614
00:21:47,807 --> 00:21:52,245
AUTOPSY IS TOO LATE TO BE ABLE 

615
00:21:52,245 --> 00:21:52,812
TO DEAL WITH PATIENTS LIKE 

616
00:21:52,812 --> 00:21:54,247
THIS. AND TOO MANY CLINICIANS 

617
00:21:54,247 --> 00:21:57,250
STOP AT ALZHEIMER'S. 

618
00:21:57,250 --> 00:22:02,388
WE REALLY NEED ACCESS TO EASY 

619
00:22:02,388 --> 00:22:02,822
BRAIN DONATION AND 

620
00:22:02,822 --> 00:22:05,691
ENCOURAGEMENT FOR DONATION. 

621
00:22:05,691 --> 00:22:06,225
WE EVEN THOUGHT TODAY AS WE 

622
00:22:06,225 --> 00:22:08,995
WERE LISTENING TO EVERYBODY, 

623
00:22:08,995 --> 00:22:09,695
HEY, HE HAS HAD LOTS OF SCANS 

624
00:22:09,695 --> 00:22:13,599
AND LOTS OF TESTS DONE.  WHAT 

625
00:22:13,599 --> 00:22:14,200
IS THE OPPORTUNITY FOR THOSE 

626
00:22:14,200 --> 00:22:20,072
WHO DON'T WANT TO DONATE THEIR 

627
00:22:20,072 --> 00:22:20,606
BRAIN TO BE ABLE TO GRANT 

628
00:22:20,606 --> 00:22:21,507
ACCESS TO THEIR SCANS AND TESTS?

629
00:22:21,507 --> 00:22:24,810
TO PUT INTO THE RESEARCH. 

630
00:22:24,810 --> 00:22:25,411
>> MY OPINION IS THAT
EVERYONE 

631
00:22:25,411 --> 00:22:29,048
SHOULD BE ASKED. 

632
00:22:29,048 --> 00:22:29,615
>> SO WE REALLY THANK YOU
FOR 

633
00:22:29,615 --> 00:22:30,116
YOUR DEDICATION TO THIS 

634
00:22:30,116 --> 00:22:31,584
RESEARCH.  AND AGAIN THANK YOU 

635
00:22:31,584 --> 00:22:38,124
FOR LETTING US PARTICIPATE. 

636
00:22:38,124 --> 00:22:41,961
>> DR. IADECOLA: IT IS OUR

637
00:22:41,961 --> 00:22:43,229
PLEASURE AND PRIVILEGE TO WORK 

638
00:22:43,229 --> 00:22:48,334
WITH YOU. AND YOUR INPUT WAS 

639
00:22:48,334 --> 00:22:48,901
VERY IMPORTANT IN SHAPING, 

640
00:22:48,901 --> 00:22:53,039
KEEPING US FOCUSED. BECAUSE 

641
00:22:53,039 --> 00:22:53,673
PEOPLE (INDISCERNIBLE) WILL GO 

642
00:22:53,673 --> 00:22:54,273
IN VERY DIFFERENT DIRECTIONS 

643
00:22:54,273 --> 00:22:55,308
AND YOU KEPT US GROUNDED AND 

644
00:22:55,308 --> 00:22:55,942
YOU GIVE US AN IDEA OF WHAT WE 

645
00:22:55,942 --> 00:22:57,643
SHOULD BE SHOOTING UP FOR. 

646
00:22:57,643 --> 00:23:06,886
THANK YOU VERY MUCH FOR THAT. 

647
00:23:06,886 --> 00:23:07,353
>> BEFORE WE GO TO THE 

648
00:23:07,353 --> 00:23:07,954
QUESTIONS, IF I COULD MAKE A 

649
00:23:07,954 --> 00:23:11,591
COMMENT TOO.  IT IS SUCH AN 

650
00:23:11,591 --> 00:23:13,125
HONOR TO BE ABLE TO SERVE HERE; 

651
00:23:13,125 --> 00:23:23,636
WE FOCUS ON RESEARCH BUT ALSO 

652
00:23:27,907 --> 00:23:28,474
WE ARE CONNECTED WITH AT LEAST 

653
00:23:28,474 --> 00:23:29,075
600,000 PEOPLE ACROSS THE US 

654
00:23:29,075 --> 00:23:32,912
AND SO AS CONSTANTINO SAID, 

655
00:23:32,912 --> 00:23:33,913
KEEPING YOU IN MIND WITH 

656
00:23:33,913 --> 00:23:34,747
EVERYTHING AND WANTING IT WOULD 

657
00:23:34,747 --> 00:23:35,281
LIKE TO EMPHASIZE IS WITH 

658
00:23:35,281 --> 00:23:40,620
MULTIPLE ETIOLOGY WE HAD IT 

659
00:23:40,620 --> 00:23:41,254
WRITTEN IN OUR TEXT BUT WE DID 

660
00:23:41,254 --> 00:23:41,887
NOT VERBALLY EMPHASIZE THAT WE 

661
00:23:41,887 --> 00:23:43,856
NEED TO GET THE FDA AND OTHER 

662
00:23:43,856 --> 00:23:46,158
REGULATORY BODIES INVOLVED TO 

663
00:23:46,158 --> 00:23:47,393
SOMEHOW TRY TO ACCELERATE 

664
00:23:47,393 --> 00:23:47,994
TREATMENTS AND PREVENTIONS. 

665
00:23:47,994 --> 00:23:50,997
RIGHT?

666
00:23:50,997 --> 00:23:51,564
BECAUSE RIGHT NOW IF YOU DEAL 

667
00:23:51,564 --> 00:23:54,600
WITH EACH ONE OF THESE FOUR OR 

668
00:23:54,600 --> 00:23:55,301
MORE  BIOMARKERS AT A TIME IT 

669
00:23:55,301 --> 00:24:00,273
WILL BE LIKE 20-30 YEARS BEFORE 

670
00:24:00,273 --> 00:24:00,706
YOU TRY TO PUT ALL 

671
00:24:00,706 --> 00:24:01,340
ACCOMMODATIONS TOGETHER. SO IF 

672
00:24:01,340 --> 00:24:04,944
YOU CAN BRING THE FDA AND OTHER 

673
00:24:04,944 --> 00:24:07,346
REVELATORY BODIES IN TO TRY TO 

674
00:24:07,346 --> 00:24:08,347
ACCELERATE GETTING NEW 

675
00:24:08,347 --> 00:24:08,981
TREATMENTS TO THE CLINIC, THAT 

676
00:24:08,981 --> 00:24:15,955
WILL HELP AFFECTED FAMILIES. 

677
00:24:15,955 --> 00:24:16,956
>> SHALL WE GO TO THE
QUESTIONS 

678
00:24:16,956 --> 00:24:24,196
CINDY?

679
00:24:24,196 --> 00:24:25,731
>> CINDY YOU ARE MUTED. 

680
00:24:25,731 --> 00:24:31,270
>> DR. CARLSSON: SORRY ANY

681
00:24:31,270 --> 00:24:31,871
QUESTIONS OR COMMENTS?

682
00:24:31,871 --> 00:24:34,907
>> WE HAVE SYLVIA-- ASKING
A 

683
00:24:34,907 --> 00:24:36,342
QUESTION. SYLVIA, GO AHEAD. 

684
00:24:36,342 --> 00:24:38,544
>> THANK YOU. 

685
00:24:38,544 --> 00:24:39,111
THANK YOU THIS WAS A GREAT 

686
00:24:39,111 --> 00:24:43,416
SESSION.  AND AS YOU ALL 

687
00:24:43,416 --> 00:24:44,450
SHOWED, AND HIS I WILL 

688
00:24:44,450 --> 00:24:48,321
REITERATE IN THE BCIB SESSION, 

689
00:24:48,321 --> 00:24:48,954
THE GREAT MAJORITY OF DEMENTIA 

690
00:24:48,954 --> 00:24:51,891
IS A COMBINATION OF ALZHEIMER'S 

691
00:24:51,891 --> 00:24:54,160
AND VASCULAR PATHOLOGY. 

692
00:24:54,160 --> 00:24:56,262
I WAS WONDERING IF WE SHOULD 

693
00:24:56,262 --> 00:24:57,930
INTENSIFY EVEN MORE IN THE 

694
00:24:57,930 --> 00:24:59,365
RECOMMENDATIONS, THAT IS VERY 

695
00:24:59,365 --> 00:25:04,503
IMPORTANT TO STUDY ALZHEIMER'S, 

696
00:25:04,503 --> 00:25:05,104
NOT IN ISOLATION AND VASCULAR 

697
00:25:05,104 --> 00:25:06,072
PATHOLOGY, NOT IN ISOLATION BUT 

698
00:25:06,072 --> 00:25:08,007
A COMBINATION OF THESE TWO 

699
00:25:08,007 --> 00:25:13,679
PATHOLOGIES IN PARTICULAR. 

700
00:25:13,679 --> 00:25:16,182
>> WELL, YOU ARE PREACHING
TO 

701
00:25:16,182 --> 00:25:16,982
THE CHOIR. 

702
00:25:16,982 --> 00:25:20,586
>> NOTED. 

703
00:25:20,586 --> 00:25:24,090
>> DR. IADECOLA:
OBVIOUSLY,  

704
00:25:24,090 --> 00:25:25,124
VASCULAR PATHOLOGY FOUND ITS 

705
00:25:25,124 --> 00:25:30,863
WAY IN ALL KINDS OF COGNITIVE 

706
00:25:30,863 --> 00:25:36,435
IMPAIRMENT. IT WOULD BE VERY 

707
00:25:36,435 --> 00:25:36,969
IMPORTANT BEING THE MOST 

708
00:25:36,969 --> 00:25:38,170
PREVALENT CONDITION. AND THE 

709
00:25:38,170 --> 00:25:38,704
INTERACTION BETWEEN YOUR 

710
00:25:38,704 --> 00:25:40,239
RECOMMENDATION AND OURS IS 

711
00:25:40,239 --> 00:25:40,873
GOING TO TELL US WHAT TO DO AND 

712
00:25:40,873 --> 00:25:42,408
HOW TO MOVE FORWARD. 

713
00:25:42,408 --> 00:25:43,776
>> EXACTLY AND WE WANT TO
TELL 

714
00:25:43,776 --> 00:25:45,978
THE NIH THAT THIS PARTICULAR 

715
00:25:45,978 --> 00:25:46,445
COMBINATION IS REALLY 

716
00:25:46,445 --> 00:25:46,879
IMPORTANT. 

717
00:25:46,879 --> 00:25:48,681
>> YEAH. 

718
00:25:48,681 --> 00:25:50,449
>> AND IF I COULD MAKE A 

719
00:25:50,449 --> 00:25:55,888
COMMENT, THE EYE IS AN 

720
00:25:55,888 --> 00:25:56,455
EXTENSION OF THE BRAIN AND 

721
00:25:56,455 --> 00:25:57,123
REALLY GOOD WINDOW TO THE BRAIN 

722
00:25:57,123 --> 00:26:00,526
AND USING THE EYE TO DIAGNOSE 

723
00:26:00,526 --> 00:26:03,162
FASTER AND CHEAPER-- IT IS A 

724
00:26:03,162 --> 00:26:03,629
LOT CHEAPER WITH THE 

725
00:26:03,629 --> 00:26:05,664
FIVE-MINUTE SCAN, THEN GOING 

726
00:26:05,664 --> 00:26:07,533
FOR A REALLY EXPENSIVE BRAIN 

727
00:26:07,533 --> 00:26:09,268
SCAN. SO TALKING ABOUT THE 

728
00:26:09,268 --> 00:26:09,935
CROSSOVER, LET'S BRING THE EYES 

729
00:26:09,935 --> 00:26:17,410
IN AS WELL. 

730
00:26:17,410 --> 00:26:19,145
>> NICOLE DO YOU WANT TO
GO 

731
00:26:19,145 --> 00:26:21,480
FORWARD?

732
00:26:21,480 --> 00:26:21,947
>> YES HI I'M A NAME IS 

733
00:26:21,947 --> 00:26:25,251
NICOLE-- FROM THE ASSOCIATION 

734
00:26:25,251 --> 00:26:28,354
OF (INDISCERNIBLE) NOT SURE 

735
00:26:28,354 --> 00:26:28,954
THIS IS THE RIGHT GROUP BUT I 

736
00:26:28,954 --> 00:26:31,123
AM WONDERING IF THERE IS 

737
00:26:31,123 --> 00:26:36,328
THINKING ABOUT THE TRAINING OF 

738
00:26:36,328 --> 00:26:37,062
POTENTIAL PEOPLE WORKING IN 

739
00:26:37,062 --> 00:26:41,967
THIS AREA AND ACROSS RELATED 

740
00:26:41,967 --> 00:26:43,135
DEMENTIAS LOOKING AT BEST 

741
00:26:43,135 --> 00:26:43,669
PRACTICES FOR CARE REALLY 

742
00:26:43,669 --> 00:26:44,303
UNDERSTANDING STATISTICALLY, IS 

743
00:26:44,303 --> 00:26:45,438
THIS MEANINGFUL?

744
00:26:45,438 --> 00:26:48,441
IS THIS BENEFICIAL?

745
00:26:48,441 --> 00:26:49,008
AND PROVIDING QUALITY OF LIFE 

746
00:26:49,008 --> 00:26:51,877
AND WELL-BEING ASSESSMENTS FOR 

747
00:26:51,877 --> 00:26:56,382
THESE PEOPLE AND CAREGIVERS. 

748
00:26:56,382 --> 00:26:56,982
ESPECIALLY WHO ARE SUFFERING 

749
00:26:56,982 --> 00:27:01,787
FROM THESE DEMENTIAS. 

750
00:27:01,787 --> 00:27:04,523
IS THERE A PLACE IN EITHER THIS 

751
00:27:04,523 --> 00:27:08,294
GROUP OR OTHERS WE CAN 

752
00:27:08,294 --> 00:27:08,894
HIGHLIGHT I GUESS STUDYING OF 

753
00:27:08,894 --> 00:27:18,938
WELL-BEING FOR THESE DEMENTIAS?

754
00:27:18,938 --> 00:27:19,505
>> INTERACT DIRECTLY WITH
HOW 

755
00:27:19,505 --> 00:27:21,574
OUR COMMITTEE, AND THE 

756
00:27:21,574 --> 00:27:25,478
EDUCATION ELEMENT GOES INTO THE 

757
00:27:25,478 --> 00:27:25,945
COMMITTEE THAT WE SAW 

758
00:27:25,945 --> 00:27:29,381
YESTERDAY. 

759
00:27:29,381 --> 00:27:31,884
>> AND NOTING THIS. THANK
YOU 

760
00:27:31,884 --> 00:27:32,451
VERY MUCH NICOLE. I THIS IS 

761
00:27:32,451 --> 00:27:32,985
SOMETHING WE CAN LOOK TO 

762
00:27:32,985 --> 00:27:36,422
INCORPORATE IN THE MED 

763
00:27:36,422 --> 00:27:37,056
IMPLEMENTATION SESSION THAT WAS 

764
00:27:37,056 --> 00:27:40,693
PRESENTED YESTERDAY, WHICH HAS 

765
00:27:40,693 --> 00:27:43,362
A RECOMMENDATION ON CARE.

766
00:27:43,362 --> 00:27:43,963
AND WE WILL SEE IF THIS CAN FIT 

767
00:27:43,963 --> 00:27:44,363
INTO THE TRAINING 

768
00:27:44,363 --> 00:27:45,130
RECOMMENDATION HERE.  THANK YOU 

769
00:27:45,130 --> 00:27:52,438
FOR THAT IMPORTANT COMMENT. 

770
00:27:52,438 --> 00:28:01,046
CAITLIN, ANYTHING TO ADD?

771
00:28:01,046 --> 00:28:01,580
>> NOTHING SPECIFIC I
THINK 

772
00:28:01,580 --> 00:28:05,451
THAT WE NEED TO-- INTEGRATING 

773
00:28:05,451 --> 00:28:09,321
YESTERDAY'S AND TODAY'S, IN HOW 

774
00:28:09,321 --> 00:28:09,922
WE ARE TREATING PATIENTS AND 

775
00:28:09,922 --> 00:28:12,458
MAKING SURE THAT THERE IS GOOD 

776
00:28:12,458 --> 00:28:14,994
COMMUNICATION I THINK ACROSS 

777
00:28:14,994 --> 00:28:15,528
BOTH SIDES FROM BENCH TO 

778
00:28:15,528 --> 00:28:16,128
BEDSIDE IS GOING TO BE REALLY 

779
00:28:16,128 --> 00:28:16,829
IMPORTANT. 

780
00:28:16,829 --> 00:28:18,531
>> BETSY?

781
00:28:18,531 --> 00:28:20,633
DO YOU WANT TO GO AHEAD?

782
00:28:20,633 --> 00:28:22,034
>> YES THANK YOU SO MUCH,
TO 

783
00:28:22,034 --> 00:28:23,669
THE DEGREE THAT WE CONSIDER 

784
00:28:23,669 --> 00:28:27,239
PCPS AS PART OF THE DEMENTIA 

785
00:28:27,239 --> 00:28:32,511
WORKFORCE, HOW CAN WE NORMALIZE 

786
00:28:32,511 --> 00:28:36,348
SIMPLE, NONINVASIVE SCREENINGS, 

787
00:28:36,348 --> 00:28:36,982
COGNITIVE SCREENINGS AS PART OF 

788
00:28:36,982 --> 00:28:37,650
WELLNESS EXAMS IN MUCH THE SAME 

789
00:28:37,650 --> 00:28:41,320
WAY THAT WE NORMALIZE NOW COLON 

790
00:28:41,320 --> 00:28:43,422
CANCER SCREENINGS AFTER A 

791
00:28:43,422 --> 00:28:46,358
CERTAIN AGE, TO DIFFUSE THE 

792
00:28:46,358 --> 00:28:48,727
FEAR OF THE GENERAL POPULATION 

793
00:28:48,727 --> 00:28:49,395
AND JUST TO CAPTURE PEOPLE AT A 

794
00:28:49,395 --> 00:28:54,934
MUCH EARLIER STAGE AND 

795
00:28:54,934 --> 00:28:55,568
IMPORTANTLY, I'M WONDERING FROM 

796
00:28:55,568 --> 00:28:59,738
THE MEDICAL PERSPECTIVE, FROM 

797
00:28:59,738 --> 00:29:00,339
THE PCP PERSPECTIVE, IS VERY 

798
00:29:00,339 --> 00:29:00,973
CONCERNED ABOUT HOW THESE WOULD 

799
00:29:00,973 --> 00:29:06,979
BE BILLED, ANY CONCERN ABOUT 

800
00:29:06,979 --> 00:29:07,680
THE PCP COMMUNITY THEY MAY HAVE 

801
00:29:07,680 --> 00:29:08,314
TROUBLE GETTING REIMBURSED FOR 

802
00:29:08,314 --> 00:29:10,883
THE SERVICES UNDER MEDICARE AND 

803
00:29:10,883 --> 00:29:11,517
COMMERCIAL CARRIERS CATCH UP TO 

804
00:29:11,517 --> 00:29:12,084
THE IDEA THAT WE SHOULD BE 

805
00:29:12,084 --> 00:29:13,385
DOING THESE SCREENINGS. 

806
00:29:13,385 --> 00:29:16,155
>> THANK YOU
(INDISCERNIBLE). 

807
00:29:16,155 --> 00:29:19,325
>> THANK YOU SO MUCH. I 

808
00:29:19,325 --> 00:29:24,530
APPRECIATE THAT. I ALSO READ 

809
00:29:24,530 --> 00:29:25,030
YOUR COMMENT AND EMAIL 

810
00:29:25,030 --> 00:29:28,467
YESTERDAY ABOUT THIS. BY THE 

811
00:29:28,467 --> 00:29:30,235
WAY WE READ EVERY SINGLE THING 

812
00:29:30,235 --> 00:29:30,836
YOU SENT TO US. THANK YOU SO 

813
00:29:30,836 --> 00:29:34,073
MUCH FOR THIS COMMENT. 

814
00:29:34,073 --> 00:29:35,507
THIS IS ESSENTIAL TO THE 

815
00:29:35,507 --> 00:29:36,075
RECOMMENDATION ON DIAGNOSIS 

816
00:29:36,075 --> 00:29:37,443
FROM THE MED IMPLEMENTATION 

817
00:29:37,443 --> 00:29:40,879
COMMITTEE YESTERDAY.  BUT I 

818
00:29:40,879 --> 00:29:41,513
APPRECIATE SOME OF THE LANGUAGE 

819
00:29:41,513 --> 00:29:43,048
THAT YOU OFFERED AROUND 

820
00:29:43,048 --> 00:29:46,785
NORMALIZING THIS FOR PCPS. AND 

821
00:29:46,785 --> 00:29:50,155
ALSO THE FOCUS ON BILLING. 

822
00:29:50,155 --> 00:29:50,689
WE ARE GOING TO THINK ABOUT 

823
00:29:50,689 --> 00:29:51,323
YOUR COMMENTS AS WE REVISE THAT 

824
00:29:51,323 --> 00:29:51,824
RECOMMENDATION. 

825
00:29:51,824 --> 00:29:55,194
>> THANK YOU. 

826
00:29:55,194 --> 00:29:57,496
>> I WAS GOING TO ADD, I
THINK 

827
00:29:57,496 --> 00:30:00,799
ONE OF THE OTHER CONSIDERATIONS 

828
00:30:00,799 --> 00:30:03,569
THAT PEOPLE HAVE, IS SUCH 

829
00:30:03,569 --> 00:30:05,204
VARIED BACKGROUNDS AND 

830
00:30:05,204 --> 00:30:05,838
EDUCATION. WE NEED TO MAKE SURE 

831
00:30:05,838 --> 00:30:09,742
WE DON'T OVER DIAGNOSE. 

832
00:30:09,742 --> 00:30:10,342
SOMETIMES HARD TO COMMUNICATE 

833
00:30:10,342 --> 00:30:12,344
INTO BUSY, PRIMARY CARE 

834
00:30:12,344 --> 00:30:12,945
PRACTICES. NOT BEING ABLE TO 

835
00:30:12,945 --> 00:30:16,348
STICK WITH THE COGNITIVE POINT, 

836
00:30:16,348 --> 00:30:16,915
HOPEFULLY A COMBINATION OF 

837
00:30:16,915 --> 00:30:24,323
BIOMARKERS AND TRAINING AND 

838
00:30:24,323 --> 00:30:24,857
COGNITIVE SCREENING TO BE 

839
00:30:24,857 --> 00:30:26,291
COMBINED, AND NOT OVERDIAGNOSED 

840
00:30:26,291 --> 00:30:26,792
AND LABEL SOMEONE, AND 

841
00:30:26,792 --> 00:30:27,326
APPROPRIATE TO MOVE THEM 

842
00:30:27,326 --> 00:30:27,726
FORWARD. 

843
00:30:27,726 --> 00:30:34,233
>> I WILL ADD TOO THAT
WITH THE 

844
00:30:34,233 --> 00:30:39,438
ID CONSORTIUM FUNDED BY THE 

845
00:30:39,438 --> 00:30:40,039
NINDS, WE ARE DOING RESEARCH 

846
00:30:40,039 --> 00:30:40,673
EVALUATE PATIENTS FOR THE BRAIN 

847
00:30:40,673 --> 00:30:41,473
HEALTH WHEN THERE IS A CONCERN, 

848
00:30:41,473 --> 00:30:44,643
RATHER THAN SCREENING 

849
00:30:44,643 --> 00:30:45,177
EVERYBODY. WE ARE TRYING 

850
00:30:45,177 --> 00:30:47,846
PATHWAYS WE ARE ASKING IF THERE 

851
00:30:47,846 --> 00:30:48,447
IS A CONCERN IN A SYSTEMATIC 

852
00:30:48,447 --> 00:30:49,114
WAY. BUT NOT ADVOCATING AT THIS 

853
00:30:49,114 --> 00:30:52,685
POINT FOR DOING A FULL 

854
00:30:52,685 --> 00:30:54,687
EVALUATION ON EVERY PERSON OF 

855
00:30:54,687 --> 00:30:57,489
OLDER AGE. BECAUSE THERE ARE 

856
00:30:57,489 --> 00:30:59,658
CONCERNS ABOUT FALSE POSITIVES, 

857
00:30:59,658 --> 00:31:01,560
AND RESOURCES AND PRIMARY CARE 

858
00:31:01,560 --> 00:31:03,829
TO PUSH FORWARD AT THIS TIME. 

859
00:31:03,829 --> 00:31:04,396
IT IS SOMETHING WE ARE ALWAYS 

860
00:31:04,396 --> 00:31:09,401
THINKING ABOUT. AND THE 

861
00:31:09,401 --> 00:31:10,035
PRACTICE AND RECOMMENDATIONS ON 

862
00:31:10,035 --> 00:31:12,104
THAT MAY CHANGE IN THE FUTURE.  

863
00:31:12,104 --> 00:31:12,738
ESPECIALLY AS BETTER TREATMENTS 

864
00:31:12,738 --> 00:31:13,539
ARE AVAILABLE.

865
00:31:13,539 --> 00:31:14,873
>> BEN?

866
00:31:14,873 --> 00:31:24,850
>> YES. HI, THANK YOU. AND

867
00:31:24,850 --> 00:31:25,350
GREETINGS FROM DRESSLER 

868
00:31:25,350 --> 00:31:27,886
UNIVERSITY. 

869
00:31:27,886 --> 00:31:28,487
YESTERDAY WE HEARD A LOT ABOUT 

870
00:31:28,487 --> 00:31:31,390
BIOCHEMICAL MARKERS, ABOUT 

871
00:31:31,390 --> 00:31:32,958
TECHNOLOGIES AND BRAIN IMAGING. 

872
00:31:32,958 --> 00:31:33,559
I'M WONDERING WHY WE HAVE NOT 

873
00:31:33,559 --> 00:31:35,360
HEARD SO MUCH ABOUT HUMAN 

874
00:31:35,360 --> 00:31:35,928
MOVEMENT, OR MOBILITY AND 

875
00:31:35,928 --> 00:31:40,099
BIOMECHANICS. 

876
00:31:40,099 --> 00:31:43,402
>> I GUESS DAVID SHOULD
ADDRESS 

877
00:31:43,402 --> 00:31:44,870
THAT, MAYBE?

878
00:31:44,870 --> 00:31:49,408
>> DR. FARDO: YES SURE.  I
OUR 

879
00:31:49,408 --> 00:31:55,147
RECOMMENDATION IS BROADLY FOR 

880
00:31:55,147 --> 00:31:55,647
BIOMARKER, BRINGING IN 

881
00:31:55,647 --> 00:31:56,281
BIOMARKERS NOT NECESSARILY FROM 

882
00:31:56,281 --> 00:32:00,652
A SPECIFIC DOMAIN. SO, IT'S ... 

883
00:32:00,652 --> 00:32:06,959
OPEN TO THE FLAVOR OF 

884
00:32:06,959 --> 00:32:12,131
BIOMARKER, THE CRUX  FROM THE 

885
00:32:12,131 --> 00:32:12,731
DATA PERSPECTIVE IS WE CAN DO 

886
00:32:12,731 --> 00:32:13,332
THINGS THAT ARE SHARED ACROSS 

887
00:32:13,332 --> 00:32:15,200
DIFFERENT GROUPS IN A WAY THAT 

888
00:32:15,200 --> 00:32:16,969
WE HAVE APPLES TO APPLES; AND 

889
00:32:16,969 --> 00:32:22,708
CAN GARNER MORE RESOURCES 

890
00:32:22,708 --> 00:32:24,543
ACROSS INSTITUTIONS, SO THAT WE 

891
00:32:24,543 --> 00:32:28,046
CAN BETTER POWER OUR STUDIES. 

892
00:32:28,046 --> 00:32:31,316
>> DR. IADECOLA: AND I
THINK 

893
00:32:31,316 --> 00:32:32,985
CORRELATING THE TRADITIONAL 

894
00:32:32,985 --> 00:32:36,321
BIOMARKER WITH MOVEMENT, 

895
00:32:36,321 --> 00:32:40,859
BIOMECHANICAL BIOMARKERS, HAS 

896
00:32:40,859 --> 00:32:44,530
REALLY PANNED OUT. BECAUSE 

897
00:32:44,530 --> 00:32:45,097
SLOWING OF THE MOVEMENT IS 

898
00:32:45,097 --> 00:32:46,265
RELATED TO WHITE MATTER DISEASE 

899
00:32:46,265 --> 00:32:46,899
FOR EXAMPLE. SO WE ARE ALREADY 

900
00:32:46,899 --> 00:32:49,802
ON THAT TRACK, AND I WE SHOULD 

901
00:32:49,802 --> 00:32:52,070
EMPHASIZE THAT MOVING FORWARD. 

902
00:32:52,070 --> 00:32:52,671
SO THANK YOU VERY MUCH FOR THE 

903
00:32:52,671 --> 00:32:53,639
COMMENT. 

904
00:32:53,639 --> 00:32:58,443
>> DR. CARLSSON: WE TRY TO

905
00:32:58,443 --> 00:32:59,044
CAPTURE THAT SO WE INITIALLY 

906
00:32:59,044 --> 00:33:02,915
HAD A LOT OF DIFFERENT TYPES OF 

907
00:33:02,915 --> 00:33:04,616
BIOMARKERS. AND SO WE GROUPED 

908
00:33:04,616 --> 00:33:05,818
THEM UNDER NEUROPHYSIOLOGICAL. 

909
00:33:05,818 --> 00:33:07,719
YOUR COMMENTS ARE WELL TAKEN 

910
00:33:07,719 --> 00:33:08,453
AND THERE WILL BE NEW MARKERS 

911
00:33:08,453 --> 00:33:11,156
PROMISING TO CAPTURE NEW ASPECT 

912
00:33:11,156 --> 00:33:11,757
WE HAVEN'T BEFORE. THANK YOU 

913
00:33:11,757 --> 00:33:12,858
FOR THAT. 

914
00:33:12,858 --> 00:33:22,968
>> JULIE?

915
00:33:24,102 --> 00:33:28,273
>> JULIETTE -- THANK YOU. 

916
00:33:28,273 --> 00:33:31,577
ONE STUDY OF ALZHEIMER'S 

917
00:33:31,577 --> 00:33:32,511
DISEASE IN THE BRAIN BUT ALSO 

918
00:33:32,511 --> 00:33:37,649
IN THE EYE, THE LENS AND 

919
00:33:37,649 --> 00:33:38,684
RETINA, I ENDORSE WHAT DIANE 

920
00:33:38,684 --> 00:33:44,289
SAID ABOUT THE EYE. IT IS A 

921
00:33:44,289 --> 00:33:44,890
WINDOW INTO THE BRAIN AND CAN 

922
00:33:44,890 --> 00:33:48,293
BE CHEAPER AND EASIER ACCESS TO 

923
00:33:48,293 --> 00:33:54,299
ACCESS THE BRAIN FOR PATIENTS. 

924
00:33:54,299 --> 00:33:54,833
ONE POINT BEFORE DIANE EVEN 

925
00:33:54,833 --> 00:33:55,467
SAID THAT IS I WANT IS A BUSY 

926
00:33:55,467 --> 00:33:59,905
BIOLOGIST TO GET MORE INTO IPAC 

927
00:33:59,905 --> 00:34:04,376
CELLS MENTIONED AS MODELS,  TO 

928
00:34:04,376 --> 00:34:06,778
STUDY THESE MEDS. 

929
00:34:06,778 --> 00:34:08,313
WHAT ABOUT MICE MODELS? 

930
00:34:08,313 --> 00:34:12,351
EXPANDING MODEL AD, THAT IS 

931
00:34:12,351 --> 00:34:16,321
MORE RELEVANT MOUSE MODELS, 

932
00:34:16,321 --> 00:34:21,593
WILL THAT BE EXPANDED TO BRING 

933
00:34:21,593 --> 00:34:22,694
DIFFERENT PATHOLOGIES TO 

934
00:34:22,694 --> 00:34:23,328
DIFFERENT MOUSE MODELS?

935
00:34:23,328 --> 00:34:26,398
>> DR. IADECOLA:
ABSOLUTELY ONE 

936
00:34:26,398 --> 00:34:26,999
STANDARD WAY OF DOING IT. ONE 

937
00:34:26,999 --> 00:34:28,300
INTERESTING ASPECT IS THAT 

938
00:34:28,300 --> 00:34:31,970
MODELS OF PATHOLOGIES, COMING 

939
00:34:31,970 --> 00:34:32,537
FROM DIFFERENT COMMUNITIES 

940
00:34:32,537 --> 00:34:33,138
WHICH DO NOT NECESSARILY TALK 

941
00:34:33,138 --> 00:34:36,074
TO EACH OTHER. FOR EXAMPLE AS 

942
00:34:36,074 --> 00:34:36,708
YOU WILL SEE THERE IS A LOT OF 

943
00:34:36,708 --> 00:34:37,542
VASCULAR PATHOLOGY BEING 

944
00:34:37,542 --> 00:34:43,615
DEVELOPED IN MICE THAT WOULD BE 

945
00:34:43,615 --> 00:34:52,024
WORTH CROSSING WITH MOUSE WITH 

946
00:34:52,024 --> 00:34:55,127
MORE NEURODEGENERATIVE 

947
00:34:55,127 --> 00:34:55,627
PATHOLOGY. AND WE NEED 

948
00:34:55,627 --> 00:34:56,962
INCENTIVES TO FACILITATE THOSE 

949
00:34:56,962 --> 00:34:57,529
INTERACTIONS, STARTING WITH 

950
00:34:57,529 --> 00:35:00,232
EXISTING MODELS, AND MOVING 

951
00:35:00,232 --> 00:35:04,703
THAT TO THE NEW MODELS AND SO 

952
00:35:04,703 --> 00:35:07,205
ON. VERY IMPORTANT POINT. THANK 

953
00:35:07,205 --> 00:35:07,506
YOU.

954
00:35:07,506 --> 00:35:09,074
>> WE HAVE TIME FOR ONE
LAST 

955
00:35:09,074 --> 00:35:09,741
QUESTION, WE ARE TECHNICALLY 

956
00:35:09,741 --> 00:35:16,782
OUT OF TIME. 

957
00:35:16,782 --> 00:35:17,316
I ENCOURAGE ANYBODY ELSE TO 

958
00:35:17,316 --> 00:35:18,116
PLEASE BRING YOUR QUESTIONS AND 

959
00:35:18,116 --> 00:35:18,717
COMMENTS FOR FURTHER PUBLIC 

960
00:35:18,717 --> 00:35:20,252
TIME THIS AFTERNOON. 

961
00:35:20,252 --> 00:35:22,721
>> THANK YOU AMBER. 

962
00:35:22,721 --> 00:35:25,691
>> CAN YOU HEAR ME?

963
00:35:25,691 --> 00:35:30,862
MY NAME IS PEPAN CANN 

964
00:35:30,862 --> 00:35:31,496
(PHONETIC), WORKING THIS MODEL 

965
00:35:31,496 --> 00:35:40,372
IN THIS COMPANY, DEVELOPING 

966
00:35:40,372 --> 00:35:41,807
AI-BASED (INDISCERNIBLE) 

967
00:35:41,807 --> 00:35:42,307
TECHNOLOGY AND WORKING 

968
00:35:42,307 --> 00:35:42,941
PREVIOUSLY AT THE ROCKEFELLER 

969
00:35:42,941 --> 00:35:44,042
INSTITUTE (INDISCERNIBLE). 

970
00:35:44,042 --> 00:35:51,483
MY QUESTION IS, WILL YOU 

971
00:35:51,483 --> 00:35:55,253
CORRELATE ALL THESE BIOMARKERS?

972
00:35:55,253 --> 00:35:56,521
BLOOD TESTS, SKIN TESTS, WITH 

973
00:35:56,521 --> 00:35:59,424
MULTIPLE ETIOLOGY OF DEMENTIA?

974
00:35:59,424 --> 00:36:02,894
>> DR. IADECOLA: LOOKS
LIKE 

975
00:36:02,894 --> 00:36:03,528
DAVID'S NAME IS WRITTEN ON THAT 

976
00:36:03,528 --> 00:36:05,097
ONE. 

977
00:36:05,097 --> 00:36:06,064
>> THAT IS WHERE YOU COME
IN. 

978
00:36:06,064 --> 00:36:08,667
>> DR. FARDO: WE ARE
ADVOCATING 

979
00:36:08,667 --> 00:36:15,240
FOR FUNDING FOR THOSE EFFORTS. 

980
00:36:15,240 --> 00:36:17,776
IT IS NOT TRIVIAL.

981
00:36:17,776 --> 00:36:18,643
I THINK OF THINGS IN CAUSAL 

982
00:36:18,643 --> 00:36:21,780
DIAGRAMS AND DR. IADECOLA 

983
00:36:21,780 --> 00:36:24,750
PRESENTED ONE ABOUT MULTIPLE 

984
00:36:24,750 --> 00:36:25,384
PATHOLOGIES EFFECTIVE COGNITIVE 

985
00:36:25,384 --> 00:36:25,951
DECLINE, POTENTIALLY GOING 

986
00:36:25,951 --> 00:36:30,255
BACK. 

987
00:36:30,255 --> 00:36:32,357
THOSE ARE ADVANCED STATISTICAL 

988
00:36:32,357 --> 00:36:32,991
METHODOLOGIES THAT ARE REQUIRED 

989
00:36:32,991 --> 00:36:34,893
TO BE ABLE TO ANSWER THOSE 

990
00:36:34,893 --> 00:36:36,595
SPECIFIC QUESTIONS. 

991
00:36:36,595 --> 00:36:39,431
AND SO THE ABILITY FOR US TO 

992
00:36:39,431 --> 00:36:43,301
EVEN ENTERTAIN THOSE IS 

993
00:36:43,301 --> 00:36:48,240
DEPENDENT ON A COMMON 

994
00:36:48,240 --> 00:36:48,807
CLASSIFICATION OR CONSENSUS 

995
00:36:48,807 --> 00:36:52,310
CLASSIFICATION SO WE CAN AGAIN 

996
00:36:52,310 --> 00:36:54,713
COMPARE APPLES TO APPLES. AT 

997
00:36:54,713 --> 00:36:55,280
LEAST READ APPLES AND GREEN 

998
00:36:55,280 --> 00:36:55,881
APPLES, RATHER THAN APPLES TO 

999
00:36:55,881 --> 00:37:06,058
ORANGES. 

1000
00:37:09,361 --> 00:37:09,795
>> DR. ERTEKIN TANER:

1001
00:37:09,795 --> 00:37:10,395
 SORRY FOR MIGHT ADD TO THAT 

1002
00:37:10,395 --> 00:37:12,697
BEFORE YOU RESPOND. I THIS IS 

1003
00:37:12,697 --> 00:37:13,331
WHERE IS A NONPROFIT FUNDER WE 

1004
00:37:13,331 --> 00:37:14,099
TO GET AS MANY FUNDERS 

1005
00:37:14,099 --> 00:37:14,633
TOGETHER, PUBLIC/ PRIVATE 

1006
00:37:14,633 --> 00:37:17,102
PARTNERSHIPS AND MOVE TOWARDS 

1007
00:37:17,102 --> 00:37:20,505
GUARANTORS FUNDING THESE. 

1008
00:37:20,505 --> 00:37:23,708
>> USED TO SAY 

1009
00:37:23,708 --> 00:37:26,812
(INDISCERNIBLE)... WE 

1010
00:37:26,812 --> 00:37:27,312
(INDISCERNIBLE) AT THE 

1011
00:37:27,312 --> 00:37:33,251
ROCKEFELLER INSTITUTE IN 2006. 

1012
00:37:33,251 --> 00:37:35,120
WE DON'T HAVE THAT MUCH 

1013
00:37:35,120 --> 00:37:37,489
MULTIPLE ETIOLOGY. WE HAVE 

1014
00:37:37,489 --> 00:37:39,958
AROUND (INDISCERNIBLE)... WHAT 

1015
00:37:39,958 --> 00:37:47,132
WE ARE DOING IN SMALL 

1016
00:37:47,132 --> 00:37:47,766
BUSINESSES AND SMALL COMPANIES, 

1017
00:37:47,766 --> 00:37:50,302
NOT CURRENT. OKAY, THIS IS FOR 

1018
00:37:50,302 --> 00:37:52,304
ALZHEIMER'S DISEASE, WE ONLY 

1019
00:37:52,304 --> 00:37:54,639
HAVE (INDISCERNIBLE). THE REST 

1020
00:37:54,639 --> 00:38:04,216
IS MIXED DEMENTIA. 

1021
00:38:04,216 --> 00:38:07,986
BRAIN IMAGING AND 

1022
00:38:07,986 --> 00:38:11,556
(INDISCERNIBLE) DIFFERENT 

1023
00:38:11,556 --> 00:38:16,361
REGIONS. SPECIFIC TO DIFFERENT 

1024
00:38:16,361 --> 00:38:17,729
DISEASES FOR EXAMPLE VASCULAR 

1025
00:38:17,729 --> 00:38:28,240
DEMENTIA, ALZHEIMER'S OR LOU 

1026
00:38:28,240 --> 00:38:30,475
GEHRIG'S DISEASE. 

1027
00:38:30,475 --> 00:38:35,780
OR WHAT SPECIFIC AGE OF 

1028
00:38:35,780 --> 00:38:36,848
ETIOLOGY (INDISCERNIBLE).... 

1029
00:38:36,848 --> 00:38:38,817
PARTICULAR PATHOLOGY. 

1030
00:38:38,817 --> 00:38:39,851
WE ARE WORKING ON THAT DATA 

1031
00:38:39,851 --> 00:38:41,786
SET. 

1032
00:38:41,786 --> 00:38:45,123
>> THANK YOU. 

1033
00:38:45,123 --> 00:38:46,925
>> IS THAT CORRECT OR NOT?

1034
00:38:46,925 --> 00:38:50,061
(INDISCERNIBLE)

1035
00:38:50,061 --> 00:38:53,865
HOW DO WE GO FOR MOLECULES?

1036
00:38:53,865 --> 00:38:58,336
>> I THINK WE DEFINITELY
HEAR 

1037
00:38:58,336 --> 00:39:02,307
YOUR QUESTION. 

1038
00:39:02,307 --> 00:39:03,942
AND REALLY APPRECIATE YOUR 

1039
00:39:03,942 --> 00:39:04,576
QUESTIONS AND THINKING. I THINK 

1040
00:39:04,576 --> 00:39:10,248
EVERYONE AGREES THAT IS A 

1041
00:39:10,248 --> 00:39:12,651
RESEARCH QUESTION THAT IS 

1042
00:39:12,651 --> 00:39:16,254
ACTIVELY PURSUED. WE WILL GO TO 

1043
00:39:16,254 --> 00:39:16,855
LUNCH RIGHT NOW AND COME BACK 

1044
00:39:16,855 --> 00:39:18,823
FOR AN ON-TIME START AT 12:40
EASTERN TIME. 

1045
00:39:18,823 --> 00:39:25,043
SO RACHEL, WE HAVE THE SLIDES
FOR LUNCH BREAK? THANK YOU. 

1046
00:39:25,043 --> 00:39:31,650
>> WE ARE BACK. 

1047
00:39:31,650 --> 00:39:35,687
DO WE HAVE OUR FIRST  SESSION 6 

1048
00:39:35,687 --> 00:39:44,162
PRESENTERS ONLINE?

1049
00:39:44,162 --> 00:39:47,966
>> YES WE COULD HEAR
SOMEBODY. 

1050
00:39:47,966 --> 00:39:54,372
>> I BELIEVE DR. GALVIN IS
UP 

1051
00:39:54,372 --> 00:39:55,040
FIRST. 

1052
00:39:55,040 --> 00:39:57,542
>> DR. GALVIN: OKAY SHOULD
I 

1053
00:39:57,542 --> 00:39:59,277
START?

1054
00:39:59,277 --> 00:40:02,214
>> YES. I THINK IT IS SLOW
TO 

1055
00:40:02,214 --> 00:40:04,249
LOAD ON MY SIDE. I AM GOOD. 

1056
00:40:04,249 --> 00:40:08,520
WELCOME BACK EVERYBODY. 

1057
00:40:08,520 --> 00:40:15,927
>> DR. GALVIN: MY NAME IS
DR. 

1058
00:40:15,927 --> 00:40:16,761
JIM GALVIN, A NEUROLOGIST AT 

1059
00:40:16,761 --> 00:40:21,266
THE MIAMI UNIVERSITY SCHOOL OF 

1060
00:40:21,266 --> 00:40:22,000
MEDICINE AND I AM GLAD TO 

1061
00:40:22,000 --> 00:40:23,201
CULTURE LIVES WITH KATHLEEN 

1062
00:40:23,201 --> 00:40:26,037
POSTON. 

1063
00:40:26,037 --> 00:40:26,638
I HAVE A BRIEF INTRODUCTION AND 

1064
00:40:26,638 --> 00:40:27,138
I WANT TO INTRODUCE THE 

1065
00:40:27,138 --> 00:40:27,572
COMMITTEE. 

1066
00:40:27,572 --> 00:40:33,245
NEXT SLIDE. 

1067
00:40:33,245 --> 00:40:35,914
WONDERFUL GROUP OF TALENTED 

1068
00:40:35,914 --> 00:40:36,514
PEOPLE WHO HAVE MET OVER THE 

1069
00:40:36,514 --> 00:40:38,650
PAST SEVERAL MONTHS TO CREATE 

1070
00:40:38,650 --> 00:40:39,618
THIS PRESENTATION. 

1071
00:40:39,618 --> 00:40:45,123
I WANT TO THANK NIH AND NINDS 

1072
00:40:45,123 --> 00:40:45,757
FOR THE OPPORTUNITY TO PRESENT 

1073
00:40:45,757 --> 00:40:47,492
THESE RECOMMENDATIONS AND 

1074
00:40:47,492 --> 00:40:50,095
PRIORITIES FOR LEWY BODY 

1075
00:40:50,095 --> 00:40:51,296
DEMENTIA. 

1076
00:40:51,296 --> 00:40:55,367
TODAY WILL COVER FOUR 

1077
00:40:55,367 --> 00:40:56,568
RECOMMENDATIONS AND TWO 

1078
00:40:56,568 --> 00:40:58,837
PRESENTERS WILL DISCUSS TWO 

1079
00:40:58,837 --> 00:41:03,708
PRIORITIES EACH. 

1080
00:41:03,708 --> 00:41:05,877
JUANTOLEDO ATUCHA WILL TALK 

1081
00:41:05,877 --> 00:41:10,982
ABOUT LBD CLINICAL TRIALS AND 

1082
00:41:10,982 --> 00:41:12,951
ELIZABETH MORMINO WILL TALK 

1083
00:41:12,951 --> 00:41:22,594
ABOUT BIOMARKERS, AND BRITTANY 

1084
00:41:22,594 --> 00:41:23,295
DUGGER WILL TALK ABOUT GENOMIC 

1085
00:41:23,295 --> 00:41:30,468
AND MULTI-OMICS AND ALICE 

1086
00:41:30,468 --> 00:41:31,903
CHEN-PLOTKIN WILL TIE ALL THIS 

1087
00:41:31,903 --> 00:41:42,047
TOGETHER. 

1088
00:41:42,047 --> 00:41:42,647
WHAT IS IMPORTANT IS WE TRY TO 

1089
00:41:42,647 --> 00:41:43,448
TAKE AS MUCH INFORMATION AS WE 

1090
00:41:43,448 --> 00:41:50,755
COULD, AND ORGANIZES INASMUCH 

1091
00:41:50,755 --> 00:41:51,189
OF ALOGICAL SET OF 

1092
00:41:51,189 --> 00:41:51,823
ACCOMMODATIONS AND PRIORITIES 

1093
00:41:51,823 --> 00:41:55,126
WITH ACTION PLANS, WITH 

1094
00:41:55,126 --> 00:41:55,627
INTERMEDIATE AND FUTURE 

1095
00:41:55,627 --> 00:41:56,361
LONG-TERM GOALS. 

1096
00:41:56,361 --> 00:41:57,896
I WILL LIKE TO TURN HER OVER TO 

1097
00:41:57,896 --> 00:42:03,468
DR. JUANTOLEDO ATUCHA, WHO WILL 

1098
00:42:03,468 --> 00:42:04,102
LEAD US TO THE FIRST SERIES OF 

1099
00:42:04,102 --> 00:42:06,905
RECOMMENDATIONS. 

1100
00:42:06,905 --> 00:42:08,873
>> DR. TOLEDO ATUCHA: CAN
I 

1101
00:42:08,873 --> 00:42:10,675
HAVE MY SLIDES?

1102
00:42:10,675 --> 00:42:16,681
NEXT SLIDE. 

1103
00:42:16,681 --> 00:42:19,851
I WANT TO THANK ALL THE 

1104
00:42:19,851 --> 00:42:21,119
COMMITTEE MEMBERS FOR THE 

1105
00:42:21,119 --> 00:42:21,786
PARTICIPATION, THOUGHTFUL IDEAS 

1106
00:42:21,786 --> 00:42:25,457
AND THE NIH FOR GIVING US THE 

1107
00:42:25,457 --> 00:42:28,126
OPPORTUNITY TO PRESENT THIS. 

1108
00:42:28,126 --> 00:42:30,628
ALL THE VIEWS THAT WE PRESENT 

1109
00:42:30,628 --> 00:42:31,196
HERE ARE FROM THE COMMITTEE 

1110
00:42:31,196 --> 00:42:31,830
MEMBERS AND DO NOT REFLECT THE 

1111
00:42:31,830 --> 00:42:32,397
OFFICIAL POLICY OF NATIONAL 

1112
00:42:32,397 --> 00:42:32,931
INSTITUE OF NEUROLOIGCAL 

1113
00:42:32,931 --> 00:42:41,206
DISORDERS AND OR THE NIH. 

1114
00:42:41,206 --> 00:42:42,273
I WILL TALK WITH THE FIRST AND 

1115
00:42:42,273 --> 00:42:42,941
SECOND RECOMMENDATIONS OF THE 

1116
00:42:42,941 --> 00:42:48,213
LEVY BODY DEMENTIA GROUP. 

1117
00:42:48,213 --> 00:42:51,116
THE FIRST WILL DEAL WITH 

1118
00:42:51,116 --> 00:42:51,683
CLINICAL TRIALS. THE MAIN 

1119
00:42:51,683 --> 00:42:55,353
RECOMMENDATION IS TO EXPAND THE 

1120
00:42:55,353 --> 00:42:56,788
LEVY BODY DEMENTIA CLINICAL 

1121
00:42:56,788 --> 00:42:57,322
TRIAL INFRASTRUCTURE AND 

1122
00:42:57,322 --> 00:43:02,293
PERFORM TRIALS THAT ALLOWS TO 

1123
00:43:02,293 --> 00:43:02,927
(INDISCERNIBLE) EITHER DELAYING 

1124
00:43:02,927 --> 00:43:04,596
OR PREVENTING THE ONSET OF 

1125
00:43:04,596 --> 00:43:07,399
SYMPTOMS. BUT WE AGREE IT IS 

1126
00:43:07,399 --> 00:43:08,433
IMPORTANT TO HAVE MEDICATIONS 

1127
00:43:08,433 --> 00:43:09,033
ALLEVIATED CLINICAL SYMPTOMS, 

1128
00:43:09,033 --> 00:43:11,002
EVEN IF THEY ARE NOT DISEASE 

1129
00:43:11,002 --> 00:43:11,469
MODIFYING. 

1130
00:43:11,469 --> 00:43:21,613
NEXT SLIDE. 

1131
00:43:30,955 --> 00:43:31,556
NEXT. I THOUGHT WE TOOK OUT THE 

1132
00:43:31,556 --> 00:43:32,190
ANIMATION. SORRY; HERE WHAT WE 

1133
00:43:32,190 --> 00:43:35,693
ARE SEEING ARE (INDISCERNIBLE), 

1134
00:43:35,693 --> 00:43:36,961
SUMMARIZING ALL THE CLINICAL 

1135
00:43:36,961 --> 00:43:37,595
TRIALS PERFORMED AND LEVY BODY 

1136
00:43:37,595 --> 00:43:42,434
DEMENTIA. 

1137
00:43:42,434 --> 00:43:43,935
THERE HAS BEEN AN INCREASE IN 

1138
00:43:43,935 --> 00:43:44,569
2022, HERE IS THE UPDATED GRAPH 

1139
00:43:44,569 --> 00:43:45,136
FOR 2025 SO YOU CAN SEE IN 

1140
00:43:45,136 --> 00:43:47,338
BLACK INK THE CURRENT NEW 

1141
00:43:47,338 --> 00:43:50,408
CLINICAL TRIALS FOR LEVY BODY 

1142
00:43:50,408 --> 00:43:52,977
DEMENTIA. AND GREY ARE THE ONES 

1143
00:43:52,977 --> 00:43:53,578
THAT WERE STARTED BEFORE AND 

1144
00:43:53,578 --> 00:43:56,714
ARE STILL ONGOING. 

1145
00:43:56,714 --> 00:43:57,515
THE ONES I CIRCLE HERE ARE THE 

1146
00:43:57,515 --> 00:44:07,992
ONES THAT RECENTLY WE READ. AND 

1147
00:44:07,992 --> 00:44:08,593
WE CAN SEE ON THE NEXT SLIDE 

1148
00:44:08,593 --> 00:44:09,060
THE RESULTS. IN THESE 

1149
00:44:09,060 --> 00:44:09,627
PRE-CLINIC TRIALS READ THE 

1150
00:44:09,627 --> 00:44:11,329
RESULTS AT THE INTERNATIONAL 

1151
00:44:11,329 --> 00:44:14,065
LEVY BODY DEMENTIA  CONFERENCE 

1152
00:44:14,065 --> 00:44:18,803
IN AMSTERDAM IN JANUARY. 

1153
00:44:18,803 --> 00:44:19,337
WE ARE PLEASED THE THREE OF 

1154
00:44:19,337 --> 00:44:19,971
THEM SHOW POSITIVE SIGNALS, TO 

1155
00:44:19,971 --> 00:44:23,508
DIFFERENT DEGREES, AFFECTING 

1156
00:44:23,508 --> 00:44:24,275
SYMPTOMS THAT WERE MOTOR, 

1157
00:44:24,275 --> 00:44:26,110
BEHAVIORAL AND COGNITIVE. 

1158
00:44:26,110 --> 00:44:31,716
THESE WERE TRACED TO AN OVERALL 

1159
00:44:31,716 --> 00:44:33,785
IDEA THAT IT WILL MOVE TO 

1160
00:44:33,785 --> 00:44:34,586
(INDISCERNIBLE) FOR MEDICATION. 

1161
00:44:34,586 --> 00:44:38,656
NEXT SLIDE. 

1162
00:44:38,656 --> 00:44:39,824
THERE HAS BEEN ALSO AN EFFORT 

1163
00:44:39,824 --> 00:44:41,326
TO INCREASE ON THE LEFT-HAND 

1164
00:44:41,326 --> 00:44:44,696
SIDE YOU SEE IMPACT IDEA, THIS 

1165
00:44:44,696 --> 00:44:45,964
IS A COMBINED EFFORT OF THE NIH 

1166
00:44:45,964 --> 00:44:50,702
AND THE ALZHEIMER'S ASSOCIATION 

1167
00:44:50,702 --> 00:44:51,302
TO TRAIN AN INCREASE IN THE 

1168
00:44:51,302 --> 00:44:54,272
GENERATION OF CLINICAL TRIALS, 

1169
00:44:54,272 --> 00:44:57,842
RESEARCH COORDINATORS AND BRING 

1170
00:44:57,842 --> 00:44:58,443
SMALL COMPANIES INTO CLINICAL 

1171
00:44:58,443 --> 00:45:01,713
TRIALS, AND ALSO THE LEVY BODY 

1172
00:45:01,713 --> 00:45:03,448
DEMENTIA ASSOCIATION INCREASING 

1173
00:45:03,448 --> 00:45:04,048
A NETWORK OF RESEARCH CENTERS 

1174
00:45:04,048 --> 00:45:09,988
OF EXCELLENCE ACROSS THE UNITED 

1175
00:45:09,988 --> 00:45:10,622
STATES TO OFFER A CLINICAL CARE 

1176
00:45:10,622 --> 00:45:11,322
AND ACCESS TO CLINICAL TRIALS 

1177
00:45:11,322 --> 00:45:12,190
TO PEOPLE WHO ARE LIVING WITH 

1178
00:45:12,190 --> 00:45:12,824
LEVY BODY DEMENTIAS. 

1179
00:45:12,824 --> 00:45:14,926
NEXT SLIDE. 

1180
00:45:14,926 --> 00:45:22,200
BUT WE STILL ...NEXT... NEXT... 

1181
00:45:22,200 --> 00:45:25,303
SO WE IDENTIFIED THERE ARE 

1182
00:45:25,303 --> 00:45:29,307
STILL SEVERAL GAPS. 

1183
00:45:29,307 --> 00:45:31,342
ONE IS THE LIMITED NUMBER OF 

1184
00:45:31,342 --> 00:45:32,810
LEVY BODY DEMENTIA CLINICAL 

1185
00:45:32,810 --> 00:45:34,579
TRIALS. 

1186
00:45:34,579 --> 00:45:35,446
YOU REMEMBER THE ONES IN BLACK 

1187
00:45:35,446 --> 00:45:39,217
WITH THE ACTIVE CLINICAL TRIALS 

1188
00:45:39,217 --> 00:45:41,886
AND YOU CAN COMPARE THESE TO 

1189
00:45:41,886 --> 00:45:42,520
THE SAME RESULTS FOR-- FOR THE 

1190
00:45:42,520 --> 00:45:43,855
SAME ACTIVE TRIALS FOR 

1191
00:45:43,855 --> 00:45:47,325
ALZHEIMER'S DISEASE AND 

1192
00:45:47,325 --> 00:45:50,161
PARKINSON'S DISEASE. YOU CAN 

1193
00:45:50,161 --> 00:45:50,828
SEE THERE ARE MANY MORE. AND 

1194
00:45:50,828 --> 00:45:51,229
THERE ARE LIMITED 

1195
00:45:51,229 --> 00:45:54,566
(INDISCERNIBLE) OF LEVY BODY 

1196
00:45:54,566 --> 00:45:55,166
DEMENTIA INTO CLINICAL TRIALS 

1197
00:45:55,166 --> 00:45:59,971
AND WE ARE LACKING LBD SPECIFIC 

1198
00:45:59,971 --> 00:46:05,577
CLINICAL SCALES AS PREVIOUS 

1199
00:46:05,577 --> 00:46:06,044
PRESENTATIONS WE NEED 

1200
00:46:06,044 --> 00:46:07,245
HARMONIZATION OF CLINICAL 

1201
00:46:07,245 --> 00:46:07,779
MEASURES, AND THERE IS A 

1202
00:46:07,779 --> 00:46:08,413
LIMITED INFRASTRUCTURE. 

1203
00:46:08,413 --> 00:46:10,748
NEXT SLIDE. 

1204
00:46:10,748 --> 00:46:11,349
BASED ON THESE COMMENTS WE FELT 

1205
00:46:11,349 --> 00:46:13,952
WE NEEDED TO PROMOTE LEVY BODY 

1206
00:46:13,952 --> 00:46:15,453
CLINICAL TRIALS AND EXPAND THE 

1207
00:46:15,453 --> 00:46:21,326
FOOTPRINT AND SCOPE.  THE 

1208
00:46:21,326 --> 00:46:22,093
SUBJECT WILL LIKELY COME FROM 

1209
00:46:22,093 --> 00:46:27,565
THE MIL. 5-8 AND SECOND WE WILL 

1210
00:46:27,565 --> 00:46:29,100
HAVE THE DESIGN AND SELECTIONS 

1211
00:46:29,100 --> 00:46:29,701
BASED ON THE CLINICAL TRIALS 

1212
00:46:29,701 --> 00:46:31,603
AND WE WANT TO PROMOTE UPLOAD 

1213
00:46:31,603 --> 00:46:34,005
SELECTION OF CLINICAL TRIAL 

1214
00:46:34,005 --> 00:46:38,142
PARTICIPANTS ACROSS DIFFERENT 

1215
00:46:38,142 --> 00:46:38,743
STAGES, AND PRESENTATIONS FOR 

1216
00:46:38,743 --> 00:46:41,346
AT RISK GROUPS. 

1217
00:46:41,346 --> 00:46:42,981
BY 2029 WE LOOK FORWARD TO 

1218
00:46:42,981 --> 00:46:43,748
HAVING AT LEAST ONE ADDITIONAL 

1219
00:46:43,748 --> 00:46:47,151
AGENT TARGETING THESE 

1220
00:46:47,151 --> 00:46:47,785
MODIFICATIONS AT LEAST ONE PER 

1221
00:46:47,785 --> 00:46:49,420
PURPOSE TRACK. WE SHOULD HAVE 

1222
00:46:49,420 --> 00:46:52,624
REACHED TWO ADDITIONAL AGENTS 

1223
00:46:52,624 --> 00:47:00,698
OF DISEASE QUALIFICATIONS AND 

1224
00:47:00,698 --> 00:47:03,101
SYMPTOMATICAL TREATMENT 

1225
00:47:03,101 --> 00:47:03,768
ENTERING CLINICAL TRIALS.

1226
00:47:03,768 --> 00:47:04,302
TO ACHIEVE THIS WE NEED TO 

1227
00:47:04,302 --> 00:47:04,769
ENHANCE THE CLINICAL 

1228
00:47:04,769 --> 00:47:05,837
INFRASTRUCTURE SUPPORTING LEVY 

1229
00:47:05,837 --> 00:47:06,270
BODY DEMENTIA TRACK 

1230
00:47:06,270 --> 00:47:10,241
DEVELOPMENT.  THIS WOULD PUT AT 

1231
00:47:10,241 --> 00:47:15,513
THE PHASE 0 CLINICAL TRIAL 

1232
00:47:15,513 --> 00:47:21,819
STAGE, GET THOSE FACILITIES AND 

1233
00:47:21,819 --> 00:47:22,387
PERSONNEL BUT BRINGING NEW 

1234
00:47:22,387 --> 00:47:22,954
PEOPLE, SO WE NEED TO BRING 

1235
00:47:22,954 --> 00:47:24,255
INTO THE FIELD RESEARCHERS INTO 

1236
00:47:24,255 --> 00:47:26,124
LEVY BODY DEMENTIA. 

1237
00:47:26,124 --> 00:47:30,428
THERE ARE NOT THAT MANY 

1238
00:47:30,428 --> 00:47:31,062
VALIDATED SCALES FOR LEVY BODY 

1239
00:47:31,062 --> 00:47:31,663
SPECIFICALLY AND WE NEED TO 

1240
00:47:31,663 --> 00:47:35,500
REFINE THEM TO HAVE THE MOST 

1241
00:47:35,500 --> 00:47:36,200
ACCURATE CLINICAL TRIAL OUTCOME 

1242
00:47:36,200 --> 00:47:43,007
MEASURES. SO WE NEED THESE 

1243
00:47:43,007 --> 00:47:43,608
SPECIFIC SCALES THAT CAPTURE 

1244
00:47:43,608 --> 00:47:44,242
ALL THE SIGNS AND SYMPTOMS THAT 

1245
00:47:44,242 --> 00:47:44,776
ARE PRESENT IN LEVY BODY 

1246
00:47:44,776 --> 00:47:45,176
DEMENTIA.

1247
00:47:45,176 --> 00:47:49,914
WE ALSO NEED TO-- THIS IS 

1248
00:47:49,914 --> 00:47:51,249
(INDISCERNIBLE) ENHANCE OPEN 

1249
00:47:51,249 --> 00:47:55,486
SOURCE INFRASTRUCTURE TO AID IN 

1250
00:47:55,486 --> 00:47:56,054
STREAMLINING THE SHARING OF 

1251
00:47:56,054 --> 00:47:56,654
DATA AND SAMPLES COLLECTED IN 

1252
00:47:56,654 --> 00:48:00,258
CLINICAL TRIALS. 

1253
00:48:00,258 --> 00:48:02,293
WE NEED TO HARMONIZE AND HAVE 

1254
00:48:02,293 --> 00:48:03,461
GENERALIZABLE MEASURES ACROSS 

1255
00:48:03,461 --> 00:48:06,397
THE LBD CLINICAL TRIAL SO WE 

1256
00:48:06,397 --> 00:48:06,998
CAN COMPARE APPLES TO APPLES 

1257
00:48:06,998 --> 00:48:07,465
THE RESULTS. 

1258
00:48:07,465 --> 00:48:10,635
NEXT SLIDE. 

1259
00:48:10,635 --> 00:48:11,402
SO HERE WE ARE GOING TO BE 

1260
00:48:11,402 --> 00:48:15,473
MOVING TO THE LBD COHORTS.  

1261
00:48:15,473 --> 00:48:17,075
HERE THE RECOMMENDATIONS ARE TO 

1262
00:48:17,075 --> 00:48:19,243
EXPAND AND DEVELOP CLINICALLY, 

1263
00:48:19,243 --> 00:48:25,083
BIOLOGICALLY AND GENETICALLY 

1264
00:48:25,083 --> 00:48:31,322
PHENOTYPE COHORTS. AS WE SAW IN 

1265
00:48:31,322 --> 00:48:31,956
PRE-IS PRESENTATIONS THESE ARE 

1266
00:48:31,956 --> 00:48:32,557
COMPLEX PROBLEMS THAT NEED TO 

1267
00:48:32,557 --> 00:48:33,091
BE TACKLED FROM MULTIPLE 

1268
00:48:33,091 --> 00:48:33,658
ANGLES. REFILL THESE BOARDS 

1269
00:48:33,658 --> 00:48:34,158
WOULD REPRESENT THE USE 

1270
00:48:34,158 --> 00:48:34,792
POPULATION OF INDIVIDUALS WILL 

1271
00:48:34,792 --> 00:48:44,001
HAVE LEVY BODY DEMENTIA. AND 

1272
00:48:44,001 --> 00:48:44,469
THIS FRAMES ON THE 

1273
00:48:44,469 --> 00:48:45,069
PRE-SYMPTOMATICALLY STAGES TO 

1274
00:48:45,069 --> 00:48:45,470
AUTOPSY. 

1275
00:48:45,470 --> 00:48:51,409
NEXT SLIDE. 

1276
00:48:51,409 --> 00:48:51,909
THERE ARE SEVERAL COVERT 

1277
00:48:51,909 --> 00:48:52,643
LOOKING AT THIS FROM DIFFERENT 

1278
00:48:52,643 --> 00:48:53,311
ANGLES. ALWAYS SHOW THE RESULTS 

1279
00:48:53,311 --> 00:48:57,014
OF THE US LEVY BODY DEMENTIA 

1280
00:48:57,014 --> 00:49:01,419
CONSORTIUM SPONSORED BY NINDS. 

1281
00:49:01,419 --> 00:49:03,554
THERE ARE ADDITIONAL COHORTS 

1282
00:49:03,554 --> 00:49:04,956
LOOKING AT PARKINSON'S DISEASE; 

1283
00:49:04,956 --> 00:49:05,523
AND THEY ARE ADEQUATE LEGAL 

1284
00:49:05,523 --> 00:49:13,097
STATUS SO NINDS IS SUPPORTING 

1285
00:49:13,097 --> 00:49:13,731
NAPS LOOKING AT BRAIN DISORDER 

1286
00:49:13,731 --> 00:49:15,099
SLEEPING BEHAVIOR, WHICH IS A 

1287
00:49:15,099 --> 00:49:15,933
CLINICAL STAGE FOR PARKINSON'S 

1288
00:49:15,933 --> 00:49:21,172
AND LEVY BODY DEMENTIA. AND 

1289
00:49:21,172 --> 00:49:21,739
PPMI IS LOOKING AT MULTIPLE 

1290
00:49:21,739 --> 00:49:22,373
STAGES OF PARKINSON'S DISEASE, 

1291
00:49:22,373 --> 00:49:28,146
AT THE (INDISCERNIBLE), GENETIC 

1292
00:49:28,146 --> 00:49:31,682
COHORT SPEARHEADED BY THE -- 

1293
00:49:31,682 --> 00:49:32,283
FOUNDATION AND THERE WILL BE 

1294
00:49:32,283 --> 00:49:36,254
ADDITIONAL COHORTS THROUGH THE 

1295
00:49:36,254 --> 00:49:36,854
CENTERS OF EXCELLENCE NETWORK 

1296
00:49:36,854 --> 00:49:37,421
AND WE WILL SHOW SOME DATA 

1297
00:49:37,421 --> 00:49:40,224
ABOUT THAT LATER. 

