I'M WALTER KOROSHETZ DIRECTOR OF NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE WE'RE LEADING THE MEETING BUT THIS IS A MEETING WITH INPUT AND LEADERSHIP FROM MULTIPLE INSTITUTES AND CENTERS AT NIH. WE ARE ALSO WORKING IN THIS MEETING WITH MULTIPLE OTHER GROUPS MENTIONED HERE ON THIS SLIDE AND WE APPRECIATE ALL THE SUPPORT THAT WE HAVE GOTTEN FROM THESE GROUPS INTELLECTUALLY AND COFFEE SUPPORT AS WELL. THANK YOU FOR THAT. I THINK THIS IS A GREAT EXAMPLE OF WHAT MAKES NIH A GREAT PLACE. THIS IS A PROCESS BY WHICH PATIENT ADVOCATES, SCIENTISTS, GOVERNMENT OFFICIALS COME TOGETHER AND FROM A BOTTOM UP P APPROACH TRY TO DEVELOP A PLAN HOW TO FIGHT THESE TERRIBLE DISORDERS AND I THINK IN THIS INSTANCE, THERE IS A SPECIAL FLAVOR TO IT BECAUSE CONGRESS HAS CERTAINLY BEEN LISTENING TO THE ADVOCACY GROUPS TELLING CONGRESS ABOUT THE PROBLEMS THAT ARE FACING THE COUNTRY DUE TO THE RISING DEMENTIA RATES AS OUR POPULATION AGES, THE SCIENTISTS PROVIDING THE DATA AND THE SCIENTISTS ARE ALSO PROVIDING HOPE THAT WE CAN AVERT THIS CRISIS WITH SOME LUCK. WITH A LOT OF CLEVER WORK AND WITH RESOURCES TO DO THAT WORK. SO THIS PROCESS WHICH IS I MENTIONED SO BEAUTIFUL BECAUSE IT'S BOTTOM UP AND EVERYBODY INVOLVED, IS NOW IN ITS SECOND PHASE. THE FIRST PHASE WAS QUITE SUCCESSFUL AS IT WAS INCORPORATED INTO THE BYPASS BUDGETS WHICH RETURNED SIGNIFICANT INCREASE FUNDING TO THE NIH FOR WORK IN THESE DISORDERS, ALZHEIMER'S DISEASE AND DISORDERS WE'LL TALK ABOUT THE NEXT TWO DAYS, ALZHEIMER'S DISEASE RELATED DEMENTIAS. SO I'M PROUD OF THE WORK DONE BY THE GROUPS WORKING VERY HARD IN THE LAST COUPLE OF MONTHS TO PUT THIS TOGETHER, BOTH GROUPS FROM THE NIH AND PARTICULARLY FROM THE SCIENTISTS, INVESTIGATORS AND PATIENT ADVOCATES WHO PUT IN LOTS OF TIMES PREPARING FOR THIS MEETING SO THEY'RE COMING IN WITH RECOMMENDATIONS THAT THEY HAVE BEEN WORKING ON FOR YOUR INPUT AS PRESENTING THEM TO THE GROUP AND GETTING A WIDER INPUT BEFORE FINALIZATION. THEN THE NIH WILL TAKE THE RECOMMENDATIONS AND USE THEM AS WE MAKE OUR PLANS GOING FORWARD FOR RESEARCH PRIORITIES. I WOULDN'T WANT TO SAY ONE -- I WOULD WANT TO SAY ONE THING BEFORE RESEARCH PRIORITIES. IN THE PAST FROM THE BEGINNING WHEN WE HAD LITTLE FUNDS APPROPRIATED FOR THIS TYPE OF WORK, PEOPLE WERE WAITING FOR SPECIAL CALLS FOR CERTAIN TYPES OF GRANTS TO GO OUT UNDER RFAs, REQUESTS FOR APPLICATIONS FOR PARTICULAR AREAS. IT'S ALSO IMPORTANT I THINK NOW THE FUNDS MORE AVAILABLE THAN THEY WERE IN THE PAST TO THE REALIZE A LOT OF INNOVATION THAT WE HAVE IN MEDICAL SCIENCE COMES FROM REALLY GOOD INVESTIGATORS COMING UP WITH BRIGHT IDEAS IN THEIR OWN LABORATORIES AND THINGS THAT CAN'T BE PRESCRIBED. SO IT'S IMPORTANT TO NOTE FUNDS THAT ARE COMING TO NIH NOT ONLY RFAs BUT ALSO PAY GRANTS COMING FROM INDIVIDUAL INVESTIGATORS' IDEAS. THAT'S THE GREAT THING ABOUT NIH COMPARED TO OTHER COUNTRIES WHICH ARE MORE TOP-DOWN, REALLY INTERESTED IN GIVING ANYBODY A CHANCE WITH A REALLY GOOD IDEA WITH GOOD PRELIMINARY DATA THAT THEY CAN DO IMPACTFUL RESEARCH. SO WITH THAT, I WANT TO AGAIN THANK EVERYBODY FOR THE WORK THEY'RE DOING AND INTRODUCE DR. RONALD PETERSEN WHO IS THE CHAIR OF THE ADVISORY COUNCIL ON ALZHEIMER'S RESEARCH CARE AND SERVICES AND A LEADER IN THE PROCESS FOR BOTH THE AVRDs AND ALZHEIMER'S DISEASE ITSELF. THANK YOU, RON. [APPLAUSE] >> THANKS VERY MUCH, WALTER, FOR THE KIND INTRODUCTION. THANKS TO WALTER AND CLEARLY ROD FROM NINDS, DAVID HOLTZMAN WHO IS LEADER IN NINDS COUNCIL TOWARDS ORGANIZING THIS MEETING AS WELL AS INPUT FROM NATIONAL INSTITUTE OF AGING, RICHARD HODES, TONY FELLPS AND COLLEAGUES SO A FUG EFFORT PUTTING THIS MEET -- A HUGE EFFORT PUTTING THIS MEETING TOGETHER. I HAVE NO IDEA WHERE MY SLIDES ARE BUT THEY'RE PROBABLY HERE SOMEWHERE. THERE WE ARE. U THANK YOU. SO WHAT I HAVE BEEN ASKED TO DO THIS MORNING IS TRY TO PUT THIS MEETING AND SIMILAR MEETINGS IN THE CONTEXT OF THE NATIONAL PLAN, THE NATIONAL PLAN TO ADDRESS ALZHEIMER'S DISEASE. SO I WOULD LIKE TO DO THAT, MANY OF YOU KNOW ABOUT THIS BUT I THOUGHT I WOULD LIKE TO REVIEW HOW THIS HAS EVOLVED OVER THE YEARS AND WHY THIS SUMMIT IS PARTICULARLY IMPORTANT IN THE OVERALL PROCESS. SO AS WE ALL KNOW, CONGRESS PASSED THE NATIONAL ALZHEIMER'S PROJECT ACT 2010, THE PRESIDENT IMMEDIATELY SIGNED IT INTO LAW THE NEXT MONTH. THE LAW CREATED AN ADVISORY COUNCIL THAT WILL ADVISE THE SECRETARY OF HHS ON WHAT'S NECESSARY TO DEVELOP THIS PLAN. THE FIRST NATIONAL PLAN WAS THEN PUBLISHED IN 2012 AND THE LAW REQUIRES THE PLAN BE REVISED AND UPDATED ANNUALLY AND THAT'S BEEN DONE EVERY YEAR SINCE THEN. ALSO THE LAW SAYS THAT THE NATIONAL ADVISORY COUNCIL WHICH IS COMPRISED OF FEDERAL AND NON-FEDERAL MEMBERS, THE NON-FEDERAL MEMBERS WILL TURN OVER PERIODICALLY SO THE FIRST WAVE OF THAT HAPPENED AT THE END OF 2015 AND E WILL HAPPEN EVERY TWO YEARS. AND CURRENTLY HHS AND PARTICULAR ASPE IS IN THE PROCESS OF GENERATING THE 2016 VERSION OF THE PLAN. BY ALZHEIMER'S DISEASE NATIONAL PLAN WE REALLY MEAN ALZHEIMER'S DISEASE AND RELATED DISORDERS. ABSOLUTELY. SO THIS IS NOT JUST PAYING HOMAGE TO OTHER DISORDERS BUT WE MEAN THE ENTIRE SPECTRUM OF DISORDERS OF COGNITIVE IMPAIRMENT. SO AGAIN THE PURPOSE WAS TO CHARGE THE SECRETARY OF HHS WITH THE JOB OF LOOKING OVER THE LANDS ESCAP WHAT IS GOING ON IN THE FEDERAL GOVERNMENT CURRENTLY WITH RESPECT TO ALZHEIMER'S DISEASE RELATED DEMENTIAS. WHAT CAN WE DO TO ACCELERATE TREATMENT, EARLY DIAGNOSIS, COORDINATION OF CARE FOR WHAT RESOURCES ARE OUT THERE, AND TO INTERACT WITH INTERNATIONAL POPULATIONS AND BRING IN THE ISSUE OF DIVERSITY AS WELL SO THE PLAN WAS GLOBAL IN ITS ULTIMATE CHARGE. SO 2012, THE FIRST VERSION WAS IN FACT PUBLISHED AND THE SUBSEQUENT VERSIONS ARE OUT THERE ON THE WEBSITE, HERE IS THE WEBSITE FOR HHS TO SEE THEM AND THE RECOMMENDATIONS OF THE COUNCIL. THE PRIMARY GOAL IS TO PREVENT DELAY ONSET, SLOW PROGRESSION OF ALZHEIMER'S DISEASE AND RELATED DEMENTIAS BY 2025. ACTUALLY THE 2025 DATE SOMEWHAT ARBITRARY BUT NEVERTHELESS IMPORTANT BECAUSE IT COMES INTO PLAY SUBSEQUENTLY AS I'LL SAY IN A FEW MINUTES, ABOUT HOW THE VARIOUS GOALS ARE BEING ROLLED OUT. SO THE OVERALL PLAN HAD FIVE GOAL, FIRST WAS RESEARCH GOAL, SECOND REFERRED TO CLINICAL ASPECTS OF THE DISEASE, THIRD TO CARE, SERVICES AND SUPPORT, FOURTH TO PUBLIC AWARENESS, ENGAGEMENT, FIFTH TO METRICS. HOW ARE WE GOING TO TRACK PROGRESS OF THE DISEASE. THE LAW ALSO REQUIRED IN ADDITION TO THE PLAN THE ADVISORY COUNCIL SHOULD ISSUE RECOMMENDATIONS A THAT GO DIRECTLY TO THE SECRETARY AND UNABRIDGED TO CONGRESS. THESE CAN SAY ANYTHING. SO THE KEY RECOMMENDATION THERE SINCE ONSET OF THIS PROCESS IS THE FACT WE RECOMMEND THE FEDERAL GOVERNMENT SHOULD BE SPENDING AROUND $2 BILLION IN RESEARCH ON ALZHEIMER'S DISEASE AND RELATED DISORDERS. THE SPECIFIC RESEARCH GOALS SOMEWHAT BROADER MEANT TO CARRY OUT WHAT'S NECESSARY FOR MAKING SUCCESS AGAINST VARIOUS DISORDERS. SO IDENTIFY THE PRIORITIES AND MILESTONES. GET BACK TO THAT IN JUST A MOMENT. FOCUSING ON PREVENTION, TREATMENT, EARLY IDENTIFICATION. THESE DISORDERS ARE SUCH MAGNITUDE FROM A PUBLIC HEALTH PERSPECTIVE THAT WE REALLY NEED TO LOOK EARLY IN THE DISEASE PROCESS. AGAIN, WE NEED TO COORDINATE THIS WITH WHAT'S GOING ON INTERNATIONALLY, AND FINALLY TO TRANSLATE THIS INTO MEDICAL PRACTICE. SO NOT JUST ACADEMIC EXERCISE BUT IN FACT WHAT DOES THIS MEAN FOR THE PRIMARY CARE PHYSICIAN OUT THERE IN HIS OR HER OFFICE. AN EXAMPLE OF THE ANNUAL REVISIONS IN 2013 WE ASKED PROGRAM STAFF AT PRIMARILY NATIONAL INSTITUTE ON AGING TO TAKE RECOMMENDATIONS OUTS OF THE PLAN AND SUMMIT IN 2012, THE FIRST ALZHEIMER'S DISEASE SUMMIT, PUT THEM INTO MILESTONES AND PUT A TIME SCALE ON THIS SO WHAT CAN WE DO IN THE NEAR FUTURE? IN THE INTERMEDIATE FUTURE, AND IN THE DISTANT FUTURE. SO TO TRY TO MAKE THIS MUCH MORE REALISTIC AND ALSO ALLOW THE COUNCIL MEANS BY WHICH WE COULD IN FACT ASSESS WHETHER PROGRESS IS BEING MADE. WITH THAT AS AN EXAMPLE OF THE 2012 FIRST AD CONFERENCE, THERE WAS PUBLIC INPUT, THE SUMMIT WAS HELD VERY MUCH IN THIS ROOM ASSESSING WHERE WE WERE WITH REGARD TO ALZHEIMER'S DISEASE FRVMENT THAT CAME SEVERAL RECOMMENDATIONS AND SPECIFIC MILESTONES, OUT OF THAT CAME ACTUAL CONCEPTS AND RFAs. SO BACK IN 2012 THOSE RECOMMENDATIONS WERE TRANSLATED INTO FUNDING OPPORTUNITIES FOR THE FIELD. WHAT WAS GOING ON IN THE FIELD, THE INTERNATIONAL ALZHEIMER'S DISEASE RESEARCH PORTFOLIO SO CALLED EYE DROP WAS GENERATED BACK THEN, TO TAKE A LOOK AT THE TOTAL LANDSCAPE OF WHAT'S HAPPENING IN ALZHEIMER'S DISEASE IN THIS COUNTRY AND AROUND THE WORLD. ARE WE SPENDING ENOUGH EFFORT IN THIS AREA OF RESEARCH, THAT AREA OF RESEARCH, ET CETERA. AND WITH THAT THEN, THE ANNUAL PROGRESS REPORT WERE GENERATED SAYING YES WE'RE DOING WELL IN THIS AREA BUT WE MIGHT BE SHORT IN THIS AREA. SO THAT BECAME INSTRUMENTAL IN HELPING US ASSESS HOW WELL WE WERE MAKING WHAT KIND OF PROGRESS WE WERE MAKING TOWARDS THE 2025 GOAL. YOU DON'T HAVE TO READ THIS, THIS IS JUST AN EXAMPLE OF HOW WE DRILL DOWN ON THOSE INDIVIDUAL RECOMMENDATIONS. THIS WAS A RECOMMENDATION RELATED TO DRUG TRIAL MILESTONES. AGAIN, VERY GRANULAR HERE WITH REGARD TO THE RECOMMENDATIONS AND AS WE SUGGESTED TO THE NIA PROGRAM STAFF TAKE THE RECOMMENDATIONS AND BREAK THEM OUT WHAT'S IN THE NEAR TERM WHAT IS IN THE INTERMEDIATE AND WHAT IS IN THE DISTANT. SO THIS IS DONE, THIS WAS DONE FOLLOWING THE 2013 ADRD SUMMIT, AGAIN, THE SECOND AD SUMMIT AND WILL BE DONE AFTER THIS SUMMIT AS WELL. SO WHILE THESE ARE SEEMINGLY ABSTRACT RECOMMENDATIONS, THEY REALLY BECOME QUITE CONCRETE TIES, IF THAT IS A WORD, OVER TIME. SO THAT'S THE PLAN, THAT'S WHAT'S GOING ON, THAT'S THE PROCESS, HAS IT HAD AN IMPACT? I'LL LEAVE TO YOU TO MAKE THAT JUDGMENT. SO HERE IS WHAT THE BUDGET LOOKED LIKE FOR ALZHEIMER'S DISEASE RELATED DISORDERS IN 2011, ABOUT $448 MILLION. IF NOTHING HAS BEEN DONE IN THE FIELD ONE WAY OR ANOTHER AND YOU TAKE INTO ACCOUNT WHAT IS NIA FUNDING WHAT IS ALZHEIMER'S DISEASE FUNDING, RELATIVE TO NIA FUNDING, NIA FUNDING RELATIVE TO NIH FUNDING, PROBABLY WOULD HAVE BEEN RELATIVELY FLAT BECAUSE THAT'S SORT OF THE STORY OF THE NIH BUDGET. BUT IN FACT AFTER NAPA PLUS WHETHER THAT WAS CAUSE AND EFFECT, FRANCIS QUOLL LINS DIRECTOR OF NIH ALLOCATED FROM HIS DISCRETIONARY FUNDS, FUNDS DEDICATED TO ALZHEIMER'S DISEASE IN 2012. 2013 SEQUESTRATION CAME ALONG BUT IN FACT DR. HODES, DR. COLLINS, PULLED FUNDS OUT THEIR DISCRETIONARY BUCKETS TO PUT TOWARDS ALZHEIMER'S DISEASE TO KEEP THE TREND GOING. IN 2014 AND 2015 A, CONGRESS MADE SPECIFIC ALLOCATIONS TOWARDS ALZHEIMER'S DISEASE AND RELATED DEMENTIAS. VERSUS AUSTERE TIMES. MODEST INCREASE IN OVERALL NIH BUDGET BUT FACT THEY ALLOCATED A SIGNIFICANT PROPORTION OF THAT TO ALZHEIMER'S DISEASE AND RELATED DISORDERS. THEN THROUGH THE WORK OF ADVOCACY GROUPS LISTED ON WALTER'S SLIDE, PRIMARILY PROMOTEDDED BY THE ALZHEIMER'S ASSOCIATION IN DECEMBER OF 2015 CONGRESS SIGNED THE FY 16 BUDGET ALLOCATING 350 MILLION NEW DOLLARS FOR ALZHEIMER'S DISEASE AND RELATED DISORDER, GETTING US TOWARD THE 1 BILLION THRESHOLD, HEADING TOWARD THE 2 BILLION BUT TOWARD THE $1 BILLION THRESHOLD. I SHOULD SAY IN 2015 -- [APPLAUSE] >> THAT'S FOR THE MONEY, NOT ME, RIGHT? IN 2015 AND 2016 THE RDDC RCDC SYSTEM OF ALLOCATING FUNDENING THE FEDERAL GOVERNMENT BROKE OUT ALZHEIMER'S DISEASE AND RELATED DISORDERS AND SO FOR THIS MEETING, IT WAS SUGGESTEDDED HOW DO THESE NUMBERS SHAKE OUT? AND HERE IS HOW THE $991 MILLION ARE ALLOCATED. I SAY THIS LOOKS LIKE A DEMARCATION ALZHEIMER'S DISEASE RELATED DISORDERS ARE DIFFERENT BUT IN FACT THEY MAY NOT BECAUSE DIFFERENT AS WE THOUGHT, I'LL COME BACK TO THAT IN JUST A MOMENT. A MORE DRAMATIC WAY TO LOOK IS HERE WE ARE IN 2011 WHEN NAPA WAS SIGNED AND HERE IS WHAT'S HAPPENED SINCE. IS IT DUE TO NAPA? YOUR JUDGMENT. I THINK CLEARLY IT IS RAISED THE AWARENESS IN THE GENERAL PUBLIC AND IN CONGRESS AS WELL WHAT'S IMPORTANT WITH REGARD TO THESE DISEASES IN THE COUNTRY. LET ME SUMMARIZE SAYING HERE IS WHAT HAPPENED BACK IN 2012. THE FIRST PLAN WAS PUBLISHED IN 2012, WE ARE THE ALZHEIMER'S SUMMIT THAT YIELDED RECOMMENDATIONS CONCEPTS AND RFAs FOR THE RESEARCH COMMUNITY. IN 2013, THE FIRST OF THESE SUMMITS THE ADRD SUMMIT WAS HELD, SIMILARLY MILESTONES WERE AND RECOMMENDATIONS CAME OUT OF THAT PROCESS, ENABLING ARELING THE COUNCIL TO ASSESS PROGRESS, ADDITIONAL RFAs. THE NOTABLE EVENTS IN 2014 WAS PASSAGE OF ALZHEIMER'S ACCOUNTABILITY ACT. THIS PARTICULAR ACT NOW ASKED, REQUIRED THE NIH TO GENERATE AN ANNUAL BUDGET SAYING HOW MUCH WILL IT TAKE IN THE NEXT YEAR IF WE MAKE THAT GOAL IN 2025 OUTLINED IN THE NATIONAL PLAN. WHAT WILL IT TAKE OVER THE COURSE OF THE NEXT YEAR? ADVOCACY ORGANIZATIONS LED BY THE ALZHEIMER'S ASSOCIATION GOT THIS BILL WRITTEN AND PASSED IN COURSE OF 2014, THAT LED TO ADDITIONAL RFAs. THEN IN 2015, THE SECOND ALZHEIMER'S DISEASE SUMMIT WAS HELD. SAME STORY MILESTONES, RECOMMENDATIONS PA BUT THESE MILESTONES NOW IN THE SETTING OF THE ALZHEIMER'S ACCOUNTABILITY ACT REQUIRED NIH TO PUT DOLLAR FIGURES ON THESE VARIOUS RECOMMENDATIONS AND MILESTONES, AND IN FACT DR. COLLINS AND DR. HODES PRESENTED THE FIRST BY PASS BUDGET TO THE ADVISORY COUNCIL LAST SUMMER RECOMMENDING AN ADDITIONAL $323 MILLION BE CONSIDERED IN FY 17 FOR CONTINUATION OF THE PROCESS TOWARD THE GOAL. THAT THEN YEELTD LED RFAs IN ANTICIPATION OF ADDITIONAL FUNDING COMING FORWARD DOWN THE ROAD. THIS YEAR, HERE NOW AT THE SECOND ADRD SUMMIT, SO THE MILESTONES GENERATED BY ALL FOUR SUMMITS WILL GO INTO THE BY PASS BUDGET AND EARLIER THIS YEAR NIA ISSUED REQUEST FOR INFORMATION FOR PUBLIC INPUT INTO THE BY PASS BUDGET BEING GENERATED IN FY 18 AND WE'LL SEE WHAT THOSE NUMBERS COME TO BE IN A FEW MONTHS. SO BOTTOM LINE THIS IS WHAT WE'RE TALKING ABOUT, THESE ARE NOT ACT DEEM EXERCISES WHERE WE GET TOGETHER AND TALK ABOUT HERE IS WHAT I'M DOING, HERE IS WHAT YOU'RE DOING WE NEED TO DO THIS BUT THESE HAVE HAVE REAL IMPACT ON PROCESS GOING DOWN AND AT THE END OF THE DAY DOLLARS AN CENTS GOING ON SO SUMMIT IN PARTICULAR THIS ADRD SUMMIT BUT THE SUMMIT IN GENERAL DETERMINE DIRECTION OF RESEARCH QUESTIONS AND THESE TRANSLATE INTO FUNDING OPPORTUNITIES TO GET THIS DONE. SO LET ME CLOSE BY RETURNING THEN TO THAT NOTION OF AD VERSUS ADRD. ARE THESE ARTIFICIAL DISTINCTIONS, IS ALZHEIMER'S DISEASE DIFFERENT FROM THE OTHER DISORDERS THAT WE'LL DISCUSS OVER THE NEXT COUPLE OF DAYS? AND YOU CAN USE WHATEVER CONCEPTUALIZATION OF COGNITIVE CONTINUUM YOU LIKE BUT TALK ABOUT NORMAL COGNITION IN AGING AND A LITTLE BIT OF IMPAIRMENT AND YOU TALK ABOUT FULLY DEVELOPED DEMENTIA, YOU HAVE SOMETHING LIKE THIS SPECTRUM. IF YOU PUT THAT SPECTRUM IN THE MIDDLE, THIS IS WHAT WE'RE TALKING ABOUT REGARDLESS OF THE UNDERLYING ETIOLOGY, OUR JOB NOW IS TO TRY TO DISSECT THIS CLINICAL PICTURE AND TRY TO SAY O OKAY WHAT'S CAUSING THE PROBLEM? CLEARLY IN AGING, AMYLOID BETA IS A MAJOR PLAYER, CLEARLY TAU IS A PLAYER. SO BY DEFINITION, THIS IS WHAT THE FIELD HAS DETERMINED BEING ALZHEIMER'S DISEASE. BUT WE ALL KNOW FROM MANY RESEARCH STUDIES OVER RECENT YEARS, THIS IS PART OF THE PICTURE. IF MANAGE IS COGNITIVELY IMPAIRED IN THEIR '70s, '8 0ES, PASSES AWAXER -- AWAY, YOU LOOK AT THE BRAIN, PROBABLY HAVE ALPHA SYNUCLEIN, PROBABLY VASCULAR CHANGES AND SURE THERE ARE OTHER PATHOLOGIC ENTITIES WE HAVEN'T DISCOVERED YET THAT ARE CONTRIBUTING. SO IT'S A COMPOSITE OF ALL THESE FACTORS THAT COME INTO PLAY TO CHARACTERIZE SOMEBODY'S COGNITIVE IMPAIRMENT DOWN THE ROAD. WHY DO YOU THAT? IF YOU PUT THOSE IN THE CENTER AND YOU SAY CAN WE MEASURE THOSE INDIVIDUAL COMPONENTS? CAN WE GET BIOMARKERS THAT PICK UP A BETA AND TAU? WE'RE WORKING ON TDD 43, ALPHA SYNUCLEIN, VARIOUS FACTORS, THE BIOMARKER FIELD BECOMES MORE AND MORE SOPHISTICATED AND TEASING OUT THESE VARIOUS COMPONENTS, THIS WILL BE THE TYPICAL APPROACH TO DEALING WITH COGNITIVE DISORDERS OF AGING. WHY DO THIS? AT THE END OF THE DAY, YOU WOULD LIKE TO DEVELOP THERAPIES AND THE THERAPIES ARE IN FACT AIMED AT THE SPECIFIC PATHOLOGIES. WE'RE GOING TO RELY ON COMBINATION THERAPY DOWN THE ROAD. I THINK THAT'S INEVITABLE, IT HAPPENS IN MANY OTHER DISORDERS, HIV AIDS HYPERTENSION SO THIS IS NOT UNCOMMON THAT THIS IS WHERE WE'RE HEADED SO THE AD, ADRD IS SUFFICIENT, IMPORTANTS HAS PRACTICAL IMPLICATIONS, HAS SAILIBILITY TO THE GENERAL PUBLIC BUT PEOPLE IN THIS ROOM APPRECIATE THE FACT THIS IS MUCH MORE COMPLEX AND THE NEXT COUPLE OF DAYS B WILL SHED LIGHT ON THESE ISSUES. SO THANK YOU AND I HOPE THAT'S GIVEN YOU SOME KIND OF DEPICTION HOW THE NATIONAL PLAN IS LED TO OUR MEETING TODAY. THANK YOU. [APPLAUSE] >> THANK YOU, RON. NOW IT'S A PLEASURE TO INTRODUCE DAVID HOLTZMAN FROM WASU UNIVERSITY, SCIENTIFIC CHAIR AND ROD CORVO CHAIR AT NINDS FOR THE NEXT TWO DAYS. DAVID. >> THANKS VERY MUCH, WALTER. PLEASURE TO BE HERE. GOOD MORNING TO EVERYBODY. I THINK THERE'S BEEN AN INCREDIBLE AMOUNT OF WORK AND I WANT TO THANK ALL OF THE PHYSICIANS AND SCIENTISTS WHO SPENT SO MUCH OF THEIR TIME PREPARING FOR THIS MEETING. I ALSO WANT TO ESPECIALLY THANK ROD CORVO, THE NINDS LEAD AND ALL HIS -- THE STAFF AT THE NINDS FOR PUTTING TOGETHER WHAT I THINK WILL BE A GREAT SUMMIT. SO OBVIOUSLY YOU'RE AT THE 2016 ADRD SUMMIT AND I WANTED TO GO THROUGH A BRIEF BIT OF HISTORY BEFORE WE MOVE TO THE PROGRAM. AS RON SAID THE NATIONAL PLAN TO ADDRESS ALZHEIMER'S DISEASE WAS IN CONSULTATION WITH STAKEHOLDERS, INSIDE AND OUTSIDE THE FEDERAL GOVERNMENT. THE NATIONAL PLAN REPRESENTS IF THE BLUEPRINT FOR ACHIEVING THE VISION OF A NATION FREE OF ALZHEIMER'S DISEASE AND RELATED DEMENTIAS AND THE RELATED DEMENTIAS WILL BE DISCUSSING TODAY ARE FRONTAL DEEM PORL DEMENTIA, LEWY BODY DEMENTIA, MIXED DEMENTIA AND VASCULAR DEMENTIAS. SO GOAL ONE OF THE PLAN WAS TO PREVENT AND EFFECTIVELY TREAT ADRD BY 2025 AND THIS WAS TO IDENTIFY RESEARCH PRIORITIES AND MILESTONES. SO IN 2013 THE NINDS NIH HELD A WORKSHOP HERE TO SOLICIT INPUT ON SPECIAL RESEARCH PRIORITIES AND TIME LINES FOR ADDRESSING RELATED DEMENTIAS. AND THIS FOLLOWED THE NIA'S PRIORITY SETTING AD SUMMIT IN 2012 AND IN 2015. SO IN 2013, WAS THE FIRST ADRD SUMMIT, IT WAS SPONSORED BY THE NINDS WITH SEVERAL OTHER AGENCIES. IN THAT SUMMIT PLANNING OCCURRED FOR 12 MONTHS PRIOR AND 80 SCIENTISTS PHYSICIANS AND ADMINISTRATORS INVOLVED. THAT WAS DHAIRED BY SCIENTIFIC -- CHAIRED BY TOM MONTEEN,. AS IN THE CURRENT CONFERENCE THE COMMITTEE PRESENTED RATIONALE FOR RECOMMENDATIONS AND TIME LINES. THERE WAS A LOT OF DISCUSSION AND FEEDBACK FROM THE AUDIENCE. SO 36 PRIORITIZED RESEARCH RECOMMENDATIONS THAT CAME FROM THAT SUMMIT. DEVELOPED BY EXPERTS AND HONED BY THE PUBLIC. SO THERE WERE FIVE SELECTEDDED TOPICS IN THAT SUMMIT. TWO WERE OVERARCHING, HEALTH DISPARITIES AND ETIOLOGY DEMENTIAS AND THE DISEASE SPECIFIC WERE LEWY BODY DEMENTIAS, FRONTAL TEMPORAL DEMENTIAS AND VASCULAR COGNITIVE IMPAIRMENT RELATED DISORDERS. SO WHAT HAPPENED AFTER THAT CONFERENCE IS THAT THERE WERE SEVERAL FUNDING OPPORTUNITIES ANNOUNCED. IN MOST OF THESE AREAS. SO THIS IS JUST A LISTING OF SOME OF THE RFAs THAT HAVE COME OUT AS A RESPONSE FROM THAT INITIAL SUMMIT. YOU CAN SEE THERE WERE TWO ON SMALL VESSEL VASCULAR CONTRIBUTIONS, ONE ON WHITE MATTER DISEASE, ONE ON LEWY BODY DEMENTIAS, ONE ON CENTER WITHOUT WALLS TO ADDRESS PATHOGENESIS. AND HEALTH DISPAIRTIES-RELATED DISPAIRTIES RELATED RO HCH 1. THERE'S NOW UNDERWAY A MOVE AD CONSORTIUM UNDERSTANDING VASCULAR CONTRIBUTIONS TO ALZHEIMER'S DISEASE. THIS IS LISTED THE NIH INVESTMENT IN ADRD BY YEAR. I WON'T GO THROUGH ALL THE NUMBERS BUT YOU CAN SEE THIS REALLY HAS LED TO NEW ADDITIONAL FUNDING FOR THESE DISORDERS. IN THE NAPA PLAN IN THIS SECTION THE NINDS, NIH IS TO CONVENE STAKEHOLDERS FOR ADRD SUMMIT TO REVIEW RESEARCH PROGRESS AND REFINE AND ADD NEW RECOMMENDATIONS AS APPROPRIATE BASED ON RECENT SCIENTIFIC EVIDENCE. HOW DO WE THINK ABOUT THIS? FROM A CLINICAL PERSPECTIVE, CERTAINLY WE SEE INDIVIDUALS WHO CLINICALLY DEVELOP WHAT WE CALL DEMENTIA OF THE ALZHEIMER'S TYPE OR THESE OTHER DISORDERS LEWY BODY DEMENTIAs, FTDs, VASCULAR CONTRIBUTIONS, MULTI-ETIOLOGY. THERE ARE INDIVIDUALS WHO APPEAR TO HAVE DISORDERS RELATIVELY PURE BUT AS RON WAS SAYING, YOU WILL HEAR MORE ABOUT DURING THIS SUMMIT, MANY PEOPLE AS THEY GET OLDER AND DEVELOP PARTICULAR DEMEANTING DISORDERS DON'T JUST HAVE ONE DISORDER SO THE MAJORITY OF PEOPLE WITH ALZHEIMER'S DISEASE CLINICALLY DIAGNOSED WHO ARE OLDER, HAVE CONTRIBUTIONS OF SEVERAL OF THESE DISORDERS PRESENT AND CONVERSELY MANY WHO DEVELOP THE OTHER DISORDERS ALSO HAVE ALZHEIMER'S DISEASE PRESENT. SO JUST IN REGARD TO THIS, THERE'S NOW GOING -- THERE IS AN RFA CAPTURING COMPLEXITY IN MOLECULAR CELLULAR MECHANISMS RELEASED TO STUDY THE OVERLAP BETWEEN THESE DISORDERS. SOFT FROM A SCIENTIFIC PERSPECTIVE, I THINK MANY PEOPLE AROUND THE COUNTRY HAVE THOUGHT IN ADDITION TO STUDYING ANY PARTICULAR COMPONENT OF THESE DEERSES YOU CAN THINK ABOUT THESE DISEASES FROM THEMATIC PERSPECTIVE, HOW ONE SCIENTIFICALLY ADDRESSES IN THIS DISORDER. ONE WAY TO THINK ABOUT THIS IS TO THINK ABOUT THE ISSUES OCCURRING IN MOST PROBLEMS SO THE NEURODEGENERATIVE DISEASES PREDOMINANTLY ARE DISORDERS OF PROTEIN AGGREGATION. U WHETHER STUDYING QUOTE UNQUOTE ALZHEIMER'S DISEASE OR OTHER DISORDERS, REALLY STUDYING THIS PHENOMENON IS GOING TO BE CRITICAL. A LOT OF EMERGING GENETIC EVIDENCE AND BIOLOGICAL EVIDENCE CLEARLY IMPLICATES THE INNATE IMMUNE SYSTEM IN THESE DISEASES, SO FURTHER STUDY ON THIS IS GOING TO BE CRITICAL TO HELP UNRAVEL DIAGNOSIS AND THERAPEUTIC APPROACHES. UNDERSTANDING WHY AXONS DENDRITES AND SYNAPSES ARE CENTERED AND DEGENERATE CROSS CUT ACROSS ALL THESE DISORDERS. EMERGING EVIDENCE HAS SHOWN SLEEP AND CIRCADIAN RHYTHM ARE DISRUPTED IN NEURODEGENERATIVE DISEASES AND CONVERSELY THERE'S A LOT OF EVIDENCE THAT ARE DISRUPTION IN SLEEP AND CIRCADIAN RHYTHM CONTRIBUTES TO THESE DISEASES. CERTAINLY PROTEIN CLEARANCE AND DEGRADATION IS A CRITICAL ISSUE OF THE CELLULAR LEVEL, EXTRA CELLULAR LEVEL AND PROBABLY IN CONTROLLING PROTEIN SPREADING WHICH YOU WILL HEAR MORE ABOUT. GENETICS HAS BEEN THE UNDERPINNING OF TRYING TO UNDERSTAND MOST DISORDERS AND YOU'RE GOING TO HEAR THIS ACROSS ALL THE SUMMIT DURING THIS MEETING. IN ADDITION TO UNDERSTANDING MORE ABOUT ATHEROSCLEROSIS AND ARTERIAL SCHOAR ROSIES, THERE'S INTERESTING -- SCLEROSIS, THERE'S A LOT OF THINGS WE NEED TO BETTER UNDERSTAND ABOUT THE NEUROVASCULAR UNIT, CONNECTION WITH BLOOD BRAIN BARRIER AND HOW THEY'RE IMPORTANT NOT JUST CAUSATION BUT REPAIR OF THE BRAIN. WHAT YOU'RE GOING TO SEE IN THE DIFFERENT TALKS IS THAT REALLY SPANS BOTH ALZHEIMER'S DISEASE AND RELATED DEMENTIAS IS THAT BIOMARKERS CHARACTERIZATIONS AND ASSESSMENT OF NOT ONLY SYMPTOMATIC INDIVIDUALS BUT ESPECIALLY PRE-SYMPTOMATIC INDIVIDUALS IS LIKELY GOING TO CHANGE THE FIELD, IT'S ALREADY STARTING TO DO THIS. IN ALZHEIMER'S DISEASE BUT ALL THESE DISORDERS SEEMS CLEAR THEY START MANY YEARS BEFORE THE SYMPTOMS BEGIN. SO IF WE'RE GOING TO MAKE AN IMPACT ON THESE DISEASES WE HAVE TO DEVELOP WAYS TO DIAGNOSE PRE-CLINICALLY TO INSTIGATE THERAPY AND OTHER LIFESTYLE CHANGES TO HAVE A BIG IMPACT. GENETIC AND EPIGENETIC ASSESSMENT OF INDIVIDUALS IS ALREADY EMERGING AS A MAJOR TOPIC ACROSS ALL THESE AREAS. AND HOW DO WE SCREEN PATIENTS FOR THESE ISSUES WHETHER EARLY OR RIGHT AT THE CUSP WHEN THEY DEVELOP A PROBLEM. THIS IS AREA THAT NEEDS MORE WORK TO DEVELOP CLINICAL QUANTITATIVE ASSESSMENT TO ACTUALLY DO ACCURATE DIAGNOSIS AND MANAGEMENT. SO WHETHER WE'RE TALKING ALZHEIMER'S DISEASE OR ALZHEIMER'S DISEASE RELATED DISORDERS, DISPARITIES AND POPULATION BASED ISSUES ARE RELEVANT TO ALL OF THEM, YOU WILL HEAR A SESSION ABOUT HEALTH DISPARITIES AND CLEARLY IMPACTS ON DEMENTIA AND ETHNIC AND RACIAL DIFFERENCES IMPACT NOT ONLY THE GENETICS OF THESE DISORDERS BUT ALSO THE COURSE OF THEM. AND WE NEED TO UNDERSTAND WHAT'S GOING ON IN THIS AREA MUCH MORE. SO IN REGARD TO THIS SUMMIT, THERE'S BEEN OVER SIX MONTHS OF PLANNING BY GREATER STHAN 80 SCIENTISTS PHYSICIANS AND ADMINISTRATORS, YOU WILL HEAR IN A MOMENT FROM ROD ABOUT WHAT'S GOING TO HAPPEN THE REST OF THE SUMMIT. THE STEERING COMMITTEE IS CONSISTED OF KAREN CHEN, TOM MONTEEN, BRUCE AND TONY FELL PES AND YOU CAN SEE THE SESSION COMMITTEES YOU HEAR FROM ARE LISTED. THE GOALS OF THE SUMMIT IS THE COMMITTEES WILL PRESENT RATIONALE FOR REVISIONSES TO THE CURRENT RESEARCH RECOMMENDATIONS AND TIME LINES AND HOPEFULLY THIS WILL PROVOKE ACTIVE DISCUSSION AT THE END OF EACH SESSION. SO WITH NO FURTHER ADIEU I WOULD LIKE TO INTRODUCE ROD P, THE NINDS LEAD FOR THIS SUMMIT TODAY. ROD. [APPLAUSE] >> WONDERFUL TO SEE SO MANY PEOPLE HERE TODAY, SO EARLY IN THE MORNING AND AFTER WORKING VERY HARD TOGETHER FOR A NUMBER OF MONTHS AS DAVE JUST SAID, REALLY WELCOME. WHAT I WOULD LIKE TO DO, A FEW LOGISTIC THINGS. IN TERMS OF UNDERSTANDING HOW WE HAVE BEEN WORKING TOGETHER AND HOW TO INTERPRET THE THINGS WE'LL BE TALKING ABOUT. WHAT I WOULD LIKE TO POINT OUT IS THAT WE'RE GOING TO HAVE PRIORITIZE RECOMMENDATIONS AND YOU WILL SEE SLIDES THAT HAVE THEM ON THE SLIDES AND A SHORT FORM FREQUENTLY YOU WILL SEE SOMETHING LIKE ONE SENTENCE WHERE YOU WILL SEE FOR EXAMPLE HERE DEVELOP NEXT GENERATION EXPERIMENTAL MOLTEDS AND TRANSLATION -- MODELSEN AND TRANSLATION IMAGING METHODS. YOU WILL SEE A TIME HERE, THIS IS A TIME FRAME, ONE TO SEVEN YEARS, THE COMMITTEE ESTIMATES THAT'S THE NUMBER OF YEARS IT WILL TAKE TO COMPLETE OR MAKE FULLY OPERATIONAL THE RECOMMENDATION. AND YOU WILL SEE HERE A TIME LINE. THAT'S A SPECIFIC YEAR. THAT'S THE SPECIFIC YEAR THAT THE COMMITTEE IS RECOMMENDING THAT THIS WORK STARTS. OF COURSE, EVERYONE IN THE ROOM UNDERSTANDS THAT'S PENDING RESOURCES AVAILABLE TO START THIS VERY IMPORTANT WORK. YOU WILL BE SEEING SOME SLIDES LIKE THIS FOR EXAMPLE DURING PANELS, THERE'S A FULL SLIDE WITH A SHORT VERSION OF RECOMMENDATIONS, THIS IS THE VASCULAR CONTRIBUTIONS TO COGNITIVE DEMENTIA IMPAIRMENT RECOMMENDATIONS. SOMETIMES PEOPLE WILL HIGHLIGHT A RECOMMENDATION BECAUSE THAT'S HA THEY'RE TALKING ABOUT FOR THE NEXT FEW SLIDES AFTER THAT. AND HELP YOU FRAME AND FOCUS ON THE SCIENCE AND THE SPECIFIC RECOMMENDATION. THE NUMBERS HERE, ONE, TWO, THREE, ONE, TWO, THREE. THE COMMITTEES HAVE RANKED THE RECOMMENDATIONS IN TERMS OF PRIORITY. NUMBER ONE MEANS THAT'S WHAT THE COMMITTEE HAS PROFESSIONALLY ESTIMATED SHOULD BE DONE FIRST WITH HIGHEST URGENCY. NUMBER TWO, AND THREE AND SO ON. SOME OF THE COMMITTEES RANKED THEIR PRIORITIES ONE THROUGH EIGHT, EACH COMMITTEE CAN HAVE UP UP TO EIGHT RECOMMENDATIONS. SOME OF THE COMMITTEES SPLIT INTO TWO FOCUS AREAS LIKE THIS PARTICULAR COMMITTEE DID. FOR VASCULAR CONTRIBUTIONS TO COGNITIVE IMPAIRMENT AND DEMENTIAS, SPLIT INTO BASIC MECHANISMS AND EXPERIMENTAL MODELS AND HUMAN BASED STUDIES, EACH THOSE TWO FOCUS AREAS HAVE A NUMBER ONE RECOMMENDATIONS. A SPECIFIC COMMITTEE CAN HAVE ONE NUMBER ONE RECOMMENDATION OR TWO BUT NO MORE THAN THAT. I WILL TALK ABOUT A FEW OF THE HIGHLIGHTS. AND I'LL SHOW THE NUMBER ONE RECOMMENDATIONS VERY BRIEFLY. THE MULTI-ETIOLOGY DEMENTIAS CHAIR I WANT TO THANK DAVE DALTON AND DAVID BENNETT FOR DOING A TREMENDOUS JOB, YOU WILL HEAR THEM NEXT. DAVID KNOPMAN. THE NUMBER ONE RECOMMENDATION IS DETECT COGNITIVE I IMPAIRMENT CONCERN TO HEALTHCARE PROVIDERS. THIS IS CRITICAL TO THE SHARED INTEREST OF US IN THIS ROOM I'M QUITE SURE OF THAT. DRAIIVE KNOPMAN WILL TALK ABOUT SOMETHING THAT COME UP A NUMBER OF TIMES IN THIS PROCESS AND NOT JUST FOR 2016 BUT OVER THE YEARS F STARTING WELL BEFORE 2016 AND THAT IS WHEN WE MAKE THESE RECOMMENDATIONS TO WHAT DEGREE ARE WE ASPIRATIONAL, SHOOTING FOR THE STARS, TRYING TO HAVE THAT HOME RUN AND THAT CURE. AND TO WHAT DEGREE ARE WE OPERATIONAL, REALIZING THERE'S CERTAIN THINGS THAT JUST REALLY HAVE TO BE DONE TO MOVE THE BALL DOWN THE FIELD AND IF WE DON'T DO THEM, WE'RE NOT GOING ANYWHERE FAST AND THEY DON'T LOOK AS GLAMOROUS TAS HOME RUN BUT NEED TO BE DONE, EVERYBODY WHO COMES TO THIS PODIUM HAS THEIR OWN TAKE AND THEIR OWN FEEL ON THE BALANCE BETWEEN ASPIRATIONAL OPERATIONAL AND IS ALL IMPORTANT. THE NON-GOVERNMENT ORGANIZATION SESSION IS CHAIRED BY SUSAN DICKINSON AND HOWARD FILLIT, I THANK THEM BOTH TREMENDOUSLY, IT'S A WONDERFUL LEARNING EXPERIENCE FOR ME PERSONALLY. THEY WILL -- LEADING A SESSION NUMBER ONE PRIORITY IS MORE EFFECTIVE COMMUNICATION BETWEEN NIH AND NON-GOVERNMENT ORGANIZATIONS. AND THEY WILL TALK ABOUT THAT. WITH SOME VISION ON HOW TO DO THAT. HEALTH DISPARITIES, JENNIFER MANLY, I SAW HER, SHE'S IN THE M ROOM, THANK YOU VERY MUCH, JENNIFER FOR CHAIRING THAT SESSION. AND THE NUMBER ONE RECOMMENDATION THERE ASSESS EPIDEMIOLOGY AND MECHANISTIC PATHWAYS OF DISPARITIES AND HEALTH BURDEN OF ALZHEIMER'S DISEASE RELATED DEMENTIAS. THE TIME FRAME ONE TO SIX YEARS TO IMPLEMENT AND TO START IN 2016 IS THE PROFESSIONAL JUDGMENT OF THE COMMITTEE. THEN WE SHOULD HAVE WHAT I THINK MAY BE A LIVELY DISCUSSION ABOUT A SPECIAL JOINT SESSION ON NOMENCLATURE, THIS EMERGED FROM A NUMBER OF COMMITTEES INTEREST IN TALKING ABOUT NOMENCLATURE WE USE IN DEMENTIA, MOST PROMINENTLY FROM THE MULTI-ETIOLOGY DEMENTIA SESSION AND NON-GOVERNMENT ORGANIZATION SESSION. ANGELA TAYLOR WILL GIVE TALK AND DAVE KNOPMAN. I HAVE THE ROSETTA STONE AND THE THEME OF COURSE MANY DIFFERENT WAYS OF TALKING ABOUT DEMENTIA AND COGNITIVE DISORDERS AND HOW DO WE MOST EFFECTIVELY DO THAT. SO WE CAN COMMUNICATE WITH OUR LOVED ONES, WITH OUR GENERAL PRACTICE DOCTORS, SPECIALISTS, FOR RESEARCH AND BASTE BASIC RESEARCHERS, IT'S VERY IMPORTANT FOR MULTIPLE REASONS THAT THEY WILL TALK. AND THOSE SESSIONS THAT I JUST MENTIONED THE NON-GOVERNMENT ORGANIZATION, THE MULTI-ETIOLOGY DEMENTIA AND HEALTH DISPARITIES, THOSE ARE CROSS CUTTING SESSIONS THAT HAVE SIGNIFICANCE ACROSS ALL PARTS OF DEMENTIA SPECTRUM AND WE HAVE OUR DISORDERS SPECIFIC SESSIONS LEWY BODY DEMENTIA, THANK YOU TO KAREN MARTYR AND DENNIS DIXON, FRONTAL TEMPORAL DEMENTIA, MICHAEL HUT TON AND BILL SEALLY AND VASCULAR DIMENSIONS TO COGNITIVE DYSFUNCTION AND DEMENTIA AND SPEAKING OF CHANGES NOMENCLATURE WE NOW HAVE THE SCIENTIFIC FIELD OFFER VASCULAR CONTRIBUTIONS TO COGNITIVE IMPAIRMENT AND DEMENTIA TO COMPLIMENT THE MORE CLINICALLY ORIENTED TERMS OF VASCULAR COGNITIVE IMPAIRMENT AND VASCULAR DEMENTIA. JUST NOW I'M CHARGED WITH TRULY LOGISTIC THINGS FOR DINING LUNCH IS ON YOUR OWN, THERE'S THE NATCHER CONFERENCE SENTENCER HAS A CAFETERIA, THERE'S A CAFETERIA IN LISTER HALL THAT WAY. BREAKS AND ALSO THE REFRESHMENTS YOU HAD THIS MORNING WHEN YOU CAME N I WANT TO THANK THE F NIH FOR DOING THIS, THIS IS SO WONDERFUL AND LUCKY AND A MEETING LIKE THIS TO BE ABLE TO HAVE THAT, BATHROOM, BESIDE AUDITORIUMS KEEP YOUR CELL PHONES SILENT. I WANT TO THANK OUR PARTNERS, WE HAVE REALLY HAD TREMENDOUS PARTNERSHIPS IN THIS MEETING. APPRECIATE IT VERY MUCH. WITH THAT I WOULD LIKE TO MOVE TO THE NEXT AGENDA T MULTI-ETIOLOGY DEMENTIAS AND I BELIEVE THAT FIRST UP WE HAVE DR. DAVID BENNETT. PLEASE WELCOME HIM. I'M SORRY, DR. DAVID KNOPMAN WALKING TOWARD ME. PLEASE WELCOME. COR VOW GLZ THANK YOU FOR INVITING ME AND COMMITTEE TO BE PART OF THIS SESSION. OUR GOAL WAS TO ADDRESS MULTI-ETIOLOGY DEMENTIA AND ALSO PRISON RELEASEE REOFFENDER LOOK AT ISSUES ABOUT CLINICAL DIAGNOSIS. MY CO-CHAIR WAS DAVID BENNETT AND THE OTHER COMMITTEE MEMBERS BRAD, BRADLEY BOEVE. HELENA CHUI, NEAL GRAPH RAD FORD, CHIADI ONYIKE AND SANDRA WEINTRAUB. APPRECIATE THEIR HELP AND JORDAN AND ROD FOR GREAT ASSISTANCE. AS ROD SAID, OUR GOALS WENT BACK AND FORTH BETWEEN OPERATIONAL AND ASPIRATIONAL AND TO START WITH THE OPERATIONAL, ONE OF THE KEY ISSUES OF -- THAT OUR COMMITTEE DEALT WITH WAS HOW TO IMPROVE THE DIAGNOSIS OF THE DEMENTIAs AND ALL OF THEM INCLUDING THE DEMENTIA DUE TO ALZHEIMER'S DISEASE AS WELL AS THE OTHER THREE PRINCIPLE ONES WE'LL TALK ABOUT HERE. WITHIN THIS TRADITIONAL VIEW, THERE CLEARLY ARE CLINICAL FEATURES THAT HAVE SIGNIFICANCE AND OUR CHARGE AND OUR CONCERN IS HOW TO IMPROVE KNOWLEDGE OF THESE DISORDERS IN THE COMMUNITY, ESPECIALLY AMOVE NEUROLOGISTS AND PSYCHIATRISTS AND GERIATRICIANS. OUR GOALS ALSO WERE ASPIRATIONAL AND DAVID HOLTZMAN MENTIONED THIS THIS AS DID RON, THAT BEING ABLE TO INCLUDE BIOMARKERS IN DIAGNOSIS IS GREAT ADVANTAGE TO US MOVING FORWARD BOTH WITH PRE-CLINICAL DIAGNOSIS AND WITH UNDERSTANDING HOW MULTIPLE ETIOLOGIES INTERACT. THESE WILL BE DISCUSSED IN GREAT DETAIL BY VARIOUS GROUPS, I'M NOT GOING TO GO INTO THEM HERE. I'LL JUST MENTION THAT WE AREN'T GOING TO TALK ABOUT THESE DISORDERS NOT BECAUSE THEY'RE NOT IMPORTANT BUT BECAUSE OF TIME CONSIDERATIONS. BUT ONE OF THE KEY ISSUES WE DEALT WITH AS A COMMITTEE WAS THAT GOING BACK TO THE VERY BEGINNING OF DIAGNOSTIC PROCESSES THAT THERE'S A PROBLEM AND I BORROWED THIS SLIDE FROM A PICTURE THAT I HAD SEEN IN THE NATIONAL ACADEMIES OF SCIENCE ENGINEERING AND MEDICINE THAT MAKES THE POINT THAT DIAGNOSIS IN AMERICAN MEDICINE NORTH AMERICAN MEDICINE, NEEDS WORK AND CERTAINLY THE CASE IN THE DEMENTIA WORLD. WE HAVE A UNIQUE PROBLEM IN THE DISEASE INVARIABLY VAST MAJORITY OF TIMES IS ASSOCIATESSED WITH LEADS TO NON-REPORT BIG PATIENT AND FAMILIES ALSO PARTICIPATE IN THAT, IT'S HUMAN NATURE. WE ALSO KNOW PRACTICES THAT GO ON AT THE PRIMARY CARE LEVEL ARE PROBLEMATIC, PHYSICIANS DON'T HAVE TIME TO QUERY PATIENTS PERFORMING MENTAL STATUS EXAM AND TALK TO FAMILIES AND ONE OF OUR PRESENTATIONS THAT WE'LL FOLLOW IS TALKING FROM THE MARE CARE -- PRIMARY CARE PERSPECTIVE THAT'S AN IMPORTANT ISSUE TO ADDRESS AND THE TISSUE ALREADY COVERED ABOUT LACK OF FA FAMILIARITY OF VARIOUS DEMEANTING ILLNESSES BESIDES ALZHEIMER'S IS SOMETHING WE ALSO WORRY ABOUT. THEN GETTING TO THE OTHER ISSUE ABOUT MULTI-ETIOLOGY, THIS IS A SLIDE I BORROWED FROM PETE NELSON, KENTUCKY, SHOWING THE REALITY, HE HAS A MORE DETAILED ONE BUT LEAVE IT AT THIS, COMPLICATED ENOUGH, THAT THESE ETIOLOGIES CO-OCCUR WITH ADVANCING AGE, THIS IS SOMETHING WE SNEAD DEAL W. IT IS THE CASE THAT WE'RE LOOK AT YOUNG PEOPLE AND IDEALIZE SETTING, WE MAY IN FACT SEE DISEASE IN MORE PURE FORM BUT WHEN WE LOOK AT THE MORE ADVANCED AGE, AS MANY OF THESE CO-OCCUR. THIS IS MY FEEBLE ATTEMPT TO DEPICT THAT BUT FROM REALITY, CLINICAL REDWRAIL, SMS -- REALITY, THIS IS SOMETHING WE NEED TO LEARN TO DEAL W WE NEED LANGUAGE WE STILL DON'T HAVE AND NEED TO CHANGE OUR CONSENT ACTUAL THINKING TO COME DATE THIS. SO THIS LED -- ACCOMMODATE THIS. THIS LED TO OUR RECOMMENDATIONS, THE KEY ONE IMPROVING DIAGNOSTIC STILL SKILLS IN THE COMMUNITY, AND WE'LL TALK ABOUT THESE IN VARIOUS WAYS. WE WANTED TO MAKE THE POINT MERE RESEARCH NOT JUST WITHIN EACH SILO, I DON'T MEAN IN PAPA JOURTIVE SENSE BUT WITHIN EACH SPECIFIC DISEASE GROUP DISCUSSED HERE, ALSO NEEDS TO INCLUDE LOOKING AT THEIR INTERACTIONS. THE ISSUE FOR SCREENING COGNITIVE IMPAIRMENT WE'LL LEAVE FOR ANOTHER DAY. LATER WITH THE NON-GOVERNMENTAL ORGANIZATION GROUP WEAL HAVE PA STUDIES CUSHION ABOUT NOSOLOGY, BECAUSE NOSOLOGY DRIVES HOW WE THINK. SO I WILL STOP HERE AND I WILL TURN THE PODIUM OVER TO THE FIRST SPEAKER FROM OUR MULTI-ETIOLOGY SECTION WHICH I THINK IS DR. GWEN WINDHAM. THANK YOU VERY MUCH. [APPLAUSE] GWEN IS A GERIATRICIAN. >> THANK YOU, THANK YOU FOR THIS OPPORTUNITY, IT -- AN HONOR TO BE AMONG YOU THINKING AND TALKING ABOUT THESE IMPORTANT ISSUES. CAN EVERYONE HEAR ME? SO I HAVE BEEN ASKED TO SPEAK ABOUT THE PROBLEMS, BARRIERS AN POTENTIAL SOLUTIONS OF DIAGNOSING DEMENTIA AND PRIMARY CARE AND I HAVE BEEN ASKED TO DO SO QUICKLY. WHICH CAN BE CHALLENGING FOR A SOUTHERNER LIKE ME. SO MOVING ALONG WITH THIS. I WANT TO FIRST POINT OUT THAT THE PRIMARY CARE OFFICE IS THE PLACE OLDER ADULTS INTERACT WITH THE HEALTHCARE SYSTEM, THE MOST OFTEN. SO THIS IS NOT A PROBLEM IT IS AN OPPORTUNITY, AN OPPORTUNITY TO IMPROVE CARE. THE PROBLEM REALLY IS THAT UP TO TWO-THIRDS OF PATIENTS WHO HAVE DEMENTIA AND SEEN IN A PRIMARY CARE SETTING DON'T HAVE THEIR DIAGNOSIS AT LEAST DOCUMENTED IN THE CHART. INTERACTING WITH THE -- BETWEEN PRIMARY CARE PHYSICIANS AND PEOPLE WHO HAVE ADDITIONAL TRAINING LIKE GERIATRICIANS DOES IMPROVE THE NUMBER OF WHO ARE DIAGNOSED WITH DEMENTIA BUT IT GOES BEYOND NUMBERS. INTERDISCIPLINARY TEAMS ADDED WORKING WITH PRIMARY CARE OFFICES HAVE BEEN SHOWN TO INCREASE ADHERENCE TO CERTAIN DEMENTIA CARE GUIDELINES. TO REDUCE SYMPTOMS OF PSYCHOLOGICAL AND BEHAVIORAL SYMPTOMS ASSOCIATEDDED WITH DO DEMENTIA. AND ALSO HAVE A POSITIVE IMPACT ON CAREGIVERS OF PATIENTS WHO HAVE DEMENTIA. SO THERE ARE REALLY GOOD THINGS THAT WE THINK DO TO HELP IMPROVE THE CARE OF PATIENTS WHO HAVE DEMENTIA IF WE IMPROVE THE CARE THROUGH THE PRIMARY CARE OFFICES. SOME OF THE BARRIERS HAVE BEEN INADEQUATE TIME AND ALSO INADEQUATE STAFF. I WOULD SKIT'S NOT JUST THAT INITIAL EVALUATION BUT THE MORE TIME CONSUMING PART COME IN AFTER DIAGNOSIS IS MADE. SO THERE ARE QUESTIONS THAT INVOLVE KNOWLEDGE AT LEAST BY THE PHYSICIAN AND OFTEN BY OTHER ANCILLARY STAFF MEMBERS WHO PROVIDE COUNSELING AND EDUCATION. SOME PHYSICIANS ALSO REPORT ISSUES WITH LOW REIMBURSEMENT ESPECIALLY FOR VERY TIME CONSUMING ENCOUNTERS. POOR KNOWLEDGE RESOURCES WHERE WHEN ESPECIALLY A DIAGNOSIS UNCOVERS SOCIAL ASPECTS THAT REQUIRE ADDITIONAL SERVICES NOT KNOWING HOW TO TAP INTO RESOURCES TO HELP THOSE PATIENTS AND FAMILIES. IS AN ISSUE. SOME PHYSICIANS FEEL LIKE THEY JUST DON'T HAVE THE TRAINING OR KNOWLEDGE OR SKILL SET TO DO THE EVALUATION AND PROVIDE ADEQUATE ONGOING CARE. A SMALL STUDY SUGGESTED THAT PERHAPS EVEN PHYSICIAN INTERESTS OR TIME POTENTIALLY CONTRIBUTES AS WELL. FOR EXAMPLE, WHEN OFFERED EDUCATIONAL PROGRAM TO IMPROVE THE OR TO EDUCATE PHYSICIANS ON HOW TO PERFORM EVALUATION AND PROVIDE ONGOING CARE, ONLY ONE IN SIX OPTED INTO THAT PROGRAM. PHYSICIANS ALSO HAVE REPORTED CONCERNS ABOUT NOT BEING ABLE TO ACCESS SPECIALISTS WHEN THEY NEED THEM. AND THEY QUESTION BENEFIT OF DIAGNOSIS, PARTICULARLY GIVEN LIMITATIONS OF OUR CURRENT TREATMENT OPTIONS. LIKELY THERE ARE ALSO PATIENT FACTORS AS WELL SO DAVE ALLUDED TO THESE, ONE STUDY HAS SHOWN THAT IN PATIENT WHOSE INITIALLY AGREE TO UNDERGO A COGNITIVE SCREENING EXAMINATION A LITTLE OVER A HALF OF THEM WHO HAD SOME CONCERNING FINDING WOULD NOT AGREE TO MOVE FORWARD WITH A FURTHER EVALUATION. HERE ARE A FEW POTENTIAL SOLUTIONS OUR GROUP TALKED ABOUT ADDRESSING EACH BARRIER THAT I PRESENTED ALREADY. SO ONE IS THAT AS A GROUP WE FELT THERE ARE ENOUGH COGNITIVE SCREENING TOOLS THROUGHOUT, WE JUST NEED TO FIND EFFECTIVE EFFICIENT ONES THAT WE CAN USE IN CLINIC SETTINGS. E WE NEED TO FIGURE OUT HOW TO ENGAGE ANCILLARY STAFF OR TECHNOLOGY, MAYBE PRIVY SIT QUESTIONNAIRES IN THE OFFICE, WAITING ROOM OR HOME TO BRING IN AND PERHAPS COUNSELING PHYSICIANS HOW TO APPROPRIATELY BILL TO GET PAY FOR WORK YOU HAVE DONE. PARTICULARLY WHEN THERE'S NOT A PROCEDURE CODE OR ENM CODE COUNSELING EDUCATION PROVIDED. ON THE PAYER SIDE WE MIGHT THINK OF WAYS TO SIMPLIFY REIMBURSEMENT PROCESS I WOULD LIKE TO PUT A PLUG IN HERE FOR SUPPORT STAFF ACROSS ALL LEVELS OF HEALTHCARE PROVIDERS AND IN ALL SETTINGS IN PATIENT AND -- IN PATIENT AND OUT. WE NEED TO TREAT -- TEACH PEOPLE HOW TO COMMUNICATE AND INTERACT WITH COGNITIVELY IMPAIRED PATIENTS. SPECIFICALLY PRIMARY CARE SETTING HAVING A POINT PERSON WOULD LIKELY BENEFIT. AND MOST OFTEN TENDS TO BE A SOCIAL WORKER BECAUSE THEY CAN PROVIDE ACCESS TO RESOURCES THERE, THEY HAVE FINGER ON THE BUTTON OF WHAT'S GOING ON IN THE COMMUNITY AND RESOURCES TO HELP FAMILIES AN CAREGIVERS. THEN ADDRESS PHYSICIAN KNOWLEDGE ISSUE. WE HAVE DISCUSSED POTENTIAL UTILITY TO HAVING RED FLAGS. PRIMARY CARE PHYSICIANS USE THIS IN OTHER TYPES OF CONDITIONS, FOR EXAMPLE LOW BACK PAIN IF A PATIENT AS RDZ FLAGS THAT WARRANT IMAGING OR REFERRAL, SOMETHING SIMILAR DONE FOR DEMENTIA. SO A RED FLAG IN HISTORY OR THE FIZZLECAL EXAM THAT MIGHT WARRANT ADDITIONAL TESTING OR REFERRAL TO SPECIALIST. WE MIGHT ALSO THINK ABOUT WAYS THAT WE CAN PARTNER WITH CERTIFICATION BOARDS OR CONTINUING MEDICAL EDUCATION SO THAT EXPERTS CAN PROVIDE ADDITIONAL TRAINING OPPORTUNITIES, THESE COULD BE DONE WITH TECHNOLOGY WE HAVE TODAY, EASY TO IMPLEMENT THIS AND TO MAKE IT MORE WIDESPREAD. I THINK BY ADDRESSING SOME OF THESE THINGS WE MIGHT LIMIT THE NEED FOR SOME OF THE ACCESS TO SPECIALISTS, ALTHOUGH THE LIMITED ACCESS TO NEUROLOGISTS AND NEUROPSYCHOLOGISTS OR OTHER EXPERTS MAY CONTINUE, WILL CONTINUE I THINK TO BE A PROBLEM. IN MISSISSIPPI WHERE I LIVE AND WORK WE'RE A VERY RURAL AREA, AND JUST A NOTE HERE FOR POTENT TOCIAL USE TECHNOLOGY. WE HAVE TAPPED INTO INFRASTRUCTURE FOR EXAMPLE, WHERE VIDEO AND BLUE TOOTH TECHNOLOGY IS BEING USED. TO CONNECT US WITH CLINICS SO WE CAN HAVE A VIDEO CONFERENCE, WE HAVE A NURSE WE HAVE TRAINED IN PERSON TO HELP WITH COGNITIVE SCREEN AND NEUROLOGICAL EXAM. THIS IS OFFERING SOME OPPORTUNITY TO TO BRING SOME ADDITIONAL EXPERTISE TO MORE RURAL AREAS. AND UNDERSERVED AREAS. REGARDING TREATMENT LIMITATIONS AND THE PERCEPTION THERE'S LACK OF BENEFIT OVERALL IN A DIAGNOSIS, THIS IS SOMETHING TA H THAT REALLY REQUIRES MORE STUDY. BUT THERE IS SOME EVIDENCE THAT PROVIDING SOME ADDITIONAL INPUT TO THE PRIMARY CARE OFFICES INCREASES THE USE OF COGNITIVE SCREENING TOOLS BY PRIMARY CARE PHYSICIANS. PHYSICIANS THEN BEGIN ALSO TO REFER OUT FOR SERVICES AVAILABLE IN THE COMMUNITY THEY HAVE BECOME AWARE OF. AND OTHER IMPORTANT OUTCOMES FOR PATIENTS AND CAREGIVERS HAVE IMPROVED BETTER SCORES ON BEHAVIORAL PSYCHOLOGICAL SYMPTOMS ASSOCIATED WITH DEMENTIA. AND MAY ALSO INCREASE COST FOR EXAMPLE PATIENTS TENDED TO HAVE MORE OFFICE VISITS. MEASURING THE EFFECT OF ANY INTERVENTIONS THAT MIGHT BE IMPLEMENTED. WE WANT TO KNOW IF THE INTERVENTION IMPROVE IT IS DIAGNOSE KNOWSIS. COMPARING THE GOLD STANDARD AND ANY INCREMENTAL INCREASE PROVIDED BY ADDITIONAL MEASURES WE MIGHT ADD. THE OUTCOMES TO NOT ONLY INCLUDE THE DIAGNOSIS AGREEMENT BUT OTHER OUTCOMES THAT ARE IMPORTANT INCLUDING THE ALL PARTICIPANT SATISFACTION WITH INTERACTION KNOWLEDGE CAREGIVER HEALTH, BEHAVIORAL AND PSYCHOLOGICAL SYMPTOMS SO FORTH. THAT CONCLUDES THE PROBLEMS BARRIERS AND POTENTIAL SOLUTIONS IN PRIMARY CARE SETTINGS. NOW I'LL PASS IT BACK OVER TO DAVE. [APPLAUSE] >> THANK YOU, GWEN. OUR NEXT SPEAKER WILL BE DR. SANDY WEINTRAUB WHO IS GOING TO BE APPROACHING THIS SAME TOPIC FROM THE TECHNOLOGY AND POINT OF VIEW AND LOOKING AT SOME NEW WAYS TO IMPROVE CARE IN THE PRIMARY CARE SETTING. SANDY. >> THANK YOU, DAVID. TO SO I'M GOING TO VERY QUICKLY TELL YOU ABOUT THE IMPORTANCE OF COMPUTERIZED ASSESSMENT AND REMOLT ASSESSMENT TO HELP WITH THESE ISSUES OF IDENTIFYING AIM PUSHING THE RIGHT BUTTON? SO WE NEED MORE EFFECTIVE METHODS AS GWEN SHADES THE TECHNOLOGY IS THERE WE NEED TO MAKE USE OF IT AND WE NEED MORE EFFICIENT METHODS TO TEST FOR COGNITIVE BEHAVIORAL SYMPTOMS BOTH SCREENING AND ALSO FOR DIFFERENTIAL DIAGNOSIS OF DEMENTIA. NEUROPSYCHOLOGICAL ASEMENT IS THE TOOL WE HAVE AVAILABLE NOW THAT A ACTUALLY FOCUSES ON THIS SYMPTOMS OF THE DEMENTIA. BUT WHAT ARE IS SYMPTOMS TESTIMONY ASSESSMENT QUANTIFY IT IS SYMPTOMS AND THAT WAY CONTRIBUTES TO DIFFERENTIAL DIAGNOSIS. SO WE'RE THE ONE WHOSE SAY WHAT'S THE DIFFERENCE USING APHASIA AND AMNESIA. THAT IS IMPORTANT BECAUSE RIGHT NOW WE DON'T HAVE VERY EFFICIENT EFFECTIVE TREATMENT SO WE NEED TO BE ABLE TO INTERVENE BEHAVIORALLY, YOU'RE NOT GOING TELL A FAMILY WITH A PATIENT TO DO SAME THINGS AS SOMEBODY WHOSE BEHAVIOR IS PROBLEMATIC. THE BIG PROBLEM WITH NEUROPSYCHOLOGICAL ASSESSMENT AS POINTED OUT, THE PROCEDURES ARE VARIABLE ACROSS CLINICAL PRACTICE. WE'RE NOT AUTISM ON THE SAME PAGE PROCEDURES ARE LENGTHYEN AND PRACTITIONERS AREN'T REALLY GENERALLY AVAILABLE FOR PEOPLE WHO ARE P IN REMOTE AREAS. WHAT DOES THE ASSESSMENT OFFER OVER PAPER AN PENCIL? A LOT OF THING, IT REMOVES EXAMINER VARIABILITY, THE DATA ARE A LITTLE MORE RELIABLE THAN IF WRITING THING DOWNS WITH PAPER AND PENCIL. DATA ARE ALSO EASILY SENT TO DATABASES FOR SCORING AND ANALYSIS. WE MEASURE MILLISECOND REACTION TIME, A BIG BENEFIT BECAUSE