1298
00:49:40,224 --> 00:49:40,792
THERE ARE SOME OF THE STUDIES 

1299
00:49:40,792 --> 00:49:42,627
OR COHORTS ABOUT MORE SPECIFIC 

1300
00:49:42,627 --> 00:49:46,464
ACTS. -- LOOKING AT THE 

1301
00:49:46,464 --> 00:49:49,367
BIOMARKERS AND FITS FOR MANY OF 

1302
00:49:49,367 --> 00:49:50,535
THE COHORTS WE TALKED TODAY TO 

1303
00:49:50,535 --> 00:49:55,873
OFFER -- (INDISCERNIBLE) AND 

1304
00:49:55,873 --> 00:49:56,507
GP2 IS FOCUSING ON THE GENETICS 

1305
00:49:56,507 --> 00:50:00,812
IN THEIR EFFORTS TO HARMONIZE 

1306
00:50:00,812 --> 00:50:01,445
WITH EUROPEAN COHORTS AND OTHER 

1307
00:50:01,445 --> 00:50:02,580
COLLEAGUES TO GET COMMON 

1308
00:50:02,580 --> 00:50:03,447
ELEMENTS. THIS HAS BEEN DONE IN 

1309
00:50:03,447 --> 00:50:05,817
THE INTERNATIONAL LEVY BODY 

1310
00:50:05,817 --> 00:50:08,019
DEMENTIA CONFERENCE, 2019, 

1311
00:50:08,019 --> 00:50:09,053
2022, 2025.

1312
00:50:09,053 --> 00:50:12,290
NEXT SLIDE. 

1313
00:50:12,290 --> 00:50:15,593
HERE I'M PRESENTING SOME 

1314
00:50:15,593 --> 00:50:21,365
RESULTS OF NAPS, THE 

1315
00:50:21,365 --> 00:50:21,933
(INDISCERNIBLE) COHORT. THE 

1316
00:50:21,933 --> 00:50:22,600
RECENTLY PRESENTED THE BASELINE 

1317
00:50:22,600 --> 00:50:25,169
DATA AND THEY ALSO SHOWED HOW 

1318
00:50:25,169 --> 00:50:31,976
THEY WERE ABLE TO VALIDATE AN 

1319
00:50:31,976 --> 00:50:32,610
RPD SPECIFIC SKILL THAT CAN BE 

1320
00:50:32,610 --> 00:50:33,177
USED IN CLINICAL TRIALS AND 

1321
00:50:33,177 --> 00:50:36,514
CLINICAL PRACTICE ALSO THE 

1322
00:50:36,514 --> 00:50:38,216
PPMI, HAS BEEN A RECENT 

1323
00:50:38,216 --> 00:50:38,716
IMPLEMENTATION OF SOME 

1324
00:50:38,716 --> 00:50:39,550
BIOMARKERS THAT WILL BE 

1325
00:50:39,550 --> 00:50:40,952
PRESENTED LATER THAT HELP WITH 

1326
00:50:40,952 --> 00:50:43,955
THE BIOLOGICAL DEFINITIONS OF 

1327
00:50:43,955 --> 00:50:45,389
LEVY BODY DISEASE ALTHOUGH WE 

1328
00:50:45,389 --> 00:50:53,731
ARE FINDING THAT THERE ARE SOME 

1329
00:50:53,731 --> 00:50:54,332
CLINICAL SYMPTOMS OF DISEASE 

1330
00:50:54,332 --> 00:50:55,566
WILL HOW THE INTERACTION 

1331
00:50:55,566 --> 00:50:56,067
ANALOGIES THAT AFFECT 

1332
00:50:56,067 --> 00:50:57,068
CORRELATION WITH BIOMARKERS AND 

1333
00:50:57,068 --> 00:50:58,936
THE OVERALL RESULTS. 

1334
00:50:58,936 --> 00:51:00,638
NEXT SLIDE. 

1335
00:51:00,638 --> 00:51:09,680
AND THE US LBD CONSORTIUM WILL 

1336
00:51:09,680 --> 00:51:11,916
EVALUATE THE (INDISCERNIBLE), 

1337
00:51:11,916 --> 00:51:14,352
AND HOW PREVALENT THE 

1338
00:51:14,352 --> 00:51:15,319
BIOMARKERS ARE. AND WE KNOW 

1339
00:51:15,319 --> 00:51:15,920
THEY AFFECT THE CLINICAL 

1340
00:51:15,920 --> 00:51:16,487
PROGRESSION AND IT WILL BE 

1341
00:51:16,487 --> 00:51:19,323
IMPORTANT FOR THE DESIGN OF 

1342
00:51:19,323 --> 00:51:25,363
CLINICAL TRIALS IN DLB FOR HALF 

1343
00:51:25,363 --> 00:51:30,234
OF THE PEOPLE THEY EVALUATE THE 

1344
00:51:30,234 --> 00:51:30,768
BIOLOGICAL DEFINITION OF 

1345
00:51:30,768 --> 00:51:31,235
BIOMARKERS...

1346
00:51:31,235 --> 00:51:32,536
>> TWO MINUTES..

1347
00:51:32,536 --> 00:51:33,971
>> DR. TOLEDO ATUCHA:
THANK 

1348
00:51:33,971 --> 00:51:39,510
YOU.  WE RECEIVED OVER 6000 

1349
00:51:39,510 --> 00:51:40,077
PEOPLE WERE EVALUATED FOR 

1350
00:51:40,077 --> 00:51:42,146
DIFFERENT DEMENTIAS. 500 OF 

1351
00:51:42,146 --> 00:51:45,950
THEM HAVE LEVY BODY DEMENTIA, 

1352
00:51:45,950 --> 00:51:49,587
BUT FROM THIS GROUP LESSON 1/4 

1353
00:51:49,587 --> 00:51:52,890
HAD LDB SKILLS. 

1354
00:51:52,890 --> 00:51:57,995
CLINICAL SCALES. WE NEED THESE 

1355
00:51:57,995 --> 00:51:58,562
COHORT SO THEY CAN FEED THE 

1356
00:51:58,562 --> 00:52:00,564
NEXT RECOMMENDATIONS THAT WILL 

1357
00:52:00,564 --> 00:52:01,132
BE PRESENTED. 

1358
00:52:01,132 --> 00:52:03,401
NEXT SLIDE. 

1359
00:52:03,401 --> 00:52:06,170
SO, OUR RECOMMENDATIONS TO 

1360
00:52:06,170 --> 00:52:11,275
EXPAND AND DEVELOP A COHORT 

1361
00:52:11,275 --> 00:52:12,777
THAT ENCOMPASSES ALL THE STAGES.

1362
00:52:12,777 --> 00:52:13,277
 WE WANT MORE FREQUENT 

1363
00:52:13,277 --> 00:52:21,285
ASSESSMENT.  AND WE ALSO THINK 

1364
00:52:21,285 --> 00:52:21,919
THE DIGITAL TOOLS AND BIO FLUID 

1365
00:52:21,919 --> 00:52:22,520
COLLECTION WILL BE HELPFUL TO 

1366
00:52:22,520 --> 00:52:23,321
GET MORE TESTING, THIS WILL 

1367
00:52:23,321 --> 00:52:27,892
HELP THE RECOMMENDATIONS 3-5.  

1368
00:52:27,892 --> 00:52:28,526
WE THINK THAT THIS PARTICIPANT 

1369
00:52:28,526 --> 00:52:29,093
IN THE STUDY SHOULD BROADLY 

1370
00:52:29,093 --> 00:52:30,394
REPRESENT US INDIVIDUALS LIVING 

1371
00:52:30,394 --> 00:52:31,329
WITH (INDISCERNIBLE). 

1372
00:52:31,329 --> 00:52:36,133
NEXT SLIDE. 

1373
00:52:36,133 --> 00:52:36,667
WE WILL NEED PHENOTYPING OF 

1374
00:52:36,667 --> 00:52:39,437
CRITICAL MEASURES.  BUT WE ALSO 

1375
00:52:39,437 --> 00:52:41,138
WANT TO INCLUDE MEASURES THAT 

1376
00:52:41,138 --> 00:52:49,513
INCLUDE (INDISCERNIBLE), 

1377
00:52:49,513 --> 00:52:50,081
COMORBIDITY CONDITIONS AND 

1378
00:52:50,081 --> 00:52:52,116
CO-PATHOLOGIES AND DIGITAL BIO 

1379
00:52:52,116 --> 00:52:52,650
MARKERS, WE NEED TO TRAIN 

1380
00:52:52,650 --> 00:52:54,852
WORKFORCE WITH THE DIFFERENT 

1381
00:52:54,852 --> 00:52:55,586
SKILLS AND EXPAND THE SCOPE OF 

1382
00:52:55,586 --> 00:52:57,822
RESEARCH ON THE PROBLEM THAT IS 

1383
00:52:57,822 --> 00:52:58,756
AVAILABLE THAT WE HAVE SHOWN IS 

1384
00:52:58,756 --> 00:53:03,661
VERY REDUCED. 

1385
00:53:03,661 --> 00:53:04,195
AND THE COMMON TOPIC TODAY, 

1386
00:53:04,195 --> 00:53:04,729
HARMONIZATION OF DATA IS 

1387
00:53:04,729 --> 00:53:08,165
NECESSARY ACROSS THE COHORT.  

1388
00:53:08,165 --> 00:53:08,833
WE NEED TO DEVELOP GUIDELINES 

1389
00:53:08,833 --> 00:53:09,367
TO HARMONIZE STUDIES AND 

1390
00:53:09,367 --> 00:53:10,768
FACILITATE COMPARISONS. 

1391
00:53:10,768 --> 00:53:21,245
NEXT I WILL GIVE THE PODIUM TO 

1392
00:53:26,650 --> 00:53:28,719
DR. MORMINO TO TALK ABOUT 

1393
00:53:28,719 --> 00:53:30,688
BIOMARKERS. 

1394
00:53:30,688 --> 00:53:35,259
>> DR. MORMINO: THANK YOU
I AM 

1395
00:53:35,259 --> 00:53:35,893
FROM THE COMMITTEE THAT DO NOT 

1396
00:53:35,893 --> 00:53:36,427
REFLECT THE POLICY OF THE 

1397
00:53:36,427 --> 00:53:36,894
NATIONAL INSTITUE OF 

1398
00:53:36,894 --> 00:53:37,561
NEUROLOIGCAL DISORDERS AND 

1399
00:53:37,561 --> 00:53:42,366
STROKE OR NIH. 

1400
00:53:42,366 --> 00:53:44,769
IN THE SPACE BIOMARKERS THAT 

1401
00:53:44,769 --> 00:53:45,302
CAPTURE HALLMARK DISEASE 

1402
00:53:45,302 --> 00:53:45,936
PATHOLOGIES AND THE PROGRESSION 

1403
00:53:45,936 --> 00:53:49,040
OF THESE PATHOLOGIES HAVE BEEN 

1404
00:53:49,040 --> 00:53:49,673
CRITICAL FOR OUR UNDERSTANDING 

1405
00:53:49,673 --> 00:53:50,608
OF THE NATURAL HISTORY OF 

1406
00:53:50,608 --> 00:53:53,411
ALZHEIMER'S DISEASE. 

1407
00:53:53,411 --> 00:53:56,514
THIS BIOMARKER WORK HAS ALSO 

1408
00:53:56,514 --> 00:53:57,081
BEEN CRITICAL FOR CLINICAL 

1409
00:53:57,081 --> 00:54:01,952
TRIAL DESIGN IN THE AD SPACE. 

1410
00:54:01,952 --> 00:54:02,520
THIS INCLUDES BOTH ENROLLMENT 

1411
00:54:02,520 --> 00:54:04,221
OF INDIVIDUALS INTO TRIALS, 

1412
00:54:04,221 --> 00:54:06,757
STRATIFICATION OF ANALYSES, AND 

1413
00:54:06,757 --> 00:54:07,324
ALSO ASSESSMENT OF DISEASE 

1414
00:54:07,324 --> 00:54:08,159
MODIFICATION. 

1415
00:54:08,159 --> 00:54:11,162
AND VERY RECENTLY IN THE AD 

1416
00:54:11,162 --> 00:54:15,132
SPACE WE ARE SEEING THESE 

1417
00:54:15,132 --> 00:54:15,733
BIOMARKERS USED IN THE ACTUAL 

1418
00:54:15,733 --> 00:54:19,303
CLINICAL CONTEXT FOR DECISIONS 

1419
00:54:19,303 --> 00:54:19,837
SURROUNDING ANTI-AMYLOID 

1420
00:54:19,837 --> 00:54:20,271
THERAPIES. 

1421
00:54:20,271 --> 00:54:22,873
NEXT SLIDE. 

1422
00:54:22,873 --> 00:54:28,546
YEAH, IN PARALLEL TO THESE AD 

1423
00:54:28,546 --> 00:54:29,080
EFFORTS MULTIPLE RECENT 

1424
00:54:29,080 --> 00:54:29,680
FRAMEWORKS HAVE BEEN PROPOSED 

1425
00:54:29,680 --> 00:54:33,484
IN THE LEVY BODY SPACE 

1426
00:54:33,484 --> 00:54:43,994
HIGHLIGHTING OPPORTUNITIES TO 

1427
00:54:44,595 --> 00:54:45,496
LEVERAGE BOTH DISEASE SPECIFIC 

1428
00:54:45,496 --> 00:54:46,097
BIOMARKERS AND BIOMARKERS OF 

1429
00:54:46,097 --> 00:54:51,936
PROGRESSION TO UNDERSTAND LEVY 

1430
00:54:51,936 --> 00:54:52,536
BODY PROGRESSION AND CLINICAL 

1431
00:54:52,536 --> 00:54:55,873
DESIGN IN RESEARCH CONTEXT. 

1432
00:54:55,873 --> 00:54:56,440
THIS FORMS THE BACKGROUND FOR 

1433
00:54:56,440 --> 00:54:57,074
THE TWO RECOGNITIONS I'M GOING 

1434
00:54:57,074 --> 00:54:59,410
TO GO OVER. RECOMMENDATION 3 IS 

1435
00:54:59,410 --> 00:55:03,147
FOCUSED ON DIAGNOSTIC 

1436
00:55:03,147 --> 00:55:05,683
BIOMARKERS, DISEASE SPECIFIC TO 

1437
00:55:05,683 --> 00:55:07,384
REFINE AND VALIDATE EXISTING 

1438
00:55:07,384 --> 00:55:08,018
BIOMARKERS IN THIS CONTEXT AND 

1439
00:55:08,018 --> 00:55:09,487
ALSO DEVELOP NEW BIOMARKERS 

1440
00:55:09,487 --> 00:55:11,422
RELATED TO ACTUAL LEVY BODY 

1441
00:55:11,422 --> 00:55:12,923
PATHOLOGY. 

1442
00:55:12,923 --> 00:55:15,526
AND ALSO APPLY THESE BIOMARKERS 

1443
00:55:15,526 --> 00:55:18,629
IN THE CONTEXT OF MULTIPLE 

1444
00:55:18,629 --> 00:55:19,864
ETIOLOGY DEMENTIA. 

1445
00:55:19,864 --> 00:55:24,268
NEXT SLIDE. 

1446
00:55:24,268 --> 00:55:24,702
SO WE HAVE SEEN TRULY 

1447
00:55:24,702 --> 00:55:25,236
REMARKABLE BREAKTHROUGHS 

1448
00:55:25,236 --> 00:55:27,505
RECENTLY IN THE FIELD, WITH THE 

1449
00:55:27,505 --> 00:55:35,880
SUCCESS OF ROBUST BIOMARKERS 

1450
00:55:35,880 --> 00:55:36,447
MEASURING ALPHA (PHONETIC) 

1451
00:55:36,447 --> 00:55:39,316
NUCLEI PATHOLOGY IN VIVO, 

1452
00:55:39,316 --> 00:55:45,489
AVAILABLE FOR SPINAL FLUID AND 

1453
00:55:45,489 --> 00:55:46,924
SKIN BIOPSIES HIGHLY SPECIFIC 

1454
00:55:46,924 --> 00:55:47,525
INITIAL VERY GOOD SENSITIVITY 

1455
00:55:47,525 --> 00:55:49,460
TO UNDERLYING PATHOLOGY. 

1456
00:55:49,460 --> 00:55:53,164
PAVING THE WAY FOR IMMEDIATE 

1457
00:55:53,164 --> 00:55:54,465
OPPORTUNITIES RELATED TO 

1458
00:55:54,465 --> 00:55:55,032
DIFFERENTIAL DIAGNOSIS AND 

1459
00:55:55,032 --> 00:55:56,100
EARLY DETECTION OF THESE 

1460
00:55:56,100 --> 00:55:56,800
PATHOLOGIES IN VIVO. 

1461
00:55:56,800 --> 00:55:59,370
NEXT SLIDE. 

1462
00:55:59,370 --> 00:56:03,007
SO THIS LEADS DIRECTLY INTO OUR 

1463
00:56:03,007 --> 00:56:05,643
RECOMMENDATION.  WE ARE VERY 

1464
00:56:05,643 --> 00:56:06,210
EXCITED ABOUT THESE CURRENT 

1465
00:56:06,210 --> 00:56:09,046
BIOMARKERS. 

1466
00:56:09,046 --> 00:56:10,147
ONE OF THE MAIN LIMITATIONS IS 

1467
00:56:10,147 --> 00:56:11,482
THAT THEY PROVIDE ONLY A BINARY 

1468
00:56:11,482 --> 00:56:13,717
READOUT, YES/NO MEASURE FOR THE 

1469
00:56:13,717 --> 00:56:17,955
MOST PART.  SO THAT IS ONE 

1470
00:56:17,955 --> 00:56:19,523
RECOMMENDATION, TO BE ABLE TO 

1471
00:56:19,523 --> 00:56:20,824
GET MORE OF A CONTINUUM OF 

1472
00:56:20,824 --> 00:56:24,995
DISEASE, RELATED TO ALPHA 

1473
00:56:24,995 --> 00:56:28,199
NUCLEUS DEPOSITION. 

1474
00:56:28,199 --> 00:56:28,799
AND THESE BIOMARKERS OBVIOUSLY 

1475
00:56:28,799 --> 00:56:29,366
DO NOT TELL US WHERE IN THE 

1476
00:56:29,366 --> 00:56:33,504
BRAIN THE A-SYNUCLEIN IS 

1477
00:56:33,504 --> 00:56:44,048
DEPOSIT AND THEY ARE CURRENTLY 

1478
00:56:45,883 --> 00:56:46,817
MULTIPLE EFFORTS UNDERWAY WE 

1479
00:56:46,817 --> 00:56:52,289
ARE SEEING EXCITING PROGRESS, 

1480
00:56:52,289 --> 00:56:55,559
NEURAL A-SYNUCLEIN  INCLUSIONS 

1481
00:56:55,559 --> 00:56:56,193
AND ANOTHER RECOGNITION RELATED 

1482
00:56:56,193 --> 00:56:57,828
TO THESE RECENT ADVANCEMENTS 

1483
00:56:57,828 --> 00:56:59,530
ARE DISCLOSURE PROTOCOLS 

1484
00:56:59,530 --> 00:57:00,097
THEMSELVES. THE ABILITY TO 

1485
00:57:00,097 --> 00:57:00,664
ACTUALLY COMMUNICATE THESE 

1486
00:57:00,664 --> 00:57:04,969
RESULTS, THESE A-SYNUCLEIN 

1487
00:57:04,969 --> 00:57:05,569
POSITIVE RESULTS BACK TO OUR 

1488
00:57:05,569 --> 00:57:13,777
RESEARCH PARTICIPANTS.  AND SO 

1489
00:57:13,777 --> 00:57:14,378
THIS IS A NEW OPPORTUNITY IN 

1490
00:57:14,378 --> 00:57:15,479
THESE PROTOCOLS. THEY NEEDED TO 

1491
00:57:15,479 --> 00:57:17,114
BE DEVELOPED AND BETTER 

1492
00:57:17,114 --> 00:57:17,681
UNDERSTOOD IN TERMS OF THE 

1493
00:57:17,681 --> 00:57:18,315
RESEARCH PROTOCOLS THAT WE HAVE 

1494
00:57:18,315 --> 00:57:20,017
THESE BINARY OPS AVAILABLE TO 

1495
00:57:20,017 --> 00:57:20,317
US. 

1496
00:57:20,317 --> 00:57:23,120
NEXT SLIDE. 

1497
00:57:23,120 --> 00:57:23,721
TO MOVING ON TO RECOMMENDATION 

1498
00:57:23,721 --> 00:57:31,228
NUMBER 4. 

1499
00:57:31,228 --> 00:57:31,862
SO HERE WE ARE FOCUSED ON OTHER 

1500
00:57:31,862 --> 00:57:32,463
PROCESSES AND MECHANISMS THAT 

1501
00:57:32,463 --> 00:57:35,165
ARE RELEVANT FOR LEVY BODY 

1502
00:57:35,165 --> 00:57:36,867
PROGRESSION BEYOND THESE 

1503
00:57:36,867 --> 00:57:37,501
BIOMARKER READOUTS OF THE 

1504
00:57:37,501 --> 00:57:39,236
DISEASE ITSELF. 

1505
00:57:39,236 --> 00:57:39,970
AND THIS IS CENTERED AROUND THE 

1506
00:57:39,970 --> 00:57:44,208
DEVELOPMENT OR REFINEMENT OF 

1507
00:57:44,208 --> 00:57:44,775
BIOMARKERS RELATED TO MANY 

1508
00:57:44,775 --> 00:57:45,342
DIFFERENT PROCESSES THAT WE 

1509
00:57:45,342 --> 00:57:46,644
FEEL ARE IMPORTANT AND THIS 

1510
00:57:46,644 --> 00:57:50,114
INCLUDES NEURAL INJURY AND 

1511
00:57:50,114 --> 00:57:53,517
NEURO TRANSMITTERS AND 

1512
00:57:53,517 --> 00:57:54,084
NEURODEGENERATION, THAT ARE 

1513
00:57:54,084 --> 00:57:54,718
BOTH PREDICTIVE AND PROGNOSTIC 

1514
00:57:54,718 --> 00:57:57,688
OF THE DISEASE, IMPORTANTLY 

1515
00:57:57,688 --> 00:57:58,322
PROVIDE MONITORING TO TRACK THE 

1516
00:57:58,322 --> 00:57:58,889
ACTUAL PROGRESSION OF THE 

1517
00:57:58,889 --> 00:58:00,724
DISEASE. 

1518
00:58:00,724 --> 00:58:05,496
THESE BIOMARKERS WILL ALSO 

1519
00:58:05,496 --> 00:58:07,331
ALLOW US TO BETTER IDENTIFY 

1520
00:58:07,331 --> 00:58:08,299
WHETHER TARGETING ENGAGEMENT IS 

1521
00:58:08,299 --> 00:58:08,866
HAPPENING IN THE CONTEXT OF 

1522
00:58:08,866 --> 00:58:09,466
THERAPEUTIC INTERVENTIONS AS 

1523
00:58:09,466 --> 00:58:09,800
WELL. 

1524
00:58:09,800 --> 00:58:12,436
NEXT SLIDE. 

1525
00:58:12,436 --> 00:58:16,707
SO HERE-- THIS IS A VERY BROAD 

1526
00:58:16,707 --> 00:58:17,274
RECOMMENDATION, AND REALLY 

1527
00:58:17,274 --> 00:58:19,777
CRITICAL.  THERE IS A LOT OF 

1528
00:58:19,777 --> 00:58:20,944
WORK TO BE DONE SO WE HAVE A 

1529
00:58:20,944 --> 00:58:21,512
FAIR AMOUNT OF DETAILED 

1530
00:58:21,512 --> 00:58:23,113
RECOMMENDATIONS TO FILL THIS 

1531
00:58:23,113 --> 00:58:25,983
GOAL. 

1532
00:58:25,983 --> 00:58:26,684
I'M GOING TO GO THROUGH THEM 

1533
00:58:26,684 --> 00:58:29,853
ONE AT A TIME HERE. 

1534
00:58:29,853 --> 00:58:30,387
SO AS I SAID, WE HAVE THESE 

1535
00:58:30,387 --> 00:58:37,328
REALLY GREAT MARKERS FOR 

1536
00:58:37,328 --> 00:58:37,961
A-SYNUCLEIN RIGHT NOW, BUT THE 

1537
00:58:37,961 --> 00:58:38,595
OTHER PROCESSES THAT NEED TO BE 

1538
00:58:38,595 --> 00:58:40,497
MEASURED IN TERMS OF 

1539
00:58:40,497 --> 00:58:41,031
BIOMARKERS, SO WE NEED TO 

1540
00:58:41,031 --> 00:58:41,832
IDENTIFY A NUMBER OF PATHWAYS 

1541
00:58:41,832 --> 00:58:48,605
HERE, SYNAPTIC, LYSOSOMAL, 

1542
00:58:48,605 --> 00:58:50,374
MITOCHONDRIAL, IMMUNOLOGIC AND 

1543
00:58:50,374 --> 00:58:51,475
OTHER PROCESSES RELATED TO 

1544
00:58:51,475 --> 00:58:54,478
A-SYNUCLEIN PATHOLOGY, 

1545
00:58:54,478 --> 00:58:55,112
DIFFERENT THAN THE PATHOLOGICAL 

1546
00:58:55,112 --> 00:58:58,349
CONCLUSION THEMSELVES. 

1547
00:58:58,349 --> 00:58:59,650
THERE'S A LOT OF WORK IN THE 

1548
00:58:59,650 --> 00:59:00,217
NEUROTRANSMITTER SPACE, AND 

1549
00:59:00,217 --> 00:59:01,051
THESE TOOLS ARE OPPORTUNITIES 

1550
00:59:01,051 --> 00:59:03,187
TO FURTHER REFINE THEM AND 

1551
00:59:03,187 --> 00:59:06,523
IMPROVE UPON THEM.  THIS IS 

1552
00:59:06,523 --> 00:59:07,157
SOMETHING THAT HAS BEEN WIDELY 

1553
00:59:07,157 --> 00:59:11,395
IMPLEMENTED IN THE LEVY BODY 

1554
00:59:11,395 --> 00:59:11,929
SPACE AND THERE IS ALSO 

1555
00:59:11,929 --> 00:59:13,630
INTEREST IN DEGENERATIVE 

1556
00:59:13,630 --> 00:59:14,164
CHANGES AND THESE CAN BE 

1557
00:59:14,164 --> 00:59:15,766
MEASURED WITH BIO FLUIDS AND 

1558
00:59:15,766 --> 00:59:26,210
ALSO MR TOOLS LOOKING FOR 

1559
00:59:29,380 --> 00:59:29,913
INSTANCE AT MELANIN, MRI, AND 

1560
00:59:29,913 --> 00:59:31,949
ION SENSITIVE MRI. 

1561
00:59:31,949 --> 00:59:32,549
WE WANTED TO HIGHLIGHT THAT THE 

1562
00:59:32,549 --> 00:59:35,452
SORT OF DISCOVERY OF NEW 

1563
00:59:35,452 --> 00:59:36,053
BIOMARKERS SHOULD INCLUDE A 

1564
00:59:36,053 --> 00:59:40,224
BROAD TYPES OF POTENTIAL 

1565
00:59:40,224 --> 00:59:46,130
SAMPLES. AND SO BLOOD, CSS, 

1566
00:59:46,130 --> 00:59:51,502
SKIN, COLON, IMAGING FRONT, 

1567
00:59:51,502 --> 00:59:52,136
DIFFERENT MODALITIES AND WE ARE 

1568
00:59:52,136 --> 00:59:53,504
IN THE SPACE WE WANT TO EXPLORE 

1569
00:59:53,504 --> 00:59:54,171
THE FULL RANGE OF POSSIBILITIES 

1570
00:59:54,171 --> 00:59:56,173
HERE. 

1571
00:59:56,173 --> 00:59:57,775
THERE SHOULD ALSO BE THESE 

1572
00:59:57,775 --> 00:59:58,409
BIOMARKERS, THEY REALLY SHOULD 

1573
00:59:58,409 --> 01:00:01,311
BE A CONNECTION BETWEEN BOTH 

1574
01:00:01,311 --> 01:00:03,280
THE HUMAN WORK AND ALSO MODEL 

1575
01:00:03,280 --> 01:00:05,849
SYSTEMS. 

1576
01:00:05,849 --> 01:00:06,383
WE THINK THAT CONNECTION IS 

1577
01:00:06,383 --> 01:00:08,552
QUITE IMPORTANT FOR THESE NOVEL 

1578
01:00:08,552 --> 01:00:10,888
DISCOVERIES. 

1579
01:00:10,888 --> 01:00:11,488
THERE'S ALSO IMPERILED TO THESE 

1580
01:00:11,488 --> 01:00:13,624
BIOLOGICAL MARKERS, A LOT OF 

1581
01:00:13,624 --> 01:00:15,292
INTEREST IN THESE MORE DIGITAL 

1582
01:00:15,292 --> 01:00:19,062
APPROACHES AS WELL. 

1583
01:00:19,062 --> 01:00:19,630
NEUROPHYSIOLOGICAL. LOTS OF 

1584
01:00:19,630 --> 01:00:24,368
IDEAS AROUND THIS. HERE WE ARE 

1585
01:00:24,368 --> 01:00:24,968
LISTING SOMEWHAT OF A LAUNDRY 

1586
01:00:24,968 --> 01:00:26,603
LIST OF THESE POTENTIAL 

1587
01:00:26,603 --> 01:00:32,776
PATHWAYS, WEARABLES, TSG, 

1588
01:00:32,776 --> 01:00:33,377
COMPUTERIZED TESTING INVERSE 

1589
01:00:33,377 --> 01:00:37,681
APPROACHES TO HOME-BASED 

1590
01:00:37,681 --> 01:00:38,148
MONITORING TO CAPTURE 

1591
01:00:38,148 --> 01:00:38,782
ECOLOGICALLY VALID MEASUREMENTS 

1592
01:00:38,782 --> 01:00:42,085
ON OUR PARTICIPANTS. WITH ALL 

1593
01:00:42,085 --> 01:00:49,092
OF THESE THERE NEEDS TO BE 

1594
01:00:49,092 --> 01:00:49,693
ATTENTION TO SCALABILITY AND 

1595
01:00:49,693 --> 01:00:50,294
ACCESSIBILITY AS WE VALIDATE 

1596
01:00:50,294 --> 01:00:52,229
THESE. 

1597
01:00:52,229 --> 01:00:52,796
GIVEN THE SCOPE OF THIS FEEL 

1598
01:00:52,796 --> 01:00:55,432
THERE SHOULD BE WORKSHOPS AND 

1599
01:00:55,432 --> 01:00:59,036
COORDINATED EFFORTS TO ADDRESS 

1600
01:00:59,036 --> 01:00:59,670
FEASIBILITY, AND IMPLEMENTATION 

1601
01:00:59,670 --> 01:01:00,270
OF THESE TOOLS AND ALSO DATA 

1602
01:01:00,270 --> 01:01:00,804
SHARING AS WELL. 

1603
01:01:00,804 --> 01:01:04,575
NEXT SLIDE. 

1604
01:01:04,575 --> 01:01:05,976
A FEW MORE RECOMMENDATIONS 

1605
01:01:05,976 --> 01:01:08,645
HERE. SO FOR ALL THE BIOMARKERS 

1606
01:01:08,645 --> 01:01:11,148
I JUST MENTIONED, THE CONTEXT 

1607
01:01:11,148 --> 01:01:11,882
OF USE IS QUITE IMPORTANT SO 

1608
01:01:11,882 --> 01:01:17,921
THESE BIOMARKERS, WILL THEY BE 

1609
01:01:17,921 --> 01:01:18,388
USED TO DEFINE FUTURE 

1610
01:01:18,388 --> 01:01:20,190
PROGRESSION AND RISK?

1611
01:01:20,190 --> 01:01:22,226
WILL THERE BE USED TO MONITOR 

1612
01:01:22,226 --> 01:01:22,793
SYMPTOMS IN THE CONTEXT OF 

1613
01:01:22,793 --> 01:01:26,497
CLINICAL TRIALS?

1614
01:01:26,497 --> 01:01:27,064
FOCUS IS IMPORTANT TO KEEP IN 

1615
01:01:27,064 --> 01:01:27,731
MIND FOR BIOMARKER DISCOVERY 

1616
01:01:27,731 --> 01:01:31,935
IMPORTANTLY THESE BIOMARKERS 

1617
01:01:31,935 --> 01:01:32,536
WILL BE CRITICAL TO ESTABLISH 

1618
01:01:32,536 --> 01:01:40,811
THAT THEY ARE ASSOCIATED WITH 

1619
01:01:40,811 --> 01:01:41,445
CLINICALLY MEANINGFUL SIGNS AND 

1620
01:01:41,445 --> 01:01:42,079
SYMPTOMS THAT WE ARE INTERESTED 

1621
01:01:42,079 --> 01:01:42,713
IN IN THE CONTEXT OF LBD. THERE 

1622
01:01:42,713 --> 01:01:45,516
IS A GENERAL SENTIMENT THAT 

1623
01:01:45,516 --> 01:01:46,149
DISTAL DISCOVERY MIGHT BENEFIT 

1624
01:01:46,149 --> 01:01:50,454
FROM COORDINATING MULTISITE BIO 

1625
01:01:50,454 --> 01:01:51,021
MARKER STUDIES WITH A BROAD 

1626
01:01:51,021 --> 01:01:51,755
RANGE OF EXPERTISE INCLUDED IN 

1627
01:01:51,755 --> 01:01:55,893
THESE STUDIES, SPANNING 

1628
01:01:55,893 --> 01:01:56,326
CLINICAL BIOMARKER, 

1629
01:01:56,326 --> 01:01:56,860
NEUROPATHIC, STATISTICAL 

1630
01:01:56,860 --> 01:02:03,934
EXPERTISE. 

1631
01:02:03,934 --> 01:02:04,501
AND WHAT SOMETHING LIKE THIS 

1632
01:02:04,501 --> 01:02:05,102
WOULD DO IT WOULD ALLOW US TO 

1633
01:02:05,102 --> 01:02:05,669
BUILD BIGGER COHORTS AND WE 

1634
01:02:05,669 --> 01:02:07,538
HEARD ABOUT THAT IN THE LAST 

1635
01:02:07,538 --> 01:02:08,171
SET OF RECOMMENDATIONS. IT WILL 

1636
01:02:08,171 --> 01:02:09,907
ALLOW US TO COLLECT HARMONIZED 

1637
01:02:09,907 --> 01:02:11,975
DATA ACROSS THE LARGER COHORTS, 

1638
01:02:11,975 --> 01:02:15,112
AND SYNCHRONIZE THOSE EFFORTS. 

1639
01:02:15,112 --> 01:02:16,246
IT WILL ALSO REALLY PROMOTE 

1640
01:02:16,246 --> 01:02:20,350
BROADER DATA SHARING.  THERE 

1641
01:02:20,350 --> 01:02:20,984
WAS A FEELING THAT IF SOMETHING 

1642
01:02:20,984 --> 01:02:22,719
LIKE THIS WERE TO TAKE PLACE, 

1643
01:02:22,719 --> 01:02:25,722
DIGITAL MARKERS SHOULD ALSO BE 

1644
01:02:25,722 --> 01:02:27,291
INCLUDED. BUT INDEPENDENT OF 

1645
01:02:27,291 --> 01:02:27,824
THIS THERE IS ALSO A FAIR 

1646
01:02:27,824 --> 01:02:28,458
AMOUNT OF DATA THAT IS ALREADY 

1647
01:02:28,458 --> 01:02:30,994
OUT THERE.  AND ALSO APPROACHES 

1648
01:02:30,994 --> 01:02:31,628
TO TAKE ADVANTAGE OF THIS DATA 

1649
01:02:31,628 --> 01:02:33,597
THAT ALREADY EXISTS, USING 

1650
01:02:33,597 --> 01:02:34,331
POSTACQUISITION HARMONIZATION 

1651
01:02:34,331 --> 01:02:35,098
PROTOCOLS. AND HERE IS THE 

1652
01:02:35,098 --> 01:02:37,134
EXAMPLE OF ...

1653
01:02:37,134 --> 01:02:42,139
>> TWO MINUTES...

1654
01:02:42,139 --> 01:02:43,907
>> THIS IS AN EXAMPLE OF A

1655
01:02:43,907 --> 01:02:44,341
STUDY THAT COULD BE 

1656
01:02:44,341 --> 01:02:46,777
IMPLEMENTED, MULTIPLE PET 

1657
01:02:46,777 --> 01:02:47,411
SCANS, PERHAPS MRI SEQUENCE TO 

1658
01:02:47,411 --> 01:02:50,948
GET AT THESE BRAIN STEM CHANGES 

1659
01:02:50,948 --> 01:02:51,582
IN OF COURSE IN BIO FLUID DATA 

1660
01:02:51,582 --> 01:02:51,982
AS WELL. 

1661
01:02:51,982 --> 01:02:56,653
NEXT SLIDE. 

1662
01:02:56,653 --> 01:03:00,657
SO SOME COMMON NEEDS ACROSS 

1663
01:03:00,657 --> 01:03:01,158
BOTH, RECOMMENDATIONS I 

1664
01:03:01,158 --> 01:03:02,292
DISCUSSED SO THE COHORTS ARE 

1665
01:03:02,292 --> 01:03:02,859
REALLY CRITICAL FOR THIS. I 

1666
01:03:02,859 --> 01:03:05,562
JUST TALKED ABOUT SPECIFICALLY 

1667
01:03:05,562 --> 01:03:15,339
THE MULTISITE STUDY, BUT THERE 

1668
01:03:15,339 --> 01:03:15,906
ARE DIFFERENT FLAVORS WHERE 

1669
01:03:15,906 --> 01:03:16,506
EXISTING OR NEW COHORTS COULD 

1670
01:03:16,506 --> 01:03:17,140
BE ESTABLISHED INTEGRATE THESE 

1671
01:03:17,140 --> 01:03:20,510
DIFFERENT BIOMARKERS. 

1672
01:03:20,510 --> 01:03:21,078
AND THERE SHOULD BE A DOCTOR 

1673
01:03:21,078 --> 01:03:21,712
DOOLITTLE COMPONENT TO LOOK AT 

1674
01:03:21,712 --> 01:03:23,313
THE PROGRESSION OF THE DISEASE. 

1675
01:03:23,313 --> 01:03:23,880
THE OPPORTUNITY TO LOOK AT 

1676
01:03:23,880 --> 01:03:24,648
POSTMORTEM COMPARISONS, ALSO 

1677
01:03:24,648 --> 01:03:25,282
ESSENTIAL TO VALIDATE THESE 

1678
01:03:25,282 --> 01:03:27,317
BIOMARKERS.  AND THE ABILITY TO 

1679
01:03:27,317 --> 01:03:32,122
ALSO LOOK AT THESE BIOMARKERS 

1680
01:03:32,122 --> 01:03:32,623
IN THE CONTEXT OF MIXED 

1681
01:03:32,623 --> 01:03:35,525
PATHOLOGIES ARE ALSO IMPORTANT. 

1682
01:03:35,525 --> 01:03:35,993
THERE IS ALSO A GENERAL 

1683
01:03:35,993 --> 01:03:36,560
CONSENSUS THAT WE SHOULD BE 

1684
01:03:36,560 --> 01:03:37,127
TARGETING ALL STAGES OF THE 

1685
01:03:37,127 --> 01:03:39,596
DISEASE. THE DISEASE INCLUDES 

1686
01:03:39,596 --> 01:03:42,165
MULTIPLE CLINICAL PHASES, 

1687
01:03:42,165 --> 01:03:44,935
STARTING WITH ASYMPTOMATIC 

1688
01:03:44,935 --> 01:03:45,636
PHASE. BY TRANSITIONING INTO 

1689
01:03:45,636 --> 01:03:48,171
SYMPTOMATIC AND THESE 

1690
01:03:48,171 --> 01:03:48,739
BIOMARKERS WILL LIKELY HAVE 

1691
01:03:48,739 --> 01:03:51,208
DIFFERENT ROLES AND MEANING AT 

1692
01:03:51,208 --> 01:03:51,708
DIFFERENT STAGES OF THE 

1693
01:03:51,708 --> 01:03:54,111
DISEASE.  IT WILL BE IMPORTANT 

1694
01:03:54,111 --> 01:03:55,345
TO INCLUDE THE BROAD RANGE OF 

1695
01:03:55,345 --> 01:03:58,348
ACTUAL STAGES WITH THE DISEASE. 

1696
01:03:58,348 --> 01:03:59,449
AND OF COURSE MANY OF THE 

1697
01:03:59,449 --> 01:04:01,418
MARKERS I MENTIONED, THEY ARE 

1698
01:04:01,418 --> 01:04:02,052
NOT THE MOST SCALABLE THEY USED 

1699
01:04:02,052 --> 01:04:09,960
TO BE AN EYE ON MEASURES THAT 

1700
01:04:09,960 --> 01:04:10,594
ARE NONINVASIVE AND SCALABLE AS 

1701
01:04:10,594 --> 01:04:14,798
WELL.

1702
01:04:14,798 --> 01:04:16,366
 I'M GOING TO PASS IT OVER TO 

1703
01:04:16,366 --> 01:04:19,169
DR. DUGGER FOR THE NEXT SET OF 

1704
01:04:19,169 --> 01:04:20,504
MILESTONES. THANK YOU. 

1705
01:04:20,504 --> 01:04:23,807
>> DR. DUGGER: THANK YOU
ALL.  

1706
01:04:23,807 --> 01:04:27,711
CAN YOU HEAR ME OKAY?

1707
01:04:27,711 --> 01:04:28,278
OKAY THANK YOU ALL FOR TAKING 

1708
01:04:28,278 --> 01:04:31,314
YOUR TIME.  YOU TOOK TIME OUT 

1709
01:04:31,314 --> 01:04:41,658
OF YOUR BUSY SCHEDULE TO ATTEND 

1710
01:04:41,658 --> 01:04:42,225
TODAY, AND TO PROVIDE THIS 

1711
01:04:42,225 --> 01:04:42,793
CRITICAL FEEDBACK ON THESE 

1712
01:04:42,793 --> 01:04:43,393
PROPOSED RECOMMENDATIONS AND 

1713
01:04:43,393 --> 01:04:43,827
PRIORITIES. 

1714
01:04:43,827 --> 01:04:46,296
NEXT SLIDE. 

1715
01:04:46,296 --> 01:04:47,130
EVEN THOUGH YOU SEE MY FACE I 

1716
01:04:47,130 --> 01:04:47,664
WILL BE PRESENTING ON THE 

1717
01:04:47,664 --> 01:04:53,570
GENETICS OR OMICS OF THE LEVY 

1718
01:04:53,570 --> 01:04:54,171
BODY DISEASE AND PINCHHITTING 

1719
01:04:54,171 --> 01:04:57,774
TODAY FOR DOCTOR SONJA SCHOLZ,  

1720
01:04:57,774 --> 01:05:00,043
AND THESE ARE THE DISCLAIMERS. 

1721
01:05:00,043 --> 01:05:01,712
THESE ARE THE REGULATIONS 

1722
01:05:01,712 --> 01:05:05,649
RELATED TO THE OMICS ASPECT AND 

1723
01:05:05,649 --> 01:05:08,819
THE FUNCTIONAL GENOMICS OF THE 

1724
01:05:08,819 --> 01:05:10,687
LEVY BODY DISEASE CONTRIBUTING 

1725
01:05:10,687 --> 01:05:16,226
TO THE ONSET AND PROGRESSION OF 

1726
01:05:16,226 --> 01:05:16,727
LEVY BODY DISEASE USING 

1727
01:05:16,727 --> 01:05:17,494
CHARACTERIZATION AND ANALYSIS 

1728
01:05:17,494 --> 01:05:18,195
TO SUPPORT DRUG DISCOVERY. 

1729
01:05:18,195 --> 01:05:21,898
NEXT SLIDE. 

1730
01:05:21,898 --> 01:05:26,303
SO, WITH THIS SLIDE, THIS IS 

1731
01:05:26,303 --> 01:05:26,937
KIND OF SHOWING GENETICS ALONG 

1732
01:05:26,937 --> 01:05:29,606
WITH BROADER MULTI-OMICS 

1733
01:05:29,606 --> 01:05:30,173
TECHNOLOGIES AND THEY HAVE 

1734
01:05:30,173 --> 01:05:30,674
PROVIDED UNPRECEDENTED 

1735
01:05:30,674 --> 01:05:33,744
OPPORTUNITIES TO DECODE LEVY 

1736
01:05:33,744 --> 01:05:34,377
BODY DEMENTIA AND THIS IS JUST 

1737
01:05:34,377 --> 01:05:35,011
A BRIEF HISTORY OF WHERE WE ARE 

1738
01:05:35,011 --> 01:05:36,646
AT TODAY. 

1739
01:05:36,646 --> 01:05:38,949
IS VERY EXCITING TO SEE THESE 

1740
01:05:38,949 --> 01:05:39,683
ADVANCES FOR OUR ABILITY TO 

1741
01:05:39,683 --> 01:05:40,350
TACKLE THIS CHALLENGING 

1742
01:05:40,350 --> 01:05:45,355
DISEASE. 

1743
01:05:45,355 --> 01:05:47,057
NEXT SLIDE. 

1744
01:05:47,057 --> 01:05:50,627
IN RECOMMENDATION NUMBER 5, WE 

1745
01:05:50,627 --> 01:05:51,228
ARE PARTICULARLY EMPHASIZING 

1746
01:05:51,228 --> 01:05:52,562
WITH THIS RECENT PROGRESS HOW 

1747
01:05:52,562 --> 01:05:55,398
COMPLEX THINGS ARE.  SO WE HAVE 

1748
01:05:55,398 --> 01:05:56,366
THE STRUCTURAL VARIANTS. THERE 

1749
01:05:56,366 --> 01:06:06,810
HAS BEEN A X-CHROMOSOMAL 

1750
01:06:11,648 --> 01:06:12,215
VARIANCE AS WELL AS EPIGENETICS 

1751
01:06:12,215 --> 01:06:12,849
AND TRANSCRIPTOMICS, IMPORTANT 

1752
01:06:12,849 --> 01:06:18,755
TO MEET THIS DISEASE. 

1753
01:06:18,755 --> 01:06:19,322
IN THE ANALYSIS ASPECT WE ARE 

1754
01:06:19,322 --> 01:06:20,791
IN THE AGE OF BIG DATA AND 

1755
01:06:20,791 --> 01:06:21,358
COMPUTATIONAL ANALYSIS FOR 

1756
01:06:21,358 --> 01:06:21,858
NOVEL INSIGHTS ON THESE 

1757
01:06:21,858 --> 01:06:23,527
DISEASES.  AND AGAIN THESE ARE 

1758
01:06:23,527 --> 01:06:27,364
JUST BRIEF, BRIEF OUTLINES. THE 

1759
01:06:27,364 --> 01:06:27,964
HAS BEEN SO MUCH WORK IN THE 

1760
01:06:27,964 --> 01:06:28,498
SPACE AND AGAIN TRYING TO 

1761
01:06:28,498 --> 01:06:29,132
HIGHLIGHT SOME OF THAT. 

1762
01:06:29,132 --> 01:06:31,134
NEXT SLIDE. 

1763
01:06:31,134 --> 01:06:35,338
AND WHEN IT COMES TO DATA AND 

1764
01:06:35,338 --> 01:06:37,607
BIO SPECIMEN PLATFORMS, THERE 

1765
01:06:37,607 --> 01:06:38,141
HAVE BEEN A LOT OF GREAT 

1766
01:06:38,141 --> 01:06:38,775
PLATFORMS THAT ARE OUT IN THE 

1767
01:06:38,775 --> 01:06:39,676
FIELD. AND YOU CAN SEE HERE 

1768
01:06:39,676 --> 01:06:47,517
WITH NICRA AND PD, BP AND SOME 

1769
01:06:47,517 --> 01:06:48,051
OTHERS THAT HAVE GREATLY 

1770
01:06:48,051 --> 01:06:48,618
ADVANCE THE FIELD. 

1771
01:06:48,618 --> 01:06:51,955
NEXT SLIDE. 

1772
01:06:51,955 --> 01:06:52,489
EVEN THOUGH THERE HAS BEEN 

1773
01:06:52,489 --> 01:06:55,091
THESE GREAT ADVANCES, AND I 

1774
01:06:55,091 --> 01:06:55,725
KNOW I WANT TO SO MUCH WORK IN 

1775
01:06:55,725 --> 01:06:56,960
SUCH A BRIEF AMOUNT OF TIME, WE 

1776
01:06:56,960 --> 01:07:02,833
ARE STILL MISSING HERITABILITY, 

1777
01:07:02,833 --> 01:07:03,934
MULTI-OMICS AND ENVIRONMENTAL 

1778
01:07:03,934 --> 01:07:08,205
DATA INTEGRATION EXTEND RISK OF 

1779
01:07:08,205 --> 01:07:12,409
MULTIGENERATIONAL GENETIC 

1780
01:07:12,409 --> 01:07:13,076
RISKS, AS WELL AS CELL TYPE IN 

1781
01:07:13,076 --> 01:07:13,643
TISSUE SPECIFIC CONTEXT OF 

1782
01:07:13,643 --> 01:07:14,711
GENETIC RISK. 

1783
01:07:14,711 --> 01:07:15,912
LARGELY DEEP PHENOTYPE COHORTS 

1784
01:07:15,912 --> 01:07:20,750
WITH MULTI-OMIC DATA AS WELL AS 

1785
01:07:20,750 --> 01:07:21,284
GENOMIC DATA FROM COHORTS 

1786
01:07:21,284 --> 01:07:21,885
REPRESENTATIVE OF THE BROADER 

1787
01:07:21,885 --> 01:07:24,654
US POPULATION.  AND A LOT OF 

1788
01:07:24,654 --> 01:07:25,255
THESE THEMES IF YOU HAVE BEEN 

1789
01:07:25,255 --> 01:07:26,323
ATTENDING MULTIPLE SESSIONS 

1790
01:07:26,323 --> 01:07:26,923
HAVE BEEN THROUGHOUT A LOT OF 

1791
01:07:26,923 --> 01:07:27,424
THESE SESSIONS. 

1792
01:07:27,424 --> 01:07:31,862
NEXT SLIDE. 

1793
01:07:31,862 --> 01:07:33,730
SO BASED ON THESE GAPS, AGAIN 

1794
01:07:33,730 --> 01:07:36,132
OUR RECOMMENDATION 5, IS TO 

1795
01:07:36,132 --> 01:07:39,102
INTEGRATE FUNCTIONAL GENOMICS 

1796
01:07:39,102 --> 01:07:40,503
OF LEVY BODY DISEASE BY THE 

1797
01:07:40,503 --> 01:07:43,607
GENETIC -- CONTRARY TO THE 

1798
01:07:43,607 --> 01:07:51,248
ONSET PROGRESSION OF LEVY BODY 

1799
01:07:51,248 --> 01:07:51,815
DISEASE AND SUPPORTING DRUG 

1800
01:07:51,815 --> 01:07:52,582
DISCOVERY, AND THE ANIMATIONS. 

1801
01:07:52,582 --> 01:07:56,219
NEXT SLIDE. 

1802
01:07:56,219 --> 01:07:56,786
SO WE WANTED TO DISCOVER AND 

1803
01:07:56,786 --> 01:07:57,254
REPLICATE GENETIC AND 

1804
01:07:57,254 --> 01:07:57,954
ENVIRONMENTAL RISK FACTORS. 

1805
01:07:57,954 --> 01:07:59,623
NEXT SLIDE. 

1806
01:07:59,623 --> 01:08:00,390
WE ALSO WANT TO INTEGRATE 

1807
01:08:00,390 --> 01:08:02,726
GENOMICS IN DEEPLY PHENOTYPE 

1808
01:08:02,726 --> 01:08:06,696
COHORTS. 

1809
01:08:06,696 --> 01:08:07,197
FUNCTIONALIZED THESE RISK 

1810
01:08:07,197 --> 01:08:09,799
VARIANCE INTO MECHANISMS, 

1811
01:08:09,799 --> 01:08:11,067
TARGETS AND BIOMARKERS. AGAIN 

1812
01:08:11,067 --> 01:08:11,735
THIS IS JUST REPEATING A LOT OF 

1813
01:08:11,735 --> 01:08:13,503
THE STUFF, MAKING SURE THAT THE 

1814
01:08:13,503 --> 01:08:17,407
MESSAGE IS GETTING ACROSS OF 

1815
01:08:17,407 --> 01:08:19,509
OUR RECOMMENDATIONS INVESTING 

1816
01:08:19,509 --> 01:08:20,310
IN MOLECULAR HETEROGENEITY 

1817
01:08:20,310 --> 01:08:22,145
ACROSS LEVY BODY DISEASE AND 

1818
01:08:22,145 --> 01:08:24,948
RELATED DISORDERS, PRIORITIZING 

1819
01:08:24,948 --> 01:08:25,482
INNOVATIVE ANALYTICS DATA 

1820
01:08:25,482 --> 01:08:25,916
PLATFORMS. 

1821
01:08:25,916 --> 01:08:29,920
NEXT SLIDE. 

1822
01:08:29,920 --> 01:08:31,354
SO NOW I'M GOING TO BE MOVING 

1823
01:08:31,354 --> 01:08:35,558
INTO THE NEUROPATHIC PORTION IN 

1824
01:08:35,558 --> 01:08:36,159
THESE ARE MY DISCLOSURES AND 

1825
01:08:36,159 --> 01:08:36,626
DISCLAIMERS. 

1826
01:08:36,626 --> 01:08:38,094
NEXT SLIDE. 

1827
01:08:38,094 --> 01:08:41,298
THIS IS RECOMMENDATION NUMBER 

1828
01:08:41,298 --> 01:08:47,971
6. WE WANT TO HARMONIZE 

1829
01:08:47,971 --> 01:08:48,538
TECHNIQUES NOT STANDARDIZE, 

1830
01:08:48,538 --> 01:08:51,541
BECAUSE A LOT OF COHORTS AND 

1831
01:08:51,541 --> 01:08:52,142
RESOURCES ALREADY EXIST,  WE 

1832
01:08:52,142 --> 01:08:52,776
DON'T WANT TO NEGATE THOSE FOR 

1833
01:08:52,776 --> 01:08:53,276
THE NEURAL PATHOLOGICAL 

1834
01:08:53,276 --> 01:08:55,712
CHARACTERIZATION OF LEVY BODY 

1835
01:08:55,712 --> 01:08:57,781
DISEASE WERE USING WELL 

1836
01:08:57,781 --> 01:08:58,481
CHARACTERIZED REPRESENTATIVE 

1837
01:08:58,481 --> 01:09:00,517
LEVY BODY COHORTS AND YOU CAN 

1838
01:09:00,517 --> 01:09:01,217
SEE THE DESCRIPTION BENEATH, 

1839
01:09:01,217 --> 01:09:01,952
TRYING TO HAVE MORE DETAILS. 

1840
01:09:01,952 --> 01:09:05,588
NEXT SLIDE. 

1841
01:09:05,588 --> 01:09:07,958
AND SO WITH RESPECT TO RECENT 

1842
01:09:07,958 --> 01:09:09,960
PROGRESS, IT IS ALWAYS GOOD TO 

1843
01:09:09,960 --> 01:09:11,294
KIND OF BENCHMARK. AND SO HERE 

1844
01:09:11,294 --> 01:09:11,928
ARE SOME OF THE DISEASES WE ARE 

1845
01:09:11,928 --> 01:09:13,496
COVERING IN THIS SUMMIT. 

1846
01:09:13,496 --> 01:09:15,131
YOU CAN SEE ALZHEIMER'S 

1847
01:09:15,131 --> 01:09:15,765
DISEASE, BASIC JUST USING THE 

1848
01:09:15,765 --> 01:09:18,468
SEARCH TERM "NEUROPATHOLOGY," 

1849
01:09:18,468 --> 01:09:21,037
AND THEN THE SPECIFIC TERMS 

1850
01:09:21,037 --> 01:09:24,741
EITHER LEVY BODY , DISEASE 

1851
01:09:24,741 --> 01:09:26,710
ALZHEIMER'S, CEREBROVASCULAR, 

1852
01:09:26,710 --> 01:09:29,612
TDP-43. 

1853
01:09:29,612 --> 01:09:33,316
 WITHOUT A SURPRISE YOU CAN 

1854
01:09:33,316 --> 01:09:33,817
SEEALZHEIMER'S DISEASE 

1855
01:09:33,817 --> 01:09:34,451
NEUROPATHOLOGY WINS BY FAR. NOW 

1856
01:09:34,451 --> 01:09:37,120
ALMOST 700 APPLICATIONS 

1857
01:09:37,120 --> 01:09:37,687
(CORRECTION) PUBLICATIONS A 

1858
01:09:37,687 --> 01:09:48,231
YEAR AND THAT FAR OUTWEIGHS TDP 

1859
01:09:48,698 --> 01:09:49,232
AND LEVY BODY SHOWN HERE DOWN 

1860
01:09:49,232 --> 01:09:49,799
ON THIS GRAPH, IT VERY MUCH 

1861
01:09:49,799 --> 01:09:50,633
REMAINS CONSTANT. PRETTY MUCH 

1862
01:09:50,633 --> 01:09:53,303
ON PAR WITH TDP-43 

1863
01:09:53,303 --> 01:09:53,803
NEUROPATHOLOGY. 

1864
01:09:53,803 --> 01:09:58,041
NEXT SLIDE. 

1865
01:09:58,041 --> 01:09:59,809
AND SO SOME OF THE PROGRESS 

1866
01:09:59,809 --> 01:10:02,278
THAT HAS BEEN MADE AND AGAIN 

1867
01:10:02,278 --> 01:10:04,247
EVEN THOUGH WE WERE TALKING IN 

1868
01:10:04,247 --> 01:10:07,150
THE DECISIONS ABOUT BIOMARKERS, 

1869
01:10:07,150 --> 01:10:10,320
A LOT OF THOSE BIOMARKERS 

1870
01:10:10,320 --> 01:10:10,854
CANNOT HAPPEN WITHOUT THE 

1871
01:10:10,854 --> 01:10:11,488
NEUROPATHOLOGY SO THE TITLE OF 

1872
01:10:11,488 --> 01:10:15,058
THE SLIDE IS, RECENT PROGRESS 

1873
01:10:15,058 --> 01:10:17,694
THAT LBD YOUR PATHOLOGY 

1874
01:10:17,694 --> 01:10:20,230
INFORMING BIOMARKER STUDIES, 

1875
01:10:20,230 --> 01:10:20,764
AND THESE ARE SOME OF THE 

1876
01:10:20,764 --> 01:10:21,398
PAPERS THAT HAVE BEEN PUBLISHED 

1877
01:10:21,398 --> 01:10:22,866
SINCE THE LAST SUMMIT. 

1878
01:10:22,866 --> 01:10:23,533
AS WELL AS THERE HAVE BEEN 

1879
01:10:23,533 --> 01:10:27,337
EFFORTS IN HARMONIZATION, 

1880
01:10:27,337 --> 01:10:29,272
ESPECIALLY WITH THE 12 MEASURES 

1881
01:10:29,272 --> 01:10:29,839
ACROSS SIX COMMUNITY-BASED 

1882
01:10:29,839 --> 01:10:30,573
AUTOPSY COHORTS OF DEMENTIA. 

1883
01:10:30,573 --> 01:10:36,146
NEXT SLIDE. 

1884
01:10:36,146 --> 01:10:36,679
ONE STUDY TO HIGHLIGHT EVEN 

1885
01:10:36,679 --> 01:10:37,313
THOUGH I KNOW THERE HAS BEEN A 

1886
01:10:37,313 --> 01:10:39,082
LOT OF OTHER SLIDES, IS THE 

1887
01:10:39,082 --> 01:10:39,716
RECENT CENTER WITHOUT WALLS FOR 

1888
01:10:39,716 --> 01:10:40,583
LEVY BODY DEMENTIA. AND THANK 

1889
01:10:40,583 --> 01:10:45,522
YOU TO DR. PAM MACLEAN FOR 

1890
01:10:45,522 --> 01:10:46,122
PROVIDING THE BASIS FOR THIS 

1891
01:10:46,122 --> 01:10:50,894
SLIDE. 

1892
01:10:50,894 --> 01:10:51,394
THIS IS VERY NICE BECAUSE 

1893
01:10:51,394 --> 01:10:52,028
NEUROPATHOLOGY IS AT THE HEART 

1894
01:10:52,028 --> 01:10:52,629
OF THIS GRANT, AND USING THE 

1895
01:10:52,629 --> 01:10:53,263
NEUROPATHOLOGY AND WORKING IN 

1896
01:10:53,263 --> 01:10:59,235
THE OMICS ASPECTS IN THE 

1897
01:10:59,235 --> 01:11:01,838
FUNCTIONAL PRESENCE USING THESE 

1898
01:11:01,838 --> 01:11:02,439
RESOURCES. I AM VERY EXCITED 

1899
01:11:02,439 --> 01:11:03,006
FOR THESE PROJECTS. 

1900
01:11:03,006 --> 01:11:06,910
NEXT SLIDE. 

1901
01:11:06,910 --> 01:11:07,477
ALTHOUGH THERE HAS BEEN AGAIN 

1902
01:11:07,477 --> 01:11:08,044
RECENT PROGRESS, THERE ARE 

1903
01:11:08,044 --> 01:11:10,180
STILL GAPS.  AND THESE TEAMS 

1904
01:11:10,180 --> 01:11:15,351
HAVE BEEN THROUGHOUT THIS NINDS 

1905
01:11:15,351 --> 01:11:17,854
SUMMIT ABOUT HARMONIZING 

1906
01:11:17,854 --> 01:11:19,522
TECHNIQUES; LOOPING SCIENTIST 

1907
01:11:19,522 --> 01:11:22,392
TO SAMPLES AND DATA IN 

1908
01:11:22,392 --> 01:11:22,992
USER-FRIENDLY PORTALS AS WELL 

1909
01:11:22,992 --> 01:11:27,297
AS DIGITAL AND IMAGE ANALYSIS 

1910
01:11:27,297 --> 01:11:27,931
AND THE LEARNING TECHNIQUES AND 

1911
01:11:27,931 --> 01:11:28,398
LAST BUT NOT LEAST IS 

1912
01:11:28,398 --> 01:11:29,065
INCREASING THE NUMBER OF DEEPLY 

1913
01:11:29,065 --> 01:11:29,599
PHENOTYPE AUTOPSY COHORTS 

1914
01:11:29,599 --> 01:11:30,100
FOCUSED ON LBD.

1915
01:11:30,100 --> 01:11:34,304
AND WHEN I SAY FOCUSED ON LEVY 

1916
01:11:34,304 --> 01:11:34,904
BODY, ALLOW THE DATA THAT WE 

1917
01:11:34,904 --> 01:11:35,538
SEE COMING OUT SPECIALLY THANK 

1918
01:11:35,538 --> 01:11:37,707
YOU TO DOCTOR TOLEDO PRESENTING 

1919
01:11:37,707 --> 01:11:41,878
FOR SOME OF THE THINGS OF THE 

1920
01:11:41,878 --> 01:11:42,512
LEVY BODY COHORTS BUT A LOT OF 

1921
01:11:42,512 --> 01:11:43,746
THE WORK BEING DONE IS BASED ON 

1922
01:11:43,746 --> 01:11:46,983
ALZHEIMER'S DISEASE CENTER 

1923
01:11:46,983 --> 01:11:51,020
COHORTS THERE IS NOT A LOT OF 

1924
01:11:51,020 --> 01:11:51,654
SPECIFIC LEVY BODY COHORTS AND 

1925
01:11:51,654 --> 01:11:57,994
PLEASE FORGIVE MY LANGUAGE, IT 

1926
01:11:57,994 --> 01:11:58,628
IS ALMOST LIKE AN AFTERTHOUGHT 

1927
01:11:58,628 --> 01:11:59,229
OR CAPITALIZATION SOME OF THE 

1928
01:11:59,229 --> 01:11:59,796
EXISTING COHORTS RELATED TO 

1929
01:11:59,796 --> 01:12:00,597
WORK ON THE BODY DISEASE. I SAY 

1930
01:12:00,597 --> 01:12:02,665
THAT VERY LIKELY NOT TO BE 

1931
01:12:02,665 --> 01:12:03,333
PROVOCATIVE, BUT TO MAKE PEOPLE 

1932
01:12:03,333 --> 01:12:03,967
AWARE OF THE SITUATION. 

1933
01:12:03,967 --> 01:12:05,668
NEXT SLIDE. 

1934
01:12:05,668 --> 01:12:09,906
AND SO, WITH THOSE GAPS-- AND 

1935
01:12:09,906 --> 01:12:13,009
IF YOU CAN MAYBE HIT A WHOLE 

1936
01:12:13,009 --> 01:12:13,643
BUNCH BECAUSE THE ANIMATIONS ON 

1937
01:12:13,643 --> 01:12:15,345
THIS GOT A LITTLE JUMBLED. 

1938
01:12:15,345 --> 01:12:17,514
THANK YOU. HIT A WHOLE BUNCH 

1939
01:12:17,514 --> 01:12:18,148
UNTIL EVERYTHING POPS UP AND I 

1940
01:12:18,148 --> 01:12:19,516
WILL LET YOU KNOW. 

1941
01:12:19,516 --> 01:12:23,486
YEAH IT GOT A LITTLE JUMBLED. 

1942
01:12:23,486 --> 01:12:24,087
THANK YOU FOR YOUR PATIENCE. 

1943
01:12:24,087 --> 01:12:28,324
STOP THERE. THANK YOU.

1944
01:12:28,324 --> 01:12:31,694
A RECOMMENDATION IS TO ENHANCE 

1945
01:12:31,694 --> 01:12:32,295
AND HARMONIZE THE TECHNIQUES 

1946
01:12:32,295 --> 01:12:32,795
FOR NEURAL PATHOLOGICAL 

1947
01:12:32,795 --> 01:12:33,429
CHARACTERIZATION OF LEVY BODY  

1948
01:12:33,429 --> 01:12:39,068
DISEASE AND USE OF LEVY BODY 

1949
01:12:39,068 --> 01:12:39,602
PATHOLOGY COHORTS AND THE 

1950
01:12:39,602 --> 01:12:40,170
ENHANCED PRACTICE FOR YOUR 

1951
01:12:40,170 --> 01:12:40,737
PATHOLOGICAL VALUATION AND 

1952
01:12:40,737 --> 01:12:42,038
DEVELOP SCALABLE METHODS FOR 

1953
01:12:42,038 --> 01:12:43,606
ASSESSING LEVY BODY ASSOCIATED 

1954
01:12:43,606 --> 01:12:44,874
PATHOLOGY AND CAPITALIZING ON 

1955
01:12:44,874 --> 01:12:45,441
THOSE EXISTING HUMAN TISSUE 

1956
01:12:45,441 --> 01:12:49,078
RESOURCES. 

1957
01:12:49,078 --> 01:12:51,347
INCREASING AUTOPSIES OF PERSONS 

1958
01:12:51,347 --> 01:12:52,115
WHO MAY DEVELOP OR ALREADY HAVE 

1959
01:12:52,115 --> 01:12:53,216
DEVELOPED LEVY BODY DISEASE AND 

1960
01:12:53,216 --> 01:12:53,850
ENHANCE INFRASTRUCTURE-- AND I 

1961
01:12:53,850 --> 01:12:58,087
LOVE THE COMMENT ABOUT THE EYES 

1962
01:12:58,087 --> 01:12:59,355
IN THE PREVIOUS SECTION AND SO 

1963
01:12:59,355 --> 01:13:06,496
THIS PERIPHERAL TISSUE SAMPLES, 

1964
01:13:06,496 --> 01:13:07,130
BECAUSE THE BRAIN IS CONNECTED 

1965
01:13:07,130 --> 01:13:07,664
TO THE BODY AND SOMETIMES 

1966
01:13:07,664 --> 01:13:08,264
THAT'S SKULL IS VERY HARD TO 

1967
01:13:08,264 --> 01:13:09,799
GET TO. 

1968
01:13:09,799 --> 01:13:11,734
I APPRECIATE THE COMMENTS IN 

1969
01:13:11,734 --> 01:13:13,670
PRIOR SESSIONS RELATED TO THAT. 

1970
01:13:13,670 --> 01:13:19,142
AND LAST BUT NOT LEAST IS A 

1971
01:13:19,142 --> 01:13:19,609
PORTAL LINKING TISSUE 

1972
01:13:19,609 --> 01:13:20,243
RESOURCES, MOLECULAR, CLINICAL, 

1973
01:13:20,243 --> 01:13:21,244
IMAGING AND BIOMARKER DATA. AND 

1974
01:13:21,244 --> 01:13:26,449
I THINK THAT IS IT. THANK YOU. 

1975
01:13:26,449 --> 01:13:34,224
>> SO, ... MY NAME IS
ALICE 

1976
01:13:34,224 --> 01:13:34,724
CHEN-PLOTKIN, PHYSICIAN 

1977
01:13:34,724 --> 01:13:36,326
SCIENTIST AT THE UNIVERSITY OF 

1978
01:13:36,326 --> 01:13:37,927
PENNSYLVANIA. 

1979
01:13:37,927 --> 01:13:40,263
I WILL BE ROUNDING OUT THE LAST 

1980
01:13:40,263 --> 01:13:40,797
TWO RECOMMENDATION FROM A 

1981
01:13:40,797 --> 01:13:43,166
WORKGROUP.  THESE ARE THE 

1982
01:13:43,166 --> 01:13:44,500
DISCLAIMERS AND DISCLOSURES. 