THAT CAN PERHAPS INCREASE SENSITIVITY TO EARLIER STAGES. IT SHORTENS TESTING. SO NIH TOOLBOX FOR EXAMPLE, WE USE ITEM RESPONSE THEORY, COMPUTER ADAPTIVE TESTING, THERE'S OTHER MEASURES TO SHORTEN AMOUNT OF TESTING YOU NEED. YOU CAN IN FIVE MINUTES GET AN EMOTIONAL SCREENING BATTERY FOR EXAMPLE. IT'S ACCESSIBLE AND APPLICABLE TO DIVERSE SETTINGS AND POPULATIONS. REMOTE COMPUTERIZE AID SEESMENT INCREASES THE PROBABILITY OF REACHING LARGE NUMBERS OF INDIVIDUAL BUS WE ALL KNOW THERE ARE SOME PROBLEMS ASSOCIATED WITH REMOTE ASSESSMENT BATTERY. YOU NEED AN INTERNET CONNECTION, SERVERS ARE UNRELIABLE. WEB-BASED SECURITY WE HAVE BEEN ENCOUNTERING THIS ISSUE THREATEN TEST INTEGRITY AND SECURITY. YOU DON'T WANT TO TEST ON THE INTERNET THAT ANYBODY CAN LOOK UP AND LEARN THE ANSWERS TO AND VIOLATE THE SECURITY OF THE TEST. REMOTE METHOD, ANYBODY WHO WANTS TO ARGUE WITH ME I'M HAPPY TO ARGUE ABOUT THIS, ARE NOT APPROPRIATE AT THIS POINT FOR DIFFERENTIAL DIAGNOSIS. I'M NOT GOING TO SPEND TIME GOING OVER BATTERIES, THAT'S NOT THE PURPOSE OF THIS PRESENTATION BUT I DO WANT TO HIGHLIGHT TWO, ONE IS COST DATE WHICH HAS BEEN VERY WELL ESTABLISHED, AS A USEFUL SHORT SCREEN BATTERY, IT'S COMPUTER-BASED, IT USES FAMILIAR STIMULI, IT WAS BRILLIANT TO USE PLAYING CARDS BECAUSE INITIALLY THE IF I RECALL CORRECTLY DAVID DARBY TOLD ME THEY WANTED TO BE ABLE TO USE THIS TEST IN ABOUT RIDGENAL POPULATIONS P IN AUSTRALIA. THE PLAYING CARDS ARE GREAT BECAUSE EVERYBODY KNOWS THEM. IT'S SHOWN TO BE ABLE TO DETECT MCI AND ALZHEIMER'S DEMENTIA. THE NIH TOOLBOX IS AN INSTRUMENT THAT WAS DEVELOPED, THERE IS A COGNITION COMPONENT BUT ALSO EMOTION MOTOR SENSORY FUNCTION COMPONENTS THAT REALLY CAN PERHAPS WIDEN THE SPECTRUM OF SYMPTOMS THAT WE'RE ABLE TO PICK UP TO SCREEN AND USE FOR DIFFERENTIAL DIAGNOSIS, SUPPORTED BY NIH BLUEPRINT. AND THE ADVANTAGE OF THIS TEST IS IT WAS DESIGNED TO TEST THE FULL SPECTRUM OF NORMAL FUNCTION BETWEEN AGE 3 AND 85. SO KIND OF POSSIBLE TO DO MORE LONGITUDINAL FOLLOW-UP. WE HAVE IT ON AN iPAD, IT ELIMINATES SECURITY AND INTEGRITY CONCERNS BECAUSE IT CAN BE DOWNLOADED SP THIS INSTRUMENT IS BEING CONSIDERED AS AN ADD ON TO INFORMED DATA SET FOR O&A DISEASE CENTER. SO WHAT DO WE NEED? WE NEED TO DEVELOP TESTS THAT CAN BE DOWNLOADED AND DON'T NEED THE INTERNET OR SERVER, WE NEED TO DWOB WEB-BASED METHODS TO PROTECT TEST SECURITY AND INTEGRITY. WE NEED TO STANDARDIZE THESE OHIO SORRY. I DON'T KNOW HOW TO TURN IT OFF. OKAY. I LIKE TO HAVE MY OWN TIMER. WE NEED TO STANDARDIZE AND INSTRUMENTS WE NEED THESE FUNDED ACROSS DIVERSE POPULATIONS ALSO PROVIDE THE TECH SUPPORT FOR USE AND IMPROVEMENT OF THESE INSTRUMENTS. TECHNOLOGY IS CHANGING DAILY. P WE NEED TO DEVELOP AUTOMATE MED SURES TO ADMINISTER IN THE HANDS OF TRAINED CLINICIANS. AND THAT'S ALL FOR ME. [APPLAUSE] Q. GOOD MORNING, I WOULD LIKE TO INTRODUCE THE NEXT SPEAKER. WHO IS DAVID BENNETT. THANK YOU, DAVID FOR THAT WOUND FOREL INTRODUCTION. -- FOR THAT WONDERFUL INTRODUCTION. SO I WANT TO THANK ROD AND THE ORGANIZERS B AND MY CO-CHAIR FOR GIVING THE OPPORTUNITY SAY A COUPLE OF THINGS ABOUT THE OVERLAP OF DIFFERENT NEURODEGENERATIVE DISEASE ETIOLOGIES AND VASCULAR ETIOLOGY. I GET TO SHARE SOME DATA. THAT ACTUALLY SUPPORT A LOT OF THINGS THAT YOU HAVE BEEN HEARING ALREADY, THERE'S A THEME RUNNING THROUGH THIS SESSION. I WANT TO THANK MY COLLEAGUES, THAT ACTUALLY GENERATEDDED A LOT OF DATA, ESPECIALLY JULIE SCHNEIDER AND ZOE AND LISA BURNS, THINK THINK THEY'RE HERE. AND NIA NINDS ALZHEIMER'S ASSOCIATION AND STUDY PARTICIPANTS. SO WHEN I WENT TO NEUROLOGY SCHOOL I WAS TAUGHT TO DO A DIFFERENTIAL DIAGNOSIS. AND DECIDE WHETHER SOMEBODY PRESENTING WITH COGNITIVE IMPAIRMENT HAS ALZHEIMER'S DISEASE OR VASCULAR DEMENTIA OR DIFFUSE LEWY BODY DISEASE OR FTD OR PROGRESSIVE AFASCIA. BUT IN FACT, THIS IS NOT HOW DEMENTIAs OCCUR. SO THESE ARE DATA FROM A CLINIC SAMPLE. OF AFRICAN AMERICANS THAT WERE TRUE TO ONE MATCHED WITH CAUCASIANS. AND WHAT YOU SEE IS AS WE'LL START HERE IS THESE PEOPLE, ABOUT 930% THAT WE LABEL HAVING ALZHEIMER'S DISEASE DO IN FACT ARE HAVE ALZHEIMER'S DISEASE. BUT MOST OF THOSE PEOPLE HAVE SOME OTHER CO-EXISTING PATHOLOGY. IN THIS CASE WE LOOK AT TWO OTHER PATHOLOGIES WHICH IS CEREBRAL INFARCTS AND LEWY BODIES. AND AFRICAN AMERICAN THERE'S MUCH MORE LIKELY TO HAVE MIXED PATHOLOGIES. SO PURE ALZHEIMER'S DISEASE EVEN TERTIARY CARE CLINIC WHERE WE SEE RELATIVELY YOUNGER PEOPLE AND SOMETIMES MORE SPECIFIC PEOPLE WHO THINK THEY HAVE ALZHEIMER'S DISEASE, IS YOU GOT THIS ENORMOUS BURDEN OF MIXED P PATHOLOGY. SO NOW I WANT TO MOVE INTO THINKING ABOUT HOW DO THESE MIXED PATHOLOGIES ACTUALLY DRIVE DEMENTIA. HERE WE HAVE TO LEAVE OUR CLINIC AND GO INTO THE COMMUNITY WHERE WE CAN SEE PEOPLE THAT DON'T HAVE ALZHEIMER'S DISEASE, DON'T HAVE DEMENTIA AND FOLLOW THROUGH TO DEMEANTING PROCESS AND EVENTUALLY TO AUTOPSY TO SEE WHAT THEY HAVE. SO DATA FROM TWO STUDIES, MANY ARE FAMILIAR WITH THEM, ONE RELIGIOUS ORDER STUDY, INVOLVES NOW OVER 1350 OLDER NUNS, PRIESTS AND BROTHERS ACROSS THE U.S., THEY AGREE TO BE TESTED EVERY YEAR, EVERYONE IS A BRAIN DO NOMPLET LARGE NUMBERS OF PEOPLE HAVE DEVELOPED DEMENTIA, AD DEMENTIA, MCI, A LOT OF AUTOPSIES. THE SECOND ONE SCALLED THE TESTIFY AGING PROJECT, MORE THAN 1850 PEOPLE, AGAIN FROM NORTH EASTERN ILLINOIS, ENROLL WITHOUT DEMENTIA, EVERYONE IS AN ORGAN DO NEW YORK CITY BRAIN SPINAL CORD MUSCLE AND NERVE, MANY DEVELOPED DEMENTIA AND MCI AND THERE'S BEEN LARGE NUMBER OF AUTOPSIES. SO LET'S LOOK AT THE RELATION OF COMMON PATHOLOGIES, TO DEMENTIA IN GENERAL AND EVEN TO THIS AD DEMENTIA SYNDROME. SO LET'S START WITH PATHOLOGY OF THREE MOST COMMON DISEASE. ANY TEXT TBOOK TELL YOU ALZHEIMER'S DISEASE, LEWY BODY DISEASE, ACCOUNT FOR 95% OF DEMENTIA. SO HERE IS ALZHEIMER'S, THERE'S A CEREBRAL INFARCT, THERE'S SOME CORTICAL LEWY BODIES. SO IF WE EYE COTMIZE ALZHEIMER'S DISEASE IN PRESENT OR ABSENT, IF WE LOOK HERE WE SEE PEOPLE WITH PROBABLE ALZHEIMER'S DISEASE, THE VAST MAJORITY DO IN FACT MEET PATHOLOGIC CRITERIA FOR ALZHEIMER'S DISEASE. BUT IT TURNS OUT MORE THAN HALF OF THEM HAVE ARE SOME TYPE OF CO-MORBID CONDITION, LEWY BODIES INFARCTS OR BOTH INFARCT AND LEWY BODIES. FOR THOSE WITH MILD COGNITIVE IMPAIRMENT, ALMOST THREE QUARTERS HAVE SOME PATHOLOGY OVER HALF HAVE ALZHEIMER'S DISEASE, MANY OF THOSE PEOPLE ALSO HAVE ALZHEIMER'S DISEASE WITH CO-EXISTING CONDITION. EVEN PEOPLE WHO ARE SQUEAKY CLEAN NORMAL COGNITIVELY, THEY DON'T MEET CRITERIA FOR DEMENTIA OR MCI HALF OF THESE PEOPLE HAVE SOME PATHOLOGY INCLUDING A THIRD WITH ALZHEIMER'S INCLUDING WITH INFARCTS, INFARCTS, LEWY BODIES SO WHAT WE WANT TO UNDERSTAND IS WHAT IS DRIVING PEOPLE THIS DIRECTION INTO GETTING CAN DEMENTIA WITH THESE PATHOLOGIES, AND ALSO WHAT IS KEEPING PEOPLE WITH THESE PATHOLOGIES FROM DEVELOPING COGNITIVE IMPAIRMENT, SO THINK ABOUT ALL COMPETING PROCESSES IN THE BRAIN. SO ONE MORE TYPE OF PATHOLOGY WHICH IS MICROSCOPIC INFARCTS. AND WE'LL LOOK AT A NUMBER OF FIGURES THAT LOOK LIKE THIS, I'LL WALK THROUGH THIS IN SOME DETAIL. WE TAKE OUR ALZHEIMER'S DISEASE AND WE MAKE IT ON TO A SCALE OF -- SO WE'RE NO LONGER LOOKING AT PATHOLOGICAL ALZHEIMER'S DISEASE OR NOT, BURDEN OF ALZHEIMER'S PATHOLOGY ON CONTINUOUS SCALE. THIS LINE REPRESENT IT IS PROBABILITY OF HAVING DEMENTIA, IF YOU BASICALLY ONLY HAVE ALZHEIMER'S DISEASE IN THE BRAIN. SO MORE PATHOLOGY YOU HAVE THE MORE LIKELY YOU ARE TO BE DIDEMENTED. ONE UNITS OF PATHOLOGY B, WHICH IS SLIGHTLY MORE THAN THE MEAN. SO YOUR PROBABILITY WITH ALZHEIMER'S DISEASE IS 40%. IF YOU HAVE ALZHEIMER'S PLUS INFARCT, IT GOES UP TO ALMOST 60% MACROSCOPIC INFARCT. MICROSCOPIC INFARCTS UP TO 65%. LEWY BODYs, YOU'RE UP TO 85% SO MORE DOUBLE YOUR ODDS OF DEMENTIA BY ADSING THESE DIFFERENT PATHOLOGIES WITH THE SAME ALZHEIMER'S PATHOLOGY. FIRST TRY TOWNS WHAT DRIVES PATHOLOGY. IN HIS CASE WE LOOK AT TIME OF DEATH HERE, THESE ARE MULTIPLE YEARS PRIOR TO DEATH AND THIS IS LATE MOCK UP MODEL TRANSITION FROM NORMAL COGNITIVE IMPAIRMENT TO MILD COGNITIVE IMPAIRMENT, TO MODERATE COGNITIVE IMPAIRMENT. THESE AREN'T CLINICALLY STAGED THIS IS EMPIRICALLY DERIVED FROM THE LONGITUDESNAL DATA THAT WE CAN LINK TO A PATHOLOGY. GETTING ALZHEIMER'S DISEASE IS A COMPETITION. IT'S A COMPETITION THAT FOR MOST OF HUMAN HISTORY, ALZHEIMER'S DISEASE LOST. UP UNTIL THE LAST 50 YEARS OR SO. THE COMPETITION IS WITH DEATH. IF YOU DIE BEFORE YOU GET ALZHEIMER'S DISEASE, YOU DO NOT GET ALZHEIMER'S DISEASE. IT WORKS EVERY TIME. HERE IS PROBABILITY OF DEATH OVER TIME, CONSTANT THROUGH OUR STUDY. LET'S START WITH PEOPLE THAT DON'T HAVE PATHOLOGIC ALZHEIMER'S DISEASE. AND HERE WE'RE GOING TO LOOK AT THE TRANSITION FROM NCI, FROM NO COGNITIVE IMPAIRMENT TO SOME TYPE OF COGNITIVE IMPAIRMENT SO WITHOUT PATHOLOGIC ALZHEIMER'S OR INFARCTS OF LEWY BODIES, YOU STILL HAVE HAVE A ABOUT A 20% LIKELIHOODS OF DEVELOPING DMOIGTIVE IMPAIRMENT BEFORE DEATH. IF YOU HAVE PATHOLOGIC ALZHEIMER'S DISEASE THAT DOUBLES TO ALMOST 40%. IF YOU ADD INFARCT IT GOES UP TO ABOUT JUST OVER 50%. AND IF YOU ADD LEWY BODY YOU'RE JUST UNDER 60%. SO ADDING DIFFERENT PATHOLOGIES ACTUALLY DRIVES THIS DEMENTIA PROCESS. AND MAKES IT MORE LIKELY THAT YOU WILL EXPERIENCE ALZHEIMER'S DISEASE ON INEVITABLE ROAD TOWARDS -- THERE'S MORE PATHOLOGY SO LET'S WALK THROUGH SOME OF THESE. I WON'T WALK THROUGH THE SAME DETAIL. I THINK THIS SLIDE NOW YOU CAN IMAGINE YOUR BAR HERE. THIS IS AMYLOID AN I DON'T KNOW THINK. -- ANOPOTHY. THIS IS RELATED TO OTHERS WE DISCUSSED SO ON TOP OF ALZHEIMER'S DISEASE, MACROSCOPIC INFARCT MICROSCOPIC INFARCT AND LEWY BODYs, HAVING MORE AMYLOID ANOPATHY CONTRIBUTES TO YOUR PROBABILITY PROBABILITY OF DEMENTIA. ADDING TO THESE SAME PATHOLOGY, HAVING HIPPOCAMPAL SCLEROSIS, TDP 43, ARE ALSO CONTRIBUTING TO TO THE LIKELIHOOD OF DEMENTIA, IN THIS CASE ALL CONTRIBUTES TO THE LIKELIHOOD OF CLINICAL SYNDROME THAT WE DIAGNOSE KNOW AS ALZHEIMER'S DISEASE. WE CAN ADD OTHER TYPES OF CEREBRAL VASCULAR MARKERS TO ATHEROSCLEROSIS. HERE IS THE BASAL ARTSRY, ARTERIAL SCLEROSIS. THIS IS PEOPLE WITH NO INFARCT OR VESSEL PATHOLOGY, GROSS INFARCTS, MACROSCOPIC INFARCTS, ALTIERIAL SCHOAR ROSIES. SO ALL -- SCLEROSIS. SO ALL THESE PATHOLOGIES ARE ADSING UP TO DETERMINE WHETHER OR NOT YOU HAVE DEMENTIA, WHETHER OR NOT AGAIN YOU MEET THIS CLINICAL AB DEMENTIA SYNDROME, INCLUDING VASCULAR TYPES OF MEASURES. ONE THING WE DON'T DO WELL WITH THE WITH AUTOPSY IS LOOK AT WHITE MATTER CHANGES. SO WE CAN DO THAT WITH POSTMORTEM IMAGING. WE CAN SHOW T-2 CHANGES IN WHITE MATTER ARE ASSOCIATED WITH EPISODIC MEMORY, WORKING MEMORY, THIS IS CONTROLLING ALSO FOR ALL THESE OTHER PATHOLOGIES IN THE BRAIN. ANOTHER TYPE OF VASCULAR MECHANISM CONTRIBUTING TO COGNITION, COGNITIVE IMPAIRMENT, AND TO ALZHEIMER'S DEMENTIA. YOUR BRAIN DOES NOT WISH TO BE DEMENTED. VASCULAR BRAIN. IT'S NOT A INNOCENT OBSERVER PASSIVE BYSTANDER WHILE PATHOLOGY IS ACCUMULATING. DAVE HOLTZMAN SUMMARIZED THE MECHANISMS AT PLAY THAT TRY AND MAINTAIN YOUR COGNITION. YOUR BRAIN IS HIGHLY PLASTIC AND HIGHLY RESPONSIVE AND THAT'S HOW WE LEARN. AND OF COURSE WITH WE HAVE ALL KINDS OF DEFENSE MECHANISMS JUST LIKE WE DO OUTSIDE OF OUR BRAINS TO DEFENDS US FROM INJURY AND DISEASE. SO LET'S TALK ABOUT ONE TYPE OF MARKER AND WEKDZ SHOW MANY BUT I'LL ILLUSTRATE THIS WITH ONE. THESE ARE PRE-SYNAPTIC PROTEINS, PRE-SYNAPTIC PROTEINS INVOLVED IN THE VESICLE RELEASE, THE SYNAPTIC TERMINAL, DAMP CHECKS SIN ONE, TWO, THIS IS A -- COMPLEXIN ONE AND TWO, IT'S A SNP 25, A COMPLEX OF THE TWO PROTEINS, THIS IS THE 10TH PERCENTILE, SORRY THE 90th PERCENTILE. THE 90th PERCENTILE, 50th, 10TH PERCENTILE OF COMPLEXIN 1. SO WHAT YOU CAN SEE IS FEWER PRE-SYNAPTIC TEENS ASSOCIATED WITH A MUCH OR LIKELIHOOD OF HAVING ALZHEIMER'S DISEASE ABOVE AND BEYOND PATHOLOGIES ACCUMULATING IN THE BRAIN. SO WE CAN PUT THIS TOGETHER, IN A MODEL THAT LOOKS LIKE THIS, WE'RE TRYING TO PREVENT AD DEMENTIA OR OTHER DEMENTIA BUT THIS IS THE PROMINENT CLINICAL DIAGNOSIS. IT'S PRECEDED BY NCI ALZHEIMER'S DISEASE F YOU LOSE COGNITION THERE'S GOT TO BE DYSFUNCTION OR DEGENERATION OF NEURAL ALBUMIN NEURONS THE SYNAPSES, DENDRITES, SPINE, AXONS, AND IN SOME CASES THIS IS ASSOCIATED WITH NEUROFIBRILLARY TANGLES. THIS BOX IS ALZHEIMER'S DISEASE, AS RON MENTIONED, THIS IS ALZHEIMER'S DISEASE THAT'S HOW WE DEFINED IT. WE CAN COME BACK AT LATER DATE AND TRY AND DEFINE DIFFERENTLY. BUT AS YOU SAW, LEWY BODIES, INFARCTIONS, HIPPOCAMPAL SCLEROSIS AND OTHER THINGS ARE DRIVING THE SAME SYNDROME. THESE ARE REALLY JUST OTHER DEMENTIAS. IN A MIXED DEMENTIA THE MOST COMMON THING WE SEE, TANDZ MOST COMMON THING WE SEE IN AD DEMENTIA. IF WE THINK ANT RISK FACTORS, AND TRYING -- ABOUT RISK FACTORS TRYING TO PREVENTS SYNDROMES YOU WILL HAVE RISK FACTORS FOR AD DEMENTIA, SOME ASSOCIATESSED WITH AD PATHOLOGY, SOME ASSOCIATESSED WITH OTHER PATHOLOGY, MANY AREN'T ASSOCIATESSED WITH ANY PATHOLOGY THAT WE KNOW OF. WE PUT THEM IN THIS BOX OF RESERVE OR RESILIENCE, SOMEWHAT OF A GARBAGE CAN FOR THINGS THAT WE PUTS IN THERE THAT WE REALLY CAN'T PUT ANY PLACE ELSE. SO I WANT TO TOUCH ON THREE IMPLICATIONS OF MIXED DEMENTIAS. SO I'LL COME BACK TO THIS SLIDE. THIS DIFFERENCIAL DIAGNOSIS, SO GLAD I DON'T HAVE TO GIVE NEAL'S TALK THAT COMES AFTER ME. I THINK IT'S A FICTION TO THINK WE COME UP WITH A PRIMARY CAUSE OF DEMENTIA IN MANY CASES. DO THESE PEOPLE HAVE PRIMARILY AD DEMENTIA? OR DEMENTIA DUE TO INFARCT OR DEMENTIA DUE TO LEWY BODY? THE ANSWER IS YES, YES, YES. TR AND THE THIS GETS BACK TO THE CONVERSATION WE'LL HAVE LATER TODAY ABOUT THE NOMENCLATURE, HOW WE'RE GOING TO TALK ABOUT THESE THINGS IN A WAY THAT MAKES SENSE AND IT'S RELATIVELY SIMPLE AND STRAIGHT FORWARD AND CAN BE UNDERSTOOD. B THE SECOND THING, MANY RISK FACTORS THAT COME OUT OF STUDIES RISK FACTORS FOR AD DEMENTIA, ARE NOT RISK FACTORS WITH A PATHOLOGY OF ALZHEIMER'S DISEASE, AND WE JUST NEED TO KEEP THAT IN MIND. SO THESE ARE THE SNPs THAT CAME OUT OF THE MOST RECENT IGAP GENOME WIDE ASSOCIATION STUDY OVER 25. ALL THESE DOWN HERE ARE ASSOCIATESSED WITH AD PATHOLOGY. AND THEN WE'RE LOOKING AT SOME OTHER SNPS ASSOCIATED WITH OTHER PATHOLOGIES. SO FO 1 ASSOCIATED WITH WITH HIPPOCAMPAL SCLEROSIS, MICROINFARCT AND LEWY BODIES, CD 33 IS ASSOCIATED WITH MACROSCOPIC INFARCTS AND APOE WITH HIPPOCAMPAL SCLEROSIS. SO WE'RE GOING TO SEE GENETICS, WE'RE GOING SEE OTHER RISK FACTORS THAT ARE DRIVING OTHER PATHOLOGIES. SO WE'RE LOOKING AT THE RELATION OF DIFFERENT PATHOLOGIES IN RELATION TO CHANGING COGNITION OVER MULTIPLE YEARS PRIOR TO DEATH. HERE IS OUR NO PATHOLOGY. HERE IS SOMEBODY WITH PATHOLOGIC AD, MA CROW SCOPIC INFARCT, MICROSCOPIC INFARCT AND CORTICAL LEWY BODIES. WE CAN ASK HOW MUCH VARIABILITY OF COGNITIVE CHANGE IS EXPLAINEDDED BY THESE DIFFERENT PATHOLOGIES? THIS IS IMPORTANT BECAUSE COGNITIVE CHANGE IS IN FACT THE THING THAT IS THE OUTCOME OF THE MOST OF OUR CLINICAL TRIALS. SO HERE WE EXPLAIN ABOUT 41% VARIANTS, ALMOST 60% VARIANTS UNEXPLAINED. I TOUCHED ON MANY THINGS THAT CONTRIBUTE TO THIS. SO WE MIGHT BE UP TO 50%, 55, POSSIBLY 60 BUT WE STILL HAVE A LONG WAY TO GO, MUCH TO LEARN. SO SUMMARY, I WANT TO SAY DEMENTIA INCLUDING AD DEMENTIA IS A COMPLEX FUNCTION OF NUMEROUS PRAIN PATHOLOGIES, NUMEROUS PROTECTIVE FACTORS, MIXED DEMENTIA IS THE MOST COMMON FINDING, DEMENTIA IN GENERAL. AND AD DEMENTIA. AND THE IMPLICATIONS AT LEAST THREE, THERE'S MANY OTHERS OF MIXED DEMENTIA IS THAT IT'S VERY DIFFICULT TO ASSIGN PRIMARY CAUSE OF DEMENTIA WHEN PEOPLE HAVE MIXED DISEASES AS THE LAW CONTRIBUTING. MANY RISK FACTORS FOR AD DEMENTIA ARE NOT REMITTED TO AD PATHOLOGY AND LASTLY, PREVENTING BETA AMYLOID ACCUMULATION WHICH IS WHERE E WE SPENT MUCH OF OUR TREASURE OVER THE LAST SEVERAL YEARS IS LIKELY TO HAVE A MUCH SMALLER EFFECT THAN ANTICIPATED AND WE NEED TON COON CERTAINED THE TRIALS WE DO ARE PROBABLY POWERED SO LET ME END IT THERE. I SEE ROD GIVING ME THE -- GET OFF THE STAGE SIGN. I WANT TO INTRODUCE OUR NEXT SPEAKER, NEAL GRAPH RAD FORD. THANK YOU O'NEIL GRAPH RAD FORD. THANK YOU SMATCH, NEAL FOR TAKING ON -- THANK YOU SMATCH, NEIL FOR TAKING THP HERCULEAN TASK. >> I'M HERE TO TELL YOU THIS NEUROLOGIST JOKE. TWO MEN WENT UP IN A HOT AIR BALLOON, THE IT WAS OVERCAST AND THEY COULDN'T FIND THEIR WAY, THEN THERE WAS A GAP AND THEY CAME DOWN AND THERE WERE TWO MEN WALKING OVER THERE AND THEY SAID CAN YOU HELP US? WHAT CAN WE DO FOR YOU? WHERE ARE WE? YOU'RE IN A HOT AIR BALLOON. THE GUYS GOT TO BE NEUROLOGIST COMPLETELY ACCURATE INFORMATION BUT NO HELP. ALL RIGHT. SO LET'S TALK ABOUT DIFFERENTIAL DIAGNOSIS AFTER DAVE'S TALK. SO THE REASON ARES YOU SHOULDN'T MAKE AN ACCURATE DIAGNOSIS IN DEMENTIA ARE WHEN A PATIENT DIES WITH DEMENTIA THEY FREQUENTLY HAVE MORE THAN ONE DISEASE, YOU HAVE JUST SEEN A BEAUTIFUL DESCRIPTION OF THAT, THERE IS NO DISEASE MODIFIED TREATMENT FOR ANY OF THE DISEASES THAT'S THE OTHER PERSPECTIVE AND PRIMARY CARE PHYSICIAN VERSUS LITTLE TIME, POOR KNOWLEDGE TO MAKE THE DIAGNOSIS AND ARE UNDERPAID TO DO THAT AS WELL. YOU HAVE HEARD TALKINGS ON THAT THIS MORNING. WHAT ARE THE ARGUMENTS THEN FOR MAKING THE ACCURATE DIAGNOSIS? TO LET -- SO LET ME TRY AND DO -- HELP WITH THAT. IF YOU DON'T MAKE AN ACCURATE DIAGNOSIS, YOU HAVE DILUTED TREATMENT STUDIES WITH WITHOUTIOUSING BIOMARKERS, IT'S GOODS EXAMPLE OF THAT ALREADY. SO THE BABANU DISIRKSM ACTB WHERE 31% PEOPLE DIAGNOSE AS PROBABLE PROBABLY ALZHEIMER'S DISEASE DIDN'T HAVE POSITIVE AMYLOID SCANS SO IF YOU USE AN ANTI-AMYLOID DRUG, IT WON'T WORK IF YOU DON'T HAVE AMYLOID IN THE BRAIN. SOFT USING BIOMARKERS CERTAINLY ENRICHES THE TARGET ACCURACY AND THAT IS NOW AS YOU KNOW PRETTY MUCH STANDARDS IN THE ANTS AMYLOID TREATMENT FIELD. AND THEN NOT ONLY THAT, AMYLOID POSITIVITY IS POSITIVE IN MANY SYNDROMES, IT'S POSITIVE NOT ONLY IN ALZHEIMER'S DISEASE, BUT OFTEN IN FRONTAL TEMPORAL DEMENTIA, VASCULAR DEMENTIA LEWY BODY DISEASE, CORTICO BASAL, SO THERE ARE OTHER DISEASES THAT ALSO HAVE CO-MORBID DISEASE -- AS DAVE HAS JUST WELL ILLUSTRATED SO IT'S IMPORTANT REALLY PROBABLY GOING TO BE TREATING MULTIPLE DISEASES. DIFFERENT ALZHEIMER'S PATHOLOGY PHENOTYPES NOT ONLY IS ALZHEIMER'S DISEASE NOT ONE DISEASE, IT'S PROBABLY MULTIPLE DISEASES, HERE SAN INTERESTING PAPER BY MELISSA MURRAY WHO IS IN THE AUDIENCE LOOK AT DIFFERENT PATHOLOGIES IN DENNIS'S COLLECTION OF AUTOPSIES SO PEOPLE WITH HIPPOCAM PAL SPARING DISEASE, THEY ARE YOUNGER PEOPLE AND THEY HAVE A RAPIDS DISEASE. PEOPLE WITH LIMBIC ENCEPHLOPPIC ALZHEIMER'S, PEOPLE WHO HAVE ALZHEIMER'S ONLY IN THE HIP CAMPUS, IT STARTS LATE AGE, IT'S BLUE AND IS A SLOW DISEASE, THESE ARE PEOPLE WITH MCI FOR TEN YEARS. THIS IS 15% OF PEOPLE, THIS IS TYPICAL ALZHEIMER'S DISEASE. SO IF YOU ARE NOT AWARE OF THE TYPE OF DISEASE YOU GET INCLUDING YOUR STUDY YOU MAY NOT BE ABLE TO POWER IT CORRECTLY. SO IN THE YOUNG ONSET PATIENTS, THIS GROUP STS A RAPID DISEASE. ARE SO THE RATE OF CHANGE IS DIFFERENT IS A SAY TO INCLUDING PEOPLE 85 AND OLDER. SO YOU ACTUALLY HAVE TO KNOW THAT THE DIFFERENT SUBSETS AND CLINICALLY YOU CAN ACTUALLY TEST YOU CAN DETECT WITH CORTICO ATROPHY OR CORTICO BASAL AND THEY HAVE GOOD -- WITH ALZHEIMER'S PATHOLOGY ELSEWHERE SO THE CLINICAL DIFFERENTIAL DIAGNOSIS IS VERY IMPORTANT IN THINKING A ABOUT THE DIFFERENT TYPES OF ALZHEIMER'S PATHOLOGY. THEN THE NON-SPECIFICITY OF THE PHENOTYPE WE ARE -- WE BELIEVE MOST OF US NEUROLOGISTS THAT WHEN WE SEE A PERSON WHO IS DEVELOPING A MEMORY PROBLEM, THAT THE BIG PROBLEM THAT THE DIAGNOSIS IS HIGHLY LIKELY TO BE ALZHEIMER'S DISEASE, AND TURNS OUT IT IS A MIMIC LIPOCAM PAL SCLEROSIS SO 40% OF OUR CONSENSUAL AUTOPSIES HAD ALZHEIMER'S DISEASE AND TURNS OUT IN THE NEXT SERIES IT'S UP TO 20% HAVE HIP CAM PAL SCHER -- HIPPOCAMPAL SCLEROSIS. YOU CAN SEE THE HIPPOCAMPAL SCLEROSIS, THE DIAGNOSIS IS MADE MORE FREQUENTLY. THIS IS VERY IMPORTANT FROM AN AGE PERSPECTIVE. YOU CAN SEE ALZHEIMER'S DISEASE PATHOLOGY IS PREDOMINANT PATHOLOGY IN YOUNG ENPEOPLE, HIPPOCAMPAL SCLEROSIS SAY OF 18 -- IS VERY LITTLE BUT BECOMES MORE IMPORTANT AS YOU GET OLDER AND LEWY BODY DISEASE IS ALSO IMPORTANT AT YOUNG AGE. SO THE AGE OF ONSETS, IN DIFFERENTIAL DIAGNOSIS AND TARGETED THERG PI IS -- THERAPY IS VERY IMPORTANT TO TAKE INTO ACCOUNT AND ALSO TO REALIZE THAT NOT EVERY MEMORY PROBLEM IS RELATED TO TAU PATHOLOGY IN HIPPOCAMPUS. SOMETHING WE GLOSS OVER BUT REALLY IMPORTANT IN DIFFERENTIAL DIAGNOSIS IS MISSING TREATABLE DISEASES. YOU HAVE TO UNDERSTAND THAT YOU HAVE TO BE ON YOUR TOES IN SORTING OUT SOME OF THE FOLKS SO SOME EXAMPLES. PATIENT PRESENTED WITH WITH MEMORY PROBLEM AND TURNED OUT THIS 60-YEAR-OLD PERSON HAD ABNORMALITY ON MRI ON CONTRAST M RIRKS SCAN OF HIPPOCAMPUS OF THE MAMMARY DIS. THAT PATIENT HAD FINDING DEFICIENCY AND ALSO SHE HAD THREE OPERATIONS ON HER ABDOMEN SO MALL ABSORPTION CAUSED MEMORY PROBLEM AND WE WERE ABLE TO TREAT HER EFFECTIVELY WITH THIGH MEAN AN COPPER. HE HAS A PERSON WHOSE BRAIN WAS SAGGING AND HAD MEMORY PROBLEMS AND IT WAS A LOW PRESSURE SAGGING PROBLEM THAT WE WERE ABLE TO TREAT. WITH BLOCKING THE AREA WHERE THE CSF WAS LEAKING. HERE IS A PATIENT WHO LAD VOLTAGE GAILTED POTASSIUM CHANNEL WHOSE M RIRKS WAS NORMAL BUT BECAUSE WE DETECTED THAT WE WERE ABLE TO TREAT THAT PERSON WITH STEROIDS AND THEN IMMUNE THERAPY AND PERSON, HERE IS A PATIENT WITH SYMPTOMATIC HYDROCEPHALUS. THIS IS NOT AFRO PHI, THIS IS SPINAL FLUIDS AT THE TOP OF THE BACK OF FISHER, THERE'S MANY PEOPLE WITH IN FACT TURNS OUTS IN MAY JOE STUDY OF AGING, 16% PEOPLE HAD LARGE VENTRICLES SO THAT'S AN IMPORTANT THING TO UNDERSTAND SO IT'S NOT THAT UNCOMMON FOR PEOPLE TO HAVE LARGE VENTRICLES AND LARGE VENTRICLES ARE VERY IMPORTANT BIOMARKER GATE ABNORMALITY AND COGNITIVE DECLINE, THOSE WITH VENTRICLES GET WORSE MORE QUICKLY AND GETS WORSE MORE QUICKLY AS WELL SO THAT'S AN IMPORTANT TREATABLE AREA. SO LISTED SOME OF THE TREATABLE ONES, MEDICATIONS ARE IMPORTANT. SLEEP APNEA, ANXIETY AND DEPRESSION AND SO ON, THERE'S A STRING OF