1983
01:13:44,500 --> 01:13:45,335
NOT MUCH EXCITING THERE. 

1984
01:13:45,335 --> 01:13:46,736
NEXT SLIDE. 

1985
01:13:46,736 --> 01:13:54,377
SO, I'M JUST BEGINNING BY 

1986
01:13:54,377 --> 01:13:54,811
COMING RIGHT TO THE 

1987
01:13:54,811 --> 01:13:56,512
RECOMMENDATIONS. RECOMMENDATION 

1988
01:13:56,512 --> 01:14:01,884
7, PRIORITY 1, , TO DEVELOP 

1989
01:14:01,884 --> 01:14:03,419
MODELS PATHOGENESIS AND 

1990
01:14:03,419 --> 01:14:04,420
MECHANISMS OF TOXICITY, AND 

1991
01:14:04,420 --> 01:14:05,021
NORMAL MOLECULAR AND CELLULAR 

1992
01:14:05,021 --> 01:14:07,957
FUNCTIONS OF A-SYNUCLEIN WITH 

1993
01:14:07,957 --> 01:14:08,524
THE AIM OF SUPPORTING DRUG 

1994
01:14:08,524 --> 01:14:11,127
DISCOVERY. 

1995
01:14:11,127 --> 01:14:11,728
THE RECOMMENDATION I WILL COVER 

1996
01:14:11,728 --> 01:14:13,029
IS NUMBER 8, WHICH WE ASSIGN 

1997
01:14:13,029 --> 01:14:14,764
PRIORITY 4. 

1998
01:14:14,764 --> 01:14:22,905
TO IDENTIFY THEM MULTIPLE 

1999
01:14:22,905 --> 01:14:23,406
ETIOLOGY MECHANISMS OF 

2000
01:14:23,406 --> 01:14:23,940
SELECTIVE VULNERABILITY, 

2001
01:14:23,940 --> 01:14:24,574
DISEASE HETEROGENEITY, DISEASE 

2002
01:14:24,574 --> 01:14:27,243
SPREAD/ PROPAGATION, AND 

2003
01:14:27,243 --> 01:14:27,744
INTERACTION WITH OTHER 

2004
01:14:27,744 --> 01:14:28,311
AGE-RELATED PATHOLOGIES AS 

2005
01:14:28,311 --> 01:14:28,911
THERAPEUTIC TARGETS. 

2006
01:14:28,911 --> 01:14:32,749
NEXT SLIDE. 

2007
01:14:32,749 --> 01:14:33,283
SO I WILL BEGIN BY KIND OF 

2008
01:14:33,283 --> 01:14:34,017
COVERING THE PROGRESS SINCE THE 

2009
01:14:34,017 --> 01:14:36,252
LAST SUMMIT IN 2022. 

2010
01:14:36,252 --> 01:14:38,655
I WILL DIVIDE THIS INTO WHAT WE 

2011
01:14:38,655 --> 01:14:39,289
HAVE LEARNED ABOUT A-SYNUCLEIN 

2012
01:14:39,289 --> 01:14:42,925
WHICH IS A LOT.  I CANNOT 

2013
01:14:42,925 --> 01:14:43,526
EMPHASIZE HOW MUCH-- I AM NOT 

2014
01:14:43,526 --> 01:14:47,530
COVERING THAT HAS BEEN DONE 

2015
01:14:47,530 --> 01:14:49,899
SINCE 2022, THE BASIS FOR OUR 

2016
01:14:49,899 --> 01:14:51,267
RECOMMENDATIONS AND 11 HAS ONE 

2017
01:14:51,267 --> 01:14:51,901
THING, WHICH IS THIS IS A VERY 

2018
01:14:51,901 --> 01:14:55,471
EXCITING TIME  FOR THE LEVY 

2019
01:14:55,471 --> 01:14:58,708
BODY DISEASES, AND SUPPORT OF 

2020
01:14:58,708 --> 01:14:59,342
THESE RESEARCH EFFORTS IS VERY 

2021
01:14:59,342 --> 01:14:59,776
IMPORTANT. 

2022
01:14:59,776 --> 01:15:02,211
NEXT SLIDE. 

2023
01:15:02,211 --> 01:15:05,682
SO IF YOU THINK THAT HAVE BEEN 

2024
01:15:05,682 --> 01:15:06,316
LEARNED. IN 2022-- AND THIS IS 

2025
01:15:06,316 --> 01:15:10,186
HAPPENING ALL THE TIME-- 

2026
01:15:10,186 --> 01:15:11,621
(INDISCERNIBLE) SHOWING US THAT 

2027
01:15:11,621 --> 01:15:12,121
THERE MAY BE DIFFERENT 

2028
01:15:12,121 --> 01:15:12,722
CONFIRMATION SHAPES IN LEVY 

2029
01:15:12,722 --> 01:15:17,660
BODY DEMENTIA  IN LEVY BODY 

2030
01:15:17,660 --> 01:15:19,962
DISEASE AND PARKINSON'S 

2031
01:15:19,962 --> 01:15:20,496
DISEASE, VERSUS MULTIPLE 

2032
01:15:20,496 --> 01:15:23,866
SYSTEMS ATROPHY WHICH IS ALSO 

2033
01:15:23,866 --> 01:15:24,434
IS SYSTEMS ATROPHY FOR 

2034
01:15:24,434 --> 01:15:25,435
INCLUSION DATA. 

2035
01:15:25,435 --> 01:15:27,670
NEXT SLIDE. 

2036
01:15:27,670 --> 01:15:30,373
THIS IS THE BASIS, THE 

2037
01:15:30,373 --> 01:15:31,007
DIFFERENCE IN CONFIRMATION AND 

2038
01:15:31,007 --> 01:15:33,509
MAY BE THE BASIS FOR WHAT 

2039
01:15:33,509 --> 01:15:34,177
SUBSEQUENT DEVELOPMENT WHICH IS 

2040
01:15:34,177 --> 01:15:37,380
A BIOMARKER TEST THAT HAS BEEN 

2041
01:15:37,380 --> 01:15:37,980
SHOWN IN PREVIOUS SLIDES. AND 

2042
01:15:37,980 --> 01:15:45,722
SO THIS IS THE PAPER FROM 

2043
01:15:45,722 --> 01:15:46,422
NATURE 2020, THAT ESSENTIALLY 

2044
01:15:46,422 --> 01:15:47,023
SHOWS THAT IN THE ABILITY TO 

2045
01:15:47,023 --> 01:15:54,297
SEE IMPLICATION IN A-SYNUCLEIN, 

2046
01:15:54,297 --> 01:15:54,864
IN SAMPLES OF PARKINSON’S 

2047
01:15:54,864 --> 01:15:55,631
DISEASE SAMPLES, RELATED TO THE 

2048
01:15:55,631 --> 01:15:59,902
CONFIRMATION OF A-SYNUCLEIN. 

2049
01:15:59,902 --> 01:16:00,336
THIS HAS ALREADY BEEN 

2050
01:16:00,336 --> 01:16:01,270
TRANSLATED IN THIS PERIOD OF 

2051
01:16:01,270 --> 01:16:05,575
TIME INTO AN FDA AVAILABLE 

2052
01:16:05,575 --> 01:16:08,678
CLINICAL TESTS.  THIS IS THE 

2053
01:16:08,678 --> 01:16:14,751
TECHNOLOGY RECORDED IN 2020 AND 

2054
01:16:14,751 --> 01:16:16,853
NOW SHOWN AND THIS IS THE SAME 

2055
01:16:16,853 --> 01:16:19,288
SEED AMPLIFICATION ASSAY SHOWN 

2056
01:16:19,288 --> 01:16:19,922
IN PREVIOUS SLIDES THAT LOOKED 

2057
01:16:19,922 --> 01:16:25,395
AT HOW THE SEED AMPLIFICATION 

2058
01:16:25,395 --> 01:16:27,663
ASSAY PERFORMED IN MANY 

2059
01:16:27,663 --> 01:16:30,099
PATIENTS.

2060
01:16:30,099 --> 01:16:30,700
AND AS YOU CAN SEE DEPENDING ON 

2061
01:16:30,700 --> 01:16:32,235
HOW YOU DEFINE PARKINSON'S 

2062
01:16:32,235 --> 01:16:35,371
DISEASE, DIFFERENT GENETIC 

2063
01:16:35,371 --> 01:16:38,708
MUTATIONS, THE SENSITIVITIES 

2064
01:16:38,708 --> 01:16:39,308
ARE VERY, VERY HIGH. WHICH IS 

2065
01:16:39,308 --> 01:16:39,876
BASICALLY WHY THIS IS NOW A 

2066
01:16:39,876 --> 01:16:41,077
DIAGNOSTIC TEST THAT A DOCTOR 

2067
01:16:41,077 --> 01:16:41,744
CAN ORDER IN THE CLINIC. 

2068
01:16:41,744 --> 01:16:49,318
NEXT SLIDE. 

2069
01:16:49,318 --> 01:16:51,454
SO EVEN THOUGH WE LEARNED A LOT 

2070
01:16:51,454 --> 01:16:53,956
ABOUT THE CONFIRMATIONS, 

2071
01:16:53,956 --> 01:16:54,590
THERE'S A LOT MORE TO LEARN SO 

2072
01:16:54,590 --> 01:16:55,992
I'M HIGHLIGHTING A FEW THINGS. 

2073
01:16:55,992 --> 01:17:01,931
IT TURNS OUT THAT WORK FROM -- 

2074
01:17:01,931 --> 01:17:02,365
AND OTHERS SHOW THE 

2075
01:17:02,365 --> 01:17:02,799
POST-TRANSLATIONAL 

2076
01:17:02,799 --> 01:17:04,100
MODIFICATIONS IN A-SYNUCLEIN, 

2077
01:17:04,100 --> 01:17:10,206
WORK DONE IN MSA LBD IN NORMAL 

2078
01:17:10,206 --> 01:17:10,840
BRAINS AS WELL AND YOU CAN SEE 

2079
01:17:10,840 --> 01:17:14,510
WITH THE DIFFERENTIATE THAT THE 

2080
01:17:14,510 --> 01:17:15,144
POST TRANSLATION MODIFICATIONS 

2081
01:17:15,144 --> 01:17:15,678
ARE LITTLE BIT DIFFERENT 

2082
01:17:15,678 --> 01:17:16,312
DEPENDING ON THE STUDY. 

2083
01:17:16,312 --> 01:17:18,648
NEXT SLIDE. 

2084
01:17:18,648 --> 01:17:20,616
AND THE OTHER THING IS THAT ONE 

2085
01:17:20,616 --> 01:17:24,654
PHOSPHORYLATION ON SERIN 129 

2086
01:17:24,654 --> 01:17:25,354
WHICH IS LONG BEEN FOUND TO BE 

2087
01:17:25,354 --> 01:17:29,892
A HALLMARK OF LEVY BODY 

2088
01:17:29,892 --> 01:17:31,627
PATHOLOGY IS WHAT WE FIND IN 

2089
01:17:31,627 --> 01:17:33,796
THE BRAINS OF PEOPLE WITH LEVY 

2090
01:17:33,796 --> 01:17:34,397
BODY DISEASE AND IT TURNS OUT 

2091
01:17:34,397 --> 01:17:38,901
IF YOU LOOK AT THE PAPER ONE 

2092
01:17:38,901 --> 01:17:39,502
THING THAT IS INTERESTING IS 

2093
01:17:39,502 --> 01:17:40,102
THAT THIS PHOSPHORYLATION IS 

2094
01:17:40,102 --> 01:17:40,670
FOUND IN NORMAL PEOPLE. AND 

2095
01:17:40,670 --> 01:17:51,180
PROVOCATIVE WORK FROM -- LAB, 

2096
01:17:53,015 --> 01:17:53,449
SHOWED THAT MAYBE THIS 

2097
01:17:53,449 --> 01:17:53,916
PHOSPHORYLATION HAS A 

2098
01:17:53,916 --> 01:17:54,550
PHYSIOLOGICAL FUNCTION.

2099
01:17:54,550 --> 01:17:57,854
NEXT SLIDE. 

2100
01:17:57,854 --> 01:17:58,654
ANOTHER THING THAT BASICALLY I 

2101
01:17:58,654 --> 01:17:59,555
WANT TO EMPHASIZE IS THAT THE 

2102
01:17:59,555 --> 01:18:02,425
REASON THAT THESE DISEASES 

2103
01:18:02,425 --> 01:18:10,032
CHANGE OVER TIME, THE REASON 

2104
01:18:10,032 --> 01:18:13,102
PATIENTS PROGRESS OVER TIME IS 

2105
01:18:13,102 --> 01:18:13,703
THE PATHOLOGY SHOWING THAT IT 

2106
01:18:13,703 --> 01:18:19,609
SPREADS FROM ONE AREA OF THE 

2107
01:18:19,609 --> 01:18:21,978
BRAIN TO ANOTHER PART OF THE 

2108
01:18:21,978 --> 01:18:22,512
BRAIN LIKE IN PARKINSON'S 

2109
01:18:22,512 --> 01:18:23,145
DISEASE AT START OF THE TREMOR 

2110
01:18:23,145 --> 01:18:26,215
AND THEN IT STARTS TO DEVELOP 

2111
01:18:26,215 --> 01:18:26,983
OTHER DISEASES, AND THE SPREAD 

2112
01:18:26,983 --> 01:18:33,623
OF PATHOLOGY FROM CELL TO CELL. 

2113
01:18:33,623 --> 01:18:34,123
OTHER THINGS BESIDE THE 

2114
01:18:34,123 --> 01:18:34,724
NUCLEON, BUT THIS IS AT LEAST 

2115
01:18:34,724 --> 01:18:35,258
ONE CORE FEATURE. 

2116
01:18:35,258 --> 01:18:37,493
NEXT SLIDE. 

2117
01:18:37,493 --> 01:18:40,329
THIS IS WORK FROM OUR LAB THAT 

2118
01:18:40,329 --> 01:18:40,930
BASICALLY HAS BEEN TRYING TO 

2119
01:18:40,930 --> 01:18:41,430
UNDERSTAND WHAT ARE THE 

2120
01:18:41,430 --> 01:18:42,098
DETERMINANTS OF THE SPREAD FROM 

2121
01:18:42,098 --> 01:18:48,804
CELL TO CELL PATHOLOGY. 

2122
01:18:48,804 --> 01:18:49,372
IT TURNS OUT THAT ONE OF THE 

2123
01:18:49,372 --> 01:18:49,972
GENES THAT CAME OUT OF THESE 

2124
01:18:49,972 --> 01:18:50,606
BIG GENOMICS PARKINSON DISEASE 

2125
01:18:50,606 --> 01:18:56,579
-- BELONGS TO A GENE CALLED 

2126
01:18:56,579 --> 01:18:59,715
GPNMB. 

2127
01:18:59,715 --> 01:19:02,718
IT APPEARS THAT NEURONS CAN NO 

2128
01:19:02,718 --> 01:19:03,452
LONGER TAKE UP THIS 

2129
01:19:03,452 --> 01:19:04,287
PATHOLOGICAL NUCLEON, MAY BE 

2130
01:19:04,287 --> 01:19:04,854
KEY TO THE SPREAD. 

2131
01:19:04,854 --> 01:19:07,857
NEXT SLIDE. 

2132
01:19:07,857 --> 01:19:13,162
SO, ANOTHER THING WE WANTED TO 

2133
01:19:13,162 --> 01:19:13,763
EMPHASIZE IN THIS CAN HAPPEN 

2134
01:19:13,763 --> 01:19:14,697
MULTIPLE SESSIONS BEFORE. 

2135
01:19:14,697 --> 01:19:15,698
EVEN THOUGH I BEEN TALKING 

2136
01:19:15,698 --> 01:19:17,066
ABOUT A-SYNUCLEIN, AND WHAT WE 

2137
01:19:17,066 --> 01:19:19,335
HAVE LEARNED ABOUT A-SYNUCLEIN, 

2138
01:19:19,335 --> 01:19:21,437
IN THE BRAIN A-SYNUCLEIN IS NOT 

2139
01:19:21,437 --> 01:19:27,877
BY ITSELF.  AND SO WE WILL SHOW 

2140
01:19:27,877 --> 01:19:28,477
YOU THE CLINICAL CASES FROM A 

2141
01:19:28,477 --> 01:19:29,078
LIVE STUDY. AND WHAT YOU CAN 

2142
01:19:29,078 --> 01:19:31,981
SEE IS THAT YELLOW PART -- THE 

2143
01:19:31,981 --> 01:19:36,586
RED PART IS JUST LEVY BODY 

2144
01:19:36,586 --> 01:19:37,987
DISEASE AND THOSE BRAINS. THE 

2145
01:19:37,987 --> 01:19:43,059
RED PLUS ORANGES LEVY BODY 

2146
01:19:43,059 --> 01:19:44,160
DISEASE PATHOLOGY PLUS A NORMAL 

2147
01:19:44,160 --> 01:19:46,395
CHANGES YOU EXPECT WITH AGING. 

2148
01:19:46,395 --> 01:19:51,400
THE YELLOW AND THE -- IS 

2149
01:19:51,400 --> 01:19:53,703
BASICALLY NEURODEGENERATIVE 

2150
01:19:53,703 --> 01:19:54,337
DISEASE, LEVY BODY DISEASES IN 

2151
01:19:54,337 --> 01:19:55,705
AGING IN ANOTHER PATHOLOGY. YOU 

2152
01:19:55,705 --> 01:19:59,709
CAN SEE THAT ABOUT ONE THIRD OF 

2153
01:19:59,709 --> 01:20:00,242
CLINICAL LBD CASES HAVE 

2154
01:20:00,242 --> 01:20:00,876
ADDITIONAL PATHOLOGIES. 

2155
01:20:00,876 --> 01:20:03,079
NEXT SLIDE. 

2156
01:20:03,079 --> 01:20:04,914
IT TURNS OUT THAT THE PATTERNS 

2157
01:20:04,914 --> 01:20:07,516
OF CO-PATHOLOGY, THE OTHER 

2158
01:20:07,516 --> 01:20:08,384
TYPES OF PATHOLOGY PROTEINS IN 

2159
01:20:08,384 --> 01:20:18,928
THE BRAIN WITH THE LEVY BODIES  

2160
01:20:21,063 --> 01:20:22,264
MAY RELATE TO THIS ORDER OF 

2161
01:20:22,264 --> 01:20:22,865
SPREAD OF REGIONS AFFECTED BY 

2162
01:20:22,865 --> 01:20:25,334
A-SYNUCLEIN PATHOLOGY. 

2163
01:20:25,334 --> 01:20:29,305
SO THESE ARE BASED ON KIND OF 

2164
01:20:29,305 --> 01:20:29,905
THINGS WE HAVE LEARNED, AND 

2165
01:20:29,905 --> 01:20:34,143
WHAT WE STILL NEED TO KNOW. 

2166
01:20:34,143 --> 01:20:34,744
THE FIRST THING IS, DO ALL 

2167
01:20:34,744 --> 01:20:37,413
MEDICAL PARKINSON'S DISEASE 

2168
01:20:37,413 --> 01:20:38,347
EXISTS WITH DEMENTIA, AND THEY 

2169
01:20:38,347 --> 01:20:40,750
HAVE  PATHOLOGY 

2170
01:20:40,750 --> 01:20:42,418
(INDISCERNIBLE), NOT ABOUT WAYS 

2171
01:20:42,418 --> 01:20:44,487
WE CAN DETECT A-SYNUCLEIN, AND 

2172
01:20:44,487 --> 01:20:51,460
YOU CAN SEE IT DOES. THE ASSAY 

2173
01:20:51,460 --> 01:20:58,234
IS NOT 100% SENSITIVE, BECAUSE 

2174
01:20:58,234 --> 01:20:58,801
THE ASSAY IS NOT SENSITIVE 

2175
01:20:58,801 --> 01:20:59,935
ENOUGH OR NOT ALL PATIENTS HAVE 

2176
01:20:59,935 --> 01:21:05,641
A-SYNUCLEIN?

2177
01:21:05,641 --> 01:21:06,208
A-SYNUCLEIN CONFIRMATIONS ARE 

2178
01:21:06,208 --> 01:21:07,777
THE SAME OR DIFFERENT ACROSS 

2179
01:21:07,777 --> 01:21:08,210
INDIVIDUALS?

2180
01:21:08,210 --> 01:21:08,744
ACROSS CLINICALLY IMPORTANT 

2181
01:21:08,744 --> 01:21:10,813
SUBTYPES?

2182
01:21:10,813 --> 01:21:11,414
I SHOW YOU SOME WORK THAT THERE 

2183
01:21:11,414 --> 01:21:12,048
MAY BE OTHER NORMAL FUNCTIONS 

2184
01:21:12,048 --> 01:21:16,519
OF ASYN. AND WE WONDER WHAT 

2185
01:21:16,519 --> 01:21:17,086
DOCTORS GATHERED ABOUT THE 

2186
01:21:17,086 --> 01:21:19,422
DIFFERENT BEHAVIORS OF ASYN IN 

2187
01:21:19,422 --> 01:21:19,889
PHYSIOLOGICAL DISEASE 

2188
01:21:19,889 --> 01:21:20,723
CONDITIONS. 

2189
01:21:20,723 --> 01:21:22,324
AND THERE IS A LOT OF OTHER 

2190
01:21:22,324 --> 01:21:28,798
PATHOLOGY. HOW DOES ASYN 

2191
01:21:28,798 --> 01:21:29,231
INTERACT WITH OTHER 

2192
01:21:29,231 --> 01:21:29,765
PATHOLOGICAL PROTEINS IN 

2193
01:21:29,765 --> 01:21:34,804
DISEASE PATHOGENESIS?

2194
01:21:34,804 --> 01:21:38,441
WHAT NON-ASYN- RELATED 

2195
01:21:38,441 --> 01:21:39,642
MECHANISM LEAD TO OR EXACERBATE 

2196
01:21:39,642 --> 01:21:40,242
DISEASE PATHOGENESIS?

2197
01:21:40,242 --> 01:21:46,048
RECOMMENDATION 7, WHICH ARE 

2198
01:21:46,048 --> 01:21:46,615
RATHER THE BEGINNING IS TO 

2199
01:21:46,615 --> 01:21:47,216
DEVELOP MODELS TO UNDERSTAND 

2200
01:21:47,216 --> 01:21:47,783
PATHOGENESIS MECHANISMS OF 

2201
01:21:47,783 --> 01:21:48,384
TOXICITY IN NORMAL MOLECULAR 

2202
01:21:48,384 --> 01:21:48,951
AND CELLULAR FUNCTIONS OF 

2203
01:21:48,951 --> 01:21:52,354
A-SYNUCLEIN. 

2204
01:21:52,354 --> 01:21:55,224
AND YOU CAN SEE THAT WE HAVE 

2205
01:21:55,224 --> 01:21:55,825
DETAILS AND THEY WILL BE MORE 

2206
01:21:55,825 --> 01:21:56,425
DETAILS IN OUR REPORT AND HOW 

2207
01:21:56,425 --> 01:21:57,026
WE THINK THIS CAN KIND OF BE 

2208
01:21:57,026 --> 01:21:57,493
WELL PURSUED. 

2209
01:21:57,493 --> 01:22:00,429
NEXT SLIDE. 

2210
01:22:00,429 --> 01:22:01,864
RECOMMENDATION 8, IS TO 

2211
01:22:01,864 --> 01:22:07,002
IDENTIFY MULTIPLE ETIOLOGY 

2212
01:22:07,002 --> 01:22:07,503
MECHANISMS OF SELECTED 

2213
01:22:07,503 --> 01:22:10,072
VULNERABILITY, DISEASE 

2214
01:22:10,072 --> 01:22:10,573
HETEROGENEITY, DISEASE 

2215
01:22:10,573 --> 01:22:11,107
SPREADING COMPETITION AND 

2216
01:22:11,107 --> 01:22:12,174
DIRECTION WITH OTHER 

2217
01:22:12,174 --> 01:22:13,709
AGE-RELATED PATHOLOGIES AS 

2218
01:22:13,709 --> 01:22:14,310
CLEAR TARGETS. AND THIS IS TO 

2219
01:22:14,310 --> 01:22:17,713
LOOK AT MIXED PATHOLOGY AND 

2220
01:22:17,713 --> 01:22:18,247
WHAT THE IMPACT IS AND TO 

2221
01:22:18,247 --> 01:22:18,914
UNDERSTAND OTHER FACTORS THAT 

2222
01:22:18,914 --> 01:22:22,384
LEAD TO NEURODEGENERATION. 

2223
01:22:22,384 --> 01:22:23,419
WITH THE IDEA THAT THESE MAY BE 

2224
01:22:23,419 --> 01:22:30,159
DISTINCT FROM THE MECHANISM. IS 

2225
01:22:30,159 --> 01:22:30,760
WHAT MAKES NEURODEGENERATION 

2226
01:22:30,760 --> 01:22:31,360
LOSS OF NEURONS, BE DIFFERENT 

2227
01:22:31,360 --> 01:22:31,894
FROM THE (INDISCERNIBLE) 

2228
01:22:31,894 --> 01:22:35,097
PATHOLOGY. 

2229
01:22:35,097 --> 01:22:35,631
BECAUSE WE THINK THE OTHER 

2230
01:22:35,631 --> 01:22:36,632
PROTEINS IN THE MIX WE WANT TO 

2231
01:22:36,632 --> 01:22:38,667
DEVELOP LBD MODELS THAT ARE 

2232
01:22:38,667 --> 01:22:39,635
NONEXCLUSIVE LEAD BASED ON 

2233
01:22:39,635 --> 01:22:42,071
A-SYNUCLEIN. 

2234
01:22:42,071 --> 01:22:43,339
AND WANT TO CONSIDER THE IMPACT 

2235
01:22:43,339 --> 01:22:43,939
OF DEMOGRAPHICS, AGE AND SEX 

2236
01:22:43,939 --> 01:22:54,283
FOR EXAMPLE ON LBD 

2237
01:22:55,451 --> 01:22:55,918
PATHOPHYSIOLOGY AND TOXIC 

2238
01:22:55,918 --> 01:23:00,790
MECHANISMS UNDERLYING DISEASE.

2239
01:23:00,790 --> 01:23:01,390
>> THANK YOU EVERYONE SO
MUCH. 

2240
01:23:01,390 --> 01:23:03,692
THAT WAS A REALLY WONDERFUL 

2241
01:23:03,692 --> 01:23:07,296
PRESENTATION FROM ALL OF OUR 

2242
01:23:07,296 --> 01:23:07,897
SESSION GROUP AND NOW WE OPEN 

2243
01:23:07,897 --> 01:23:10,166
IT UP TO QUESTIONS FROM THE 

2244
01:23:10,166 --> 01:23:13,536
PUBLIC. 

2245
01:23:13,536 --> 01:23:14,537
AND I WILL MODERATE AND ASSIGN 

2246
01:23:14,537 --> 01:23:18,507
QUESTIONS TO THE PANELISTS. IF 

2247
01:23:18,507 --> 01:23:21,911
YOU DON'T MIND TURNING THE 

2248
01:23:21,911 --> 01:23:26,849
CAMERA YOURSELF. 

2249
01:23:26,849 --> 01:23:27,383
>> EVERYONE ON THE PANEL
IS 

2250
01:23:27,383 --> 01:23:27,917
WELCOME TO TURN ON THEIR 

2251
01:23:27,917 --> 01:23:28,517
CAMERAS SO YOU CAN POP UP ON 

2252
01:23:28,517 --> 01:23:28,951
THE SCREEN. 

2253
01:23:28,951 --> 01:23:39,094
THANK YOU. 

2254
01:23:40,830 --> 01:23:45,367
>> I SEE HELEN. YOUR HAND
IS 

2255
01:23:45,367 --> 01:23:46,068
RAISED. PLEASE UNMUTE YOURSELF 

2256
01:23:46,068 --> 01:23:49,772
WITH YOUR QUESTION. 

2257
01:23:49,772 --> 01:23:52,441
>> CAN YOU HEAR ME? 

2258
01:23:52,441 --> 01:23:55,344
>> YES WE CAN THANK YOU. 

2259
01:23:55,344 --> 01:24:04,119
>> THANK YOU DR. POSSTON. 

2260
01:24:04,119 --> 01:24:04,687
THANK YOU FOR THIS INCREDIBLE 

2261
01:24:04,687 --> 01:24:05,287
ANALYSIS OF ACROSS THE BROAD 

2262
01:24:05,287 --> 01:24:09,625
SPECTRUM OF SCIENCE. IS VERY, 

2263
01:24:09,625 --> 01:24:10,659
VERY IMPORTANT TO ME AS MANY 

2264
01:24:10,659 --> 01:24:14,697
OTHER PEOPLE ON BOARD HERE 

2265
01:24:14,697 --> 01:24:21,403
TODAY, I HAVE OVER 35 YEARS IN 

2266
01:24:21,403 --> 01:24:22,037
THE TRENCHES WITH THIS DISEASE 

2267
01:24:22,037 --> 01:24:22,671
DUE TO MULTIPLE GENERATIONS IN 

2268
01:24:22,671 --> 01:24:25,708
MY FAMILY. 

2269
01:24:25,708 --> 01:24:26,308
IS A LOOK FORWARD TO THE FUTURE 

2270
01:24:26,308 --> 01:24:26,842
OF MY FAMILY IN THE NEXT 

2271
01:24:26,842 --> 01:24:27,443
GENERATIONS I AM VERY, VERY 

2272
01:24:27,443 --> 01:24:29,445
CONCERNED ABOUT SATURDAY THE 

2273
01:24:29,445 --> 01:24:31,347
LACK OF FUNDING.  AND SO 

2274
01:24:31,347 --> 01:24:31,947
HOPEFULLY THAT CAN BE PUSHED 

2275
01:24:31,947 --> 01:24:34,850
FORWARD. 

2276
01:24:34,850 --> 01:24:39,488
BECAUSE AT THIS POINT, I HAVE 

2277
01:24:39,488 --> 01:24:40,022
BEEN DIRECTLY INVOLVED IN 

2278
01:24:40,022 --> 01:24:40,623
RESEARCH NOW AS A PARTICIPANT 

2279
01:24:40,623 --> 01:24:42,391
FOR OVER 18 YEARS.  AND OF 

2280
01:24:42,391 --> 01:24:44,426
COURSE THAT STARTED WITH JUST 

2281
01:24:44,426 --> 01:24:46,428
BEING PART OF PARKINSON'S 

2282
01:24:46,428 --> 01:24:50,299
STUDY. THERE WAS NO DLB STUDIES 

2283
01:24:50,299 --> 01:24:53,502
GOING ON. 

2284
01:24:53,502 --> 01:24:56,906
BUT AGAIN IT IS ME GOING OUT TO 

2285
01:24:56,906 --> 01:24:57,907
FIND WHAT IS GOING TO BE 

2286
01:24:57,907 --> 01:24:58,540
RELEVANT-- AND THE MOST RECENT 

2287
01:24:58,540 --> 01:25:02,378
I AM NOW PART OF NAPPS. 

2288
01:25:02,378 --> 01:25:11,253
BUT THAT CONCERNS ME THAT THERE 

2289
01:25:11,253 --> 01:25:11,854
ISN'T AN INTERCONNECTEDNESS 

2290
01:25:11,854 --> 01:25:13,689
CONSISTENT ACROSS ALL 

2291
01:25:13,689 --> 01:25:14,290
INSTITUTES. IS THERE ANY WAY 

2292
01:25:14,290 --> 01:25:17,626
THAT WE CAN HARMONIZE AND 

2293
01:25:17,626 --> 01:25:21,463
DE-SILO SOME OF THESE-- SO THE 

2294
01:25:21,463 --> 01:25:25,401
COHORTS CAN EXPAND SHARING OF 

2295
01:25:25,401 --> 01:25:26,802
INDIVIDUAL BASIC INFORMATION 

2296
01:25:26,802 --> 01:25:32,474
INCLUDING IT IN THE CONSENT 

2297
01:25:32,474 --> 01:25:33,008
WHEN THEY ARE SIGNING THE 

2298
01:25:33,008 --> 01:25:33,475
CONSENT FORM YOU HAVE 

2299
01:25:33,475 --> 01:25:35,010
PERMISSION TO SHARE WITH OTHER 

2300
01:25:35,010 --> 01:25:39,581
INSTITUTIONS, PURSUING SIMILAR 

2301
01:25:39,581 --> 01:25:46,055
SAMPLING.  ALL RELATIVE STUDIES.

2302
01:25:46,055 --> 01:25:46,655
 SO WE CAN GET THIS EXPANDED 

2303
01:25:46,655 --> 01:25:50,459
MORE RAPIDLY. 

2304
01:25:50,459 --> 01:25:50,926
>> THANK YOU FOR THAT 

2305
01:25:50,926 --> 01:25:53,595
OUTSTANDING QUESTION. 

2306
01:25:53,595 --> 01:25:54,997
I'M GOING TO MAKE A COMMENT, 

2307
01:25:54,997 --> 01:26:00,069
AND THEN PASS IT OVER TO DR. 

2308
01:26:00,069 --> 01:26:00,703
MORMINO WHO HAS DONE SOME HAVE 

2309
01:26:00,703 --> 01:26:03,005
THIS TYPE OF WORK WITHIN THE 

2310
01:26:03,005 --> 01:26:03,572
IMAGING SPACE WHICH MAY BE 

2311
01:26:03,572 --> 01:26:09,144
RELEVANT BROADLY. 

2312
01:26:09,144 --> 01:26:09,712
BUT I AGREE THAT ALL SAMPLES, 

2313
01:26:09,712 --> 01:26:10,679
THE SHARING OF THE SAMPLES AND 

2314
01:26:10,679 --> 01:26:12,014
SHARING OF DATA BROADLY IS 

2315
01:26:12,014 --> 01:26:12,648
REALLY AT THE HEART OF MULTIPLE 

2316
01:26:12,648 --> 01:26:13,615
RECOMMENDATIONS. 

2317
01:26:13,615 --> 01:26:16,885
AND I ALSO THINK-- I REALLY 

2318
01:26:16,885 --> 01:26:17,486
APPRECIATE YOUR COMMENT THERE 

2319
01:26:17,486 --> 01:26:20,122
ABOUT IT BEING ADDRESSED AT THE 

2320
01:26:20,122 --> 01:26:23,559
LEVEL OF THE CONSENT FORM.  I 

2321
01:26:23,559 --> 01:26:24,159
HAVE ALSO FOUND THAT IF IT IS 

2322
01:26:24,159 --> 01:26:25,794
NOT ON THE CONSENT FORM, THERE 

2323
01:26:25,794 --> 01:26:27,730
IS VERY LITTLE WE CAN DO DOWN 

2324
01:26:27,730 --> 01:26:29,531
THE ROAD. AND BEING VERY 

2325
01:26:29,531 --> 01:26:30,132
PROACTIVE ABOUT THIS, MOVING 

2326
01:26:30,132 --> 01:26:31,767
FORWARD. 

2327
01:26:31,767 --> 01:26:34,336
AND THAT IS ACTUALLY-- I DON'T 

2328
01:26:34,336 --> 01:26:39,641
THINK WE DIRECT THE ADDRESSED 

2329
01:26:39,641 --> 01:26:40,242
THAT IN OUR RECOMMENDATION SO 

2330
01:26:40,242 --> 01:26:40,876
THAT IS A GREAT WANT FOR US TO 

2331
01:26:40,876 --> 01:26:45,180
UPDATE AS WE MOVE FORWARD. 

2332
01:26:45,180 --> 01:26:45,748
ANY COMMENT FROM THE IMAGING 

2333
01:26:45,748 --> 01:26:47,216
PERSPECTIVE WITH THIS REGARD, 

2334
01:26:47,216 --> 01:26:50,085
OTHER WORK YOU HAVE DONE HERE?

2335
01:26:50,085 --> 01:26:50,686
>> THIS IS A PROBLEM
ACROSS ALL 

2336
01:26:50,686 --> 01:26:51,420
STUDIES THAT WE DO. NOT 

2337
01:26:51,420 --> 01:26:57,092
SPECIFIC TO LEVY BODY DEMENTIA. 

2338
01:26:57,092 --> 01:26:57,659
 IS CERTAINLY HARDER GOING 

2339
01:26:57,659 --> 01:26:59,762
BACKWARDS, COMBINING DATA 

2340
01:26:59,762 --> 01:27:02,097
BECAUSE OF THIS ISSUE YOU'RE 

2341
01:27:02,097 --> 01:27:02,731
BRINGING UP. BECAUSE OF THE 

2342
01:27:02,731 --> 01:27:07,469
CONSENT.  BUT THERE ARE SOME 

2343
01:27:07,469 --> 01:27:08,070
CLEAR EXAMPLES OF SUCCESS IN 

2344
01:27:08,070 --> 01:27:13,542
THE SPACE. LIKE THE AT ME 

2345
01:27:13,542 --> 01:27:14,176
(PHONETIC) STUDY, SHARING DATA 

2346
01:27:14,176 --> 01:27:15,210
BROADLY IN THE CONTEXT OF 

2347
01:27:15,210 --> 01:27:20,616
ALZHEIMER'S DISEASE. AND STUDY 

2348
01:27:20,616 --> 01:27:21,183
DESIGNS, PUTTING THIS LAND 

2349
01:27:21,183 --> 01:27:21,817
WITHIN THE CONTENT IS CRITICAL 

2350
01:27:21,817 --> 01:27:23,619
FOR BROAD DATA SHARING. 

2351
01:27:23,619 --> 01:27:24,219
AND FROM THE IMAGING SIDE THERE 

2352
01:27:24,219 --> 01:27:24,887
ARE CONCERNED NOT JUST WITH 

2353
01:27:24,887 --> 01:27:25,487
IMAGING, BUT ALL THE DATA WE 

2354
01:27:25,487 --> 01:27:31,527
COLLECT.  THERE ARE ISSUES WITH 

2355
01:27:31,527 --> 01:27:36,065
THE IDENTIFICATION OF THE DATA. 

2356
01:27:36,065 --> 01:27:36,698
AND THAT IS A CONCERN BALANCING 

2357
01:27:36,698 --> 01:27:37,933
THE TWO SIDES ARE PROTECTING 

2358
01:27:37,933 --> 01:27:39,501
RESEARCH PARTICIPANTS IN TERMS 

2359
01:27:39,501 --> 01:27:42,304
OF IDENTIFICATION. BUT WE ARE 

2360
01:27:42,304 --> 01:27:42,871
HEARING MORE AND MORE FROM 

2361
01:27:42,871 --> 01:27:43,772
PARTICIPANTS HOW IMPORTANT IT 

2362
01:27:43,772 --> 01:27:51,146
IS THAT THE DATA IS SHARED.

2363
01:27:51,146 --> 01:27:51,680
AND IN THE CONSENT, WE MAKE 

2364
01:27:51,680 --> 01:27:52,214
THESE RISKS STATED IN THE 

2365
01:27:52,214 --> 01:27:52,981
PARTICIPANTS NEED TO BE AWARE 

2366
01:27:52,981 --> 01:27:53,515
OF THESE RISKS AND MAKE A 

2367
01:27:53,515 --> 01:27:55,350
CHOICE OF WHETHER OR NOT THEY 

2368
01:27:55,350 --> 01:27:56,685
WANT TO PARTICIPATE IN THIS 

2369
01:27:56,685 --> 01:27:57,252
STUDY, AND THIS BROAD DATA 

2370
01:27:57,252 --> 01:27:59,988
SHARING. 

2371
01:27:59,988 --> 01:28:00,522
ONE SPECIFIC ISSUE WITH THE 

2372
01:28:00,522 --> 01:28:03,392
IMAGING DATA FOR INSTANCES YOU 

2373
01:28:03,392 --> 01:28:04,059
CAN IDENTIFY THE FACE FROM SOME 

2374
01:28:04,059 --> 01:28:04,560
OF THE IMAGES THAT ARE 

2375
01:28:04,560 --> 01:28:10,732
COLLECTED. AND THAT REQUIRES 

2376
01:28:10,732 --> 01:28:11,366
ADDITIONAL PROTECTION MEASURES 

2377
01:28:11,366 --> 01:28:12,067
TO BE PLACED ON THAT IMAGING 

2378
01:28:12,067 --> 01:28:14,236
MODALITY IN PARTICULAR. 

2379
01:28:14,236 --> 01:28:16,572
I ABSOLUTELY AGREE WITH YOU I 

2380
01:28:16,572 --> 01:28:17,139
WE SHOULD HAVE THIS IN OUR 

2381
01:28:17,139 --> 01:28:19,541
CONSENTS.  AND PARTICIPANT 

2382
01:28:19,541 --> 01:28:20,175
SHOULD BE AWARE AND THEY SHOULD 

2383
01:28:20,175 --> 01:28:22,544
BE A MOVE TOWARDS BROAD DATA 

2384
01:28:22,544 --> 01:28:25,347
SHARING ACROSS THESE DIFFERENT 

2385
01:28:25,347 --> 01:28:28,851
STUDIES WHEN AT ALL POSSIBLE.

2386
01:28:28,851 --> 01:28:38,360
 >> DR. CHEN?

2387
01:28:38,360 --> 01:28:42,764
>> DR. CHEN-PLOTKIN: THE
ONE I 

2388
01:28:42,764 --> 01:28:43,332
KNOW THE MOST ABOUT IS THE 

2389
01:28:43,332 --> 01:28:43,866
PARKINSON'S IS BIOMARKER 

2390
01:28:43,866 --> 01:28:46,201
PROGRAM MORE PDP EXISTENCES 

2391
01:28:46,201 --> 01:28:48,971
2012.  YOU MAY HAVE ENROLLED IN 

2392
01:28:48,971 --> 01:28:55,777
THE STUDY THROUHG A SITE, FOR 

2393
01:28:55,777 --> 01:28:56,378
THE CONSENT IS BROUGHT IN THE 

2394
01:28:56,378 --> 01:28:56,979
REASON I KNOW THAT IS BECAUSE 

2395
01:28:56,979 --> 01:28:59,148
I'M A USER OF MANY OF THE 

2396
01:28:59,148 --> 01:29:01,950
SAMPLES AND SO I DO THINK THAT 

2397
01:29:01,950 --> 01:29:02,584
THERE IS AWARENESS AT THE LEVEL 

2398
01:29:02,584 --> 01:29:05,721
OF BIO SAMPLES ORGANIZED IN THE 

2399
01:29:05,721 --> 01:29:09,558
(INDISCERNIBLE) LEVEL, HAVING 

2400
01:29:09,558 --> 01:29:10,159
CONSENT FOR BROAD SHARING AND 

2401
01:29:10,159 --> 01:29:12,494
ESSENTIALLY HAVING A COMMITTEE 

2402
01:29:12,494 --> 01:29:13,128
OF PEOPLE WHO LOOK AT REQUESTS 

2403
01:29:13,128 --> 01:29:14,496
TO SEE THE REQUESTS A 

2404
01:29:14,496 --> 01:29:15,130
REASONABLE AND THEN SHARE OUT 

2405
01:29:15,130 --> 01:29:16,031
THE SAMPLES. 

2406
01:29:16,031 --> 01:29:21,403
THAT IS DEFINITELY HAPPENING.  

2407
01:29:21,403 --> 01:29:21,904
MY LAB FOR EXAMPLE HAS 

2408
01:29:21,904 --> 01:29:22,971
BENEFITED GREATLY FROM THAT.

2409
01:29:22,971 --> 01:29:30,245
>> THANK YOU. 

2410
01:29:30,245 --> 01:29:30,846
>> VIKI, YOUR HAND IS UP
IF YOU 

2411
01:29:30,846 --> 01:29:31,680
DON'T MIND AND MUTING HERSELF 

2412
01:29:31,680 --> 01:29:32,214
AND ASKING A QUESTION OR 

2413
01:29:32,214 --> 01:29:32,581
COMMENT.

2414
01:29:32,581 --> 01:29:34,183
>> HI. MY MOTHER HAS BEEN 

2415
01:29:34,183 --> 01:29:39,588
DIAGNOSED -- WELL, ACTUALLY SHE 

2416
01:29:39,588 --> 01:29:40,189
REALLY HASN'T BEEN DIAGNOSED 

2417
01:29:40,189 --> 01:29:40,756
WITH ANYTHING. THAT IS MY 

2418
01:29:40,756 --> 01:29:42,124
QUESTION. 

2419
01:29:42,124 --> 01:29:45,360
AT FIRST, SHE DID GET A 

2420
01:29:45,360 --> 01:29:49,331
DIAGNOSIS OF ... MILD COGNITIVE 

2421
01:29:49,331 --> 01:29:51,700
IMPAIRMENT.  AND NOW IT SAYS ON 

2422
01:29:51,700 --> 01:29:55,437
HER CHART, "MAJOR 

2423
01:29:55,437 --> 01:29:59,007
NEUROMUSCULAR, OR 

2424
01:29:59,007 --> 01:30:02,477
NEURODEGENERATIVE" SOMETHING. 

2425
01:30:02,477 --> 01:30:03,912
ANYWAY I WAS WONDERING WHAT 

2426
01:30:03,912 --> 01:30:07,216
KIND OF TESTS SHOULD I INSIST 

2427
01:30:07,216 --> 01:30:07,783
UPON OR DO I EVEN HAVE THE 

2428
01:30:07,783 --> 01:30:15,357
RIGHT TO TRY TO FIND OUT A MORE 

2429
01:30:15,357 --> 01:30:16,992
DEFINITIVE DIAGNOSIS? I GUESS.

2430
01:30:16,992 --> 01:30:20,529
>> DR. -- WHICH LIKE TO
ADDRESS 

2431
01:30:20,529 --> 01:30:31,039
THIS ISSUE? OR DR. TOLEDO, TO 

2432
01:30:32,808 --> 01:30:33,375
TALK ABOUT WHERE WE ARE AT THIS 

2433
01:30:33,375 --> 01:30:34,009
POINT TO ONE OF THE CHALLENGES 

2434
01:30:34,009 --> 01:30:38,981
IS THE BALANCE OF THE 

2435
01:30:38,981 --> 01:30:39,615
BIOMARKERS FROM THE PERSPECTIVE 

2436
01:30:39,615 --> 01:30:40,182
OF THE RESEARCH USE VERSUS 

2437
01:30:40,182 --> 01:30:40,716
WHERE WE ARE IN CLINICAL 

2438
01:30:40,716 --> 01:30:41,483
IMPLEMENTATION AND THERE IS A 

2439
01:30:41,483 --> 01:30:44,253
DISTINCTION THERE. IF YOU TWO 

2440
01:30:44,253 --> 01:30:44,853
WOULD NOT MIND COMMENTING ON 

2441
01:30:44,853 --> 01:30:46,388
THAT. 

2442
01:30:46,388 --> 01:30:50,926
>> THANK YOU FOR YOUR
QUESTION. 

2443
01:30:50,926 --> 01:30:51,526
 IT IS AN IMPORTANT ONE, AND 

2444
01:30:51,526 --> 01:30:59,968
ONE THAT WE HEAR FROM OFTEN.  

2445
01:30:59,968 --> 01:31:00,502
IS A CHANCE TO IDENTIFY A 

2446
01:31:00,502 --> 01:31:01,136
CLINICIAN WHO HAS KNOWLEDGE IN 

2447
01:31:01,136 --> 01:31:04,339
THIS AREA. AND IF YOU HAPPEN TO 

2448
01:31:04,339 --> 01:31:07,609
NOT BE FORTUNATE TO MEET WITH A 

2449
01:31:07,609 --> 01:31:13,548
KNOWLEDGEABLE CLINICIAN 

2450
01:31:13,548 --> 01:31:14,149
INITIALLY, SEEK INPUT TO MEET 

2451
01:31:14,149 --> 01:31:14,783
WITH SOMEONE ELSE AND THERE ARE 

2452
01:31:14,783 --> 01:31:15,284
AMPLE DIAGNOSTIC TESTS 

2453
01:31:15,284 --> 01:31:18,020
AVAILABLE. 

2454
01:31:18,020 --> 01:31:28,063
AND THE CLINICIAN FOR WHATEVER 

2455
01:31:28,063 --> 01:31:28,664
REASON DOESN'T HAPPEN TO KNOW 

2456
01:31:28,664 --> 01:31:29,298
ABOUT THEM HONESTLY THEY WON'T 

2457
01:31:29,298 --> 01:31:29,865
BE USED. I SHOULD POINT OUT 

2458
01:31:29,865 --> 01:31:39,508
THAT THAT THE -- CENTER FOR 

2459
01:31:39,508 --> 01:31:40,108
EXCELLENCE PROGRAM THERE ARE 

2460
01:31:40,108 --> 01:31:40,709
OVER TWO DOZEN SPREAD ACROSS 

2461
01:31:40,709 --> 01:31:41,310
COUNTRY AND THAT NETWORK BUT 

2462
01:31:41,310 --> 01:31:41,943
DESIGNED FOR CLINICIANS WHO DO 

2463
01:31:41,943 --> 01:31:43,679
THIS FOR A LIVING. 

2464
01:31:43,679 --> 01:31:45,480
AND SO IF YOU HAPPEN TO LIVE 

2465
01:31:45,480 --> 01:31:46,081
FAR FROM ONE OF THE CENTERS, 

2466
01:31:46,081 --> 01:31:46,615
THAT DOES CREATE SOME 

2467
01:31:46,615 --> 01:31:49,017
CHALLENGES. BUT HOPEFULLY THAT 

2468
01:31:49,017 --> 01:31:50,919
IS AT LEAST PARTIALLY HELPFUL. 

2469
01:31:50,919 --> 01:31:52,554
>> OKAY THANK YOU. I
APPRECIATE 

2470
01:31:52,554 --> 01:32:00,262
THAT.

2471
01:32:00,262 --> 01:32:02,764
>> ADDITIONAL QUESTIONS
FOR 

2472
01:32:02,764 --> 01:32:03,165
PANELISTS?

2473
01:32:03,165 --> 01:32:13,642
I SEE ... MIKE LEE.  WOULD YOU 

2474
01:32:15,577 --> 01:32:16,078
MIND UNMUTING YOURSELF? YOU 

2475
01:32:16,078 --> 01:32:18,113
SHOULD BE ABLE TO. 

2476
01:32:18,113 --> 01:32:20,115
>> OKAY THANK YOU. 

2477
01:32:20,115 --> 01:32:22,417
>> I CAN HEAR YOUR GO
AHEAD. 

2478
01:32:22,417 --> 01:32:25,320
>> REALLY WONDERFUL 

2479
01:32:25,320 --> 01:32:25,821
PRESENTATIONS. I REALLY 

2480
01:32:25,821 --> 01:32:26,355
APPRECIATE IT. I LOVE THE 

2481
01:32:26,355 --> 01:32:27,422
ACTION ITEMS. 

2482
01:32:27,422 --> 01:32:31,493
ONE THING THAT I DID WANT TO 

2483
01:32:31,493 --> 01:32:32,894
MENTION IS THAT AS YOU ALL KNOW 

2484
01:32:32,894 --> 01:32:34,930
LEVY BODY DEMENTIA UNLIKE 

2485
01:32:34,930 --> 01:32:38,867
ALZHEIMER'S DISEASE IS 

2486
01:32:38,867 --> 01:32:39,434
ASSOCIATED WITH VERY LITTLE 

2487
01:32:39,434 --> 01:32:40,068
NEURODEGENERATION AT LEAST IN 

2488
01:32:40,068 --> 01:32:42,104
THE LIMBIC AREA. 

2489
01:32:42,104 --> 01:32:46,341
AND I WE NEED TO MAYBE PUT MORE 

2490
01:32:46,341 --> 01:32:56,385
EMPHASIS ON WHAT NUCLEON 

2491
01:32:56,385 --> 01:32:57,018
PATHOLOGY DOES AT THE CELLULAR 

2492
01:32:57,018 --> 01:33:02,858
LEVEL AND CIRCUIT LEVEL. THERE 

2493
01:33:02,858 --> 01:33:03,425
IS THE OPPORTUNITY THERE TO 

2494
01:33:03,425 --> 01:33:04,059
UNDERSTAND THE PATHOBIOLOGY AS 

2495
01:33:04,059 --> 01:33:04,693
A CERTAIN LEVEL WHAT YOU HAVE 

2496
01:33:04,693 --> 01:33:07,596
DEMENTIA IN LEVY BODY DEMENTIA. 

2497
01:33:07,596 --> 01:33:10,799
WE ARE IN ALZHEIMER'S, 

2498
01:33:10,799 --> 01:33:15,137
OBVIOUSLY YOU ARE LOSING 

2499
01:33:15,137 --> 01:33:15,804
NEURONS. THAT IS NOT SURPRISING 

2500
01:33:15,804 --> 01:33:17,339
THAT I WAS SURPRISED THAT THERE 

2501
01:33:17,339 --> 01:33:20,575
WAS NOT AS MUCH OF THAT FOCUS.  

2502
01:33:20,575 --> 01:33:21,276
AND I THINK WE REALLY NEED TO 

2503
01:33:21,276 --> 01:33:24,379
HAVE A BETTER UNDERSTANDING OF 

2504
01:33:24,379 --> 01:33:25,447
WHAT IS GOING ON WITH THE 

2505
01:33:25,447 --> 01:33:27,749
NEURONS. 

2506
01:33:27,749 --> 01:33:37,426
>> GREAT QUESTION. DR. 

2507
01:33:37,426 --> 01:33:38,193
CHEN-PLOTKIN?

2508
01:33:38,193 --> 01:33:41,830
>> DR. CHEN-PLOTKIN: YOU
IF YOU 

2509
01:33:41,830 --> 01:33:43,365
KNOW THE TWOS REGULATIONS I 

2510
01:33:43,365 --> 01:33:43,832
HAVE, ONE FOCUSED ON 

2511
01:33:43,832 --> 01:33:47,636
A-SYNUCLEIN.  THAT WAS ACTUALLY 

2512
01:33:47,636 --> 01:33:48,570
A BOLD MOVE FROM A COMMITTEE TO 

2513
01:33:48,570 --> 01:33:49,905
KIND OF PUT A LOT OF EMPHASIS 

2514
01:33:49,905 --> 01:33:54,109
ON A-SYNUCLEIN, AND 

2515
01:33:54,109 --> 01:33:56,878
UNDERSTANDING THE FUNCTIONS 

2516
01:33:56,878 --> 01:34:03,418
A-SYNUCLEIN HAS IN NEURONS. AND 

2517
01:34:03,418 --> 01:34:04,519
SPREAD THE CONFIRMATIONS.

2518
01:34:04,519 --> 01:34:05,754
THE REASON THERE IS EMPHASIS ON 

2519
01:34:05,754 --> 01:34:06,354
THAT IN THE COMMITTEE IS THAT 

2520
01:34:06,354 --> 01:34:06,988
SO MUCH HAS BEEN LEARNED ABOUT 

2521
01:34:06,988 --> 01:34:09,357
A-SYNUCLEIN.  AND AS I SAID IT 

2522
01:34:09,357 --> 01:34:11,193
IS NOW IN CLINICAL TESTING. SO 

2523
01:34:11,193 --> 01:34:12,027
WE REALLY NEED TO UNDERSTAND 

2524
01:34:12,027 --> 01:34:13,728
THIS. OKAY?

2525
01:34:13,728 --> 01:34:17,132
AT THE SAME TIME, THE 8TH 

2526
01:34:17,132 --> 01:34:19,501
RECOMMENDATIONS ABOUT BASICALLY 

2527
01:34:19,501 --> 01:34:20,569
THE DIRECTION OF OTHER THINGS 

2528
01:34:20,569 --> 01:34:22,838
WITH A-SYNUCLEIN. 

2529
01:34:22,838 --> 01:34:26,074
WE COMPLETELY AGREE WITH YOU. 

2530
01:34:26,074 --> 01:34:26,641
WHY IS IT THAT IN SOME PEOPLE 

2531
01:34:26,641 --> 01:34:27,175
SOME CIRCUITS ARE MORE 

2532
01:34:27,175 --> 01:34:28,877
VULNERABLE? RIGHT?

2533
01:34:28,877 --> 01:34:32,547
IS IT RELATED TO THE 

2534
01:34:32,547 --> 01:34:37,419
ALZHEIMER'S DISEASE PATHOLOGY 

2535
01:34:37,419 --> 01:34:37,986
THAT OCCURS IN SOME PEOPLE 

2536
01:34:37,986 --> 01:34:38,553
VERSUS NOT, WHICH ONE STUDY 

2537
01:34:38,553 --> 01:34:39,654
SUGGESTS IS THE CASE. 

2538
01:34:39,654 --> 01:34:40,722
IS THAT RELATED TO OTHER 

2539
01:34:40,722 --> 01:34:42,123
FACTORS?

2540
01:34:42,123 --> 01:34:45,594
GENETIC, GENOMIC, BIOMARKER 

2541
01:34:45,594 --> 01:34:46,561
ENVIRONMENTAL FACTORS?

2542
01:34:46,561 --> 01:34:49,998
THAT IS CAPTURED IN 8.  WHAT 

2543
01:34:49,998 --> 01:34:50,532
YOU ARE RIGHT WE NEED TO 

2544
01:34:50,532 --> 01:34:57,472
UNDERSTAND THIS BETTER. 

2545
01:34:57,472 --> 01:34:58,073
>> I WANT TO FOLLOW UP ON
THAT 

2546
01:34:58,073 --> 01:34:58,607
BECAUSE I UNDERSTAND YOUR 

2547
01:34:58,607 --> 01:34:59,241
PERSPECTIVE IN TERMS OF HOW IT 

2548
01:34:59,241 --> 01:35:00,008
IS GREAT IN THE CIRCUIT FASHION.

2549
01:35:00,008 --> 01:35:03,411
THAT IS A PATHOLOGY. 

2550
01:35:03,411 --> 01:35:04,012
I'M TALKING MORE ABOUT ACTUALLY 

2551
01:35:04,012 --> 01:35:07,482
AT A FUNCTIONAL LEVEL. WE HAVE 

2552
01:35:07,482 --> 01:35:08,250
A VERY, VERY LIMITED 

2553
01:35:08,250 --> 01:35:12,687
UNDERSTANDING OF HOW THE 

2554
01:35:12,687 --> 01:35:15,323
NUCLEON PATHOLOGY, WHY IS IT 

2555
01:35:15,323 --> 01:35:15,857
NOT DEAD?

2556
01:35:15,857 --> 01:35:16,424
CORTICAL NEURONS, THEY DON'T 

2557
01:35:16,424 --> 01:35:19,361
DIE WHEN YOU HAVE NUCLEON 

2558
01:35:19,361 --> 01:35:19,928
PATHOLOGY, BUT WE HAVE VERY 

2559
01:35:19,928 --> 01:35:20,729
LITTLE UNDERSTANDING OF HOW 

2560
01:35:20,729 --> 01:35:27,335
THAT AFFECTS THE NEURAL 

2561
01:35:27,335 --> 01:35:28,503
FUNCTION AND HOW THAT NEURON IN 

2562
01:35:28,503 --> 01:35:29,037
THAT CONTEXT AFFECTS THE 

2563
01:35:29,037 --> 01:35:33,275
CIRCUIT, WHICH IS VERY, VERY 

2564
01:35:33,275 --> 01:35:34,409
SIGNIFICANT THING IN TERMS OF 

2565
01:35:34,409 --> 01:35:39,548
HOW HUMANS ACTUALLY BEHAVE. 

2566
01:35:39,548 --> 01:35:40,148
THAT IS SOMETHING WE NEED TO 

2567
01:35:40,148 --> 01:35:40,882
HAVE A BETTER UNDERSTANDING. 

2568
01:35:40,882 --> 01:35:49,624
>> DR. CHEN-PLOTKIN: WE
AGREE 

2569
01:35:49,624 --> 01:35:51,359
WITH YOU AND I APOLOGIZE IF I 

2570
01:35:51,359 --> 01:35:57,866
WAS NOT CLEAR ENOUGH. THAT WAS 

2571
01:35:57,866 --> 01:35:58,466
A DECISION WAS TRYING TO MAKE 

2572
01:35:58,466 --> 01:35:59,000
BETWEEN FACTORS OF NEURAL 

2573
01:35:59,000 --> 01:35:59,401
PATHOLOGY VERSUS 

2574
01:35:59,401 --> 01:35:59,968
NEURODEGENERATION. THEY ARE 

2575
01:35:59,968 --> 01:36:00,602
RELATED TO EACH OTHER BUT THEY 

2576
01:36:00,602 --> 01:36:06,942
ARE NOT THE SAME. 

2577
01:36:06,942 --> 01:36:09,377
>> THANK YOU FOR THE
COMMENT. 

2578
01:36:09,377 --> 01:36:10,946
WE HAVE A FEW HANDS HERE. I 

2579
01:36:10,946 --> 01:36:16,418
APOLOGIZE. NUMBER ONE, ... IF 

2580
01:36:16,418 --> 01:36:22,090
YOU WOULDN'T MIND UNMUTING. 

2581
01:36:22,090 --> 01:36:23,758
>> (CLARIFY THE
PRONUNCIATION)

2582
01:36:23,758 --> 01:36:26,261
(INDISCERNIBLE). 

2583
01:36:26,261 --> 01:36:28,530
I WANTED TO ASK THE QUESTION 

2584
01:36:28,530 --> 01:36:29,965
CONCERNING LEVY BODY DEMENTIA 

2585
01:36:29,965 --> 01:36:37,138
IN 21 CHROMOSOME TRISOMICS 

2586
01:36:37,138 --> 01:36:38,974
(PHONETIC). 

2587
01:36:38,974 --> 01:36:42,944
QUICK QUESTION. 

2588
01:36:42,944 --> 01:36:43,545
>> IF YOU COULD REPEAT
THAT. I 

2589
01:36:43,545 --> 01:36:44,779
DID NOT QUITE UNDERSTAND. 

2590
01:36:44,779 --> 01:36:46,681
>> THE QUESTION IS ABOUT
LEVY 

2591
01:36:46,681 --> 01:36:52,454
BODY DEMENTIA, IT HAS 

2592
01:36:52,454 --> 01:36:56,124
A-SYNUCLEIN NEUROPATHY IN 21 

2593
01:36:56,124 --> 01:36:59,060
CHROMOSOME TRISOMICS IN DOWN 

2594
01:36:59,060 --> 01:37:11,375
SYNDROME. 

2595
01:37:11,375 --> 01:37:14,712
THAT WAS NOT COVERED. 

2596
01:37:14,712 --> 01:37:20,384
>> NO. THAT WAS NOT. 

2597
01:37:20,384 --> 01:37:23,287
MY GENERAL UNDERSTANDING, NOT 

2598
01:37:23,287 --> 01:37:23,888
BEING THE GENETICIST ON THIS 

2599
01:37:23,888 --> 01:37:25,656
PANEL, IS THAT WHILE 

2600
01:37:25,656 --> 01:37:26,157
ALZHEIMER'S-ASSOCIATED 

2601
01:37:26,157 --> 01:37:29,160
PATHOLOGY AND DEMENTIA IS 

2602
01:37:29,160 --> 01:37:33,631
HEAVILY ASSOCIATED WITH TRISOMY 

2603
01:37:33,631 --> 01:37:38,402
21 DOWN SYNDROME AND LEVY BODY 

2604
01:37:38,402 --> 01:37:39,504
DEMENTIA PATHOLOGY IS LESS 

2605
01:37:39,504 --> 01:37:42,740
LIKELY ASSOCIATED. DOCTOR-- IF 

2606
01:37:42,740 --> 01:37:46,677
YOU COULD CLARIFY THIS PERMIT 

2607
01:37:46,677 --> 01:37:50,314
PATHOLOGICAL PERSPECTIVE, THAT 

2608
01:37:50,314 --> 01:37:51,315
WE DO NOT SEE LEVY BODY 

2609
01:37:51,315 --> 01:37:57,255
PATHOLOGY?

2610
01:37:57,255 --> 01:37:57,889
>> I HAVE NOT SEEN MANY
DOWN 

2611
01:37:57,889 --> 01:37:58,523
SYNDROME BRAINS. I WISH I COULD 

2612
01:37:58,523 --> 01:38:02,159
KNOW THE LITERATURE. FEEL FREE 

2613
01:38:02,159 --> 01:38:02,793
TO EMAIL ME AND I CAN GET BACK 

2614
01:38:02,793 --> 01:38:03,461
TO YOU, TO MAKE SURE IT IS 

2615
01:38:03,461 --> 01:38:04,695
ANSWERED. THIS IS BEING 

2616
01:38:04,695 --> 01:38:05,329
RECORDED. SO WE WILL HAVE THIS 

2617
01:38:05,329 --> 01:38:06,097
RECORDED. 

2618
01:38:06,097 --> 01:38:07,865
>> DR. TOLEDO?

2619
01:38:07,865 --> 01:38:09,934
>> DR. TOLEDO ATUCHA:
ACTUALLY 

2620
01:38:09,934 --> 01:38:15,206
IT IS PRETTY PREVALENT. THE 

2621
01:38:15,206 --> 01:38:19,010
LEVY BODY IS ACTING IN 

2622
01:38:19,010 --> 01:38:21,546
(INDISCERNIBLE) PATHOLOGY AND 

2623
01:38:21,546 --> 01:38:22,346
WE NEED SOME CORE SYMPTOMS 

2624
01:38:22,346 --> 01:38:30,488
PEOPLE WHO HAVE TRISOMIC 

2625
01:38:30,488 --> 01:38:34,425
PATHOLOGY -- THINK THAT IS VERY 

2626
01:38:34,425 --> 01:38:35,560
COMPLEX BECAUSE AS YOU SAW IN 

2627
01:38:35,560 --> 01:38:38,529
THE PREVIOUS TALK, THE NORM IS 

2628
01:38:38,529 --> 01:38:42,800
HAVING MULTIPLE CO-PATHOLOGIES. 

2629
01:38:42,800 --> 01:38:43,434
 BUT WE ACKNOWLEDGE THAT THOSE 

2630
01:38:43,434 --> 01:38:46,704
PEOPLE WITH DEMENTIA THEY HAVE 

2631
01:38:46,704 --> 01:38:49,273
PEOPLE WITH ALZHEIMER'S DISEASE 

2632
01:38:49,273 --> 01:38:54,011
WITH (INDISCERNIBLE) PATHOLOGY. 

2633
01:38:54,011 --> 01:38:54,645
>> THAT IS PART OF WHAT
THE 

2634
01:38:54,645 --> 01:38:55,279
PREVIOUS SESSION WAS TRYING TO 

2635
01:38:55,279 --> 01:38:57,415
ADDRESS.  HOW DO WE THINK ABOUT 

2636
01:38:57,415 --> 01:39:01,285
THESE MIXED ETIOLOGY SITUATIONS 

2637
01:39:01,285 --> 01:39:08,125
IN A MORE COMPREHENSIVE WAY?

2638
01:39:08,125 --> 01:39:09,794
AND GENETICALLY DEFINED 

2639
01:39:09,794 --> 01:39:10,361
NEURODEGENERATIVE DISORDERS 

2640
01:39:10,361 --> 01:39:11,028
REALLY DO FALL UNDER THAT. SOME 

2641
01:39:11,028 --> 01:39:16,334
OF THEM ARE ONE PATHOLOGY, 

2642
01:39:16,334 --> 01:39:16,968
OTHERS HAVE A MIXED PICTURE FOR 

2643
01:39:16,968 --> 01:39:17,568
THE CLINICAL PRESENTATION IS 

2644
01:39:17,568 --> 01:39:20,271
NOT TYPICAL FOR THE CLASSIC 

2645
01:39:20,271 --> 01:39:24,308
PHENOTYPE. 

2646
01:39:24,308 --> 01:39:24,842
I BELIEVE THAT IS ACTUALLY 

2647
01:39:24,842 --> 01:39:25,476
SOMETHING THAT VERY MUCH NEEDS 

2648
01:39:25,476 --> 01:39:26,944
TO BE ADDRESSED.  THANK YOU FOR 

2649
01:39:26,944 --> 01:39:29,213
BRINGING THAT UP. 

2650
01:39:29,213 --> 01:39:33,417
>> WE ARE AT THE END OF
TIME. 

2651
01:39:33,417 --> 01:39:35,820
WE ENCOURAGE PEOPLE TO BRING 

2652
01:39:35,820 --> 01:39:41,592
THEIR REMAINING QUESTIONS TO 

2653
01:39:41,592 --> 01:39:42,126
THE FURTHER PUBLIC INPUT 

2654
01:39:42,126 --> 01:39:45,663
SESSION SCHEDULED TO START AT 

2655
01:39:45,663 --> 01:39:48,466
2:50 THIS AFTERNOON. 

2656
01:39:48,466 --> 01:39:49,000
>> THANK YOU TO ALL THE 

2657
01:39:49,000 --> 01:39:51,535
PRESENTERS. 

2658
01:39:51,535 --> 01:40:01,879
>> THANK YOU EVERYONE. 

2659
01:40:04,682 --> 01:40:06,717
>> WE WILL HAVE A SHORT
BREAK 

2660
01:40:06,717 --> 01:40:07,318
WHILE WE GET THE NEXT SESSION 

2661
01:40:07,318 --> 01:40:07,918
SET UP, AND THEN GO STRAIGHT 

2662
01:40:07,918 --> 01:40:13,224
INTO THE LAST SESSION OF TODAY. 

2663
01:40:13,224 --> 01:40:16,938
WE WILL BE BACK IN 3 MINUTES.
THANK YOU. 

2664
01:40:16,938 --> 01:40:19,574
>> IS THE SESSION READY TO
GET 

2665
01:40:19,574 --> 01:40:21,442
STARTED?

2666
01:40:21,442 --> 01:40:26,747
>> DR. FOSSATI: I AM CAN
YOU 

2667
01:40:26,747 --> 01:40:27,114
HEAR ME?

2668
01:40:27,114 --> 01:40:29,083
>> I CAN. 

2669
01:40:29,083 --> 01:40:32,687
>> DR. FOSSATI: IT WAS
REALLY 

2670
01:40:32,687 --> 01:40:33,254
AN HONOR AND A PLEASURE TO 

2671
01:40:33,254 --> 01:40:33,855
COCHAIR THE SESSION TOGETHER 

2672
01:40:33,855 --> 01:40:37,091
WITH HANZHANG LU. 

2673
01:40:37,091 --> 01:40:37,725
AND SO I WILL GIVE YOU A BRIEF 

2674
01:40:37,725 --> 01:40:41,696
INTRODUCTION ON VCID MECHANISMS 

2675
01:40:41,696 --> 01:40:43,331
AND THEN GO AHEAD AND GIVE YOU 

2676
01:40:43,331 --> 01:40:45,900
LIKE THE FIRST TWO 

2677
01:40:45,900 --> 01:40:48,202
RECOMMENDATIONS THAT ARE ON THE 

2678
01:40:48,202 --> 01:40:50,872
BASIC MECHANISMS.

2679
01:40:50,872 --> 01:40:54,509
WHAT IS VCID?

2680
01:40:54,509 --> 01:40:55,109
THESE ARE MY VIEWS AND I DON'T 

2681
01:40:55,109 --> 01:40:55,710
HAVE ANY DISCLOSURES. 

2682
01:40:55,710 --> 01:40:56,644
NEXT SLIDE. 

2683
01:40:56,644 --> 01:41:02,416
WHAT IS VCID?

2684
01:41:02,416 --> 01:41:03,818
VASCULAR CONTRIBUTIONS TO 

2685
01:41:03,818 --> 01:41:04,352
COGNITIVE IMPAIRMENT AND 

2686
01:41:04,352 --> 01:41:04,752
DEMENTIA?

2687
01:41:04,752 --> 01:41:12,326
THE SCIENCE OF VCID IS 

2688
01:41:12,326 --> 01:41:17,265
SIGNIFICANT COGNITIVE 

2689
01:41:17,265 --> 01:41:27,275
IMPAIRMENT, RESULTING IN BRAIN 

2690
01:41:27,275 --> 01:41:30,878
LESION, LIKE MICRO INFARCT, 

2691
01:41:30,878 --> 01:41:31,445
ARTERIOSCLEROSIS, SYSTEMIC 

2692
01:41:31,445 --> 01:41:38,085
ATTACKS AND SEVERAL OTHERS. 

2693
01:41:38,085 --> 01:41:39,820
VCID IS NOT ONLY A BRAIN ISSUE 

2694
01:41:39,820 --> 01:41:40,354
BUT IS IMPORTANT SYSTEMIC 

2695
01:41:40,354 --> 01:41:40,955
COMPONENTS, VERY COMMON WITH 

2696
01:41:40,955 --> 01:41:42,990
AGING. 

2697
01:41:42,990 --> 01:41:43,591
AND WE ALL KNOW THAT IT IS AT 

2698
01:41:43,591 --> 01:41:44,292
LEAST IN PART PREVENTABLE. 

2699
01:41:44,292 --> 01:41:47,595
SO, THE COGNITIVE OUTCOMES 

2700
01:41:47,595 --> 01:41:52,066
ASSOCIATED WITH VCID CAN VARY 

2701
01:41:52,066 --> 01:41:59,540
IN TERMS OF LIKE HOW SERIOUS 

2702
01:41:59,540 --> 01:42:00,174
THESE INJURIES ARE. BUT ALSO IN 

2703
01:42:00,174 --> 01:42:07,949
ANATOMICAL LOCATION OF THE 

2704
01:42:07,949 --> 01:42:08,482
INJURY, COMORBIDITIES IN 

2705
01:42:08,482 --> 01:42:09,016
VASCULAR RISK FACTORS AND 

2706
01:42:09,016 --> 01:42:09,650
SEVERAL OTHER FACTORS. 

2707
01:42:09,650 --> 01:42:10,818
NEXT SLIDE. 

2708
01:42:10,818 --> 01:42:11,385
OF COURSE WE HAVE TO KEEP IN 

2709
01:42:11,385 --> 01:42:16,424
MIND THAT VCID DOESN'T EXIST IN 

2710
01:42:16,424 --> 01:42:17,258
ISOLATION, BUT IN MANY CASES IT 

2711
01:42:17,258 --> 01:42:19,927
HAPPENS TOGETHER WITH 

2712
01:42:19,927 --> 01:42:21,462
ALZHEIMER'S DISEASE PATHOLOGY 

2713
01:42:21,462 --> 01:42:29,103
SO AMYLOID -- PATHOLOGY. 

2714
01:42:29,103 --> 01:42:29,637
WE HAVE TO CONSIDER ALL OF 

2715
01:42:29,637 --> 01:42:30,204
THESE TOGETHER AND WE KNOW 

2716
01:42:30,204 --> 01:42:32,373
RIGHT NOW AS MANY OF THE 

2717
01:42:32,373 --> 01:42:32,873
COMMITTEE MEMBERS HAVE 

2718
01:42:32,873 --> 01:42:43,317
HIGHLIGHTED IT MAKES THE 

2719
01:42:44,051 --> 01:42:44,552
PATHOLOGY DEMENTIA THE MOST 

2720
01:42:44,552 --> 01:42:45,186
COMMON FORM, AND VASCULAR-- OF 

2721
01:42:45,186 --> 01:42:45,953
THE MOST FREQUENT COMBINATION. 

2722
01:42:45,953 --> 01:42:48,289
WE HAVE TO HIGHLIGHT THAT THE 

2723
01:42:48,289 --> 01:42:54,161
SCIENCE OF VCID IS VERY MUCH 

2724
01:42:54,161 --> 01:42:54,762
MULTIDISCIPLINARY. IT HAS TO 

2725
01:42:54,762 --> 01:42:55,396
ACCOUNT VASCULAR PATHOLOGY AND 

2726
01:42:55,396 --> 01:42:59,700
RISK FACTORS, AND A LOT OF 

2727
01:42:59,700 --> 01:43:00,334
THINGS THAT HAPPENED LIKE HYPER 

2728
01:43:00,334 --> 01:43:00,968
PERFUSION, BLOOD BRAIN BARRIER 

2729
01:43:00,968 --> 01:43:04,005
PROBLEMS, FLOW ISSUES, 

2730
01:43:04,005 --> 01:43:04,705
CLEARANCE ISSUES, ETC. 

2731
01:43:04,705 --> 01:43:10,978
NEXT SLIDE. 

2732
01:43:10,978 --> 01:43:12,446
SO IF WE TAKE INTO ACCOUNT IN 

2733
01:43:12,446 --> 01:43:14,382
THOSE FAMOUS BIOMARKER CURVES 

2734
01:43:14,382 --> 01:43:21,856
THE VASCULAR BIOMARKERS IF WE 

2735
01:43:21,856 --> 01:43:23,224
ASSUME THAT THESE ARE 

2736
01:43:23,224 --> 01:43:23,791
IRRESPECTIVE OF HISTOLOGIC 

2737
01:43:23,791 --> 01:43:24,358
PROCESSES WE CAN SEE IN THE 

2738
01:43:24,358 --> 01:43:25,426
LIGHT BROWN CURVE IS THE 

2739
01:43:25,426 --> 01:43:31,799
VASCULAR BIOMARKERS. AND 

2740
01:43:31,799 --> 01:43:32,400
VASCULAR DISREGULATION MAY BE 

2741
01:43:32,400 --> 01:43:35,236
EARLY SIGNS OF BRAIN FACTOR, 

2742
01:43:35,236 --> 01:43:36,437
ASSOCIATED WITH ALZHEIMER'S 

2743
01:43:36,437 --> 01:43:37,038
DISEASE DEVELOPMENT. 

2744
01:43:37,038 --> 01:43:42,643
NEXT SLIDE. 

2745
01:43:42,643 --> 01:43:49,850
WE TALK ABOUT VCID, WE REALLY 

2746
01:43:49,850 --> 01:43:52,486
HAVE TO TALK ABOUT THE 

2747
01:43:52,486 --> 01:43:53,054
NEUROVASCULAR UNIT AND THE 

2748
01:43:53,054 --> 01:43:53,688
CEREBRAL VASCULAR SYSTEM WE CAN 

2749
01:43:53,688 --> 01:43:54,288
ACCOMPLISH UNIT OF CELLS THAT 

2750
01:43:54,288 --> 01:43:55,356
SURROUND AND INCLUDE THE 

2751
01:43:55,356 --> 01:44:00,161
CEREBRAL VESSELS. AND THESE 

2752
01:44:00,161 --> 01:44:00,761
CHANGES VARY DEPENDING ON THE 

2753
01:44:00,761 --> 01:44:01,696
SIZE OF THE VESSELS, 

2754
01:44:01,696 --> 01:44:05,533
MICROVASCULAR VESSELS, BIG 

2755
01:44:05,533 --> 01:44:06,167
VESSELS. BUT ALSO WHERE IN THE 

2756
01:44:06,167 --> 01:44:09,470
BRAIN WE ARE. THE BRAIN 

2757
01:44:09,470 --> 01:44:11,405
LOCALIZATION, HIPPOCAMPUS 

2758
01:44:11,405 --> 01:44:11,872
VERSUS CORTEX.

2759
01:44:11,872 --> 01:44:13,374
AND WE HAVE TO REMEMBER THAT 

2760
01:44:13,374 --> 01:44:16,477
THE CONTROL OF CEREBROVASCULAR 

2761
01:44:16,477 --> 01:44:19,246
FUNCTION DOES NOT ONLY DEPEND 

2762
01:44:19,246 --> 01:44:24,351
ON BRAIN FACTORS, SOCIAL 

2763
01:44:24,351 --> 01:44:26,420
NEUROVASCULAR COUPLING, BUT 

2764
01:44:26,420 --> 01:44:26,987
ALSO ON PERIPHERAL SYSTEMIC 

2765
01:44:26,987 --> 01:44:27,621
FACTORS SUCH AS BLOOD PRESSURE, 

2766
01:44:27,621 --> 01:44:28,322
PRESSURE OF CO2 AND OTHERS. 

2767
01:44:28,322 --> 01:44:31,525
NEXT SLIDE. 

2768
01:44:31,525 --> 01:44:33,961
AND VCID OF COURSE AS MANY RISK 

2769
01:44:33,961 --> 01:44:40,201
FACTORS.  A LOT OF THEM ARE 

2770
01:44:40,201 --> 01:44:40,768
SHARED WITH CARDIOVASCULAR 

2771
01:44:40,768 --> 01:44:45,606
DISEASES. 

2772
01:44:45,606 --> 01:44:46,140
WE HAVE NONMODIFIABLE RISK 

2773
01:44:46,140 --> 01:44:46,707
FACTORS LIKE AGE, SEX, AND 

2774
01:44:46,707 --> 01:44:47,241
GENETICS. BEHAVIORAL AND 

2775
01:44:47,241 --> 01:44:48,209
LIFESTYLE RISK FACTORS, BUT 

2776
01:44:48,209 --> 01:44:49,777
ALSO PSYCHOSOCIAL, 

2777
01:44:49,777 --> 01:44:50,411
SOCIOECONOMIC AND OTHER RISK 

2778
01:44:50,411 --> 01:44:52,713
FACTORS. 

2779
01:44:52,713 --> 01:44:55,416
WANTED A REALLY IMPORTANT TO 

2780
01:44:55,416 --> 01:44:56,016
FOCUS ON OUR METABOLIC RISK 

2781
01:44:56,016 --> 01:44:58,552
FACTORS SUCH AS OBESITY, 

2782
01:44:58,552 --> 01:44:59,120
DIABETES, HYPERTENSION, AND 

2783
01:44:59,120 --> 01:44:59,587
MANY OTHERS. 

2784
01:44:59,587 --> 01:45:05,426
NEXT SLIDE. 

2785
01:45:05,426 --> 01:45:09,797
AND SO, THESE RECEPTORS 

2786
01:45:09,797 --> 01:45:11,232
TOGETHER CAN PROMOTE  DEMENTIA 

2787
01:45:11,232 --> 01:45:14,401
PATHOLOGY. 

2788
01:45:14,401 --> 01:45:16,837
AND WE LOOK AT THE RISK FACTORS 

2789
01:45:16,837 --> 01:45:19,373
DEPENDING ON SEX, ACTUALLY THE 

2790
01:45:19,373 --> 01:45:19,874
RISK FACTORS MAY HAVE A 

2791
01:45:19,874 --> 01:45:29,350
DIFFERENT IMPACT IN MEN VERSUS 

2792
01:45:29,350 --> 01:45:30,818
WOMEN FOR EXAMPLE HEART DISEASE 

2793
01:45:30,818 --> 01:45:34,588
IS MORE OF A FACTOR IN MEN AND 

2794
01:45:34,588 --> 01:45:35,122
HYPERTENSION IS MORE OF A 

2795
01:45:35,122 --> 01:45:35,689
FACTOR FOR WOMEN. 

2796
01:45:35,689 --> 01:45:38,092
NEXT SLIDE. 

2797
01:45:38,092 --> 01:45:40,661
SO TO FINISH THIS INTRODUCTION, 

2798
01:45:40,661 --> 01:45:41,295
I REALLY WANT TO THANK ALL THE 

2799
01:45:41,295 --> 01:45:43,564
COMMITTEE MEMBERS.  THIS WAS AN 

2800
01:45:43,564 --> 01:45:44,899
INCREDIBLY COHESIVE AND 

2801
01:45:44,899 --> 01:45:48,269
COLLABORATIVE PROCESS.  AND 

2802
01:45:48,269 --> 01:45:56,477
ESPECIALLY I WANT TO THANK -- 

2803
01:45:56,477 --> 01:45:57,111
THAT HELP TOGETHER AND ORGANIZE 

2804
01:45:57,111 --> 01:45:57,745
THIS COMMITTEE. COULD NOT HAVE 

2805
01:45:57,745 --> 01:45:58,379
DONE THIS WITHOUT THEM. 

2806
01:45:58,379 --> 01:46:00,481
NEXT SLIDE. 

2807
01:46:00,481 --> 01:46:03,851
SO I'LL GO NOW INTO THE BASIC 

2808
01:46:03,851 --> 01:46:06,253
SCIENCE RECOMMENDATIONS. 

2809
01:46:06,253 --> 01:46:08,289
THE FIRST ONE PRIORITY ONE IS 

2810
01:46:08,289 --> 01:46:13,360
TO UNDERSTAND MECHANISMS OF 

2811
01:46:13,360 --> 01:46:13,928
VASCULAR DISEASE ONSET AND 

2812
01:46:13,928 --> 01:46:15,763
PROGRESSION, SPECIFIC CELL 

2813
01:46:15,763 --> 01:46:16,363
TYPES AND INTERACTIONS IN THE 

2814
01:46:16,363 --> 01:46:20,835
CONTEXT OF COGNITIVE DECLINE. 

2815
01:46:20,835 --> 01:46:21,368
AND SO FOCUSING ON SPECIFIC 

2816
01:46:21,368 --> 01:46:22,002
SYMPTOMS AND THEIR INTERACTIONS 

2817
01:46:22,002 --> 01:46:31,111
AND THIS SHOULD INCLUDE CELLS 

2818
01:46:31,111 --> 01:46:31,679
OF OF THE CEREBRAL POPULAR 

2819
01:46:31,679 --> 01:46:32,279
SYSTEM INCLUDING ENDOTHELIAL 

2820
01:46:32,279 --> 01:46:32,880
CELLS, ASTROCYTES, MICROGLIA 

2821
01:46:32,880 --> 01:46:34,748
AND OTHERS. 

2822
01:46:34,748 --> 01:46:39,820
IF YOU LOOK AT THE 

2823
01:46:39,820 --> 01:46:40,421
(INDISCERNIBLE) FOR SPECIFIC 

2824
01:46:40,421 --> 01:46:41,055
CELL TYPES OF THE NEUROVASCULAR 

2825
01:46:41,055 --> 01:46:41,722
UNIT YOU SEE THERE IS A GROWING 

2826
01:46:41,722 --> 01:46:46,260
NUMBER OF CITATIONS WITH 60 

2827
01:46:46,260 --> 01:46:46,894
RESULTS IN 2024. BUT OF COURSE 

2828
01:46:46,894 --> 01:46:48,395
WE NEED TO DO MORE. 

2829
01:46:48,395 --> 01:46:52,233
THIS ALSO ALLOWED THE 

2830
01:46:52,233 --> 01:46:53,067
DEVELOPMENT OF NEW TECHNOLOGIES 

2831
01:46:53,067 --> 01:46:53,701
THAT GAVE US THE POSSIBILITY TO 

2832
01:46:53,701 --> 01:46:57,004
DO SINGLE CELL RNA SEQUENCING 

2833
01:46:57,004 --> 01:47:00,741
OR SINGLE CELL ANALYSIS IN 

2834
01:47:00,741 --> 01:47:01,475
CELLS OF THE HUMAN BRAIN 

2835
01:47:01,475 --> 01:47:02,910
VASCULATURE ACROSS DISEASE AND 

2836
01:47:02,910 --> 01:47:06,780
IN ALZHEIMER'S DISEASE AND 

2837
01:47:06,780 --> 01:47:07,281
VASCULAR DYSFUNCTION IN 

2838
01:47:07,281 --> 01:47:07,715
PARTICULAR. 

2839
01:47:07,715 --> 01:47:09,750
NEXT SLIDE. 

2840
01:47:09,750 --> 01:47:16,223
AND ALSO THANKS TO THESE RNA 

2841
01:47:16,223 --> 01:47:16,857
SEQUENCING STUDIES WE HAVE BEEN 

2842
01:47:16,857 --> 01:47:19,693
ABLE TO PINPOINT WHERE 

2843
01:47:19,693 --> 01:47:20,261
IMPORTANT PATHWAYS AND 

2844
01:47:20,261 --> 01:47:25,633
MECHANISMS. 

2845
01:47:25,633 --> 01:47:26,200
WE KNOW THAT THE STUDY SHOULD 

2846
01:47:26,200 --> 01:47:26,800
CLARIFY ALL THESE MECHANISMS 

2847
01:47:26,800 --> 01:47:28,202
INCLUDING LOSS OF BLOOD BRAIN 

2848
01:47:28,202 --> 01:47:35,476
BARRIER INTEGRITY, 

2849
01:47:35,476 --> 01:47:36,110
ANGIOGENESIS, AND HOW THE LAWS 

2850
01:47:36,110 --> 01:47:38,545
OF BLOOD BARRIER INTEGRITY 

2851
01:47:38,545 --> 01:47:39,146
AFFECTS BRAIN BIOMARKERS, AND 

2852
01:47:39,146 --> 01:47:41,015
WE HAVE TO DO MORE INTERESTED 

2853
01:47:41,015 --> 01:47:43,050
IN HOW THESE PATHWAYS CHANGE 

2854
01:47:43,050 --> 01:47:45,486
AND HOW THESE CELLS INTERACT IN 

2855
01:47:45,486 --> 01:47:46,220
DETERMINING THE CHANGES. 

2856
01:47:46,220 --> 01:47:50,257
NEXT SLIDE. 

2857
01:47:50,257 --> 01:47:54,561
AND, OF COURSE, AB PATHOLOGY IS 

2858
01:47:54,561 --> 01:47:55,195
INVOLVED IN THIS MECHANISMS AS 

2859
01:47:55,195 --> 01:47:55,629
WELL. 

2860
01:47:55,629 --> 01:48:00,167
WE KNOW THAT -- DEPOSITS IN THE 

2861
01:48:00,167 --> 01:48:04,405
VESSELS, CAA IN PARTICULAR BUT 

2862
01:48:04,405 --> 01:48:11,145
RECENT STUDIES HAVE SHOWN THAT 

2863
01:48:11,145 --> 01:48:12,346
TAU ACCUMULATING THE BRAIN 

2864
01:48:12,346 --> 01:48:13,013
VASCULATURE. WE ARE STARTING TO 

2865
01:48:13,013 --> 01:48:23,524
UNDERSTAND THE TAU EFFECTS OF 

2866
01:48:25,025 --> 01:48:25,559
THE BLOOD BRAIN BARRIER THAT 

2867
01:48:25,559 --> 01:48:26,093
AFFECTS ENDOTHELIAL CELLS 

2868
01:48:26,093 --> 01:48:26,727
REDUCING PYRAMID ABILITY. THIS 

2869
01:48:26,727 --> 01:48:27,361
SHOULD ALSO BE STUDIED. 

2870
01:48:27,361 --> 01:48:29,396
NEXT SLIDE. 

2871
01:48:29,396 --> 01:48:30,230
WE WANT TO IMPROVE THE 

2872
01:48:30,230 --> 01:48:30,864
UNDERSTANDING OF THE EFFECTS OF 

2873
01:48:30,864 --> 01:48:35,202
THE CID ON THE INTERACTION 

2874
01:48:35,202 --> 01:48:35,836
BETWEEN DIFFERENT CELL TYPES AS 

2875
01:48:35,836 --> 01:48:36,403
WELL AS ON THE MOVEMENT AND 

2876
01:48:36,403 --> 01:48:39,807
CLEARANCE OF MOLECULES ACROSS 

2877
01:48:39,807 --> 01:48:42,776
THE PERIVASCULAR SPACE, CSF AND 

2878
01:48:42,776 --> 01:48:46,046
BLOOD-BRAIN BARRIER. AND MANY 

2879
01:48:46,046 --> 01:48:46,647
MECHANISMS HAVE BEEN POINTED 

2880
01:48:46,647 --> 01:48:47,381
OUT SUCH AS INTRAMURAL 

2881
01:48:47,381 --> 01:48:52,286
DRAINAGE, LYMPHATIC DRAINAGE,  

2882
01:48:52,286 --> 01:48:57,057
MENINGEAL LYMPHATIC CLEARANCE 

2883
01:48:57,057 --> 01:48:59,593
AND PERIVASCULAR LEARN 

2884
01:48:59,593 --> 01:49:00,160
MICROPHAGES. THIS MOVEMENT 

2885
01:49:00,160 --> 01:49:00,661
AFFECT THE MOVEMENT AND 

2886
01:49:00,661 --> 01:49:02,262
CLEARANCE OF MOLECULES AND HOW 

2887
01:49:02,262 --> 01:49:02,863
THEY INTERACT WITH EACH OTHER 

2888
01:49:02,863 --> 01:49:03,597
IS A VERY IMPORTANT QUESTION. 

2889
01:49:03,597 --> 01:49:06,934
NEXT SLIDE. 

2890
01:49:06,934 --> 01:49:12,206
AND WE SHOULD ALSO CONSIDER 

2891
01:49:12,206 --> 01:49:22,683
VASCULAR PATHOLOGY SUCH AS 

2892
01:49:28,288 --> 01:49:28,856
CEREBRAL ANGIOGRAPHY, CEREBRAL 

2893
01:49:28,856 --> 01:49:29,490
ARTERIAL SCLEROSIS, AND HOW WE 

2894
01:49:29,490 --> 01:49:30,024
CAN PREVENT DISEASES FOR 

2895
01:49:30,024 --> 01:49:33,694
EXAMPLE CARDIOVASCULAR DISEASE, 

2896
01:49:33,694 --> 01:49:34,862
DEMENTIA IN A DIFFERENT WAY WE 

2897
01:49:34,862 --> 01:49:35,429
SHOULD CONSIDER ALL OF THEM 

2898
01:49:35,429 --> 01:49:36,163
TOGETHER OR IN COMBINATION. 

2899
01:49:36,163 --> 01:49:38,465
NEXT SLIDE. 

2900
01:49:38,465 --> 01:49:45,706
SO, IN ADDITION TO COGNITIVE 

2901
01:49:45,706 --> 01:49:46,340
DECLINE WE SHOULD ALSO CONSIDER 

2902
01:49:46,340 --> 01:49:47,941
OUTCOMES THAT ARE RELATED TO 

2903
01:49:47,941 --> 01:49:48,509
COGNITIVE DECLINE, BUT MORE 

2904
01:49:48,509 --> 01:49:49,076
VASCULAR SPECIFICS SUCH AS 

2905
01:49:49,076 --> 01:49:49,710
MARKER HEMORRHAGES, WHITE 

2906
01:49:49,710 --> 01:49:59,887
MATTER (INDISCERNIBLE) IN LARGE 

2907
01:49:59,887 --> 01:50:00,487
PERIVASCULAR SPACES AND LYPO 

2908
01:50:00,487 --> 01:50:01,088
PERFUSION. AND THERE ARE SOME 

2909
01:50:01,088 --> 01:50:02,623
NICE ANIMAL MODELS, FOR EXAMPLE 

2910
01:50:02,623 --> 01:50:04,858
MARKER HEMORRHAGES ON THE LEFT 

2911
01:50:04,858 --> 01:50:06,393
SIDE, AND YOU CAN SEE A RAT 

2912
01:50:06,393 --> 01:50:07,795
MODEL WHICH ALLOWS US TO SEE 

2913
01:50:07,795 --> 01:50:11,065
WHITE MATTER ISSUES BETTER THAN 

2914
01:50:11,065 --> 01:50:12,366
MOUSE MODELS. 

2915
01:50:12,366 --> 01:50:14,735
AND ON THE RIGHT SIDE, YOU CAN 

2916
01:50:14,735 --> 01:50:18,172
SEE HOW THE NOVEL TECHNOLOGIES 

2917
01:50:18,172 --> 01:50:18,772
ALLOW US TO MONITOR CEREBRAL 

2918
01:50:18,772 --> 01:50:19,473
BLOOD FLOW FOR EXAMPLE IN MICE 

2919
01:50:19,473 --> 01:50:24,878
THAT ARE ALIVE AND AWAKE AND WE 

2920
01:50:24,878 --> 01:50:29,616
CAN SEE CAPILLARY STALL IN THE 

2921
01:50:29,616 --> 01:50:30,317
RECENT PAPER WE PUBLISHED. 

2922
01:50:30,317 --> 01:50:33,020
NEXT SLIDE. 

2923
01:50:33,020 --> 01:50:35,155
SO THE NEXT RECOMMENDATION, THE 

2924
01:50:35,155 --> 01:50:36,457
SECOND RECOMMENDATION PRIORITY 

2925
01:50:36,457 --> 01:50:39,993
2, IS TO DISCOVER VCID 

2926
01:50:39,993 --> 01:50:40,527
MECHANISMS AND POTENTIAL 

2927
01:50:40,527 --> 01:50:43,630
TARGETS BY LEVERAGING DATA AND 

2928
01:50:43,630 --> 01:50:51,238
BY ESTABLISHING, REFINING AND 

2929
01:50:51,238 --> 01:50:51,839
UTILIZING HUMAN, ANIMAL, AND 

2930
01:50:51,839 --> 01:50:52,473
CELL-BASED EXPERIMENTERS MODELS 

2931
01:50:52,473 --> 01:50:53,006
AND TECHNOLOGIES. 

2932
01:50:53,006 --> 01:51:03,484
NEXT SLIDE. THESE MODELS SHOULD 

2933
01:51:10,157 --> 01:51:10,624
INCLUDE ALSO SYSTEMIC AND 

2934
01:51:10,624 --> 01:51:11,258
CHRONIC PERIVASCULAR DISEASES, 

2935
01:51:11,258 --> 01:51:11,859
FOR EXAMPLE HYPERTENSION AND 

2936
01:51:11,859 --> 01:51:12,493
HEART CARDIAC FAILURE, AND TRY 

2937
01:51:12,493 --> 01:51:13,494
TO MODEL THEM. 

2938
01:51:13,494 --> 01:51:15,596
HERE UNLESS YOU SEE A RAT MODEL 

2939
01:51:15,596 --> 01:51:16,163
THAT INCLUDES A SET OF THE 

2940
01:51:16,163 --> 01:51:21,835
SMALL VESSEL DISEASE IN THE 

2941
01:51:21,835 --> 01:51:22,369
PRESENCE OF MANY OF THESE 

2942
01:51:22,369 --> 01:51:24,238
CARDIOVASCULAR RISK FACTORS 

2943
01:51:24,238 --> 01:51:29,743
SUCH AS HYPERTENSION, AGING, 

2944
01:51:29,743 --> 01:51:31,512
AND CEREBRAL LIPO PERFUSION AND 

2945
01:51:31,512 --> 01:51:32,112
WHEN YOU PUT THEM ALTOGETHER 

2946
01:51:32,112 --> 01:51:32,746
YOU HAVE AN INCREDIBLE LOSS OF 

2947
01:51:32,746 --> 01:51:33,347
CEREBRAL BLOOD FLOW. 

2948
01:51:33,347 --> 01:51:35,749
AND WE MODEL TWO OF THESE 

2949
01:51:35,749 --> 01:51:40,287
VASCULAR PATHOLOGY SUCH AS CAA, 

2950
01:51:40,287 --> 01:51:48,095
AND HYPER HOMO STEMIA 

2951
01:51:48,095 --> 01:51:48,595
(PHONETIC), THERE IS AN 

2952
01:51:48,595 --> 01:51:52,266
EFFECTIVE LOSS OF FUNCTION 

2953
01:51:52,266 --> 01:51:53,767
PROCESS AND THE CORRESPONDING 

2954
01:51:53,767 --> 01:51:56,570
ANIMAL MODEL THAT GIVES US THE 

2955
01:51:56,570 --> 01:51:58,672
SAME RESULTS ON BLOOD-BRAIN 

2956
01:51:58,672 --> 01:51:59,273
BARRIER PERMEABILITY. 

2957
01:51:59,273 --> 01:52:04,278
NEXT SLIDE. 

2958
01:52:04,278 --> 01:52:04,845
AND THE STUDY SHOULD CLARIFY 

2959
01:52:04,845 --> 01:52:07,748
THE MECHANISMS AND MOLECULAR 

2960
01:52:07,748 --> 01:52:12,619
TARGETS OF VASCULAR DISEASE AND 

2961
01:52:12,619 --> 01:52:13,253
OTHER KEEP PATHOGENIC PROCESSES 

2962
01:52:13,253 --> 01:52:18,592
RESULTING IN COGNITIVE 

2963
01:52:18,592 --> 01:52:19,193
IMPAIRMENT. FOR EXAMPLE MICRO 

2964
01:52:19,193 --> 01:52:19,760
HEMORRHAGES IN MANY OF THE 

2965
01:52:19,760 --> 01:52:21,595
OTHER ONES WE TALK ABOUT.

2966
01:52:21,595 --> 01:52:23,030
THERE MANY ANIMAL MODELS 

2967
01:52:23,030 --> 01:52:23,630
ALREADY DEVELOPED FOR EXAMPLE 

2968
01:52:23,630 --> 01:52:26,934
FOR CAA, IN MANY OF THESE 

2969
01:52:26,934 --> 01:52:28,769
PATHOLOGIES SUCH AS THIS ONE, , 

2970
01:52:28,769 --> 01:52:32,673
AND SEVERAL OTHER ANIMAL MODELS 

2971
01:52:32,673 --> 01:52:34,641
BUT SOME PRIVATE MODELS ARE 

2972
01:52:34,641 --> 01:52:36,243
COMING UP...

2973
01:52:36,243 --> 01:52:37,177
>> TWO MINUTES. 

2974
01:52:37,177 --> 01:52:42,382
>> DR. FOSSATI: FOR
EXAMPLE, 

2975
01:52:42,382 --> 01:52:42,916
THE SQUIRREL MONKEYS THAT 

2976
01:52:42,916 --> 01:52:47,654
DEVELOP CAA THAT DEVELOPS 

2977
01:52:47,654 --> 01:52:48,288
SPONTANEOUSLY WITH AGE. 

2978
01:52:48,288 --> 01:52:52,593
NEXT SLIDE. 

2979
01:52:52,593 --> 01:52:53,126
WE SHOULD GIVE ATTENTION TO 

2980
01:52:53,126 --> 01:52:53,627
LIFESTYLE VASCULAR AND 

2981
01:52:53,627 --> 01:52:55,329
METABOLIC FACTORS ASSOCIATED 

2982
01:52:55,329 --> 01:52:55,929
WITH NORMAL AGING AND CHRONIC 

2983
01:52:55,929 --> 01:52:58,031
CONDITION, IN ADDITION TO 

2984
01:52:58,031 --> 01:53:00,133
(INDISCERNIBLE) PATHOLOGY. 

2985
01:53:00,133 --> 01:53:00,734
AND SO THE RISK FACTORS INCLUDE 

2986
01:53:00,734 --> 01:53:03,904
OF COURSE VASCULAR RISK 

2987
01:53:03,904 --> 01:53:05,706
FACTORS, TRAUMATIC BRAIN 

2988
01:53:05,706 --> 01:53:09,243
INJURY, MENOPAUSE FOR WOMEN, 

2989
01:53:09,243 --> 01:53:10,811
AND WE CAN HAVE THINGS SUCH AS 

2990
01:53:10,811 --> 01:53:14,248
(INDISCERNIBLE) SIZE THAT CAN 

2991
01:53:14,248 --> 01:53:14,815
HELP PREVENT VASCULAR RISK 

2992
01:53:14,815 --> 01:53:16,350
FACTORS. 

2993
01:53:16,350 --> 01:53:16,917
HERE IS A NICE IMAGE TO SHOW 

2994
01:53:16,917 --> 01:53:19,820
FOR EXAMPLE IMMUNE REGULATION 

2995
01:53:19,820 --> 01:53:21,255
IS CHANGING AT DIFFERENT TIMES 

2996
01:53:21,255 --> 01:53:21,922
DURING AND AFTER TRAUMATIC RAIN 

2997
01:53:21,922 --> 01:53:25,993
INJURY. (CORRECTION) TRAUMATIC 

2998
01:53:25,993 --> 01:53:26,960
BRAIN INJURY. 

2999
01:53:26,960 --> 01:53:28,729
NEXT SLIDE. 

3000
01:53:28,729 --> 01:53:34,368
WHICH ALSO CONSIDER USING 3D 

3001
01:53:34,368 --> 01:53:36,870
AND PSC MODELS TO INCORPORATE 

3002
01:53:36,870 --> 01:53:37,704
FLOW TO HAVE A MORE 

3003
01:53:37,704 --> 01:53:38,305
PERSONALIZED MEDICINE CREATE 

3004
01:53:38,305 --> 01:53:41,675
DIFFERENT CELL TYPES AND 3D 

3005
01:53:41,675 --> 01:53:42,276
CHIP MODELS WILL INCORPORATE 

3006
01:53:42,276 --> 01:53:44,177
THE FLOW. 

3007
01:53:44,177 --> 01:53:44,745
AND WE CAN TAKE SOME OF THESE 

3008
01:53:44,745 --> 01:53:48,115
FROM THE CARDIOVASCULAR FIELD.  

3009
01:53:48,115 --> 01:53:48,715
OF COURSE WE HAVE TO INCLUDE 

3010
01:53:48,715 --> 01:53:49,283
ALL THE OTHER CELLS OF THE 

3011
01:53:49,283 --> 01:53:56,056
NEUROVASCULAR UNIT. THERE ARE 

3012
01:53:56,056 --> 01:53:56,623
3D ORGANOIDS THAT ARE BEING 

3013
01:53:56,623 --> 01:53:57,257
DEVELOPED EVEN THOUGH THEY ARE 

3014
01:53:57,257 --> 01:54:01,928
NOT YET FUNCTIONAL AND 3D CHIPS 

3015
01:54:01,928 --> 01:54:02,529
THAT CAN HELP US RECAPITULATE 

3016
01:54:02,529 --> 01:54:03,130
THE NEUROVASCULAR UNIT REALLY 

3017
01:54:03,130 --> 01:54:03,664
HELPFUL AS WELL. 

3018
01:54:03,664 --> 01:54:06,800
NEXT SLIDE. 

3019
01:54:06,800 --> 01:54:15,809
WE SHOULD ALSO CONSIDER THE 

3020
01:54:15,809 --> 01:54:16,443
SEX-LINK BIOLOGY AND MENOPAUSE 

3021
01:54:16,443 --> 01:54:18,378
IN THE INTERACTIONS. WOMEN ARE 

3022
01:54:18,378 --> 01:54:22,215
AT HIGHER RISK OF VCID, AND THE 

3023
01:54:22,215 --> 01:54:22,716
MENOPAUSE TRANSITION IS 

3024
01:54:22,716 --> 01:54:29,256
IMPORTANT TO UNDERSTAND THIS 

3025
01:54:29,256 --> 01:54:29,823
RISK. WE SHOULD LOOK AT THE 

3026
01:54:29,823 --> 01:54:31,792
RELATIVE CONSIDERATION OF 

3027
01:54:31,792 --> 01:54:32,826
THEIRS MECHANISMS AND MANY OF 

3028
01:54:32,826 --> 01:54:33,460
THESE CLEARANCE MECHANISMS HAVE 

3029
01:54:33,460 --> 01:54:34,094
BEEN CLARIFIED IN THE LAST FEW 

3030
01:54:34,094 --> 01:54:38,298
YEARS.  BUT WE REALLY NEED TO 

3031
01:54:38,298 --> 01:54:38,799
UNDERSTAND BETTER THEIR 

3032
01:54:38,799 --> 01:54:39,266
INTERACTIONS. 

3033
01:54:39,266 --> 01:54:39,733
THANK YOU. 

3034
01:54:39,733 --> 01:54:43,737
NEXT SLIDE. 

3035
01:54:43,737 --> 01:54:44,304
I WILL KNOW LEAVE THE 

3036
01:54:44,304 --> 01:54:54,614
MICROPHONE TO GARETH HOWELL 

3037
01:54:54,614 --> 01:54:57,150
PULLED RECOMMENDATIONS. 

3038
01:54:57,150 --> 01:54:57,751
>> WAS A PLEASURE TO BE
PART OF 

3039
01:54:57,751 --> 01:54:58,218
THIS PANEL. 

3040
01:54:58,218 --> 01:55:00,020
NEXT SLIDE. 

3041
01:55:00,020 --> 01:55:03,590
I HAVE, THESE ARE MY 

3042
01:55:03,590 --> 01:55:04,191
DISCLAIMERS AND DISCLOSURES I 

3043
01:55:04,191 --> 01:55:07,160
AM GARETH HOWELL, PROFESSOR AT 

3044
01:55:07,160 --> 01:55:13,567
THE -- CHAIR AND LABORATORY. 

3045
01:55:13,567 --> 01:55:14,067
I'M GOING TO COVER 

3046
01:55:14,067 --> 01:55:16,436
RECOMMENDATIONS 3 AND 4. 

3047
01:55:16,436 --> 01:55:18,038
RECOMMENDATION 3, PRIORITY OF 

3048
01:55:18,038 --> 01:55:22,676
4, 

3049
01:55:22,676 --> 01:55:24,544
CROSS VALIDATE THE MECHANISMS 

3050
01:55:24,544 --> 01:55:25,112
OF ANIMAL MODELS AND HUMAN 

3051
01:55:25,112 --> 01:55:28,315
STUDIES TO ENSURE PHASE AND 

3052
01:55:28,315 --> 01:55:29,583
CONSTRUCT VALIDITY INCLUDING 

3053
01:55:29,583 --> 01:55:32,052
MIX PATHOLOGIES, NORMAL 

3054
01:55:32,052 --> 01:55:32,652
VASCULAR AGING AND COMMUNITY 

3055
01:55:32,652 --> 01:55:36,423
BASED COHORT. 

3056
01:55:36,423 --> 01:55:38,225
UNDERLINING THIS ONE OF THE 

3057
01:55:38,225 --> 01:55:38,859
FIRST BULLET OF THIS IS TO WORK 

3058
01:55:38,859 --> 01:55:39,526
TRANSLATIONALLY TO CHARACTERIZE 

3059
01:55:39,526 --> 01:55:40,060
THE INTERRELATIONSHIPS OF 

3060
01:55:40,060 --> 01:55:44,698
VASCULAR RISK FACTORS AND AD 

3061
01:55:44,698 --> 01:55:45,298
MECHANISMS DISCOVERED IN CELL 

3062
01:55:45,298 --> 01:55:45,932
AND ANIMAL MODELS TO BIOMARKERS 

3063
01:55:45,932 --> 01:55:47,667
OF CEREBROVASCULAR DISEASE. 

3064
01:55:47,667 --> 01:55:48,235
BOTH RECOMMENDATIONS HOW DID 

3065
01:55:48,235 --> 01:55:48,735
THE NEED TO IMPROVE THE 

3066
01:55:48,735 --> 01:55:51,538
TRANSLATION BETWEEN MODELS AND 

3067
01:55:51,538 --> 01:55:53,807
THE CLINICAL DISEASE. 

3068
01:55:53,807 --> 01:55:55,842
AND SO IN A WAY WE THINK ABOUT 

3069
01:55:55,842 --> 01:55:56,376
EXAMPLES OF VCID AS WAS 

3070
01:55:56,376 --> 01:56:01,748
DESCRIBED PREVIOUSLY, WITH 

3071
01:56:01,748 --> 01:56:08,955
THINK ABOUT CEREBRAL AMYLOID, 

3072
01:56:08,955 --> 01:56:11,925
AND CEREBRAL MICROBLEEDS. 

3073
01:56:11,925 --> 01:56:12,526
THERE IS A NEED HERE TO REALLY 

3074
01:56:12,526 --> 01:56:13,160
POTENTIALLY REDEFINE THE 

3075
01:56:13,160 --> 01:56:15,362
BIOLOGICAL ASPECTS OF VCID 

3076
01:56:15,362 --> 01:56:16,329
OBSERVED IN THE CLINIC. 

3077
01:56:16,329 --> 01:56:22,836
SIMPLY OBSERVING THE PATHOLOGY 

3078
01:56:22,836 --> 01:56:23,470
FOR INSTANCE IN THE MASS MODEL 

3079
01:56:23,470 --> 01:56:24,171
DOES NOT NECESSARILY MEAN IT IS 

3080
01:56:24,171 --> 01:56:24,805
DRIVEN BY THE SAME FACTORS THAT 

3081
01:56:24,805 --> 01:56:27,941
WOULD BE SEEN IN THE CLINIC. 

3082
01:56:27,941 --> 01:56:28,442
WE NEED TO WORK HARDER TO 

3083
01:56:28,442 --> 01:56:29,042
UNDERSTAND THESE BOTH IN THE 

3084
01:56:29,042 --> 01:56:29,643
HUMAN CONDITIONS, BUT ALSO IN 

3085
01:56:29,643 --> 01:56:30,076
OUR MODELS. 

3086
01:56:30,076 --> 01:56:35,515
NEXT SLIDE. 

3087
01:56:35,515 --> 01:56:36,483
ANOTHER IMPORTANT COMPONENT OF 

3088
01:56:36,483 --> 01:56:37,818
THIS RECOMMENDATION IS TO 

3089
01:56:37,818 --> 01:56:42,489
EVALUATE THE MECHANISMS LEADING 

3090
01:56:42,489 --> 01:56:45,992
TO AMYLOID RELATED IMAGING 

3091
01:56:45,992 --> 01:56:48,328
ABNORMALITIES ASSOCIATED WITH 

3092
01:56:48,328 --> 01:56:55,802
THESE AMYLOID IMMUNOTHERAPIES 

3093
01:56:55,802 --> 01:56:56,303
AND USING THE HUMAN AND 

3094
01:56:56,303 --> 01:56:56,937
EXPERIMENTAL MODELS, IMPORTANT 

3095
01:56:56,937 --> 01:56:58,338
TO RECOGNIZE THAT MODELS HAVE A 

3096
01:56:58,338 --> 01:57:00,373
HARD TIME IN THIS PATIENT WAS 

3097
01:57:00,373 --> 01:57:00,974
SHOWN MORE THAN 20 YEARS AGO 

3098
01:57:00,974 --> 01:57:01,942
THAT YOU WOULD BE ABLE TO CLEAR 

3099
01:57:01,942 --> 01:57:02,509
AMYLOID FROM RAINS AND EVEN 

3100
01:57:02,509 --> 01:57:10,183
LEAD TO ARIA-LIKE PATHOLOGIES. 

3101
01:57:10,183 --> 01:57:12,152
IT WAS NOT CALLED ARIA BACK 

3102
01:57:12,152 --> 01:57:14,721
THEN. 

3103
01:57:14,721 --> 01:57:15,288
IT CAN BE MORE PREDICTABLE AS 

3104
01:57:15,288 --> 01:57:15,956
WE THINK ABOUT IMPROVING 

3105
01:57:15,956 --> 01:57:18,625
THERAPIES FOR THINGS LIKE 

3106
01:57:18,625 --> 01:57:19,359
ALZHEIMER'S DISEASE AND RELATED 

3107
01:57:19,359 --> 01:57:26,733
DIMENSIONS IN THE VCID SPACE. 

3108
01:57:26,733 --> 01:57:27,734
AND THE SQUIRREL MONKEYS SYLVIA 

3109
01:57:27,734 --> 01:57:31,004
POINTED TO, WE NEED TO THINK 

3110
01:57:31,004 --> 01:57:31,805
ABOUT EXPANDING NOT JUST IN THE 

3111
01:57:31,805 --> 01:57:32,572
CELL SPACE BUT ALSO IN THE 

3112
01:57:32,572 --> 01:57:33,139
ANIMAL MODEL SPACE. 

3113
01:57:33,139 --> 01:57:39,713
NEXT SLIDE. 

3114
01:57:39,713 --> 01:57:41,381
AND I WHEN WE THINK ABOUT 

3115
01:57:41,381 --> 01:57:47,854
IMPROVING OUR MODEL COLLECTION, 

3116
01:57:47,854 --> 01:57:48,622
AND AS WE BUILD TO CROSS 

3117
01:57:48,622 --> 01:57:49,923
VALIDATE ASSETS, WE NEED TO 

3118
01:57:49,923 --> 01:57:52,893
THINK ABOUT ALL THE DIFFERENT 

3119
01:57:52,893 --> 01:57:53,493
FACTORS THAT ARE OBSERVED IN 

3120
01:57:53,493 --> 01:57:57,197
THE CLINIC INCLUDING SEX AND 

3121
01:57:57,197 --> 01:58:00,634
AGE AS BIOLOGICAL BARRIERS, 

3122
01:58:00,634 --> 01:58:01,268
EXPERIMENTAL APPROACHES SHOULD 

3123
01:58:01,268 --> 01:58:01,868
INCLUDE ANIMAL MODELS AND THE 

3124
01:58:01,868 --> 01:58:02,502
EXTENT OF DIVERSITY IN THIS IS 

3125
01:58:02,502 --> 01:58:04,170
PARTICULARLY IMPORTANT WHEN WE 

3126
01:58:04,170 --> 01:58:04,771
THINK ABOUT THE ENVIRONMENTAL 

3127
01:58:04,771 --> 01:58:06,139
RISK FACTORS AS WAS DESCRIBED 

3128
01:58:06,139 --> 01:58:08,141
BEFORE, AS WELL AS THE GENETICS 

3129
01:58:08,141 --> 01:58:11,711
PRESENT IN HUMAN POPULATIONS. 

3130
01:58:11,711 --> 01:58:12,312
AND THERE'S A REAL FEELING THAT 

3131
01:58:12,312 --> 01:58:12,913
SOMETIMES WE DO THE QUICK AND 

3132
01:58:12,913 --> 01:58:16,249
EASY EXPERIMENT IN THE MASS 

3133
01:58:16,249 --> 01:58:22,122
MODELS, OR EVEN ANY  ANIMAL 

3134
01:58:22,122 --> 01:58:22,689
MODEL DESPITE THE FACT THAT 

3135
01:58:22,689 --> 01:58:23,323
THERE IS A WEALTH OF RESOURCES 

3136
01:58:23,323 --> 01:58:23,957
THAT CAN BE ACCESSED THAT HAVE 

3137
01:58:23,957 --> 01:58:24,457
BEEN SHOWN TO BE REALLY 

3138
01:58:24,457 --> 01:58:25,025
IMPORTANT IN IMPROVING THE 

3139
01:58:25,025 --> 01:58:25,659
TRANSLATION BETWEEN HUMANS AND 

3140
01:58:25,659 --> 01:58:26,626
MICE. 

3141
01:58:26,626 --> 01:58:27,127
I AM SHOWING HERE ON THE 

3142
01:58:27,127 --> 01:58:27,827
LEFT-HAND SIDE THAT WE COMMONLY 

3143
01:58:27,827 --> 01:58:34,367
USE C57 BLACK 6. BUT THERE'S A 

3144
01:58:34,367 --> 01:58:36,236
WHOLE ARRAY OF OTHER THINGS 

3145
01:58:36,236 --> 01:58:37,337
LISTED HERE ESSENTIALLY 

3146
01:58:37,337 --> 01:58:37,971
INCORPORATING AS MUCH GENETIC 

3147
01:58:37,971 --> 01:58:41,808
VARIATION AS YOU CAN SEE  IN 

3148
01:58:41,808 --> 01:58:42,409
THE HUMAN POPULATION AND YOU 

3149
01:58:42,409 --> 01:58:43,043
CAN GET QUITE DIFFERENT RESULTS 

3150
01:58:43,043 --> 01:58:44,077
IF YOU TRY AND DRIVE A HUMAN 

3151
01:58:44,077 --> 01:58:44,711
RELEVANT PATHOLOGY DEPENDING ON 

3152
01:58:44,711 --> 01:58:46,313
THE STRAIN. 

3153
01:58:46,313 --> 01:58:49,683
ON THE LEFT-HAND SIDE I AM 

3154
01:58:49,683 --> 01:58:52,252
SHOWING A PHOTOGRAPH OF 

3155
01:58:52,252 --> 01:58:54,287
CEREBRAL AMYLOID -- TAKING BY 

3156
01:58:54,287 --> 01:58:54,788
OLIVIA-- IN MY LAB AND 

3157
01:58:54,788 --> 01:58:58,992
HIGHLIGHTS THAT THE B STRAIN 

3158
01:58:58,992 --> 01:58:59,626
CARRIES THE GENETIC THAT MAKES 

3159
01:58:59,626 --> 01:59:03,196
MICE MORE SUSCEPTIBLE TO CAA.  

3160
01:59:03,196 --> 01:59:03,797
SO I WE NEED TO DO BETTER IN 

3161
01:59:03,797 --> 01:59:08,735
INCORPORATING AND LEVERAGING 

3162
01:59:08,735 --> 01:59:09,235
ALL OF THE MASS GENETIC 

3163
01:59:09,235 --> 01:59:09,736
RESOURCES THAT WE HAVE 

3164
01:59:09,736 --> 01:59:10,170
AVAILABLE. 

3165
01:59:10,170 --> 01:59:16,743
NEXT SLIDE. 

3166
01:59:16,743 --> 01:59:25,785
SO WE RECOMMEND 4, PRIORITY 3. 

3167
01:59:25,785 --> 01:59:28,788
DEVELOP AND ADVANCE ESSENTIAL 

3168
01:59:28,788 --> 01:59:29,389
NEW THERAPEUTICS AND SELL AN 

3169
01:59:29,389 --> 01:59:29,956
ANIMAL MODEL TO PREVENT OR 

3170
01:59:29,956 --> 01:59:32,225
TREAT VCID. TO TARGET 

3171
01:59:32,225 --> 01:59:37,030
PREVENTION OR TREATMENT OF 

3172
01:59:37,030 --> 01:59:37,664
VCID-RELATED COGNITIVE DECLINE 

3173
01:59:37,664 --> 01:59:38,231
WORKING TOWARDS OPTIMIZING 

3174
01:59:38,231 --> 01:59:38,765
TRANSLATION FROM CELL AND 

3175
01:59:38,765 --> 01:59:39,332
ANIMAL MODELS TO CLINICAL 

3176
01:59:39,332 --> 01:59:40,634
TRIALS. 

3177
01:59:40,634 --> 01:59:41,735
THIS DIAGRAM HAS BEEN SHOWN 

3178
01:59:41,735 --> 01:59:43,169
BEFORE, ABOUT WHERE WE ARE WITH 

3179
01:59:43,169 --> 01:59:45,672
ALZHEIMER'S DISEASE.  AND I 

3180
01:59:45,672 --> 01:59:46,272
REALLY DON'T NEED TO SEE ALL 

3181
01:59:46,272 --> 01:59:48,074
THE DETAILS OF THIS.  YOU CAN 

3182
01:59:48,074 --> 01:59:48,608
SEE THAT THERE IS A LARGE 

3183
01:59:48,608 --> 01:59:51,511
NUMBER OF CLINICAL TRIALS THAT 

3184
01:59:51,511 --> 01:59:52,812
ARE AT DIFFERENT PHASES FOR 

3185
01:59:52,812 --> 01:59:59,653
ALZHEIMER'S DISEASE. AND THE 

3186
01:59:59,653 --> 02:00:00,286
MECHANISMS OF ACTION ARE VARIED 

3187
02:00:00,286 --> 02:00:00,887
SO A LOT OF AMYLOID BUT ALSO 

3188
02:00:00,887 --> 02:00:04,224
EMERGING IN OTHER AREAS SUCH AS 

3189
02:00:04,224 --> 02:00:04,858
NEURAL INFLAMMATION, EPIGENETIC 

3190
02:00:04,858 --> 02:00:05,592
REGULATIONS, MITOCHONDRIAL 

3191
02:00:05,592 --> 02:00:09,996
HEALTH, ETC.

3192
02:00:09,996 --> 02:00:10,563
BOTH OF THESE CATEGORIES YOU 

3193
02:00:10,563 --> 02:00:12,232
NOTICE THERE AREN'T REALLY ANY 

3194
02:00:12,232 --> 02:00:13,733
SPECIFICALLY TARGETING OR 

3195
02:00:13,733 --> 02:00:21,307
IMPROVING THE HEALTH OF 

3196
02:00:21,307 --> 02:00:23,610
CEREBRAL VASCULAR AND LYMPHATIC 

3197
02:00:23,610 --> 02:00:24,144
CELLS, WHICH WE SHOULD BE 

3198
02:00:24,144 --> 02:00:24,611
TARGETING POTENTIALLY 

3199
02:00:24,611 --> 02:00:25,178
UNDERLYING MECHANISMS SO WE 

3200
02:00:25,178 --> 02:00:25,812
REALLY WANT TO SEE THIS CHANGE 

3201
02:00:25,812 --> 02:00:26,312
MOVING FORWARD. 

3202
02:00:26,312 --> 02:00:32,419
NEXT SLIDE. 

3203
02:00:32,419 --> 02:00:33,653
THIS WAS BROUGHT UP EARLIER 

3204
02:00:33,653 --> 02:00:34,988
ABOUT MODEL AD. 

3205
02:00:34,988 --> 02:00:43,596
IN THE ALZHEIMER'S SPACE WE 

3206
02:00:43,596 --> 02:00:44,197
ALREADY DEVELOPED NEW WAYS OF 

3207
02:00:44,197 --> 02:00:44,831
DEVELOPING MASS MODELS THAT ARE 

3208
02:00:44,831 --> 02:00:45,365
MUCH MORE HUMAN RELEVANT, 

3209
02:00:45,365 --> 02:00:45,965
ENSURING THAT WE START WITH 

3210
02:00:45,965 --> 02:00:52,305
CLINICAL DATA, AND BUILDING 

3211
02:00:52,305 --> 02:00:52,939
MODELS BASED ON CLINICAL DATA, 

3212
02:00:52,939 --> 02:00:53,473
PARTICULARLY THE GENETIC 

3213
02:00:53,473 --> 02:01:00,947
INFORMATION THAT IS AVAILABLE. 

3214
02:01:00,947 --> 02:01:01,514
GENETIC IN COMBINATION WITH 

3215
02:01:01,514 --> 02:01:02,115
ENVIRONMENTAL MONEY RELATION 

3216
02:01:02,115 --> 02:01:03,817
SUCH AS HIGH-FAT DIET AND TOXIC 

3217
02:01:03,817 --> 02:01:04,350
METALS, THAT IMPROVE THE 

3218
02:01:04,350 --> 02:01:07,053
VALIDITY OF THOSE MASS MODELS 

3219
02:01:07,053 --> 02:01:07,620
AND THE TRANSLATABLE METHOD 

3220
02:01:07,620 --> 02:01:14,127
SUCH AS FLUID -- AND WE DO THE 

3221
02:01:14,127 --> 02:01:14,694
CLINICAL SCREENINGS SUCH AS 

3222
02:01:14,694 --> 02:01:15,261
DRUG TESTING YOU KNOW THESE 

3223
02:01:15,261 --> 02:01:16,930
MODELS HAVE BEEN ALIGNED TO THE 

3224
02:01:16,930 --> 02:01:17,530
CLINICAL DISEASE THAT YOU ARE 

3225
02:01:17,530 --> 02:01:18,098
ACTUALLY STARTING. 

3226
02:01:18,098 --> 02:01:22,235
NEXT SLIDE. 

3227
02:01:22,235 --> 02:01:24,704
AND THEN FINALLY UNLESS 

3228
02:01:24,704 --> 02:01:25,438
RECOMMENDATION THERAPEUTICS 

3229
02:01:25,438 --> 02:01:28,241
PREVENTION OF PRECISION MEDS 

3230
02:01:28,241 --> 02:01:32,178
APPROACHES SHOULD ADDRESS ARIA 

3231
02:01:32,178 --> 02:01:32,812
COMPONENT WHICH IS AN IMPORTANT 

3232
02:01:32,812 --> 02:01:35,448
COMPONENT AS IT INVOLVES 

3233
02:01:35,448 --> 02:01:39,886
VCID-RELATED ABNORMALITIES. 

3234
02:01:39,886 --> 02:01:40,453
THE KEY POINT I WANT TO MAKE 

3235
02:01:40,453 --> 02:01:41,054
YOUR THAT AS WE THINK ABOUT 

3236
02:01:41,054 --> 02:01:43,456
DEVELOPING THERAPIES THERE MAY 

3237
02:01:43,456 --> 02:01:44,124
NOT BE A SINGLE TREATMENT BUT 

3238
02:01:44,124 --> 02:01:44,758
MORE MORE THESE ARE GOING TO BE 

3239
02:01:44,758 --> 02:01:47,227
COMBINATORIAL THERAPIES, EVEN 

3240
02:01:47,227 --> 02:01:48,394
IN COMBINATION WITH HEALTHIER 

3241
02:01:48,394 --> 02:01:50,296
LIVING RECOMMENDATIONS. IS 

3242
02:01:50,296 --> 02:01:51,431
GOING TO BE VERY DIFFICULT JUST 

3243
02:01:51,431 --> 02:01:52,065
IN THE HUMAN SPACE, OR EVEN IN 

3244
02:01:52,065 --> 02:01:55,502
THE CELL SPACE TO UNDERSTAND 

3245
02:01:55,502 --> 02:01:57,570
HOW THE COMBINATION OF 

3246
02:01:57,570 --> 02:01:59,973
THERAPIES ARE GOING TO REFLECT 

3247
02:01:59,973 --> 02:02:00,573
THE BRAIN AND THE REST OF THE 

3248
02:02:00,573 --> 02:02:03,443
BODY IF YOU THINK ABOUT VCID 

3249
02:02:03,443 --> 02:02:07,914
AND ADIDS, AS A WHOLE BODY 

3250
02:02:07,914 --> 02:02:11,951
DISEASE SO WE NEED TO MAKE SURE 

3251
02:02:11,951 --> 02:02:12,585
WE IMPROVE CLINICAL STUDIES IN 

3252
02:02:12,585 --> 02:02:18,625
ORDER TO FEED THAT INFORMATION 

3253
02:02:18,625 --> 02:02:19,259
INTO MORE APPROPRIATE CLINICAL 

3254
02:02:19,259 --> 02:02:19,893
TRIALS AND OBSOLETE A RESULT OF 

3255
02:02:19,893 --> 02:02:20,426
THOSE CAN GET FED BACK TO 

3256
02:02:20,426 --> 02:02:21,094
IMPROVE CLINICAL STUDIES. 

3257
02:02:21,094 --> 02:02:31,337
WITHOUT A WILL STOP. 

3258
02:02:31,337 --> 02:02:31,938
>> THANK YOU. AGAIN A
PRIVILEGE 

3259
02:02:31,938 --> 02:02:32,839
TO BE PART OF THIS GROUP.

3260
02:02:32,839 --> 02:02:34,274
THESE ARE MY DISCLOSURES. 

3261
02:02:34,274 --> 02:02:37,177
>> DR. SESHADRI: I WILL BE

3262
02:02:37,177 --> 02:02:37,677
ADDRESSING HUMAN STUDY 

3263
02:02:37,677 --> 02:02:39,712
RECOMMENDATIONS 5 AND 6. 

3264
02:02:39,712 --> 02:02:42,816
IN RECOMMENDATION 5, WE 

3265
02:02:42,816 --> 02:02:45,885
ADVOCATE FOR ADVANCING 

3266
02:02:45,885 --> 02:02:51,958
INTERVENTIONS AND PREVENTION TO 

3267
02:02:51,958 --> 02:02:52,525
REDUCE VASCULAR DISEASE BY 

3268
02:02:52,525 --> 02:02:53,059
VASCULAR BRAIN INJURY IN 

3269
02:02:53,059 --> 02:02:53,660
POPULATIONS AT INCREASED RISK 

3270
02:02:53,660 --> 02:02:54,060
FOR VCID. 

3271
02:02:54,060 --> 02:02:56,095
THIS IS PRIORITY 2. 

3272
02:02:56,095 --> 02:03:01,734
SO WE ENCOURAGE PHASES 1-4 IN 

3273
02:03:01,734 --> 02:03:03,036
PRIMARY CLINICAL TRIALS OF VCID 

3274
02:03:03,036 --> 02:03:07,874
TESTING INTERVENTIONS SHOWN TO 

3275
02:03:07,874 --> 02:03:08,775
BE EFFICACIOUS IN REDUCING 

3276
02:03:08,775 --> 02:03:13,813
HEART ATTACKS AND STROKE.  THIS 

3277
02:03:13,813 --> 02:03:14,414
INCLUDES THINGS LIKE MANAGING 

3278
02:03:14,414 --> 02:03:18,885
BLOOD PRESSURES, DIABETES, 

3279
02:03:18,885 --> 02:03:19,485
OPTIMIZING DIET AND EXERCISE 

3280
02:03:19,485 --> 02:03:20,920
AND SLEEP ENVIRONMENT AND 

3281
02:03:20,920 --> 02:03:21,554
BEHAVIOR. AND THIS IS THE STAGE 

3282
02:03:21,554 --> 02:03:28,595
OF SOMEBODY WHO HAS NO REST 

3283
02:03:28,595 --> 02:03:29,128
BRAIN INJURY DETECTABLE, 

3284
02:03:29,128 --> 02:03:31,130
DRIVING PREVENTION IS PERHAPS 

3285
02:03:31,130 --> 02:03:31,764
SOMEBODY WHO HAS ALREADY HAD A 

3286
02:03:31,764 --> 02:03:35,869
STROKE.  AND AGAIN EMPHASIZING 

3287
02:03:35,869 --> 02:03:36,436
TRIALS AS WELL THAT IMPROVE 

3288
02:03:36,436 --> 02:03:40,306
QUALITY OF LIFE. 

3289
02:03:40,306 --> 02:03:40,907
FOR EXAMPLE IN PHYSICAL THERAPY 

3290
02:03:40,907 --> 02:03:41,407
INTERVENTION TO IMPROVE 

3291
02:03:41,407 --> 02:03:43,076
MUSCULAR STRENGTH, GATE AND 

3292
02:03:43,076 --> 02:03:51,684
BALANCE. 

3293
02:03:51,684 --> 02:03:52,185
WE ARE PRIORITIZING WHICH 

3294
02:03:52,185 --> 02:03:56,155
INTERVENTION SHOULD GO TO TRIAL 

3295
02:03:56,155 --> 02:03:56,756
CAN BE STRENGTHENED BY USING 

3296
02:03:56,756 --> 02:03:57,390
MEDICAL RELEVANT COHORTS THAT 

3297
02:03:57,390 --> 02:04:00,426
ARE NOW EXISTING. FOR EXAMPLE 

3298
02:04:00,426 --> 02:04:03,763
LOOKING AT COGNITION TWO YEARS 

3299
02:04:03,763 --> 02:04:04,397
AFTER AN ACUTE STROKE AND EVERY 

3300
02:04:04,397 --> 02:04:07,800
AND SEEING THE PREDICTORS, AND 

3301
02:04:07,800 --> 02:04:09,469
CONSEQUENCES AND PROGRESSION OF 

3302
02:04:09,469 --> 02:04:11,004
WHITE MATTER HYPER INTENSITY IN 

3303
02:04:11,004 --> 02:04:11,804
VCID. 

3304
02:04:11,804 --> 02:04:15,275
NEXT SLIDE. 

3305
02:04:15,275 --> 02:04:15,742
THE RATIONALE FOR THIS 

3306
02:04:15,742 --> 02:04:16,342
RECOGNITION OF THE FACT THAT 

3307
02:04:16,342 --> 02:04:25,118
OVER THE LAST SEVERAL DECADES, 

3308
02:04:25,118 --> 02:04:28,454
WE HAVE A LOT OF OBSERVATIONAL 

3309
02:04:28,454 --> 02:04:29,055
DATA, ESPECIALLY FOCUSING ON 

3310
02:04:29,055 --> 02:04:32,125
COGNITIVE IMPAIRMENT AND 

3311
02:04:32,125 --> 02:04:34,527
DEMENTIA. NOT WHAT WE HOPE THEM 

3312
02:04:34,527 --> 02:04:35,161
PERHAPS TODAY THE MOST HOPEFUL 

3313
02:04:35,161 --> 02:04:35,762
ONE INTENSIVE BLOOD PRESSURE 

3314
02:04:35,762 --> 02:04:38,131
CONTROL IS SEEN 

3315
02:04:38,131 --> 02:04:38,765
(INDISCERNIBLE), IN PEOPLE WHO 

3316
02:04:38,765 --> 02:04:40,500
ARE ALREADY AT HIGH RISK. 

3317
02:04:40,500 --> 02:04:43,036
AND SO WE ARE RECOGNIZING 

3318
02:04:43,036 --> 02:04:44,037
THINGS LIKE, HOW EFFECT OF THE 

3319
02:04:44,037 --> 02:04:44,871
INTERVENTION?

3320
02:04:44,871 --> 02:04:47,307
WHAT IS THE STAGE OF THE 

3321
02:04:47,307 --> 02:04:47,674
DISEASE?

3322
02:04:47,674 --> 02:04:48,241
WHAT IS THE AGE OF THE PEOPLE 

3323
02:04:48,241 --> 02:04:49,509
WHO ARE IN THE STUDY?

3324
02:04:49,509 --> 02:04:50,009
WHAT IS THE TYPE OF 

3325
02:04:50,009 --> 02:04:51,477
INTERVENTION?

3326
02:04:51,477 --> 02:04:53,913
WHAT ARE THE MOLECULAR PATHWAYS 

3327
02:04:53,913 --> 02:04:59,686
THAT UNDERLIE AN EFFECTIVE OR 

3328
02:04:59,686 --> 02:05:00,353
INEFFECTIVE INTERVENTION?

3329
02:05:00,353 --> 02:05:00,954
AND SO THE HEART AND BRAIN ARE 

3330
02:05:00,954 --> 02:05:03,756
DIFFERENT TARGETS. 

3331
02:05:03,756 --> 02:05:04,824
WHAT ARE THE SUBJECTS LIKE 

3332
02:05:04,824 --> 02:05:05,425
SPECIFIC CHARACTERISTIC LIKE 

3333
02:05:05,425 --> 02:05:10,129
GENETICS, AND ENVIRONMENT?

3334
02:05:10,129 --> 02:05:10,663
WHAT IS THE COMBINATION OF 

3335
02:05:10,663 --> 02:05:11,297
THESE INTERVENTIONS THAT MAY BE 

3336
02:05:11,297 --> 02:05:13,599
SYNERGISTIC OR NOT?