TREATABLE THINGS SO THE DIFFERENTIAL DIAGNOSIS IS REALLY IMPORTANT TO THESE PARTICULAR PEOPLE. DIAGNOSE AND MANAGE LEWY BODY DISEASE, LEWY BODY DISEASE IS SYMPTOMATICALLY REALLY -- YOU CAN REALLY HELP PATIENTS WITH LEWY BODY DISEASE IF YOU DON'T MISS THE DIAGNOSIS. THESE ARE THE KEY CRITERIA. I DON'T WANT YOU TO READ IT BUT THE CRITERIA HAS A SENSITIVITY OF 85% AND A SPECIFICITY OF 73% SO KNOWING THE KEY CRITERIA ARE IMPORTANT, RBD OUT OF 172 AUTOPSIES, THIS IS BRAD BOEVE'S WORK, ALL -- ALMOST ALL HAVE -- HAD SYNUCLEIN PATHOLOGY DUE TO PARKINSONS OR LEWY BODY DISEASE OR MOLTS PL SYSTEM ATROPHY. SO SLEEP DISORDER IS IMPORTANT. IMAGING, THIS IS DR. KEPT KEN (INAUDIBLE) WORK PET SCANNING WITH AMYLOID MRI, SHE CAN SORT OUT DIFFERENT LEWY BODY DISEASES FROM ALZHEIMER'S DISEASE THAT SCAN 70% SENSITIVE AND THE CARDIAC SCAN 68 OR 70% SENSITIVE. SO THERE ARE WAYS TO DIAGNOSE AND CONFIRM LEWY BODY DISEASE AND WHY THAT'S IMPORTANT MANAGING LEWY BODY DISEASE IS IMPORTANT, IS NOW VERY GOOD META ANALYSIS. COLONs RACE INHIBITORS HELPFUL COGNITIVELY AND PSYCH EAT TRICKICALLY. -- PSYCHIATRICALLY, HYPERTENSION, NEUROPSYCHIATRIC FEATURES WITH THINGS LIKE COLON ESTERASE INHIBITORS. SO BEING ABLE TO DIAGNOSE FRONTAL TEMPORAL DEMENTIA IS ALSO IMPORTANT AND SENSITIVITY OF THE REVISED DIAGNOSTIC CRITERIA FOR BEHAVIORAL VARIANT IS NOT TOO BAD. IN THE PROBABLE POSSIBLE ALZHEIMER'S DISEASE IN THE 80% RANGE. SO KNOWING THE SUBCATEGORIES AND RECOGNIZING THEM IS IMPORTANT. LOOKING AT THE DIFFERENT APHASEIA, THE THREE APHASEIAS ISN'T GOOD AUTOPSY STUDIES THAT ARE RELIABLE, THAT'S AN AREA THAT I THINK WOULD REALLY LIKE TO SEE MORE CLINICAL PATHOLOGICAL STUDIES. FROM MANAGING FRONTAL TEMPORAL DEMENTIA SPEECH THERAPY AN SAFETY ISSUES, LIKE WEAPONS IN THE HOUSE, CAREGIVER SUPPORT OR NON-PHARMACOLOGICAL INTERVENTIONS ARE NOT GOOD SO WE NEED MORE STUDIES IN THIS AREA, THE THIS IS THE ONLY DOUBLE BLIND STUDY IN TREATMENT OF VARIOUS FRONTAL TEMPORAL DEMENTIAS. VASCULAR RISK FACTORS IN MANAGING DEMENTIA IS IMPORTANT. HERE IS THE MULTI-VARIANT MIXED REGRESSION MODEL OF MM PROGRESSION OF TIME WITH PEOPLE WITH ALZHEIMER'S DISEASE WITHOUT SERO VASCULAR DISEASE AND THESE ARE PEOPLE WITH VASCULAR RISK FACTORS TREATED, SOME VASCULAR RISK FACTORS TREATED AND NOVAS QUEUE LAR RISK FACTORS TREATED. -- VASCULAR REIS FACTOR TREATEDDED. SO -- RISK FACTOR TREAT SOD IF YOU HAVE A DRUG EFFECTIVE AS THIS, THE FDA MIGHT APPROVE IT. SO YOU DO HAVE A DRUG. YOU CAN TREAT BLOOD PRESSURE, YOU CAN TREAT CHOLESTEROL, IT'S REALLY IMPORTANT WHAT DAVE WAS SHOWING YOU IS THAT WE ARE SEEING MANY TREATABLE PREVENTION FACTORS SO MIDDLE AGE PEOPLE SHOULD HAVE VAS VASCULAR RISK FACTORS TREATED APPROPRIATELY AND YOU'LL HEAR MORE ABOUT THAT IN A MINUTE. THIS IS IMAGING FEATURES OF ALZHEIMER'S DISEASE AND VASCULAR PATHOLOGY AND THIS IS HELENA'S MODEL OF THAT DEALING WITH THE VARIOUS VASCULAR RISK FACTORS. SO WHAT ARE THE RECOMMENDATIONS THEN? PRAY MARE CARE, THEY NEEDS TO RECOGNIZE EXISTING COGNITIVE IMPAIRMENT, AS PART OF MEDICARE WELLNESS EXAM, PAINFUL MEDICARE PHYSICIANS SHOULD PERFORM STANDARDIZED SHORT TEST AND INTERVIEW AN INFORMANT ABOUT COGNITIVE ISSUES, THAT'S OFTEN OVERLOOKED. INTERVIEW AN INFORMANT YOU GET A LOT MORE INFORMATION IN THE COGNITIVE WORLD. AND THEN THEY SHOULD RECOGNIZE RED FLAGS WITH TREATABLE DEMENTIAS, THAT SHOULD BE WIDELY PUBLICIZED. IT SHOULD BE ON THE ALZHEIMER'S WEBSITE. I LOOKED ON ET YESTERDAY. I DIDN'T SEE IT. WE WANT TO SEE RED FLAGS FOR THE TREATABLE DEMENTIAS. RAPIDLY PROGRESSIVE, SETTING OF IMMUNE DEFICIENCY, MAL ABSORPTION. SO THOSE ARE REALLY IMPORTANT AREAS. SO ALL REFERRED WITH COGNITIVE DECLINE SHOULD SEE A PHYSICIAN WITH TRAINING AND DEMENTIA, SO THESE WE'RE TALKING ABOUT SIGH PSYCHIATRISTS, NEUROLOGISTS AND GERIATRICIANS WHO IN RESIDENCY HAVE TRAINING AND MAKE ACCURATE DIAGNOSIS IS AND RECOGNIZE WHEN TO REFER TO SUBSPECIALISTS LIKE A TYPICAL -- SUCH AS SUBACUTE EARLY ONSET, MANAGEMENT OF HYDROCEPHALUS, MANAGEMENT OF LEWY BODY, LIMBIC ENCEPHALITIS, THOSE ARE NOT NECESSARILY COMFORTSABLE, SOME ARE, SOME AREN'T BURKS THEY SHOULD REFER THEM ON. THEN THEY NEED TO DEVELOP A COMPREHENSIVE CARE PLAN INCLUDING THE CAREGIVER. SUBSPECIALISTS SHOULD HAVE WIDE AND DEEP DIAGNOSIS, PROFESSIONALLY TRAINDZ, MANAGE THE COMPLICATED CASES, BEWARE OF CLINICAL TRIALS AND REFER TO CLINICAL TRIALS AND BACK TO PRIMARY SPECIALIST WITH A GOOD MANAGEMENT PLAN BECAUSE THEY CAN'T LOOK AFTER ALL CASES, IT SHOULD BE A TEAM EFFORT. I THINK WHETHER THE RECOMMENDATION SHOULD BE TO THE PUBLIC THEY SHOULD RECOGNIZE WHEN THERE MAYBE COGNITIVE DECLINE AND THAT SHOULD BE -- THAT ALREADY ON THE WEBSITE, THAT'S A GOOD THOSE SHOULD BE RED FLAGS WITH TREATABLE CAUSES AND SHOULD BE A LIST OF MEDICATIONS THAT AGGREGATE OR CAUSE COGNITIVE DECLINE AGAIN COULD BE ON THE ALZHEIMER'S WEBSITE OR OTHER WEBSITES. SO THOSE ARE SOME OF THE RECOMMENDATIONS. THEN THERE ARE RECOMMENDATIONS IN THE EDUCATION PROGRAM IN ALL THE SOCIETIES PARTICULARLY TO RECOGNIZE AND TREAT TREATABLE DEMENTIAS, RECOGNIZE ALZHEIMER'S AND INSTITUTE SIMILAR SYMPTOMATIC TREATMENT, INCLUDE VASCULAR RISK FACTORS, MAKE APPROPRIATE USE OF BIOMARKERS TO MAKE ACCURATE DIAGNOSIS. THERE SHOULD BE MORE PERSPECTIVE CLINICAL STUDIES PARTICULARLY FTD VASCULAR LEWY BODY DISEASE, WE HAVE SEEN WONDERFUL ONES, DAVID'S ARE EXEMPLARY. CLINICAL TRIALS SYMPTOM IMPROVEMENT IN LEWY BODY DISEASE AND THEN WE SHOULD TEST THE HYPOTHESIS THAT TREATING VASCULAR RISK FACTORS IN ALZHEIMER'S DISEASE MIGHT MODIFY MIXED DEMENTIA DISEASE. SO THOSE ARE THE RECOMMENDATIONS AND I'LL STOP THERE. THANK YOU P. [APPLAUSE] >> THANK YOU, NEAL, TO FINISH UP THIS SESSION WE WILL BE MOVING MORE FROM THE O'NEIL'S WHICH WOULD BE MORE OPERATIONAL AS ROD SAID, WHAT WE CAN DO NOW AND HOW THESE CLINICAL FEATURES MAKE A DIFFERENCE IN CLINICAL PRACTICE TO MORE ASPIRATIONAL. AND HELENA CHUI FROM THE UNIVERSITY OF SOUTHERN CALIFORNIA AND BRAD BOEVE WILL TEAM UP TO TALK ABOUT SOME OF THE FUTURE BIOMARKERS DIAGNOSIS IN THESE DISORDERS. >> WONDERFUL TO BE HERE. I REMEMBER BACK HERE 30 YEARS AGO I WAS CONSIDERED AN AGING SCIENTIST NOW I'M AN AGED SCIENTIST. WE'RE SHIFTING NOW TO FROM THAT WONDERFUL VIEW OF OUR PLANET THAT DPAIF BENNETT GAVE US OVER TIME AN SPACE TO COMING DOWN TO SEE THE MULTIPLE CULTURAL DIVERSITIES AND THE INDIVIDUAL DIFFERENCES AMONG THE DEMENTIA NEIL DISCUSSED TO TALK ABOUT AND FOCUS ON ASYMPTOMATIC PERSONS AND WHAT NEW BIOMARKERS WE MIGHT BE THINKING OF. I WILL TALK VASCULAR COGNITIVE I IMPAIRMENT AND BRAD BOEVE ABOUT FTD AND LEWY BODY DISEASE. SO HERE HE AND E WILL BE TO -- AND I WILL BE TO CUSSING ON NOT DEMENTIA MCI BUT PRE-SYMPTOMATIC PRODROMAL PERIODS FOR VCI AND THESE OTHER NEURODEGENERATIVE DISEASES. B VASCULAR RISK FACTORS ARE VERY IMPORTANT MANY SPEAKERS HERE FROM THE MAYO CLINIC, RON PETERSEN'S LAY MAY OWE AGING STUDY ABOUT 1400 PEOPLE, AND VASCULAR RISK FACTORS PLAY A VERY IMPORTANT ROLE IN PREDICTING INCIDENCE MCI STROKE DIABETES, HISTORY OF ATRIAL FIBRILLATION. WE'RE FAMILIAR WITH MULTIPLE INFARCTS, PLEADS, CONFLUENT WHITE MATTER CHANGES AND VASCULAR COGNITIVE IMPAIRMENT WITH A FEW INFARCTS, MICROBLEEDS AN EARLY WHITE MATTER HYPERINTENSITIES IF WE ARE VERY FAMILIAR IN PRIMARY CARE SETTINGS WITH VASCULAR RISK FACTORS B FRAMINGHAM CORONARY, FRAMINGHAM STROKE PROFILE. FOCUSING ON HYPERTENSION, HYPERLIPIDEMIA, DIABETES, SMOKING ATRIAL FIBRILLATION. MY COMMENTS TODAY FOCUS CAN ON PRE-SIMILAR TO THEMATIC INDIVIDUALS AND MARKERS FOR CEREBRAL VASCULAR DISEASE. FOR EXAMPLE, BASAL REACTIVITY ENDOTHELIAL CELLS, PERRY SITES, THE BLOOD BRAIN BARRIER, NEUROVASCULAR UNIT AND CSF MARKERS. IN THE NEURAL PSYCHOLOGICAL AREA FOR VASCULAR RISK FACTORS WE NEED TO PAY IMPORTANT ATTENTION TO EXECUTIVE FUNCTION AND TO PROCESSING SPEED. IN THE CLINICAL WORLD THERE'S INEXPENSIVE MEASURES LIKE ANKLE L BRACHIAL INDICES OR AORTIC PULSE WAVE VELOCITY THOUGH NOT OBTAINED USUALLY IN PRIMARY CARE SETTINGS. THERE IS A VERY ACCESS BIBLE NEW -- ACCESSIBLE NEW TECHNOLOGY CALLED RETINAL OCULAR COMPUTED TOMOGRAPHY AND GEOGRAPHY A WHICH CAN NOW DISPLAY WITHOUT ANY CONTRAST ON -- OR FLUOROSCENE MICROVESSELS, CAPILLARY LEVELS, FROM DIFFERENT LEVELS FROM THE INNER RETINA TO THE MID RETINA TO THE OUTER RETINA. SHOWN IN COLOR HERE. THIS MAY GIVE A WINDOW ON CAPILLARY HEALTH WE CAN'T SEE IN MRI. THERE ARE GENETIC, I WAS INTERESTED TO SEE THE GWAS FOR MICROINFARCTS THAT DAVE BENNETT SHOWED FROM OUR GROUP AT USC, POINTED OUT THESE PROMISING PLATELET GROWTH FACTOR BETA, OTHERS HAVE SHOWN METALLO PROTONASE 9 CSF MARKERS FOR VASCULAR DISEASE. IN MCI WE LOOK AT T-1, T-THE 2 OR FLAIR FOR SILENT VASCULAR INJURIES, WHITE MATTER CHANGES AND SUSCEPTIBILITY WEIGHTED IMAGING OR GRADIANT ECHOS FOR MICROBLEEDS. FOR PRO ARE DROPPLAL PERSONS WE CAN START TO LOOK IN AT DIFFUSION TENSOR IMAGING FOR FRACTIONAL ANTI-HIGH TROUGH PI AND DIFFUSESIVETY AND ARTERIAL SPIN LABELING FOR CEREBRAL REACTIVITY IN RESPONSE TO CO 2 INHALED CONSENT THRAITED CO-2 OR DIFFERENCES BETWEEN INS PRIGSAL EXPIRATIONAL CO-2. AND DYNAMIC CONTRAST MRI WITH GADOLINIUM NOW, THOUGH I WISH THERE WERE WAYS TO DO WITHOUT USING GAT GADOLINIUM BASED CONTRAST BECAUSE THEY MAYBE POTENTIALLY RETAINED IN THE BRAIN. MARKERS ARE HERE FOR ALZHEIMER'S TYPE PATHOLOGY WHICH COMMONLY OCCUR TOGETHER WITH RISK FACTORS NOT THAT THEY'RE RELATE BUD WE'RE GETTING OLDER. IT IS GOOD TO HAVE NOMENCLATURE OR RATING FOR WHITE MATTER CHANGES. IT HAS A STUDY -- A SCALE FROM 0 TO 8 TO 8 PLUS AND EUROPEANS USE THE ZIKA SCALE WHICH IS SIMPLE ENOUGH BEGINNING CONFLUENCE AND 3 LARGE CONFLUENCE, WE START TO HAVE CLEAR COGNITIVE CHANGES HERE BUT EVEN HERE IT'S GOING TO SEE CHANGES IN EXECUTIVE FUNCTION AND PROCESSING SPEED. DIFFUSION TENSOR IMAGING IS NOW QUITE WIDESPREAD AND RESEARCH CENTERS FRACTIONAL ANTI-ATROPHY AND MEAN DIFFUSESIVETY AND PERSONS WITH SYMPTOMATIC SUBCORTICAL VASCULAR THE DEMENTIA, FA OR MD CORRELATE WITH TENSION AND WITH PSYCHOMOTOR SPEED, BUT WHEN ONE CONTROLS FOR INFACTOR AND WHITE MATTER HYPERINTENSITY, THE ATTENTION COMPONENT GOES AWAY BUT PSYCHOMOTOR SPEED PERSISTS SO MAYBE THIS WOULD BE A MEASURE FOR PSYCHOMOTOR SPEED WHICH IS PROMINENTLY IMPAIRED IN DIABETES. WE DON'T HAVE A PARTICULAR GOOD-BYE MARKER FOR DIABETIC CHANGES PERHAPS THIS THIS MIGHT BE ONE CANDIDATE, ALABAMA THOUGH NOT SPECIFIC. THIS TECHNIQUE OF CEREBRAL VASCULAR REACTIVITY HAS BEEN AROUND A LONG TIME, NOT CLEAR YET HOW MUCH INCREMENTAL VALUE WILL ADD, STILL NEEDS TO BE LOOKED AT IN RESEARCH SETTINGS. IN NORMAL TENSIVE INDIVIDUALS WHO INHALE INCREASE CONCENTRATIONS OF CO-2, THERE'S INCREASE BLOOD FLOW ACTIVITY MEASURED WITH WAR A TIERIAL SPIN LABELING BUT WITH PERSONS WITH HYPERTENSION WE DON'T SEE OFTEN THAT INCREASE IN CEREBRAL VASCULAR REACTIVITY. SO THIS GIVES A TOOL FOR PICKING UP SOMETHING IN PRE-SYMPTOMATIC INDIVIDUALS. AT SEVERAL CENTERS INCLUDING USC WE USE DYNAMIC CONTRAST ENHANCEMENT MRI, GADOLINIUM BASED CONTRAST AGENTS AND THE SOPHISTICATED MODELING USING PAT LACK AND SOME ADVANCED MODIFICATIONS TO SEE, PICK UP PERMEABILITY OF -- ACROSS THE BLOOD BRAIN BARRIER FOR GADOLINIUM. AND DR.S LOKAVIC AND TEAM HAS SHOWN INCREASED PERMEABILITY IN HIPPOCAMPUS AND PERSONS WITH NORMAL AGING AND MCI. SO I'LL END HERE. MY COMMENTS IN A MINUTE. JUST CAVEAT THAT A LOT OF PEOPLE WITH VASCULAR RISK FACTORS ALSO HAVE AMYLOID BETA AMYLOID. HERE IS ALZHEIMER'S DISEASE AND HERE IS PATIENTS WITH VASCULAR DEMENTIA. AS AGE, THERE WILL BE OFTEN AMYLOID AS WELL AS AGING WITHOUT A DIAGNOSIS INCREASE BETA AMYLOID. THIS WILL ALSO BE IMPORTANT IN LEWY BODIES LESS IMPORTANT IN FRONTAL TEMPORAL DEMENTIAS. [APPLAUSE] >> GOOD MORNING. THANKS TO ROD, DAVE, DAVID AND MANY OTHER ORGANIZERS AND MEMBERS OF THE COMMITTEE. I'LL FOCUS ON THE LAST TWO SUBJECTS HERE, LEWY BODY DISEASE. USING THE SAME CONCEPTUAL FRAMEWORK, LO FOCUSING AT NOT SO MUCH ON SYMPTOMATIC OR OVERTLY SYMPTOMATIC BEHAVIORAL FRONTAL TEMPORAL DEMENTIA OR AFASCIA TO FOCUS CAN ON EARLIER PHASES. WHAT WE KNOW FROM THE OVERTLY SYMPTOMATIC PHASE THOUGH WE HAVE MANY SCALES THAT DO HELP WITH DIAGNOSIS, MANY DO TRACK WITH DISEASE PROGRESSION, THESE ARE CLINICAL ONES, MANY NEUROPSYCHOLOGICAL MEASURES, MOST PEOPLE WITH FTD DO HAVE EXECUTIVE ATTENTION SOCIAL COGNITION IMPAIRMENT, THOSE WITH PPA, OBVIOUSLY LANGUAGE. THEN SOME OF THE OTHER NON-BEHAVIORAL NEUROPSYCHOLOGICAL MEASURES MEASURES OF BIOFLUID, BLOOD MEASURES ARE LACKING AT LEAST IN TERMS OF CONSENSUS ON BLOOD BASED BIOMARKERS. THERE ARE CSF PROTEINS THAT ARE QUANTIFIABLE IN THIS UNDERLYING PROTEINOPATHY DRIVING THE DISEASE. MANY GENES HAVE BEEN IDENTIFIED WITH FAMILIAL FTD AND/OR PPA T SO CALLED BIG THREE TAU GRAND LYNN IN CHROMOSOME 9 OPEN READING FRAME 72. THERE ARE MANY OTHERS, IMAGING HAS BEEN QUITE HELPFUL, AGAIN, TO HELP DIAGNOSIS AND TRACK WITH DISEASE. STRUCTURAL MRI, MORE NOVEL MRI MEASURES, MR SPECTROSCOPY, FOR THE GLUCOSE PET AND MOLECULAR PET IMAGING. EEG HAS BEEN USED AS WELL. THE CHALLENGE IS IN THE PRE-SYMPTOMATIC PHASE. AS ALL THE CLINICIANS KNOW, MAKING A DIAGNOSIS EARLY IN SPORADIC FTD OR PPA IS CHALLENGING. IT'S CHALLENGING FOR SPECIALISTS, EVEN MORE CHALLENGING FOR THOSE WHO DON'T SEE MANY PATIENTS, PARTICULARLY CHALLENGING IN THE PRIMARY CARE SETTING. SO TO MAKE A DENT IN THE PRE-SYMPTOMATIC AND INTERMEDIATE PHASES WILL LIKELY NEED TO FOCUS ON FRONTAL THEM DEMENTIA MUTATION CARRIERS. TO USE STANDARD AND NOVEL CLINICAL NEUROB PSYCHOLOGICAL BLOOD CSF IMAGING AN ELECTROPHYSIOLOGIC MEASURES TO BETTER CHARACTERIZE THE DISEASE. SO SOME RESEARCH DIRECTIONS THEN ON WHERE TO GO P ONE TO EXPLOIT EXISTING PROTOCOLS, THERE ARE TWO RECENTLY FUNDED STUDIES FOCUSED ON FAMILIAL FTD. THE SO CALLED LEFTY STUDY AND ARTFUL STUDY, -- WORKING QUITE WELL IN EUROPE ADDRESSING THE THE SAME ISSUE. THESE ARE FUNDED BY NIA AND NINDS. AND SEVERAL MEASURES PART OF THE FRONTAL TEMPORAL DEGENERATION MODULE, AS PART OF THE ADC PROGRAM COORDINATED WITH THE KNACK PROGRAM IS ALREADY IN PROGRESS. I SHOULD ADD THAT THE ASSOCIATION FOR FRONTAL TEMPORAL DEGENERATION WAS CRITICAL IN MOVING THIS FIELD FORWARD ENOUGH FTD. IDENTIFY OTHER NOVEL GENETIC MARKERS OR MANY PRESUMABLY MANY GENETIC MARKERS OUT THERE, THERE ARE SEVERAL FAMILIES WITH CLEAR AUTOSOMAL DOMINANT DISEASE THAT DO NOT HAVE IDENTIFIED PATHOGENIC MUTATION IN ANY KNOWN GENES. CHARACTERIZE THE PROTEINS INVOLVED, A KEY ISSUE IN THE ASYMPTOMATIC PHASE IS WE DON'T KNOW WHAT THE DETERMINANTS ARE FOR THE PHENO CONVERSION SO GOING FROM NORMAL TO THE MCI OR INTERMEDIATE PHASE EQUIVALENT, WHAT PHENOTYPE EXHIBIT IN THE RATE OF PROGRESSION. AND APPLY THE MANY MEASURES THAT OUTLINE AD MINUTE AGO. AGAIN, EMPHASIZE ONE CHARGE OF THIS COMMITTEE, HOW DO WE HELP PRIMARY CARE CLINICIAN COLLEAGUES IN EARLY DIAGNOSIS AND THIS IS A CHALLENGE FOR SPORADIC BUT AT LEAST WITH FAMILIAL CASES IF THERE IS A FAMILY HISTORY OF DEMENTIA PARKINSON, ARCLS OR COMBINATION, THERE'S -- ALS THAT'S A PLACE TO START. MOVING TO LEWY BODY DISEASE. THE SAME CONCEPTUAL FRAMEWORK WITH DEMENTIA LEWY BODY IN PARKINSON DISEASE WITH DEMENTIA MEAN THE OVERTLY SYMPTOMATIC PHASE AND INTERMEDIATE PHASE PRESYMPTOMATIC PRODROMAL. MCI IS DRIVING WITH THE INTERMEDIATE PHASE SOME HAVE MCI PHASE IF IN FTD AS WELL AS IN THE LEWY BODY SPHERE, BUT IT MAY BE EXPANDING BEYOND PURE COGNITIVE IMPAIRMENT P AS PART OF THIS INTERMEDIATE PHASE. THIS IS NOT WELL CHARACTERIZED IN DOP PDD AND FCD. MANY FEATURES, AS NEIL WENT OVER, LEWY BODY DISEASE IS -- COGNITIVE MOTOR NEUROPSYCHIATRIC SLEEP AUTONOMIC NAN MANIFESTATION OF THE DISEASE, THESE FORM THE CORE OF THE DIAGNOSIS FOR DOB AND SEVERAL OF THESE ALSO PDD. THERE IS NEUROPSYCHOLOGICAL PROFILE THAT'S FAIRLY TYPICAL. OVERT SYMPTOMATIC PDD. AND SOME BIOMARKERS, BLOOD CSF, HAS NOT BEEN FRUITFUL AS IN ALZHEIMER'S DISEASE AND TO SOME EXTENT FTD, WORK CONTINUES, SOME GENETIC MARKERS, MANY IMAGING STUDIES WITH SPECK MIBG CARDIAC IMAGING, QUITE SENSITIVE RELATIVELY SPECIFIC. POLYSO -- WAKEFULNESS TEST. WHERE TO FOCUS ON THE PRE-SYMPTOMATIC OR PRODROMAL PHASE, LOOKING AT CLINICAL MARKERS THIS WOULDN'T BE THAT DIFFICULT. THIS IS WHERE EVEN IN SPORADIC DISEASE, THERE ARE CLINICAL FEATURES, THAT ARE RELATIVELY SPECIFIC AND SENSITIVE, RBD PARTICULARLY, I'LL TOUCH ON THAT AGAIN IN A MINUTE AND TO APPLY THE SAME MEASURES DURING THE PRODROMAL PHASE. SO WHAT TO DO FROM A RESEARCH PERSPECTIVE. AGAIN EXPLOIT THE EXISTING PROTOCOLS OR EXPAND THE SCOPE. THE BIOMARKER PROGRAM IS IN PROGRESS, HAS BEEN FOR SOME TIME, THE PPI MI STUDY. THE PRODROMAL PPMI ONE OF THE AVENUES WAS FOCUSED ON THOSE WITH RBD O TWO MUTATION CARRIERS SO EXPANDING THAT TYPE OF INITIATIVE WOULD BE APPEALING. SOME WORK AGAIN IS BEING DONE AS PART OF THE ADC KNACK PROGRAM. I SHOULD ADD THE CRITICAL LEWY BODY DEMENTIA ASSOCIATION AND A LOT OF WORK IN THE DOB SPHERE. RESEARCH DIRECTION SIMILAR TO FCD. COMING BACK TO THE THIS PER SPECK THETIVE FOR PRIMARY CARE CLINICIANS AGAIN REM SLEEP BEHAVIOR DISCAN ORDER IS NOT CHALLENGING TO SUSPECT BASED ON JUST SIMPLE QUESTIONS TO DOES YOUR BED PARTNER TEND TO ACT OUT DREAMS. THERE ARE VALIDATED SCREENING MEASURES FOR PATIENTS AS WELL AS FOR BED PARTNERS, HIGHLY SENSITIVE AND SPECIFIC AND COULD BE USED IN A MASS SCREENING MECHANISM. OBVIOUSLY WE WANT POLYSO PHOTOGRAPHY TO CONFIRM IT. ASNOSMIA, NOT AS SPECIFIC BUT A REASONABLE AND RELATIVELY EASY THING TO SCREEN FOR. SO FROM A PRIMARY CARE PERSPECTIVE, A SIMPLE QUESTIONNAIRE OR A QUESTIONS BY CLINICIAN AS WELL AS SMALL TESTING, IT'S NOT USURPER CHEAP FOR SMELL TEST BUG CAN BE DONE. I'LL END THERE AND COME BACK, THIS IS OUR FINAL SLIDE AND WE'LL DISCUSS THIS IN MORE DETAIL. THANK YOU. [APPLAUSE] >> NOW WE WILL HAVE A 15-MINUTE SESSION OF OPEN MIC AND QUESTIONS FOR THE MULTI-ETIOLOGY DEMENTIA SESSION, MODERATOR WILL BE DR. DAVID DALTON. >> IF PEOPLE HAVE QUESTIONS, MICROPHONES ARE THERE. -- MODERATOR DAVID KNOPMAN. JOHN FIRST THEN GO OVER THERE. >> MOST INFORMATIVE -- >> SPEAK CLOSER TO THE MIC, JOHN. >> MOST INFORMATIVE MORNING, >> CUT YOU DOWN TO SIZE. >> BUILT FOR SMALL PEOPLE AND EMPHASIZING WHAT I SUBSCRIBE TO, THE MIXED PATHOLOGIES OF WHAT APPEARS CLINICALLY TO BE ALZHEIMER'S DISEASE. THERE HAS BEEN BEEN AN OVERARCHING HYPOTHESIS ABOUT ALZHEIMER'S DISEASE PROPOSED MANY, MANY YEARS AGO AT THE AMYLOID CASCADE HYPOTHESIS. I WONDER IF THERE'S ANYONE IN THE ROOM WHO IS A PROPONENT OF THE AMYLOID CASCADE HYPOTHESIS WHO WE GIN TO -- BEGIN TO KNIT TOGETHER HOW AMYLOID HYPOTHESIS BRINGS HIPPOCAMPAL SCLEROSIS LEWY BODIES INTO THE BRAIN OF PEOPLE WITH CLINICAL ALZHEIMER'S DISEASE, I CONTINUE TO BE PERPLEXED ABILITY HOW TO THINK ABOUT THAT. -- ABOUT HOW TO THINK ABOUT THAT. JOHN HARDY GETTING UP. >> CAN I -- (OVERLAPPING SPEAKERS) >> I REALIZE YOU CALLED HIM OUT. I THINK IT IS KIND OF OFF THE SUBJECT, FOR THIS PARTICULAR GROUP. AND THERE ARE PEOPLE WHO WOULD OBJECT. >> MAINLY FOCUS OF THERAPY IS A BETA SO ISN'T IT APPROPRIATE TO CONSIDER WHAT OUR TARGETS ARE? >> COULD I ASK DAVE BENNETT TO RESPOND? I THINK WHAT YOU'RE SAYING JOHN, IS ARE THERE SYNERGISTIC INTERACTIONS BETWEEN THE MULTIPLE ETIOLOGIES. >> THAT'S WHAT I RECALL THE HYPOTHESIS. >> THERE'S A LINK BETWEEN AMYLOID DEPOSITION AND TAUOFORMATION BUT YOU CAN ALSO GET TAU THROUGH OTHER MECHANISMS INDEPENDENT OF A BETA. AFTER THAT, MOST OF THESE OTHER PATHOLOGIES ARE ESSENTIALLY ADDITIVE. THERE ARE SOME SMALL EFFECTS, APOE STRONGLY RELATED TO L AMYLOID AND TAU, WEAK ASSOCIATION WITH LEWY BODY HIPPOEXAMPLE SCLEROSIS. INFARCTS. OTHER THAN APOE, MOST OF THESE OTHER THINGS ARE ADDITIVE. SO I THINK WHAT'S JUXTAPOSED HERE FROM A TARGET, IS RON'S SLIDE WHERE EVERY PATHOLOGY IS TARGETED, I THINK SOMETHING DAVE WAS GETTING AT, I DON'T WANT TO PUT WORDS IN YOUR MOUTH, WHERE AFTER THE PATHOLOGIES YOU GET TO SOME B COMMON MECHANISMS THAT ARE DRIVING DEMENTIA. AND IF YOU CAN TARGET THOSE AGNOSTIC TO THE INDIVIDUAL INSULTS, I THINK IT'S MORE TRACTABLE. >> I THINK ALSO YOUR SLIDE POINTING OUT THE SNPS THAT INCREASE THE RISK FOR THE VARIOUS -- MY ONLY POINT IS THAT WE SHOULD I THINK STEP BACK AND REALIZE THAT THERE'S MANY GENETIC CONTRIBUTORS AND THAT WE'LL FAIL TO KEEP OUR EYE ON THE BALL OF TARGETS FOR THERAPY UNLESS WE ARE MINDFUL OF THESE OTHER PATHWAYS. >> THANK YOU, JOHN. PLEASE IDENTIFY YOURSELF. >> JANE TILLEY WITH U.S. ADMINISTRATION ON AGING. AND I WOULD LIKE TO ASK FOLKS TO TALK A LITTLE BIT MORE ABOUT MEDICATION. PARTICULARLY IN CONTEXT OF PRIMARY CARE PHYSICIAN WHERE THE THERE'S SO MANY MEDICATIONS LIKE SLEEP AIDS, ANTI-ANXIETY, ANTIDEPRESSANTS THAT CAN AFFECT COGNITION AND HOW TO EDUCATE PHYSICIANS ABOUT THIS AND I WOULD LIKE TO SEE MORE MENTION OF THAT IN YOUR RECOMMENDATIONS. I CAN'T REMEMBER WHICH GROUP BUT THERE WAS MENTION OF MEDICATION. JUST A LITTLE MORE FULL DISCUSSION OF THAT WOULD BE HELPFUL. >> GWEN, COMMENT THEN OTHER PEOPLE. >> THANK YOU. SPECIFICALLY YOU'RE ASKING HOW WE CAN REACH OUT TO PHYSICIANS TO EDUCATE MORE? BECAUSE I THINK THAT INFORMATION IS OUT THERE. >> IT'S NOT JUST A QUESTION OF REACHING OUT TO PHYSICIANS MORE, I THINK IT'S ALSO A QUESTION OF LONG TERM USE OF MEDICATIONS, CONTRIBUTE TO IN SOME WAY TO THE COGNITIVE EFFECTS THAT WE'RE SEEING. IT'S BOTH. AND GIVEN SOME OF THE EXPERIENCES I HAVE HAD PERSONALLY AND OTHERS I HAVE KNOWN, THE INFORMATION MAYBE OUT THERE, I'M NOT SURE IT'S GETTING TO THE PHYSICIANS SO IF YOU CAN TALK TWO THINGS THAT WOULD BE HELPFUL. >> I THINK THERE'S ACTUALLY A RECENT PAPER ON WHETHER LONG TERM USE OF BENZODIAZEPINE IS ASSOCIATESSED WITH DEMENTIA RISK. I DON'T THINK THAT QUESTION HAS BEEN FULLY ANSWERED YET. I THINK THERE'S ALSO REVERSE CAUSALITY SO AS PEOPLE ARE BEGINNING TO DEVELOP COGNITIVE PROBLEMS AND MAYBE PSYCHOLOGICAL OR SYMPTOMS ASSOCIATED, IT'S OFTEN TREATED WITH SOME OF THE SAME MEDICINES. SO THE MEDICINES IN AND OF THEMSELVES MAY NOT BE CAUSING, HOW DO WE GET THAT INFORMATION INTO PRACTICE MORE, IS IT A VERY IMPORTANT AND CHALLENGING QUESTION? WHAT ARE ALTERNATIVES THAT WE CAN USE I THINK THAT THE NON-CARP