3337
02:05:13,599 --> 02:05:14,167
ONE MAY ALSO NOT JUST LOOK AT 

3338
02:05:14,167 --> 02:05:18,771
THINGS LIKE BLOOD PRESSURE THAT 

3339
02:05:18,771 --> 02:05:20,039
WE ARE CURRENTLY SEEING CLINIC 

3340
02:05:20,039 --> 02:05:21,741
BUT FURTHER UPSTREAM. THINGS 

3341
02:05:21,741 --> 02:05:22,342
LIKE ARTERIAL STIFFNESS THAT 

3342
02:05:22,342 --> 02:05:22,909
HAVE A LONG-TERM EFFECT ON 

3343
02:05:22,909 --> 02:05:27,080
DEMENTIA RISK.  BUT PROCEED 

3344
02:05:27,080 --> 02:05:27,680
EVEN DETECTABLE HIGHER BLOOD 

3345
02:05:27,680 --> 02:05:28,081
PRESSURE. 

3346
02:05:28,081 --> 02:05:32,986
NEXT SLIDE. 

3347
02:05:32,986 --> 02:05:33,586
SO, WHEN ONE THINKS ABOUT WHAT 

3348
02:05:33,586 --> 02:05:35,989
TO PRIORITIZE, THERE ARE THE 

3349
02:05:35,989 --> 02:05:36,689
VARIOUS MODIFIABLE RISK 

3350
02:05:36,689 --> 02:05:42,128
FACTORS, AS HIGHLIGHTED BY THE 

3351
02:05:42,128 --> 02:05:42,729
LANCET (PHONETIC) POPULATION 

3352
02:05:42,729 --> 02:05:46,599
THAT HAVE SIGNIFICANT  A 

3353
02:05:46,599 --> 02:05:48,434
POPULATION AT RISK OR 

3354
02:05:48,434 --> 02:05:51,738
HIGHLIGHTED BY THE AHA AND 

3355
02:05:51,738 --> 02:05:52,372
THESE SEEM TO HAVE THE MAXIMUM 

3356
02:05:52,372 --> 02:05:55,475
IMPACT IN MIDLIFE. 

3357
02:05:55,475 --> 02:05:56,009
AND SO THE BENEFITS ARE NOT 

3358
02:05:56,009 --> 02:05:57,510
MAYBE DETECTABLE AS MUCH AS 20 

3359
02:05:57,510 --> 02:06:00,380
YEARS OR GREATER LATER.  AND AS 

3360
02:06:00,380 --> 02:06:02,382
YOU HEARD THROUGHOUT THIS, 

3361
02:06:02,382 --> 02:06:03,016
THESE RISK FACTORS MAY NOT ONLY 

3362
02:06:03,016 --> 02:06:07,253
BE ACTING THROUGH TRADITIONAL 

3363
02:06:07,253 --> 02:06:07,820
VASCULAR MECHANISMS, BUT TO 

3364
02:06:07,820 --> 02:06:10,323
THEIR IMPACT ON VARIOUS 

3365
02:06:10,323 --> 02:06:10,857
(INDISCERNIBLE) AND OTHER 

3366
02:06:10,857 --> 02:06:11,224
THINGS. 

3367
02:06:11,224 --> 02:06:12,925
NEXT SLIDE. 

3368
02:06:12,925 --> 02:06:16,863
SO KEEPING THESE IN MIND, ONE 

3369
02:06:16,863 --> 02:06:18,297
DOES HAVE, HOWEVER, A LOT OF 

3370
02:06:18,297 --> 02:06:24,237
DATA TO MINE.  FOR EXAMPLE THIS 

3371
02:06:24,237 --> 02:06:26,406
NIH WEBSITE, YOU SEE THE 

3372
02:06:26,406 --> 02:06:28,541
VARIOUS LEGITIMATE DATA FROM 

3373
02:06:28,541 --> 02:06:39,052
AGE 10-100.  THE STUDY IS IN 

3374
02:06:43,222 --> 02:06:43,623
BLUE THAT ARE NEARLY 

3375
02:06:43,623 --> 02:06:44,257
OBSERVATIONAL, AS WELL AS ONES 

3376
02:06:44,257 --> 02:06:44,857
IN GREAY, INTERVENE TO CHANGE 

3377
02:06:44,857 --> 02:06:45,958
DIABETES RISK. THEN THE 

3378
02:06:45,958 --> 02:06:46,559
DIFFERENCES BETWEEN THE HEART 

3379
02:06:46,559 --> 02:06:48,628
AND THE BRAIN  FOR EXAMPLE FOR 

3380
02:06:48,628 --> 02:06:54,767
HEART DISEASE ONE MAY NEED AT 

3381
02:06:54,767 --> 02:06:56,002
LEAST 30 MINUTES OF MODERATE TO 

3382
02:06:56,002 --> 02:06:56,602
AGGRESSIVE ACTIVITY TO REMOVE 

3383
02:06:56,602 --> 02:06:58,638
(INDISCERNIBLE). 

3384
02:06:58,638 --> 02:06:59,839
WHEN WE COMBINE THESE DATA SETS 

3385
02:06:59,839 --> 02:07:00,540
WITH BIOMARKERS THAT ARE ABLE 

3386
02:07:00,540 --> 02:07:04,210
TO BE SEEN IN AN AGNOSTIC 

3387
02:07:04,210 --> 02:07:08,081
MANNER YOU FIND THAT 

3388
02:07:08,081 --> 02:07:08,714
(INDISCERNIBLE) HIGHLIGHT NOVEL 

3389
02:07:08,714 --> 02:07:09,248
PATHWAYS LIKE CHANGES IN 

3390
02:07:09,248 --> 02:07:10,116
GLUTAMINE LEVELS. 

3391
02:07:10,116 --> 02:07:12,518
NEXT SLIDE. 

3392
02:07:12,518 --> 02:07:13,719
NEXT. 

3393
02:07:13,719 --> 02:07:21,761
IN FACT, THERE ARE A LOT OF 

3394
02:07:21,761 --> 02:07:22,361
LARGE NUMBER OF-- EVEN IF YOU 

3395
02:07:22,361 --> 02:07:22,995
CONSIDER ONE MODALITY OF 

3396
02:07:22,995 --> 02:07:26,499
EXERCISE, A LARGE NUMBER OF 

3397
02:07:26,499 --> 02:07:28,434
(INDISCERNIBLE) THE RELEASE 

3398
02:07:28,434 --> 02:07:30,303
THAT HAVE AN EFFECT ON 

3399
02:07:30,303 --> 02:07:32,105
NEUROGENESIS AND ANGIOGENESIS, 

3400
02:07:32,105 --> 02:07:34,307
BUT THIS AFFECTS 

3401
02:07:34,307 --> 02:07:34,907
PERSON-TO-PERSON FOR EXAMPLE 

3402
02:07:34,907 --> 02:07:35,975
THE IMPACT OF PHYSICAL ACTIVITY 

3403
02:07:35,975 --> 02:07:36,609
ON MOOD OR COGNITION SEEMS TO 

3404
02:07:36,609 --> 02:07:42,181
VARY IN , ACUTE OR MORE CHRONIC 

3405
02:07:42,181 --> 02:07:42,782
SETTINGS BASED ON WHETHER THE 

3406
02:07:42,782 --> 02:07:46,152
PERSON IS HOMOZYGOTES OR 

3407
02:07:46,152 --> 02:07:47,153
(INDISCERNIBLE) CARRIER. 

3408
02:07:47,153 --> 02:07:53,426
NEXT SLIDE. 

3409
02:07:53,426 --> 02:07:53,860
ONE THING TO MULTIPLE 

3410
02:07:53,860 --> 02:07:54,427
INTERVENTIONS AGAIN SOME OF 

3411
02:07:54,427 --> 02:08:04,937
THESE LIKE IMPACTING OMEGA-3 

3412
02:08:07,373 --> 02:08:07,940
FATTY ACIDS, OR BLOOD PRESSURE 

3413
02:08:07,940 --> 02:08:16,849
CONTROL WERE NOT AFFECTED WITH 

3414
02:08:16,849 --> 02:08:17,483
-- EFFECTIVE FOR BLOOD PRESSURE 

3415
02:08:17,483 --> 02:08:20,052
CONTROL BUT NOT MUCH ADDITIONAL 

3416
02:08:20,052 --> 02:08:20,586
VALUE AND SO STUDIES ARE 

3417
02:08:20,586 --> 02:08:21,187
EXTENDING WHAT WAS DONE IN A 

3418
02:08:21,187 --> 02:08:21,754
SWEETIE SETTING TO A LARGE 

3419
02:08:21,754 --> 02:08:24,257
NUMBER OF HEALTH SYSTEMS AND 

3420
02:08:24,257 --> 02:08:24,891
PATIENT POPULATION TO SEE WHAT 

3421
02:08:24,891 --> 02:08:25,491
THE BENEFIT MIGHT BE. 

3422
02:08:25,491 --> 02:08:26,959
NEXT SLIDE. 

3423
02:08:26,959 --> 02:08:31,964
RECOMMENDATION 6 THEREFORE 

3424
02:08:31,964 --> 02:08:32,899
EMPHASIZES LOOKING AT THE 

3425
02:08:32,899 --> 02:08:35,601
HETEROGENEITY, UNDERSTANDING 

3426
02:08:35,601 --> 02:08:36,202
THE IMPACT OF SPECIFIC, SMALL 

3427
02:08:36,202 --> 02:08:38,037
VESSEL DISEASE PATHOLOGIES AND 

3428
02:08:38,037 --> 02:08:38,571
VASCULAR RISK FACTORS OF 

3429
02:08:38,571 --> 02:08:42,508
COGNITIVE CHANGE DECLINE.  

3430
02:08:42,508 --> 02:08:43,009
RECOGNIZING THAT THESE 

3431
02:08:43,009 --> 02:08:48,314
HETEROGENEOUS PATHOLOGIES MAY 

3432
02:08:48,314 --> 02:08:49,815
CO-AUTHOR, MAY IMPACT THE 

3433
02:08:49,815 --> 02:08:50,449
POPULATION DEPENDING ON WHAT IS 

3434
02:08:50,449 --> 02:08:51,017
HAPPENING IN THE VASCULAR 

3435
02:08:51,017 --> 02:08:54,587
SETTING. 

3436
02:08:54,587 --> 02:08:55,188
AND WE WANT TO REALLY INTERVENE 

3437
02:08:55,188 --> 02:08:56,589
AT THE PRECLINICAL STAGE, WHEN 

3438
02:08:56,589 --> 02:09:00,459
THESE PATHOLOGIES ARE THERE BUT 

3439
02:09:00,459 --> 02:09:00,960
THEY ARE NOT HAVING ANY 

3440
02:09:00,960 --> 02:09:02,328
DISCERNIBLE EFFECT ON 

3441
02:09:02,328 --> 02:09:07,900
COGNITION. ANALOGOUS TO THE 

3442
02:09:07,900 --> 02:09:12,405
PRECLINICAL AMYLOID ARGUMENT 

3443
02:09:12,405 --> 02:09:12,872
ADDED IN AN ASSET WAS 

3444
02:09:12,872 --> 02:09:16,442
EMPHASIZED WE HAVE FEW NOVEL 

3445
02:09:16,442 --> 02:09:17,043
TARGETS EMPHASIZING THE VALUE 

3446
02:09:17,043 --> 02:09:17,743
ON THE BRAIN IN PARTICULAR. 

3447
02:09:17,743 --> 02:09:21,380
NEXT SLIDE. 

3448
02:09:21,380 --> 02:09:21,948
AND SO HOW CAN WE PERHAPS GET 

3449
02:09:21,948 --> 02:09:24,884
AROUND THAT?

3450
02:09:24,884 --> 02:09:25,418
YOU HAVE ALREADY HEARD THAT 

3451
02:09:25,418 --> 02:09:27,620
CATEGORIZING THE DIFFERENT 

3452
02:09:27,620 --> 02:09:28,254
SUBTYPES DEPENDS ON LOOKING AT 

3453
02:09:28,254 --> 02:09:30,523
THE STATUS OF THE HEART, THE 

3454
02:09:30,523 --> 02:09:32,959
BLOOD VESSELS, THE BLOOD-BRAIN 

3455
02:09:32,959 --> 02:09:36,662
BARRIER, LOW MRI MEASURES AND 

3456
02:09:36,662 --> 02:09:37,263
WHITE MATTER HYPER INTENSITY 

3457
02:09:37,263 --> 02:09:39,398
AND PERIVASCULAR SPACES. 

3458
02:09:39,398 --> 02:09:43,970
 BUT AS WE GET MORE SENSITIVE 

3459
02:09:43,970 --> 02:09:44,537
BIOMARKERS WHICH WILL HEAR 

3460
02:09:44,537 --> 02:09:45,137
ABOUT LATER WE ALSO HAVE THE 

3461
02:09:45,137 --> 02:09:45,871
QUESTION ABOUT WHAT IS THERE. 

3462
02:09:45,871 --> 02:09:48,307
NEXT SLIDE. 

3463
02:09:48,307 --> 02:09:56,716
AND THERE ARE INTERACTIONS WITH 

3464
02:09:56,716 --> 02:09:57,450
THE, FOR EXAMPLE, 

3465
02:09:57,450 --> 02:09:57,984
POSTMENOPAUSAL STATUS, SO 

3466
02:09:57,984 --> 02:09:58,451
VASCULAR AND AMYLOID 

3467
02:09:58,451 --> 02:10:02,488
SYNERGISTICALLY ACT ON TAU 

3468
02:10:02,488 --> 02:10:03,022
ACCUMULATING THIS IN TURN 

3469
02:10:03,022 --> 02:10:03,789
MEDIATES THE COGNITIVE DECLINE. 

3470
02:10:03,789 --> 02:10:05,524
NEXT SLIDE. 

3471
02:10:05,524 --> 02:10:11,964
SO, WHEN ONE TAKES A LUMPING 

3472
02:10:11,964 --> 02:10:12,498
APPROACH TO MAXIMIZE THE 

3473
02:10:12,498 --> 02:10:16,802
ABILITY TO FIND SMALL EFFECTS, 

3474
02:10:16,802 --> 02:10:17,336
ONE FINDS NEW BIOLOGICAL 

3475
02:10:17,336 --> 02:10:19,905
PATHWAYS.  ONE CAN UNDERSTAND 

3476
02:10:19,905 --> 02:10:21,307
THE CONTEXT IN BOTH THE 

3477
02:10:21,307 --> 02:10:24,076
CELLULAR AND -- LAST SLIDE 

3478
02:10:24,076 --> 02:10:27,780
PLEASE --  BOTH CELL AND 

3479
02:10:27,780 --> 02:10:31,250
SPATIAL LEVEL USING SINGLE CELL 

3480
02:10:31,250 --> 02:10:31,784
AND SPATIAL MIX. 

3481
02:10:31,784 --> 02:10:41,727
NEXT SLIDE. 

3482
02:10:41,727 --> 02:10:42,295
WE CONSIDER HOMOGENEOUS HYPER 

3483
02:10:42,295 --> 02:10:44,730
INTENSITY AS WELL, WHEN WE TAKE 

3484
02:10:44,730 --> 02:10:45,331
(INDISCERNIBLE) WE FIND THERE 

3485
02:10:45,331 --> 02:10:51,537
IS HETEROGENEITY OF BIOLOGY FOR 

3486
02:10:51,537 --> 02:10:53,306
EXAMPLE PERIVENTRIC OF 

3487
02:10:53,306 --> 02:10:58,277
SUBCORTICAL. 

3488
02:10:58,277 --> 02:10:58,844
CAN LEAD TO THE DETECTION OF 

3489
02:10:58,844 --> 02:10:59,512
NEW BIOLOGICAL PATHWAYS. 

3490
02:10:59,512 --> 02:11:01,781
NEXT SLIDE. 

3491
02:11:01,781 --> 02:11:06,986
WHAT IS THE VALUE OF THIS?

3492
02:11:06,986 --> 02:11:07,586
FOR EXAMPLE WE TALKED ABOUT NOT 

3493
02:11:07,586 --> 02:11:08,220
HAVING SPECIFIC TARGET FOR THE 

3494
02:11:08,220 --> 02:11:12,224
LYMPHATIC SYSTEM WHEN ONE TAKES 

3495
02:11:12,224 --> 02:11:13,025
PERIVASCULAR SPACES, IDENTIFIED 

3496
02:11:13,025 --> 02:11:19,665
UNDERLYING GENETICS, AND 

3497
02:11:19,665 --> 02:11:20,266
CORRELATES AND SEES WHAT ARE 

3498
02:11:20,266 --> 02:11:20,833
THE GENES WHOSE LEVELS ARE 

3499
02:11:20,833 --> 02:11:23,636
IMPACTED BY AVAILABLE, 

3500
02:11:23,636 --> 02:11:26,072
REPURPOSABLE DRUGS, THIS MAY 

3501
02:11:26,072 --> 02:11:26,872
LEAD TO NEW TARGETS FOR THE 

3502
02:11:26,872 --> 02:11:28,374
HUMAN TRACKS. 

3503
02:11:28,374 --> 02:11:29,508
THANK YOU.

3504
02:11:29,508 --> 02:11:37,049
NEXT. 

3505
02:11:37,049 --> 02:11:40,486
>> DR. LU: THANK YOU VERY
MUCH. 

3506
02:11:40,486 --> 02:11:50,563
CAN YOU HEAR ME?

3507
02:11:50,563 --> 02:12:00,773
>> YES WE CAN. 

3508
02:12:04,076 --> 02:12:06,445
NOW WE CANNOT. 

3509
02:12:06,445 --> 02:12:12,551
>> WE LOST YOU. 

3510
02:12:12,551 --> 02:12:13,152
>> I COULD HEAR YOU
BEFORE. IF 

3511
02:12:13,152 --> 02:12:13,786
YOU ARE SPEAKING NOW, WE CANNOT 

3512
02:12:13,786 --> 02:12:15,287
HEAR YOU. 

3513
02:12:15,287 --> 02:12:25,631
>> THE SCREEN IS BLACK. 

3514
02:12:41,847 --> 02:12:44,817
>> YOU MAY HAVE TO LEAVE
AND 

3515
02:12:44,817 --> 02:12:55,027
OCME BACK. 

3516
02:12:55,494 --> 02:12:58,497
>> I THINK HE LEFT. 

3517
02:12:58,497 --> 02:13:00,666
WE WILL SEE HIM AGAIN SHORTLY. 

3518
02:13:00,666 --> 02:13:04,537
HE'S BACK. 

3519
02:13:04,537 --> 02:13:06,772
>> DR. LU: VERY SORRY
ABOUT 

3520
02:13:06,772 --> 02:13:08,574
THAT. 

3521
02:13:08,574 --> 02:13:09,608
>> YEAH WE HAVE YOU BACK. 

3522
02:13:09,608 --> 02:13:14,146
>> DR. LU: OKAY SORRY. 

3523
02:13:14,146 --> 02:13:15,881
>> THANK YOU. 

3524
02:13:15,881 --> 02:13:19,919
>> DR. LU: NEXT. 

3525
02:13:19,919 --> 02:13:20,853
I HAVE NOTHING TO DISCLOSE. 

3526
02:13:20,853 --> 02:13:23,722
NEXT. 

3527
02:13:23,722 --> 02:13:27,259
SO, THE COMMITTEE MADE TO 

3528
02:13:27,259 --> 02:13:27,827
RECOMMENDATIONS RELATED TO 

3529
02:13:27,827 --> 02:13:30,663
BIOMARKERS OF VCID. 

3530
02:13:30,663 --> 02:13:34,300
RECOMMENDATIONS 7 AND 8. 

3531
02:13:34,300 --> 02:13:35,401
THE DIFFERENCE BETWEEN THESE 

3532
02:13:35,401 --> 02:13:39,004
TWO LIES IN THE STAGE OF THE 

3533
02:13:39,004 --> 02:13:43,042
DEVELOPING PROCESS OF THE 

3534
02:13:43,042 --> 02:13:46,745
BIOMARKERS. I WANT TO NOTE THAT 

3535
02:13:46,745 --> 02:13:47,379
HERE, BY DIFFERENT STAGE AT ALL 

3536
02:13:47,379 --> 02:13:48,447
MEAN DISEASE SEVERITY STAGE. I 

3537
02:13:48,447 --> 02:13:49,081
MEAN INSTEAD DEVELOPMENT STAGE 

3538
02:13:49,081 --> 02:13:51,584
OF THE BIOMARKER PROCESS. 

3539
02:13:51,584 --> 02:13:55,988
SO RECOMMENDATION 7 IS TO 

3540
02:13:55,988 --> 02:13:56,622
DEVELOP AND VALIDATE CANDIDATE 

3541
02:13:56,622 --> 02:14:00,359
BIOMARKERS OF VCID IN 

3542
02:14:00,359 --> 02:14:02,261
PRECLINICAL MODELS AND 

3543
02:14:02,261 --> 02:14:02,895
HIGH-RISK POPULATIONS THAT SPAN 

3544
02:14:02,895 --> 02:14:06,198
THE TYPES OF BIOMARKERS 

3545
02:14:06,198 --> 02:14:08,267
ENCOMPASSING IMAGING, BIO 

3546
02:14:08,267 --> 02:14:12,104
FLUID, MULTI-OMIC, DIGITAL, AI, 

3547
02:14:12,104 --> 02:14:16,842
AND IN OTHER NOVEL BIOMARKERS, 

3548
02:14:16,842 --> 02:14:17,443
INCLUDING IN THE MOST COMMON 

3549
02:14:17,443 --> 02:14:20,446
SCENARIO WHERE VCID IS 

3550
02:14:20,446 --> 02:14:21,013
ACCOMPANIED BY BETA AMYLOID 

3551
02:14:21,013 --> 02:14:24,783
PLAQUES AND TAU TANGLES. 

3552
02:14:24,783 --> 02:14:27,019
NEXT SLIDE. 

3553
02:14:27,019 --> 02:14:28,320
THERE ARE NO CURRENT VALIDATED 

3554
02:14:28,320 --> 02:14:31,590
BIOMARKERS FOR VCID. 

3555
02:14:31,590 --> 02:14:32,157
THE COMMITTEE RECOMMENDS THAT 

3556
02:14:32,157 --> 02:14:38,364
THE PROCESS TO DEVELOP VCID 

3557
02:14:38,364 --> 02:14:38,931
BIOMARKERS SPANS ACROSS THE 

3558
02:14:38,931 --> 02:14:41,867
RANGE OF STEPS AND PHASES. 

3559
02:14:41,867 --> 02:14:42,468
THIS RECOMMENDATION SUPPORT THE 

3560
02:14:42,468 --> 02:14:43,302
DISCOVERY AND EARLY STAGE OF 

3561
02:14:43,302 --> 02:14:44,103
IMPLEMENTING THE VALIDATION OF 

3562
02:14:44,103 --> 02:14:44,970
VCID BIOMARKERS. 

3563
02:14:44,970 --> 02:14:46,505
NX1

3564
02:14:46,505 --> 02:14:52,344
NEXT SLIDE. 

3565
02:14:52,344 --> 02:14:52,845
ONE CONSIDERATION IN THIS 

3566
02:14:52,845 --> 02:14:54,914
RECOMMENDATION IS THAT THE 

3567
02:14:54,914 --> 02:14:55,414
COMMITTEE WOULD LIKE TO 

3568
02:14:55,414 --> 02:14:56,715
LEVERAGE FINDINGS FROM 

3569
02:14:56,715 --> 02:14:59,585
PRECLINICAL AND (INDISCERNIBLE) 

3570
02:14:59,585 --> 02:15:02,121
TO DEVELOP THE NEW BIOMARKERS. 

3571
02:15:02,121 --> 02:15:05,658
PRECLINICAL AND BASE STUDIES 

3572
02:15:05,658 --> 02:15:09,261
ACKNOWLEDGE THE MECHANISM OF 

3573
02:15:09,261 --> 02:15:12,665
VCID; SOME OF THEM IF THEY CAN 

3574
02:15:12,665 --> 02:15:13,732
BE MEASURED IN NONINVASIVE OR 

3575
02:15:13,732 --> 02:15:14,233
MINIMALLY INVASIVE CAN 

3576
02:15:14,233 --> 02:15:14,833
POTENTIALLY BE TRANSLATED TO 

3577
02:15:14,833 --> 02:15:17,336
BECOME BIOMARKERS. 

3578
02:15:17,336 --> 02:15:21,574
FOR EXAMPLE IN THIS PARTICULAR 

3579
02:15:21,574 --> 02:15:22,207
EXAMPLE WE MEASURE THE COVERAGE 

3580
02:15:22,207 --> 02:15:22,841
OF PARASITES, IMPORTANT TO THE 

3581
02:15:22,841 --> 02:15:26,011
ELEMENT OF NEUROVASCULAR UNIT. 

3582
02:15:26,011 --> 02:15:26,612
THEY SHOW THAT THIS PARASITE 

3583
02:15:26,612 --> 02:15:36,355
MEASUREMENT CAN BE STRONGLY 

3584
02:15:36,355 --> 02:15:38,457
CORRELATED TO SERUM BASED 

3585
02:15:38,457 --> 02:15:40,459
(INDISCERNIBLE), POTENTIAL 

3586
02:15:40,459 --> 02:15:42,995
(INDISCERNIBLE) FOR BIOMARKERS 

3587
02:15:42,995 --> 02:15:44,063
FOR VCID. 

3588
02:15:44,063 --> 02:15:49,768
NEXT SLIDE. 

3589
02:15:49,768 --> 02:15:50,302
SO, ANOTHER ASPECT THAT THE 

3590
02:15:50,302 --> 02:15:50,903
COMMITTEE CONSIDERED IS THEY 

3591
02:15:50,903 --> 02:15:55,541
WANT TO HAVE BIOMARKERS 

3592
02:15:55,541 --> 02:15:56,108
SPECIFIC TO CERTAIN TYPE OF 

3593
02:15:56,108 --> 02:15:56,942
SMALL VESSEL PATHOLOGY.

3594
02:15:56,942 --> 02:16:00,212
AS WE JUST HEARD A 

3595
02:16:00,212 --> 02:16:10,689
(INDISCERNIBLE) COMMON IN ADID. 

3596
02:16:10,689 --> 02:16:12,558
ACTUALLY VCID IS NOT ONE 

3597
02:16:12,558 --> 02:16:14,093
DISEASE. PATIENTS WHO HAVE 

3598
02:16:14,093 --> 02:16:16,228
DIFFERENT VASCULAR PATHOLOGIES, 

3599
02:16:16,228 --> 02:16:19,098
SO IS DESIRABLE FOR BIOMARKERS 

3600
02:16:19,098 --> 02:16:19,732
TO HAVE A SPECIFIC RELATIONSHIP 

3601
02:16:19,732 --> 02:16:20,232
TO A TYPE OF VASCULAR 

3602
02:16:20,232 --> 02:16:22,067
PATHOLOGY. 

3603
02:16:22,067 --> 02:16:27,606
AND THE PATHOLOGY, EXAMPLE SUCH 

3604
02:16:27,606 --> 02:16:32,111
AS -- ARTERIAL SCLEROSIS-- IN 

3605
02:16:32,111 --> 02:16:32,578
THIS EXAMPLE WE COULD 

3606
02:16:32,578 --> 02:16:37,483
POTENTIALLY SEE THAT AB 42 - 

3607
02:16:37,483 --> 02:16:40,352
ONE RATIO BETWEEN AB 42 AND 

3608
02:16:40,352 --> 02:16:43,922
BEETA  IS A MEASURE OF CSF CAN 

3609
02:16:43,922 --> 02:16:44,523
BE USED FOR THE PATHOLOGY OF 

3610
02:16:44,523 --> 02:16:46,959
THE A B PATHOLOGY MARKER. 

3611
02:16:46,959 --> 02:16:50,295
NEXT SLIDE. 

3612
02:16:50,295 --> 02:16:52,731
SO FAR, I WILL GIVE YOU 

3613
02:16:52,731 --> 02:16:54,967
EXAMPLES OF BIO FLUID WITH THE 

3614
02:16:54,967 --> 02:16:55,534
COMMITTEE ALSO RECOGNIZE WE 

3615
02:16:55,534 --> 02:16:57,302
SHOULD USE THE FULL SPECTRUM OF 

3616
02:16:57,302 --> 02:16:57,936
BIOMARKER TECHNOLOGY AVAILABLE 

3617
02:16:57,936 --> 02:16:59,571
TO US. 

3618
02:16:59,571 --> 02:17:03,108
ONE EXAMPLE IS IMAGING.  IN 

3619
02:17:03,108 --> 02:17:03,742
THIS PARTICULAR EXAMPLE YOU CAN 

3620
02:17:03,742 --> 02:17:07,179
SEE THAT THESE INVESTIGATOR USE 

3621
02:17:07,179 --> 02:17:10,549
MI TO MEASURE (INDISCERNIBLE), 

3622
02:17:10,549 --> 02:17:12,217
AND THIS CAN PROVIDE A 

3623
02:17:12,217 --> 02:17:13,118
PHYSIOLOGICAL ASSESSMENT OF THE 

3624
02:17:13,118 --> 02:17:15,320
LESION AND DAMAGE IN VCID 

3625
02:17:15,320 --> 02:17:16,321
PATIENTS. 

3626
02:17:16,321 --> 02:17:24,496
NEXT SLIDE. 

3627
02:17:24,496 --> 02:17:25,030
SIMILARLY,  THERE HAS BEEN 

3628
02:17:25,030 --> 02:17:26,031
TREMENDOUS PROGRESS IN 

3629
02:17:26,031 --> 02:17:27,633
MULTI-OMIC TECHNOLOGY, AND SOME 

3630
02:17:27,633 --> 02:17:31,870
OF THIS IF THEY CAN BE 

3631
02:17:31,870 --> 02:17:32,371
(INDISCERNIBLE) TO THE 

3632
02:17:32,371 --> 02:17:32,971
INDIVIDUAL LEVEL THAT CAN BE 

3633
02:17:32,971 --> 02:17:34,707
LEVERAGED TO DO BE DEVELOPED AS 

3634
02:17:34,707 --> 02:17:38,310
A BIOMARKER FOR VCID. 

3635
02:17:38,310 --> 02:17:40,212
FOR EXAMPLE IN THIS REGULAR 

3636
02:17:40,212 --> 02:17:44,683
EXAMPLE INVESTING SHOW THAT 

3637
02:17:44,683 --> 02:17:48,420
TRANS MULTI-OMIC DATA CAN BE 

3638
02:17:48,420 --> 02:17:58,063
USED IN THE CELL PERI VASCULAR 

3639
02:17:58,063 --> 02:17:58,964
SPACE, SO THIS TECHNOLOGY CAN 

3640
02:17:58,964 --> 02:17:59,531
BE QUITE USEFUL FOR FUTURE 

3641
02:17:59,531 --> 02:18:00,265
DEVELOPMENT OF BIOMARKERS IN 

3642
02:18:00,265 --> 02:18:00,799
VCID. 

3643
02:18:00,799 --> 02:18:05,337
NEXT SLIDE. 

3644
02:18:05,337 --> 02:18:08,507
FINALLY THE COMMITTEE 

3645
02:18:08,507 --> 02:18:09,141
RECOGNIZED THAT THERE HAS BEEN 

3646
02:18:09,141 --> 02:18:09,641
TREMENDOUS PROGRESS IN 

3647
02:18:09,641 --> 02:18:10,209
ARTIFICIAL INTELLIGENCE AND 

3648
02:18:10,209 --> 02:18:10,776
MACHINE LEARNING. THEREFORE 

3649
02:18:10,776 --> 02:18:15,581
THEY RECOMMEND TO USE AI 

3650
02:18:15,581 --> 02:18:16,181
MACHINE LEARNING IN ADVANCED 

3651
02:18:16,181 --> 02:18:17,616
MATHEMATICAL MODELING 

3652
02:18:17,616 --> 02:18:18,217
TECHNIQUES FOR ADVANCING THE 

3653
02:18:18,217 --> 02:18:25,924
BIOMARKERS IN THE VCID SPACE. 

3654
02:18:25,924 --> 02:18:26,525
AND THE GOAL IS TO HAVE MINIMAL 

3655
02:18:26,525 --> 02:18:27,126
EXPERIMENTAL DATA TO ACHIEVE 

3656
02:18:27,126 --> 02:18:27,693
THE HIGHEST SENSITIVITY AND 

3657
02:18:27,693 --> 02:18:29,762
SPECIFICITY FOR PATIENT 

3658
02:18:29,762 --> 02:18:32,464
BIOMARKER APPLICATION. 

3659
02:18:32,464 --> 02:18:32,998
IN THIS PARTICULAR EXAMPLE 

3660
02:18:32,998 --> 02:18:35,667
INVESTING IT IS USED A SMALL 

3661
02:18:35,667 --> 02:18:38,737
SIMPLE MI IMAGE TO USE MACHINE 

3662
02:18:38,737 --> 02:18:41,373
LEARNING AND SHOW THE VASCULAR 

3663
02:18:41,373 --> 02:18:44,476
DEMENTIA OR DISEASE REFLECT THE 

3664
02:18:44,476 --> 02:18:49,815
REASONS FOR DEMENTIA OR DISEASE 

3665
02:18:49,815 --> 02:18:51,717
PRIMARILY AFFECT THE 

3666
02:18:51,717 --> 02:18:52,451
HIPPOCAMPAL REGION. 

3667
02:18:52,451 --> 02:18:54,486
NEXT SLIDE. 

3668
02:18:54,486 --> 02:18:56,989
LET'S MOVE ON TO RECOMMENDATION 

3669
02:18:56,989 --> 02:19:01,527
8. TO CONDUCT STUDIES OF 

3670
02:19:01,527 --> 02:19:02,094
BIOMARKERS IN LATE STAGE OF 

3671
02:19:02,094 --> 02:19:02,661
DEVELOPMENT IN INSTRUMENTAL 

3672
02:19:02,661 --> 02:19:03,695
CLINICAL VALIDATION, DEFINING 

3673
02:19:03,695 --> 02:19:08,801
THE BIOMARKER CATEGORIES IN THE 

3674
02:19:08,801 --> 02:19:09,401
CONTEXT OF USE INCLUDING FOR 

3675
02:19:09,401 --> 02:19:10,035
EXAMPLE INTEGRATIVE ACTIVITIES 

3676
02:19:10,035 --> 02:19:12,504
OF DAILY LIVING, QUALITY OF 

3677
02:19:12,504 --> 02:19:13,138
LIFE METRICS WITH THE ULTIMATE 

3678
02:19:13,138 --> 02:19:13,872
GOAL OF REGULATORY APPROVAL. 

3679
02:19:13,872 --> 02:19:14,973
THIS IS PRIORITY NUMBER 1. 

3680
02:19:14,973 --> 02:19:19,878
NEXT SLIDE. 

3681
02:19:19,878 --> 02:19:22,848
SO WHAT IS THE RATIONALE HERE?

3682
02:19:22,848 --> 02:19:23,816
THERE ARE A NUMBER OF PROMISING 

3683
02:19:23,816 --> 02:19:28,954
CANDIDATE VCID BIOMARKERS. BUT 

3684
02:19:28,954 --> 02:19:29,521
FEW IF ANY HAVE REACHED THE 

3685
02:19:29,521 --> 02:19:32,391
LEVEL OF REGULAR TREE 

3686
02:19:32,391 --> 02:19:32,925
(CORRECTION) REGULATORY 

3687
02:19:32,925 --> 02:19:41,400
APPROVAL. 

3688
02:19:41,400 --> 02:19:41,867
WE KNOW THAT REGULATORY 

3689
02:19:41,867 --> 02:19:42,467
APPROVAL IS IMPORTANT. IT IS 

3690
02:19:42,467 --> 02:19:43,068
DESIRABLE TO HAVE ONE OR MORE 

3691
02:19:43,068 --> 02:19:48,373
OF THESE BIOMARKERS OF VCID TO 

3692
02:19:48,373 --> 02:19:50,309
CROSS THE FINISH LINE OF THE 

3693
02:19:50,309 --> 02:19:52,144
FDA APPROVAL OR QUALIFICATION.

3694
02:19:52,144 --> 02:19:52,711
AND ONCE AGAIN BORROWING FROM 

3695
02:19:52,711 --> 02:19:54,279
THE EXPERIENCE FROM -- IN THE 

3696
02:19:54,279 --> 02:19:58,450
AD FIELD, THE FIRST DEVELOPED 

3697
02:19:58,450 --> 02:20:05,057
AMYLOID AND TALL BIOMARKERS 

3698
02:20:05,057 --> 02:20:06,225
USED TO ACCELERATE THE 

3699
02:20:06,225 --> 02:20:13,298
TREATMENT. ONE OF THESE VCID 

3700
02:20:13,298 --> 02:20:13,932
BIOMARKERS CAN BE VALIDATED OR 

3701
02:20:13,932 --> 02:20:14,466
APPROVED THAT CAN HELP TO 

3702
02:20:14,466 --> 02:20:15,033
DEVELOP IN THE FUTURE LESS 

3703
02:20:15,033 --> 02:20:16,702
EXTENSIVE AND MORE ACCESSIBLE 

3704
02:20:16,702 --> 02:20:23,709
BIOMARKERS. IN THE AD SPACE, WE 

3705
02:20:23,709 --> 02:20:24,343
CAN SEE NEW PLASMA MARKERS THAT 

3706
02:20:24,343 --> 02:20:24,943
CAN BE DEVELOPED AND APPROVED 

3707
02:20:24,943 --> 02:20:34,620
USING THE EARLIER PET MARKER-- 

3708
02:20:34,620 --> 02:20:35,220
AS LONG AS WE CAN ONE OR MORE 

3709
02:20:35,220 --> 02:20:35,821
TRULY VALIDATED AND QUALIFIED 

3710
02:20:35,821 --> 02:20:36,421
APPROVED BIOMARKERS. 

3711
02:20:36,421 --> 02:20:44,162
NEXT SLIDE. 

3712
02:20:44,162 --> 02:20:47,599
ONE PURSUIT OF THIS AT THIS 

3713
02:20:47,599 --> 02:20:48,500
LATE STAGE, ONE HAS TO HAVE 

3714
02:20:48,500 --> 02:20:49,101
CLINICAL VALIDATION OF THESE 

3715
02:20:49,101 --> 02:20:51,670
BIOMARKERS.  AND THERE ARE A 

3716
02:20:51,670 --> 02:20:52,404
FEW METRICS ONE CAN ASK IF YOU 

3717
02:20:52,404 --> 02:20:56,508
HAVE TWO RESEARCHERS TO PERFORM 

3718
02:20:56,508 --> 02:21:04,316
THE SAME ASSAY,  ON THE SAME 

3719
02:21:04,316 --> 02:21:04,917
PATIENT SAMPLES, DO THEY GET 

3720
02:21:04,917 --> 02:21:09,221
THE SAME RESULTS?

3721
02:21:09,221 --> 02:21:11,456
AND IT WOULD COME BACK AFTER A 

3722
02:21:11,456 --> 02:21:12,024
SHORT INTERVAL YOU CAN SEE 

3723
02:21:12,024 --> 02:21:12,524
WHETHER THE MEASURE IS 

3724
02:21:12,524 --> 02:21:14,459
COMPATIBLE OR CONSISTENT. 

3725
02:21:14,459 --> 02:21:16,495
SIMILARLY, IF YOU CAN DO MI 

3726
02:21:16,495 --> 02:21:21,500
MEASUREMENTS ON TWO DIFFERENT 

3727
02:21:21,500 --> 02:21:22,134
-- YOU CAN SEE WHETHER THE DATA 

3728
02:21:22,134 --> 02:21:30,976
YOU OBTAIN IS REPRODUCIBLE. 

3729
02:21:30,976 --> 02:21:31,410
CALLED INTER VENDOR 

3730
02:21:31,410 --> 02:21:34,212
REPRODUCIBILITY. 

3731
02:21:34,212 --> 02:21:37,983
AND SHOWS INSTRUMENTAL 

3732
02:21:37,983 --> 02:21:38,583
VALIDATION. AND IT SHOWS THE 

3733
02:21:38,583 --> 02:21:40,385
SCATTER PATTERN IS HOPEFULLY TO 

3734
02:21:40,385 --> 02:21:50,862
SHOW THE RESULT ON THE SAME 

3735
02:21:52,097 --> 02:21:52,631
LINE WITH LITTLE VARIATION IN 

3736
02:21:52,631 --> 02:21:53,231
THE SPACE TO MOVE TO FOR THE 

3737
02:21:53,231 --> 02:21:54,733
VALIDATION STEPS. 

3738
02:21:54,733 --> 02:21:55,400
THE COMMITTEE NOTED THAT THE 

3739
02:21:55,400 --> 02:22:01,073
FDA AND MH HAVE SOME GUIDELINES 

3740
02:22:01,073 --> 02:22:01,673
FOR BIOMARKER DEVELOPMENT AND 

3741
02:22:01,673 --> 02:22:03,709
THEY JOINTLY DEVELOP THESE 

3742
02:22:03,709 --> 02:22:06,111
BIOMARKERS END POINTS AND OTHER 

3743
02:22:06,111 --> 02:22:08,714
TOOLS. 

3744
02:22:08,714 --> 02:22:09,815
AND UNDER THIS FRAMEWORK THE 

3745
02:22:09,815 --> 02:22:10,916
DEFINED THE DIFFERENT 

3746
02:22:10,916 --> 02:22:14,119
CATEGORIES FOR BIOMARKERS. AND 

3747
02:22:14,119 --> 02:22:18,857
THERE ARE SEVEN POSSIBLE 

3748
02:22:18,857 --> 02:22:19,491
CATEGORIES. ACCESSIBILITY RISK, 

3749
02:22:19,491 --> 02:22:20,325
DIAGNOSTIC, MONITORING, 

3750
02:22:20,325 --> 02:22:21,893
PROGNOSTIC, PREDICTIVE, 

3751
02:22:21,893 --> 02:22:26,064
PHARMACODYNAMIC, AND SAFETY.

3752
02:22:26,064 --> 02:22:26,631
SO WHEN YOU HAVE A BIOMARKER 

3753
02:22:26,631 --> 02:22:31,403
FOR CONSIDERATION AND EVENTUAL 

3754
02:22:31,403 --> 02:22:31,970
APPROVAL BY THE REGULATORY 

3755
02:22:31,970 --> 02:22:32,604
AGENCIES, YOU WANT TO PUT THIS 

3756
02:22:32,604 --> 02:22:36,575
CATEGORY IN MIND. 

3757
02:22:36,575 --> 02:22:37,576
SIMILARLY YOU HAVE TO OPPOSE 

3758
02:22:37,576 --> 02:22:38,143
EACH BIOMARKER AND HAVE AT 

3759
02:22:38,143 --> 02:22:40,445
LEAST ONE IF NOT MORE CONTENT 

3760
02:22:40,445 --> 02:22:47,085
USE. CONSIDER INCLUSION, 

3761
02:22:47,085 --> 02:22:47,719
EXCLUSION CRITERIA IN THE TRIAL 

3762
02:22:47,719 --> 02:22:48,220
OR EVALUATING TREATMENT 

3763
02:22:48,220 --> 02:22:48,620
RESPONSE. 

3764
02:22:48,620 --> 02:22:51,023
NEXT SLIDE. 

3765
02:22:51,023 --> 02:22:55,093
AND THE COMMITTEE NOTED THAT 

3766
02:22:55,093 --> 02:22:57,929
MOST OF THE CURRENT BIOMARKERS 

3767
02:22:57,929 --> 02:22:58,363
HAVE BEEN BASED ON 

3768
02:22:58,363 --> 02:23:03,035
OBSERVATIONAL STUDIES.  AND WE 

3769
02:23:03,035 --> 02:23:08,106
FELT IT WOULD BE USEFUL-- -- 

3770
02:23:08,106 --> 02:23:10,609
THE VALIDATION OF THE BIOMARKER 

3771
02:23:10,609 --> 02:23:11,209
IF THE BIOMARKER CAN ALSO BE 

3772
02:23:11,209 --> 02:23:11,810
TACIT IN SOME INTERVENTIONAL 

3773
02:23:11,810 --> 02:23:13,145
STUDIES. 

3774
02:23:13,145 --> 02:23:16,214
IN THIS PARTICULAR EXAMPLE, 

3775
02:23:16,214 --> 02:23:18,050
INVESTIGATORS USED  VASCULAR 

3776
02:23:18,050 --> 02:23:22,254
ACTIVITY -- AS THE PRIMARY 

3777
02:23:22,254 --> 02:23:23,321
OUTCOME BIOMARKER MEASURE TO 

3778
02:23:23,321 --> 02:23:26,391
EVALUATE A SUITE OF CLASSES OF 

3779
02:23:26,391 --> 02:23:27,092
HYPERTENSIVE DRUGS. 

3780
02:23:27,092 --> 02:23:31,196
NEXT SLIDE. 

3781
02:23:31,196 --> 02:23:34,232
AND FINALLY, MOST OF THE 

3782
02:23:34,232 --> 02:23:41,673
VALIDATION WORK OF BIOMARKERS 

3783
02:23:41,673 --> 02:23:42,174
ABUSE CONTENT MEASURES, 

3784
02:23:42,174 --> 02:23:42,774
CLINICAL DIMENSION READING OR 

3785
02:23:42,774 --> 02:23:43,875
DIAGNOSTIC CATEGORIES. 

3786
02:23:43,875 --> 02:23:48,280
WE FELT IT WOULD BE USEFUL TO 

3787
02:23:48,280 --> 02:23:50,248
ALSO CONSIDER THINGS SUCH AS 

3788
02:23:50,248 --> 02:23:50,816
ACTIVITIES OF DAILY LIVING, 

3789
02:23:50,816 --> 02:23:53,185
QUALITY OF LIFE METRICS. 

3790
02:23:53,185 --> 02:23:54,486
SO THESE METRICS HAVE BEEN 

3791
02:23:54,486 --> 02:23:56,521
INCLUDED IN THE NEW UDS OF THE 

3792
02:23:56,521 --> 02:24:00,459
SORT OF PROTOCOL. AND THEY HAVE 

3793
02:24:00,459 --> 02:24:03,795
SOMETHING CALLED "FUNCTIONAL 

3794
02:24:03,795 --> 02:24:07,065
ASSESSMENT SCALE," FAS. 

3795
02:24:07,065 --> 02:24:08,633
AND THE BENEFIT IS TO ACTIVATE 

3796
02:24:08,633 --> 02:24:12,404
-- (INDISCERNIBLE)  THE 

3797
02:24:12,404 --> 02:24:16,374
SPECIFIC TASKS IN OUR DAILY 

3798
02:24:16,374 --> 02:24:17,309
LIFE. WHETHER THEY ARE 

3799
02:24:17,309 --> 02:24:17,909
FUNCTIONING PROPERLY WHEN YOU 

3800
02:24:17,909 --> 02:24:18,443
PERFORM THESE DAILY LIFE 

3801
02:24:18,443 --> 02:24:19,678
FUNCTIONAL WORK. 

3802
02:24:19,678 --> 02:24:21,046
>> TWO MINUTES. 

3803
02:24:21,046 --> 02:24:24,716
>> DR. LU: THIS MEASURE 

3804
02:24:24,716 --> 02:24:26,718
REQUIRES LESS SKILLS AND 

3805
02:24:26,718 --> 02:24:27,385
TRAINING TO ADMINISTER. 

3806
02:24:27,385 --> 02:24:30,222
NEXT SLIDE. 

3807
02:24:30,222 --> 02:24:36,495
SO SHOWN HERIS AN ILLUSTRATION 

3808
02:24:36,495 --> 02:24:44,369
OF THE NACC UDS  FAS FORM AND 

3809
02:24:44,369 --> 02:24:45,704
THEY ASKED SPECIFIC QUESTION, 

3810
02:24:45,704 --> 02:24:47,205
YOU CAN PREPARE A BALANCED MEAL 

3811
02:24:47,205 --> 02:24:50,842
AND WHETHER (INDISCERNIBLE) SO 

3812
02:24:50,842 --> 02:24:51,576
THIS PERFORMANCE IS REALLY WHAT 

3813
02:24:51,576 --> 02:24:53,645
MATTERS TO OUR PATIENTS.  

3814
02:24:53,645 --> 02:24:54,446
THEREFORE IT IS USEFUL TO 

3815
02:24:54,446 --> 02:24:59,417
VALIDATE THE VCID BIOMARKER IN 

3816
02:24:59,417 --> 02:25:00,085
THE CONTEXT OF THESE DAILY LIFE 

3817
02:25:00,085 --> 02:25:01,052
PERFORMANCE MEASURES. 

3818
02:25:01,052 --> 02:25:11,196
NEXT SLIDE. 

3819
02:25:14,032 --> 02:25:14,733
SO, WE HAVE THE OPPORTUNITY TO 

3820
02:25:14,733 --> 02:25:18,670
SHOW COMMITTEE MEMBERS THEY 

3821
02:25:18,670 --> 02:25:19,204
WORK REALLY HARD AND MADE 

3822
02:25:19,204 --> 02:25:19,838
IMPORTANT CONTRIBUTIONS DO THIS 

3823
02:25:19,838 --> 02:25:20,372
WORK AND I WOULD LIKE TO 

3824
02:25:20,372 --> 02:25:21,139
ACKNOWLEDGE THEM ONE MORE TIME. 

3825
02:25:21,139 --> 02:25:23,375
NEXT SLIDE. 

3826
02:25:23,375 --> 02:25:24,643
TO SUMMARIZE THESE AS THE 

3827
02:25:24,643 --> 02:25:27,279
RECOMMENDATIONS THAT THE VCID 

3828
02:25:27,279 --> 02:25:28,313
COMMITTEE CAME UP WITH AS A 

3829
02:25:28,313 --> 02:25:29,347
REMINDER THEY ARE CATEGORIZED 

3830
02:25:29,347 --> 02:25:34,486
INTO FOUR DIFFERENT CATEGORIES. 

3831
02:25:34,486 --> 02:25:37,656
RECOMMENDATIONS 1 AND 2, 

3832
02:25:37,656 --> 02:25:39,491
INVOLVING MAGNETIC STUDIES OF 

3833
02:25:39,491 --> 02:25:43,395
VCID AND RECOMMENDATION 4 MOVE 

3834
02:25:43,395 --> 02:25:44,062
TO TRANSLATION AND EXPANDING 

3835
02:25:44,062 --> 02:25:50,101
THE MECHANISM AND 5 AND 6, DEAL 

3836
02:25:50,101 --> 02:25:50,735
WITH HUMAN RELATED STUDIES SUCH 

3837
02:25:50,735 --> 02:25:52,571
AS INTERVENTION, TREATMENT AND 

3838
02:25:52,571 --> 02:25:53,138
THE DISEASE FROM THE HUMAN 

3839
02:25:53,138 --> 02:25:54,172
POINT OF VIEW. 

3840
02:25:54,172 --> 02:25:58,176
FINALLY RECOMMENDATIONS 7 AND 8 

3841
02:25:58,176 --> 02:26:01,179
DEAL WITH BIOMARKER DEVELOPMENT 

3842
02:26:01,179 --> 02:26:02,480
FROM EARLY-STAGE TO LATER STAGE 

3843
02:26:02,480 --> 02:26:03,114
EVENTUALLY HOPEFULLY TOWARDS 

3844
02:26:03,114 --> 02:26:04,316
REGULATORY APPROVAL. 

3845
02:26:04,316 --> 02:26:14,626
THANK YOU VERY MUCH. 

3846
02:26:17,762 --> 02:26:19,397
>> THANK YOU WILL GO TO 

3847
02:26:19,397 --> 02:26:19,931
QUESTIONS AND COMMENTS. I 

3848
02:26:19,931 --> 02:26:20,465
ENCOURAGE EVERYONE ON THE 

3849
02:26:20,465 --> 02:26:24,469
COMMITTEE FOR THE VCID SESSION 

3850
02:26:24,469 --> 02:26:29,808
TO TURN ON YOUR CAMERAS. 

3851
02:26:29,808 --> 02:26:32,744
THE MICROPHONE SHOULD BE UNDER 

3852
02:26:32,744 --> 02:26:43,288
YOUR CONTROL TO TURN ON OR OFF. 

3853
02:26:54,232 --> 02:26:56,401
>> THE FIRST QUESTION. THE

3854
02:26:56,401 --> 02:26:58,803
FIRST IS FROM HELEN. 

3855
02:26:58,803 --> 02:27:01,106
>> HELLO, YES, I WAS
ACTUALLY 

3856
02:27:01,106 --> 02:27:02,707
GOING TO LOOK AT WHEN WE LOOK 

3857
02:27:02,707 --> 02:27:04,542
AT CONTRIBUTIONS TO YOU KNOW, 

3858
02:27:04,542 --> 02:27:10,515
NOT JUST  VASCULAR 

3859
02:27:10,515 --> 02:27:16,154
CONTRIBUTIONS BUT TO GENERAL 

3860
02:27:16,154 --> 02:27:16,688
DEMENTIA, ONE OF THE BEST 

3861
02:27:16,688 --> 02:27:20,525
PHRASES I HEARD FROM A 

3862
02:27:20,525 --> 02:27:20,992
CLINICIAN WHAT IN THE 

3863
02:27:20,992 --> 02:27:21,626
INDIVIDUAL NOT ONLY PHYSICALLY 

3864
02:27:21,626 --> 02:27:22,294
ENGAGED, OBVIOUSLY INTRODUCE 

3865
02:27:22,294 --> 02:27:26,331
EXERCISE. BUT SOCIALLY ENGAGED. 

3866
02:27:26,331 --> 02:27:26,965
AND IN MY WORK IN THE FIELD, I 

3867
02:27:26,965 --> 02:27:31,036
FIND THAT ISOLATION AND LACK OF 

3868
02:27:31,036 --> 02:27:31,936
SOCIAL ENGAGEMENT IS A HUGE 

3869
02:27:31,936 --> 02:27:35,040
CONTRIBUTOR. 

3870
02:27:35,040 --> 02:27:36,474
SO I AM CURIOUS AS TO WHETHER 

3871
02:27:36,474 --> 02:27:38,543
THAT IS BEING LOOKED INTO, WHEN 

3872
02:27:38,543 --> 02:27:39,144
WE LOOK AT ALL OF THE FACTORS 

3873
02:27:39,144 --> 02:27:41,446
THAT MAY BE CONTRIBUTING. 

3874
02:27:41,446 --> 02:27:42,380
>> YEAH ABSOLUTELY. 

3875
02:27:42,380 --> 02:27:44,482
>> DR. FOSSATI: YOU WANT
TO 

3876
02:27:44,482 --> 02:27:46,184
COMMENT ON THIS? 

3877
02:27:46,184 --> 02:27:51,122
>> THANK YOU HELEN FOR ALL
YOUR 

3878
02:27:51,122 --> 02:27:51,690
INSIGHTFUL COMMENTS IN YOUR 

3879
02:27:51,690 --> 02:27:54,125
ABSOLUTE RIGHT. 

3880
02:27:54,125 --> 02:27:56,861
BOTH THE DENSITY OF SOCIAL 

3881
02:27:56,861 --> 02:27:58,697
NETWORKS, AS WELL AS PERCEIVED 

3882
02:27:58,697 --> 02:27:59,264
LONELINESS SEEM TO HAVE AN 

3883
02:27:59,264 --> 02:28:02,901
IMPACT ON VASCULAR RISK, STROKE 

3884
02:28:02,901 --> 02:28:10,275
RISK, DEMENTIA RISK, AND GIVEN 

3885
02:28:10,275 --> 02:28:12,677
AN AMOUNT OF BRAIN INJURY, THE 

3886
02:28:12,677 --> 02:28:13,478
COGNITIVE FUNCTION. SO THE 

3887
02:28:13,478 --> 02:28:14,079
FUNCTIONAL LINK AS WELL AND 

3888
02:28:14,079 --> 02:28:14,579
THAT IS SOMETHING VERY 

3889
02:28:14,579 --> 02:28:17,349
IMPORTANT AND YOU CORRECTED 

3890
02:28:17,349 --> 02:28:20,151
POINTED OUT THAT THAT SHOULD BE 

3891
02:28:20,151 --> 02:28:23,288
MENTIONED AS SOMETHING TO TAKE 

3892
02:28:23,288 --> 02:28:23,822
INTO DIFFERENT PHASES OF 

3893
02:28:23,822 --> 02:28:24,422
TRIALS, AS WELL AS PRAGMATIC 

3894
02:28:24,422 --> 02:28:25,023
TRIALS. 

3895
02:28:25,023 --> 02:28:26,524
>> GREAT. 

3896
02:28:26,524 --> 02:28:36,768
THANK YOU SUDHA. 

3897
02:28:42,607 --> 02:28:44,476
>> WE HAVE ANOTHER?

3898
02:28:44,476 --> 02:28:50,014
I DON'T SEE ANOTHER. 

3899
02:28:50,014 --> 02:28:50,582
IF YOU HAVE A QUESTION PLEASE 

3900
02:28:50,582 --> 02:28:59,557
UNMUTE YOURSELF. 

3901
02:28:59,557 --> 02:29:04,863
>> PRESS STAR 6.  TO ASK A

3902
02:29:04,863 --> 02:29:09,801
QUESTION.  GIVE IT A TRY. 

3903
02:29:09,801 --> 02:29:11,669
>> I HAVE A QUESTION ABOUT
THE 

3904
02:29:11,669 --> 02:29:14,105
NEURON ITSELF. 

3905
02:29:14,105 --> 02:29:21,246
AND WHO ARE (CORRECTION) 

3906
02:29:21,246 --> 02:29:21,780
THROUGH THE PRESENTATIONS 

3907
02:29:21,780 --> 02:29:24,215
YESTERDAY AND TODAY WE ARE 

3908
02:29:24,215 --> 02:29:27,185
TALKING ABOUT VARIOUS PROTEINS. 

3909
02:29:27,185 --> 02:29:32,557
YOU HAVE TAU AND YOU HAVE THE 

3910
02:29:32,557 --> 02:29:35,860
TDP 43 AND SO FORTH. 

3911
02:29:35,860 --> 02:29:41,099
AND WE TALKED ABOUT A-SYNUCLEIN 

3912
02:29:41,099 --> 02:29:46,738
TODAY.  ARE ALL OF THESE 

3913
02:29:46,738 --> 02:29:51,609
PROTEINS CURLED UP AND PACKED 

3914
02:29:51,609 --> 02:29:52,143
INTO THE NUCLEUS?

3915
02:29:52,143 --> 02:29:59,451
I KNOW THE TAU MOLECULE IS VERY 

3916
02:29:59,451 --> 02:30:00,018
LONG. IT CAN GET WRAPPED UP 

3917
02:30:00,018 --> 02:30:00,618
AGAINST ITSELF. WHEN IT DOES 

3918
02:30:00,618 --> 02:30:04,489
THAT IT SCREWS UP THE NEURON TO 

3919
02:30:04,489 --> 02:30:05,056
BE ABLE TO COMMUNICATE WITH 

3920
02:30:05,056 --> 02:30:07,025
OTHER NEURONS. 

3921
02:30:07,025 --> 02:30:09,994
AND THEN IT GETS WORRIED. IT 

3922
02:30:09,994 --> 02:30:10,628
THINK SOMETHING IS WRONG AND IT 

3923
02:30:10,628 --> 02:30:13,965
COMMITS SUICIDE.  AND YOU GET A 

3924
02:30:13,965 --> 02:30:14,599
WHOLE BUNCH OF THOSE HAPPENING. 

3925
02:30:14,599 --> 02:30:17,135
AND THEN YOU HAVE ... THE 

3926
02:30:17,135 --> 02:30:19,671
PROBLEMS THAT WE'RE DEALING 

3927
02:30:19,671 --> 02:30:21,906
WITH. 

3928
02:30:21,906 --> 02:30:28,646
ARE ALL OF THESE PROTEINS WE 

3929
02:30:28,646 --> 02:30:29,681
ARE TALKING ABOUT WRAPPED UP IN 

3930
02:30:29,681 --> 02:30:32,283
THE NUCLEUS ITSELF OF THE 

3931
02:30:32,283 --> 02:30:33,751
NEURON?

3932
02:30:33,751 --> 02:30:36,788
>> I CAN TAKE THIS IF YOU
WANT. 

3933
02:30:36,788 --> 02:30:37,388
 SO YES THAT IS A GREAT 

3934
02:30:37,388 --> 02:30:39,190
QUESTION. 

3935
02:30:39,190 --> 02:30:39,924
WE ARE TALKING ABOUT MULTIPLE 

3936
02:30:39,924 --> 02:30:43,127
PATHOLOGIES. RIGHT?

3937
02:30:43,127 --> 02:30:47,365
WE ARE AFFECTING THE NEURONS 

3938
02:30:47,365 --> 02:30:47,999
FROM MULTIPLE SIDES AND ALL OF 

3939
02:30:47,999 --> 02:30:48,533
THESE PATHOLOGIES COME IN 

3940
02:30:48,533 --> 02:30:49,267
DIFFERENT FLAVORS WE CAN SAY. 

3941
02:30:49,267 --> 02:30:56,307
SO WE HAVE TAU, YES, A PROTEIN 

3942
02:30:56,307 --> 02:30:59,143
THAT (INDISCERNIBLE) AN ESCAPE 

3943
02:30:59,143 --> 02:31:02,247
FROM THE NEURON. TRANSFERS FROM 

3944
02:31:02,247 --> 02:31:02,881
CELL TO CELL AND GOES TO OTHER 

3945
02:31:02,881 --> 02:31:04,716
CELLS. 

3946
02:31:04,716 --> 02:31:06,551
AMYLOID BETA MOSTLY PRODUCED 

3947
02:31:06,551 --> 02:31:10,788
FROM INSIDE THE (INDISCERNIBLE) 

3948
02:31:10,788 --> 02:31:11,856
IT GOES OUT IN THE BRAIN AND 

3949
02:31:11,856 --> 02:31:12,524
FORMS PLAQUES IN THE MATRIX, IN 

3950
02:31:12,524 --> 02:31:14,592
THE BRAIN, IN THE EXTRACELLULAR 

3951
02:31:14,592 --> 02:31:17,629
SPACES. 

3952
02:31:17,629 --> 02:31:19,831
WE ARE TALKING IN OUR CASES OF 

3953
02:31:19,831 --> 02:31:20,365
VASCULAR PATHOLOGY. VERY 

3954
02:31:20,365 --> 02:31:24,536
IMPORTANT FOR NEURON FUNCTION. 

3955
02:31:24,536 --> 02:31:26,337
WE HAVE TO CONSIDER THAT WE 

3956
02:31:26,337 --> 02:31:28,306
LOSE BLOOD FLOW. THAT IS WHAT 

3957
02:31:28,306 --> 02:31:30,875
GIVES NEURONS THE OXYGEN, THE 

3958
02:31:30,875 --> 02:31:31,442
GLUCOSE, ALL THE FUNCTIONAL 

3959
02:31:31,442 --> 02:31:34,512
SUBSTANCES TO MAKE THEM LIVE 

3960
02:31:34,512 --> 02:31:36,548
AND SURVIVE AND THRIVE.

3961
02:31:36,548 --> 02:31:40,485
 AND SO ALL OF THESE 

3962
02:31:40,485 --> 02:31:41,085
PATHOLOGIES ACTING DIFFERENT 

3963
02:31:41,085 --> 02:31:41,653
WAYS INSIDE OR OUTSIDE THE 

3964
02:31:41,653 --> 02:31:43,054
NEURONS.  BUT SOMEHOW THEY WILL 

3965
02:31:43,054 --> 02:31:46,724
AFFECT THEM. THAT IS WHY WE END 

3966
02:31:46,724 --> 02:31:48,726
UP WITH DEMENTIA. 

3967
02:31:48,726 --> 02:31:49,861
AND WE HAVE TO UNDERSTAND HOW 

3968
02:31:49,861 --> 02:31:53,131
EACH PATHOLOGY SPECIFICALLY 

3969
02:31:53,131 --> 02:31:53,731
AFFECTED NEURON. THAT IS VERY 

3970
02:31:53,731 --> 02:31:55,500
IMPORTANT. 

3971
02:31:55,500 --> 02:31:56,968
>> WELL IT CERTAINLY
FOLLOWS 

3972
02:31:56,968 --> 02:32:03,308
THE ... EXAMPLE THAT IS 

3973
02:32:03,308 --> 02:32:06,144
SOMETIMES GIVEN. BLIND PEOPLE 

3974
02:32:06,144 --> 02:32:11,382
LOOKING AT AN ELEPHANT, GETTING 

3975
02:32:11,382 --> 02:32:12,016
ONE PIECE TO LOOK AT AND THEN 

3976
02:32:12,016 --> 02:32:12,584
ANOTHER PIECE, AND DESCRIBE 

3977
02:32:12,584 --> 02:32:14,152
WHAT THEY SEE. 

3978
02:32:14,152 --> 02:32:15,920
NOW THIS IS REALLY TINY STUFF 

3979
02:32:15,920 --> 02:32:18,089
YOU ARE LOOKING AT.  I DID NOT 

3980
02:32:18,089 --> 02:32:24,228
UNDERSTAND THAT TAU FOR EXAMPLE 

3981
02:32:24,228 --> 02:32:26,364
MIGRATE OUT OF THE NEURON, 

3982
02:32:26,364 --> 02:32:28,666
FLOATING AROUND AMONGST THE 

3983
02:32:28,666 --> 02:32:38,376
MICROGLIA CELLS AND SO FORTH. 

3984
02:32:38,376 --> 02:32:42,413
ALL I CAN SAY IS WOW, TRYING TO 

3985
02:32:42,413 --> 02:32:44,182
TRACK ALL THAT STUFF IS MIND 

3986
02:32:44,182 --> 02:32:44,782
BLOWING. I AM JUST A REGULAR 

3987
02:32:44,782 --> 02:32:47,518
GUY. 

3988
02:32:47,518 --> 02:32:49,721
I WANT TO SAY I REALLY 

3989
02:32:49,721 --> 02:32:51,856
APPRECIATE WHAT YOU HAVE DONE. 

3990
02:32:51,856 --> 02:32:55,026
AND MS. MCCARTHY, THANK YOU FOR 

3991
02:32:55,026 --> 02:32:58,997
FIXING ME UP, SO AT LEAST I CAN 

3992
02:32:58,997 --> 02:33:00,231
ASK A QUESTION OF THESE FOLKS. 

3993
02:33:00,231 --> 02:33:05,069
BECAUSE RIGHT NOW MY ... 

3994
02:33:05,069 --> 02:33:05,703
COMMUNICATION SYSTEM ISN'T SO 

3995
02:33:05,703 --> 02:33:07,071
GOOD. 

3996
02:33:07,071 --> 02:33:15,146
THANK YOU SO MUCH. 

3997
02:33:15,146 --> 02:33:22,820
>> HI, THANK YOU. PERFECT 

3998
02:33:22,820 --> 02:33:23,454
SESSION. APOLOGIES IF I MISSED 

3999
02:33:23,454 --> 02:33:27,458
THIS. 

4000
02:33:27,458 --> 02:33:28,726
WONDERING WHERE IN THE 

4001
02:33:28,726 --> 02:33:29,827
RECOGNITION WE WOULD FIND 

4002
02:33:29,827 --> 02:33:34,932
(INDISCERNIBLE) ISSUES,  

4003
02:33:34,932 --> 02:33:35,533
PARTICULARLY THINKING OF TWO 

4004
02:33:35,533 --> 02:33:36,434
EXAMPLES. MAYBE THIS IS NOT 

4005
02:33:36,434 --> 02:33:39,604
COUNT AS EXPOSURE BECAUSE IT IS 

4006
02:33:39,604 --> 02:33:42,807
IN AN INDIVIDUAL LEVEL, 

4007
02:33:42,807 --> 02:33:44,409
EXPOSURE COLLECT SOME STRESS 

4008
02:33:44,409 --> 02:33:46,644
AND A VARIETY OF ISMS, AND THE 

4009
02:33:46,644 --> 02:33:53,618
OTHER IS MORE ON COVID. 

4010
02:33:53,618 --> 02:33:57,021
>> DR. FOSSATI: THERE IS A

4011
02:33:57,021 --> 02:33:57,588
WHOLE SESSION IN JUNE THAT 

4012
02:33:57,588 --> 02:33:59,791
FOCUSES ON EXPOSURE.  AS YOU 

4013
02:33:59,791 --> 02:34:00,425
KNOW TWO YEARS AGO THERE WAS A 

4014
02:34:00,425 --> 02:34:08,266
WHOLE SESSION ON COVID AND I 

4015
02:34:08,266 --> 02:34:11,436
NOW INFECTIONS INCLUDING 

4016
02:34:11,436 --> 02:34:12,837
SARS-COVID-2 AND INFORMATION 

4017
02:34:12,837 --> 02:34:15,373
AND (INDISCERNIBLE) RESPONSES 

4018
02:34:15,373 --> 02:34:16,441
WOVEN INTO THIS AND WILL BE 

4019
02:34:16,441 --> 02:34:19,110
PART OF THE EXPOSURE SESSION. 

4020
02:34:19,110 --> 02:34:22,647
>> BUT I HAVE TO SAY THAT
YEAH, 

4021
02:34:22,647 --> 02:34:23,281
WE PROBABLY HAVE TO COORDINATE 

4022
02:34:23,281 --> 02:34:26,484
WITH THE EXPOSURE SESSION TO 

4023
02:34:26,484 --> 02:34:29,821
MAKE SURE WE ALSO INCLUDE THESE 

4024
02:34:29,821 --> 02:34:31,222
RECOMMENDATIONS FOR THAT EFFECT 

4025
02:34:31,222 --> 02:34:33,591
SPECIFICALLY ON VCID. YEAH, 

4026
02:34:33,591 --> 02:34:37,695
THAT IS SOMETHING TO NOTE. 

4027
02:34:37,695 --> 02:34:38,229
>> I WILL ADD THAT WE
THINK 

4028
02:34:38,229 --> 02:34:39,430
ABOUT BUILDING MORE COMPLEX 

4029
02:34:39,430 --> 02:34:41,232
MODELS THAT MORE TRULY REFLECT 

4030
02:34:41,232 --> 02:34:42,867
THE COMPLEXITY OF THE HUMAN 

4031
02:34:42,867 --> 02:34:43,468
CONDITION, YOU WANT TO START 

4032
02:34:43,468 --> 02:34:46,337
WITH GENETICS.  THE ALSO WANT 

4033
02:34:46,337 --> 02:34:46,871
TO COMBINE GENETICS WITH 

4034
02:34:46,871 --> 02:34:49,774
ENVIRONMENTAL EXPOSURES.  AND 

4035
02:34:49,774 --> 02:34:50,408
BY DOING THAT BY UNDERSTANDING 

4036
02:34:50,408 --> 02:34:52,343
HOW YOU BUILD THEM, YOU 

4037
02:34:52,343 --> 02:34:52,910
UNDERSTAND HOW YOU MIGHT BE 

4038
02:34:52,910 --> 02:34:56,447
ABLE TO FIX THEM. AND WHAT THE 

4039
02:34:56,447 --> 02:35:00,017
MECHANISMS ARE. THE 

4040
02:35:00,017 --> 02:35:06,057
CONTRIBUTIONS OF THE EXPOSEM 

4041
02:35:06,057 --> 02:35:06,691
(PHONETIC),   IT IS A CRITICAL 

4042
02:35:06,691 --> 02:35:07,325
COMPONENT IN MANY CASES AND YOU 

4043
02:35:07,325 --> 02:35:08,426
MAKE A GENETIC MANY RELATION IN 

4044
02:35:08,426 --> 02:35:09,026
THE MODEL AND IT DOES NOT GO 

4045
02:35:09,026 --> 02:35:11,229
FAR ENOUGH. BUT INCREASES 

4046
02:35:11,229 --> 02:35:11,863
SUSCEPTIBILITY WHEN YOU COMBINE 

4047
02:35:11,863 --> 02:35:14,132
THAT WITH A HIGH-FAT DIET, AND 

4048
02:35:14,132 --> 02:35:17,068
EXPOSURE TO STRESS. YOU CAN 

4049
02:35:17,068 --> 02:35:18,736
PUSH THE PHENOTYPE MORE TOWARDS 

4050
02:35:18,736 --> 02:35:20,138
THE DISEASE. 

4051
02:35:20,138 --> 02:35:22,673
TICKLY AS WE THINK ABOUT IN A 

4052
02:35:22,673 --> 02:35:26,444
MULTI-OMICS APPROACH YEAR, IF 

4053
02:35:26,444 --> 02:35:27,044
YOU CAN ALIGN YOUR MODELS NOT 

4054
02:35:27,044 --> 02:35:31,682
SO MUCH DOES IT HAVE A 

4055
02:35:31,682 --> 02:35:32,283
PATHOLOGY YES OR NO, WHAT ARE 

4056
02:35:32,283 --> 02:35:32,917
THE MOLECULAR CHANGES? 

4057
02:35:32,917 --> 02:35:38,189
WE HAVE MULTI-OMICS, AND 

4058
02:35:38,189 --> 02:35:40,391
THERE'S A LOT MORE WE CAN DO IN 

4059
02:35:40,391 --> 02:35:40,958
CREATING BETTER MODELS AND 

4060
02:35:40,958 --> 02:35:41,559
ALIGNING THEM AT THE LEVEL OF 

4061
02:35:41,559 --> 02:35:45,196
PROTEIN GENES AND THE METABOLIC 

4062
02:35:45,196 --> 02:35:48,266
CHANGES. 

4063
02:35:48,266 --> 02:35:48,833
>> I APPRECIATE THE
REMINDER 

4064
02:35:48,833 --> 02:35:49,467
THAT WE HAVE A SESSION IN JUNE. 

4065
02:35:49,467 --> 02:35:51,969
WHICH FEELS LIKE A LONG WAY 

4066
02:35:51,969 --> 02:35:58,609
AWAY ABOUT EXPOSUM. (PHONETIC). 

4067
02:35:58,609 --> 02:35:59,076
I WOULD ENCOURAGE YOUR 

4068
02:35:59,076 --> 02:36:00,444
WORKGROUP AND EACH OF THE OTHER 

4069
02:36:00,444 --> 02:36:06,150
DISEASE SPECIFIC WORK GROUPS TO 

4070
02:36:06,150 --> 02:36:08,219
THINK ABOUT EMBEDDING LANGUAGE 

4071
02:36:08,219 --> 02:36:08,920
TO SPECIFIC RISK FACTORS, AND 

4072
02:36:08,920 --> 02:36:12,456
NOT LEADING TO THE CROSSCUTTING 

4073
02:36:12,456 --> 02:36:14,091
ALONG. I WORRY THAT IN THE 

4074
02:36:14,091 --> 02:36:18,696
ENVIRONMENT THAT NIH IS FACING 

4075
02:36:18,696 --> 02:36:20,398
IN THE MONTH YEARS AHEAD IT 

4076
02:36:20,398 --> 02:36:23,501
COULD BE LOST. AND IT COULD BE 

4077
02:36:23,501 --> 02:36:24,101
BETTER IF IT WERE IN THREE OR 

4078
02:36:24,101 --> 02:36:24,702
FOUR PLACES RATHER THAN JUST 

4079
02:36:24,702 --> 02:36:29,073
ONE. 

4080
02:36:29,073 --> 02:36:29,640
>> A LOT OF THE RISK
FACTORS 

4081
02:36:29,640 --> 02:36:30,208
AND EXPOSURES, FOR EXAMPLE 

4082
02:36:30,208 --> 02:36:31,409
SLEEP-DISORDERED SO 

4083
02:36:31,409 --> 02:36:31,943
ENVIRONMENTAL FACTORS CAN 

4084
02:36:31,943 --> 02:36:33,411
AFFECT VASCULAR DISEASE. AND 

4085
02:36:33,411 --> 02:36:36,881
VASCULAR DISEASE AFFECTS VCID.  

4086
02:36:36,881 --> 02:36:37,381
SO THEY ARE ALL LINKED 

4087
02:36:37,381 --> 02:36:39,784
TOGETHER, DEFINITELY. 

4088
02:36:39,784 --> 02:36:45,356
>> LET'S MOVE ON TO --
NAPHALI?

4089
02:36:45,356 --> 02:36:48,359
>> YES, I HEARD WHEN THE 

4090
02:36:48,359 --> 02:36:54,332
COMMENTS ABOUT THE 

4091
02:36:54,332 --> 02:36:57,168
PROTEINOPATHY TO BE THE CORE OF 

4092
02:36:57,168 --> 02:37:00,004
DEMENTIA-CAUSING DISEASES.  IN 

4093
02:37:00,004 --> 02:37:00,605
REFERENCE TO THAT I WANTED TO 

4094
02:37:00,605 --> 02:37:02,874
ADD MY COMMENT. SO IN 

4095
02:37:02,874 --> 02:37:05,910
ALZHEIMER'S DISEASE PATHOLOGY, 

4096
02:37:05,910 --> 02:37:08,112
WHEN WE TAKE A SECTION OF THE 

4097
02:37:08,112 --> 02:37:11,182
BRAIN AFFECTED BY ALZHEIMER'S 

4098
02:37:11,182 --> 02:37:12,617
DISEASE, WE NOT ONLY SEE THE 

4099
02:37:12,617 --> 02:37:16,354
PLAQUES THAT ARE FORMED WITHIN 

4100
02:37:16,354 --> 02:37:19,290
THE CORTEX BUT WE SEEN THEM 

4101
02:37:19,290 --> 02:37:23,861
ALSO ON THE VESSELS.  WHICH IS 

4102
02:37:23,861 --> 02:37:26,364
SOMETHING THAT COULD BE AN 

4103
02:37:26,364 --> 02:37:30,501
EVIDENCE THAT ONE MORE 

4104
02:37:30,501 --> 02:37:32,203
EVIDENCE, SHOWING THAT THIS 

4105
02:37:32,203 --> 02:37:37,008
COULD BE ALSO A VASCULAR 

4106
02:37:37,008 --> 02:37:47,218
PATHOLOGY. 

4107
02:37:49,687 --> 02:37:52,290
MAYBE PLAQUE MAYBE THE 

4108
02:37:52,290 --> 02:37:53,791
PROTEINOPATHY IS TOUCHING ONE 

4109
02:37:53,791 --> 02:37:54,425
ELEMENT AND MISSING THE REST. I 

4110
02:37:54,425 --> 02:37:58,229
WANTED TO ADD THIS. 

4111
02:37:58,229 --> 02:38:00,631
>> TOTALLY RIGHT WHICH
IS-- 

4112
02:38:00,631 --> 02:38:01,265
WHAT YOU DESCRIBE THE POSITION 

4113
02:38:01,265 --> 02:38:02,366
AROUND THE VESSELS IS ONE OF 

4114
02:38:02,366 --> 02:38:03,901
THE MAIN PATHOLOGICAL FEATURES 

4115
02:38:03,901 --> 02:38:08,272
OF VCID.  IT IS ONE OF THE MAIN 

4116
02:38:08,272 --> 02:38:09,340
FOCUSES OF OUR MECHANISTIC 

4117
02:38:09,340 --> 02:38:12,209
STUDIES, TOGETHER WITH OTHER 

4118
02:38:12,209 --> 02:38:12,810
VASCULAR PATHOLOGIES. THANK 

4119
02:38:12,810 --> 02:38:19,016
YOU. 

4120
02:38:19,016 --> 02:38:23,321
>> ANOTHER PART OF THE
BLIND 

4121
02:38:23,321 --> 02:38:26,223
METAPHOR SO YOU MENTIONED 

4122
02:38:26,223 --> 02:38:28,492
MULTIPLE PATHOLOGIES. YOU PUT 

4123
02:38:28,492 --> 02:38:29,827
(INDISCERNIBLE) YOU INCREASE 

4124
02:38:29,827 --> 02:38:33,864
THE AMOUNT OF CAA AND SOME ALSO 

4125
02:38:33,864 --> 02:38:35,599
FOLLOWING THE ELEPHANT ANALOGY, 

4126
02:38:35,599 --> 02:38:36,200
WE HAVE TO LOOK AT THE WHOLE 

4127
02:38:36,200 --> 02:38:37,268
ELEPHANT. 

4128
02:38:37,268 --> 02:38:39,503
>> NEXT WE HAVE --. 

4129
02:38:39,503 --> 02:38:45,343
GREG?

4130
02:38:45,343 --> 02:38:45,910
>> FANTASTIC.
REPRESENTATIONS 

4131
02:38:45,910 --> 02:38:48,813
AND GREAT SUMMARIES. NICE TO 

4132
02:38:48,813 --> 02:38:49,413
SEE SOME OF YOU THAT HAVE NOT 

4133
02:38:49,413 --> 02:38:50,047
SEEN SO LONG AND OTHERS I HAVE 

4134
02:38:50,047 --> 02:38:52,083
SEEN MORE RECENTLY. 

4135
02:38:52,083 --> 02:38:52,850
YOU KNOW ONE OF THE CONCEPTS 

4136
02:38:52,850 --> 02:38:55,686
AND PLEASE THROW VIRTUAL 

4137
02:38:55,686 --> 02:38:56,287
TOMATOES AT ME IF I MISSED 

4138
02:38:56,287 --> 02:38:58,422
THIS. 

4139
02:38:58,422 --> 02:38:58,956
ONE OF THE ISSUES WE REALLY 

4140
02:38:58,956 --> 02:39:06,797
STRUGGLED WITH ARE THESE 

4141
02:39:06,797 --> 02:39:09,133
MULTIPLE ETIOLOGIES OFTEN 

4142
02:39:09,133 --> 02:39:09,767
AFFECTING DIFFERENT REGIONS OF 

4143
02:39:09,767 --> 02:39:20,311
THE BRAIN SO A LOT OF VASCULAR 

4144
02:39:23,647 --> 02:39:24,382
DISEASE BURDEN IS FOUND 

4145
02:39:24,382 --> 02:39:27,385
SUBCORTICALLY (INDISCERNIBLE) 

4146
02:39:27,385 --> 02:39:29,553
-- BUT BEGINNING TO BRING 

4147
02:39:29,553 --> 02:39:32,023
TOGETHER HOW DO THESE DISEASES 

4148
02:39:32,023 --> 02:39:33,791
INTERACT WHEN THEY ARE 

4149
02:39:33,791 --> 02:39:37,661
REGIONALLY IN DIFFERENT AREAS?

4150
02:39:37,661 --> 02:39:38,662
AND REALLY BEGINNING TO 

4151
02:39:38,662 --> 02:39:42,433
INVESTIGATE THAT.  I REALLY SEE 

4152
02:39:42,433 --> 02:39:42,967
SOMETHING THAT IS REALLY 

4153
02:39:42,967 --> 02:39:45,770
IMPORTANT. 

4154
02:39:45,770 --> 02:39:48,205
WE TALK ABOUT VASCULAR DISEASE 

4155
02:39:48,205 --> 02:39:49,173
BURDEN AS IF IT WERE EQUIVALENT 

4156
02:39:49,173 --> 02:39:49,740
THROUGHOUT ALL AREAS OF THE 

4157
02:39:49,740 --> 02:39:51,609
BRAIN.  WE KNOW THAT IS VERY 

4158
02:39:51,609 --> 02:39:54,678
DIFFERENT, THE SAME AS WITH 

4159
02:39:54,678 --> 02:39:58,282
TDP-43, A-SYNUCLEIN, TAU AND/OR 

4160
02:39:58,282 --> 02:40:01,986
AMYLOID. 

4161
02:40:01,986 --> 02:40:02,586
AND TELL ME WHEN YOU'RE WORKING 

4162
02:40:02,586 --> 02:40:05,322
GROUP HOW MUCH DISCUSSION, AND 

4163
02:40:05,322 --> 02:40:05,956
IS THAT BUILDING TO ANY OF YOUR 

4164
02:40:05,956 --> 02:40:11,429
RECOMMENDATIONS?

4165
02:40:11,429 --> 02:40:14,198
>> DR. LU: THANK YOU VERY
MUCH 

4166
02:40:14,198 --> 02:40:18,302
FOR THIS QUESTION.  SO THE 

4167
02:40:18,302 --> 02:40:20,571
COMMITTEE DID TALK ABOUT USING 

4168
02:40:20,571 --> 02:40:24,375
MULTIPLE TECHNOLOGIES, 

4169
02:40:24,375 --> 02:40:27,611
ESPECIALLY TECHNOLOGY LOOKING 

4170
02:40:27,611 --> 02:40:28,212
AT ALL ASPECTS OF THE DISEASE 

4171
02:40:28,212 --> 02:40:31,148
BIOLOGY AND ALSO CONSIDERING 

4172
02:40:31,148 --> 02:40:31,715
(INDISCERNIBLE), AND OTHER 

4173
02:40:31,715 --> 02:40:35,619
TYPES OF PROTEIN OPPOSITE IN 

4174
02:40:35,619 --> 02:40:37,855
THIS REGARD I FEEL IMAGING 

4175
02:40:37,855 --> 02:40:38,489
BIOMARKER CAN PLAY PARTICULARLY 

4176
02:40:38,489 --> 02:40:39,123
USEFUL ROLE IN THE SENSE THAT 

4177
02:40:39,123 --> 02:40:40,157
YOU CAN LOOK AT THE ENTIRE 

4178
02:40:40,157 --> 02:40:46,263
BRAIN AND BIO FLUID AND LOOK AT 

4179
02:40:46,263 --> 02:40:47,565
THE ENTIRE BRAIN AND LOCALIZE 

4180
02:40:47,565 --> 02:40:48,099
FOR INSTANCE FRONTAL LOBE 

4181
02:40:48,099 --> 02:40:50,668
VERSUS CAA WHICH IS MORE 

4182
02:40:50,668 --> 02:40:56,340
OCCIPITAL LOBE AND BIO MATTER 

4183
02:40:56,340 --> 02:40:59,376
IS MORE CLASSICAL  VASCULAR 

4184
02:40:59,376 --> 02:41:04,148
DISEASE SO THAT DEEP NUCLEUS. 

4185
02:41:04,148 --> 02:41:04,715
SO BRINGING TOGETHER THIS 

4186
02:41:04,715 --> 02:41:05,216
IMAGING TECHNOLOGY CAN 

4187
02:41:05,216 --> 02:41:05,783
POTENTIALLY TEASE APART THE 

4188
02:41:05,783 --> 02:41:07,485
MIXED CONTRIBUTION OF DIFFERENT 

4189
02:41:07,485 --> 02:41:08,119
PATHOLOGIES TO THE PARTICULAR 

4190
02:41:08,119 --> 02:41:17,261
PERSON. 

4191
02:41:17,261 --> 02:41:20,664
>> I WONDER IF DAVID WANTS
TO 

4192
02:41:20,664 --> 02:41:21,265
ADD SOMETHING TO THAT?

4193
02:41:21,265 --> 02:41:22,833
THAT IS DEFINITELY AN AREA HE 

4194
02:41:22,833 --> 02:41:23,400
HIGHLIGHTS IN A GREAT EMAIL 

4195
02:41:23,400 --> 02:41:27,738
EARLIER TODAY. 

4196
02:41:27,738 --> 02:41:34,512
>> I WILL ADD WHILE DAVID,
IF 

4197
02:41:34,512 --> 02:41:35,246
YOU WANT TO SAY SOMETHING IN A 

4198
02:41:35,246 --> 02:41:38,782
MOMENT -- I WONDER IF THIS IS 

4199
02:41:38,782 --> 02:41:39,416
GOING TO REFLECT THE EXPANSION 

4200
02:41:39,416 --> 02:41:41,919
OF AI CAPABILITIES. I IT WILL 

4201
02:41:41,919 --> 02:41:42,520
HELP A LOT HERE TAKING THESE 

4202
02:41:42,520 --> 02:41:48,692
DATA SETS AND -- HAS 

4203
02:41:48,692 --> 02:41:50,761
EXPERIENCED MACHINE LEARNING 

4204
02:41:50,761 --> 02:41:51,362
AND APPLYING THOSE TO LOOK AT 

4205
02:41:51,362 --> 02:41:52,596
MORE REGIONAL CHANGES. CLEARLY 

4206
02:41:52,596 --> 02:41:56,467
AN IMPORTANT AREA TO STUDY. 

4207
02:41:56,467 --> 02:41:57,001
>> IF I COULD CHIME IN
JUST 

4208
02:41:57,001 --> 02:42:00,271
QUICKLY. THAT WAS A GREAT POINT 

4209
02:42:00,271 --> 02:42:00,905
ABOUT LOOKING AT MANY REGIONS 

4210
02:42:00,905 --> 02:42:05,276
THROUGHOUT THE BRAIN.  AND I 

4211
02:42:05,276 --> 02:42:08,412
THINK THERE'S A LOT OF 

4212
02:42:08,412 --> 02:42:12,616
TECHNOLOGIES THAT ARE COMING TO 

4213
02:42:12,616 --> 02:42:13,217
THE POINT THAT THEY COULD BE 

4214
02:42:13,217 --> 02:42:15,486
USEFUL. 

4215
02:42:15,486 --> 02:42:18,822
MY CONCERN GOING FORWARD IS WE 

4216
02:42:18,822 --> 02:42:19,423
HAVE GOOD MOLECULAR MARKERS, 

4217
02:42:19,423 --> 02:42:19,957
WHICH MEANS WE HAVE GOOD 

4218
02:42:19,957 --> 02:42:23,260
FLORESCENT DIES OR DIES THAT 

4219
02:42:23,260 --> 02:42:27,164
HAVE CONTRAST UNDER ULTRASOUND. 

4220
02:42:27,164 --> 02:42:27,765
AND THIS SHOULD ALLOW US TO DO 

4221
02:42:27,765 --> 02:42:29,833
LONGITUDINAL STUDIES ON THE 

4222
02:42:29,833 --> 02:42:32,536
PROGRESSION OF DISEASE. MORE 

4223
02:42:32,536 --> 02:42:42,913
SO, ALLOW US TO PROBE 

4224
02:42:44,248 --> 02:42:49,954
MODULATORY REGIONS AND MIDRANGE 

4225
02:42:49,954 --> 02:42:51,088
REGIONS FUNDAMENTAL FOR FACIAL 

4226
02:42:51,088 --> 02:42:56,961
ACTIONS, DAILY LIFE. 

4227
02:42:56,961 --> 02:42:57,561
I THE TECHNOLOGY FROM THE POINT 

4228
02:42:57,561 --> 02:42:59,763
OF VIEW OF MARKERS AND FROM 

4229
02:42:59,763 --> 02:43:00,431
INSTRUMENTATION HAS BEEN 

4230
02:43:00,431 --> 02:43:01,165
SHOOTING UP IN THE LAST FEW 

4231
02:43:01,165 --> 02:43:02,766
YEARS. THIS COULD HAVE A BIG 

4232
02:43:02,766 --> 02:43:05,402
IMPACT ON VCID MEASUREMENTS AND 

4233
02:43:05,402 --> 02:43:08,072
MODELS. 

4234
02:43:08,072 --> 02:43:16,847
>> I CAN ADD TO THAT. 

4235
02:43:16,847 --> 02:43:18,582
THE REGIONALITY IS SUCH AN 

4236
02:43:18,582 --> 02:43:19,116
IMPORTANT ASPECT OF SMALL 

4237
02:43:19,116 --> 02:43:21,685
VESSEL DISEASE. CAA AFFECT 

4238
02:43:21,685 --> 02:43:22,319
DIFFERENT REGIONS OF THE BRAIN 

4239
02:43:22,319 --> 02:43:24,221
COMPARED TO ARTERIOSCLEROSIS, 

4240
02:43:24,221 --> 02:43:24,788
AND SO WE LOOK AT DIFFERENT 

4241
02:43:24,788 --> 02:43:28,292
REGIONS OF THE BRAIN, WE CAN 

4242
02:43:28,292 --> 02:43:30,728
ACTUALLY PARSE OUT UNDERLYING 

4243
02:43:30,728 --> 02:43:31,295
ETIOLOGIES. IN FACT WE HAVE 

4244
02:43:31,295 --> 02:43:34,498
USED MACHINE LEARNING TO DO 

4245
02:43:34,498 --> 02:43:36,400
CLUSTERING ALGORITHMS TO TRY TO 

4246
02:43:36,400 --> 02:43:40,204
DISTINGUISH PATTERNS OF LIGHT, 

4247
02:43:40,204 --> 02:43:40,838
OR HYPER INTENSITIES RAISED IN 

4248
02:43:40,838 --> 02:43:45,309
THE UNDERLYING ETIOLOGY. THAT 

4249
02:43:45,309 --> 02:43:45,909
IS BEEN A PRODUCTIVE APPROACH 

4250
02:43:45,909 --> 02:43:46,477
TO PHENOTYPING WHITE MATTER 

4251
02:43:46,477 --> 02:43:47,011
HYPER INTENSITIES. GREAT 

4252
02:43:47,011 --> 02:43:49,113
QUESTION. THANKS. 

4253
02:43:49,113 --> 02:43:50,581
>> THERE IS ONE MORE
QUESTION. 

4254
02:43:50,581 --> 02:43:51,949
GABE?

4255
02:43:51,949 --> 02:44:02,426
>> YEAH DR. SESHADRI
MENTIONED 

4256
02:44:06,397 --> 02:44:06,830
ARTERIAL  STIFFNESS AND 

4257
02:44:06,830 --> 02:44:09,166
HYPERTENSION -- IS THAT 

4258
02:44:09,166 --> 02:44:12,336
SOMETHING THAT NEEDS TO BE 

4259
02:44:12,336 --> 02:44:12,936
CONCENTRATED ASIDE FROM THESE 

4260
02:44:12,936 --> 02:44:14,471
STRUCTURAL BELLS AND WHISTLES, 

4261
02:44:14,471 --> 02:44:15,105
THE FUNCTIONAL PART OF WHAT IS 

4262
02:44:15,105 --> 02:44:16,240
CONTROLLING A WHAT BECOMES 

4263
02:44:16,240 --> 02:44:22,179
INTERRUPTED THAT CAUSES THE 

4264
02:44:22,179 --> 02:44:22,746
DILATION-- CAUSES THE BLOOD 

4265
02:44:22,746 --> 02:44:24,081
PRESSURE TO GO UP WHICH IS 

4266
02:44:24,081 --> 02:44:24,715
DEFINITELY LINK TO THE SYSTEMIC 

4267
02:44:24,715 --> 02:44:25,616
CARDIOVASCULAR DISEASE, 

4268
02:44:25,616 --> 02:44:29,853
DEMENTIA AND DEATH. 

4269
02:44:29,853 --> 02:44:33,157
CAN YOU TALK ABOUT THAT PLEASE?

4270
02:44:33,157 --> 02:44:35,959
>> I CAN TAKE THAT. 

4271
02:44:35,959 --> 02:44:42,399
SO IN THE MOCK VCID STUDY THAT 

4272
02:44:42,399 --> 02:44:43,667
I HAPPEN TO BE INVOLVED WITH, 

4273
02:44:43,667 --> 02:44:50,641
WE ARE MEASURING THIS DILATION 

4274
02:44:50,641 --> 02:44:51,241
CAPACITY AND IN THIS CASE WE 

4275
02:44:51,241 --> 02:44:51,875
USED COMMON DIOXIDE AS A BASAL 

4276
02:44:51,875 --> 02:44:52,543
STIMULUS. AND WE MEASURE HOW TO 

4277
02:44:52,543 --> 02:44:55,112
EXTEND (INDISCERNIBLE) AND 

4278
02:44:55,112 --> 02:44:59,249
DILATE.  THIS IS SOMETHING WE 

4279
02:44:59,249 --> 02:44:59,850
ARE ACTUALLY PURSUING. THANK 

4280
02:44:59,850 --> 02:45:02,853
YOU VERY MUCH FOR THIS QUESTION.

4281
02:45:02,853 --> 02:45:04,655
>> YES, DAVID? 

4282
02:45:04,655 --> 02:45:07,691
>> DR. FARDO: IF I COULD
ADD TO 

4283
02:45:07,691 --> 02:45:08,625
THAT IT IS A GREAT QUESTION. 

4284
02:45:08,625 --> 02:45:14,698
GOING BACK TO THE 1980S, THERE 

4285
02:45:14,698 --> 02:45:16,033
WAS THIS SORT OF HYPOTHESIS 

4286
02:45:16,033 --> 02:45:20,771
THAT BASICALLY WHAT VESSELS , 

4287
02:45:20,771 --> 02:45:21,372
ARE DILATING AS YOU POINT OUT 

4288
02:45:21,372 --> 02:45:30,981
THEY ARE NATURALLY DILATING DUE 

4289
02:45:30,981 --> 02:45:31,582
TO VASAL MOTION, ALMOST A 20% 

4290
02:45:31,582 --> 02:45:33,650
DILATION ABOUT ONCE EVERY 20 

4291
02:45:33,650 --> 02:45:34,151
SECONDS, IN ADDITION TO 

4292
02:45:34,151 --> 02:45:35,719
DILATION THAT CAN HAPPEN WITH 

4293
02:45:35,719 --> 02:45:38,489
INCREASED SENSORY STIMULUS. 

4294
02:45:38,489 --> 02:45:45,929
AND ... (AUDIO CUTTING OUT)... 

4295
02:45:45,929 --> 02:45:48,665
YOU HAVE STICKY BLOOD VESSELS. 

4296
02:45:48,665 --> 02:45:50,601
IN FACT YOU WILL BE ABLE TO 

4297
02:45:50,601 --> 02:45:53,070
EXTRUDE PROTEINS FROM THE BRAIN 

4298
02:45:53,070 --> 02:45:56,173
THESE ARE CALLED MIXTURE MODELS 

4299
02:45:56,173 --> 02:45:56,807
EARLY ON. IF YOU WANT TO THINK 

4300
02:45:56,807 --> 02:45:57,374
OF IT OF SORT OF A WASHING 

4301
02:45:57,374 --> 02:45:58,776
MACHINE, NOT THAT FAR FROM THE 

4302
02:45:58,776 --> 02:46:00,744
PHYSICAL TRUTH. 

4303
02:46:00,744 --> 02:46:01,445
AND THE POINT YOU BRING UP IS 

4304
02:46:01,445 --> 02:46:03,547
VERY IMPORTANT.  AND AGAIN THIS 

4305
02:46:03,547 --> 02:46:04,081
IS SOMETHING WE CAN GET A 

4306
02:46:04,081 --> 02:46:12,289
BETTER HANDLE ON WITH NOT -- 

4307
02:46:12,289 --> 02:46:12,823
WITH MINIMALLY INVASIVE, 

4308
02:46:12,823 --> 02:46:13,424
LONGITUDINAL MEASUREMENTS AND 

4309
02:46:13,424 --> 02:46:14,525
POST MARKERS. 

4310
02:46:14,525 --> 02:46:20,564
>> ALSO, WHAT
INTERVENTIONS CAN 

4311
02:46:20,564 --> 02:46:21,165
IMPROVE VASODILATION?

4312
02:46:21,165 --> 02:46:31,575
>> DR. FARDO: MAYBE.
MAYBE.

4313
02:46:34,411 --> 02:46:36,880
>> LIKE BLOCKING ANGIO
TENSION 

4314
02:46:36,880 --> 02:46:37,748
-- PART OF MY LIFE. 

4315
02:46:37,748 --> 02:46:44,455
>> DR. FARDO: SOME OF THE 

4316
02:46:44,455 --> 02:46:47,758
HYPERTENSIVE DRUGS HAVE 

4317
02:46:47,758 --> 02:46:48,392
INTENSIVE, AND I SUPPOSE THEY 

4318
02:46:48,392 --> 02:46:48,892
WILL IMPROVE THE VASAL 

4319
02:46:48,892 --> 02:46:53,730
REACTIVITY. 

4320
02:46:53,730 --> 02:46:54,231
>> EXPLAINS WHY THE MUCUS 

4321
02:46:54,231 --> 02:46:54,765
LOWERING DRUGS SEEM TO BE 

4322
02:46:54,765 --> 02:46:56,400
HAVING AN IMPROVED EFFECT ON 

4323
02:46:56,400 --> 02:47:00,437
REDUCING DEMENTIA?

4324
02:47:00,437 --> 02:47:01,438
STIRS INFORMATION 

4325
02:47:01,438 --> 02:47:06,710
(INDISCERNIBLE) ... FIBROSIS 

4326
02:47:06,710 --> 02:47:13,116
CARRIES VASAL DILATION. 

4327
02:47:13,116 --> 02:47:13,717
>> I THAT IS VERY COMPLEX
THOSE 

4328
02:47:13,717 --> 02:47:14,918
DRUGS INTERACT IN MANY 

4329
02:47:14,918 --> 02:47:15,519
DIFFERENT WAYS. THAT COULD BE 

4330
02:47:15,519 --> 02:47:17,254
ONE OF THEM. 

4331
02:47:17,254 --> 02:47:21,525
WE HAVE TO GET THE PIPELINE 

4332
02:47:21,525 --> 02:47:22,125
GOING. WE HAVE A LOT OF DRUGS 

4333
02:47:22,125 --> 02:47:22,759
IN THE PRECLINICAL STAGE AND I 

4334
02:47:22,759 --> 02:47:24,828
CAN TELL YOU IN MY LAP FOR 

4335
02:47:24,828 --> 02:47:26,997
EXAMPLE THE DO EXACTLY THAT THE 

4336
02:47:26,997 --> 02:47:29,233
IMPROVE HYPERACTIVITY TOGETHER 

4337
02:47:29,233 --> 02:47:31,168
WITH OTHER THINGS SUCH AS 

4338
02:47:31,168 --> 02:47:31,668
IMPROVING METABOLIC AND 

4339
02:47:31,668 --> 02:47:32,269
MITOCHONDRIAL FUNCTION AND WE 

4340
02:47:32,269 --> 02:47:32,870
HAVE TO GET INTO THE CLINICAL 

4341
02:47:32,870 --> 02:47:33,237
STAGE. 

4342
02:47:33,237 --> 02:47:35,772
SO THE TRANSLATIONAL 

4343
02:47:35,772 --> 02:47:36,340
RECOMMENDATIONS EXACTLY SAY 

4344
02:47:36,340 --> 02:47:38,775
THAT.  TO KIND OF FACILITATE 

4345
02:47:38,775 --> 02:47:44,281
THAT TRANSITION. 

4346
02:47:44,281 --> 02:47:44,681
>> SO IT IS REALLY 

4347
02:47:44,681 --> 02:47:45,516
MULTI-ELASTICAL?

4348
02:47:45,516 --> 02:47:48,118
THANK YOU. 

4349
02:47:48,118 --> 02:47:54,858
>> WE ARE OUT OF TIME FOR 

4350
02:47:54,858 --> 02:47:55,559
QUESTIONS FOR THIS SESSION.

4351
02:47:55,559 --> 02:47:56,126
SO WE WILL MOVE STRAIGHT INTO 

4352
02:47:56,126 --> 02:47:58,862
THE NEXT SESSION WHICH IS THE 

4353
02:47:58,862 --> 02:48:01,465
FURTHER PUBLIC INPUT. 

4354
02:48:01,465 --> 02:48:05,736
WE THANKED THIS COMMITTEE. 

4355
02:48:05,736 --> 02:48:06,270
WE HAVE A SLOW START TO THE 

4356
02:48:06,270 --> 02:48:08,906
NEXT SESSION BECAUSE, ANYBODY 

4357
02:48:08,906 --> 02:48:10,073
NEEDS TO GET UP AND STRETCH AND 

4358
02:48:10,073 --> 02:48:10,707
THEN COME BACK, WE WILL BE HERE 

4359
02:48:10,707 --> 02:48:17,648
FOR THE NEXT HOUR WITH OPEN 

4360
02:48:17,648 --> 02:48:18,282
MICROPHONE FOR ANYONE WHO WOULD 

4361
02:48:18,282 --> 02:48:19,950
LIKE TO SAY SOMETHING. 

4362
02:48:19,950 --> 02:48:22,853
AND DAVID, I SEE YOUR HAND. 

4363
02:48:22,853 --> 02:48:33,330
>> NO, NO. MY HAND IS NOT
UP. I 

4364
02:48:38,502 --> 02:48:39,069
WAS THANKING MY COLLEAGUES FOR 

4365
02:48:39,069 --> 02:48:42,706
A GREAT PRESENTATION. 

4366
02:48:42,706 --> 02:48:43,307
>> FOR THE SESSION WE ONLY
HAVE 

4367
02:48:43,307 --> 02:48:45,475
ONLY 25 OPEN CAMERAS. RIGHT?

4368
02:48:45,475 --> 02:48:48,912
SHOULD WE ...

4369
02:48:48,912 --> 02:48:59,356
>> WE WILL LET EVERYBODY,
SO 

4370
02:48:59,957 --> 02:49:00,490
ALL THE SPEAKERS FOR THE LAST 

4371
02:49:00,490 --> 02:49:01,124
TWO DAYS ARE SETTING UP SO YOUR 

4372
02:49:01,124 --> 02:49:01,758
CAMERA AND MICROPHONE ARE UNDER 

4373
02:49:01,758 --> 02:49:02,659
YOUR CONTROL SO THERE ENABLED 

4374
02:49:02,659 --> 02:49:04,361
WHETHER YOU JOIN AS A PRESENTER 

4375
02:49:04,361 --> 02:49:12,836
OR AN ATTENDEE TODAY. WE WILL 

4376
02:49:12,836 --> 02:49:13,470
BE ACTIVELY TRYING TO SPOTLIGHT 

4377
02:49:13,470 --> 02:49:14,037
PEOPLE ON THE SCREEN SO THE 

4378
02:49:14,037 --> 02:49:16,607
SPEAKERS ARE POPPING UP TO THE 

4379
02:49:16,607 --> 02:49:17,240
FRONT, BUT THERE ARE LIMITS. WE 

4380
02:49:17,240 --> 02:49:18,775
CAN ONLY SPOTLIGHT SEVEN AT A 

4381
02:49:18,775 --> 02:49:19,343
TIME. FEEL FREE TO USE YOUR 

4382
02:49:19,343 --> 02:49:21,178
MICROPHONE AND CAMERA.

4383
02:49:21,178 --> 02:49:26,149
AND I THINK WE HAVE THAT ALL 

4384
02:49:26,149 --> 02:49:36,426
SET UP ALREADY. 

4385
02:49:37,961 --> 02:49:38,528
>> WHAT A GREAT JOB HAVE
DONE 

4386
02:49:38,528 --> 02:49:39,162
ON MAKING THIS VIRTUAL SESSION 

4387
02:49:39,162 --> 02:49:40,397
FEEL SO REAL AND PRODUCTIVE. 

4388
02:49:40,397 --> 02:49:40,964
>> THANK YOU SO MUCH FOR
THAT 

4389
02:49:40,964 --> 02:49:44,101
FEEDBACK. 

4390
02:49:44,101 --> 02:49:45,535
IT IS A BIG TEAM. 

4391
02:49:45,535 --> 02:49:49,473
I'M GOING TO ... HAND IT OVER 

4392
02:49:49,473 --> 02:49:59,750
TO KATE POSSIN. 

4393
02:50:00,951 --> 02:50:10,594
>> DR. POSSIN: I HOPE
EVERYBODY 

4394
02:50:10,594 --> 02:50:11,228
HAD A GENESIS STRETCH AS WE GOT 

4395
02:50:11,228 --> 02:50:17,000
INTO THE LAST SESSION TODAY BUT 

4396
02:50:17,000 --> 02:50:17,634
BEFORE WE START I WANT TO MAKE 

4397
02:50:17,634 --> 02:50:18,268
SURE EVERYONE IS AWARE THERE IS 

4398
02:50:18,268 --> 02:50:18,835
A THIRD DAY OF THE SUMMIT. 

4399
02:50:18,835 --> 02:50:20,904
GOING TO BE ON JUNE 2. TODAY WE 

4400
02:50:20,904 --> 02:50:21,538
WANT TO HEAR YOUR COMMENTS BUT 

4401
02:50:21,538 --> 02:50:24,474
IF YOU DO NOT TELL US YOUR 

4402
02:50:24,474 --> 02:50:25,042
COMMENTS TODAY OR SOMETHING 

4403
02:50:25,042 --> 02:50:27,010
OCCURS LATER, THERE IS ANOTHER 

4404
02:50:27,010 --> 02:50:27,644
CHANCE. PLEASE JOIN US ON JUNE 

4405
02:50:27,644 --> 02:50:31,048
2 AND PROVIDE INPUT THERE. 

4406
02:50:31,048 --> 02:50:32,082
I HAVE A QUESTION FOR AMBER 

4407
02:50:32,082 --> 02:50:35,419
MCCARTNEY. 

4408
02:50:35,419 --> 02:50:35,986
IS THERE A WAY FOR PEOPLE TO 

4409
02:50:35,986 --> 02:50:36,553
EMAIL FEEDBACK BETWEEN THE 

4410
02:50:36,553 --> 02:50:37,888
MEETINGS?

4411
02:50:37,888 --> 02:50:46,063
>> THERE WILL NOT BE A
LIVE  

4412
02:50:46,063 --> 02:50:46,596
FEEDBACK BUTTON ACTIVE IN 

4413
02:50:46,596 --> 02:50:48,765
BETWEEN BUT YOU CAN EMAIL ... 

4414
02:50:48,765 --> 02:50:51,802
QUESTIONS TO ME. 

4415
02:50:51,802 --> 02:50:54,738
I CAN HELP YOU FIND THE RIGHT 

4416
02:50:54,738 --> 02:50:55,272
PERSON FIVE NOT THE RIGHT 

4417
02:50:55,272 --> 02:50:59,042
PERSON TO ASK. FEEL FREE TO 

4418
02:50:59,042 --> 02:50:59,576
REACH OUT TO ME. MY EMAIL 

4419
02:50:59,576 --> 02:51:09,786
ADDRESS IS 

4420
02:51:16,326 --> 02:51:18,829
AMBER.MCCARTNEY@NIH.GOV.

4421
02:51:18,829 --> 02:51:20,797
WE WILL FOLLOW-UP WITH EVERYONE 

4422
02:51:20,797 --> 02:51:21,431
WHO ATTENDED TODAY WITH A LINK 

4423
02:51:21,431 --> 02:51:26,803
TO JOIN THE MEETING HOW THE 

4424
02:51:26,803 --> 02:51:27,437
SECOND, AND THE UPDATED AGENDA 

4425
02:51:27,437 --> 02:51:31,074
AND PROGRAM BOOK. 

4426
02:51:31,074 --> 02:51:31,575
>> THANK YOU THAT IS VERY 

4427
02:51:31,575 --> 02:51:32,175
HELPFUL AND I SEE WE HAVE OUR 

4428
02:51:32,175 --> 02:51:35,078
FIRST QUESTION. 

4429
02:51:35,078 --> 02:51:35,679
SO I AM NOT-- I CANNOT SEE YOU 

4430
02:51:35,679 --> 02:51:36,480
NEVER WOULD YOU UNMUTE YOURSELF?

4431
02:51:36,480 --> 02:51:40,250
IS YOUR NAME DEBBIE YELPS? 

4432
02:51:40,250 --> 02:51:41,218
(PHONETIC)

4433
02:51:41,218 --> 02:51:49,226
>> NO. 

4434
02:51:49,226 --> 02:51:52,996
>> I SEE MARICE FIRST. 

4435
02:51:52,996 --> 02:51:56,299
>> I AM NEUROSCIENTIST.
THIS IS 

4436
02:51:56,299 --> 02:51:56,833
A QUESTION AS I HAVE BEEN 

4437
02:51:56,833 --> 02:51:57,400
TRACKING YOUR PRESENTATIONS 

4438
02:51:57,400 --> 02:52:00,070
WHICH I THOROUGHLY ENJOYED. 

4439
02:52:00,070 --> 02:52:03,507
WHEN YOU TALK ABOUT 

4440
02:52:03,507 --> 02:52:04,107
MULTI-ETIOLOGY, I'M WONDERING 

4441
02:52:04,107 --> 02:52:04,608
IF WE ARE TALKING ABOUT 

4442
02:52:04,608 --> 02:52:05,542
ULTIMATE OR PROXIMATE. ARE WE 

4443
02:52:05,542 --> 02:52:08,845
TALKING ABOUT TAU VS. AMYLOID 

4444
02:52:08,845 --> 02:52:16,253
VS. LEVY BODIES?

4445
02:52:16,253 --> 02:52:16,753
I WOULD TALK ABOUT HEART 

4446
02:52:16,753 --> 02:52:18,955
FAILURE OR MAYBE OBESITY?

4447
02:52:18,955 --> 02:52:19,456
MAYBE BECAUSE I AM NOT A 

4448
02:52:19,456 --> 02:52:20,090
CLINICIAN BUT I DON'T KNOW WHAT 

4449
02:52:20,090 --> 02:52:20,657
IT MEANS TO HAVE MULTIPLE 

4450
02:52:20,657 --> 02:52:25,295
ETIOLOGY. 

4451
02:52:25,295 --> 02:52:33,603
>> THIS IS SUDHA, I LIKE
TO 

4452
02:52:33,603 --> 02:52:35,772
PASS IT TO YOU. 

4453
02:52:35,772 --> 02:52:38,975
>> DR. SESHADRI: WHEN WE
USED 

4454
02:52:38,975 --> 02:52:41,411
TO MAKE A CLINICAL DIAGNOSIS 

4455
02:52:41,411 --> 02:52:42,012
BASED ON THE PREPONDERANCE OF 

4456
02:52:42,012 --> 02:52:46,449
THE CLINICAL EVIDENCE, A LOT OF 

4457
02:52:46,449 --> 02:52:47,050
THE TIME WHEN WE COMPARE THAT 

4458
02:52:47,050 --> 02:52:57,561
WITH WHAT WE SEE AT THE BRAIN 

4459
02:53:04,367 --> 02:53:04,935
(INDISCERNIBLE), AS YOU SAID WE 

4460
02:53:04,935 --> 02:53:05,569
ARE SEEING THINGS THAT MIGHT BE 

4461
02:53:05,569 --> 02:53:06,136
SUFFICIENT IN THEMSELVES TO 

4462
02:53:06,136 --> 02:53:08,905
CAUSE THE SYMPTOMS. 

4463
02:53:08,905 --> 02:53:09,439
I DON'T KNOW THAT WE HAVE A 

4464
02:53:09,439 --> 02:53:10,006
FULL PROOF WAY TO KNOW THAT 

4465
02:53:10,006 --> 02:53:10,607
YOUR SYMPTOMS ARE BECAUSE OF 

4466
02:53:10,607 --> 02:53:11,074
THIS OR THAT. 

4467
02:53:11,074 --> 02:53:15,212
IF SOMEBODY HAS AMYLOID, TAU, 

4468
02:53:15,212 --> 02:53:18,882
(INDISCERNIBLE) AND ALL OF THE 

4469
02:53:18,882 --> 02:53:26,289
ABOVE SO WE ARE TALKING ABOUT 

4470
02:53:26,289 --> 02:53:26,923
PATHOLOGIES THAT WE THINK EACH 

4471
02:53:26,923 --> 02:53:27,390
CAN LEAD TO COGNITIVE 

4472
02:53:27,390 --> 02:53:27,991
IMPAIRMENT AND DEMENTIA. AND 

4473
02:53:27,991 --> 02:53:30,927
THE COEXISTENCE OF THESE. 

4474
02:53:30,927 --> 02:53:32,395
BASED ON THE WAY WE CAME WE CAN 

4475
02:53:32,395 --> 02:53:42,906
SOMETIMES SAY OKAY, YOU HAVE 

4476
02:53:48,411 --> 02:53:48,945
HALLUCINATIONS, WE THINK THIS 

4477
02:53:48,945 --> 02:53:49,579
WAS PERHAPS RESPONSIBLE FOR 

4478
02:53:49,579 --> 02:53:50,113
THIS BUT IF SOMEBODY HAS 

4479
02:53:50,113 --> 02:53:50,714
DIFFICULTY WITH PLANNING AND 

4480
02:53:50,714 --> 02:53:51,314
EXECUTION, WAS IT BECAUSE OF 

4481
02:53:51,314 --> 02:53:52,782
THE TAU?

4482
02:53:52,782 --> 02:53:55,886
WAS IT BECAUSE OF THE 

4483
02:53:55,886 --> 02:53:56,319
A-SYNUCLEIN?

4484
02:53:56,319 --> 02:53:58,688
THAT CAN BE CHALLENGING. 

4485
02:53:58,688 --> 02:53:59,289
>> THAT IS SUPER HELPFUL.
THANK 

4486
02:53:59,289 --> 02:54:00,123
YOU SO MUCH. 

4487
02:54:00,123 --> 02:54:02,158
>> ALL RIGHT. 

4488
02:54:02,158 --> 02:54:06,630
DEBBIE?

4489
02:54:06,630 --> 02:54:07,163
>> IS THERE ANYONE ELSE
WHO 

4490
02:54:07,163 --> 02:54:15,739
WANTS TO ADDRESS THE QUESTION?

4491
02:54:15,739 --> 02:54:19,442
>> HI EVERYBODY, SUDHA I
LOVE 

4492
02:54:19,442 --> 02:54:22,712
YOUR ANSWER. MY VOICE IS NOT 

4493
02:54:22,712 --> 02:54:24,381
TOO GREAT BUT OVER TIME IT HAS 

4494
02:54:24,381 --> 02:54:28,251
BEEN AS SUDHA SAID, RECOGNIZE 

4495
02:54:28,251 --> 02:54:30,654
THAT THERE ARE MULTIPLE 

4496
02:54:30,654 --> 02:54:32,122
PATHOLOGIES THAT MAY CONTRIBUTE 

4497
02:54:32,122 --> 02:54:35,625
TO DEMENTIA. 

4498
02:54:35,625 --> 02:54:36,826
AND I A LITTLE BIT OF THE 

4499
02:54:36,826 --> 02:54:37,427
CHALLENGE, OF KNOWING WHAT TO 

4500
02:54:37,427 --> 02:54:45,835
SAY IS THAT WE'RE ON THE PATH 

4501
02:54:45,835 --> 02:54:48,438
TO CERTAINTY OF WHICH OF THOSE 

4502
02:54:48,438 --> 02:54:48,972
PATHOLOGIES ARE ACTUALLY 

4503
02:54:48,972 --> 02:54:52,242
CAUSAL. 

4504
02:54:52,242 --> 02:54:52,842
OR WHETHER IT IS SOMETHING THAT 

4505
02:54:52,842 --> 02:54:53,443
IS UPSTREAM OF THE PATHOLOGY 

4506
02:54:53,443 --> 02:54:56,913
THAT IS CAUSAL.  AND WHEN YOU 

4507
02:54:56,913 --> 02:54:58,081
HAVE-- AND THOSE THREE 

4508
02:54:58,081 --> 02:55:01,217
DIFFERENT PATHOLOGIES IN THE 

4509
02:55:01,217 --> 02:55:03,820
BRAIN ALL OF WHICH MAY BE 

4510
02:55:03,820 --> 02:55:04,421
CONTRIBUTING, BUT ALSO ALL OF 

4511
02:55:04,421 --> 02:55:05,021
WHICH MIGHT BE KIND OF ALONG 

4512
02:55:05,021 --> 02:55:08,925
FOR THE RIDE, OR DOWNSTREAM. IT 

4513
02:55:08,925 --> 02:55:09,559
GETS VERY HARD TO KNOW WHAT TO 

4514
02:55:09,559 --> 02:55:11,995
SAY. IF THAT MAKES SENSE. 

4515
02:55:11,995 --> 02:55:18,535
SO A MIXED-ETIOLOGY DEMENTIA, 

4516
02:55:18,535 --> 02:55:20,303
WE ARE REFERRED TO IS A BIT OF 

4517
02:55:20,303 --> 02:55:21,404
AN OBLIQUE WAY OF ACKNOWLEDGING 

4518
02:55:21,404 --> 02:55:23,139
THERE IS A LOT WE DON'T KNOW.  

4519
02:55:23,139 --> 02:55:25,742
AND THAT INCLUDES OUR 

4520
02:55:25,742 --> 02:55:29,112
UNDERSTANDING OF CAUSES. 

4521
02:55:29,112 --> 02:55:32,248
>> AND IF I MIGHT JUST
ASK, 

4522
02:55:32,248 --> 02:55:35,552
WOULD YOU SAY THINGS LIKE, "I 

4523
02:55:35,552 --> 02:55:36,386
DON'T KNOW BLOOD BRAIN BARRIER 

4524
02:55:36,386 --> 02:55:38,254
INTEGRITY, NEURO- 

4525
02:55:38,254 --> 02:55:40,457
INFLAMMATION." YOU DON'T KNOW 

4526
02:55:40,457 --> 02:55:42,125
YET IF THEY ARE UPSTREAM, 

4527
02:55:42,125 --> 02:55:44,160
CAUSAL, ETC.?

4528
02:55:44,160 --> 02:55:48,565
>> YEAH.  I WOULD SAY IT
LIKE 

4529
02:55:48,565 --> 02:55:49,799
THEY ARE CERTAINLY IN THE 

4530
02:55:49,799 --> 02:55:53,737
PICTURE. THEY ARE LIKELY TO BE 

4531
02:55:53,737 --> 02:55:54,304
IMPORTANT. BUT IN TERMS OF 

4532
02:55:54,304 --> 02:55:57,207
HARD-BOILED, RIGOROUS PROOF, 

4533
02:55:57,207 --> 02:55:57,807
THAT IS WHAT PUTS US IN THIS 

4534
02:55:57,807 --> 02:56:00,076
SPACE OF SAYING THINGS LIKE 

4535
02:56:00,076 --> 02:56:01,811
MULTIPLE ETIOLOGY. 

4536
02:56:01,811 --> 02:56:06,483
I MIGHT REPHRASE IT AND SAY, 

4537
02:56:06,483 --> 02:56:10,086
MULTIPLE PATHOLOGY DEMENTIA. 

4538
02:56:10,086 --> 02:56:10,653
MY PERSPECTIVE WHAT THAT COME 

4539
02:56:10,653 --> 02:56:11,254
FROM IS THAT WHEN PEOPLE SEE 

4540
02:56:11,254 --> 02:56:19,129
MULTIPLE PATHOLOGIES IN 

4541
02:56:19,129 --> 02:56:19,696
ABSTAINING THAT IS WHAT IS 

4542
02:56:19,696 --> 02:56:20,296
RECOGNIZE BUT THAT IS MY TWO 

4543
02:56:20,296 --> 02:56:21,197
BITS. 

4544
02:56:21,197 --> 02:56:24,401
>> AND IF I CAN ADD
SOMETHING 

4545
02:56:24,401 --> 02:56:28,505
TO WHAT DAVE BEAUTIFULLY SAID, 

4546
02:56:28,505 --> 02:56:31,307
WE DO NOT KNOW WHAT IS CAUSAL. 

4547
02:56:31,307 --> 02:56:31,941
BUT IN ADDITION TO THAT THINGS 

4548
02:56:31,941 --> 02:56:34,644
MAY BE CAUSAL TO EACH OTHER IN 

4549
02:56:34,644 --> 02:56:45,088
A FEET-FORWARD LOOK. FOR 

4550
02:56:46,656 --> 02:56:47,190
EXAMPLE VERY PER MOBILITY AND 

4551
02:56:47,190 --> 02:56:47,791
INFLAMMATION CAN BE CAUSAL TO 

4552
02:56:47,791 --> 02:56:50,026
COGNITIVE FUNCTION BUT ALSO 

4553
02:56:50,026 --> 02:56:51,061
(INDISCERNIBLE), SO IS A LITTLE 

4554
02:56:51,061 --> 02:56:56,566
BIT OF A (INDISCERNIBLE). 

4555
02:56:56,566 --> 02:56:58,334
>> ALICE, IF YOU WANT TO 

4556
02:56:58,334 --> 02:56:59,903
COMMENT ON THIS?

4557
02:56:59,903 --> 02:57:04,574
OR SOMETHING ELSE?

4558
02:57:04,574 --> 02:57:06,943
>> YEAH I WANTED TO SAY I
DO 

4559
02:57:06,943 --> 02:57:07,477
LIKE QUESTION VERY MUCH. 

4560
02:57:07,477 --> 02:57:08,078
BECAUSE I IT GET TO THE FACT 

4561
02:57:08,078 --> 02:57:08,678
THAT WE ARE SPEAKING ON TWO 

4562
02:57:08,678 --> 02:57:10,747
LEVELS. RIGHT?

4563
02:57:10,747 --> 02:57:11,347
WE ARE SPEAKING ON THE CLINICAL 

4564
02:57:11,347 --> 02:57:14,117
LEVEL AND ALSO SPEAKING AT A 

4565
02:57:14,117 --> 02:57:16,786
MECHANISTIC SCIENTIFIC LEVEL. 

4566
02:57:16,786 --> 02:57:19,789
AT A CLINICAL LEVEL WHOM WE ARE 

4567
02:57:19,789 --> 02:57:20,323
TALKING TO PATIENT WE ARE 

4568
02:57:20,323 --> 02:57:20,957
THINKING ABOUT THE HEAD INJURY. 

4569
02:57:20,957 --> 02:57:22,625
YOU KNOW?

4570
02:57:22,625 --> 02:57:26,296
BASICALLY THE LITTLE STROKE. 

4571
02:57:26,296 --> 02:57:26,896
THOSE ARE THE THINGS WE ARE 

4572
02:57:26,896 --> 02:57:31,901
TALKING ABOUT AS ETIOLOGIES.  

4573
02:57:31,901 --> 02:57:32,535
BUT WHEN WE ARE THINKING ABOUT 

4574
02:57:32,535 --> 02:57:36,406
THIS MECHANISTICALLY-- AND WE 

4575
02:57:36,406 --> 02:57:36,840
HAVE TO THINK ABOUT 

4576
02:57:36,840 --> 02:57:37,373
MECHANISTICALLY IF WE ARE 

4577
02:57:37,373 --> 02:57:39,075
TRYING TO TARGET AND DEVELOP 

4578
02:57:39,075 --> 02:57:40,176
THERAPIES-- INFERRING THAT 

4579
02:57:40,176 --> 02:57:45,782
CAUSE, THE STROKE, THE HEAD 

4580
02:57:45,782 --> 02:57:49,652
INJURY MAY LEAD TO SOMETHING. 

4581
02:57:49,652 --> 02:57:50,286
ESSENTIALLY IN THE CASE OF THE 

4582
02:57:50,286 --> 02:57:52,122
HEAD INJURY MAY BE TAU. 

4583
02:57:52,122 --> 02:57:55,158
SOMETHING LIKE THAT. 

4584
02:57:55,158 --> 02:58:02,565
AND THAT I IS THE FIRST THING. 

4585
02:58:02,565 --> 02:58:03,166
THE WAY ETIOLOGIES HAVE BEEN 

4586
02:58:03,166 --> 02:58:03,733
USED IN TWO DIFFERENT WAYS 

4587
02:58:03,733 --> 02:58:09,005
ACROSS DIFFERENT PRESENTATIONS. 

4588
02:58:09,005 --> 02:58:09,639
FROM THE PERSPECTIVE OF TRYING 

4589
02:58:09,639 --> 02:58:10,240
TO INTERRUPT THEM WE HAVE TO 

4590
02:58:10,240 --> 02:58:11,908
THINK LIKE SCIENTISTS, THINKING 

4591
02:58:11,908 --> 02:58:13,309
ABOUT THE MECHANISTIC PIECES. 

4592
02:58:13,309 --> 02:58:16,246
AND I DO THINK SOME OF THE 

4593
02:58:16,246 --> 02:58:19,182
CAUSALITY CAN BE HELPED BY THE 

4594
02:58:19,182 --> 02:58:19,749
FACT THAT THERE IS A LOT OF 

4595
02:58:19,749 --> 02:58:23,086
GENETICS AND GENOMICS TOO.  

4596
02:58:23,086 --> 02:58:23,887
THAT INFERS A CERTAIN AMOUNT OF 

4597
02:58:23,887 --> 02:58:26,956
CAUSALITY THERE. 

4598
02:58:26,956 --> 02:58:30,693
>> DEBBIE?

4599
02:58:30,693 --> 02:58:31,227
PLEASE UNMUTE AND ASK YOUR 

4600
02:58:31,227 --> 02:58:33,963
QUESTION OR COMMENT. 

4601
02:58:33,963 --> 02:58:35,098
>> CAN YOU HEAR ME OKAY? 

4602
02:58:35,098 --> 02:58:36,266
>> YES. 

4603
02:58:36,266 --> 02:58:42,705
>> SO THANK YOU SO MUCH
FOR 

4604
02:58:42,705 --> 02:58:43,306
THIS WONDERFUL UPDATE ON ALL 

4605
02:58:43,306 --> 02:58:43,940
THE WORK STREAMS THAT HAVE BEEN 

4606
02:58:43,940 --> 02:58:47,343
HAPPENING. 

4607
02:58:47,343 --> 02:58:48,511
IT REALLY IS HEARTENING, 

4608
02:58:48,511 --> 02:58:50,847
ESPECIALLY TO HEAR THE PEOPLE 

4609
02:58:50,847 --> 02:58:53,783
WHO PRESENTED WHAT HAS EMERGED 

4610
02:58:53,783 --> 02:58:55,718
IN THE LAST THREE YEARS, SINCE 

4611
02:58:55,718 --> 02:58:57,020
THE LAST SUMMIT. 

4612
02:58:57,020 --> 02:59:05,562
I LOST MY HUSBAND TO A GENERIC 

4613
02:59:05,562 --> 02:59:06,196
(INDISCERNIBLE) DISEASE IN THE 

4614
02:59:06,196 --> 02:59:06,796
RIVERS AND FAMILIES WHO HAVE 

4615
02:59:06,796 --> 02:59:08,998
LOST LOVED ONES TO SPORADIC AND 

4616
02:59:08,998 --> 02:59:12,335
GENETIC. 

4617
02:59:12,335 --> 02:59:14,737
ONE THING I DID NOT HEAR IN THE 

4618
02:59:14,737 --> 02:59:15,238
RECOMMENDATIONS IN THE 

4619
02:59:15,238 --> 02:59:16,206
PRIORITIES IN THE WORK TEAMS, 

4620
02:59:16,206 --> 02:59:24,614
IS REPRESENTATION OF PREOM 

4621
02:59:24,614 --> 02:59:25,248
(PHONETIC) DISEASE AND WHEN WE 

4622
02:59:25,248 --> 02:59:27,984
ARE LOOKING TO RUB TOGETHER SO 

4623
02:59:27,984 --> 02:59:28,585
MUCH IS HAPPENING IN SO MANY 

4624
02:59:28,585 --> 02:59:29,519
DIFFERENT DIMENSIONS, TO ME 

4625
02:59:29,519 --> 02:59:32,222
THAT FEELS LIKE A LOSS. 

4626
02:59:32,222 --> 02:59:39,062
SO MY COMMENT IS, COULD THAT BE 

4627
02:59:39,062 --> 02:59:39,696
CONSIDERED AS YOU PROCEED WITH 

4628
02:59:39,696 --> 02:59:40,296
THESE RECOMMENDATIONS?

4629
02:59:40,296 --> 02:59:41,564
>> THANK YOU DEBBIE. THAT
WAS 

4630
02:59:41,564 --> 02:59:45,468
VERY WELL SAID. 

4631
02:59:45,468 --> 02:59:46,035
AMBER, I KNOW THERE HAS BEEN 

4632
02:59:46,035 --> 02:59:46,636
SOME HISTORY ABOUT INCLUDING 

4633
02:59:46,636 --> 02:59:51,708
PREON HERE. SO IMPORTANT. 

4634
02:59:51,708 --> 02:59:52,575
DO YOU HAVE A COMMENT ON THAT 

4635
02:59:52,575 --> 03:00:02,919
FROM A POLICY SIDE?

4636
03:00:05,054 --> 03:00:06,289
>> I DON'T THINK IT IS A
POLICY 

4637
03:00:06,289 --> 03:00:07,957
QUESTION IN TERMS OF INCLUDING 

4638
03:00:07,957 --> 03:00:11,427
PREONS UNDER THE UMBRELLA OF 

4639
03:00:11,427 --> 03:00:19,469
ADRD. 

4640
03:00:19,469 --> 03:00:20,036
THAT IS A SCIENTIFIC QUESTION 

4641
03:00:20,036 --> 03:00:20,637
INCLUDED TALKING RIGHT NOW TO 

4642
03:00:20,637 --> 03:00:21,271
FIGURE OUT IF I COULD JUST ASK 

4643
03:00:21,271 --> 03:00:21,904
A QUESTION ABOUT REPRESENTATION 

4644
03:00:21,904 --> 03:00:23,339
OF PRION. 

4645
03:00:23,339 --> 03:00:25,975
WE ARE NOTING IT AND WE WILL 

4646
03:00:25,975 --> 03:00:28,244
FOLLOW-UP. 

4647
03:00:28,244 --> 03:00:34,083
>> DOES ANYBODY ELSE WANT
TO?

4648
03:00:34,083 --> 03:00:38,888
>> THIS IS DIANE --, I
DON'T 

4649
03:00:38,888 --> 03:00:42,892
KNOW IF MY CAMERA IS WORKING 

4650
03:00:42,892 --> 03:00:45,662
HERE, BUT ANYWAYS YOU CAN HEAR 

4651
03:00:45,662 --> 03:00:46,596
ME.  MORE AND MORE PEOPLE ARE 

4652
03:00:46,596 --> 03:00:50,133
SHOWING ALZHEIMER'S DISEASE AND 

4653
03:00:50,133 --> 03:00:55,238
RELATED DEMENTIA. AND THE 

4654
03:00:55,238 --> 03:00:56,539
INFECTIONS. THERE IS A RECENT 

4655
03:00:56,539 --> 03:01:02,011
PAPER FROM SOME EUROPEANS AND 

4656
03:01:02,011 --> 03:01:02,612
SOMEONE IN THE US SHOWED THAT 

4657
03:01:02,612 --> 03:01:03,279
SHINGLES VACCINE CAN REDUCE THE 

4658
03:01:03,279 --> 03:01:04,213
INCIDENCE AT LEAST. 

4659
03:01:04,213 --> 03:01:06,316
AND SO I MEAN I THINK THAT 

4660
03:01:06,316 --> 03:01:09,786
PRION DISEASE SHOULD ALSO BE 

4661
03:01:09,786 --> 03:01:13,790
INCLUDED IN THIS. 

4662
03:01:13,790 --> 03:01:17,727
>> YEAH AND IF I MAY ADD--
THIS 

4663
03:01:17,727 --> 03:01:24,233
IS CONSTANTINO -- THE PRION 

4664
03:01:24,233 --> 03:01:26,135
MECHANISM HAS BEEN INVOLVED IN 

4665
03:01:26,135 --> 03:01:28,805
TAU PROPAGATION. 

4666
03:01:28,805 --> 03:01:31,874
AND SO WE WE TALK ABOUT 

4667
03:01:31,874 --> 03:01:34,043
SOMETHING LIKE MAD COW DISEASE, 

4668
03:01:34,043 --> 03:01:34,677
THE MECHANISM IS SOMETHING THAT 

4669
03:01:34,677 --> 03:01:35,244
NEEDS TO BE APPLIED AND IF 

4670
03:01:35,244 --> 03:01:36,079
THERE IS ONE CONDITION WHERE 

4671
03:01:36,079 --> 03:01:37,914
THIS IS GOING TO BE HIGHLY 

4672
03:01:37,914 --> 03:01:43,986
RELEVANT, IS MULTI ETIOLOGY 

4673
03:01:43,986 --> 03:01:46,923
DEMENTIA. 

4674
03:01:46,923 --> 03:01:49,258
IN THE CONTEXT OF VASCULAR 

4675
03:01:49,258 --> 03:01:53,596
INSUFFICIENCY OFTEN, THERE ARE 

4676
03:01:53,596 --> 03:01:54,497
CONDITIONS  THAT WILL PROMOTE 

4677
03:01:54,497 --> 03:02:00,403
THE PRION MECHANISM WHICH IS 

4678
03:02:00,403 --> 03:02:01,738
CERTAINLY HIGHLY RELEVANT TO 

4679
03:02:01,738 --> 03:02:05,408
THIS. ALTHOUGH IT MAY BE A PURE 

4680
03:02:05,408 --> 03:02:07,977
PRION DISEASE, BUT THE 

4681
03:02:07,977 --> 03:02:11,347
MECHANISM IS HIGHLY RELEVANT. 

4682
03:02:11,347 --> 03:02:12,215
WALTER CAN SAY SOMETHING ABOUT 

4683
03:02:12,215 --> 03:02:14,183
THAT TOO. 

4684
03:02:14,183 --> 03:02:22,725
>> YEAH.  A LITTLE BIT OF
A 

4685
03:02:22,725 --> 03:02:27,964
(INDISCERNIBLE) TOPIC HERE.  I 

4686
03:02:27,964 --> 03:02:28,531
GUESS, THERE ARE REALLY TWO 

4687
03:02:28,531 --> 03:02:31,334
ANSWERS TO YOUR POINT. 

4688
03:02:31,334 --> 03:02:36,172
THE ANSWER TO AT NINDS, PRION 

4689
03:02:36,172 --> 03:02:40,243
DISEASE IS REALLY IMPORTANT.  

4690
03:02:40,243 --> 03:02:40,810
WE ARE FUNDING RESEARCH IN 

4691
03:02:40,810 --> 03:02:42,078
PRION DISEASE, PUTTING 

4692
03:02:42,078 --> 03:02:48,818
POTENTIAL TREATMENTS FOR PRION 

4693
03:02:48,818 --> 03:02:51,954
DISEASE. 

4694
03:02:51,954 --> 03:02:52,588
WHEN FUNDING CAME FROM CONGRESS 

4695
03:02:52,588 --> 03:02:57,160
FOR ALZHEIMER'S AND 

4696
03:02:57,160 --> 03:03:00,163
ALZHEIMER'S-RELATED DEMENTIAS, 

4697
03:03:00,163 --> 03:03:01,931
THEY DO NOT INCLUDE ALL 

4698
03:03:01,931 --> 03:03:02,999
DEMENTIAS IN THE FUNDING 

4699
03:03:02,999 --> 03:03:04,867
APPROPRIATION. 