COLOGIC MANAGEMENT OF SYMPTOMS IN COGNITIVELY IMPAIRED AND UNIMPAIRED PERSONS IS VERY IMPORTANT IN ORDER TO MAXIMIZE OPPORTUNITIES RETAINING COGNITIVE FUNCTION, HIGH LEVELS OF FUNCTION WITH AGING. >> AS A PRACTICING NEUROLOGIST THE POINT ABOUT POLYPHARMACY IS VERY WELL TAKEN. I HAVEN'T SEEN VERY MUCH IMPROVEMENT OVER THE YEARS, IN FACT IT JUST SEEMS MORE AND MORE MEDICATIONS, NUTRACEUTICAL SUPPLEMENTS ARE PILED ON. WE HAVE THE SAME AGE OLD RECOMMENDATIONS, THE CRITERIA, GO DOWN THE CHECKLIST, REMOVE ANTI-CHOLINERGIC, THERE'S MEDICATIONS BEING PRESCRIBED FOR SLEEP, FOR NEURAL PATHIC PAIN, BEHAVIORAL DISORDERS AND I THINK EACH SUBSPECIALIST PILES ON THEIR OWN ONE OR TWO MEDICATIONS. SO IT IS CLEARLY A NEED TO COMMUNICATE WITH PRIMARY CARE PHYSICIANS SIMPLIFYINGEN, REDUCING MEDICATIONS. >> MAYBE WANT TO FOLLOW AS A GERIATRICIAN I WOULD -- (INAUDIBLE) POLYPHARMACY IS A HUGE ISSUE IN OLDER ADULT, 10 TO 14 MEDICATIONS AT ANY TIME, I THINK SOMETIMES YOU DON'T REALIZE THE INTERACTION THESE MEDICATIONS HAVE IN THEMSELVES THE INTERACTION THEY HAVE WITH EXISTING DISEASES, AND MANY OF THESE HAVE MULTIPLE CO-MORBID CONDITIONS. AND THE LONG TERM USE OF MEDICATION ADVERSELY EFFECT COGNITION, IN CONTRAST THERE'S EVIDENCE MEDICATION LIKE ACE INHIBITORS AND HYPERINTENSIVES AND DIABETES MEDICATIONS MAY HAVE BENEFICIAL EFFECTS SO THE INTERACTION IS VERY COMPLEX AND AS CLINICIANS WE HAVE TO BE AWARE AND BE SELECT INEFFECTIVE WHAT WE USE IN TERMS OF NEW MEDICATIONS OR AS IT BECOMES VERY DIFFICULT FOR PHYSICIAN AND PATIENT, THE CONSEQUENCE CAN BE GRAVE FOR MANY PATIENTS. >> BRIEF COMMENT THEN WE'LL MOVE ON. >> JUST I THINK GIVING PUBLIC EDUCATING THE LICK ABOUT IT, I -- PUBLIC ABOUT IT IS REALLY IMPORTANT WEAPON BECAUSE THEY I'M COME IN AND ASK THEIR DOCTOR ABOUT IT AND PUT IT ON THINGS LIKE THE ALZHEIMER'S WEBSITE OR WATCH OUT FOR THESE DRUGS, AND MIGHT BE A USEFUL ADDITIVE. >> JUST FROM A PSYCHIATRIC PERSPECTIVE. I THINK SOME OF THIS IS DIFFERENTIAL DIAGNOSIS AND BASIC DIAGNOSTIC PROCESSES. WHEN YOU HAVE A BUNCH OF MEDICINES SCREENED, PSYCHOTROPICS YOU ALSO HAVE DELIRIUM, IT'S A DIFFERENT PROBLEM FROM DEMENTIA AND SOMETIMES THEREFORE WITHDRAWAL TRIALS ARE IN FACT DIAGNOSTIC PROCESSES. >> THANK YOU. LET ME GO TO SUDA. >> BOSTON UNIVERSITY FRAMINGHAM HART STUDY. THANKS TO THE PANELISTS FOR A WONDERFUL OVERVIEW. I WANT TO DRAW ATTENTION TO TWO THAT MIGHT BE RELEVANT TO GWEN'S TALK. A FEW YEARS AGO AT THE URGING OF NIA WE PUT TOGETHER DATA FROM FRAMINGHAM CARDIOVASCULAR HEALTH STUDY, HEALTH AND RETIREMENT STUDY AND THIS IS PUBLISHED WITH (INAUDIBLE) LEAD AUTHOR IN ALZHEIMER'S DEMENTIA IN 2014. THERE WAS A MANDATE FOR COGNITIVE SCREENING AT THE INITIAL MEDICARE VISIT. AND IT CAN BE CHALLENGING IN A PRIMARY CARE SETTING WITH LIMITED TIME AS WELL AS POSSIBILITY OF FALSE POSITIVES SO ACROSS THESE FOUR COHORTS, OVER AGE 18 THERE WAS ONE IN FOUR CHANCE THAT ON A SCREENING YOU WOULD ACTUALLY HAVE COGNITIVE IMPAIRMENT SO SEEMS LIKE ALL THOSE PEOPLE DO NEED TO HAVE SCREENING, WHATEVER BETWEEN 65 TO 79, OBVIOUSLY THE RISK RISES EXPONENTIALLY SO ON PAGE, EDUCATION OF 12 YEARS, HAVING STROKE, DIABETES, INCREASE IN BMI WHETHER YOU MANAGEMENT AND MONEY AND TWO QUESTIONS ABOUT DEPRESSIVE SYMPTOMS SEEM TO -- YOU HAVE A SET OF SIMPLE POINTS SCALE WEB-BASED TO TO GET OVER 22 YOUR RISK BECOMES THE SAME AS SOMEBODY OVER THE AGE OF 18 THERE IS ONE IN FOUR. SO THIS IS SOMETHING CLEARLY NEEDS FURTHER VALIDATION CLINICAL SETTING, AND SOME DATA BEING ACCRUED BUT THOUGHT IT MIGHT BE SOMETHING FOR FOLKS TO CONSIDER. >> THANKS. I WOULD LIKE TO COMMENT THAT WE HAVE THAT AS OUR AIM 5 BUT NOTICE HOW OR THE GOAL. THERE WAS A CONSENSUS IN OUR GROUP THAT SCREENING IN THE EMPIRIC DATA MORE OR LESS SUPPORTS IT HAS NOT BEEN WELL RECEIVED OF. AND THERE ARE MANY REASONS FOR IT SO WE -- WITHOUT GOING INTO DETAIL DECIDED TO PUT THAT DOWN ON OUR LIST AND SO WE EMPHASIZE AS ROD STARTED OFF, WITH PEOPLE GO TO THE DOCTOR AND SAY I HAVE A PROBLEM, THAT'S WHERE OUR FOCUS IS NOW. >> JENNIFER MAN HI, COLUMBIA UNIVERSITY. TWO QUESTIONS. ONE IS -- MANLY COLUMBIA UNIVERSITY. ASK SANDY TO EXPANDS ON HER STATEMENT THAT AMONG WITHIN YOUR VERY WELL DONE TALK, THAT DIFFERENTIAL DIAGNOSIS CAN'T BE DONE REMOTELY AND MAYBE THE ENTIRE PANEL CAN HAVE A DISCUSSION ABOUT THAT. THE OTHER QUESTION FOR THE PANEL IS THAT COGNITIVE IMPAIRMENT IS MORE PREVALENT AND IN DISPARITIES POPULATIONS. YET, UNDERDIAGNOSED. SO HOW DID THAT INFLUENCE YOUR RECOMMENDATION? >> SO WHAT I MEANT BY THAT, IF YOU'RE THINKING ABOUT JUST USING YOUR OWN CHECK YOUR OWN MENTAL HEALTH BY GOING ON REMOTE BATTERY AND DRAWING A CONCLUSION ABOUT THAT FOR DIFFERENTIAL DIAGNOSIS, WITH WE'RE NOT THERE YET. MAYBE IN 20 YEARS, HOPEFULLY LESS, WE WILL BE THERE, WHEN WE CAN IDENTIFY SOME REALLY GOOD MARKERS THAT HELP US DIFFERENTIATE AMONG DIFFERENT CAUSES OF DEMENTIA. IT ALSO DOESN'T ALLOW US TO DETERMINE WHAT THE SPECIFIC SYMPTOMS ARE. AND I THINK RIGHT NOW, I WOULD ARGUE THAT YOU CAN USE COMPUTERIZED ASSESSMENT BUT THE INTERPRETATION FOR HOW YOU INTERPRET THE RESULTS THAT YOU GET WILL TRANSLATE INTO REASONABLE RECOMMENDATIONS OR MANAGEMENT AND FOR DIFFERENTIAL DIAGNOSIS. DO I UNDERSTAND YOUR QUESTION? (OFF MIC) >> BECAUSE THE -- A LOT OF WHAT YOU'RE ASKING OVER THE PHONE, YOU CAN DEFINITELY DO IT WITH SKYPE, FOR SURE. BUT I THINK MY COMMENT WAS REALLY LIMITED TO GOING ON LINE, TAKING A TEST. BUT I'M SORRY. YOU CAN DEFINITELY -- I WANT TO SEE THE PERSON. WHEN I MAKE A DIFFERENTIAL DIAGNOSIS. >> YOU NEED A NEUROLOGIC EXAM IN MANY INSTANCES. ANYBODY ELSE? ANY COMMENTS? >> I WONDER IF TELEMEDICINE IS SOMETHING WHICH IS BEING USED INCREASINGLY AND CERTAINLY I CAN THE TELL YOU IN THE DEPARTMENT OF VETERANS AFFAIRS, IT IS QUITE ADVANCED. THEY ARE DOING TELENEUROPSYCHOLOGY, THEY CAN DO NEUROPSYCHOLOGICAL TESTING THROUGH TELEMEDICINE, NOT ONLY EXAMINE -- YOU CAN DO A LOT OF MANAGEMENT DIAGNOSIS AND ESPECIALLY IN RURAL AREAS RAISED IN THE PRESENTATION TODAY, THAT COULD BE AS ADVANCES AN PEOPLE ARE BETTER TRAINED, IN TELEMEDICINE TO PLAY A MAJOR ROLE IN EARLY DIAGNOSIS AND MANAGEMENT OF THESE PATIENTS ESSENTIALLY CANNOT PHYSICALLY COME TO MORE CENTRALIZED HOSPITALS. >> SOLVE OVER HERE THEN ZOE. >> I WANT TO ASK A RHETORICAL QUESTION TO DAVE, MAYBE TO LEAD TO A RECOMMENDATION. ONE SLIDE YOU SHOWED INDICATING MULTIPLE ETIOLOGIES, THE MOST PROXIMAL EVENT COMMON EVENT IS THE LOSS OF SYNAPSE AND PRUNING AND SO ON. FROM THE POINT OF VIEW DIFFERENCES IN CLINICAL EXPRESSION, WHAT DIFFERENCE DOES IT MAKE, HOW THE NEURONS GET LOSE THEIR SYNAPSE? THAT'S SUPERFICIALLY THAT WOULD BE THE QUESTION, CLEARLY THAT ARE OUR DIFFERENT NETWORKS INVOLVED THAT GIVE SPECIFICITY. THE PROBLEM IS WE DON'T HAVE THE TECHNOLOGY FOR DOING CAREFUL ANALYSIS STUDY OF NETWORKS INVOLVED. IMAGING TECHNIQUES WE HAVE ARE TWO GROSS. WE NEED THE NANOTECHNOLOGIES IN ORDER TO BE ABLE TO IMAGE DELICATE INTRICACIES OF DIFFERENT NETWORKS ARE INVOLVED IN, DIFFERENT NEUROLOGICAL DISORDERS. THEY MAY HAVE COMMON FEATURES SYNAPTIC BUT THERE ARE ALSO SIGNIFICANT DIFFERENCES. SO ONE RECOMMENDATION IS TO BUILD ON THE RFA NUMBER OF YEARS AGO, GMS HAD A RFA TO PROMOTE NANOIMAGING TECHNOLOGIES AND ALZHEIMER'S ASSOCIATION HAD DONE THAT ALSO NEUROLOGY AND AGE REEXAMINE THE DEVELOPMENT OF THOSE TECHNOLOGIES TO IMPROVE ON THAT. THE SECOND TECHNOLOGY IS PERHAPS TO EXPLOIT SOME OF THE FINDINGS ARE FROM JOHN AND VIRGINIA WHERE THEY'RE SHOWING THAT THERE IS TRANSSYNAPTIC TRANSMISSION OF THE TAU PATHOLOGY, COULD THAT BE EXPLOITED IN ORDER FOR US TO ANALYZE HOW THIS SYSTEM CAN PROGRESS FROM ONE NEURON TO THE OTHER, HOW THE SYSTEM GETS INVOLVED IN IT. RECOMMENDATION WOULD BE TO GIVE TON OF MONEY TO VIRGINIA AND -- >> MAYBE INTEREST OTHER PEOPLE ASK QUESTIONS, JUST HAVE DAVE -- >> THOSE ARE TWO AREAS. >> THE SECOND RFA IS VIRGINIA AND THE FIRST ONE IS FOR THE REST OF US. >> A VERY BRIEF RESPONSE, I VERY MUCH THINK THAT A BRIEF THOUGHT EXPERIMENT WILL TELL YOU THE TARGETING PIECE OF THE PUZZLE ON THE FRONT END LEADING TO NEURODEGENERATION IS GOING TO BE VERY DIFFICULT, VERY EXPENSIVE, YOU WILL BE PUTTING IT INTO PEOPLE THAT ARE VERY OLD WITH AGING KIDNEYS AND LIVERS. AND ULTIMATELY THE MOST TRACTABLE PART WHICH MIGHT BE MORE ASPIRATIONAL IS THE COMMON MECHANISMS THAT WE TAKE LOSS OF COGNITION AND NEURAL ELEMENTS. THAT'S WHAT WE'RE GOING HAVE TO GO TO FINE SOMETHING THAT IS GOING TO HELP PEOPLE AGNOSTIC OF WHATEVER IT IS THAT THE INITIAL FACTOR CAUSING THE DAMAGE. >> THANKS. OVER THERE. >> STEVE FROM AUSTIN, TEXAS, BOARD MEMBER, I'M ALL IN FOR THIS HAVING LOST TWO SIBLINGS AT AGE 57 TO F THETD WITH GENETIC DISORDER. I WANT TO REITERATE THE FIRST IMPROVING DIAGNOSTIC SKILLS. ALSO LEADS TO CAREGIVER GROUP WITH OVER 100 CAREGIVERS AND THEY ALL TELL THE COMPLETE STORY OF MISDIAGNOSIS AFTER MISDIAGNOSIS AFTER MISDIAGNOSIS. FROM MY HUSBAND IS CRAZY, HE'S GOT DEPRESSION, HE'S BIPOLAR. HE'S GOT ANXIETY DISORDER AND IF WE CAN SEND PEOPLE INTO SPACE SURELY WE CAN GET GENERAL PRACTITIONERS TO GET AN ACCURATE DIAGNOSIS. THANK YOU. >> THANK YOU. >> CERTAINLY EMPATHIZE, ZOE BRIEFLY. >> WHY DON'T YOU MOVE BACK. >> THANKS VERY MUCH. I WANT TO QUICKLY BRING UP THE IDEA IN THIS PARTICULAR SESSION ABOUT MULTIPLE ETIOLOGY DEMENTIAS THAT METABOLIC DISORDERS ARE EXTREMELY COMMON AS WE ALL KNOW, I WANT TO DOVE TAIL ON HELENA'S TALK ABOUT ASYMPTOMATIC INDIVIDUALINGS. EARLIER IN LIFE HAVING DIABETES IN MID ADULTHOOD AND OLDER PLACES YOU AT MUCH HIGHER RISK OF DEMENTIA, TWO FOLD INCREASE RISK. SHOULD WE BE THINKING MORE ABOUT METABOLIC DISORDERS. SHOULD WE THINK ABOUT BIOMARKERS? I'M TALKING ABOUT YOUR FIRST BULLET POINT THERE, DIAGNOSIS OF -- BIOMARKERS OF METABOLIC DISORDERS THAT ARE TIED WITH DEMENTIA. WE SHOULD THINK ABOUT BRIG INSULIN RESISTANCE AND WHAT IT MIGHT BE. >> THANKS. I'M GOING CUT YOU OFF, SORT OF RUNNING OUT OF TIME, ALSO YOU GUYS PROVIDED US WITH INFORMATION ABOUT THAT, I JUST POINT OUT THAT DIABETES IS CERTAINLY DISCUSSED AMONG THE RISK FACTORS I DON'T THINK THAT WE IGNORED IT AND I LEAVE IT THERE. HOW MUCH TIME DO WE HAVE? >> HELENA. >> WE CAN ADD TO DAVE'S OVERVIEW OF SCIENTIFIC THEMES LIPS AND SNAPS AND REPAIR. >> I HAVE TWO POINTS. ONE IS PRACTICAL, ADDRESSING GWEN'S EXCELLENT PRESENTATION REGARDING HOW TO ENCOURAGE PRACTITIONERS TO WANT TO DIAGNOSE THEM, DEMENTIA, THE MOST PRACTICAL MECHANISM TO PAY FOR SOCIAL WORKER. THAT'S THE PIECE THAT'S MISSING, I'M A GERIATRICIAN EPIDEMIOLOGIST, THERE'S A INFRASTRUCTURE TO PAY FOR SOCIAL WORKER, PRIMARY CARE PHYSICIANS ARE FOUGHT GOING TO TAKE ON HER ROLE OF BEING THE SOCIAL WORKER AND BE THE DIAGNOSTICIAN AND TRYING TO PAY FOR THE NURSES TIME TO ANSWER FOR ALL THE DEMENTIA PATIENTS AND FAMILY. THE SECOND THING IS TO TIE ON TO ZOE'S COMMENT REGARDING METABOLIC DISEASE CHRONIC DIDNY DISEASE IS OFTEN IGNORED ETIOLOGY OF COGNITIVE IMPAIRMENT. >> I AGREE, WE HAVE A SOCIAL WORKER CAME ABOUT THROUGH PRIVATE TO HELP WITH THAT, IT'S NOT -- IT'S A LUXURY FROM A CLINIC BUT I AGREE COMPLETELY IT'S A NECESSITY. >> YOU GOT THE LAST WORD. >> BRAD DICKINSON, BOSTON. >> I WAS REALLY IMPRESSED BY THIS SESSION AND ALSO A LITTLE BIT BLOWN BY THE COMPLEXITY OF THESE ISSUES. I WANT TO RELATE THOSE FEELINGS TO A COUPLE OF YOUR POINTS HERE, I THINK TO DEVELOP DIAGNOSTICS AND BIOMARKERS IN ASYMPTOMATIC PEOPLE, WE NEED TO BE STUDYING THAT OURSELVES AS WE'RE DOING, I JUST DONE SEE THAT AS BEING SOMETHING WE CAN TRY TO ROLL OUT TO THE COMMUNITY, ANY TIME SOON, I THINK IN THAT THIRD SLOT WE NEED TO DETECT COGNITIVE IMPAIRMENT, WE NEED TO DEVELOP DIFFERENTIAL DIAGNOSES AND UNDERSTAND HOW WE AS EXPERT COMMUNITY USE THESE BIOMARKERS IN OUR PRACTICES SO THAT WE CAN TEACH LESS EXPERT CLINICIANS HOW THEY SHOULD BEGIN THAT PROCESS AND HELP THEM UNDERSTAND MORE ABOUT WHAT THE RED FLAG SHOULD BE LEAD THEM TO WANT TO REFER AND THEN TAKE ADVANTAGE OF THINGS SANJAY RAISED ABOUT TELEMEDICINE WHICH ARE STROKE NEUROLOGISTS DO EXAMS THROUGH ALL THE TIME. AND TRY TO PARTNER AND DEVELOP PROGRAMS TO DEVELOP EFFECTIVENESS BETWEEN EXPERTS AND COMMUNE DIPROVIDERS. SO ENPROVIDERS SO ENCOURAGE REVISIONSES ALONG THOSE LINES TOO. WHAT WE'RE TRYING TO ROLL TOUT THE PRACTITIONERS. P GIVE MELANGE TO K. >> WE CAN TAKE ONE MORE, UNLESS -- >> (INAUDIBLE) BOSTON UNIVERSITY. WE DEVELOPED AT POSTMORTEM 3-D SPACE WHICH GOES DOWN IN CHOLINERGIC DEFICITS OR DATABASE. I DON'T KNOW IF IN FTD OR OTHER DIFFERENTIAL DIAGNOSTICS MAY HAVE. THIS IS POSTMORTEM VALIDATED FOR THE CHOLINERGIC SPACE. IT'S A VERY >> MAYBE COME UP. WE CAN GET THAT AFTER THE BREAK OR DURING THE BREAK. WANT TO THANK THE PANELISTS VERY MUCH FOR THIS THIS GREAT SESSION AND WE'LL TAKE A BREAK NOW. ANY COMMENTS? >> WE WILL START AGAIN ON TIME AT 10:35, IT WILL BE A SHORT BREAK. >> I WOULD LIKE TO INTRODUCE THE -- OUR CO-CHAIR OF THE NON-GOVERNMENTAL ORGANIZATION COMMITTEE, SUSAN DICKINSON FROM THE ASSOCIATION FOR FRONTAL TEMPORAL DEMENTIA. AND SHE'S DONE A LOT OF WORK, HAS BEEN KEY IN THIS PROCESS KEEPING ME ORGANIZED ACTUALLY, I TRIED TO HELP TOO. SO THANK YOU, VERY MUCH. TAKE IT AWAY. >> THANK YOU, RON. I THINK IT WAS RECOGNIZED EARLIER THIS MORNING, THIS SESSION 3 FROM NON-GOVERNMENTAL ORGANIZATIONS IS THE ONE SESSION THAT HAS BEEN ADDED TO THE STRUCTURE OF THE ADRD RESEARCH SUMMIT AS CARRIED OUT BACK IN 2013, THE FIRST TIME. AND I WANT TO TAKE THE OPPORTUNITY TO THANK DR. HOLTZMAN, PETERSEN, DR. KOROSHETZ, ROD CORRIVEAU, WE APPRECIATE THIS RECOGNITION THE NGOs HAVE AN IMPORTANT ROLE TO PLAY IN THE ADRD RESEARCH PLAN, MAKE A PLAN AND CARRYING IT OUT. WE VERY MUCH APPRECIATE BEING INCLUDED IN THE PROCESS FROM THE START AND SEE INPUTS RECOGNITION THAT WE CAN BE OF VALUE AND HAVE IMPORTANT PARTNERS IN THE WHOLE PROCESS. SO WHAT IS AN NGO? THE DICTIONARY SAYS IT'S CITIZEN BASED ASSOCIATION USUALLY A NON-PROFIT, THAT OPERATES INDEPENDENTLY OF GOVERNMENT TO DELIVER RESOURCES OR SERVE SOCIAL OR POLITICAL PURPOSE. IN OUR SETTINGS HERE THIS MORNING CLEARLY WE ARE SOME COMBINATION OF NON-PROFIT DISEASE ASSOCIATION, PATIENT ADVOCACY ASSOCIATIONS AND PRIVATE FOUNDATIONS. PROUD TO RECOGNIZE MY EIGHT COME PATE TREEIOTS WHO PARTICIPATED IN THIS COMMITTEE. HOWARD FILLIT MY CO-CHAIR, MARIA CORILLO. GUY AKEN CANNOT BE HERE BUT HE SENT MICHAEL BUCKLEY TO TAKE HIS PLACE, WE APPRECIATE THAT. COSTANTINO IADECOLA, RODNEY PEARL MAN, SIMON RIDLEY FROM INTERNATIONAL UK. TODD SHERER FROM MICHAEL J. FOX AND ANGELA TAYLOR FROM THE LEWY BODY DEMENTIA ASSOCIATION. BETWEEN US WE REPRESENT VARIOUS SIZE ORGANIZATION, VARIABLE IN SCOPE, SOME REPRESENT SINGLE DEMENTIAS, OTHERS ARE MORE UMBRELLA ORGANIZATIONS FOR A GROUP OF DISEASES. AND THE APPROACH WE TOOK WAS TWO FOLD, ONE WAS TO HAVE GET TO KNOW EACH OTHER A LITTLE BIT AND DETERMINE FROM THESE VERY PERSPECTIVES WHAT COULD WE DO COMING TOGETHER TO BRING TO BARE ON THE ADRD RECOMMENDATIONS. BUT ALSO MORE SPECIFICALLY, COLLECTIVELY, WHEN WE WORK AS A GROUP P REALLY IDENTIFY GIVEN OUR UNIQUE PERSPECTIVE OF STRATEGIES, AND STRENGTH, WHAT DO WE AS GROUP OF NGO HAVE TO BRING TO BEAR ON THE TASK AT HAND IN TERMS OF CRAFTING A PLAN FOR THE A DOCs. -- ADRDs. EARLY ON WE IDENTIFIED THESE TWO FOCUS AREAS THAT WE WANTED TO ADDRESS. AS ALREADY NOTED, THE FOCUS AREA NOMENCLATURE AS DUG INTO IT WE HEARD FROM ROD THAT OTHER GROUPS IDENTIFIED THIS AS AN ISSUE AS WELL SO YOU SEE THAT'S BROKEN OUT AN WILL BE A SEPARATE SESSION FOLLOWING OURS. SO WHAT WE'RE GOING TO DO THE NEXT 40 MINUTES IS FOCUS ON WHAT WE AS NGOs BRING THAT'S UNIQUE TO THE EQUATION. WHAT IS IT ABOUT THE PROGRAMS AND PARTNERSHIPS AND WAY WE WORK TO CATALYZE RESEARCH IN A DIFFERENT WAY THAN OTHER PLAYERS THAT YOU WILL HEAR FROM DURING THE MEETING. SO WHAT DOES MAKING AN NGO FUNDER UNIQUE? WHAT DISTINGUISHES US FROM GOVERNMENT FUNDERS, THOSE IN ACADEMIA, AND THOSE FROM INDUSTRY? IN THE PHASE IF YOU ASK WHAT ARE WE DOING, IT'S THE SAME THING, WE'RE CONDUCTING AND FUNDING VERGE. YOU GET INTO THE DIFFERENCE IS WHEN YOU LOOK AT WHO WE REPRESENT. WHY WE EVEN EXIST AND WE AS NGOs ARE FOUNDED BY ARE FUNDED BY AND ARE CHARGE -- OUR CHARGE IS CREATED BY THIS LIST OF ENTITIES YOU SEE WE REPRESENT. WE HAVE OUR GENESIS FROM THE PATIENT COMMUNITY ITSELF, FROM THE FAMILIES. FROM OUR DONORS, THE VERGERS, CLINICIANS AND ADVOCATES WHO ALSO WORK ON THESE VARIOUS PARTS OF THE DISEASE. YOU HAVE TO UNDERSTAND THIS IS WHY ORGANIZATIONS EXIST AS WHOLE, IT'S THE MISSION UPON WHICH WE'RE FOUNDED THAT ARE BRINGING THESE DISPARATE PLAYERS TOGETHER AND GIVEN WE ARE SOME SUBMISSION ORIENTED THAT IMPACTS HOW WE WORK, THE FACT WE CAN ACCOMPLISH THINGS AND EMPLOY DIFFERENT STRATEGY THANS THE OTHER FUNDERS THAT STRATEGIES THAN THE OTHER FUNDERS LISTED HERE. SO WE IDENTIFIED RIGHT AWAY WE CAN BE MORE CUSSED AT TIMES, FLEXIBLE, FROM OUR PERSPECTIVE AT THE TABLE, WE CAN BUILD COLLABORATIONS OTHER FUNDSERS CAN. AS WE DISCUSS THIS AS A GROUP WE DUG INTO THE SEEMS THAT WE CAN IDENTIFY FLESHING OUT THESE IDEAS. AT TIMES WE CAN MOVE FASTER. WE CAN TARGET OUR FUNDING PROGRAMS MUCH MORE PRECISELY ON A SPECIFIC PROGRAM. WE CAN TOLERATE RISK OFTEN PRIVATE FUNDERS FUND THE EARLY STAGE RESEARCH OR ENTERING MORE INTO THE VALLEY OF DEATH BETWEEN THE LAB AND CLINIC. WE CAN USE A VARIETY OF STRATEGIES SO IN ADDITION TO THE CONGRATULATIONAL PROCESS OFP PEER REVIEWED GRANT PROCESS WE CAN IDENTIFY SPECIFIC PIs AND FUND SPECIFIC CONSORTIUM AND GET THEM TO WORK TOGETHER. WE CAN FUND CONTRACT RESEARCH, WE CAN OFFER APPRAISES TO STIMULATE WORK TOWARD A VERY SPECIFIC GOAL THAT WE NEED TO BE ESTABLISHED. WE CAN ALSO BROKER COLLABORATIONS FROM THE NON-PROFIT STANDPOINT. WE CAN MAKE THESE COLLABORATIONS ACROSS DIFFERENT DISEASES, ACROSS INTERNATIONAL BORDERERS AND DEFINITE LAY CROSS STAKEHOLDERS LISTED HERE. AS YOU ALL KNOW THE BOTTOM LINE GOAL WAS TO COME UP WITH RECOMMENDATIONS TO ENSURE THAT THAT HE RECOLLECTSDRD, THIS PLAN CAN BE ACCOMPLISHED AND FOLLOWED THROUGH ON. WE ARE RECOMMENDING WE ESTABLISH MORE EFFECTIVE COMMUNICATION BETWEEN NIH AND THE NGOs AND SPECIFICALLY THAT THIS COMMUNICATION LAST IN THE YEARS BETWEEN WHEN PLANNING FOR THESE RESEARCH SUMMITS. WE WERE REALLY PLEASED AS WE MET WITH NIH AND WITH MY FELLOW NGOs ACROSS THE LAST SIX MONTHS PLANNING FOR THIS PROGRAM, WE HAD AN OPPORTUNITY TO LEARN IN MUCH MORE DEPTH WHAT EACH OF US WAS FUNDING WHAT EACH PRIORITY WERE AND IT WAS CLEAR THIS ENHANCED COMMUNICATION, ENABLE US TO COORDINATE MORE SUCCESSFULLY. WHICH IS GOING TO INCREASE IMPACT OF OUR INDIVIDUAL PROGRAMS, AS WELL AS ENABLE US TO DEVELOP SYNERGIES TO MAKE SURE THE GOALS ARE ACCOMPLISHED ACROSS THE BOARD. SO WE'LL RETURN TO THIS RECOMMENDATION AT THE END, HOWARD FILLIT WILL FLESH IT OUT. WE HAVE FOUR SPECIFIC IDEAS FOR STRATEGIES TO ACCOMPLISH THIS IN THE OFF YEARS AS I SAY WHEN NOT MEETING AS A WHICH I FEEL WHAT WE WILL DO FIRST IS RAPID FIRE. FIVE WILL PRESENT A COUPLE OF PROGRAMS FROM EACH OF OUR ORGANIZATIONINGS THAT DEMONSTRATE THE POINT THAT I WAS MAKING EARLIER. ABOUT THE FACT THERE ARE WAYS WE CAN WORK AND THEREFORE WE CAN HAVE A DIFFERENT IMPACT. WITH THAT AS THE INTRODUCTION. I ACTUALLY GET TO GO FIRST. REALLY QUICKLY FOR THOSE WHO MAY NOT BE FAMILIAR WITH AFTD WE WERE FOUNDED IN 2002 BY A CAREGIVER, WE ARE STILL LED BY BOARD OF DIRECTORS OF OF ALL CAREGIVERS. AS WE HAVE GROWN OVER THE PAST 13 YEARS WE HAVE BEEN ABLE TO IDENTIFY AND INTERACT WITH IN GROWING AMOUNTS THESE OTHER STAKEHOLDERS IN OUR COMMUNITY SO CLINICS RESEARCHERS, GOVERNMENT, INDUSTRY, AND INCREASINGLY IN MOST RECENT YEARS WITH THE PATIENTS THEMSELVES. WORKING FROM THE HUB OF THIS GROWING COMMUNITY. E WE ARE DRIVING FIVE ASPECTS OF OUR PRETTY BROAD MISSION. OBVIOUSLY RESEARCH IS THE REASON WE'RE GOING TALK ABOUT MORE TODAY. WE ALSO PROVIDE INFORMATION INTO SUPPORT PATIENT AND FAMILY, WORK TO EDUCATE CLINICIANS AND PROFESSIONAL CARE PROVIDERS. WE ADVOCATE FOR IMPROVED SERVICES AND INCREASED FUNDING. AND AS A RARE DISEASE OUR AWARENESS WORK IS ESPECIALLY IMPORTANT. WE SEE IT'S FUNDAMENTAL TO EVERYTHING ELSE WE WANT TO ACCOMPLISH FOR OUR COMMUNITY. AS FAR AS RESEARCH FUNDING WE AWARDED FIRST PILOT GRANT IN 2005, YOU CAN SEE IT WAS $35,000. FLASH FORWARD THIS YEAR WHERE WE HAVE WORKED HARD TO EXPAND THE MECHANISMS WITH WHICH WE AWARD GRANT FUNDING AND WE'RE REALLY PROUD AND PLEASED TO BE ABLE TO BE AWARDING MORE THAN $3 MILLION IN 2016. SO WHAT IS UNIQUE HOW WE CAN DO THIS? I'M GOING TO HIGHLIGHT TWO SPECIFIC POINTS WE ESPECIALLY THE RARE DISEASE ORGANIZATION CAN HAVE THAT THE OTHER PLAYERS CANNOT. THE FIRST ONE IS AS I DESCRIBE BECAUSE WE HAVE GENESIS FROM THE PATIENT COMMUNITY, FAMILY COMMUNITY, WE ARE THE ONES WHO BRING THESE PEOPLE TO THE TABLE GET THEIR BUY IN ON THE RESEARCH PROGRAM, GET THEM TO HELP INPUT AND INFORM DESIGN OF RESEARCH PROGRAMS WHICH IS SO IMPORTANT WHEN CONSIDERING WE NEED THE BUY IN FROM THIS COMMUNITY TO PARTICIPATE IN THE RESEARCH PROGRAMS WHEN THEY GET TO THEICALLY NICHE. THE OTHER THING IS, FOCUSED SPECIFICALLY AS A RARE DISEASE, OUR ORGANIZATION IS IN A UNIQUE POSITION TO REALLY COLLECT THE LEARNINGS FROM ORGANIZATIONS AND GOVERNMENT FUNDERS AND INDUSTRY PEOPLE WHO HAVE BEEN WORKING ON THESE PROGRAMS AND OTHER DISEASES, FOR A MUCH LONGER TIME AND WE'RE IN A POSITION TO BROKER COLLABORATIONS AND LEVERAGE THESE RELATIONSHIPS TO HOPEFULLY BRING MORE POWER TO BARE ON OUR VERY SPECIFIC RELATED DISEASE. SO I'LL RUN THROUGH A HAHNFUL OF PROGRAMS THAT WE'RE RUNNING THAT HOPEFULLY DEMONSTRATE THOSE POINTS FOR YOU. THE FIRST PROGRAM IS THE FTD DISORDERS REGISTRY WHICH WE ARE CREATING WITH WITH OUR PARTNERS, THE BLOOM FIELD PROJECT TO CURE FTD. THE IDEA BEHIND THIS REGISTRY IS NOT UNIQUE. BUT IT IS FOCUSED ON THE FTD DISORDERS, WE INCLUDE BEHAVIORAL FTD THE PRIMARY PROGRESSIVE AFASCIAS AS WELL AS MOVEMENT DISOTHERS PS AND PCD SO THIS IS A CLOUD BASE DATABASE, IT IS GOING TO CONSIST SOLELY OF DATA ENTERED BY THE LAY PUBLIC. SO THIS IS DATA BY PATIENTS BY THEIR CAREGIVERS AND FAMILY MEMBERS. WE WILL HAVE A GOOD INTERFACE SO WE WILL LINK