4700
03:03:04,867 --> 03:03:05,902
THERE ARE A NUMBER OF OTHER 

4701
03:03:05,902 --> 03:03:08,571
FORMS OF DEMENTIA THAT ARE NOT 

4702
03:03:08,571 --> 03:03:11,574
INCLUDED IN THE FUNDING THAT IS 

4703
03:03:11,574 --> 03:03:12,108
PARTICULARLY COMING FROM 

4704
03:03:12,108 --> 03:03:14,644
CONGRESS FOR THAT PURPOSE. 

4705
03:03:14,644 --> 03:03:15,178
SO I GUESS THERE ARE TWO 

4706
03:03:15,178 --> 03:03:25,588
THINGS. ONE IS, AS COS 

4707
03:03:26,022 --> 03:03:27,323
MENTIONED, MECHANISM BY WHICH 

4708
03:03:27,323 --> 03:03:29,926
PRION SPREADS IS SO RELEVANT TO 

4709
03:03:29,926 --> 03:03:31,360
THE OTHER GENERATIONS THAT WERE 

4710
03:03:31,360 --> 03:03:36,933
LISTED. WHICH ARE LEVY BODY 

4711
03:03:36,933 --> 03:03:37,667
DEMENTIA, CARDIOVASCULAR 

4712
03:03:37,667 --> 03:03:41,103
IMPAIRMENT -- AND  

4713
03:03:41,103 --> 03:03:44,073
FRONTOTEMPORAL DEMENTIA.  THERE 

4714
03:03:44,073 --> 03:03:46,876
IT IS RELEVANT TO USE THOSE 

4715
03:03:46,876 --> 03:03:47,210
FUNDS.

4716
03:03:47,210 --> 03:03:48,277
BUT OTHERWISE WE USE REGULAR 

4717
03:03:48,277 --> 03:03:57,787
NINDS FUNDS FOR STUDYING PEOPLE 

4718
03:03:57,787 --> 03:03:58,387
WITH PRION DISEASE. I KNOW IT 

4719
03:03:58,387 --> 03:04:03,659
IS A TECHNICAL THING.  BUT WE 

4720
03:04:03,659 --> 03:04:04,126
HAVE TO ABIDE BY THE 

4721
03:04:04,126 --> 03:04:04,694
APPROPRIATION LANGUAGE THAT 

4722
03:04:04,694 --> 03:04:15,037
CONGRESS GIVES US. 

4723
03:04:20,943 --> 03:04:21,511
>> CAN I SAY-- I KNOW
WALTER- 

4724
03:04:21,511 --> 03:04:22,144
CAN I ASK A QUESTION YOU DON'T 

4725
03:04:22,144 --> 03:04:23,946
HAVE TO ANSWER THIS. 

4726
03:04:23,946 --> 03:04:24,514
WHATEVER CONDITIONS THAT ARE 

4727
03:04:24,514 --> 03:04:26,949
NOT CONGRESSIONALLY MANDATED, 

4728
03:04:26,949 --> 03:04:27,517
CAN THAT BE INCLUDED IN THE 

4729
03:04:27,517 --> 03:04:28,751
REPORT AS A REFERENCE?

4730
03:04:28,751 --> 03:04:29,719
FOR OTHERS. 

4731
03:04:29,719 --> 03:04:35,625
>> DR. KOROSHETZ: YEAH, 

4732
03:04:35,625 --> 03:04:36,259
WHATEVER YOU THINK IS IMPORTANT 

4733
03:04:36,259 --> 03:04:36,826
THAT IS WHAT GOES INTO THE 

4734
03:04:36,826 --> 03:04:37,760
REPORT.  NOT A POLITICAL 

4735
03:04:37,760 --> 03:04:39,128
DOCUMENT. 

4736
03:04:39,128 --> 03:04:43,099
>> GREAT.  BECAUSE AS I
WAS 

4737
03:04:43,099 --> 03:04:46,736
TRYING TO SAY, THIS  IS WHERE 

4738
03:04:46,736 --> 03:04:52,575
PRIVATE FUNDERS -- AND 

4739
03:04:52,575 --> 03:04:53,142
INTERNATIONAL FUNDERS WOULD 

4740
03:04:53,142 --> 03:04:53,676
COME IN AND PARTNER OR DO 

4741
03:04:53,676 --> 03:04:55,811
THINGS INTERNATIONALLY.  AND SO 

4742
03:04:55,811 --> 03:05:00,016
IT IS GREAT. I WANT TO HAVE 

4743
03:05:00,016 --> 03:05:00,583
THIS DOCUMENT BE A SHINING 

4744
03:05:00,583 --> 03:05:06,856
EXAMPLE ON THE HILL, WHATEVER 

4745
03:05:06,856 --> 03:05:07,390
YOU WANT TO CALL IT; THE 

4746
03:05:07,390 --> 03:05:08,024
DEFINITIVE RECOMMENDATION TO GO 

4747
03:05:08,024 --> 03:05:08,624
INTO THE NATIONAL PLAN. THANK 

4748
03:05:08,624 --> 03:05:10,359
YOU. 

4749
03:05:10,359 --> 03:05:12,828
>> ALL RIGHT THANK YOU. 

4750
03:05:12,828 --> 03:05:14,931
LET' SEE. 

4751
03:05:14,931 --> 03:05:16,232
TRYING TO SEE THE NAME. I 

4752
03:05:16,232 --> 03:05:21,270
CANNOT SEE THE WHOLE NAME. ERIC 

4753
03:05:21,270 --> 03:05:30,880
-- I THINK YOU ARE NEXT. 

4754
03:05:30,880 --> 03:05:33,983
>> CAN YOU HEAR ME?

4755
03:05:33,983 --> 03:05:35,518
(INDISCERNIBLE). 

4756
03:05:35,518 --> 03:05:43,726
ALL RIGHT.  SO -- I WANTED TO 

4757
03:05:43,726 --> 03:05:45,127
THANK YOU ALL FOR THE GREAT 

4758
03:05:45,127 --> 03:05:45,761
PRESENTATIONS OVER THE PAST TWO 

4759
03:05:45,761 --> 03:05:49,031
DAYS.  I THINK IT IS BEEN VERY, 

4760
03:05:49,031 --> 03:05:50,866
VERY INFORMATIVE FOR ME. 

4761
03:05:50,866 --> 03:06:00,242
SO I HAVE ... THREE QUESTIONS. 

4762
03:06:00,242 --> 03:06:02,912
THREE POINTS I WANTED TO MAKE.

4763
03:06:02,912 --> 03:06:03,646
I GUESS I WOULD DO ONE AT A 

4764
03:06:03,646 --> 03:06:04,580
TIME.

4765
03:06:04,580 --> 03:06:05,214
THE FIRST ONE IS A NEURO- 

4766
03:06:05,214 --> 03:06:07,249
INFLAMMATION.  IF WE LOOK AT 

4767
03:06:07,249 --> 03:06:17,693
ALL OF THIS NEURO-GENETIC 

4768
03:06:19,161 --> 03:06:19,528
DISORDER, SPREADING 

4769
03:06:19,528 --> 03:06:20,096
PROGRESSION, INFORMATION IS 

4770
03:06:20,096 --> 03:06:20,730
INVOLVED IN ALL OF THEM. SEEMS 

4771
03:06:20,730 --> 03:06:23,299
TO BE THE DRIVER. 

4772
03:06:23,299 --> 03:06:25,401
IN TERMS OF PRIORITIZATION BY 

4773
03:06:25,401 --> 03:06:29,071
THIS COMMITTEE, HOW 

4774
03:06:29,071 --> 03:06:34,844
(INDISCERNIBLE) FROM THIS?

4775
03:06:34,844 --> 03:06:38,347
IN TERMS OF EMPHASIS ON THE 

4776
03:06:38,347 --> 03:06:39,281
IMPORTANCE, WHERE DO YOU RANK 

4777
03:06:39,281 --> 03:06:39,849
NEURO- INFLAMMATION?

4778
03:06:39,849 --> 03:06:41,317
EXPECTING TO SEE BIO MATICS 

4779
03:06:41,317 --> 03:06:48,024
(PHONETIC). 

4780
03:06:48,024 --> 03:06:48,491
>> THANK YOU THAT IS A 

4781
03:06:48,491 --> 03:06:50,359
COST-CUTTING TOPIC. I'M 

4782
03:06:50,359 --> 03:06:50,993
WONDERING IF SOMEBODY FROM THE 

4783
03:06:50,993 --> 03:06:56,399
MED BASIC AND CLINICAL 

4784
03:06:56,399 --> 03:06:56,999
COMMITTEE MIGHT BE WILLING TO 

4785
03:06:56,999 --> 03:07:00,536
TAKE THIS QUESTION ABOUT NEURO- 

4786
03:07:00,536 --> 03:07:01,103
INFLAMMATION, AND HOW IT IS 

4787
03:07:01,103 --> 03:07:03,739
BEING CONSIDERED AND IF IT IS 

4788
03:07:03,739 --> 03:07:04,373
BEING GIVEN ADEQUATE PRIORITY. 

4789
03:07:04,373 --> 03:07:05,708
OR ANYONE ELSE. 

4790
03:07:05,708 --> 03:07:10,946
>> SO INFLAMMATION HAS
WORKED 

4791
03:07:10,946 --> 03:07:21,457
ITS WAY IN ALL KINDS OF ACUTE 

4792
03:07:21,657 --> 03:07:24,694
AND CHRONIC DISEASES, INCLUDING 

4793
03:07:24,694 --> 03:07:25,227
NEURO- GENETIC DISEASES. 

4794
03:07:25,227 --> 03:07:25,861
THERE'S A TREMENDOUS EFFORT TO 

4795
03:07:25,861 --> 03:07:27,263
UNDERSTAND THE ROLE OF IMMUNE 

4796
03:07:27,263 --> 03:07:27,863
CELLS WITHIN THE BRAIN WHICH 

4797
03:07:27,863 --> 03:07:28,698
RECENTLY HAVE BEEN IDENTIFIED 

4798
03:07:28,698 --> 03:07:31,500
AND THEY WERE NOT KNOWN 

4799
03:07:31,500 --> 03:07:32,234
PREVIOUSLY TO BE SO MUCH 

4800
03:07:32,234 --> 03:07:33,169
INVOLVED BECAUSE OF THE LACK OF 

4801
03:07:33,169 --> 03:07:38,074
PROPER MARKERS AND SO ON. 

4802
03:07:38,074 --> 03:07:38,607
AND SO NOW THERE IS A GREAT 

4803
03:07:38,607 --> 03:07:39,408
EFFORT TO UNDERSTAND THE ROLE 

4804
03:07:39,408 --> 03:07:40,309
OF MICROGLIA IN BOTH IN THE 

4805
03:07:40,309 --> 03:07:43,245
CONTEXT OF  VASCULAR DISEASE 

4806
03:07:43,245 --> 03:07:48,384
AND IN THE CONTEXT OF TAU, TDP 

4807
03:07:48,384 --> 03:07:51,220
43, AMYLOID AND SO ON. 

4808
03:07:51,220 --> 03:07:55,157
THERE IS AN EMERGING ROLE OF 

4809
03:07:55,157 --> 03:07:56,659
THE MILO SALES ASSOCIATE WITH 

4810
03:07:56,659 --> 03:08:00,563
THE BORDER OF THE BRAIN MOTOR 

4811
03:08:00,563 --> 03:08:03,199
ASSOCIATED MACROPHAGES, WHICH 

4812
03:08:03,199 --> 03:08:03,833
ARE THE CONSTANT CAUSES OF THE 

4813
03:08:03,833 --> 03:08:06,969
MICROGLIA INVOLVED IN AN NUMBER 

4814
03:08:06,969 --> 03:08:07,603
OF CRITICAL FUNCTIONS RELEVANT 

4815
03:08:07,603 --> 03:08:08,137
TO DEMENTIA. FOR EXAMPLE 

4816
03:08:08,137 --> 03:08:11,941
CLEARANCE OF AMYLOID AND TAU. 

4817
03:08:11,941 --> 03:08:13,075
THERE IS ALSO AN EMERGING ROLE 

4818
03:08:13,075 --> 03:08:17,113
OF T CELLS. BOTH THE INNATE 

4819
03:08:17,113 --> 03:08:26,555
KIND LIKE THE DTP 17 AND GAMMA 

4820
03:08:26,555 --> 03:08:27,123
DELTA T CELLS THAT PRODUCE 

4821
03:08:27,123 --> 03:08:28,090
TOXIC CYTOKINES WHICH ARE 

4822
03:08:28,090 --> 03:08:28,691
INVOLVED IN THE MECHANISMS OF 

4823
03:08:28,691 --> 03:08:35,731
DEMENTIA. 

4824
03:08:35,731 --> 03:08:36,332
SO I THE NEURO-INFLAMMATION IS 

4825
03:08:36,332 --> 03:08:38,367
KIND OF AN ESSENTIAL COMPONENT 

4826
03:08:38,367 --> 03:08:41,470
OF THIS THAT CONSTITUTES THE 

4827
03:08:41,470 --> 03:08:44,507
DEMENTIA FIELD. PARTICULARLY 

4828
03:08:44,507 --> 03:08:52,748
MULTI- (INDISCERNIBLE) 

4829
03:08:52,748 --> 03:08:53,249
DEMENTIA, WHERE ALL THE 

4830
03:08:53,249 --> 03:08:53,749
PATHOGENIC FACTORS INTO 

4831
03:08:53,749 --> 03:08:54,250
CONVERGENT CAUSE NEURO- 

4832
03:08:54,250 --> 03:08:55,951
INFLAMMATION. 

4833
03:08:55,951 --> 03:08:56,719
>> I AM THINKING MORE
ALONG THE 

4834
03:08:56,719 --> 03:09:03,893
LINES OF IF THERE IS A 

4835
03:09:03,893 --> 03:09:04,360
PARTICULAR ORDER OF 

4836
03:09:04,360 --> 03:09:06,395
PRIORITIZATION OR RANK. IS 

4837
03:09:06,395 --> 03:09:08,564
THERE ANY FUNDING OR RESOURCES, 

4838
03:09:08,564 --> 03:09:12,835
DIRECTIONAL RESOURCES?

4839
03:09:12,835 --> 03:09:16,539
THAT IS WHY I AM CURIOUS. 

4840
03:09:16,539 --> 03:09:20,609
ANOTHER WAS A TALK, SOME ITEMS 

4841
03:09:20,609 --> 03:09:26,549
WERE PRIORITIZED AS 1, 2, 3...

4842
03:09:26,549 --> 03:09:27,216
>> OFF THE TOP OF MY HEAD
THERE 

4843
03:09:27,216 --> 03:09:34,456
ARE A NUMBER OF OTHER PHASES 

4844
03:09:34,456 --> 03:09:35,090
FOCUSING ON THE INFORMATION IS 

4845
03:09:35,090 --> 03:09:36,725
ONE OF THE MECHANISMS INVOLVED 

4846
03:09:36,725 --> 03:09:38,661
IN BRAIN DISEASES AND SOMEONE 

4847
03:09:38,661 --> 03:09:40,329
FROM DNH MAY BE MORE QUALIFIED 

4848
03:09:40,329 --> 03:09:41,230
TO ADDRESS SPECIFICALLY THE 

4849
03:09:41,230 --> 03:09:51,073
FUNDS. ALLOTTED TO THAT. 

4850
03:09:51,073 --> 03:09:55,344
>> I CAN ALSO MAKE SURE WE
NOTE 

4851
03:09:55,344 --> 03:10:05,821
THIS. AND AS WE REVIEW THE 

4852
03:10:09,959 --> 03:10:10,492
RECOMMENDATIONS, WE CAN MAKE 

4853
03:10:10,492 --> 03:10:11,126
SURE THAT INFORMATION IS AT AN 

4854
03:10:11,126 --> 03:10:14,563
APPROPRIATELY HIGH-PRIORITY.

4855
03:10:14,563 --> 03:10:15,731
CAN YOU MOVE TO YOUR NEXT 

4856
03:10:15,731 --> 03:10:16,332
QUESTION BECAUSE YOU SAID YOU 

4857
03:10:16,332 --> 03:10:16,899
HAD THREE QUESTIONS?

4858
03:10:16,899 --> 03:10:21,737
>> YES, THE NEXT ONE,
BIOMARKER 

4859
03:10:21,737 --> 03:10:29,645
IMAGING. 

4860
03:10:29,645 --> 03:10:31,313
I KNOW CURRENTLY, 

4861
03:10:31,313 --> 03:10:36,685
(INDISCERNIBLE) HAVE PROVIDED 

4862
03:10:36,685 --> 03:10:37,319
SO MUCH ADDITIONAL INFORMATION 

4863
03:10:37,319 --> 03:10:37,853
AND UNDERSTANDING OF THE 

4864
03:10:37,853 --> 03:10:38,287
DISEASE. 

4865
03:10:38,287 --> 03:10:42,424
BUT ACCESS TO PET IS DIFFICULT. 

4866
03:10:42,424 --> 03:10:46,896
COST. WE ALL KNOW.  IN TERMS OF 

4867
03:10:46,896 --> 03:10:54,637
(INDISCERNIBLE), IS THERE SOME 

4868
03:10:54,637 --> 03:10:55,170
PRIORITIZATION OF ALL THE 

4869
03:10:55,170 --> 03:11:03,212
IMAGING TECHNOLOGIES OF PET FOR 

4870
03:11:03,212 --> 03:11:03,712
ADRD LOOKING AT?

4871
03:11:03,712 --> 03:11:08,050
HOW DO THEY RANK?

4872
03:11:08,050 --> 03:11:10,819
HIGH RISK, HIGH REWARD FOR ALL 

4873
03:11:10,819 --> 03:11:11,787
THE IMAGING TECHNOLOGIES OTHER 

4874
03:11:11,787 --> 03:11:18,527
THAN PET?

4875
03:11:18,527 --> 03:11:20,596
>> WOULD YOU TAKE THAT?

4876
03:11:20,596 --> 03:11:21,864
>> HAPPY TO TAKE THAT.

4877
03:11:21,864 --> 03:11:24,433
THAT IS A REALLY, REALLY GREAT 

4878
03:11:24,433 --> 03:11:25,034
QUESTION AND SOMETHING THAT 

4879
03:11:25,034 --> 03:11:28,537
WITHIN THE LEVY BODY DEMENTIA 

4880
03:11:28,537 --> 03:11:31,640
SESSION WE DISCUSSED IN THE 

4881
03:11:31,640 --> 03:11:32,241
CONTEXT OF USE AND WHY THESE 

4882
03:11:32,241 --> 03:11:35,511
DIFFERENT BIOMARKERS NEED TO BE 

4883
03:11:35,511 --> 03:11:36,545
DEVELOPED AND BALANCING BETWEEN 

4884
03:11:36,545 --> 03:11:37,112
THESE VERY HIGHLY DETAILED 

4885
03:11:37,112 --> 03:11:38,714
BIOMARKERS. 

4886
03:11:38,714 --> 03:11:43,452
 FOR INSTANCE THE PET IMAGING 

4887
03:11:43,452 --> 03:11:44,653
GIVES US THE SPATIAL RESOLUTION 

4888
03:11:44,653 --> 03:11:45,254
THAT COULD BE VERY IMPORTANT 

4889
03:11:45,254 --> 03:11:48,123
FOR MOVING CERTAIN THERAPIES-- 

4890
03:11:48,123 --> 03:11:52,361
LET'S SAY FROM ASSAYS TO PHASES 

4891
03:11:52,361 --> 03:11:58,600
-- OR FROM PHASE 1 TO 2.  TO 

4892
03:11:58,600 --> 03:11:59,234
GIVE YOU A SPECIALIST REGIONAL 

4893
03:11:59,234 --> 03:12:01,537
PROTEINS. 

4894
03:12:01,537 --> 03:12:02,037
ARE GOING BACK TO A PRIOR 

4895
03:12:02,037 --> 03:12:04,440
COMMENT WHETHER OR NOT CERTAIN 

4896
03:12:04,440 --> 03:12:06,475
PROTEINS IN CERTAIN REGIONS OF 

4897
03:12:06,475 --> 03:12:07,109
THE BRAIN DO OR DO NOT HAVE AN 

4898
03:12:07,109 --> 03:12:07,643
INFLUENCE ON THE CLINICAL 

4899
03:12:07,643 --> 03:12:09,945
PICTURE. RIGHT?

4900
03:12:09,945 --> 03:12:10,579
SO THAT IS WHERE THOSE CAN COME 

4901
03:12:10,579 --> 03:12:14,750
INTO IMPORTANCE.  THEY MAY NOT 

4902
03:12:14,750 --> 03:12:15,317
BE REALLY THE ONES THAT YOU 

4903
03:12:15,317 --> 03:12:15,851
WANT TO PUSH FORWARD ON A 

4904
03:12:15,851 --> 03:12:20,356
SCALABLE LEVEL FOR USE IN BROAD 

4905
03:12:20,356 --> 03:12:30,599
CLINICAL USE. 

4906
03:12:32,067 --> 03:12:32,534
>> 

4907
03:12:32,534 --> 03:12:36,705
>> 

4908
03:12:36,705 --> 03:12:43,746
(AUDIO LOST)

4909
03:12:43,746 --> 03:12:49,418
>> ... COULD BE DONE AT
SCALE 

4910
03:12:49,418 --> 03:12:49,952
ACROSS MULTIPLE DIFFERENT 

4911
03:12:49,952 --> 03:12:52,287
SECTORS BOTH ACADEMIC AND NOT. 

4912
03:12:52,287 --> 03:12:52,888
I THINK THE KEY HERE IS FOR ALL 

4913
03:12:52,888 --> 03:12:55,824
THE RECOMMENDATIONS TO REALLY 

4914
03:12:55,824 --> 03:13:00,329
THINK ABOUT NOT JUST IMAGING, 

4915
03:13:00,329 --> 03:13:03,632
BUT WE NEED IMAGING OF WHAT, 

4916
03:13:03,632 --> 03:13:04,266
FOR WHAT AND IN WHAT CONTEXT TO 

4917
03:13:04,266 --> 03:13:06,201
USE. THAT IS A REALLY CRITICAL 

4918
03:13:06,201 --> 03:13:06,835
PART. YOU HAVE TO BALANCE THOSE 

4919
03:13:06,835 --> 03:13:08,637
WITH THE PRIORITIES. YOU NEED 

4920
03:13:08,637 --> 03:13:09,671
THEM BOTH BUT IN DIFFERENT 

4921
03:13:09,671 --> 03:13:14,576
SITUATIONS FROM MY PERSPECTIVE. 

4922
03:13:14,576 --> 03:13:16,245
>> IF I MAY ALSO COMMENT,
YOU 

4923
03:13:16,245 --> 03:13:19,248
RAISE A REALLY GOOD QUESTION. 

4924
03:13:19,248 --> 03:13:21,683
DEPENDING ON WHAT YOU WANT TO 

4925
03:13:21,683 --> 03:13:22,818
MEASURE, I THINK YOU REALLY SEE 

4926
03:13:22,818 --> 03:13:33,295
A LOT OF PET WORK AND NOVEL 

4927
03:13:36,465 --> 03:13:37,099
TRACES AND MODALITIES.

4928
03:13:37,099 --> 03:13:37,566
SO IT IS VERY IMPORTANT 

4929
03:13:37,566 --> 03:13:42,538
QUESTION TO ADDRESS DEPENDING 

4930
03:13:42,538 --> 03:13:43,138
ON WHAT KIND OF QUESTION YOU 

4931
03:13:43,138 --> 03:13:43,772
WANT TO SORT OF ADDRESS WHETHER 

4932
03:13:43,772 --> 03:13:48,110
PROTEIN MEASUREMENT, OR YOUR 

4933
03:13:48,110 --> 03:13:48,544
INTEREST IS MORE OF 

4934
03:13:48,544 --> 03:13:50,712
PHYSIOLOGICAL MEASUREMENT.

4935
03:13:50,712 --> 03:13:55,117
>> AND AS WE THINK ABOUT
EARLY 

4936
03:13:55,117 --> 03:13:56,618
DIAGNOSES, BRAIN IMAGING IS NOT 

4937
03:13:56,618 --> 03:13:57,252
WIDELY ACCESSIBLE ACROSS ALL OF 

4938
03:13:57,252 --> 03:13:59,254
THE UNITED STATES OTHER THAN IN 

4939
03:13:59,254 --> 03:14:01,857
MAINE. LARGE SWATHES OF RURAL 

4940
03:14:01,857 --> 03:14:02,491
MAINE DON'T EVEN HAVE ACCESS TO 

4941
03:14:02,491 --> 03:14:10,232
PET CT OR EVEN MRI. 

4942
03:14:10,232 --> 03:14:10,799
AND SO THAT IS WHAT WE THINK 

4943
03:14:10,799 --> 03:14:11,433
ABOUT RARE DANCING AND THE NEED 

4944
03:14:11,433 --> 03:14:12,234
TO FILTER PATIENTS WE USED TO 

4945
03:14:12,234 --> 03:14:22,744
THINK PURELY ON COGNITION AND 

4946
03:14:40,295 --> 03:14:40,829
NOW WE ARE THINKING IMAGING. 

4947
03:14:40,829 --> 03:14:41,430
AND HIGHLIGHT THE BLOOD-BRAIN 

4948
03:14:41,430 --> 03:14:45,300
BIOMARKERS WE DISCUSSED.

4949
03:14:45,300 --> 03:14:45,868
>> IF I MAY ADD THE
PROGRESS 

4950
03:14:45,868 --> 03:14:50,672
MADE IN BIOMARKERS HAS BEEN 

4951
03:14:50,672 --> 03:14:51,373
AMAZING. THERE WAS A RECENT 

4952
03:14:51,373 --> 03:14:57,112
STUDY FROM BRAIN 

4953
03:14:57,112 --> 03:14:57,746
(INDISCERNIBLE), SHOWING THAT 

4954
03:14:57,746 --> 03:14:58,280
THE SECURITY LEVELS OF A 

4955
03:14:58,280 --> 03:14:58,714
PARTICULAR FORM OF 

4956
03:14:58,714 --> 03:15:01,817
PHOSPHORYLATED TAU  IS AS GOOD 

4957
03:15:01,817 --> 03:15:04,653
AS PET PLEA DIAGNOSIS.  IS 

4958
03:15:04,653 --> 03:15:05,287
GOING TO BE CHEAPER AND BETTER 

4959
03:15:05,287 --> 03:15:08,557
FOR SCREENING, FOR LARGE, HIGH 

4960
03:15:08,557 --> 03:15:12,594
THROUGHPUT APPROACHES. 

4961
03:15:12,594 --> 03:15:15,931
AND I ESPECIALLY FOR LOCATIONS 

4962
03:15:15,931 --> 03:15:17,799
WHERE IMAGING IS OTHERWISE 

4963
03:15:17,799 --> 03:15:18,367
AVAILABLE, VERY COSTLY AND 

4964
03:15:18,367 --> 03:15:21,803
REQUIRE SPECIALIZED PEOPLE. 

4965
03:15:21,803 --> 03:15:26,642
IT WOULD BE GREAT TO ALSO CROSS 

4966
03:15:26,642 --> 03:15:27,176
THE BLOOD BARRIER MARKER. 

4967
03:15:27,176 --> 03:15:27,809
UNFORTUNATELY FOR THE VASCULAR 

4968
03:15:27,809 --> 03:15:35,918
COMPONENT OF DEMENTIA THERE IS 

4969
03:15:35,918 --> 03:15:36,451
MUCH GOING ON PROMISING. 

4970
03:15:36,451 --> 03:15:37,085
SOMETHING IS PROMISING BUT NOT 

4971
03:15:37,085 --> 03:15:37,653
AS STRONG AS IT IS FOR THE 

4972
03:15:37,653 --> 03:15:43,659
ALZHEIMER'S DEMENTIA ASPECTS. 

4973
03:15:43,659 --> 03:15:52,134
>> CAN I JUMP IN QUICKLY?

4974
03:15:52,134 --> 03:15:52,634
I APPRECIATE THE REALLY 

4975
03:15:52,634 --> 03:16:00,642
IMPORTANT RESEARCH AND SCALING 

4976
03:16:00,642 --> 03:16:08,951
THAT DR. POSTIN MADE. 

4977
03:16:08,951 --> 03:16:09,518
WE DON'T WANT TO BE DEPENDENT 

4978
03:16:09,518 --> 03:16:10,118
ON ANY IMAGING MODALITIES IN 

4979
03:16:10,118 --> 03:16:10,752
THE INCREDIBLY VALUABLE AND WE 

4980
03:16:10,752 --> 03:16:11,386
NEED TO PURSUE THAT SCIENCE FOR 

4981
03:16:11,386 --> 03:16:21,830
ADVANCING TO THE CLINICAL 

4982
03:16:27,269 --> 03:16:27,836
STATION WE WILL ALWAYS NEED FOR 

4983
03:16:27,836 --> 03:16:28,337
SOME CASES IN CLINICAL 

4984
03:16:28,337 --> 03:16:28,937
EVALUATION. IT WISHERS ABOUT 

4985
03:16:28,937 --> 03:16:29,538
SCALING NOT JUST DOMESTICALLY 

4986
03:16:29,538 --> 03:16:30,105
WHERE IMAGING IS MINIMALLY 

4987
03:16:30,105 --> 03:16:35,143
ACCESSIBLE AT ALL,  BUT 

4988
03:16:35,143 --> 03:16:35,777
GLOBALLY WILL HAVE TO INVEST ON 

4989
03:16:35,777 --> 03:16:36,278
THE RESEARCH TO DEVELOP 

4990
03:16:36,278 --> 03:16:43,385
CLINICAL MODALITY TESTING THAT 

4991
03:16:43,385 --> 03:16:44,019
CAN BE PROVIDED THROUGHOUT BOTH 

4992
03:16:44,019 --> 03:16:44,586
OF IN THE GLOBAL MORE THAN 

4993
03:16:44,586 --> 03:16:46,188
GLOBAL SOUTH. 

4994
03:16:46,188 --> 03:16:48,123
BUT AS OTHERS HAVE SAID 

4995
03:16:48,123 --> 03:16:51,493
HOPEFULLY ENVISION-- ULTIMATELY 

4996
03:16:51,493 --> 03:16:52,094
IT WILL BE SALIVA AND OTHER 

4997
03:16:52,094 --> 03:16:54,730
MORE READILY ACCESSIBLE AND 

4998
03:16:54,730 --> 03:16:56,832
ANALYZABLE FLUIDS. 

4999
03:16:56,832 --> 03:17:00,068
SO IT IS A CONTINUUM.  WE ARE 

5000
03:17:00,068 --> 03:17:00,702
NEVER GOING TO BE ABLE TO JUST 

5001
03:17:00,702 --> 03:17:04,206
SKIP ANYTHING. BUT WHERE WE ARE 

5002
03:17:04,206 --> 03:17:08,243
IN BALANCE PUT OUR FOCUS FOR 

5003
03:17:08,243 --> 03:17:09,378
CLINICAL APPLICATION IN THE 

5004
03:17:09,378 --> 03:17:12,347
GLOBAL CONTEXT, 90% OF THE 

5005
03:17:12,347 --> 03:17:12,948
CASES OF COGNITIVE IMPAIRMENT 

5006
03:17:12,948 --> 03:17:16,251
ARE NOT IN ADVANCED, WESTERN 

5007
03:17:16,251 --> 03:17:21,657
ECONOMIES. WE ARE GOING TO HAVE 

5008
03:17:21,657 --> 03:17:22,257
TO GET THOSE OTHER MODALITIES 

5009
03:17:22,257 --> 03:17:25,727
OF PROTECTION AND DIAGNOSIS, 

5010
03:17:25,727 --> 03:17:27,296
BOTH CLINICAL OBSERVATION BUT 

5011
03:17:27,296 --> 03:17:27,796
IN A MORE SENSITIVE AND 

5012
03:17:27,796 --> 03:17:28,864
SPECIFIC WAY. BUT ALSO FLUID 

5013
03:17:28,864 --> 03:17:34,503
SAMPLES THAT ARE EASILY 

5014
03:17:34,503 --> 03:17:35,037
ANALYZED WITH AGAIN HIGH 

5015
03:17:35,037 --> 03:17:37,239
SPECIFICITY AND SENSITIVITY. 

5016
03:17:37,239 --> 03:17:40,208
>> THANK YOU. 

5017
03:17:40,208 --> 03:17:45,314
>> MY FINAL CONTRIBUTION, 

5018
03:17:45,314 --> 03:17:52,354
QUESTION OR COMMENT. SLEEP 

5019
03:17:52,354 --> 03:17:56,491
DEFICIT AND OLFACTORY DEFICITS. 

5020
03:17:56,491 --> 03:17:58,860
CURRENTLY MY UNDERSTANDING IS 

5021
03:17:58,860 --> 03:18:00,262
THAT, FOR A PATIENT TO BE 

5022
03:18:00,262 --> 03:18:07,669
REFERRED TO RECEIVE A PET SCAN 

5023
03:18:07,669 --> 03:18:12,240
FOR AMYLOID THEY MUST HAVE GONE 

5024
03:18:12,240 --> 03:18:16,445
THROUGH AN ELEMENTAL EXAM. 

5025
03:18:16,445 --> 03:18:20,048
PROBABLY (INDISCERNIBLE) WHEN 

5026
03:18:20,048 --> 03:18:20,682
THE PATIENT IS REFERRED TO GET 

5027
03:18:20,682 --> 03:18:23,485
A PET SCAN. 

5028
03:18:23,485 --> 03:18:32,594
IS THAT CORRECT?

5029
03:18:32,594 --> 03:18:33,161
IT IS ALSO NOW COMMON IN THIS 

5030
03:18:33,161 --> 03:18:36,398
SMALL ANIMAL MODELS, THAT SLEEP 

5031
03:18:36,398 --> 03:18:40,235
DEFICIT AND OLFACTORY DEFICIT 

5032
03:18:40,235 --> 03:18:48,677
... THEY MAY COME REALLY EARLY 

5033
03:18:48,677 --> 03:18:50,645
WHEN THE DISEASE IS IN THE 

5034
03:18:50,645 --> 03:18:51,213
EARLY STAGES BEFORE IT GETS 

5035
03:18:51,213 --> 03:18:56,418
INTO THE COGNITIVE IMPAIRMENT. 

5036
03:18:56,418 --> 03:18:56,818
AND THERE ARE BIG 

5037
03:18:56,818 --> 03:19:03,592
CONSIDERATIONS IN THIS 

5038
03:19:03,592 --> 03:19:04,593
COMMITTEE, THINKING ABOUT MAYBE 

5039
03:19:04,593 --> 03:19:05,160
RANKING, PUTTING THE SLEEP 

5040
03:19:05,160 --> 03:19:06,094
DISORDERS COMMITTEE, OLFACTORY 

5041
03:19:06,094 --> 03:19:13,502
DEFICITS AS APPOINTED WE SHOULD 

5042
03:19:13,502 --> 03:19:14,469
RAISE FOR AN INDIVIDUAL TO GET 

5043
03:19:14,469 --> 03:19:21,042
A PET SCAN. ACCOMPANIED BY THE 

5044
03:19:21,042 --> 03:19:22,677
(INDISCERNIBLE) BIOMARKERS, AND 

5045
03:19:22,677 --> 03:19:23,879
WE HAVE A COMBINATION OF 

5046
03:19:23,879 --> 03:19:31,153
(INDISCERNIBLE) BIOMARKERS IN 

5047
03:19:31,153 --> 03:19:34,356
ANY OF THESE DEFICITS. 

5048
03:19:34,356 --> 03:19:34,890
IS THERE A POINT WHERE YOU 

5049
03:19:34,890 --> 03:19:37,492
START THINKING ABOUT A PET SCAN?

5050
03:19:37,492 --> 03:19:38,026
>> ALICE IT LOOKS LIKE YOU

5051
03:19:38,026 --> 03:19:39,060
MIGHT HAVE A THOUGHT. 

5052
03:19:39,060 --> 03:19:44,232
>> I WANTED TO ADDRESS
WHAT IAN 

5053
03:19:44,232 --> 03:19:44,866
SAID PREVIOUS TO THIS ALSO WHAT 

5054
03:19:44,866 --> 03:19:47,402
ERIC SAID RIGHT NOW. 

5055
03:19:47,402 --> 03:19:52,941
AND SO TO THE FIRST COMMENT, I 

5056
03:19:52,941 --> 03:19:56,244
THINK THAT WE HAVE TO REMEMBER 

5057
03:19:56,244 --> 03:19:58,113
THAT AT THIS MOMENT FOR THESE 

5058
03:19:58,113 --> 03:20:00,248
DISORDERS WE HAVE MINIMAL 

5059
03:20:00,248 --> 03:20:01,016
DISEASE MODIFYING THERAPIES. SO 

5060
03:20:01,016 --> 03:20:03,618
WHAT WE ARE TRYING TO DO RIGHT 

5061
03:20:03,618 --> 03:20:05,520
NOW IS NOT ONLY KIND OF DEVELOP 

5062
03:20:05,520 --> 03:20:08,023
DIAGNOSTICS BUT ALSO TRYING TO 

5063
03:20:08,023 --> 03:20:10,158
ENABLE TRIALS THAT WOULD THEN 

5064
03:20:10,158 --> 03:20:10,692
ENABLE DISEASE MODIFYING 

5065
03:20:10,692 --> 03:20:11,827
THERAPIES TO BE DEVELOPED. 

5066
03:20:11,827 --> 03:20:12,861
IF YOU THINK ABOUT THE HISTORY 

5067
03:20:12,861 --> 03:20:17,866
OF ALZHEIMER'S DISEASE, WITHOUT 

5068
03:20:17,866 --> 03:20:23,271
THE BASIC AMYLOID DIES, JOE 

5069
03:20:23,271 --> 03:20:23,839
STRAUSS WOULD NOT HAVE BEEN 

5070
03:20:23,839 --> 03:20:27,375
ABLE TO GO THE WAY THEY DID. I 

5071
03:20:27,375 --> 03:20:31,313
AM NOT ORDERING AMYLOID STAINS 

5072
03:20:31,313 --> 03:20:32,414
ON MY PATIENTS AND SO THERE ARE 

5073
03:20:32,414 --> 03:20:33,715
THINGS THAT ENABLE TRIALS SO WE 

5074
03:20:33,715 --> 03:20:34,316
CAN DEVELOP THERAPIES AND WE 

5075
03:20:34,316 --> 03:20:36,051
HAVE TO WORK ON THOSE. BECAUSE 

5076
03:20:36,051 --> 03:20:36,718
WE DON'T HAVE THERAPIES AND AT 

5077
03:20:36,718 --> 03:20:38,753
THE SAME TIME WE HAVE TO THINK 

5078
03:20:38,753 --> 03:20:39,354
ABOUT HOW WE TRANSLATE THESE 

5079
03:20:39,354 --> 03:20:42,591
BIOMARKERS IN ALZHEIMER'S, FOR 

5080
03:20:42,591 --> 03:20:53,101
THE CSF, TAU AND AB MARKERS.  

5081
03:20:53,502 --> 03:20:53,935
THAT GIVES US A LITTLE 

5082
03:20:53,935 --> 03:20:54,569
BLUEPRINT FOR HOW TO DEAL WITH 

5083
03:20:54,569 --> 03:20:57,339
OTHER DISEASES. 

5084
03:20:57,339 --> 03:20:59,808
AND WITH RESPECT TO ERIC'S 

5085
03:20:59,808 --> 03:21:03,578
QUESTION, THIS IS THE MOST 

5086
03:21:03,578 --> 03:21:04,179
RELEVANT, OLFACTORY AND SLEEP 

5087
03:21:04,179 --> 03:21:09,885
DEFICIT FOR THE BODY DISORDERS. 

5088
03:21:09,885 --> 03:21:14,055
YOU BOTH HYPOSMIA ARE AT 

5089
03:21:14,055 --> 03:21:16,925
INCREASED RISK FOR LEVY BODY 

5090
03:21:16,925 --> 03:21:18,960
DEMENTIA DISORDERS AND PEOPLE 

5091
03:21:18,960 --> 03:21:20,095
WITH (INDISCERNIBLE) AND I 

5092
03:21:20,095 --> 03:21:22,998
WOULD SAY THAT I KNOW THAT WHEN 

5093
03:21:22,998 --> 03:21:26,701
DR. TOLEDO  SPELL BEFORE HE 

5094
03:21:26,701 --> 03:21:33,508
TALKED ABOUT THE COHORT, THERE 

5095
03:21:33,508 --> 03:21:34,109
IS THAT COHORT OF PEOPLE WITH 

5096
03:21:34,109 --> 03:21:34,709
SLEEP DISORDERS. AND MANY OF 

5097
03:21:34,709 --> 03:21:35,243
THE OTHER COHORTS WE TALK 

5098
03:21:35,243 --> 03:21:44,052
ABOUT, PPMI COHORT AND 

5099
03:21:44,052 --> 03:21:44,686
PARKINSON'S PROGRESSION MARKER 

5100
03:21:44,686 --> 03:21:45,186
INITIATIVE COHORT, THEY 

5101
03:21:45,186 --> 03:21:46,821
INCORPORATE HYPOSMIA, OLFACTORY 

5102
03:21:46,821 --> 03:21:50,158
TESTING. 

5103
03:21:50,158 --> 03:21:50,759
I WANTED TO REASSURE YOU, THAT 

5104
03:21:50,759 --> 03:21:55,564
IS NOT BEING MISSED RIGHT NOW. 

5105
03:21:55,564 --> 03:21:56,131
>> THANK YOU SO MUCH ERIC
FOR 

5106
03:21:56,131 --> 03:21:56,965
THOSE POINTS. 

5107
03:21:56,965 --> 03:21:58,433
I'M GOING TO TURN IT OVER TO 

5108
03:21:58,433 --> 03:22:08,810
DALE DINA (PHONETIC). 

5109
03:22:25,460 --> 03:22:28,964
WE CAN HEAR YOU JUST YET. 

5110
03:22:28,964 --> 03:22:29,531
>> GIVE IT A TRY AGAIN
WITH 

5111
03:22:29,531 --> 03:22:31,099
STAR SIX. 

5112
03:22:31,099 --> 03:22:34,903
>> HOW IS THAT?

5113
03:22:34,903 --> 03:22:36,905
>> PERFECT WE CAN HEAR
YOU. 

5114
03:22:36,905 --> 03:22:41,209
>> GOOD. FIRST I WANT TO
HAND 

5115
03:22:41,209 --> 03:22:41,776
OUT A BEAUTIFUL BOUQUET OF 

5116
03:22:41,776 --> 03:22:46,147
FLOWERS TO EACH OF YOU. FROM 

5117
03:22:46,147 --> 03:22:46,581
WAY... I HAVE BEEN 

5118
03:22:46,581 --> 03:22:47,782
PARTICIPATING IN THESE PROGRAMS 

5119
03:22:47,782 --> 03:22:50,118
NOW FIVE OR SIX YEARS AND I 

5120
03:22:50,118 --> 03:23:00,662
WOULD LIKE TO SAY THAT AND THE 

5121
03:23:01,529 --> 03:23:03,732
EVOLUTION OF THESE SESSIONS HAS 

5122
03:23:03,732 --> 03:23:04,733
BEEN SPECTACULAR.

5123
03:23:04,733 --> 03:23:05,300
ONE OF THE FIRST SESSIONS AND 

5124
03:23:05,300 --> 03:23:08,236
SO FORTH WAS DIFFICULTY FROM 

5125
03:23:08,236 --> 03:23:11,473
UNIVERSITY RESEARCH TO ANOTHER 

5126
03:23:11,473 --> 03:23:12,007
UNIVERSITY RESEARCH, THE 

5127
03:23:12,007 --> 03:23:12,574
VERNACULAR WAS FOR THE SAME 

5128
03:23:12,574 --> 03:23:14,743
THING VERY DIFFERENT. 

5129
03:23:14,743 --> 03:23:15,310
AND SO THE DIFFICULTY REALLY 

5130
03:23:15,310 --> 03:23:24,953
UNDERSTANDING ONE ANOTHER, LET 

5131
03:23:24,953 --> 03:23:25,553
ALONE A GUY LIKE ME OFF THE 

5132
03:23:25,553 --> 03:23:28,957
STREET. 

5133
03:23:28,957 --> 03:23:32,627
EARLY ON THIS IS A COMMITTEE TO 

5134
03:23:32,627 --> 03:23:33,261
STANDARDIZE THE VERNACULAR. AND 

5135
03:23:33,261 --> 03:23:33,895
THAT HAS BEEN DONE AND WE DON'T 

5136
03:23:33,895 --> 03:23:35,563
EVEN HAVE TO THINK ABOUT IT 

5137
03:23:35,563 --> 03:23:36,297
ANYMORE. OR EARLY START IS WHAT 

5138
03:23:36,297 --> 03:23:38,733
IT APPEARS LIKE TO ME. 

5139
03:23:38,733 --> 03:23:39,968
ALSO THE PROCEDURE OF SETTING 

5140
03:23:39,968 --> 03:23:45,473
UP GOALS AND STUFF FOR 

5141
03:23:45,473 --> 03:23:46,074
ACCOMPLISHING THOSE GOALS AND 

5142
03:23:46,074 --> 03:23:48,410
SO FORTH, THAT WAS AN EVOLUTION 

5143
03:23:48,410 --> 03:23:57,852
FROM WAY BACK THEN. JUSTICE 

5144
03:23:57,852 --> 03:23:58,486
PARTICULAR PROCESS AND LOOK AT 

5145
03:23:58,486 --> 03:23:59,087
IT NOW EACH OF YOU HAS AT ANY 

5146
03:23:59,087 --> 03:24:00,689
TO STANDARDIZE AND IN A WAY 

5147
03:24:00,689 --> 03:24:07,162
THAT I IS A SPECTACULAR.

5148
03:24:07,162 --> 03:24:12,033
NOW BACK IN 2000 WE HAD A GOAL. 

5149
03:24:12,033 --> 03:24:12,667
NIH SAID THAT WITHIN FIVE YEARS 

5150
03:24:12,667 --> 03:24:17,505
WE WOULD HAVE CURED ONE OF THE 

5151
03:24:17,505 --> 03:24:19,340
DEMENTIAS. WELL WE HAVEN'T, BUT 

5152
03:24:19,340 --> 03:24:21,609
WE ARE WORKING ON IT. 

5153
03:24:21,609 --> 03:24:22,177
THE FIRST PART OF MY QUESTION 

5154
03:24:22,177 --> 03:24:25,714
IS,  WHICH ONE OF THE DEMENTIAS 

5155
03:24:25,714 --> 03:24:31,186
IS THE BEST CANDIDATE IN YOUR 

5156
03:24:31,186 --> 03:24:31,519
VIEW?

5157
03:24:31,519 --> 03:24:34,689
MY FIRST QUESTION.

5158
03:24:34,689 --> 03:24:37,092
>> I LOVE THAT QUESTION. 
WHO 

5159
03:24:37,092 --> 03:24:39,294
WANTS TO TAKE IT?

5160
03:24:39,294 --> 03:24:44,799
>> WELL, IT'S...IT MIGHT
NOT BE 

5161
03:24:44,799 --> 03:24:52,607
ANSWERABLE. 

5162
03:24:52,607 --> 03:24:53,141
>> NOT SURE HE IS HERE, HE

5163
03:24:53,141 --> 03:24:53,742
MIGHT HAVE A GOOD ANSWER BUT 

5164
03:24:53,742 --> 03:24:54,843
WHO CAN SPEAK TO THIS IMPORTANT 

5165
03:24:54,843 --> 03:24:55,243
QUESTION?

5166
03:24:55,243 --> 03:24:58,513
>> CONSTANTINO MIGHT. I
SEE HIM 

5167
03:24:58,513 --> 03:25:03,551
SMILING AND SHAKING HIS HEAD. 

5168
03:25:03,551 --> 03:25:04,119
>> EVERYONE ON THE CALL
WANTS 

5169
03:25:04,119 --> 03:25:05,153
TO ANSWER. 

5170
03:25:05,153 --> 03:25:09,424
GREAT PINT. 

5171
03:25:09,424 --> 03:25:13,461
>> DR. IADECOLA: WE CAN
GIVE 

5172
03:25:13,461 --> 03:25:15,864
YOU OUR TAKE OUR PERSONAL...

5173
03:25:15,864 --> 03:25:16,765
>> I AM INTERESTED IN
YOURS. 

5174
03:25:16,765 --> 03:25:20,301
>> DR. IADECOLA: I THINK
THE 

5175
03:25:20,301 --> 03:25:24,405
MAJOR ADVANCE THAT YOU HAVE 

5176
03:25:24,405 --> 03:25:25,473
SEEN TODAY, AND WE HOPE THAT 

5177
03:25:25,473 --> 03:25:29,177
THIS IS GOING GO BACK TO THE 

5178
03:25:29,177 --> 03:25:29,811
OVERALL MEDICAL COMMUNITY WHICH 

5179
03:25:29,811 --> 03:25:30,845
IS NOT THE CASE IS THAT 

5180
03:25:30,845 --> 03:25:34,315
DEMENTIA OF AGE IS NOT REALLY 

5181
03:25:34,315 --> 03:25:38,486
ONE DISEASE. 

5182
03:25:38,486 --> 03:25:39,454
SO IF WE WERE ABLE TO GET THE 

5183
03:25:39,454 --> 03:25:44,492
GENERAL PRACTITIONERS AND 

5184
03:25:44,492 --> 03:25:45,126
NEUROLOGISTS AND EVERYBODY ELSE 

5185
03:25:45,126 --> 03:25:46,327
TO UNDERSTAND THAT, THAT WILL 

5186
03:25:46,327 --> 03:25:48,696
BE A GREAT SUCCESS. 

5187
03:25:48,696 --> 03:25:52,000
BECAUSE WE KNOW HOW TO PREVENT 

5188
03:25:52,000 --> 03:25:52,534
AND PARTIALLY TREAT SOME 

5189
03:25:52,534 --> 03:25:54,402
ASPECTS OF THIS DEMENTIA 

5190
03:25:54,402 --> 03:25:55,203
PROCESS. 

5191
03:25:55,203 --> 03:25:57,472
FOR EXAMPLE THE  VASCULAR 

5192
03:25:57,472 --> 03:26:03,378
PROCESS.  WE HAVE MADE 

5193
03:26:03,378 --> 03:26:04,412
TREMENDOUS PROGRESS IN 

5194
03:26:04,412 --> 03:26:06,548
TREATING, AND PREVENTING 

5195
03:26:06,548 --> 03:26:07,081
STROKES FOR EXAMPLE. THE 

5196
03:26:07,081 --> 03:26:10,185
MORTALITY FOR STROKE SINCE THE 

5197
03:26:10,185 --> 03:26:11,619
1960S IS REDUCED BY 60%. 

5198
03:26:11,619 --> 03:26:14,289
BUT WHEN IT COMES TO DEMENTIA, 

5199
03:26:14,289 --> 03:26:15,757
IT IS A LITTLE BIT MORE 

5200
03:26:15,757 --> 03:26:17,725
COMPLICATED. WHY?

5201
03:26:17,725 --> 03:26:20,795
BECAUSE THERE ARE MULTIPLE 

5202
03:26:20,795 --> 03:26:21,663
THINGS GOING ON. AND SO I THINK 

5203
03:26:21,663 --> 03:26:22,263
IT IS NOT GOOD TO BE A SILVER 

5204
03:26:22,263 --> 03:26:24,365
BULLET THAT EVERYBODY LIKES. 

5205
03:26:24,365 --> 03:26:25,200
ALL RIGHT?

5206
03:26:25,200 --> 03:26:30,104
IF YOU WANT TO PUBLISH IN 

5207
03:26:30,104 --> 03:26:32,307
NATURE, YOU HAVE TO PROPOSED A 

5208
03:26:32,307 --> 03:26:32,907
SINGLE BULLET. BUT LIFE DOES 

5209
03:26:32,907 --> 03:26:38,513
NOT WORK LET WAY. 

5210
03:26:38,513 --> 03:26:40,014
I THINK THAT IT IS GOING TO BE 

5211
03:26:40,014 --> 03:26:42,483
A COMBINATION OF PREVENTION, 

5212
03:26:42,483 --> 03:26:45,553
VASO PROTECTIVE APPROACHES LIKE 

5213
03:26:45,553 --> 03:26:53,695
STATINS AND GOP'S WHATEVER YOU 

5214
03:26:53,695 --> 03:26:56,764
WANT. MAYBE AMYLOID IN ONE 

5215
03:26:56,764 --> 03:26:58,499
CASE, TAU AND OTHERS. AND THAT 

5216
03:26:58,499 --> 03:26:59,367
IS WHY WE ARE STRUGGLING SO 

5217
03:26:59,367 --> 03:27:07,108
MUCH WITH THESE BIOMARKERS. 

5218
03:27:07,108 --> 03:27:08,576
WE KNOW FOR EXAMPLE HOW TO 

5219
03:27:08,576 --> 03:27:09,143
DECREASE AMYLOID LEVELS NOT 

5220
03:27:09,143 --> 03:27:16,084
SPECTACULAR. WHY?

5221
03:27:16,084 --> 03:27:16,618
BECAUSE OF THE FIVE OR SIX 

5222
03:27:16,618 --> 03:27:17,252
THINGS GOING ON THAT WE ARE NOT 

5223
03:27:17,252 --> 03:27:17,886
ABLE TO ADDRESS SO MY ANSWER IS 

5224
03:27:17,886 --> 03:27:19,387
A COMBINATION APPROACH, AND 

5225
03:27:19,387 --> 03:27:20,255
PREVENTION BEING ONE OF THEM. 

5226
03:27:20,255 --> 03:27:23,324
AND VASO PROTECTION IS ONE OF 

5227
03:27:23,324 --> 03:27:25,894
THE MAJOR FEATURES. 

5228
03:27:25,894 --> 03:27:26,361
>> THANK YOU VERY MUCH 

5229
03:27:26,361 --> 03:27:32,233
CONSTANTINO.  THAT IS EASY FOR 

5230
03:27:32,233 --> 03:27:35,503
ME TO FOLLOW. AND THE 

5231
03:27:35,503 --> 03:27:39,707
VERNACULAR FOR ME, FOR EACH 

5232
03:27:39,707 --> 03:27:40,208
INDIVIDUAL, FOR ALL THE 

5233
03:27:40,208 --> 03:27:40,775
DIFFERENT VARIETIES AND SO 

5234
03:27:40,775 --> 03:27:41,943
FORTH AND DIFFERENT MIXES OF 

5235
03:27:41,943 --> 03:27:46,481
THOSE VARIETIES ALMOST HAVE TO 

5236
03:27:46,481 --> 03:27:48,216
WHIP UP A COCKTAIL FOR EACH ONE 

5237
03:27:48,216 --> 03:27:51,619
OF PEOPLE THAT HAS A PROBLEM. 

5238
03:27:51,619 --> 03:27:52,253
BALANCING IN SUCH A WAY THAT IT 

5239
03:27:52,253 --> 03:27:53,488
WILL TREAT EACH ONE OF THOSE 

5240
03:27:53,488 --> 03:27:56,624
PIECES.  I KNOW THAT IS A BIG, 

5241
03:27:56,624 --> 03:28:00,662
TALL ORDER. 

5242
03:28:00,662 --> 03:28:06,834
I KNOW YOU GUYS ARE WORKING ON 

5243
03:28:06,834 --> 03:28:07,435
IT. AND IS ONE MEMBER OF THE 

5244
03:28:07,435 --> 03:28:08,002
PUBLIC ARE JUST WANT TO SAY 

5245
03:28:08,002 --> 03:28:10,805
THANK YOU VERY MUCH. 

5246
03:28:10,805 --> 03:28:16,344
BACK WHEN WE STARTED, WE HAD 

5247
03:28:16,344 --> 03:28:19,347
THE TECHNOLOGICAL PEOPLE 

5248
03:28:19,347 --> 03:28:19,914
TALKING, ONCE THEY GOT THE 

5249
03:28:19,914 --> 03:28:24,285
NOMENCLATURE STANDARDIZED. 

5250
03:28:24,285 --> 03:28:24,886
BUT THERE WAS LITTLE MENTION OF 

5251
03:28:24,886 --> 03:28:33,061
THE CAREGIVER. AND THE 

5252
03:28:33,061 --> 03:28:33,695
TECHNOLOGICAL DISCUSSION AND SO 

5253
03:28:33,695 --> 03:28:34,162
FORTH WAS AMONGST THE 

5254
03:28:34,162 --> 03:28:36,631
RESEARCHERS WHO DO THAT WORK.  

5255
03:28:36,631 --> 03:28:45,173
AND, YOU'VE GOT A WAY  OF 

5256
03:28:45,173 --> 03:28:45,807
COMMUNICATING WITH ONE ANOTHER. 

5257
03:28:45,807 --> 03:28:50,745
LATIN, GREEK AND SO FORTH. THE 

5258
03:28:50,745 --> 03:28:51,379
COMMON GUY OFF THE STREET DOES 

5259
03:28:51,379 --> 03:28:59,087
NOT UNDERSTAND. 

5260
03:28:59,087 --> 03:29:01,456
YOU HAVE TRIED TO...I REALLY 

5261
03:29:01,456 --> 03:29:03,691
APPRECIATE YOU HAVE MADE THE 

5262
03:29:03,691 --> 03:29:04,292
EFFORT IN A VERY GOOD ONE TO 

5263
03:29:04,292 --> 03:29:05,059
RESOLVE THAT SO GUYS LIKE ME 

5264
03:29:05,059 --> 03:29:13,034
CAN UNDERSTAND WHAT IT IS. WE 

5265
03:29:13,034 --> 03:29:13,634
ARE ALL SPEAKING ENGLISH BUT 

5266
03:29:13,634 --> 03:29:14,202
THEN THERE'S ALL DIFFERENT 

5267
03:29:14,202 --> 03:29:16,537
KINDS OF ENGLISH. 

5268
03:29:16,537 --> 03:29:17,238
I WOULD LIKE TO SAY A QUESTION 

5269
03:29:17,238 --> 03:29:21,476
ON THE NEURON WALL.  I JUST 

5270
03:29:21,476 --> 03:29:22,010
LEARNED FROM MY PREVIOUS 

5271
03:29:22,010 --> 03:29:28,249
QUESTION THAT TAU MIGHT MIGRATE 

5272
03:29:28,249 --> 03:29:32,320
SOMEWHERE IN AND OUT OF THE 

5273
03:29:32,320 --> 03:29:32,754
NEURON.

5274
03:29:32,754 --> 03:29:35,757
HOW DOES IT DO THAT?

5275
03:29:35,757 --> 03:29:36,324
IS THE NEURON WALL SEMI 

5276
03:29:36,324 --> 03:29:44,132
PERMEABLE?

5277
03:29:44,132 --> 03:29:46,567
>> WHO WOULD LIKE TO TAKE?

5278
03:29:46,567 --> 03:29:49,437
>> I CAN TAKE IT IF YOU
WANT. 

5279
03:29:49,437 --> 03:29:49,971
>> THANK YOU THAT WILL BE 

5280
03:29:49,971 --> 03:29:52,040
WONDERFUL. 

5281
03:29:52,040 --> 03:29:52,640
>> SO THERE ARE MANY
MECHANISMS 

5282
03:29:52,640 --> 03:29:55,610
BY WHICH TAU CAN MIGRATE FROM 

5283
03:29:55,610 --> 03:30:03,551
ONE CELL TO THE OTHER.  SOME OF 

5284
03:30:03,551 --> 03:30:04,118
THEM INVOLVE FORMING LITTLE 

5285
03:30:04,118 --> 03:30:04,719
VESICLES IN THE CELL MEMBRANE 

5286
03:30:04,719 --> 03:30:05,653
AND THESE LITTLE VESICLES THEY 

5287
03:30:05,653 --> 03:30:15,763
PUT TAU OUTSIDE OF THE CELL 

5288
03:30:15,763 --> 03:30:16,330
MEMBRANE. AND THE NEXT CELL 

5289
03:30:16,330 --> 03:30:16,864
PICKED IT UP IN A LITTLE 

5290
03:30:16,864 --> 03:30:19,500
VESICLE AND INCLUDED IN ITSELF.

5291
03:30:19,500 --> 03:30:20,101
THERE ARE ALSO RECEPTORS IN THE 

5292
03:30:20,101 --> 03:30:20,902
NEURAL MECHANISM. THERE ARE 

5293
03:30:20,902 --> 03:30:25,673
SOME RECEPTORS THAT CAN 

5294
03:30:25,673 --> 03:30:26,240
RECOGNIZE TAU, USUALLY NOT 

5295
03:30:26,240 --> 03:30:31,145
SPECIFICALLY TAU BUT THEY CAN 

5296
03:30:31,145 --> 03:30:31,779
RECOGNIZE TAU AND BRING IT INTO 

5297
03:30:31,779 --> 03:30:34,582
THE OTHER CELL. 

5298
03:30:34,582 --> 03:30:36,551
SO THERE ARE MANY MECHANISMS 

5299
03:30:36,551 --> 03:30:39,287
THAT COORDINATE THIS 

5300
03:30:39,287 --> 03:30:39,921
TRANSMISSION AND IS INTERESTING 

5301
03:30:39,921 --> 03:30:40,555
BECAUSE NOW WE SEE THAT TAU IS 

5302
03:30:40,555 --> 03:30:44,225
ALSO NOT JUST INSIDE THE NEURON 

5303
03:30:44,225 --> 03:30:54,602
BUT ALSO OUTSIDE THE 

5304
03:30:56,671 --> 03:30:57,138
VASCULATURE, LIKE IN THE 

5305
03:30:57,138 --> 03:30:57,772
ENDOTHELIAL CELLS. SO THERE'S A 

5306
03:30:57,772 --> 03:30:58,372
LOT OF PROGRESS IN THAT FIELD 

5307
03:30:58,372 --> 03:31:02,076
RIGHT NOW. 

5308
03:31:02,076 --> 03:31:03,644
>> SO YOU THINK ABOUT IT
LIKE 

5309
03:31:03,644 --> 03:31:07,915
FOOTBALL, THEY CAN PICK TAU, 

5310
03:31:07,915 --> 03:31:08,449
ENDED HAND IT OFF WANT TO 

5311
03:31:08,449 --> 03:31:11,486
ANOTHER IN A WAY. 

5312
03:31:11,486 --> 03:31:16,290
>> THAT IS HOW TAU IS
SPREAD IN 

5313
03:31:16,290 --> 03:31:16,924
THE BRAIN FROM ONE AREA TO THE 

5314
03:31:16,924 --> 03:31:18,392
OTHER. 

5315
03:31:18,392 --> 03:31:21,596
>> MY LAST COMMENT. 

5316
03:31:21,596 --> 03:31:22,563
YOU FOLKS ARE PROBABLY FAMILIAR 

5317
03:31:22,563 --> 03:31:29,670
WITH THE KIPLINGER LETTER WHICH 

5318
03:31:29,670 --> 03:31:30,771
COMES TO YOUR MAIL BOX EVERY 

5319
03:31:30,771 --> 03:31:31,105
WEEK.

5320
03:31:31,105 --> 03:31:36,310
THIS WEEK IT SAYS AI HAS 

5321
03:31:36,310 --> 03:31:41,482
UNCOVERED 200 MILLION PROTEIN 

5322
03:31:41,482 --> 03:31:44,519
STRUCTURES, FAR MORE THAN THE 

5323
03:31:44,519 --> 03:31:45,153
200,000 THAT WERE KNOWN IN THE 

5324
03:31:45,153 --> 03:31:47,555
YEAR 2020. RESEARCHERS AT 

5325
03:31:47,555 --> 03:31:48,189
STANFORD HAVE CREATED A VIRTUAL 

5326
03:31:48,189 --> 03:31:56,998
LAB WITH AI MODELS TRAINED ON 

5327
03:31:56,998 --> 03:31:57,598
SPECIFIC MEDICAL KNOWLEDGE TO 

5328
03:31:57,598 --> 03:32:02,670
COORDINATE NEW DRUGS. 

5329
03:32:02,670 --> 03:32:03,237
WELL, WHAT DO YOU KNOW ABOUT 

5330
03:32:03,237 --> 03:32:07,742
THAT?

5331
03:32:07,742 --> 03:32:08,342
IS THIS A COMMON KIND OF THING 

5332
03:32:08,342 --> 03:32:11,112
OF USING AI?

5333
03:32:11,112 --> 03:32:11,712
IS IT DEPENDABLE ENOUGH FOR YOU 

5334
03:32:11,712 --> 03:32:14,515
TO WORK WITH?

5335
03:32:14,515 --> 03:32:15,116
BECAUSE I KNOW IT CAN GIVE YOU 

5336
03:32:15,116 --> 03:32:18,553
MISLEADING ANSWERS. 

5337
03:32:18,553 --> 03:32:20,321
IS A TOOL THAT YOU ARE USING?

5338
03:32:20,321 --> 03:32:26,160
I GUESS THAT IS THE QUESTION. 

5339
03:32:26,160 --> 03:32:31,732
>> THANK YOU.  I THINK
THIS IS 

5340
03:32:31,732 --> 03:32:32,366
A CROSSCUTTING THEME. I MANY OF 

5341
03:32:32,366 --> 03:32:33,000
US ACROSS ALL OF THE COMMITTEES 

5342
03:32:33,000 --> 03:32:35,770
ARE THINKING ABOUT HOW TO USE 

5343
03:32:35,770 --> 03:32:36,504
AI TO ADVANCE OUR SCIENTIFIC 

5344
03:32:36,504 --> 03:32:40,841
WORK.  AND SO WE ARE GOING TO 

5345
03:32:40,841 --> 03:32:41,475
NOTE THIS AND DISCUSS THIS WHEN 

5346
03:32:41,475 --> 03:32:42,877
WE COME TOGETHER. 

5347
03:32:42,877 --> 03:32:47,215
>> OKAY. 

5348
03:32:47,215 --> 03:32:47,782
>> THANK YOU AND GOING TO
TRY 

5349
03:32:47,782 --> 03:32:48,382
TO MOVE ON BECAUSE WE HAVE A 

5350
03:32:48,382 --> 03:32:50,184
FEW OTHER HANDS RAISED IN ONLY 

5351
03:32:50,184 --> 03:32:50,818
FIVE MORE MINUTES LEFT FOR THE 

5352
03:32:50,818 --> 03:32:52,019
DISCUSSION. 

5353
03:32:52,019 --> 03:32:52,553
THANK YOU SO MUCH FOR THOSE 

5354
03:32:52,553 --> 03:32:58,025
POINTS. 

5355
03:32:58,025 --> 03:32:58,593
I'M GOING TO GO TO STEPHEN -- 

5356
03:32:58,593 --> 03:33:00,828
WHO IS THE NEXT PERSON. 

5357
03:33:00,828 --> 03:33:03,664
>> THANKS CAN YOU HEAR ME
ALL 

5358
03:33:03,664 --> 03:33:05,266
RIGHT?

5359
03:33:05,266 --> 03:33:05,866
YESTERDAY I ASKED THE QUESTION 

5360
03:33:05,866 --> 03:33:07,468
ABOUT DRUG DELIVERY TO THE 

5361
03:33:07,468 --> 03:33:08,269
BRAIN WHICH IS KNOWN TO BE A 

5362
03:33:08,269 --> 03:33:08,869
MAJOR BARRIER TO TREATING ALL 

5363
03:33:08,869 --> 03:33:12,907
OF THE DEMENTIAS TALK ABOUT 

5364
03:33:12,907 --> 03:33:13,574
TODAY AND YESTERDAY AND I GOT 

5365
03:33:13,574 --> 03:33:14,141
AN ANSWER ABOUT ENDOTHELIAL 

5366
03:33:14,141 --> 03:33:22,083
CELLS, ETC., BEING INCLUDED  IN 

5367
03:33:22,083 --> 03:33:22,650
SOME OF THESE STUDIES AS A 

5368
03:33:22,650 --> 03:33:23,184
POTENTIAL DRIVER FOR THE 

5369
03:33:23,184 --> 03:33:23,818
DISEASE AND THOSE EXPERIMENTERS 

5370
03:33:23,818 --> 03:33:24,518
ARE DISTINCT FROM THOSE THAT 

5371
03:33:24,518 --> 03:33:25,086
REVEAL HOW TRANSPORT WORKS 

5372
03:33:25,086 --> 03:33:27,455
ACROSS THE BLOOD BRAIN BARRIER 

5373
03:33:27,455 --> 03:33:27,955
IN DIFFERENT CONTEXTS, 

5374
03:33:27,955 --> 03:33:29,457
INCLUDING A HEALTHY CONTEXT. 

5375
03:33:29,457 --> 03:33:36,631
PREVENTING DEMENTIA AND HOW TO 

5376
03:33:36,631 --> 03:33:37,231
POTENTIALLY LEVERAGE THAT FOR 

5377
03:33:37,231 --> 03:33:37,865
DRUG DELIVERY WHICH MAY HAVE A 

5378
03:33:37,865 --> 03:33:38,499
LARGE IMPACT ON OUR ABILITY TO 

5379
03:33:38,499 --> 03:33:39,200
TREAT ALL OF THE DISEASES. 