THIS DATA WITH CLINICAL DATA ON A DEIDENTIFIED MANNER. WE COLLECT EXPERIENCE FROM THOSE LIVING WITH THIS DISEASE EVERY DAY, IT'S CRITICAL WHEN WE LOOK AT DESIGNING CLINICAL TRIALS, BOTH WHAT IS THE TRIAL DESIGN MOST SUCCESSFUL, VALIDATED OUTCOME MEASURES WE'RE GOING USE, AND WE NEED A COMMUNITY THAT IS EMPOWERED AND EDUCATED TO BE PARTNERS IN THE PROCESS. OF COURSE IT WILL THEN ALSO SERVE AS A CRITICAL L TOOL FOR RECRUITMENT FOR THESE CLINICAL TRIALS F. ANOTHER STUDY WE'RE ENGAGING THIS WEEK SPECIFICALLY THAT RELIES ON HEAVY INVOLVEMENT FROM THE CAREGIVER POPULATION, I THINK WE ALL KNOW THE POWER OF HEALTH ECONOMIC STUDIES. LOOK AT PREVALENT DISEASES LIKE CANCER AN DIABETES, IT'S EASY FOR THEM TO COLLECT DATA ON THE FINANCIAL BURDEN OF THOSE DISEASES ON SOCIETY AS A WHOLE AND THAT DATA IS USED EFFECTIVELY TO DRIVE RESEARCH AGENDAS AND DETERMINE THE ALLOCATION OF ASSETS. WHILE IN A RARE DISEASE LIKE OURS NOBODY HAS DONE SOMETHING LIKE THAT. NOBODY ELSE'S JOB TO BOTHER TO FUND AN ECONOMIC BURREN STUDY ON A DISEASE OF 50 OR 60,000 PEOPLE, WHILE IT IS THE RARE DISEASE ORGANIZATION REPRESENTING THIS COMMUNITY. SO THIS YEAR WE'RE WORKING WITH DR. JIM GAL VIN AND WE JUST CLOSED A COLLECTION OF THE DATA THROUGH ONLINE SURVEY AND WE DO ANTICIPATE PUBLICATION BY THE END OF THIS YEAR. AND THIS STUDY WILL PROVIDE THE QUANTITATIVE MEASURE OF COST OF FTD DIAGNOSIS TO A FAMILY AND THEN TO SOCIETY AS A WHOLE. WE WILL USE THIS DATA TO ADVOCATE SPREAD AWARENESS FOR OUR COMMUNITY. WE DO HOPE THE INVESTIGATORS WORKING IN FTD CAN USE THIS DATA AS THEY MAKE THEIR CASES AND GRANT APPLICATIONS FOR FUNDING. AS FAR AS PARTNERING AND LEVERAGING, ONE EXCELLENT EXAMPLE IS TEN YEARS AGO WE WERE APPROACHED BY THE ALZHEIMER'S DRUG DISCOVERY FOUNDATION, THE PERSON CO-CHAIR YOU'LL MEET IN A COUPLE OF MINUTE, DR. HOWARD FILET. THIS IS A TIME YOU AWE -- FILET. WE WERE AWARDING $35,000 A YEAR TOTAL AND NO WAY TO PRESUME TO THINK ABOUT FUNDING PRE-CLINICAL OR CLINICAL DATA IN THE FTDs. HOWARD'S ORGANIZATION THEIR ENTIRE BUSINESS FUNDING DRUG DISCOVERY. AND HE APPROACHED US AND MADE THE INCREDIBLE GENEROUS OFFER MY BRINGING THEIR INFRASTRUCTURE AND EXPERTISE TO BARE. THEY ADDED THEY WOULD MATCH DOLLARS TWO TO ONE, WHAT WE HAD TO BRING TO THE EQUATION WAS CERTAINLY A VERY FOCUSED DONOR COMMUNITY AND ACCESS TO THE EXPERTS BOTH BASIC AND CLINICAL IN THE FTDs. SO TEN YEARS LATER I THINK INCREDIBLY SUCCESSFUL PARTNERSHIPS WE AWARDED $3.5 MILLION FOR FTD DRUG DOSE DISCOVERY. IT'S ABOUT A COUPLE DOZEN AWARDS OVERALL IN PRE-CLINICAL AND CLINICAL SPACE. WE HOPE WE HELP JUMP START THE WORK IN THAT AREA. ANOTHER EXAMPLE OF BRINGING BROADER EXPERTISE TO BARE ON OUR RARE DISEASE, LAST YEAR WE WERE VERY PLEASED TO BE APPROACHED BY A PRIVATE FUNDER WHO WANTED TO MOVE THE NEEDLE IN FTD RESEARCH. AND WE KNEW THAT WE WERE WANTED TO DO SOMETHING IN BIOMARKER, WE HEARD BIOMARKERS THIS MORNING AND YOU HEARD MORE THROUGHOUT THE TWO DAYS I'M SURE. BUT WHEN WE KNOW WE'RE NOT THE FIRST AT THIS TABLE, THERE'S OTHER GROUPS WORKING IN BIOMARKERS FOR A LONG TIME. SO FIRST THING WE DID WAS PICK UP THE PHONE AND H MANY OF YOU IN THIS ROOM GOT THESE PHONE CALLS FROM US ONE WAY OR THE OTHER T. WE COLLECTED DATA FROM NON-PROFITS FROM OUR GOVERNMENT COLLEAGUES HERE AT NIH FROM INDUSTRY. ASKING WHAT HAS BEEN SUCCESSFUL IN THE OTHER DISEASE, WHERE HAVE YOU MADE MISSTEPS WHERE WE CAN HOPEFULLY BENEFIT FROM THE MISTAKES AND SUCCESSES THAT YOU HAVE ACCOMPLISHED. AND WE HAVE BEEN ABLE TO INCORPORATE THAT GENEROUS ADVICE AND LEARNING INTO ADVISORY PANEL WHICH DOES CONSIST OF NGOs OF CLINICAL EXPERTS AND INDUSTRY EXPERTS. WE NOTE MAKE REAL EFFORTS TO INCORPORATE THE RESOURCES THAT NIH FUNDED, YOU HAVE HEARD ABOUT ARTFUL LEFTIES THIS MORNING FROM BRAD BOEVE, AND THE WONDERFUL BIOREPOSITORY NIH STARTED TO FUND. WE VERY MUCH HOPE TO LEVERAGE THOSE THROUGH THE BIMARKER AWARD AS WELL. A LITTLE PLUG, THE RFP IS AVAILABLE ON THE INFO TABLE IN THE LOBBY AND THE LOI IS THREE WEEKS AWAY. WE WELCOME ALL COMERS AND WE WILL INVEST A LOT OF TIME IN DISCUSSING WITH THE APPLICANTS AND HOPEFULLY PUTTING PARTNERSHIPS TOGETHER. SO YOU HAVE A GREAT IDEA BUT NO ACT THOSE FTD SAMPLES, DON'T LET THAT STOP YOU. WE HOPE TO HELP PARTNER DIFFERENT PEOPLE TO PUT TOGETHER SUCCESSFUL PROPOSALS. >> MY FINAL EXAMPLE, SOMETHING WE CALL FTD TREATMENT STUDY GROUP MODELED LOOSELY ON THE ALZHEIMER'S RESEARCH ROUND TABLE. ABOUT EVERY TWO YEARS, WE SPONSOR A MEETING PULLING TOGETHER THE NGO, NIH, CLINICAL EXPERTS, INDUSTRY AND FDA AND HOPEFULLY WE BROKER A DISCUSSION ABOUT CURRENT CHALLENGES, THAT'S IN OUR WAY TO GET INTO MORE COMPOUNDS INTO THE CLINIC AND RUN SUCCESSFUL CLINICAL TRIALS WITH THE IDEA BEING TOGETHER WE CAN COME UP WITH CREATIVE WAYS TO ADDRESS THOSE CHALLENGES. MY RED LIGHT IS BLINKING. THESE ARE JUST FIVE EXAMPLES OF WAYS THAT YOU CAN SEE NGO BROKERS COLLABORATIONS AND BRINGS RESOURCES TO BARE GIVEN OUR SPECIFIC MISSION. AND NOW I'M GOING TO TURN THE MICROPHONE OVER TO RODNEY PEARLMAN FROM THE BLOOM FIELD PROJECT TO CURE FTD. [APPLAUSE] >> I WOULD LIKE THANK ORGANIZERS FOR INVITING US TO PRESENT. IT'S A GREAT NEATING AND I WAS HERE THREE YEARS AGO AND I'M VERY MUCH IMPRESSED WITH THE PROGRESS THAT'S BEEN MADE. THE BLOOM FIELD PROJECT IS A RESEARCH FOUNDATION, NOT FOR PROFIT, 501C 3. WE HAVE TWO ARMS ONE CONSORTIUM FOR FRONTOTHEMTORAL RESEARCH, MORE RESEARCH TIDE, BIOLOGY GENETICS OF THE THE DISEASE AND BLOOM FIELD PROJECT WHICH MANAGES THE FINANCE, MANAGING THE PROGRAMS AND WE'RE MORE FOCUSED AT BLOOM FIELD ON TRANSLATION AND DRUG DEVELOPMENT. THE STRATEGY WE HAVE INVOKED IS REALLY TO SEVERAL FOLD. THE MOST IMPORTANT ONE THINK IS TO RAISE AWARENESS OF THIS RARE GENETIC DISEASE AND SPORADIC DISEASE OF FTD. WE ALSO WANT TO HELP IDENTIFY TARGETS, WE FOCUS ON FTD THOUGH WE SUPPORT OTHER FORMS OF FTD. WE SUPPORT STRATEGIC RELATED PROGRAMS, AS MENTIONED A COUPLE OF TIME, NATURAL HISTORY PROJECTS, THE PATIENT REGISTRY AND PARTNERSHIP WITH AF THETD AND BIOMARKER DISCOVERY EFFORTS. SOMETHING IS DIFFERENT ABOUT OUR ORGANIZATION WE REALLY UNDERSTAND AN NGO OR SMALL NON-PROFIT CANNOT DEVELOP A DRUG, WE CANNOT AFFORD THE COST, THE TIME, THE TECHS PER TEASE, SO OUR METHOD OUR APPROACH IS TO DEVELOP OUR PARTNERSHIPS WITH WITH PHARMA AND BIOTECH COMPANIES TO RAISE AWARENESS AND TO LOWER THE BARRIER OF ENTRY TO WORK ON RARE DISEASE. WE HAVE HAD SEVERAL SUCCESSFUL DISCUSSION AND COLLABORATIONS IN PROGRESS NOW. ONE KEY TO THIS IS HAS BEEN A NEW AGREEMENT FOR RESEARCH AVAILABLE TO AGGREGATE IP TOOLS, SAMPLES AND PRESENT THEM IN ONE STOP SHOPPING TO PHARMA PARTNERS. SO THEIR THAN DEALING WITH DIFFERENT UNIVERSITIES, DIFFERENT PARTNERSHIPS, WE HAVE ONE SIMPLE COLLABORATION WITH US. AND WE'RE ABLE TO SUBLICENSE TECHNOLOGY FROM THE WORK WE HAVE FUNDED SO IT'S BEEN A VERY IMPORTANT BREAK THROUGH TO BE ABLE TO HARNESS THINGS LIKE THAT. WHAT THIS ENABLES US TO DO IS SUPPLY ON THE RESEARCH SIDE, UNDERSTANDING THE BIOLOGY OF DISEASE, ANIMAL MODEL, TOOLS, SCREENING DRUGS, AND THEN ON THE HUMAN PATIENT SIDE BEING ABLE TO PROVIDE INFORMATION ON BIOMARKERS NATURAL HISTORY PATIENT REGISTRIES AND SAMPLES AND IN TURN PARTNER WITH PHARMACEUTICAL AND BIOTECH COMPANIES. OUR FUNDING PRIORITIES THESE ARE FOUR PARTS OF A DO NUT, DISCOVERY TARGETED IDENTIFICATION AND CLINICAL, WE'RE FOCUSED ON THEM ALL AND AS TIME IS CHANGED WE'RE FOUNDED IN 2008, THE SHIFT WAS FROM 80% ON DISCOVERY, AND NOW ABOUT 50/50 DISCOVERY TO TARGET AND ALSO CLINICAL TRANSLATION. FOUR EXAMPLES TO SHOW HOW AN NG IMPACTS THE FIELD. THIS IS A RESEARCH GRANT WE HAVE ABOUT 17 RESEARCH GRANTS THAT WE PROVIDE AND FUND EACH YEAR TO PIs FROM (INDISCERNIBLE) UT SOUTHWEST AND JUST BY SCREENING THE IDE IFED A CLASS OF HDEK INHIBITORS THAT UP REGULATE PROGLAND GRAND LYNN, VERY INTERESTING WORK, WE'RE DOING MORE WORK WITH STEVE HAGGERTY NOW AT MGH TO UNDERSTAND HOW TO HDAX WORK AND UNDERSTAND AND FLESH OUT MECHANISM, THIS IS LED TO INTERESTING OBSERVATIONS AND FOUR HAVE STARTED CLINICAL TRIAL AND HDAC INHIBITOR IN FTD. ANOTHER ONE THAT I WAS PARTICULARLY INTERESTED IN WAS A HAPPENSTANCE CONVERSATION BETWEEN BRAD BOEVE, HOWIE ROSE AND MYSELF AND APPLYING FOR A U GRANT WITH NIH. AND THEY SAID YOU WERE HAVING TROUBLE COLLATING DATA. A LOT OF PATIENT DATA WAS SITTING IN THE FILES. RESEARCH SYSTEMS FOR THEIR TIME TO TAKE DEDICATED TIME TO COMPILE THE DATA. SO WE FUNDED THREE RAs, TWO AT MAYO, ONE AT UCSF AND JOB WAS TO COMPILE PATIENT RECORDS, HISTORIES AND COME UP WITH SOME DATA THAT WAS ADDED TO THE GRANT IT WAS GREATLY SUPPORTIVE AND HELPED TO FUND THE GRANT WHICH IS NOW LEFT USE. SIMILAR WITH ADAM BOX THERE WAS NO MRI OR IMAGE DATA IN HIS ORIGINAL PROPOSAL SO HE ASKED TO SUPPORT THAT AND WE WROTE A LETTER TO NIH SAYING WE WOULD SUPPORT THE MRI STUDIES FOR THIS PROJECT. SO ANOTHER WAY OF BEING ABLE TO LEVERAGE OUR FUNDING IN A VERY INTERESTING MANNER TO HELP SUPPORT AND GENERATE FURTHER FUNDING, THIS YEAR, WE HAVE PROVIDED FUNDS TO GENFE TO HELP CAPTURE BIOSPECIMEN DATA FROM THAT STUDY AS WELL. SO BEING ABLE TO WORK IN SUCH A MANNER QUITE DIVERSE FOUR TOPICS WE FUND QUITE A FEW MORE, PROPOSITION IS BASED ON SEVERAL ELEMENTS, WE THINK ABOUT IT ALL THE TIME. WE HAVE A BOARD WHO IS VERY MOTIVATED, VERY MUCH LOOKING TO US TO DEVELOP THIS TRANSLATION NOW TO A CURE. WE HAVE EXTERNAL ADVISORS, MANY OF WHOM ARE IN THE ROOM TODAY. WE HAVE URGENCY ADMISSION SO WE HAVE SPEED AND FLEXIBILITY TO HAVE FUNDING, FUNDS OFFERED, GRANTS SUBMIT AND RAPID TURN AROUND AROUND ACCESS TO CAPITAL, WE THINK IS REALLY IMPORTANT. ONE POINT THAT SUSAN MENTIONED IS COLLABORATION WE FIND KEY WITHIN CONSORTIUM AND OTHER FOUNDATIONS AND PHARMA. SO IF YOU FIND TYPICALLY WHEN COLLABORATORS RESEARCH WORK TOGETHER THERE'S A SYNERGY AND WE FOUND IT TO BE TRUE FOR US DRIVE OR TECHNIQUE OR PANEL, WE PUT THEM TOGETHER THE FACT THIS APPROACH IS IMPORTANT. LIKEWISE WORE FOUNDATIONS WORKING WITH AFTD AND OTHERS WORKING WITH THE TAU CONSORTIUM WE FIND IT FRUITFUL AND VERY MUCH HELPING TO SOLVE EACH OTHER'S WORRIES AND PROBLEMS, SOME SITTING AN MEETING AND TALKING ABOUT SIMILAR PROBLEMS BEING IMPORTANT. THIS CATALYTIC APPROACH TO PROVIDE DOLLARS LEVERAGED TO OTHER FUNDING OPPORTUNITIES N SOME CASES WE GET MATCHING FUNDS, OTHER TIMES WE WILL PROVIDE FUNDING THAT IS A SEED FOR FURTHER WORK. LASTLY BRINGING VALUE TO PARTNERSHIPS, WE PROVIDE TO PHARMA THEY CAN'T ACCOMPLISH THEMSELVES, FRUITFUL USE OF OUR TIME AN MONEY. LAST TO ACKNOWLEDGE OUR COLLABORATOR, ADVISOR, SAB, LAURA MITIK A VALUABLE PARTNER THAT MAKES THINGS WORK AND HAPPEN AND COLLABORATIVE UNIVERSITIES. THANK YOU FOR YOUR TIME. [APPLAUSE] >> NEXT WE HAVE SIMON RIDLEY FROM ALZHEIMER'S RESEARCH UK. >> THANK YOU VERY MUCH. FIRST THANK THE ORGANIZERS FOR THE INVITATION TO SPEAK AT THIS VERY INTERESTING BUT ALSO VERY IMPORTANT EVENT. I'M ALSO PRIVILEGED TO BE REPRESENTING NGOs FROM THE UK, A LOT GOING ON NOW IN THE UK IN TERMS OF DEMENTIA RESEARCH AND SOME WHICH I WOULD LIKE TO SHARE WITH YOU, HOPE YOU DEMONSTRATE EXAMPLES OF THE WORK WE'RE DOING WHICH MAY RESONATE WITH THIS AUDIENCE. ALZHEIMER'S UK WE ARE A CHARITY AS WE TEND TO SAY, WE EXIST TO FUND BIOMEDICAL DEMENTIA RESEARCH, WE HAVE A GREAT INTEREST NO NON-ALZHEIMER'S DEMENTIA. WE'LL GO THROUGH SOME GENERAL POINTS ABOUT WHAT WHAT ORGANIZATIONS IN THE SECTOR CAN CAN DO TO SUPPORT RESEARCH AND SOME IN GENERAL I TRY TO APPROACH THESE PERHAPS WITH A UK PERSPECTIVE WHICH MAYBE INTERESTING FOR PEOPLE, SO FIRST I THINK WE CAN SUPPORT RESEARCH INDIRECTLY, WE CAN HELP WITH PUBLIC AWARENESS AN PUBLIC INFORMATION. I THINK ONE OF THE CONSEQUENCES OF INCREASE INTEREST IN MEDIA, INTEREST IN DEMENTIA IS A LOT OF US ARE BUSIER IN DEALING WITH REQUEST IN RESPONSE TO NEWS STORIES AND QUESTIONS FROM THE PUBLIC. SO I THINK WE HAVE AN IMPORTANT ROLE THERE. SO WE ALSO -- WE HAVE EVIDENCE HERE THAT WE CAN HELP RAISE PROFILE AND ADVISE POLITICAL AND POLICY LEVEL AND I THINK MANY OF US SUCCESSFUL IN THIS REGARD, UK THE CONVERSATION WE HAVE BEEN HAVING WITH OUR COLLEAGUES IN GOVERNMENT FUNDING A AGENCIES MHR, MRC IN PARTICULAR THOSE CONVERSATIONS LAST FIVE YEARS COMING THROUGH SOMETHING ON DEMENTIA TO HOW WE BEST YOUR RESOURCES AND WORK TOGETHER. THAT'S FAR MORE INTERESTING AND PRODUCTIVE DISCUSSION AND I THINK WE'RE SEEING THE RESULTS OF THAT AND WE WILL OVER THE NEXT FEW YEARS. AS WE MENTION PARTICIPATION ARE RESEARCH THROUGH A NUMBER OF GROUPS, THE UK OURSELVES, TO ESTABLISH A JOINT RESEARCH, WHICH IS GETTING PEOPLE INVOLVED IN DEMENTIA VERGE. SO YOU CAN DIRECTLY SUPPORT RESEARCH AS WELL. THROUGH OUR OWN FOUNDING, AUGMENT OR COMPLIMENT, FUNDING PROVIDED BY GOVERNMENT AGENCIES. IN ABSOLUTE TERMS WE'RE DOING REASONABLY WELL WE'RE FUNDING ABOUT JUST UNDER $50 MILLION WORTH OF RESEARCH THROUGH VARIOUS MEANS AT THE MOMENT, WE LOOK RELATIVELY TO OTHER WORTHY BUY MEDICAL CAUSES CHARITABLE CAUSES IN THE UK WE'RE QUITE A GOOD AND STRONG TRADITION OF SUPPORTING PUBLIC SUPPORT RESEARCH DEMENTIA LACK MIND SIGNIFICANTLY SO. WE HAVE WORK TO DO THERE. OUR OWN CONTRIBUTION IN RELATIVE TERMS, GOVERNMENT ORGANIZATIONS, THAT IS CHANGING LANDSCAPE AS I SAID AND IT'S CHANGING FOR THE GOOD. THE ONE SENSE IT'S NICE TO FEEL THAT ARE OUR OWN CONTRIBUTION IS QUITE SIGNIFICANT AND QUITE LARGE BUT AT THE SAME TIME WE SEE THE KINDS OF INVESTMENTS BEING MADE OVER THIS SIDE OF THE ATLANTIC, I FEEL SOMEWHAT ENVYIOUS AND I WOULD MUCH RATHER CONTRIBUTION WAS MUCH SMALLER. SO LEVERAGE I THINK IS A COMMON THEME, WE CAN LEVERAGE ADDITIONAL FUNDING THROUGH DIFFERENT ROUTE, PASSIVELY OR CONSEQUENTIALLY. FUNDING A SMALL PILOT DATA, SUPPLY FOR LARGER GRANTSES, ORGANIZATIONS OR PERHAPS THROUGH PEOPLE SO FELLOWSHIPS, STUDENTSHIPS, WE SUPPORT THOSE. AND AGAIN THOSE PEOPLE GO ON TO DEVELOP -- SUPPORT BY OTHER ORGANIZATIONS THAT WE FEEL WE CAN -- JOB WELL DONE. THE OTHER MECHANISM FOR LEVERAGE, A COUPLE OF EXAMPLES, PARTNERSHIP, THAT'S AN IMPORTANT THEME FOR MANY OF US TO TAKE. DRUG DISCOVERY AND DEVELOPMENT, WE THINK ABOUT HOW THOSE ARE TRADITIONALLY FUND, FAIR TO SAY THE GOVERNMENT FUNDING TENTS TO BE WEIGHTED, THIS IS UK PERSPECTIVE TENDS TO BE WEIGHTED ON THE LEFT-HAND SIDE. WHEN WE LOOK WITHIN ACADEMIC BASIC RESEARCH ONE CAN VIEW THAT DIVIDE THAT BETWEEN DEMENTIA, DEMENTIA SPECIFIC RESEARCH AN MORE GENERAL. I THINK AS WE SEE INCREASES IN VERY WELCOME INCREASES IN GOVERNMENT SUPPORT FOR DEMENTIA RESEARCH, ALL OF US SHOULD ACKNOWLEDGE THE DEPENDENCY WE HAVE ON RESEARCH FOR MORE FUNDAMENTAL BIOLOGY AND MORE FUNDAMENTAL MECHANISMS AND I GIVE EXAMPLES OF HITS AND INTEREST MEMBRANE TRAFFICKING COLLATERAL METABOLISM, IF WE WANT TO CAPITALIZE ON THAT, WE NEED OTHER AGENCIES TO BE FUNDING THAT FUNDAMENTAL RESEARCH ASKING THOSE FUNDAMENTAL BIOLOGY QUESTIONS. SAME IS TRUE, TECHNOLOGY, WE SEE CRISPER AND OTHER GENE EDITING AND OPTOGENETICS. WE ARE BENEFITING DISEASE CHANNELS AND WE NEED TO BE SEEING CONTINUED SUPPORT FOR FUNDAMENTAL RESEARCH, DEPENDS ON THIS AS WELL. WE CAN SEE THE RIGHT HAND SIDE ON BIOTECH SEEMS TO BE PUTTING THE MOST INVESTMENT INTO DRUG DISCOVERY INVESTMENT. WE ARE LOOK AT THE -- WHERE THERE MAYBE GAPS. FOR NGO WE'LL HERE FROM HOWARD LATER WE'RE NOT THE ONLY PEOPLE INTERESTED IN THIS GUESS THESE GAP BUS THESE ARE AREAS WE'RE TRYING TO DO SOMETHING ABOUT, ONE LEVEL OF FUNDING PRE-CLINICAL TARGET VALIDATION STUDIES, IF WE WANT PHARMA TO OR INDUSTRY TO ADOPT POTENTIAL DRUG TARGETS PERHAPS GWAS OR NEUROPATHOLOGY STUDIES THE IF WASN'T INDUSTRY TO GET INTERESTED WE DO DERISKING AND EARLY STAGE L&E PRE-CLINICAL VALIDATION BECAUSE THAT IS A GREAT POTENTIAL INCENTIVE FOR THAT FURTHER INVESTMENT. SO THE OTHER GAP WE FELT EXISTED IN THIS SPACE AND CERTAINLY UK, WAS THE LEVEL OF DRUG DISCOVERY CAPABILITY WITHIN ACADEMIC CENTERS. NOW THAT'S NOT THE SAME AS NOT THE SAME AS ACADEMIC DRUG DISCOVERY, MORE DRUG DISCOVERY WITHIN ACADEMIA, SO WE WANT -- WE LIKE THE IDEA OF EMBEDDING AND PLACING EXPERIENCED DRUG DISCOVERY EXPERTISE WITH INCENTIVES WHERE THERE'S EXPERTISE CRITICAL MASS BASIC BIOLOGY IN CLINICAL KNOWLEDGE EXPERTISE, AS WE HAVE HEARD THIS MORNING, DRUG DISCOVERY IS ITSELF BY NATURE REDUCTIONIST BUT WE NEED OUR COLLEAGUES TO REMIND US OF COMPLEXITIES OF A REAL DISEASE AND I THINK ANY DRUG DISCOVERY AND DEVELOPMENT PROCESS ONE NEEDS TO HAVE THAT BACKGROUND KNOWLEDGE. ANOTHER PHRASE WE'LL HEAR TODAY BROKERING SO FARM -- I THINK CHARITIES NGOs CAN BE HELPFUL TO BROKER INVESTMENT AND OPPORTUNITIES THIS IS A LITTLE VAGUE, IT'S DOWN ON THE RIGHT HAND SIDE, IT CAN APPLY AT ANY LEVEL BUT CERTAINLY OUR OWN ACTIVITIES NOT SUFFICIENTLY FUNDED TO BRING DRUGS TO MARKET SO WE NEED TO BE PARTNERING AND BROKERING THOSE PARTNERSHIPS TO ENSURE THAT HAPPENS. BRIEFLY TWO EXAMPLES WHICH WHERE SOME OF THIS IS ACTION. WHAT THEY HAVE IN COMMON IS THEY'RE BOTH DRUG DISCOVERY, EXAMPLES, THEY ALSO DELIBERATIVELY TRY TO AVOID WORKING IN AREAS PHARMA HAS WORKED PREVIOUSLY ORER IS WORKED CURRENTLY, NO POINT TRYING TO DUPLICATE WHAT PHARMA IS UP TO, THE OTHER THING THEY HAVE IN COMMON IS DEVELOPED BY ERIC KAREN WHEN HE WAS WITH US, THAT BROUGHT A HUGE AMOUNT TO OUR STRATEGY BECAUSE HE WAS COMING WITH THE SPEAKER PERSPECTIVE WHAT WILL WILL PHARMA NEED WITH THESE PIPELINES SO THAT WAS A GOOD STARTING POINT FOR US. THE CONSORTIUM IS CONSORTIUM BETWEEN PHARMA COMPANIES, THIS IS ABOUT DERISKING NOVEL TARGETS, PEOPLE WHO COMPLY FROM AROUND THE WORLD FOR FUNDING, TO DO EARLY STAGE TARGET VALIDATION AND STARTED DRUG DISCOVER PIPELINE WHICH GOES PROMISINGLY AND WELL, PHARMA PARTNERS IN THE CONSORTIUM ADOPT SUCCESSFUL. P MODEST FUNDING IS CURRENT ENVELOPE OVER $6 MILLION WITH HALF OF THAT COMING FROM OURSELVES. SO SAME MRCT ORGANIZATION THEY STARTED AS A GOVERNMENT ORGANIZATION NOW NON-GOVERNMENT ORGANIZATION SO INDEPENDENT FROM MEDICAL RESEARCH COUNCIL BUT THEY CO-LEAD, THEY ORGANIZE P APPLICATION OF REVIEW PROJECT MANAGEMENT ELEMENTS. TECH TRANSFER EXPERTS AND IN HOUSE DRUG DISCOVERY. THE OPTION TO PURSUE ANY TARGET POST VALIDATION. WE INSTIGATED THIS THROUGH CURRENT AND REMAINED SINGLE FUNDER. WE'RE FUNDING MORE NEARLY INDIVIDUAL PHARMA COMPANY BUT TOGETHER AS CONSORTIUM GROWS THE PHARMA COMPANIES ARE PUTTING IN MORE THAN WE ARE. SO GOOD EXAMPLE. I'LL JUST BRIEFLY TALK ABOUT THE DRUG DISCOVER ALLIANCE, THIS IS THE IDEA EMBEDDING PHARMA LEVEL DRUG DISCOVERY EXPERTISE WITHIN THREE LEADING UK CENTER RESEARCH, DRUGGER TARGETS WITHIN CENTERS, BEYOND THE CENTERS, INITIAL FUNDING HE WILL ENVELOPE $30 MILLION SIX YEARS, GOOD -- UNIVERSITY HEALTHYNESS WITHIN DIRECT COSTS AND ONE EXCITING DEVELOPMENT IN THE UK, GLOBAL RESEARCH IS MEDICAL RESEARCH COUNCIL DEVELOPING NEW DEMENTIA RESEARCH INSTITUTE IN THE TUCK AND WE LOOK FORWARD TO WORKING VERY CLOSELY WITH THEM FOR TO SEE TRANSLATION OF FUNDAMENTAL RESEARCH TOWARDS NEW TREATMENTS. I'LL STOP THERE. THANK YOU. [APPLAUSE] >> WE HAVE TODD SHERER FROM THE MYGALE J FOX FOUNDATION. OUR ROLE OKAY SELL RATING RESEARCH IN THIS AREA. ONE RELEVANT TO THE DISCUSSION THIS MORNING ABOUT THE COMPLEXITY OF THE PATHOLOGY, ACROSS DIFFERENT DISEASES PARKINSON'S AND THE ALZHEIMER'S RELATED DEMENTIAS. AND THE EXAMPLE IS THIS PROGRAM CALLED BIOMARKERS ACROSS NEURODEGENERATIVE DISEASES, IT'S AN INTERESTING EXAMPLE BECAUSE A LOT OF TIMES NON-PROFIT ORGANIZATIONS WILL BE FRUSTRATED BY THE LACK OF COLLABORATION IN THE ACADEMIC AND INDUSTRY RESEARCH SPACE. THERE'S NOT ALWAYS GREAT EXAMPLES OF COLLABORATION IN THE FUND SPACE. THIS IS A GREAT EXAMPLE WHERE YOU HAVE ORGANIZATIONS LIKE THE FOX FOUNDATION AND SOME OF THE ALZHEIMER'S ASSOCIATION LIKE ALZHEIMER'S ASSOCIATION ALZHEIMER'S UK AND WESTERN BRAIN INITIATIVE, A CANADIAN BASED NEURODEGENERATIVE FOUNDATION, THEY WILL COME TOGETHER TO LAUNCH A FUNDING PROGRAM THAT IS ENCOURAGING INVESTIGATORS TO LOOK AT BIOMARKERS ACROSS NEURODEGENERATIVE DISEASES. AND TO LEVERAGE EXISTING DATA SETS LIKE THE ADNE AND P THE PAR KIN CHON'S PROGRESSION MARKERS. IT'S DATA AN LIT TYPE PROGRAM, THERE'S TWO ROUNDS OF THIS PROGRAM AND WHAT'S UNIQUE IS THAT ALL THE FOUNDATIONS HAVE COME TOGETHER TO HAVE ONE A APPLICATION PROCESS AND ONE REVIEW COMMITTEE. THEN SELECT PROJECTS TO SOLELY FUND OR CO-FUND. SO A LOT OF EFFICIENCY IN TERMS OF APPLICATION PROCESS AND THE NUMBER OF APPLICATIONS THAT RESEARCHERS HAVE TO PUT TOGETHER. THEN THERE'S A COMBINED PROCESS IN TERMS OF MANAGEMENT AND REVIEW OF THOSE PROJECTS GOING FORWARD SO IT'S ADDRESSING A CRITICAL SCIENTIFIC CHALLENGE THAT WAS RAISED THIS MORNING, HOW WE START TO BRING RESEARCH TOGETHER TO GO ACROSS OUR TRADITIONAL VIEWS OF THESE DISEASES AND THEN TO USE THE CAPABILITIES OF THE FOUNDATIONS TO MOVE ON THIS QUICKLY. ANOTHER EXAMPLE THAT I WANTED TO HIGHLIGHT IS FOX FOUNDATION DEVELOPED A RESEARCH TOOL CONSORTIUM, THIS IS FOCUS CANNED ON PRE-CLINICAL TOOLS SUCH AS ANTI-G VIRAL VECTORS, CELLULAR MODELS AND ANIMAL MODELS, IT'S A COLLABORATION BETWEEN INDUSTRY ACADEMICKINGS AND THE FOUNDATION -- ACADEMICS AND FOUNDATION INDUSTRY. WHAT'S UNIQUE ABOUT THIS IS THE WAY THESE TOOLS ARE DEVELOPED SO THERE'S SOLICITATION FROM THE ACADEMIC COMMUNITY AND INDUSTRY, TO IDENTIFY IMPORTANT TOOLS WE NEED IN THE FIELD, THEN THE PROCESS THROUGH WHICH THE FOUNDATION CONTRACTS OUT GENERATION OF THOSE TOOLS IN A WAY THAT THEY ARE MADE FREELY AT COST AVAILABLE WITH NO IP OR OTHER RESTRICTS TO THE RESEARCHERS. I THINK WHAT'S IMPORTANT ABOUT THIS IS THEN RESEARCHERS ARE USING SIMILAR TOOLS IN THEY WERE ANALYSIS SO ONE WE HAVEN'T HEARD A LOT TALKED ABOUT TODAY IS THIS CHALLENGE WE HAVE HAD WITH REPLICATION AND UNDERSTANDING ABOUT WHAT ARE TRUE FINDINGS. PROVIDING SIMILAR TOOLS TO RESEARCHERS, WE DON'T SPEND TIME AND RESOURCES DUPLICATING THEY EXIST BUT ALSO THEY HAVE SYCES TO -- ACCESS TO THIS. ANTIBODIES AND VECTORS AVAILABLE THROUGH PLACES LIKE JACK SOB LABS AND OTHER REPOSITORIES THAT RESEARCHERS CAN CAN BE EASES. SO A GOOD ROLE FOR A FOUNDATION TO PLAY TO COORDINATE THIS TYPE OF WORK. [APPLAUSE] HOWARD IS COMING UP NEXT. >> SO I WAS