5380
03:33:39,200 --> 03:33:44,405
WHY DON'T THE RECOMMENDATIONS 

5381
03:33:44,405 --> 03:33:44,939
MENTIONED EXPLICITLY THIS 

5382
03:33:44,939 --> 03:33:45,539
EFFORT TO DEVELOP DRUGS THAT 

5383
03:33:45,539 --> 03:33:48,276
CROSS THE BLOOD BRAIN BARRIER 

5384
03:33:48,276 --> 03:33:48,743
MORE EFFICIENTLY AND 

5385
03:33:48,743 --> 03:33:53,414
SELECTIVELY?

5386
03:33:53,414 --> 03:33:58,719
>> WHO CAN TAKE THAT?

5387
03:33:58,719 --> 03:34:02,657
>> I CAN TRY. 

5388
03:34:02,657 --> 03:34:03,257
I MEAN IT IS A VERY IMPORTANT 

5389
03:34:03,257 --> 03:34:06,260
QUESTION.  AND A VERY IMPORTANT 

5390
03:34:06,260 --> 03:34:08,763
ISSUE FOR THE FIELD. 

5391
03:34:08,763 --> 03:34:10,564
FOR PART OF THIS IN ALZHEIMER'S 

5392
03:34:10,564 --> 03:34:17,605
AND OTHER DEMENTIAS IS MADE A 

5393
03:34:17,605 --> 03:34:18,205
LITTLE BIT EASIER BY THE FACT 

5394
03:34:18,205 --> 03:34:18,839
THAT THE BLOOD BARRIER BRAIN IS 

5395
03:34:18,839 --> 03:34:19,407
ALREADY LEAKING IN SOME OF 

5396
03:34:19,407 --> 03:34:22,610
THESE CASES.  SOME OF THE DRUGS 

5397
03:34:22,610 --> 03:34:24,378
CAN PASS A LITTLE BIT BETTER 

5398
03:34:24,378 --> 03:34:26,314
BECAUSE OF THAT, BUT STILL I IT 

5399
03:34:26,314 --> 03:34:27,448
HAS TO BE A QUESTION THAT IS ON 

5400
03:34:27,448 --> 03:34:29,250
THE SPECIFIC CLINICAL TRIAL. 

5401
03:34:29,250 --> 03:34:30,685
AND THE SPECIFIC PRECLINICAL 

5402
03:34:30,685 --> 03:34:35,890
STUDY ON THAT SPECIFIC DRUG. 

5403
03:34:35,890 --> 03:34:36,457
OF COURSE THIS DRUG WILL ONLY 

5404
03:34:36,457 --> 03:34:36,991
WORK IF IT IS A DRUG THAT 

5405
03:34:36,991 --> 03:34:41,162
TARGETS NEURONS, IF IT IS ABLE 

5406
03:34:41,162 --> 03:34:41,662
TO PASS THE BLOOD BRAIN 

5407
03:34:41,662 --> 03:34:43,397
BARRIER. AND SO AT THE 

5408
03:34:43,397 --> 03:34:44,398
TRANSLATIONAL LEVEL, WE HAVE TO 

5409
03:34:44,398 --> 03:34:47,401
BE ABLE TO CREATE DRUGS-- THE 

5410
03:34:47,401 --> 03:34:48,035
SPECIFIC DRUG THAT YOU WANT TO 

5411
03:34:48,035 --> 03:34:48,669
ANALYZE TO MAKE IT A MOLECULE 

5412
03:34:48,669 --> 03:34:49,303
THAT IS ABLE TO PASS THE BLOOD 

5413
03:34:49,303 --> 03:34:51,539
BRAIN BARRIER. AND ONLY IF IT 

5414
03:34:51,539 --> 03:34:55,109
CAN DO THAT, THEN WE CAN MOVE 

5415
03:34:55,109 --> 03:34:55,743
TO THE CLINICAL LEVEL AND STUDY 

5416
03:34:55,743 --> 03:34:56,210
IT IN HUMANS. 

5417
03:34:56,210 --> 03:35:00,781
AND SO I THINK THE NIH IS 

5418
03:35:00,781 --> 03:35:01,415
CREATING SYSTEMS LIKE THAT AND 

5419
03:35:01,415 --> 03:35:02,049
MAYBE WALTER WANT TO TALK ABOUT 

5420
03:35:02,049 --> 03:35:05,753
IT.  BUT THEY ARE KIND OF LIKE 

5421
03:35:05,753 --> 03:35:09,523
MEDIATED BY STEPS. 

5422
03:35:09,523 --> 03:35:13,127
AND WE CAN DO A PRECLINICAL 

5423
03:35:13,127 --> 03:35:13,761
STEP WHEN WE MAKE SURE THE DRUG 

5424
03:35:13,761 --> 03:35:14,295
WILL PASS THE BLOOD BRAIN 

5425
03:35:14,295 --> 03:35:14,929
BARRIER AND THEN WE CAN MOVE ON 

5426
03:35:14,929 --> 03:35:16,364
TO THE CLINICAL STEP. 

5427
03:35:16,364 --> 03:35:19,633
>> THANK YOU FOR THAT
ANSWER. 

5428
03:35:19,633 --> 03:35:21,469
GO AHEAD, PLEASE. 

5429
03:35:21,469 --> 03:35:24,338
>> IF I MAY, THERE IS
ALREADY A 

5430
03:35:24,338 --> 03:35:26,040
LOT OF INTEREST IN DEVELOPING 

5431
03:35:26,040 --> 03:35:36,384
(INDISCERNIBLE). FOR EXAMPLE 

5432
03:35:36,384 --> 03:35:36,951
ROCHE HAS A TRIAL SHOWN TO 

5433
03:35:36,951 --> 03:35:37,585
REDUCE THE AMYLOID YOU HAVE TO 

5434
03:35:37,585 --> 03:35:41,522
HAVE A GOOD DRUG FIRST, AND 

5435
03:35:41,522 --> 03:35:42,156
THEN YOU HAVE TO FIGURE OUT FOR 

5436
03:35:42,156 --> 03:35:44,592
EXAMPLE THE BRAIN SHUTTLE USES 

5437
03:35:44,592 --> 03:35:45,226
A TRANSFERENCE REFLECTOR HIGHLY 

5438
03:35:45,226 --> 03:35:52,400
BROUGHT INTO THE BRAIN. AND 

5439
03:35:52,400 --> 03:35:53,033
THINGS ARE ALREADY ONGOING AND 

5440
03:35:53,033 --> 03:35:53,667
WE NEED THE DRUG AND THEN WILL 

5441
03:35:53,667 --> 03:35:58,839
BE READY TO GO.

5442
03:35:58,839 --> 03:35:59,440
>> I HAVE TO ADD TO THE
POINT. 

5443
03:35:59,440 --> 03:36:03,811
THERE'S A LOT OF EFFORTS GOING 

5444
03:36:03,811 --> 03:36:07,982
UNNECESSARY LISTED AS ADRD OR 

5445
03:36:07,982 --> 03:36:11,685
IRRELEVANT TO ADRD, MECHANISMS 

5446
03:36:11,685 --> 03:36:14,321
DELIVER THINGS TO DIFFERENT 

5447
03:36:14,321 --> 03:36:14,922
TISSUES, SPECIFICITY AND THE 

5448
03:36:14,922 --> 03:36:15,656
BRAIN IS INCLUDED IN SOME OF 

5449
03:36:15,656 --> 03:36:17,958
THOSE CONSORTIUMS. MAY BE ABLE 

5450
03:36:17,958 --> 03:36:20,161
WHOSE IS TO INCLUDE IT IN THE 

5451
03:36:20,161 --> 03:36:20,661
RECOMMENDATIONS TO LOOK 

5452
03:36:20,661 --> 03:36:22,263
OUTWARDS ABOUT HOW THESE DRUGS, 

5453
03:36:22,263 --> 03:36:24,265
THOSE TYPES OF DRUG DELIVERY 

5454
03:36:24,265 --> 03:36:24,865
MECHANISMS-- WE DON'T WANT TO 

5455
03:36:24,865 --> 03:36:28,202
BE REINVENTING ANYTHING. 

5456
03:36:28,202 --> 03:36:32,606
>> THANKS. THAT MAKES A
LOT OF 

5457
03:36:32,606 --> 03:36:36,377
SENSE AND I WILL GENTLY SUGGEST 

5458
03:36:36,377 --> 03:36:37,011
THAT TRANSFERRING RECEPTORS ARE 

5459
03:36:37,011 --> 03:36:40,481
IMPERFECT AND THE EFFICIENCIES 

5460
03:36:40,481 --> 03:36:41,015
WILL BE LOW AND DRUGS ARE 

5461
03:36:41,015 --> 03:36:42,516
GETTING TO OTHER ORGANS AND I 

5462
03:36:42,516 --> 03:36:48,255
WOULD ALSO SAY THAT I WILL BE 

5463
03:36:48,255 --> 03:36:48,889
INTERESTED IN FINDING SOMETHING 

5464
03:36:48,889 --> 03:36:49,790
BETTER THAN TRANSFERRING 

5465
03:36:49,790 --> 03:36:50,424
RECEPTOR  OR ANTIBODY TARGETING 

5466
03:36:50,424 --> 03:36:51,759
IT BEFORE KNOWING WHICH DRUG 

5467
03:36:51,759 --> 03:36:52,359
WAS GOING TO DELIVER. MIGHT 

5468
03:36:52,359 --> 03:36:52,860
EVEN SUGGEST THE DRUGS 

5469
03:36:52,860 --> 03:37:00,968
TARGETING ANY OF THESE 

5470
03:37:00,968 --> 03:37:01,569
DEMENTIAS CAN BE APPENDED TO 

5471
03:37:01,569 --> 03:37:03,304
SUCH A SHUTTLE SO IT CAN BE A 

5472
03:37:03,304 --> 03:37:03,938
GENERAL WITH BROADER CAPABILITY 

5473
03:37:03,938 --> 03:37:05,139
TO ALL OF THESE IMAGES. 

5474
03:37:05,139 --> 03:37:09,910
>> THANK YOU FOR THAT. 

5475
03:37:09,910 --> 03:37:10,511
>> ONE MORE THING
IMPORTANT THE 

5476
03:37:10,511 --> 03:37:11,011
PERIPHERAL IMMUNE CELLS 

5477
03:37:11,011 --> 03:37:15,549
MENTIONED IN MANY OF THESE 

5478
03:37:15,549 --> 03:37:16,183
DEMENTIAS, CELLS ARE MAKING IT 

5479
03:37:16,183 --> 03:37:16,784
INTO THE BRAIN FROM THE BLOOD 

5480
03:37:16,784 --> 03:37:19,487
SYSTEM FROM THE BONE MARROW, 

5481
03:37:19,487 --> 03:37:20,654
SOME ENABLING THOSE CELLS IN 

5482
03:37:20,654 --> 03:37:21,288
ORDER TO PRODUCE WHATEVER MIGHT 

5483
03:37:21,288 --> 03:37:24,058
BE HELPFUL IS ALSO AN AREA THAT 

5484
03:37:24,058 --> 03:37:24,658
IS HUGELY UNDERSTUDIED. IT WE 

5485
03:37:24,658 --> 03:37:25,259
CAN LEVERAGE WHAT IS ALREADY 

5486
03:37:25,259 --> 03:37:25,893
HAPPENING IN THE DISEASE 

5487
03:37:25,893 --> 03:37:30,464
THROUGH IPS TECHNOLOGIES AND 

5488
03:37:30,464 --> 03:37:31,098
GENETICS, THAT IS A HUGE AREA 

5489
03:37:31,098 --> 03:37:34,235
THAT NEEDS TO BE THOUGHT ABOUT. 

5490
03:37:34,235 --> 03:37:36,337
>> SO WE HAVE JUST A
COUPLE OF 

5491
03:37:36,337 --> 03:37:36,971
MINUTES. I WOULD LOVE IT IF WE 

5492
03:37:36,971 --> 03:37:41,375
COULD HEAR FROM HOLLAND MESKER 

5493
03:37:41,375 --> 03:37:42,009
(PHONETIC) AND JULIE SCHNEIDER 

5494
03:37:42,009 --> 03:37:42,610
TO CLOSE IS OUT OF THE PUBLIC 

5495
03:37:42,610 --> 03:37:43,477
COMMENT. 

5496
03:37:43,477 --> 03:37:49,717
SESSION GO AHEAD PLEASE HELEN. 

5497
03:37:49,717 --> 03:37:50,251
>> I WILL KEEP IT BRIEF
AND 

5498
03:37:50,251 --> 03:37:50,784
THERE'S A LOT OF THINGS I 

5499
03:37:50,784 --> 03:37:54,455
WANTED TO GIVE. BUT THAT CAN 

5500
03:37:54,455 --> 03:37:57,958
WAIT. 

5501
03:37:57,958 --> 03:37:58,425
WE LOOK AT A VARIETY OF 

5502
03:37:58,425 --> 03:37:59,026
DISEASES TO DATE AND PUSHING 

5503
03:37:59,026 --> 03:38:02,763
FORWARD PARTICULARLY IN LEVY 

5504
03:38:02,763 --> 03:38:08,569
BODY'S REALM, WE ARE LOOKING AT 

5505
03:38:08,569 --> 03:38:09,169
GENETIC CODES AND LOOKING AT 

5506
03:38:09,169 --> 03:38:12,439
ALMOST EXCLUSIVELY THE HIGH 

5507
03:38:12,439 --> 03:38:15,609
PENETRANCE MUTATIONS, VERSUS 

5508
03:38:15,609 --> 03:38:16,210
ALSO BEING INCLUSIVE OF THOSE 

5509
03:38:16,210 --> 03:38:16,677
VARIANCE WE KNOW OUR 

5510
03:38:16,677 --> 03:38:19,280
CONTRIBUTORY. 

5511
03:38:19,280 --> 03:38:19,847
AND SO I AM WONDERING WHY WE 

5512
03:38:19,847 --> 03:38:23,651
DON'T LOOK TO ACCELERATE THE 

5513
03:38:23,651 --> 03:38:24,251
SCIENCES ACROSS A BROADER 

5514
03:38:24,251 --> 03:38:27,521
SPECTRUM AND ENGAGE A LARGER 

5515
03:38:27,521 --> 03:38:28,088
COHORT. WHY WE AREN'T DOING 

5516
03:38:28,088 --> 03:38:31,759
CONCURRENT STUDIES IN 

5517
03:38:31,759 --> 03:38:32,259
WELL-KNOWN CONTRIBUTORY 

5518
03:38:32,259 --> 03:38:41,835
VARIANTS. 

5519
03:38:41,835 --> 03:38:42,269
>> I OPEN IT UP TO MY 

5520
03:38:42,269 --> 03:38:46,874
COLLEAGUES TO ANSWER. 

5521
03:38:46,874 --> 03:38:47,374
>> I THAT IS STARTING TO 

5522
03:38:47,374 --> 03:38:49,276
HAPPEN, YOU KNOW?

5523
03:38:49,276 --> 03:38:51,145
I YOU ARE ABSOLUTELY RIGHT IN 

5524
03:38:51,145 --> 03:38:56,483
THESE DISEASES BASICALLY THE 

5525
03:38:56,483 --> 03:39:04,725
TARGETED ELEMENT WAS BASED ON 

5526
03:39:04,725 --> 03:39:05,359
THE SIGNATURE NEUROPATHOLOGIES 

5527
03:39:05,359 --> 03:39:07,995
AND THE HIGH PENETRANCE GENETIC 

5528
03:39:07,995 --> 03:39:10,698
MUTATIONS. BUT WE ARE SEEING 

5529
03:39:10,698 --> 03:39:11,131
THAT THEY ARE BEING 

5530
03:39:11,131 --> 03:39:12,266
FUNCTIONALIZED, MEANING THAT IS 

5531
03:39:12,266 --> 03:39:19,006
ONE OF THE -- CERTAINLY THE 

5532
03:39:19,006 --> 03:39:19,406
LBD-- ONE OF THE 

5533
03:39:19,406 --> 03:39:19,907
RECOMMENDATIONS WAS TO 

5534
03:39:19,907 --> 03:39:22,476
FUNCTIONALIZED THESE GENETIC 

5535
03:39:22,476 --> 03:39:24,478
VARIANTS. THE THOUGHT IS WE 

5536
03:39:24,478 --> 03:39:26,413
SHOULD BE KIND OF LIKE USING 

5537
03:39:26,413 --> 03:39:26,981
THAT DATA TO IDENTIFY MORE 

5538
03:39:26,981 --> 03:39:28,415
TARGETS. RIGHT?

5539
03:39:28,415 --> 03:39:32,453
>> THANK YOU. 

5540
03:39:32,453 --> 03:39:36,323
>> JULIE, COULD YOU OFFER
SOME 

5541
03:39:36,323 --> 03:39:39,126
CLOSING COMMENTS?

5542
03:39:39,126 --> 03:39:43,998
>> I ACTUALLY HAD A THANK
YOU. 

5543
03:39:43,998 --> 03:39:44,598
WONDERFUL TO HEAR EVERYBODY, 

5544
03:39:44,598 --> 03:39:46,266
ALL THE DISCUSSION. 

5545
03:39:46,266 --> 03:39:47,901
MINE WAS KIND OF QUICK. MY 

5546
03:39:47,901 --> 03:39:48,535
COMMENT IN QUESTION WAS FOR THE 

5547
03:39:48,535 --> 03:39:56,243
LEVY BODY GROUP, DISCUSSED THAT 

5548
03:39:56,243 --> 03:39:59,580
LEVY BODIES ARE COMMON OF MIXED 

5549
03:39:59,580 --> 03:40:03,250
PATHOLOGY EXHIBITING SPECIFIC 

5550
03:40:03,250 --> 03:40:03,817
CLINICAL SYMPTOMS BUT IN MY 

5551
03:40:03,817 --> 03:40:04,451
VIEW AND I WOULD LIKE TO HEAR 

5552
03:40:04,451 --> 03:40:06,987
THEIR THOUGHTS, WHY NOT OPEN IT 

5553
03:40:06,987 --> 03:40:07,287
UP?

5554
03:40:07,287 --> 03:40:08,455
WE KNOW THAT IN THE GENERAL 

5555
03:40:08,455 --> 03:40:12,226
POPULATION 15-20% OF PEOPLE 

5556
03:40:12,226 --> 03:40:22,736
HAVE LEVY BODIES OR MORE. AND 

5557
03:40:23,671 --> 03:40:24,104
MAY HAVE HALLUCINATION, 

5558
03:40:24,104 --> 03:40:27,408
FLUCTUATIONS, ETC. 

5559
03:40:27,408 --> 03:40:27,941
IT IS A PROBLEM AND I DON'T 

5560
03:40:27,941 --> 03:40:28,542
KNOW IF IT WAS EXACTLY BEING 

5561
03:40:28,542 --> 03:40:36,350
ADDRESSED. 

5562
03:40:36,350 --> 03:40:36,917
>> THANK YOU SO MUCH FOR
THAT 

5563
03:40:36,917 --> 03:40:37,451
COMMENT JULIE, SO WE ARE 

5564
03:40:37,451 --> 03:40:39,053
SPECIFICALLY USING LANGUAGE 

5565
03:40:39,053 --> 03:40:39,620
THAT TALK ABOUT INDIVIDUALS 

5566
03:40:39,620 --> 03:40:43,891
FROM THE PRESENT THEMATIC, 

5567
03:40:43,891 --> 03:40:44,425
NONSPECIFIC SYMPTOMATIC, 

5568
03:40:44,425 --> 03:40:45,025
CLASSICS AND THEMATIC ALL THE 

5569
03:40:45,025 --> 03:40:45,893
WAY THROUGH AUTOPSY IN ORDER TO 

5570
03:40:45,893 --> 03:40:47,928
ADDRESS THAT ISSUE. 

5571
03:40:47,928 --> 03:40:48,495
BECAUSE WE KNOW THAT A LOT OF 

5572
03:40:48,495 --> 03:40:54,001
INDIVIDUALS WILL DEVELOP A LEVY 

5573
03:40:54,001 --> 03:40:54,535
BODY TYPE OF SYNDROME GO 

5574
03:40:54,535 --> 03:40:56,637
THROUGH A VERY NONSPECIFIC TIME 

5575
03:40:56,637 --> 03:40:57,705
FROM WHERE THEY DON'T HAVE 

5576
03:40:57,705 --> 03:40:58,338
THOSE CLASSIC SYMPTOMS. WE ALSO 

5577
03:40:58,338 --> 03:41:00,240
KNOW THERE ARE OTHERS WHO NEVER 

5578
03:41:00,240 --> 03:41:05,379
DEVELOPED THE CLASSIC LEVY BODY 

5579
03:41:05,379 --> 03:41:08,248
SYMPTOMS THAT MAY HAVE 

5580
03:41:08,248 --> 03:41:08,816
IMPORTANT CONTRIBUTIONS TO 

5581
03:41:08,816 --> 03:41:15,723
THEIR LEVY BODY PATHOLOGY AND 

5582
03:41:15,723 --> 03:41:16,356
THAT WAS BAKED INTO THE COHORTS 

5583
03:41:16,356 --> 03:41:16,990
RECOMMENDATIONS AS WELL AS INTO 

5584
03:41:16,990 --> 03:41:17,925
THE BIOMARKERS PIECE OF IT. AND 

5585
03:41:17,925 --> 03:41:22,930
ALSO ON THE PATHOLOGY SIDE OF 

5586
03:41:22,930 --> 03:41:23,530
THINGS IN ORDER TO HAVE THAT 

5587
03:41:23,530 --> 03:41:24,131
HARMONIZATION ACROSS MULTIPLE 

5588
03:41:24,131 --> 03:41:24,765
DIFFERENT COHORT TO MAKE SURE 

5589
03:41:24,765 --> 03:41:28,569
LEVY BODIES ARE BEING LOOKED AT 

5590
03:41:28,569 --> 03:41:29,203
IN A SYSTEMATIC WAY REGARDLESS 

5591
03:41:29,203 --> 03:41:29,803
OF HOW SOMEBODY WAS RECRUITED 

5592
03:41:29,803 --> 03:41:35,142
INTO THAT PATHOLOGICAL STUDY. 

5593
03:41:35,142 --> 03:41:35,743
SUPER IMPORTANT IMPORTANT THANK 

5594
03:41:35,743 --> 03:41:36,376
YOU SO MUCH FOR MENTIONING IT. 

5595
03:41:36,376 --> 03:41:37,311
AND WE WILL MAKE SURE THAT OUR 

5596
03:41:37,311 --> 03:41:37,945
REVISED RECOMMENDATIONS INCLUDE 

5597
03:41:37,945 --> 03:41:39,046
THAT. 

5598
03:41:39,046 --> 03:41:43,016
>> THANK YOU SO MUCH. 

5599
03:41:43,016 --> 03:41:43,550
>> THIS CONCLUDES OUR OPEN

5600
03:41:43,550 --> 03:41:48,088
INPUT PERIOD. 

5601
03:41:48,088 --> 03:41:48,655
I WANT TO REMIND YOU THAT YOU 

5602
03:41:48,655 --> 03:41:49,289
CAN STILL PROVIDE YOUR WRITTEN 

5603
03:41:49,289 --> 03:41:50,791
FEEDBACK TODAY, AND JOIN US 

5604
03:41:50,791 --> 03:41:54,895
ALSO ON JUNE 2, WHERE WE WILL 

5605
03:41:54,895 --> 03:41:55,462
HAVE MORE PERIODS FOR YOUR 

5606
03:41:55,462 --> 03:41:59,566
INPUT. 

5607
03:41:59,566 --> 03:42:00,000
I WOULD LIKE FOR OUR 

5608
03:42:00,000 --> 03:42:02,136
CONTRACTORS TO SHARE MY SLIDES, 

5609
03:42:02,136 --> 03:42:02,636
AS I WILL DO MY BEST TO 

5610
03:42:02,636 --> 03:42:04,037
SUMMARIZE SOME OF THE REALLY 

5611
03:42:04,037 --> 03:42:10,477
IMPORTANT INPUT THAT WE HAVE. 

5612
03:42:10,477 --> 03:42:11,111
GATHERED DURING THESE TWO DAYS 

5613
03:42:11,111 --> 03:42:11,745
AND WE WILL USED TO REVISE THE 

5614
03:42:11,745 --> 03:42:12,279
RECOMMENDATIONS. 

5615
03:42:12,279 --> 03:42:12,946
NEXT SLIDE. 

5616
03:42:12,946 --> 03:42:18,452
>> DR. POSSIN: SO I WANT
TO 

5617
03:42:18,452 --> 03:42:19,052
START BY SAYING THANK YOU FOR 

5618
03:42:19,052 --> 03:42:22,723
YOUR PARTICIPATION AND INPUT. 

5619
03:42:22,723 --> 03:42:24,858
THESE RECOMMENDATIONS THAT WE 

5620
03:42:24,858 --> 03:42:25,425
THOUGHT ABOUT OVER THE LAST 

5621
03:42:25,425 --> 03:42:26,593
COUPLE OF DAYS HAVE BEEN 

5622
03:42:26,593 --> 03:42:29,163
DRAFTED BY NINE COMMITTEES WITH 

5623
03:42:29,163 --> 03:42:32,499
135 MANY MEMBERS, MOST OF WHOM 

5624
03:42:32,499 --> 03:42:36,537
ARE SCIENTISTS, BUT ALSO PEOPLE 

5625
03:42:36,537 --> 03:42:37,104
WOULD LIVED EXPERIENCE AND 

5626
03:42:37,104 --> 03:42:37,738
PEOPLE WHO WORK IN GOVERNMENT 

5627
03:42:37,738 --> 03:42:41,608
AND POLICY. 

5628
03:42:41,608 --> 03:42:42,075
I AM SO GRATEFUL TO OUR 

5629
03:42:42,075 --> 03:42:42,643
COMMITTEE MEMBERS WHO WERE 

5630
03:42:42,643 --> 03:42:43,744
FLEXIBLE AND GENEROUS WITH OUR 

5631
03:42:43,744 --> 03:42:49,449
MOVE FROM THE IN PERSON MEETING 

5632
03:42:49,449 --> 03:42:49,983
IN MARCH TO THIS VIRTUAL 

5633
03:42:49,983 --> 03:42:56,256
MEETING AND THE CHANGE OF DATE. 

5634
03:42:56,256 --> 03:42:56,890
ESPECIALLY DURING THE TIME THAT 

5635
03:42:56,890 --> 03:42:58,692
HAS BEEN OFTEN CHALLENGING FOR 

5636
03:42:58,692 --> 03:43:00,327
SCIENTISTS. SO THANK YOU FOR 

5637
03:43:00,327 --> 03:43:05,199
THE AMENDMENT TO THIS PROCESS. 

5638
03:43:05,199 --> 03:43:05,799
IT HAS BEEN INSPIRING AND WE 

5639
03:43:05,799 --> 03:43:06,400
HAVE 2100 PEOPLE REGISTER FOR 

5640
03:43:06,400 --> 03:43:07,034
THE MEETING AS OF THIS MORNING 

5641
03:43:07,034 --> 03:43:07,568
AND THERE MAY BE MORE AND 

5642
03:43:07,568 --> 03:43:10,204
ACROSS THE TEAMS MEETING IN 

5643
03:43:10,204 --> 03:43:11,572
VIDEOCAST WE HAD UP TO 1000 

5644
03:43:11,572 --> 03:43:12,139
PEOPLE ADDING ONE TIME, SO 

5645
03:43:12,139 --> 03:43:14,208
RECORD ENGAGEMENT.

5646
03:43:14,208 --> 03:43:23,851
WE HAD EIGHT LIVE PUBLIC INPUT 

5647
03:43:23,851 --> 03:43:24,484
SESSIONS WITH MORE TO COME AND 

5648
03:43:24,484 --> 03:43:25,085
SOME WONDERFUL AND INSIGHTFUL 

5649
03:43:25,085 --> 03:43:25,586
EMAIL FEEDBACK. 

5650
03:43:25,586 --> 03:43:28,021
NEXT SLIDE. 

5651
03:43:28,021 --> 03:43:28,522
I WILL REVIEW SOME OF THE 

5652
03:43:28,522 --> 03:43:29,156
OVERARCHING THEMES THAT I HEARD 

5653
03:43:29,156 --> 03:43:31,191
AT THE SUMMIT. 

5654
03:43:31,191 --> 03:43:32,826
THE FIRST IS THAT THERE HAS 

5655
03:43:32,826 --> 03:43:33,460
BEEN AN INCREDIBLE PROGRESS IN 

5656
03:43:33,460 --> 03:43:38,999
THE ADRD RESEARCH FIELD EVEN 

5657
03:43:38,999 --> 03:43:39,900
JUST SINCE THE 2022 SUMMIT AND 

5658
03:43:39,900 --> 03:43:40,534
YET THERE IS AN URGENCY TO KEEP 

5659
03:43:40,534 --> 03:43:42,402
MOVING FORWARD. 

5660
03:43:42,402 --> 03:43:42,903
THERE IS AN APPRECIATION 

5661
03:43:42,903 --> 03:43:49,009
EXPRESS FOR NIH'S INVESTMENT IN 

5662
03:43:49,009 --> 03:43:51,778
THE SCIENTIFIC PROGRESS; THE 

5663
03:43:51,778 --> 03:43:52,379
MASSIVE REPORT WE HEARD THIS 

5664
03:43:52,379 --> 03:43:52,880
MORNING HIGHLIGHTED THE 

5665
03:43:52,880 --> 03:43:54,514
SIGNIFICANT CONTINUED 

5666
03:43:54,514 --> 03:43:55,282
INVESTMENT IN PRIORITY RESEARCH 

5667
03:43:55,282 --> 03:44:05,092
AND IT MUST CONTINUE. 

5668
03:44:05,092 --> 03:44:08,262
AND WE HEARD THAT WHEN CHOOSING 

5669
03:44:08,262 --> 03:44:16,169
RESEARCH PRIORITIES, PLEASE 

5670
03:44:16,169 --> 03:44:16,803
KEEP THE PATIENTS AND FAMILIES 

5671
03:44:16,803 --> 03:44:17,404
OF THE TOP OF MIND. WE HEARD 

5672
03:44:17,404 --> 03:44:18,005
THAT FROM SOMEBODY FROM LIVED 

5673
03:44:18,005 --> 03:44:18,405
EXPENSES. 

5674
03:44:18,405 --> 03:44:22,175
DEMENTIA IS NOT POLITICAL. IT 

5675
03:44:22,175 --> 03:44:22,709
AFFECTS ALL OF US IT IS A 

5676
03:44:22,709 --> 03:44:26,747
BIPARTISAN ISSUE. 

5677
03:44:26,747 --> 03:44:27,281
RACE COMPLEXITY WAS ANOTHER 

5678
03:44:27,281 --> 03:44:28,081
THING. WE KNOW ANYTHING DISCUSS 

5679
03:44:28,081 --> 03:44:31,919
THE DIAGNOSIS OF ADRD IS NOT A 

5680
03:44:31,919 --> 03:44:39,126
YES/NO SITUATION. IT IS CAUSED 

5681
03:44:39,126 --> 03:44:39,726
BY MULTIFACETED INTERPLAY OF 

5682
03:44:39,726 --> 03:44:40,160
BIOLOGIC, GENETIC, 

5683
03:44:40,160 --> 03:44:44,264
ENVIRONMENTAL SOCIAL BEHAVIOR 

5684
03:44:44,264 --> 03:44:46,066
ELEMENTS AND  TO UNDERSTAND 

5685
03:44:46,066 --> 03:44:46,700
THESE DISEASES WELL WE NEED TO 

5686
03:44:46,700 --> 03:44:47,200
INTEGRATE DATA SOURCES, 

5687
03:44:47,200 --> 03:44:51,371
PERSPECTIVES AND METHODS.

5688
03:44:51,371 --> 03:44:51,872
MOST PATIENTS HAVE MIXED 

5689
03:44:51,872 --> 03:44:53,373
ETIOLOGIES CALCIUM THEIR 

5690
03:44:53,373 --> 03:44:56,476
DEMENTIA AND THE PATHOLOGICAL 

5691
03:44:56,476 --> 03:44:57,110
OVERLAP IN THE DISEASES THAT WE 

5692
03:44:57,110 --> 03:45:00,280
STUDIED. 

5693
03:45:00,280 --> 03:45:00,881
I REALLY ENJOYED THE DISCUSSION 

5694
03:45:00,881 --> 03:45:03,283
ABOUT HOW POST-TDI IS TRULY AN 

5695
03:45:03,283 --> 03:45:06,420
MED. 

5696
03:45:06,420 --> 03:45:06,853
WE HAVE TO RAISE THIS 

5697
03:45:06,853 --> 03:45:07,487
COMPLEXITY AND THERE WERE 

5698
03:45:07,487 --> 03:45:09,122
COMMENTS MADE ABOUT IMPROVING 

5699
03:45:09,122 --> 03:45:09,723
MED CODING IN THE ELECTRONIC 

5700
03:45:09,723 --> 03:45:12,592
HEALTH RECORDS TO IMPROVE CARE 

5701
03:45:12,592 --> 03:45:13,226
AND IMPROVE DATA HARMONIZATION 

5702
03:45:13,226 --> 03:45:17,230
OPPORTUNITIES.  AND ALSO 

5703
03:45:17,230 --> 03:45:18,632
ADVANCING AND APPLYING 

5704
03:45:18,632 --> 03:45:19,266
ARTIFICIAL INTELLIGENCE METHODS 

5705
03:45:19,266 --> 03:45:22,669
TO UNDERSTAND AND ACCOMMODATE 

5706
03:45:22,669 --> 03:45:23,303
FOR THE COMPLEXITY THAT WE ARE 

5707
03:45:23,303 --> 03:45:23,704
STUDYING. 

5708
03:45:23,704 --> 03:45:27,407
NEXT SLIDE. 

5709
03:45:27,407 --> 03:45:30,911
THEME 3, COLLABORATIVE 

5710
03:45:30,911 --> 03:45:31,445
APPROACHES ARE NEEDED AT 

5711
03:45:31,445 --> 03:45:35,248
MULTIPLE LEVELS. 

5712
03:45:35,248 --> 03:45:35,782
ACROSS EVERY SESSION IT WAS 

5713
03:45:35,782 --> 03:45:42,656
MENTIONED THAT WE NEED TO KEEP 

5714
03:45:42,656 --> 03:45:43,256
IMPROVING OUR APPROACHES FOR 

5715
03:45:43,256 --> 03:45:43,790
HARMONIZATION, AND MOVING 

5716
03:45:43,790 --> 03:45:46,493
TOWARDS BROAD DATA SHARING.

5717
03:45:46,493 --> 03:45:47,060
WE NEED EXTENSIVE BIOMARKERS 

5718
03:45:47,060 --> 03:45:48,662
THAT CAN BE WIDELY COLLECTED IN 

5719
03:45:48,662 --> 03:45:53,500
STANDARD WAYS. WE NEED TO 

5720
03:45:53,500 --> 03:45:54,034
LEVERAGE PRIVATE/ PUBLIC 

5721
03:45:54,034 --> 03:45:54,501
PARTNERSHIPS IN DATA 

5722
03:45:54,501 --> 03:45:55,135
REPOSITORIES AND WE NEED COMMON 

5723
03:45:55,135 --> 03:45:55,902
DEFINITIONS AND NOMENCLATURE TO 

5724
03:45:55,902 --> 03:45:56,536
SUPPORT DATA HARMONIZATION FOR 

5725
03:45:56,536 --> 03:46:04,945
EXAMPLE AROUND FTLD DIAGNOSIS. 

5726
03:46:04,945 --> 03:46:05,545
WE NEED TO ENGAGE A VARIETY OF 

5727
03:46:05,545 --> 03:46:06,146
STAKEHOLDERS IN ALL STEPS OF 

5728
03:46:06,146 --> 03:46:07,981
RESEARCH, INCLUDING PEOPLE WITH 

5729
03:46:07,981 --> 03:46:08,515
LIVED EXPERIENCE.

5730
03:46:08,515 --> 03:46:11,151
WE WANT TO CONTINUE OUR 

5731
03:46:11,151 --> 03:46:15,522
PARTNERSHIPS ACROSS FEDERAL 

5732
03:46:15,522 --> 03:46:16,156
AGENCIES THAT HAVE BEEN CRUCIAL 

5733
03:46:16,156 --> 03:46:16,757
FOR THE PROBLEMS THAT WE HAVE 

5734
03:46:16,757 --> 03:46:20,894
SEEN DURING THIS SUMMIT. 

5735
03:46:20,894 --> 03:46:21,294
AND PRIVATE/ PUBLIC 

5736
03:46:21,294 --> 03:46:21,862
PARTNERSHIPS AND CRUCIAL AS 

5737
03:46:21,862 --> 03:46:22,496
WELL FOR ADVANCING TIMES AND WE 

5738
03:46:22,496 --> 03:46:26,099
HEARD THAT NIH SUPPORT IS 

5739
03:46:26,099 --> 03:46:26,967
CRITICAL FOR THESE PARTNERSHIPS 

5740
03:46:26,967 --> 03:46:31,638
TO CONTINUE ESPECIALLY IN AN 

5741
03:46:31,638 --> 03:46:32,272
FTD AREA THAT WAS DISCUSSED IN 

5742
03:46:32,272 --> 03:46:33,874
MULTIDISCIPLINARY RESEARCH TO 

5743
03:46:33,874 --> 03:46:34,474
TACKLE THESE COMBOS PROBLEMS 

5744
03:46:34,474 --> 03:46:38,612
HIGHLIGHTED BY NASEM AND ALSO 

5745
03:46:38,612 --> 03:46:39,246
NEED COLLABORATION IN OUR CARE 

5746
03:46:39,246 --> 03:46:39,780
PATHWAYS AND AS WE TRY TO 

5747
03:46:39,780 --> 03:46:40,414
IMPROVE ACCESS TO CARE. 

5748
03:46:40,414 --> 03:46:45,052
NEXT SLIDE. 

5749
03:46:45,052 --> 03:46:50,290
BIOMARKERS!

5750
03:46:50,290 --> 03:46:50,891
WE MADE SO MUCH PROGRESS IN THE 

5751
03:46:50,891 --> 03:46:54,694
LAST THREE YEARS AND MORE, BUT 

5752
03:46:54,694 --> 03:46:55,328
THERE IS SO MUCH MORE PROGRESS 

5753
03:46:55,328 --> 03:46:55,896
THAT IS NEEDED BECAUSE THE 

5754
03:46:55,896 --> 03:46:57,097
AIKIDO DISENTANGLING CLINICAL, 

5755
03:46:57,097 --> 03:46:58,832
PATHOLOGICAL, HETEROGENEITY AND 

5756
03:46:58,832 --> 03:47:01,201
NAD. 

5757
03:47:01,201 --> 03:47:02,235
WE NEED THEM FOR DIAGNOSIS FOR 

5758
03:47:02,235 --> 03:47:06,606
EXAMPLE WE HEARD HOW LATE IS 

5759
03:47:06,606 --> 03:47:07,207
ONLY DIAGNOSED AT AUTOPSY AND 

5760
03:47:07,207 --> 03:47:10,210
WE NEED BETTER BIOMARKERS FOR 

5761
03:47:10,210 --> 03:47:12,579
MED, POST-TBI, WHERE WE CAN SEE 

5762
03:47:12,579 --> 03:47:20,454
SO MANY DIFFERENT ETIOLOGIES 

5763
03:47:20,454 --> 03:47:24,524
PRESENT IN THE PATIENTS. TDP-43 

5764
03:47:24,524 --> 03:47:26,693
BIOMARKER IS PARTICULARLY 

5765
03:47:26,693 --> 03:47:27,294
NEEDED. AND AS POINTED OUT BY 

5766
03:47:27,294 --> 03:47:31,531
KAREN AND LARRY, HAVING 

5767
03:47:31,531 --> 03:47:32,165
RELIABLE BIOMARKERS IS CRITICAL 

5768
03:47:32,165 --> 03:47:33,100
AN AUTOPSY IS TOO LATE. WE 

5769
03:47:33,100 --> 03:47:34,601
CANNOT JUST HAVE BIOMARKERS FOR 

5770
03:47:34,601 --> 03:47:38,138
AD. 

5771
03:47:38,138 --> 03:47:38,705
IT IS CRITICAL FOR MONITORING 

5772
03:47:38,705 --> 03:47:41,675
ESPECIALLY FOR MONITORING 

5773
03:47:41,675 --> 03:47:42,309
AGENTS AND ACCESS TO BIOMARKERS 

5774
03:47:42,309 --> 03:47:43,110
AS PART OF THE SCALABLE, 

5775
03:47:43,110 --> 03:47:43,944
DIAGNOSTIC PATHWAYS. 

5776
03:47:43,944 --> 03:47:47,013
NEXT SLIDE. 

5777
03:47:47,013 --> 03:47:48,615
I THINK THIS IS MY LAST 

5778
03:47:48,615 --> 03:47:50,517
OVERARCHING THEME. FOSTERING 

5779
03:47:50,517 --> 03:47:51,118
INCLUSIVE RESEARCH AND ACCESS 

5780
03:47:51,118 --> 03:47:56,256
TO CARE. WE NEED TO STUDY THE 

5781
03:47:56,256 --> 03:47:57,891
POPULATIONS MOST AT RISK. IT 

5782
03:47:57,891 --> 03:47:59,359
WAS SUGGESTED THAT RIGOROUS 

5783
03:47:59,359 --> 03:48:00,594
SCIENCE REQUIRES ADDRESSING 

5784
03:48:00,594 --> 03:48:02,796
HEALTH EQUITY AND WE SHOULD 

5785
03:48:02,796 --> 03:48:04,598
THINK ABOUT USING THE RIGHT, 

5786
03:48:04,598 --> 03:48:05,165
CLEAR, DECISIVE LANGUAGE ON 

5787
03:48:05,165 --> 03:48:12,305
THIS IN ADVANCE RESEARCH THAT 

5788
03:48:12,305 --> 03:48:12,906
WILL HELP THE MOST VULNERABLE 

5789
03:48:12,906 --> 03:48:13,540
AND UNDERSERVED PATIENTS IT IS 

5790
03:48:13,540 --> 03:48:14,574
SO IMPORTANT AND WE NEED 

5791
03:48:14,574 --> 03:48:15,041
GENOMIC DATA THAT IS 

5792
03:48:15,041 --> 03:48:15,575
REPRESENTATIVE OF THE US 

5793
03:48:15,575 --> 03:48:16,009
POPULATION. 

5794
03:48:16,009 --> 03:48:19,412
NEXT SLIDE. 

5795
03:48:19,412 --> 03:48:21,448
SO I HAVE TAKEN CAREFUL NOTE OF 

5796
03:48:21,448 --> 03:48:23,416
THE INPUT WE RECEIVED IN THESE 

5797
03:48:23,416 --> 03:48:24,017
SESSIONS THAT YOU HAVE BEEN A 

5798
03:48:24,017 --> 03:48:28,121
PART OF.  AND ALSO THE WRITTEN 

5799
03:48:28,121 --> 03:48:29,356
FEEDBACK THAT I RECEIVED FROM 

5800
03:48:29,356 --> 03:48:29,923
YESTERDAY. HAVE NOT GOTTEN 

5801
03:48:29,923 --> 03:48:30,557
THROUGH THE WRITTEN FEEDBACK WE 

5802
03:48:30,557 --> 03:48:32,225
GOT TODAY, BUT I'M VERY EXCITED 

5803
03:48:32,225 --> 03:48:34,394
TO DO SO AND I AM SUMMARIZING 

5804
03:48:34,394 --> 03:48:35,061
THOSE IN THE SESSION AND I WILL 

5805
03:48:35,061 --> 03:48:36,863
HIGHLIGHT A FEW THINGS. 

5806
03:48:36,863 --> 03:48:39,833
IN THE FIRST SESSION WHICH WAS 

5807
03:48:39,833 --> 03:48:40,467
ON RESEARCH AND IMPLEMENTATION 

5808
03:48:40,467 --> 03:48:42,435
OF DISCOVERIES INTO PRACTICE, 

5809
03:48:42,435 --> 03:48:44,604
THERE WAS FEEDBACK THAT THAT 

5810
03:48:44,604 --> 03:48:45,805
WHEN LOOKING AT DIAGNOSIS IN 

5811
03:48:45,805 --> 03:48:48,175
PRIMARY CARE NEED TO MAKE SURE 

5812
03:48:48,175 --> 03:48:48,808
THAT LESS TYPICAL SYMPTOMS ARE 

5813
03:48:48,808 --> 03:48:51,211
NOT MISSED. 

5814
03:48:51,211 --> 03:48:51,845
WE NEED TO NORMALIZE BRAIN 

5815
03:48:51,845 --> 03:48:55,749
HEALTH EVALUATIONS. 

5816
03:48:55,749 --> 03:48:56,249
AND WE NEED TO PRIORITIZE 

5817
03:48:56,249 --> 03:48:56,750
RESEARCH ON CULTURALLY 

5818
03:48:56,750 --> 03:48:57,617
COMPETENT COMMUNICATION OF 

5819
03:48:57,617 --> 03:49:01,955
BRAIN HEALTH INFORMATION. 

5820
03:49:01,955 --> 03:49:06,092
CARE APPROACHES NEED TO THINK 

5821
03:49:06,092 --> 03:49:06,626
ABOUT NONPHARMACOLOGICAL 

5822
03:49:06,626 --> 03:49:08,695
APPROACHES TO NEUROPSYCHIATRIC 

5823
03:49:08,695 --> 03:49:09,196
SYMPTOMS. AND FOCUS ON 

5824
03:49:09,196 --> 03:49:13,567
WELL-BEING AS A KEY OUTCOME. 

5825
03:49:13,567 --> 03:49:14,167
 ACCESS TO CARE SHOULD CONSIDER 

5826
03:49:14,167 --> 03:49:14,668
FINANCIAL AND SYSTEMIC 

5827
03:49:14,668 --> 03:49:18,939
BARRIERS.  AND SUPPORT AXIS TWO 

5828
03:49:18,939 --> 03:49:19,472
SUPPORTS AND SERVICES FOR 

5829
03:49:19,472 --> 03:49:22,209
PEOPLE WHO LIVE ALONE. 

5830
03:49:22,209 --> 03:49:22,742
WE ALSO NEED TO THINK ABOUT 

5831
03:49:22,742 --> 03:49:24,611
PEOPLE IN RURAL AREAS, AND HOW 

5832
03:49:24,611 --> 03:49:27,881
THEY CAN ACCESS QUALITY CARE. 

5833
03:49:27,881 --> 03:49:29,950
THERE WAS A COMMENT I RECEIVED 

5834
03:49:29,950 --> 03:49:33,620
VIA EMAIL THAT SAID "AN OUNCE 

5835
03:49:33,620 --> 03:49:34,254
OF PREVENTION IS WORTH A POUND 

5836
03:49:34,254 --> 03:49:37,057
OF CURE."

5837
03:49:37,057 --> 03:49:37,624
SHOULD PREVENTION BE A HIGHER 

5838
03:49:37,624 --> 03:49:38,225
PRIORITY? IS CURRENTLY RANKED 

5839
03:49:38,225 --> 03:49:41,628
AT NUMBER 4. 

5840
03:49:41,628 --> 03:49:42,162
WE WILL CONSIDER THAT AS A 

5841
03:49:42,162 --> 03:49:45,865
STEERING COMMITTEE.

5842
03:49:45,865 --> 03:49:46,399
AND ALSO AS A SUGGESTION TO 

5843
03:49:46,399 --> 03:49:47,033
PARTNER WITH CELEBRITY ADVOCATE 

5844
03:49:47,033 --> 03:49:47,701
TO GET OUR MESSAGES OUT. 

5845
03:49:47,701 --> 03:49:48,802
NEXT SLIDE. 

5846
03:49:48,802 --> 03:49:53,740
IN THE FTD SESSION IT WAS 

5847
03:49:53,740 --> 03:49:56,309
HIGHLIGHTED THAT THE HIGHEST 

5848
03:49:56,309 --> 03:49:56,943
PRIORITY IS RESEARCH TO IMPROVE 

5849
03:49:56,943 --> 03:50:04,150
DIAGNOSIS AND TREATMENT. THIS 

5850
03:50:04,150 --> 03:50:04,751
WAS REALLY GUIDED BY SOMEONE 

5851
03:50:04,751 --> 03:50:05,318
WITH LIVED EXPERIENCE. AND 

5852
03:50:05,318 --> 03:50:05,819
THERE WAS AN IMPORTANT 

5853
03:50:05,819 --> 03:50:06,386
DISCUSSION ABOUT POTENTIAL 

5854
03:50:06,386 --> 03:50:07,887
THERAPEUTIC TARGETS. 

5855
03:50:07,887 --> 03:50:08,622
WE NEED TREATMENTS WITH MORE 

5856
03:50:08,622 --> 03:50:09,923
THAN A MODEST EFFECT THAT CAN 

5857
03:50:09,923 --> 03:50:10,557
WORK FOR PATIENTS AT DIFFERENT 

5858
03:50:10,557 --> 03:50:13,593
STAGES OF DISEASE. 

5859
03:50:13,593 --> 03:50:16,496
PUBLIC/ PRIVATE PARTNERSHIPS 

5860
03:50:16,496 --> 03:50:17,631
ARE ESSENTIAL. AND THERE WAS A 

5861
03:50:17,631 --> 03:50:18,164
SENSE OF URGENCY AT THIS 

5862
03:50:18,164 --> 03:50:20,433
SESSION. 

5863
03:50:20,433 --> 03:50:22,535
ONE QUOTE I RECEIVED VIA EMAIL 

5864
03:50:22,535 --> 03:50:26,539
FROM THE VIDEOCAST WAS, "FTD IS 

5865
03:50:26,539 --> 03:50:28,208
UNIQUELY CRUEL BECAUSE IT OFTEN 

5866
03:50:28,208 --> 03:50:28,808
AFFECTS A PERSON IN THE PRIME 

5867
03:50:28,808 --> 03:50:31,678
OF THEIR CAREER AND THE COST OF 

5868
03:50:31,678 --> 03:50:32,412
LOST PRODUCTIVITY IS HUGELY 

5869
03:50:32,412 --> 03:50:35,015
IMPACTFUL FOR FAMILIES. OFTEN 

5870
03:50:35,015 --> 03:50:36,516
BOTH THE PATIENT AND THE 

5871
03:50:36,516 --> 03:50:38,785
CAREGIVER ARE FORCED TO LEAVE 

5872
03:50:38,785 --> 03:50:39,419
THEIR CAREERS AND ARE STUCK IN 

5873
03:50:39,419 --> 03:50:39,919
THIS SITUATION FOR MANY 

5874
03:50:39,919 --> 03:50:42,289
TORTURERS, AND DISABLED YEARS. 

5875
03:50:42,289 --> 03:50:46,426
NIH PLEASE HELP US END FTD."

5876
03:50:46,426 --> 03:50:47,127
I THINK WE FEEL THIS URGENCY. 

5877
03:50:47,127 --> 03:50:52,766
NEXT SLIDE. 

5878
03:50:52,766 --> 03:50:58,138
FTD POST TDI, WE NEED TO THINK 

5879
03:50:58,138 --> 03:50:58,772
ILLICITLY AND COLLABORATE WITH 

5880
03:50:58,772 --> 03:50:59,372
THE BROADER FIELD BECAUSE TDI 

5881
03:50:59,372 --> 03:51:06,012
IS TRULY AN MED. 

5882
03:51:06,012 --> 03:51:06,613
LOOK FOR OPPORTUNITIES TO LEARN 

5883
03:51:06,613 --> 03:51:07,147
MORE ABOUT THE IMPACTS OF 

5884
03:51:07,147 --> 03:51:07,747
DOMESTIC PARTNER VIOLENCE AND 

5885
03:51:07,747 --> 03:51:16,022
UNDERSTAND HOW TBI IN LATE LIFE 

5886
03:51:16,022 --> 03:51:16,456
INTERACT WITH OTHER 

5887
03:51:16,456 --> 03:51:17,390
NEURODEGENERATIVE PROCESSES,  

5888
03:51:17,390 --> 03:51:17,857
AND COLLABORATE WITH 

5889
03:51:17,857 --> 03:51:18,358
INTERNATIONAL RESEARCH 

5890
03:51:18,358 --> 03:51:20,360
COMMUNITIES ESPECIALLY WITH 

5891
03:51:20,360 --> 03:51:20,894
COUNTRIES WITH EXTENSIVE 

5892
03:51:20,894 --> 03:51:27,233
HISTORY OF COMBAT RELATED TBIS. 

5893
03:51:27,233 --> 03:51:32,439
MED - LATE. 

5894
03:51:32,439 --> 03:51:33,006
WE GOT SOME HELPFUL COMMENTS 

5895
03:51:33,006 --> 03:51:33,473
FROM SOME OF WE LIVED 

5896
03:51:33,473 --> 03:51:36,276
EXPERIENCE WITH SAID IT WAS A 

5897
03:51:36,276 --> 03:51:36,876
GAME CHANGER TO FIND OUT THE 

5898
03:51:36,876 --> 03:51:37,510
ACTUAL DIAGNOSIS, GETTING THE 

5899
03:51:37,510 --> 03:51:40,280
WORD OUT IS EVERYTHING. 

5900
03:51:40,280 --> 03:51:40,814
WE NEED TO EDUCATE FAMILIES 

5901
03:51:40,814 --> 03:51:44,284
ABOUT WHAT TO EXPECT. EDUCATE 

5902
03:51:44,284 --> 03:51:45,151
CLINICIANS INCLUDING PRIMARY 

5903
03:51:45,151 --> 03:51:45,652
CARE, AND DEVELOP CARE 

5904
03:51:45,652 --> 03:51:46,152
GUIDELINES AND WE NEED 

5905
03:51:46,152 --> 03:51:51,825
BIOMARKERS FOR LATE. 

5906
03:51:51,825 --> 03:51:52,392
DEFINITIVE DIAGNOSIS IS ONLY 

5907
03:51:52,392 --> 03:51:53,026
POSSIBLE AT AUTOPSY. THIS IS A 

5908
03:51:53,026 --> 03:51:54,361
HUGE BARRIER FOR CLINICAL 

5909
03:51:54,361 --> 03:51:55,895
TRIALS AND FOR DIAGNOSIS. BUT 

5910
03:51:55,895 --> 03:51:56,696
IT ALSO AFFECTS OUR STUDY OF 

5911
03:51:56,696 --> 03:51:58,064
OTHER PATHOLOGIES. 

5912
03:51:58,064 --> 03:52:01,368
FOR EXAMPLE WE NEED TO RULE OUT 

5913
03:52:01,368 --> 03:52:03,903
TDP-43 WHEN WE ARE SELECTING 

5914
03:52:03,903 --> 03:52:04,504
PATIENTS FOR AN AD TREATMENT 

5915
03:52:04,504 --> 03:52:06,373
TRIAL. 

5916
03:52:06,373 --> 03:52:06,840
WE ALSO NEED TO ADDRESS 

5917
03:52:06,840 --> 03:52:08,975
CONSISTENCIES AND DIAGNOSIS OF 

5918
03:52:08,975 --> 03:52:12,979
HIPPOCAMPAL SCLEROSIS, AND 

5919
03:52:12,979 --> 03:52:13,580
ADVANCED RESEARCH TO IDENTIFY 

5920
03:52:13,580 --> 03:52:14,214
THE CHARACTERISTIC SIGNATURES 

5921
03:52:14,214 --> 03:52:19,219
OF LATE WITH OR WITHOUT AD 

5922
03:52:19,219 --> 03:52:19,652
CO-PATHOLOGY USING 

5923
03:52:19,652 --> 03:52:20,286
RETROSPECTIVE STUDIES. 

5924
03:52:20,286 --> 03:52:23,623
NEXT SLIDE. 

5925
03:52:23,623 --> 03:52:24,791
IN THE CLINICAL AND BASIC 

5926
03:52:24,791 --> 03:52:28,228
SCIENCE SESSION, WE HEARD INPUT 

5927
03:52:28,228 --> 03:52:28,862
THAT WE NEED TO REALLY FOCUS ON 

5928
03:52:28,862 --> 03:52:30,630
THAT COMBINATION OF AD AND  

5929
03:52:30,630 --> 03:52:33,400
VASCULAR. 

5930
03:52:33,400 --> 03:52:34,234
WE NEED RESEARCH ON THE 

5931
03:52:34,234 --> 03:52:40,140
RELATIVE CONTRIBUTIONS OF EACH 

5932
03:52:40,140 --> 03:52:40,740
ETIOLOGY, IN A WAY THAT WILL 

5933
03:52:40,740 --> 03:52:44,944
HELP PATIENTS AND FAMILIES. 

5934
03:52:44,944 --> 03:52:45,545
FOR BIOMARKERS WE NEED TO MAKE 

5935
03:52:45,545 --> 03:52:46,079
SURE WE ARE RECOMMENDING 

5936
03:52:46,079 --> 03:52:46,713
RESEARCH THAT IS BROAD ENOUGH. 

5937
03:52:46,713 --> 03:52:47,247
AND THERE WAS EMPHASIS ON 

5938
03:52:47,247 --> 03:52:50,216
COLLECTING BIOMARKERS IN A 

5939
03:52:50,216 --> 03:52:50,817
STANDARDIZED WAY TO SUPPORT 

5940
03:52:50,817 --> 03:52:51,451
HARMONIZATION. 

5941
03:52:51,451 --> 03:52:56,623
AI AND  ADVANCED STATISTICAL 

5942
03:52:56,623 --> 03:52:57,524
METHODS ARE NEEDED, BUT FOR 

5943
03:52:57,524 --> 03:52:58,158
THESE TO WORK WELL WE NEED THAT 

5944
03:52:58,158 --> 03:53:00,160
COMMON CLASSIFICATION. 

5945
03:53:00,160 --> 03:53:03,196
THE EYE IS A WINDOW TO THE 

5946
03:53:03,196 --> 03:53:03,763
BRAIN AND THERE WAS TALK OF 

5947
03:53:03,763 --> 03:53:04,297
EXPANDING MODELS. 

5948
03:53:04,297 --> 03:53:07,434
NEXT SLIDE. 

5949
03:53:07,434 --> 03:53:16,209
AND LBD. WE TALKED ABOUT 

5950
03:53:16,209 --> 03:53:16,743
HARMONIZING DATA SETS AND 

5951
03:53:16,743 --> 03:53:18,511
SAMPLES ACROSS COHORTS. AND 

5952
03:53:18,511 --> 03:53:19,045
BETTER UNDERSTANDING AT A 

5953
03:53:19,045 --> 03:53:19,679
FUNCTIONAL LEVEL WHY THERE IS 

5954
03:53:19,679 --> 03:53:24,984
CELLULAR DYSFUNCTION IN 

5955
03:53:24,984 --> 03:53:25,385
DEMENTIA WITHOUT 

5956
03:53:25,385 --> 03:53:26,786
NEURODEGENERATION. 

5957
03:53:26,786 --> 03:53:28,421
AND FINALLY WANT TO THINK ABOUT 

5958
03:53:28,421 --> 03:53:31,391
RESEARCH ON A-SYNUCLEIN CO 

5959
03:53:31,391 --> 03:53:32,025
PATHOLOGY IN PEOPLE WITH DOWN 

5960
03:53:32,025 --> 03:53:33,226
SYNDROME AND AD. 

5961
03:53:33,226 --> 03:53:37,864
NEXT SLIDE. 

5962
03:53:37,864 --> 03:53:40,467
AND IT IS IMPORTANT FOR 

5963
03:53:40,467 --> 03:53:41,067
PATIENTS TO ENGAGE PHYSICALLY 

5964
03:53:41,067 --> 03:53:41,968
BUT ALSO SOCIALLY SO WE NEED TO 

5965
03:53:41,968 --> 03:53:43,169
CONSIDER THIS IN OUR 

5966
03:53:43,169 --> 03:53:46,005
RECOMMENDATIONS. CONSIDER THE 

5967
03:53:46,005 --> 03:53:49,342
EXPOZOME AND THEIR EFFECTS ON 

5968
03:53:49,342 --> 03:53:55,648
VCID. AND SEE ABOUT HOW DO THE 

5969
03:53:55,648 --> 03:53:56,216
MEDS INTERACT WITH THEIR IN 

5970
03:53:56,216 --> 03:53:56,850
DIFFERENT REGIONS OF THE BRAIN 

5971
03:53:56,850 --> 03:53:59,018
AND LASTLY MAKE SURE TO THINK 

5972
03:53:59,018 --> 03:54:03,022
ABOUT VASODILATION AND CCA IN 

5973
03:54:03,022 --> 03:54:07,827
OUR RESEARCH. 

5974
03:54:07,827 --> 03:54:08,728
IN THE CLOSING SESSION WE HAD 

5975
03:54:08,728 --> 03:54:09,329
REALLY FANTASTIC INPUT AND I 

5976
03:54:09,329 --> 03:54:11,664
HAVE TAKEN NOTE OF ALL OF IT 

5977
03:54:11,664 --> 03:54:12,298
AND NOT GOING TO REVIEWED HERE 

5978
03:54:12,298 --> 03:54:14,267
BECAUSE YOU WERE JUST THERE. 

5979
03:54:14,267 --> 03:54:14,901
BUT WILL CONSIDER ALL THE GREAT 

5980
03:54:14,901 --> 03:54:15,635
INPUT WE GOT IN THAT SESSION. 

5981
03:54:15,635 --> 03:54:19,672
NEXT SLIDE. 

5982
03:54:19,672 --> 03:54:22,108
SO IN CLOSING, I WANT TO 

5983
03:54:22,108 --> 03:54:23,743
EXPRESS MY GRATITUDE TO OUR 

5984
03:54:23,743 --> 03:54:29,082
COLLEAGUES AT NINDS AND ALS AT 

5985
03:54:29,082 --> 03:54:29,582
NIH FOR MAKING SOME IT 

5986
03:54:29,582 --> 03:54:30,984
HAPPENED. 

5987
03:54:30,984 --> 03:54:32,452
OVER THESE LAST FEW MONTHS MANY 

5988
03:54:32,452 --> 03:54:36,856
OF OUR COLLEAGUES AT NIH AND AT 

5989
03:54:36,856 --> 03:54:37,457
SOME OF THE FEDERAL AGENCIES 

5990
03:54:37,457 --> 03:54:37,991
HAVE FACED UNANTICIPATED 

5991
03:54:37,991 --> 03:54:42,462
CHALLENGES.  CHANGES IN THE 

5992
03:54:42,462 --> 03:54:43,062
RULES COVERING THEIR WORK AND 

5993
03:54:43,062 --> 03:54:45,298
IN DOWNSIZING THEIR TEAMS. 

5994
03:54:45,298 --> 03:54:46,499
WHETHER WE AGREE WITH THE 

5995
03:54:46,499 --> 03:54:48,034
CHANGES ARE NOT, THEY HAVE 

5996
03:54:48,034 --> 03:54:51,004
ADDED EXTRA CHALLENGES FOR OUR 

5997
03:54:51,004 --> 03:54:51,571
NIH COLLEAGUES IN PREPARING 

5998
03:54:51,571 --> 03:54:52,605
THIS SUMMIT. 

5999
03:54:52,605 --> 03:54:57,911
FOR EXAMPLE, SOME OF THE NIH 

6000
03:54:57,911 --> 03:54:58,444
LEADS AND STAFF WHO WERE 

6001
03:54:58,444 --> 03:54:59,245
WORKING ON THE SUMMIT WHEN WE 

6002
03:54:59,245 --> 03:55:00,313
STARTED ARE NO LONGER EMPLOYED 

6003
03:55:00,313 --> 03:55:03,383
AT NIH. 

6004
03:55:03,383 --> 03:55:11,824
AND ALSO, CHALLENGES WERE FACED 

6005
03:55:11,824 --> 03:55:12,425
IN SETTING THE SUMMIT DATES, 

6006
03:55:12,425 --> 03:55:13,026
AND GETTING THEM APPROVED AND 

6007
03:55:13,026 --> 03:55:14,294
AS WE SHIFT FROM IMPERSONAL 

6008
03:55:14,294 --> 03:55:17,564
MEETING TO VIRTUAL, FINDING A 

6009
03:55:17,564 --> 03:55:18,798
TECHNOLOGY PROBLEM THAT WILL 

6010
03:55:18,798 --> 03:55:19,432
WORK FOR THIS MEETING AND ALSO 

6011
03:55:19,432 --> 03:55:19,999
WAS ALLOWABLE. THAT WAS A 

6012
03:55:19,999 --> 03:55:21,734
CHALLENGE. 

6013
03:55:21,734 --> 03:55:22,302
AND SO THIS SUMMIT WOULD NOT 

6014
03:55:22,302 --> 03:55:25,471
HAVE HAPPENED IF NOT FOR THE 

6015
03:55:25,471 --> 03:55:27,373
PERSISTENCE, CREATIVITY AND THE 

6016
03:55:27,373 --> 03:55:27,840
DEDICATION OF OUR NIH 

6017
03:55:27,840 --> 03:55:29,742
COLLEAGUES. 

6018
03:55:29,742 --> 03:55:39,152
 I WANT TO THANK THE NIH STAFF 

6019
03:55:39,152 --> 03:55:40,453
TO WORK ON THE SUMMIT AND THE 

6020
03:55:40,453 --> 03:55:42,956
LOGISTICS CONTRACTOR AND I WANT 

6021
03:55:42,956 --> 03:55:43,523
TO SPECIFICALLY THANK AMBER 

6022
03:55:43,523 --> 03:55:46,726
MCCARTNEY FOR HER LEADERSHIP. 

6023
03:55:46,726 --> 03:55:47,360
SHE HAS WORKED TERRIBLY WITH A 

6024
03:55:47,360 --> 03:55:47,994
HUMBLE SPIRIT AND NEVER GAVE UP 

6025
03:55:47,994 --> 03:55:49,095
ON OUR GOAL TO HOST THIS SUMMIT 

6026
03:55:49,095 --> 03:55:51,331
NO MATTER THE CHALLENGES. 

6027
03:55:51,331 --> 03:55:52,632
I ALSO WANT TO SPECIFICALLY 

6028
03:55:52,632 --> 03:55:58,805
THANK ROD -- WHO LED THE PRIOR 

6029
03:55:58,805 --> 03:55:59,439
ADRD SUMMITS AND I WANT TO WISH 

6030
03:55:59,439 --> 03:56:01,474
HIM WELL ON HIS NEXT STEPS 

6031
03:56:01,474 --> 03:56:09,215
GUIDING ADRD WORK. 

6032
03:56:09,215 --> 03:56:09,816
WITH JOIN ME BY USING THE REACT 

6033
03:56:09,816 --> 03:56:11,918
FEATURE AT THE TOP OF YOUR 

6034
03:56:11,918 --> 03:56:12,552
BROWSER, IN OFFERING GRATITUDE 

6035
03:56:12,552 --> 03:56:13,186
FOR THE WORK AND DEDICATION OF 

6036
03:56:13,186 --> 03:56:21,861
OUR COLLEAGUES AT NIH. 

6037
03:56:21,861 --> 03:56:22,462
>> THANK YOU SO MUCH FOR
THOSE 

6038
03:56:22,462 --> 03:56:26,666
KIND WORDS. 

6039
03:56:26,666 --> 03:56:27,634
IT IS REALLY AN HONOR TO BE 

6040
03:56:27,634 --> 03:56:28,234
ABLE TO DO THIS AND LEAD THIS 

6041
03:56:28,234 --> 03:56:29,769
SUMMIT. IT IS REALLY AN 

6042
03:56:29,769 --> 03:56:35,375
IMPORTANT EVENT. 

6043
03:56:35,375 --> 03:56:35,975
WE WILL ALWAYS BE GRATEFUL FOR 

6044
03:56:35,975 --> 03:56:36,609
ALL THE INPUT FROM PEOPLE THAT 

6045
03:56:36,609 --> 03:56:38,511
WE RECEIVED IN THE COMMITTEE 

6046
03:56:38,511 --> 03:56:46,719
SENT TO THE LAST TWO DAYS.

6047
03:56:46,719 --> 03:56:47,253
AND WE ARE NOT DONE. WE'RE 

6048
03:56:47,253 --> 03:56:47,854
GOING TO HAVE A THIRD DAY ON 

6049
03:56:47,854 --> 03:56:48,221
JUNE 2. 

6050
03:56:48,221 --> 03:56:50,890
>> DR. POSSIN: NEXT SLIDE
WHILE 

6051
03:56:50,890 --> 03:56:53,559
AMBER IS TALKING. 

6052
03:56:53,559 --> 03:56:56,295
>> PERFECT.  THANK YOU. 

6053
03:56:56,295 --> 03:57:00,500
>> DR. POSSIN: ALL RIGHT
WELL 

6054
03:57:00,500 --> 03:57:02,735
THANK YOU. AND YES THANK YOU 

6055
03:57:02,735 --> 03:57:03,269
ALL FOR BEING HERE AND WE 

6056
03:57:03,269 --> 03:57:05,838
REALLY LOOK FORWARD TO A 

6057
03:57:05,838 --> 03:57:06,472
WONDERFUL THIRD DAY THE SUMMIT. 

6058
03:57:06,472 --> 03:57:16,472
SEE YOU THEN.