GOING TO INTRODUCE MYSELF IN THE SPIRIT OF DAVID BENNETT. TO SAY I'M HOWARD PHI LET. WE ATTEMPTED TO FILL THE SPACE THAT WE KIND OF COIN THE TERM -- PREEXISTING, ABOUT VENTURE PHILANTHROPY AND I'LL GIVE YOU A FLAVOR ABOUT WHAT WE'RE TALKING ABOUT HERE BUT BASICALLY OUR SOLE MISSION IS DRUG DISCOVER, THAT'S ALL WE DO, ALL WE FUNDS. AND IT'S REALLY HAVING THAT VISION HAS DRIVEN OUR WORK VERY CLEARLY, THREE TO -- WE LIVE IN FINANCING GAP IN THE VALLEY OF DEATH EVERY DAY. THIS IS DATA FROM THE EYE DROP DATABASE THAT WAS DEVELOPED BY THE NIH AND THE ALZHEIMER'S ASSOCIATION AND YOU CAN SEE IN THE UPPER LEFT THERE, KNOW WHERE MY POINTER S SORRY. YOU CAN SEE IN THE GREEN THAT WHEN GRANTS ARE CODED BY TYPE THAT WE REALLY STICK TO OUR KNITTING AND OUR GRANTS ARE SOLE PURPOSE IS TO ACCELERATE RAPIDLY ACCELERATE DRUG DISCOVERY FOR ALZHEIMER'S DISEASE AND RELATED DEMENTIAS. SO SENSE 1999, WE HAVE SEEN OVER 3,500 -- THIS IS RIDICULOUS. OVER 3,500 NEW IDEAS FOR NEW DRUGS FOR ALZHEIMER'S DISEASE, WE HAVE REVIEWED JUST ABOUT EVERYONE OF THEM, WE FUNDED OVER 500 PROGRAMS IN 18 COUNTRIES WITH OVER $80 MILLION INVESTED AND WE'RE CARRYING A POINT OF LAW 100 ACTIVE DRUG DISCOVERY PROGRAMS. ONE UNIQUE POINT OF OUR PROGRAM WHICH WE HAVE HAD FROM THE VERY BEGINNING IS THE ABILITY TO FUND BIOTECH COMPANIES TO BOTH HELP ACADEMIC CENTERS TO START A BIOTECH COMPANIES AND FUND EARLY STAGE VIRTUAL COMPANIES IN THEIR WORK. THIS HAS BEEN A CRITICAL PART OF OUR PORTFOLIO. THE $80 MILLION WE HAVE INVESTED SO FAR HAS RESULTED IN OVER $2 BILLION IN FOLLOW ON FINANCING FROM VARIOUS SOURCES. AND WE HAVE HELPED TO STARTUP COMPANIES LIKE AVID PHARMACEUTICALS AND PHARMA TROPICS HIGHLIGHTED TON FRONT PAGE OF TIME MAGAZINE. SO THE BIOTECH, EMPHASIS HAS BEEN HELPFUL BECAUSE IT CATALYZES ALL THE WORK INTO ONE PLACE. TAKES ADVANTAGE OF THE SPIRIT OF ENTREPRENEURIALISM, THE ABILITY TO FINANCE PROJECT WHERE IS MONEY IS NEEDED FROM COMPANY SOURCES TO FINANCE DRUG DISCOVERY SO INTEGRAL PART OF WHAT WE DO. PARTNERSHIP IS CRITICAL AS YOU HEARD FROM MANY OF THE SPEAKERS. AND WE HAVE MANY PARTNERSHIPS, I DON'T HAVE TIME TO GO INTO THESE WE'RE PROUD OF THE AFTD PARTNERSHIP WE FUNDED AFTD BIORESEARCH FOR TEN YEARS NOW. IN OUR TENTH YEAR. AND WE PARTNER WITH INDUSTRY WITH PFIZER THROUGH THE CTI WITH LILY NOW. AND WITH OTHERS AND PARTICULAR THE NIH. SO PARTNERSHIP HAS BEEN CRITICAL AS YOU HAVE HEARD AND WE'RE ALSO IN THAT AS WELL. WE HAVE GREAT PARTNERSHIP WITH THE ALZHEIMER'S SOCIETY IN THE UK AS WELL AS OTHERS. ALONG THE WAY WE REALIZENA BOTH PEARL STAGE BIOTECH COMPANIES VIRTUAL AND ACADEMIC RESEARCHERS TRYING TO DO THEIR WORK DON'T HAVE ACCESS TO DRUG DISCOVER SERVICES. WHAT WE DID WITH HELP OF ANONYMOUS DONOR WORKED INITIALLY THROUGH THE FOUNDATION AND WITH A COMPANY CALLED ON DECK BIO. A MECHANISM, ONLINE MATCH.COM FOR -- WE VETTED ALMOST 100 CROs FOR THEIR ABILITY TO CONDUCT VARIOUS SERVICES THAT ARE NEEDED TO DO DRUG DISCOVERY MEDICINAL CHEMISTRY HIGH THROUGH PUT SCREENING IND ENABLING RESEARCH AND SO ON. WE VETTED THOSE PARTICULARLY FOR THEIR ABILITY TO WORK IN THE AREA AND EXPERIENCE IN CNS SO THIS IS A VIRTUAL NETWORK OF CROs AND CONSULTANTS AND FROM THAT WE FITTED PROJECT MANAGEMENT TOOL, ADVISORY BOARD OF VARIOUS SECTORS AND ONE THING POINTED OUT WAS THAT ACADEMIC SCIENTISTS AND EARLY STAGE BIOTECHS DON'T HAVE CAPABILITY FOR CONTRACTING MANAGEMENT, PROJECT MANAGEMENT, AND MONITORING OF UPON GOING WORK SO WE BUILT INTO THIS WEBSITE THE ABILITY TO DO ALL THOSE THINGS AND MORE EVENTUALLY WE BUILT IN A LIBRARY EDUCATIONAL RESOURCES FOR DRUG DISCOVERY TO TEACH PEOPLE HOW TO DO THIS. WE'RE IN OUR 10TH YEAR CONDUCTING A DRUG DISCOVERY FOR NEURODEGENERATION CONFERENCE. WE JUST HAD OUR LAST IN MYANY. WE'RE HAVING ONE -- MIAMI. WE'RE HAVING ONE IN BUDAPEST IN MAY AND THIS IS QUESTIONS FUNDED BY THE NIH. SOLVE WE'RE TRYING TO RAISE THE BAR ACROSS ACADEMIA AND EARLY STAGE BIOTECH SUPPORT. CONDUCTING THIS WORK ACCELERATE AND FACILITATING AND BASICALLY SORT OF BRIEFLY HOW IT WORKS. P P AGAIN, THIS IS DONE THROUGH -- WITH A PARTNERSHIP MORE RECENTLY OF ACCOMPANY THAT SERVICE IT IS BIOTECH INDUSTRY IN GENERAL, THEY'RE THE PROVIDER OF THE SERVICE TO AN -- THE BIOTECH KNOWLEDGE INDUSTRY ORGANIZATION. I THINK IT'S CALLED BIOTECHNOLOGY INNOVATION ORGANIZATION WHICH HAS MEMBERSHIP OF 35,000 PEOPLE FROM ALL OVER THE WORLD. IN THE BIOTECH SECTOR. AND IF ANYBODY WANTS MORE INFORMATION, I WANT TO THANK OUR PARTNERS, BRAD -- CHILDREN'S ALZHEIMER'S ASSOCIATION HELPING TO FUND THIS. AND LAUREN FRIEDMAN, DR. FRIEDMAN LEADS ON THIS AT OUR FOUNDATION FOR ANYONE WHO WANTS TO LEARN MORE ABOUT IT. THE OTHER EXAMPLE TO I WANT TO GIVE IS THAT WE ALL RECOGNIZE THAT MANY WORTHY HEN GRANTS GO UNFUNDED, PEOPLE ARE SUFFER WITH THE NEW MONEY COMING IN THAT THE SUCCESS RATES FOR NIH GRANTS OBVIOUSLY WILL BE BETTER BUT CERTAINLY ABOUT SEVEN YEARS AGO WE'RE TALKING WITH NIH STAFF I SHOULD SAY AND NINDS AND REALIZE WE WOULD BE MORE THAN WILLING AN HAPPY TO RECEIVE NIH GRANTS THAT WERE AT THE PAY LINE OR JUST BELOW THE PAY LINE. PARTICULARLY THOSE THAT WERE DRUG DISCOVERY GRANTS BECAUSE THERE WAS THIS SENSE THAT DRUG DISCOVERY GRANTS WERE BIAS AGAINST, THE STUDY SECTIONS WITH WERER PRIMARILY FUNDING BASIC RESEARCH AND DRUG DISCOVERY THINGS LIKE THE ROUTINE SCREENS AND THAT SORT OF THING CREATED REAL RESEARCH I THINK MANY OF US REALIZE NOW DRUG DISCOVERY RESEARCH IS A FASCINATING FIELD THAT REQUIRES A VERY SPECIAL SKILL SET OF MEDICINAL CHEMISTRY, PHARMACEUTICAL SCIENCE, REGULATORY WORK AND SO ON. SO WE WORK TO RECEIVE NIH GRANTS, RECEIVE REVIEW AROUND RAPIDLY TURN THEM AROUND IN 30 DAYS AND PROVIDE FUNDING TO GRANTS THAT WEREN'T FUNDED FOR ENOUGH CASES -- OR IN CASE WHERE IS FUNDING WAS CUT BUT GRANT WAS APPROVED, TO PROVIDE SUPPLEMENTAL FUNDING TO APPROVE GRANTS. THIS WORKED PRETTY WELL, IT PUTS A BIT OF A BURDEN ON NIH STAFF RIGHT NOW, IT'S CURRENTLY AN INFORMAL PROCESS, NIH STAFF ARE HAVE TO THINK ABOUT IT AND SUGGEST TO INVESTIGATORS WE TRIED TO RAISE AWARENESS ABOUT THIS PROGRAM THROUGH OUR WEBSITE. AND OUR REVIEW IS ITERATIVE AND WE WORK WITH INVESTIGATORS TO THOUGH WE'RE RECEIVING THE FLAT NIH GRANT WE'RE WORKING WITH INVESTIGATORS TO FUND SPECIFIC AIMS THAT ACT SEMIRATE SO THEY CAN GET MORE -- ACCELERATE THEM TO GET MORE DATA ON THE NEXT ROUND, IT TAKES NINE MONTHS TO TURN AROUND AND OFTEN PEOPLE AROUND FUNDED FOR 18 MONTHS. SO THIS HELPS PEOPLE TO GET THAT ADDITIONAL DATA TO GET THE SECOND REVIEW HOPEFULLY APPROVED WE HAVE PROOF OF CONCEPT THAT THIS NGO NIH MECHANISM FOR FUNDING REALLY WORKS MORE RECENTLY IN THE LAST WEEK OR SO, WITH WE HAVE COME ACROSS NIH WIDE EFFORT THROUGH AN ORGANIZATION CALLED ON PAR WHICH WE'RE NOT -- WE TALKED ABOUT IT THROUGH THE STAFF, NOT CLEAR HOW IT WILL WORK. AND IT MAY SUPERSEDE THIS BUT HOPE NOT, WE'RE FOCUSED ON RECEIVING THE DRUG DISCOVERY GRANTS, WE WANT TO FOCUS CAN ON THAT. SO IT'S PROOF OF CONCEPT THERE'S NIH EFFORT TO DO THIS SO NGOs A ACROSS ALL DISEASE STATES CAN GET IN ON HELPING TO FUND PROJECTS BUT FOR NEURODEGENERATION, FOR RARE DISEASES LIKE FTD WHERE FUNDING IS SPECIFICALLY NEEDED AND WE NEED TO CONNECT THE NG SPECIFICALLY, I THINK THIS KIND OF MECHANISM CAN BE IMPROVED UPON AND WE NEED TO FIND WAYS TO OF INVOLVE OTHER NON-PROFITS IN OUR FIELD, AFTD, LEWY BODY DEMENTIA ASSOCIATION, SO ON ALL THE OTHERS HERE TODAY, TO HAVE FIND WAYS TO MINIMIZE BURDEN, CONTINUE TO FUND WORTHY DRUG -- WORTHY GRANTS FLOWER FIELD AND OBVIOUSLY FROM OUR POINT OF VIEW WORTHY DRUG DISCOVERY GRANTS TWO EXAMPLES. AND THAT'S REALLY CONCLUDES MY TALK. WHAT I WANTED TO DO NOW IS GO THROUGH SOME OF THE SUMMARY RECOMMENDATIONS BEFORE WE HAVE OUR PANEL. SUSAN DICKINSON MENTIONED THAT THE RECOMMENDATION NUMBER ONE FROM OUR GROUP WAS TO ESTABLISH MORE EFFECTIVE COMMUNICATION BETWEEN NIH AND THE NON-GOVERNMENTAL ORGANIZATIONS ON ACTIVITIES AND PROGRESS TOWARD THE ADC POLLS IN THE OFF YEARS BETWEEN THE TRY ANNUAL ADRD RESEARCH SUMMITS. I'LL READ THESE AS YOU READ THEM. ALL MILESTONES IMPLEMENTATION PLANS AN SUCCESS CRITERION SUPPORT THESE GOALS WILL BE PUBLICLY MADE ON THE -- THE SITE AND NINDS WILL HAVE OFFICIAL REPRESENTATION AT THE NAPA COUNSELING MEETINGS THAT NINDS WILL PRESENT ANNUALLY TO THE NAPA PROGRESS AND WILL HAVE AN ANNUAL SATELLITE MEETING TO THE IN PA COUNCIL NINDS AND NIA AND NGO FUNDING PROGRESS TOWARDS THE GOALS. THANK YOU VERY MUCH. IF I CAN CALL UP MARIE CARRILLO TO MODERATE OUR PANEL DISCUSSION AND MODERATE THE OPEN SESSION AND THE OTHER PANELISTS IN THIS SESSION. IF YOU WOULD COME UP, PLACE. THANK YOU VERY MUCH. [APPLAUSE] >> THANK YOU VERY MUCH. TO OUR PANEL iS WHO JUST SPOKE. I KNOW THERE WERE -- THERE ARE OTHER PANELISTS HERE WHO DIDN'T HAVE THE OPPORTUNITY TO GIVE YOU SOME EXAMPLES OF WHAT THEY'RE DOING BUT BEFORE I OPEN UP FOR QUESTIONS, I SEE JOHN IS ALREADY UP THERE, I WANTED TO -- WE'RE MISSING A PANELIST. IS COSTANTINO IN THE ROOM? HOPEFULLY WE CAN FIND HIM. SO I THINK -- WHAT I WANT TO START OFF BY SAYING IS THAT SOME OF THE WORDS THAT I THINK WERE I HEARD THAT WERE UNIQUE TO WHAT NON-PROFIT ORGANIZATIONS NGOs CAN OFFER TO THIS PARTICULAR FIELD TO OUR FIELD, WERE WORDS LIKE LASER FOCUS. PREYLY FOCUS ON THAT FUNDING. CATALYZE, COLLABORATES. CONVENE. WHERE OTHERS CAN'T OR OTHERS WON'T. WE ARE RAISING AWARENESS, AWARENESS OF VERY IMPORTANT DISEASES THAT MANY TIMES DON'T HAVE THE OPPORTUNITY TO HAVE A VOICE, BECAUSE THEY MIGHT BE A SMALLER OR MIGHT BE -- MIGHT HAVE STIGMA ATTACHED TO THEM, PEOPLE DON'T WANT TALK ABOUT THEM. WE TALK ABILITY FUNDING GAP Z BECAUSE THAT'S PART OF WHAT WE OFFER AS NGOs. THANKS, FOR JOINING US. SO I WANTED TO ALSO ENSURE THAT ALL OF YOU KNEW THAT WE ARE AS NGOs OPEN TO OTHER IDEAS, AND WAYS OF TALKING ABOUT PARTNERSHIPS AND COLLABORATION THAT YOU AS COMMUNITY MIGHT THINK OF, THIS IS A GREAT OPPORTUNITY BUT IT'S NOT THE ONLY ONE, TO COME TO US AS ORGANIZATIONS AND TELL US WHAT YOU THINK ARE OTHER AREAS WE MIGHT BE ABLE TO FOCUS ON AND UNIQUELY CONTRIBUTE TO. WITH THAT I'LL OPEN TO JOHN AND SEE WHAT QUESTIONS MIGHT BE IN THE AUDIENCE. >> TERRIFIC SERIES OF PRESENTATIONS, I'M SO GLAD GRATIFIED TO SEE COLLABORATIONS BETWEEN NGOs AND SOMETHING THAT'S COME UP A NUMBER OF TIMES FTD MEETINGS AND ALZHEIMER'S MEETINGS. LEWY BODY MEETINGS AS OFTEN SO MANY NGOs WORKING ON DISEASE OR FTD AND IT WOULD BE GREAT BENEFIT OBVIOUSLY FROM COLLABORATING, IN FACT PAN AND MICHAEL J. FOX ARE MERGE, THAT'S GREAT IDEA, NOT THAT EVERYONE HAS TO MERGE BUT CERTAINLY PARTNERSHIPS ARE HUGE. I'LL REMIND PEOPLE OF THE IMPACT THAT CAN COME FROM THESE ADNE WAS FUNDED IN 2004, JUST GOT ADNE 3 WAS JUST RENEWED SO I HAVE A JOB FOR ANOTHER FIVE YEARS DOING BIOMARKER WORK WITH LES SHAW, THE IMPORTANT POINT OF ADNE IS IT IS ABSOLUTELY TRANSFORMED CLINICAL TRIALS FOR ALZHEIMER'S DISEASE, SOMETHING UNHEARD OF WHEN ADNE GOT STARTED IN 2004 WAS PREVENTION TRIALS, NOW WE ARE DOING TRIALS BASED ON BIOMARKERS AND I THINK EVERYONE AGREES THE EARLIEST INTERVENTION IS ONE MOST LIKELY TO HAVE AN IMPACT SO I APPLAUD YOU ALL, YOU POINTED OUT YOUR SUCCESS, I'M POINTING OUT TO ANOTHER HUGE SUCCESS AND THIS IS THE KIND OF THING THAT NEEDS TO BE DONE NOT JUST FOR AD AND PARKINSON DISEASE BUT FTD AS WELL AND PLEASED TO SAY THIS PARTNERSHIP IS GOING FORWARD WONDERFUL -- KEEP UP THE GOOD COLLABORATIONS. >> THANK YOU, JOHN. I DON'T KNOW IF YOU FOUND AFFECT LAXER YOU MIGHT SAY ANYTHING AT THIS POINT BECAUSE YOU REPRESENTATIVE ON THE FEDERAL ADVISORY COUNCIL FOR THE NATIONAL PLAN. >> THANK YOU. >> REALLY EXCITING TO BE HERE, BE PART OF THIS MEETING. I THINK THAT THE NGOs PLAY A VITAL ROLE BECAUSE IT BRINGS THE VOICE OF THE PATIENT COMMUNITY AND CAREGIVER COMMUNITY TO THE FOREFRONT NOT JUST ON CLINICAL MATTERS BUT ON RESEARCH MATTERS QUALITIES OF CARE ACCESS TO SERVICES, ET CETERA. I THINK THERE'S AN OPPORTUNITY TO WORK MORE CLOSELY WITH THE SCIENTIFIC COMMUNITY, ASSESSING THE NEEDS OF THE PATIENT BASE. I KNOW THAT ONE OF THE AREAS WE HAVEN'T HAD AN OPPORTUNITY TO REALLY DO IS TAP INTO THE PATIENT BASED LBD FOR EXAMPLE, TO ASK PIVOTAL QUESTIONS WHAT THEIR INTEREST IN THESE ARE FROM A RESEARCH PERSPECTIVE. WE WOULD LOVE THE OPPORTUNITY TO COLLABORATE WITH RESEARCHERS TO DEVELOP QUESTIONS THAT GUIDE YOU AND YOUR WORK, THAT WILL ALSO REPRESENT THE PEOPLE THAT WE REPRESENT. SO I WANT TO EXPRESS OUR ORGANIZATION MUCH LIKE OTHERS INTERESTED IN ON GOING ENGAGEMENT WITH YOU AS INCENTIVE COMMUNITY. >> ANY QUESTION? >> BRIEF COMMENT. MY NAME IS BETH WALTER, FORMER BOARD CHAIR OF AFTD SACRAMENTO, CALIFORNIA NOW BACK ON THE BOARD I WANT TO SAY A FEW WORDS ON BEAND A HALF OF THE PATIENTS THE FAMILIES AND THANK NINDS, NIA AND NOW THE NAPA FOR ALL THE REALLY GREAT WORK THAT'S GOING ON IN COLLABORATION IS JUST OUTSTANDING WHEN I STARTED IT WITH AFTD ORGANIZATION, SEVEN OR EIGHT YEARS AGO THIS WASN'T HAPPENING, THIS IS WHAT WE HAVE JUST DREAMED OF FOR A REALLY LONG TIME. THE LAST COUPLE OF YEARS HAVE BEEN UPLIFTING NOT JUST FOR THE MEDICAL COMMUNITY AND FAMILIES THAT YOU ARE HELPING ALONG WITH. >> THANK YOU FOR YOUR COMMENT. APPRECIATE IT. >> THANK YOU VERY MUCH, ELIAS (INAUDIBLE) FROM UC SAN DIEGO. I THINK THE WORK THAT WAS PRESENTED AND THE PROBLEM THAT WAS PRESENTED IN TERMS OF SYNERGISMS, BETWEEN NGOs AND NIH -- REALLY FANTASTIC AND I THINK TRYING TO ADVANCE THE WORKABLE ON THE SO CALLED VALLEY OF DEATH, IS FANTASTIC AS WELL BUT I THINK ONE AREA WHERE NGOs COULD REALLY HAVE A TREMENDOUS IMPACT ON I THINK FOR US ALSO SO INCREDIBLY IMPORTANT FUNDING YOUNG AND NEW INVESTIGATOR, I THINK FOR THE YOUNG PEOPLE IT'S EXTREMELY DIFFICULT THE PROGRAMS NIH IS PUTTING FORWARD, IT'S STILL TOUGH TO GET FUNDING. AND I FIND IN MY CASE, I WAS MY FIRST GRANT CAME FROM ALZHEIMER'S FOUNDATION THAT'S HOW I STARTED MY CAREER AND ALL PEOPLE STARTED LIKE THAT. SO I THINK HAVING SYNERGISM NOT ONLY IN ADVANCING CLINICAL TRIALS OR DRUG DISCOVERY AT HIGHER LEVEL; BUT IN TERMS OF FUND NEWING GENERATION OF SCIENTISTS PAN YOUNG PEOPLE TO START ON THAT LINE OF TRANSLATIONAL RESEARCH WILL BE SUPER IMPORTANT. I THINK IT'S SOMETHING THAT COULD BE ACCOMPLISHED MUCH BETTER GGOs AND OTHER INSTITUTES SO LEVEL OF FUNDING, I DON'T KNOW IF YOU'RE WORKING ON THAT NICHE INITIATIVE OR IS THERE A SPECIFIC MILESTONE OR RECOMMENDATION FOR THAT PURPOSE? >> THANK YOU FOR THE QUESTION. DOES ANYBODY HAVE A COMMENT ON EARLY CAREER INVESTIGATORS AND INVESTMENTS? >> T AT FTD WE DON'T HAVE TREMENDOUS MONEY TO INVEST THAT WAY BUT WE DO HAVE TWO POST-DOCTORAL FELLOWSHIPS, TWO YEARS EACH AND IT'S AN AREA WHERE IN THE LEAN YEARS WE ASK OUR MEDICAL ADVISORY COUNCIL IF WE CAN'T FUND EVERYTHING THIS YEAR WHAT COMES FIRST TIME AND TIME AGAIN. THEY AGREE WITH YOU, THEY SAY THAT THOSE FELLOWSHIPS WE GET THE BENEFIT OF A PILOT PROJECT AS WELL AS THE YOUNG INVESTIGATOR WHO HOPEFULLY WITH WE CAN HOOK THEM, THEY'LL SPEND THE REST OF THEIR CAREER RARE DISEASE, SO I SECOND YOUR POINT TREMENDOUSLY. >> THANK YOU, SUSAN. SIMON. >> NUMBER OF GRANTS FOR YOUNG INVESTIGATORS LIKE THE -- (INDISCERNIBLE) POST-DOCTORAL FELLOWSHIP GRANT WHICH BRINGS THE ISSUE OF TRAINING OVER THE NEXT GENERATION AND FEW MONEY IS GOING TOWARD THE NEXT GENERATION TO REREPLACE US. THOUGH THAT'S RELEVANT TO THE INVESTIGATOR FUNDING IT'S RELEVANT TO A INFRASTRUCTURE THAT WILL ALLOW THAT -- PEOPLE TO APPLY FOR THE GRANT. NOT APPLYING. >> THANK YOU. SIMON NEXT THEM. >> (INDISCERNIBLE) HOW HE WAS GOING TO GO INTO PUBLIC HEALTH RESEARCH UNTIL I THINK THE SOCIETY HELPED HIM GET EARLY STAGE HIS CAREER SO WE ARE AWARE OF, ONE FLIP SIDE IS WE ARE VERY COGNIZANT IN INERM OF ACADEMIA, ONE OVERINVESTS IN THE SOAPS Ph.D. STUDENTS MOST WILL THEN LEAVE BECAUSE OF THE. SYSTEM, THE SYSTEM THIS THAT IS TOUGH PYRAMID. I THINK THAT'S SOMETHING BEYOND CERTAINLY NGOs CAN FIX. I THINK WORTHY OF WHAT -- ANOTHER DISCUSSION. >> MICHAEL BOX, BRIGHT FOCUS FOUNDATION. BRIGHT FOCUS SPONSORS ALZHEIMER'S AS PART OF OUR OVERALL COMMITMENT TO ADVANCING NEWER PEOPLE IN THE FIELD. AND WE WORK IN PARTNERSHIP WITH NUMBER OF ORGANIZATIONS HERE. >> THANK YOU VERY MUCH. YOU'RE RIGHT AND YOU HAVE BEEN PART OF ACCORDANCES OF THE ALZHEIMER'S ASSOCIATION OR MEDICAL SCIENTIFIC ADVISORY COUNCIL HAS MADE A SIGNIFICANT DECISION THAT OUR FUNDING OF INVESTIGATOR INITIATED PROJECTS WOULD BE SHIFTING. AWAY FROM MORE ESTABLISHED INVESTIGATORS TO EXPAND THE EARLY CAREER ONE TO TEN -- UNDER TEN YEAR TIME FRAME WE PREVIOUSLY HAD TO LESS THAN 15 P YOU FOCUS MOST OF THAT FUNDING TOWARDS THAT EARLY CAREER BRACKET TO SUPPORT THIS. WE COGNIZANT OF CONVERSATIONS WE HAD WITH PROGRAM OFFICER AT NATIONAL INSTITUTE ON AGE, GREAT PARTNERSHIP WITH PAUL OF US. AS NGOs THE NIA NINDS WITH THE KNOWLEDGE THAT MORE FUNNING FOR GREAT WORK WITH SUCCESS IN PUBLIC POLICY ADVOCACY MORE DOLLARS ALZHEIMER'S AND RELATED DEMENTIA MEANS THAT WE NEED TO SUPPORT NEW GENERATIONS COMING TAKING ADVANTAGE OF THOSE IDEAS AND GROWING IN THE FIELD. SOMETHING ELSE WE HAVE SEEN AND WE HAVE ALL EXPERIENCED THIS AS WE SURVEY THE FIELD, THERE IS A DERTH OF RESEARCHERS OF TRAINED RESEARCHERS CLINICAL RESEARCHERS GERIATRICIANS THAT SPAN A 20 YEAR TIME FRAME WHERE WE HAD WE WERE NOT AS SUCCESSFUL IN FUNDING AND OBTAINING FUNDING FOR ALZHEIMER'S AND RELATED DEMENTIA. THAT'S CHANGING NOW. HOWEVER W WHAT THAT MEANS IS WE NEED TO BRING MORE PEOPLE IN TO THE FIELD AND WE NEED TO BE ABLE TO SUPPORT THEM SO I THINK THAT IS DEFINITELY ONE THING WE'RE COGNIZANT OF AT THIS TABLE BUT THANK YOU VERY MUCH FOR THAT STATEMENT. WE HOPE TO BE ABLE TO DO MORE. ANOTHER QUESTION. >> TOM CAR MICHAEL, UCLA, NOT SO MUCH A GUIDELINE RELATED COMMENT BUT A SCENE FOR FUTURE CONSIDERATIONS SINCE MANY FOUNDATIONS MOVE BETWEEN INDUSTRY, THE THE DONOR COMMUNITY AND ACADEMIA, I NOTICE THE MENTION OF VENTURE PHILANTHROPY, THIS IS A PROBLEM THAT'S PARTICULARITY PUBLIC UNIVERSITIES IN DONOR ROUTE REACH, HOW WE HANDLE DONOR GIFT THAT COMES WITH IP INTERESTS AND PAY OUT. PUBLIC UNIVERSITY VERSUS A CERTAIN INABILITY TO DEAL WITH THAT IN A FLEXIBLE WAY AND IT WILL BE USEFUL AS YOU GUYS MOVE FORWARD AS YOU MOVE FORWARD TO UNDERSTAND WAYS IN WHICH SOLUTIONS ARE COMMUNICATED BROADLY. YOU SEE A LOT OUT OF SILICON VALLEY DONOR MAKING A NICE DONATION BUT EXPECT 20% RETURN ON IP. AND WHERE DOES THAT COME FROM IN THE PROCESS? HOW DOES PUBLIC UNIVERSITY DEAL WITH THAT? THESE ARE THORNY ISSUES MOST SOLVE INDIVIDUALLY AD HOC AS WE MOVE FORWARD, IT MIGHT BE A NICE OPPORTUNITY TO SYSTEM MATIZE OR PASS ON EXPERIENCES FROM OTHER LOCATIONS. >> HOWARD. >> YOU'RE RIGHT IN IDENTIFYING THE ISSUE, WE HAVE MADE OVER 400 CONTRACTS WITH DIFFERENT UNIVERSITIES AROUND THE WORLD. INCLUDING UNIVERSITY OF CALIFORNIA. WE AS FOUNDATION O DON'T TAKE IP, WE DON'T SEEK TO TAKE IT BUT WE SEEK TO RETURN ON EVERY GRANT THAT WE MAKE. PANNED I THINK THE SPIRIT OF THAT IS THAT OUR DOLLARS ARE AS GOOD AS ANYBODY ELSES, EVERY DOLLAR WE GET IN RETURN WHETHER PUBLIC OR PRIVATE GOES TO FUND RESEARCH. SO EVERY CONCEPT THAT WE HAVE -- THIS HAS ALSO BEEN RAISED AS A GENERAL ISSUE AT THE HEALTH RESEARCH ALLIANCE, CONSORTIUM OF 65 NON-PROFITS A AT THE LAST MEETING, WE HA HAD THE DISCUSSION ABOUT THIS, I THINK THERE'S GOING TO BE MORE AWARENESS OF THIS ISSUE ACROSS TECHNOLOGY TRANSFER OFFICES AROUND THE COUNTRY, TECHNOLOGY TRANSFER OFFICES, RISING AND KNOWLEDGE EXPERIENCE AND CAPABILITIES AND FOUNDATIONS ARE ALSO AT THE SAME TIME REALIZEING A THAT WE PLAY A VERY IMPORTANT ROLE IN FUNDING RESEARCH AND PARTICULARLY IN OUR SPACE AND DRUG DISCOVERY AND DEVELOPMENT. SO I THINK IT'S CLEARLY A SOLUBLE ISSUE, WE JUST EVERY TIME WE NEGOTIATE WE NEGOTIATE IN GOOD SPIRIT WITH GOOD WILL. AND WE GET SOMETHING? RETURN, I DON'T THINK IT PIECE AN UNFAIR PROBLEM BECAUSE FROM THERE'S TWO SIDES AND UNSOLVABLE. >> WE HAVE TIME FOR TWO SHORT QUESTIONS. FOR THE FOLKS STANDING UP. >> MY MY NAME IS SANDRA CO LARKS THET YOUNG INVESTIGATOR ASSISTANT PROFESSOR CRYPT SCRIPTURES SEARCH IN CALIFORNIA MY LAB DIRECTLY BENEFITTED FROM THE FUNDING FROM NGO SO I WANT TO TO THANK YOUR EFFORTS FOR THAT. TRANSFORMATIVE IN ANIMY EARLY STAGE CAREER. THE QUESTION I HAVE TO ECHO THOUGHTS A ABOUT YOUNG INVESTIGATOR FUNDING AND SUPPORT, I LIKE WHAT I HEARD IN SYNERGY BETWEEN NGOs BETWEEN AMONG YOURSELVES AND ALSO WITHIN NIH AND I GUESS THE QUESTION I HAVE IS THERE AN IDEA TO CREATE A PORTAL, ONLINE LIKEWISE, WHERE THERE COULD BE A UNIFYING OF INFORMATION OF THESE PARTNERSHIPS BETWEEN NGO AND/OR WITHIN NIH WHERE YOUNG INVESTIGATORS AND OTHER PEOPLE OTHER RESEARCHERS BENEFIT FROM GOING TOWARD AND SEEING SYNERGIES THAT ARE HAPPENING BETWEEN NGOs AND WITHIN NIH. >> THANK YOU. SO THERE IS A -- TODD DO YOU WANT TO THANS IN >> I DIDN'T HAVE AN ANSWER TO THAT QUESTION. I THINK IT'S A GREAT IDEA BUT I WANT TO MAKE A COMMENT BACK TO AN EXAMPLE I HAD INTRODUCED IN TERMS OF YOUNG INVESTIGATORS. BECAUSE I THINK THERE IS TWO ASPECTS IN TERMS OF THE FUNDING. OBVIOUSLY THE DIRECT FUNDING PROGRAMS BUT THERE IS A REAL VALUE WORK DONE NON-PROFITS AND INITIATIVES THROUGH NIH MAKING SAMPLES AVAILABLE AND RESEARCH TOOLS AVAILABLE BECAUSE IT ACTUALLY MAKES IT'SIER FOR YOU TO DEVELOP PRELIMINARY DATA OR TO DO A GRANT. WE NEED TO PUSH NUTTER TERMS OF ANIMAL A MODELS AND RESOURCES SO ALL INVESTIGATORS INCLUDING YOUNG INVESTIGATORS GET ACCESS TO THEM TO ACTUALLY DEVELOP A RESEARCH PROGRAM. AND I THINK THAT'S A RATE LIMITING STEP AS EQUAL TO BEING ABLE TO GET THE GRANTS. SO I JUST THINK IT'S IMPORTANT TO REALLY CONTINUE TO EMPHASIZE THAT WITH ALL THE NEW INITIATIVES WE DO. >> THERE IS A RESEARCH -- AN ARTICLE THAT'S PUBLISHED AN UPDATED I BELIEVE EVERY TWO OR THREE YEARS, THE FIRST IS HEATHER SCHNEIDER ALZHEIMER'S AND DEMENTIA, GOES THROUGH ABOUT 50 PARTNERSHIPS THAT EXIST. SO YOU MIGHT TAKE A LOOK AT THAT AS WELL. >> SHORT QUESTION, MICHAEL I NEED TO CLOSE THE CONFERENCE. >> MY NAME IS MICHAEL (INAUDIBLE) A PATIENT ADS VOW KATE. I HAVE A COMMENT HERE. I THINK IT'S GREAT THAT YOU FOLKS ARE STARTING COCOLLABORATE MORE WITH EACH OTHER BUT I THINK THERE NEEDS TO BE MORE -- SO MANY NGOs I WOULD LIKE TO SEE MORE WORKING MORE TOGETHER SO YOU HAVE A BIGGER VOICE FOR ADVOCACY AS DEMENTIA RATHER THAN SPECIFIC INDIVIDUAL FRONTOTEMPORAL LOBEOR VASCULAR DEMENTIA, ALL FALL UNDER ONE THING AS DEMENTIA. >> GREAT POINT TO END ON BECAUSE ONE OF THE THINGS WE CAN TAKE AWAY FROM THIS PARTICULAR SUMMIT ADRD SUMMIT THIS TIME IS TO SEE ADVANCEMENT OF ALL CONVERSATIONS THAT HAVE HAPPENED AND THE EXAMPLE OF A PARTNERSHIP YOU HAVE HERE, THAT ALSO ALLOW US TO GET TO KNOW EACH OTHER BETTER AND TO GET TO KNOW WHAT WE ARE EACH DOING IN DIFFERENT SPACES TO FIND THOSE OPPORTUNITIES AND EXPAND ON THEM. THANK YOU VERY MUCH. THANK YOU ALL, THANK YOU TO THE PANELISTS. [APPLAUSE] >> TO WARM US UP FOR OUR LUNCH BREAK. WE'RE NOW GOING TO GO INTO THE SPECIAL JOINT SESSION ON NOMENCLATURE. AND THIS THIS SESSION WAS INSPIRED BY THE NON-GOVERNMENTAL ORGANIZATIONS COMMITTEE AS WELL AS WITH THE MULTI-ETIOLOGY COMPLY. MANY OTHER VERSUS TAKEN A STRONG INTEREST SO I WOULD LIKE TO START PROBABLY WITH OUR PRIMARY INSTIGATOR, ANGELA TAYLOR, WOULD YOU PLEASE COME TO THE PODIUM. [APPLAUSE] >> HI, EVERYBODY, HONOR TO BE HERE TO BE PART OF THIS EVENT. I WAS HERE THREE YEARS AGO. REALLY EXCITING PATIENT ADVOCATE TO WATCH THE PROCESS PARTICIPATE IN THE PROCESS AND TO WEIGH IN AS THE PROCESS UNFOLDS OVER THE YEARS. MY GOAL TODAY IS TO OPEN THE NATIONAL DIALOGUE ON BEAND A HALF OF PATIENT ADVOCACY ORGANIZATIONS THAT ARE REPRESENTED UP HERE, WE FEEL IT'S TIME TO HAVE A DIALOGUE ABOUT THE TERMS WE USE WHEN WE TALK ABOUT DEMENTIA. THAT REQUIRES WE IDENTIFY ADVANCE THE NEEDS OF THE KEY AUDIENCES AND THE STAKEHOLDER GROUPS. WHEN WE TALK DEMENTIA IN GENERAL REGARDLESS OF WHAT THE UNDERLYING ETIOLOGY IS, LOOKING AT THE SPECIFIC CLINICAL SYNDROMES THAT ARE REPRESENTED TODAY AND IN IN THE OTHER SUMMIT, ALSO THE ACTUAL UNDERLYING ETIOLOGY WHETHER THOSE THERE'S ONE OR MANY. WORDS CLEARLY MATTER. I WAS LOOKING FOR A QUOTE THAT WOULD REALLY MAKE THE POINT THEY DIDN'T FEEL LIKE I WOULD BE ARTICULATE ENOUGH TO DO ON OUR OWN SO JUST GOING TO READ THIS. SOME WORDS AND METAPHORS ARE USED LIBERALLY AND PAINT A BIASED PICTURE. WHILE OTHERS ARE AVOIDED AND CONSIDERED DIMEANING, DEPERSONALIZING AND INSULTING. STANDARD MEDICAL TERMS ARE SOMETIMES USED WITH GREAT CAUTION. DUE TO AWARENESS OF POSSIBLE IMPACT ON PEOPLE'S LIVES AND WELL BEING. WORDS CLEARLY MATTER. THEY DEDO SCRIBE COMMUNICATE AND REINFORCE CURRENT PERCEPTIONS OF DEMENTIA. WITH AWARENESS, WE CAN TRY TO USE POSITIVELY TO CHALLENGE PORTRAYALS OF DEMENTIA AND PROMOTE MORE POSITIVE IMAGE OF DEMENTIA AND PEOPLE WITH DEMENTIA. I THINK CHANGING A LEXICON ISN'T EASY BUT PIT'S EXTREMELY IMPORTANT AND IT'S NECESSARY TO THAT HE TACKLE NO MATTER HOW HARD IT'S GOING TO BE, WE'RE NOT THE FIRST TO PROPOSE CHANGE. AS I DID RESEARCH FOR TODAY'S PRESENTATION I FOUND A NUMBER OF ORGANIZATIONINGS ACROSS THE WORLD WHO ARE REALLY PROACTIVELY TRYING TO TAKE A STANCE TO REALLY MAKE THE WORLD A LITTLE FRIENDLIER PLACE FOR FAMILIES DEALING WITH DEMENTIA. IN THE TUCK THERE'S PROGRAM CALLED THE DEMENTIA ENGAGEMENT AND EMPOWERMENT PROGRAM. AND THIS IS REALLY BEING DRIVEN BY PEOPLE LIVING WITH DEMENTIA THEMSELVES TO RAISE PUBLIC AWARENESS. IN AUSTRALIA, IN AUSTRALIA THEY DEVELOPED A DEMENTIA LANGUAGE GUIDELINE, IDENTIFYING WORDS THAT ARE REALLY STIGMATIZING AND. CREATE EVEN IN A SENSE OF EVE MOTIONAL BURDEN ON THE FAMILIES LIVING WITH THE DEMENTIA. CREATING MORE INCLUSIVE LANGUAGE RECOMMENDATIONS AND THINGS THAT ARE NON-STIGMATIZING. AND IN THE US-BASED OFF EFFORTS IN MINNESOTA, DEMENTIA FRIENDLY AMERICA. THESE COMMUNITIES ARE BEING BROUGHT INTO MORE AWARENESS ABOUT DEMENTIA AND THE NEED OF FAMILIES LIVING WITH IT, PROVIDING SAFE AND RESPECTFUL OPTIONS FOR THEM WHEN THEY WORK WITH SERVICE PROVIDERS, RETAILERS, AND ALL SORTS OF DIFFERENT SECTORS IN THEIR COMMUNITY JUST TO FOSTER A BETTER QUALITY OF LIFE. WHEN WE LOOK AT WHAT'S GOING ON HERE IN THE U.S., YOU WILL SEE THERE'S VARIOUS TERMS USED WHEN WE TALK ALZHEIMER'S OR DEMENTIA RELATED DEMENTIA, ACROSS FEDERAL AGENCIES. SO IN THE NATIONAL PLAN TO ADDRESS ALZHEIMER'S DISEASE AS YOU ALL REALLY WELL KNOW, IT IS INCLUSIVE OF MORE THAN JUST ALZHEIMER'S DISEASE. BUT THE PLAN LARGELY REFERS TO ALZHEIMER'S DISEASE, AND I WILL TELL YOU IN MY DISCUSSIONS WITH REPRESENTATIVES FROM OTHER DISEASE ORGANIZATIONS, ESPECIALLY OUTSIDE DEMENTIA SPHERE AS A PRIMARY SYMPTOM, THERE WERE ORGANIZATIONS THAT DEAL WITH DEMENTIA NOT IN TUNE WITH THE FACT THAT THIS PLAN WAS RELEVANT TO THEM AS WELL. SO WE HAVE TO LOOK AT THIS HERE IN THE U.S. SO THAT WE HAVE A GREATER ENGAGEMENT OF ALL DIFFERENT STAKEHOLDER GROUPS. IN THE NATIONAL PLAN, WE USE ADRD AS AN ACRONYM BUT SOMETIMES THEY'RE REFERRING TO THAT AS ALL DIMENSIONS IN GENERAL, ALZHEIMER'S DISEASE AND RELATED DEMENTIAS BUT OTHER TIMES IS SPECIALLY FOR THIS MEETING, IS ALZHEIMER'S DISEASE DASH RELATED DEMENTIA, WE CAN DO A BETTER JOB. THE DEPARTMENT OF HEALTH AND HUMAN SERVICES AS PART OF THE NATIONAL ALZHEIMER'S PLAN HAS PUBLIC AWARENESS CAMPAIGN. BUT IF YOU GO TO THE WITH WEBSITE LISTED HERE, IT FOCUSES ONLY ON ALZHEIMER'S DISEASE, THERE'S RELATED THE DEMENTIAS THAT NEED MORE VISIBILITY TO THE GENERAL PUBLIC. EVEN THE CENTERS FOR DISEASE CONTROL, THEY HAVE THEIR OWN LANGUAGE. IN THEIR HEALTHY PEOPLE 2020 INITIATIVE, THEY USE THE TERM DEMENTIA INCLUDING ALZHEIMER'S DISEASE AND OTHER DEMENTIAS. I KNOW THAT WE CAN DO A BETTER JOB TO COME UP WITH CONSISTENT LANGUAGE SO THIS SLIDE IS AN EXAMPLE TO ME AS A LAY PERSON PART OF THE PROBLEM. WE HAVE SO MANUFACTURE DIFFERENT TERMS THAT OVERLAP, SOME OF THESE ARE VERY IMPORTANT FOR THE STAKEHOLDER GROUPS THAT THEY WERE DEVELOPED BY AND WHO THEY ARE USED BY. BUT A LOT OF THIS OVERLAPS EVEN WITHIN THIS MEETING YOU HERE A LOT OF THE SAME DISEASE BEING REFERRED TO SLIGHTLY DIFFERENT. LEWY BODY DISEASE, LEWY BODY DEMENTIA, DEMENTIA WITH LEWY BODY, MY FAVORITE IS THE OVERLAP LEWY BODY DISEASE, LEWY BODY DISORDERS AND LEWY BODY DEMENTIAS ALL MEANING THREE DIFFERENT THINGS. IN EVERY DISEASE YOU WILL SEE THESE VARIATIONSN'T ALZHEIMER'S DISEASE OR THE NEW DIAGNOSTIC CRITERIA THAT SAYS DEMENTIA DUE TO ALZHEIMER'S DISEASE. FRONTOTEMPORAL DEMENTIA OR DEGENERATION, THERE'S REASONS FOR THESE EVOLUTIONS BUT THEY'RE CONFUSING ESPECIALLY WHEN YOU TALK ABOUT THE LAY PUBLIC AND P PEEL WHOA ARE DEALING WITH THIS AN HA THEY NEED TO BE ABLE TO ARTICULATE BACK AND FORTH WITH, THEIR DOCTORS THEIR CAROLINA PROVIDERS, ET CETERA, AS AN NGO COMMITTEE WE IDENTIFIEDED THREE STAKEHOLDER GROUPS. THE PATIENT AND CARE COMMUNITY WHICH INCLUDES OBVIOUSLY ALL PATIENTS CAREGIVERS BUT IS INCLUDES THE HEALTH DISPARITIES COMMUNITIES, ALL THE PROVIDERS WHO OFFER SERVICES TO THOSE COMMUNITIES, OUTSIDE OF DIRECT CLINICAL CARE, AND THE PATIENT ADVOCACY ORGANIZATION AS WELL. THE HEALTHCARE SYSTEM INCLUDES BOTH PROVIDERS AND THE PAYERS. WHO HAVE THEIR OWN UNIQUE NEEDS. THE SCIENTIFIC REGULATORY COMMUNITY HAVE HIGHLY SPECIFIC NEEDS. WE WANT TO MAKE SURE WE UNDERSTAND THE UNIQUE NEEDS OF EACH STAKE HOLD OTHER GROUP AND THAT WE STRIVE TO DEVELOP A LEXICON THAT MEETS THEIR NEEDS BOTH IN DETAIL AND THEN ALSO AT BROAD LEVEL SPEAK AGO CROSS STAKEHOLDER GROUPS TOUCHTONE O OTHER. SO BREAKING IT DOWN LATE EXIT BY STAKEHOLDER GROUP, SO THAT -- A LITTLE BIT BY STAKEHOLDER GROUP TO SEE HOW NOMENCLATURE EVOLVE, THE PROGRESS WE'RE MAKING AND HAVE MEANINGFUL OUTCOMES. SO FROM THE PATIENT CAREGIVER PERSPECTIVE EARLY DIFFERENTIAL DIAGNOSIS WE ALL UNDERSTAND HOW IMPORTANT THAT IS. BUT CAN KNOW MEN LAY CLAYTURE BE LEVERAGED TO IM-- NOMENCLATURE IMPROVE SYMPTOM REPORTING AND AWARENESS ABOUT THE DIFFERENT TYPES OF DEMENTIA. WE HEARD ABOUT PRIMARY CARE PHYSICIAN LEVEL OF ABILITY TO DIAGNOSE DEMENTIA BUT IT'S NOT JUST THEIR ABILITY TO DIAGNOSE, THE FAMILIARITY WITH THESE DISEASES IN GENERAL. WE WANT TO TALK ABOUT IMPROVING QUALITY OF LIFE AND SLOW DISEASE PROGRESSION LEVERAGING BETTER TERMS GOING INTO THE PROCESS OF INCREASED ACCESS TO SAVE AND A EFFECTIVE THERAPIES. OR RECRUITING PATIENTS TO PARTICIPATE IN THE CLINICAL TRIALS THAT WILL RESULT IN THOSE SAFER THERAPIES. IMPROVING ACCESS TO CARE AND SERVICES. WE NEED AS A SOCIETY TO BE CLEAR WHEN WE TALK ABOUT SERVICES FOR FAMILIES AFFECTED BY DEMENTIA, THAT THOSE SERVICES ARE RELEVANT TO ALL OF US WHO ARE DEALING WITH ANY FORM OF DEMENTIA. AND THAT IS THE A CHALLENGE. I WILL SHARE MORE ABOUT THAT LATER. THE APPRECIATION OF PERSON HOOD REGARDLESS L OF LEVEL OF COGNITIVE IMPAIRMENT. THERE'S A TREMENDOUS STIGMA AS YOU KNOW ABOUT DEMENTIA. BUT HOW CAN WE USE THE LEXICON TO IMPROVE THAT? FROM PA HEALTH DISPARITIES COMMUNITY THERE'S A LOT THAT I DON'T KNOW AND I KNOW THERE'S A LOT WE AS AS A COMMUNITY OF DEMENTIA STAKEHOLDERS DON'T KNOW AND WANT TO KNOW BETTER. SO ALL OF THESE NEEDS ARE QUESTION MARKS, THEY'RE POSSIBLE NEEDS THAT WE HAVE TO EXPAND -- INVEST IN FURTHER TO UNDERSTAND HOW LANGUAGE EFFECTS THEM. CAN WE INCREASE THE PROPORTION OF PEOPLE WHO RECEIVE DEMENTIA DIAGNOSIS BY USING DIFFERENT TERMINOLOGY. CAN WE PROVIDE MORE CULTURALLY SENSITIVE EDUCATION AN SUPPORT BY TAILORING OUR DEMENTIA EDUCATION AND PROGRAMS FOR THE HEALTH DISPARITIES COMMUNITIES. AND FROM A PREVENTION STRATEGY STANDPOINT CAN WE INCREASE THE TRUST WITH THE SCIENTIFIC COMMUNITY BY UNDERSTANDING THEIR NEEDS, APPROACHING THEM WITH SENSITIVITY, AND BRINGING MORE INTO RESEARCH STUDIES. FROM A SIGNATURE LA PERSPECTIVE, WE HAVE SEEN SO MANY DISORDERS COME BEFORE US THAT ARE NO LONGER DISCUSSED IN WHISPERS OR DISCUSSED WITH EMBARRASSMENT AND HERE ARE JUST A FEW. CERTAINLY I WAS YOUNG WHEN WE WERE -- WHEN THE AWARENESS OF HIV AIDS CAME UP, THAT REALLY WAS IMPACTFUL TO ME PERSONALLY AND NOW OVER TIME AS THE DECADES EVOLVED, I DON'T HAVE NEARLY THE SAME SENSE OF STIGMA THAT SOCIETY AND INDIVIDUALS REALLY ASSOCIATE WITH THIS -- AS A DISEASE. ERECTILE DYSFUNCTION, HALLELUIAH VIAGRA YOU HAVE DONE A WONDERFUL JOB MAKING A B PROBLEM THAT AFFECTS MANY PEOPLE ACCESSIBLE, WE CAN TALK TO OUR DOCTORS, WE CAN JOKE ABOUT IT. CANCER IS NO LONGER WHISPERED. AND MENTAL HEALTH DISORDERS, SPEAKING AS A PARENT WITH A CHILD WHO HAS ONE, THESE ARE NOW PART OF THE EVERY DAY CONVERSATION AMONG TEENS AND ADOLESCENTS. THERE'S NOT THE SAME STIGMA ASSOCIATED WITH IT. WHY CAN'T WE DO MORE WITH THAT FROM A DEMENTIA PERSPECTIVE? BUT I THEY REQUIRES TWO THINGS. THAT REQUIRES WE PUT CONCERTED PUBLIC AWARENESS EFFORT TOGETHER WHERE WE ARE USING SIMILAR LANGUAGE AND WE ARTICULATE THAT THIS IS A MEDICAL CONDITION. I THINK THERE'S A LOT OF MISINFORMATION, A LOT OF ASSUMPTION WHAT IT IS, WHAT IT ISN'T AND WHAT CAN BE DONE ABOUT IT. WE ALSO NEED THE PATIENT COMMUNITIES STAND OUT, STAND UP, SPEAK ABOUT LIVING WITH DEMENTIA. AND I KNOW THAT THAT'S -- THERE ARE A LOT OF PEOPLE MICHAEL, THANK YOU FOR BEING ONE OF THOSE PEOPLE STANDING UP AND SAYING I'M STILL HERE, I MAY NOT FUNCTION THE SAME. BUT I'M STILL HERE AND STILL MATTER AND I WANT YOU TO LISTEN. WHEN WE TALK ABOUT THE LANGUAGE WE USE FROM PUBLIC STANDPOINT WE HAVE MADE TREMENDOUS STRIDES BECAUSE OF THE WORK OF THE PATIENT ADVOCACY ORGANIZATIONS THAT ARE HERE. WE HAVE SEEN AMAZING PUBLIC AWARENESS GROW ON ALZHEIMER'S DISEASE, I WOULD LIKE TO THANK ALZHEIMER'S ASSOCIATION FOR THE WORK THEY HAVE DONE AND BEING A LEADER IN TAKING THIS TO THE NATIONAL PLATFORM FROM A LEGISLATIVE STANDPOINT. THIS IS BRINGING GREATER FEDERAL RESOURCES, AS - AGAIN UNDER THE BANNER OF ALZHEIMER'S DISEASE, THAT ARE BENEFITING ALL OF US TOUCHED BY RELATED DEMENTIA. BUT IT COMES WITH WITH A DOWN SIDE. IF YOU ASK THE GENERAL PUBLIC THEY WON'T P ABLE TO TELL YOU WHAT THE DIFFERENCE IS BETWEEN ALZHEIMER'S AND DEMENTIA. THERE'S LOW PUBLIC A AWARENESS THAT THERE ARE OTHER FORMS OF DEMENTIA AND FROM MY PERSONAL STANDPOINT I LIKE TO THINK MYSELF AS A RELATIVELY SPELL GENT PERSON BUT WHEN MY BAND DEVELOPED LEWY BODY DEMENTIA, I DIDN'T KNOW THOSE SERVICES THAT WERE OUT THERE FOR FAMILIES DEALING WITH ALZHEIMER'S DISEASE, HAD ANY RELEVANCE TO ME. I DON'T THINK I'M ALONE ANDS DON'T THINK IT'S ACCEPTABLE TO USE ONE TERM WHEN YES TALKING A BROADER DISEASE TYPE. SO FROM THE HEALTHCARE SYSTEM, I'M GOING TO TALK HEALTHCARE SYSTEM BRIEFLY AND ALSO ABOUT THE SCIENTIFIC REGULATORY STANDPOINT BECAUSE WE VEAL ANOTHER SPEAKER WHO DOES OOH BETTER JOB. WE NEED SPECIFIC DIAGNOSTIC CRITERIA FOR THE PRODROMAL AND CLINICALLY RELEVANT SYNDROME, MILESTONES TO KNOW WHEN TO REFER PATIENTS OUT BUT HAVE THOSE BEEN DEFINED, ARE WE COMMUNICATE TO THEM, WHEN THIS IS -- THE FAMILY IS HERE, YOU NEED TO DO THIS SO THAT THEY ARE NOT STRUGGLING WITH FIND RESOURCES TO STAY IN THE HOME LONGER. CERTAINLY LANGUAGE THAT CAN BE COMBINE COMMUNICATED ACROSS CARE SETTINGS. HAVE HAVING SAID THAT WE HAVE TO KEEP THINGS IN MIND WHAT THE LANGUAGE COULD OR SHOULD BE. WE NEED TO MAKE SURE WE CAN EFFECTIVELY INFORM PATIENT AND CAREGIVERS WHAT THEY'RE CLINICAL SYNDROME IS, WHETHER WE KNOW IT OR NOT BASED ON BIOMARKERS. SO WHAT IS COGNITIVE STATUS. WHAT IS THE CLINICAL SYNDROME THEY PRESENT WITH, AND WHAT ARE THE POSSIBLE UNDERLYING ETIOLOGIES AT PLAY. THERE'S WORK THAT WENT INTO SDS -- DSM V AND WHAT WE CAN DO TO IMPROVE THE LANGUAGE WE USE NOW. CERTAINLY ON SCIENTIFIC REGULATORY SIDE, THAT WILL CONTINUE DIFFERENTIATION BETWEEN UNDERLYING ETIOLOGIES AND CLINICAL SYNDROME. LOOKING AT THE DIFFERENCE BETWEEN THE DISEASE STAGE, PRE-CLINICAL PRODROMAL PRE-SYMPTOMATIC ARE WE USING THOSE TERMS TO MEAN THE STATEMENT THING? I SAY THAT BY SAYING DOES PRODROMAL MEAN AT RISK OR LIKELY TO DEVELOP? FROM WE NEED EFFICIENT REGULATORY PATHWAY, HOW DO THE TERMS WE WITH USE ALL THE WAY TO BROADSER SYNDROME AFFECT THAT PATHWAY. SO WE NEED TO BE MINDFUL OF THE EVOLUTION THAT WE HAVE SEEN IN DIFFERENT DIAGNOSTICS CRITERIA. THERE'S WORK AND THOUGHT THAT WENT INTO THAT. WE CAN'T DERAIL THAT WORK COME TO PASS, WE RECOGNIZE THE NEEDS FOR CLINICAL PATHOLOGICAL CORRELATES ARE GOING HELP UNDERSTAND HOW TO DIAGNOSE THE DISORDERS EARLY DIFFERENT SYNDROMES EVOLVE AND CERTAINLY THAT POLITICAL MOMENTUM, WE HAVE SEEN ALL THE WORK THAT HAS BEEN DONE IN RECENT YEARS TO BRING US TO THIS MEETING AND THE ONE IN 2015, 2014, 2013 AND 2012. WHICH CAN'T DERAIL THAT. IT MAY BE AN EVOLUTIONARY PROCESS TO MAKE SMALL CHANGES BUT IT DOESN'T MEAN WE DON'T MAKE ANY CHANGES SO WE NEED TO KEEP THAT IN MIND. HOW WE CONTINUE TO BUILD MOMENTUM GOING FORWARD SO WE HAVE GREATER FUNDING, GREATER ATTENTION OF THE DIFFERENT FEDERAL AGENCIES WORKING TOGETHER. AND AT THE SAME TIME, KEEP AN EYE ON GLOBAL EFFORTS. MY PRESENTATION HAS NO ANSWERS SO I APOLOGIZE IF YOU HOPE THERE WILL BE SOME. ICE A QUESTION WHAT SHOULD WE BE ASKING. IS IT TIME TO CONSIDER A BULL'S EYE FORMAT WHERE AT THE BROADEST LEVEL WE ARE TALKING ABOUT UMBRELLA TERM FOR DEMENTIA AND COGNITIVE IMPAIRMENT. ARE WE TALKING CLINICAL SYNDROME AND AS WE HAVE BIOMARKERS THAT ARE SPECIFIC ARE WE TALKING ABOUT THE ETIOLOGY ITSELF OR THE DISEASE MECHANISM. CAN WE USE A MODEL? I DON'T KNOW. WE SHOULD ASK OURSELVES AND HAVE CHALLENGING CONVERSATION? ABSOLUTELY. SO THE RECOMMENDATION FROM NON-GOVERNMENT ORGANIZATION COMMITTEE WE ORGANIZE A WORKING GROUP OF DEMENTIA STAKEHOLDERRERS INCLUDING FOUNDING PARTNERSHIPS WITH DISPARITIES COMMUNITIES TO REVIEW NOMENCLATURE IN PUBLIC AWARENESS, CLINICAL CARE AND RESEARCH AND PROPOSE STRATEGIES TO HELP ADVANCE EARLY DIAGNOSIS AND THE UNDERSTANDING OF DEMENTIA AND ITS UNDERLYING CAUSES. THANK YOU VERY MUCH. [APPLAUSE] >> I WANT TO THANK ANGELA AND ALSO ROD AND ORGANIZERS FOR ALLOWING US TO ARE HAVE THIS DISCUSSION. SO I WILL TAKE A SLIGHTLY DIFFERENT PERSPECTIVE FROM AFFECT LAXER BUT SEE THAT IT'S BOTH COMPLIMENTARY AND POINTS OUT THE PROBLEM. MY PERSPECTIVE FROM SCIENTIFIC THERAPEUTIC POINT OF VIEW IS DIFFERENT. THERE WERE DIFFERENT ISSUES THAT COME UP AND THERE WERE IN LIES THE PROBLEM WITH ONE OF THE PROBLEMS WITH NOMENCLATURE. SO CONSIDER THESE TWO STATEMENTS HOW MANY TIMES YOU HAVE SEEN SOMETHING LIKE THIS. A POPULATION BASED STUDY SHOWS ASSOCIATION BETWEEN HYPERTENSION AND ALZHEIMER'S DISEASE. WHAT DO YOU THINK? OR A PHASE 3 CLINICAL TRIAL. I THROUGH IN VITAMIN B E. SLOWS THE PRODEPRESSION OF ALZHEIMER'S DISEASE. IS THAT WHAT THEY MEANT? OF COURSE NOT. THEY WERE REFERRING TO A CLINICALLY DIAGNOSED CONDITION THAT WE SPENT THE MORNING TALKING ABOUT, HAS MULTIPLE ETIOLOGIES, AND ONE OF MY THEMES HERE ANGELA'S WAS AS WELL IS WORDS MATTER AND WORTH TAKE ON A LIFE OF THEIR OWN. A I ASSERT THESE KIND OF EXAMPLES MAKE US THINK THE WRONG WAY. WE THINK ABOUT THERAPEUTIC AS TREATMENT OF ALZHEIMER'S DISEASE WHEN WE SHOULD BE THINKING ABILITY MULTIPLE ETIOLOGIES IN ANY WAY, YOU GET THE POINT. THE TERMINOLOGY IN THIS DISEASE, THIS SET OF CONDITIONS HAS GROWN UP IN INDIRECT UNDIRECTED MANNER OVER 50 OR 60 YEARS AND YOU ALL REMEMBER REMOVES PAST ORGANIC BRAIN SYNDROME AND THINGS LIKE THAT, ALSO BACK TOP THE IDEA TO SIMPLIFY THINGS LIEUTHROUGH REDUCTIONIST THINKING AND CLINICAL PATHOLOGIC ENTITIES SOMETIMES WORK, SOMETIMES DOESN'T BUT SOMETIME WORDS ARE WELL BEHAVED, SOMETIMES NASTY AND ILL BEHAVED. THE IDEA OF SYNDROMIC MULTI-DOMAIN IS ALZHEIMER'S. SO THAT'S THE -- SOME PEOPLE'S MINDS IS CLINICAL PATHOLOGIC ENTITY BUT WE SPENT THE WHOLE MORNING TALKING ABOUT THIS AND THIS. THE FACT THAT AT LEAST IN THE ALZHEIMER'S SPACE, THERE IS MULTI-POLICETY OF RELATIONSHIPS MAKES THAT TERM -- TERMINOLOGY A PROBLEM. THERE'S THIS ISSUE. IMAGINE THIS. CONGRESSMAN JONES I'M HERE FUNDING FOR MAJOR NEURAL COGNITIVE DISORDER, I WOULD ASSERT THAT NEOJISM, WITH RESPECT TO PEOPLE WHO ARE ON THE COMMITTEE INCLUDING MY BEST FRIEND RON, IT GOT US AWAY FROM THINKING ABOUT THE BRAND IDENTITY OF DEMENTIA THAT ANGELA HAMMERED ON CORRECTLY AND ALZHEIMER'S DISEASE, BUT ESPECIALLY DEMENTIA IN THAT PARTICULAR SITUATION. I ARGUE MCI IS IN THE -- NOT COMPLETELY ESTABLISHED AS A BRAND BUT GETTING THERE. HOPEFULLY WITH FRONTOTEMPORAL DEGENERATIONS AN LEWY BODY DISEASE WILL GET THERE WITH OTHER PEOPLE BUT THERE ARE ALTERNATIVE APPROACHES. DPA PPHMT, WE SHOULD ADOPT. AND SOME OF YOU KNOW I'M MASTER OF TERMINOLOGY THAT DOESN'T WORK. BUT THAT WOULD BE BETTER, WOULDN'T IT? NO. NOT BECAUSE OF THE BRAND. ANYWAY, COUPLE OF OTHER MOVING ON DONE OF ISSUES. ONE THING THAT OUR GROUP RON AND CLIFF AND BRAD AND I RAN INTO IN SOME PAPERS AN SURE MANY OF YOU HAVE AS WELL, THERE'S NO FORMAL DEFINITION OF COGNITIVE NORMALITY. AND IT IS A PROBLEM BECAUSE IN THINKING ABILITY COGNITIVE IMPAIRMENT, YOU NEED TO KNOW WHAT NOT TO KNOW WHAT NOT DOING ANITIVELY NORMAL IS, YOU HAVE TO KNOW WHAT NORMAL S SO THIS IS AN AREA THAT NEEDS TO BE ADDRESSED, IT ISN'T IN ANY OF OUR CRITERIA. DIAGNOSIS OF DEMENTIA, NOT ONLY HAS THAT BRAND IDENTITY AND I WOULD ASSERT IT IS NOT PEJORATIVE. THAT IT IS WIDELY ACCEPTED THAT THIS MEANING IS KNOWN BY MOST PEOPLE. IT IS A SIMPLE STRAIGHT FORWARD DEFINITION. I DON'T KNOW IF WE NEED TO RENEGOTIATE THAT ONE. THE PROBLEM THOUGH COMES WITH THE MILDEST STAGE OF SYMPTOMATIC COGNITIVE IMPAIRMENT, SO THIS IS AN AREA. THERE'S A GREAT DEAL OF CONTROVERSY AND TERMINOLOGY, WHAT DUE DOW COULD THAT ZONE IN BETWEEN COGNITIVE NORMALITY AND DEMENTIA, DEPENDENCE WHAT YOU MEAN BY COGNITIVE NORMALITY. SHOULD THERE BE INTERMEDIARY TERMINOLOGY? SOME SAY NO BUT THE OVERWHELMING USAGE BOTH IN U.S. AND EUROPE EMPIRICAL DATA SAY YES. BUT DEPENDS ON THE AUDIENCE AND BRINGS UP THE ISSUE, SOME AUDIENCE TERMINOLOGY WORKS AND SOME AUDIENCES IT DOESN'T WORK. LOSS OF FUNCTION VARIES DEPEND PONG YOUR SOCIAL CIRCUMSTANCES, IS THAT -- SHOULD THAT BE USEFUL? I THINK SO. BUT IT'S A QUESTION THAT NEEDS TO BE DISCUSSED, IS IT TOO SUBJECTIVE FOR SOME USES? PERHAPS. PANDS SHOULD THE DISTINCTION BE ETIOLOGY DEPENDENT? I THINK ABSOLUTE ARELY YES. FOR PEOPLE WHO JUST WORK ON THE ALZHEIMER'S WORLD, MCI HAS TAKEN ON A MEANING THAT'S WAY TOO FOCUSED. WHEREAS WE WHO WORK IN THE CEREBROVASCULAR LEWY BODY OR FRONTOTEMPORAL DEGENERATION WORLDS NEED SIMILAR TERMINOLOGY FOR THAT EARLY STAGE HERE. THERE ARE CIRCUMSTANCES WHERE CLINICAL PATHOLOGIC ENTITIES WORK AND HUNTINGTON'S DISEASE IS ONE THAT NAME IS REASONABLY WELL MAY HAVED ENTITY. THERE ARE EXTREMELY PHO DISEASES THAT PRODUCE APOPTOSIS, THERE ARE FEW BUT RARE AND VICE VERSA, IF YOU HAVE THE PATHOLOGY OF HUNTINGTON'S DISEASE, IT IS HIGHLY LIKELY THAT IT'S GOING TO BE EXPRESENCED IN THE TYPICAL WAY -- EXPRESSED IN THE DAME WAY WITH THE EXCEPTION OF CHILDREN. IN CONTRAST, ALZHEIMER'S DISEASE IS REALLY A NOT WELL BEHAVED CLINICAL PATHOLOGIC ENTITY FOR REASONS I MENTIONED. AS A CLINICAL DIAGNOSIS BY ITSELF, IT HAS PROBLEMS. SOME PEOPLE KNOW WHO I'M TALKING TO WHEN I HAVE THIS ARGUMENT BUT I THINK THAT THIS THIS NOTION THAT IT'S A CLINICAL PATHOLOGIC ENTITY NEED ON CLINICAL NEEDS TO BE DISCARDED. LEWY BODY DISEASE, MAYBE WORKS PRETTY WELL BUT THERE ARE OTHER CAUSES OF PARKINSONISM SO ON CLINICAL GROUNDS LEWY BODY DISEASE ISN'T GREAT BUT CLOSER AND AS NEAL POINTED OUT, THE VALUE SOME OF THE VERY SPECIFIC SYMPTOMS OF LEWY BODY DISEASE LIES IN THEIR ABILITY TO TREAT THEM LIKE SLEEP DISRDER LIKE PARKINSONISM LIKE COGNITIVE DISORDER, ORTHO STATIC HYPERTENSION, SON. FRONTOTEMPORAL DEGENERATION ON THE OTHER HAND ARE REALLY THE POSTER CHILD OF A POORLY DEFINED MAY HAVED PATHOLOGICAL INTI PHI BECAUSE OF THE DIVERSITY OF SYMPTOMS AND THE DIVERSITY OF NEUROPATHCAL PROCESSES AN MOLECULAR PROCESSES THAT FALL IN THAT RUBRIC SO FROM THAT WORLD MOVING TO THE P&A WORLD IT SEEMS OBVIOUS THAT WE WOULD BE SPECIFIC IN TALKING ABOUT A SYNDROME LIKE PPA AND THEN TALKING ABOUT AN ETIOLOGY IF WE KNEW TAUOPATHY TD 343 SPACEOPATHY SO FRONTOTERM PERFORM DEGENERATIONS ARE ARE IN A SENSE A -- FRONTOTEMPORAL GENERATIONS ARE IN A SENSE SEPARATING ITSOLOGY IS CRITICAL BECAUSE IF YOU DON'T, YOU'LL MAKE ALL KINDS OF MISTAKES AN ASSUMPTIONS THAT FRONTOTEMPORAL DEGENERATION IS SOME KIND OF UNIFIED ENTITY WHEN IT MOST CERTAINLY ISN'T. SO I THINK IN PRINCIPLE ETIOLOGIC DIAGNOSIS IS LESS CONTROVERSIAL THAN FIGURING MCI OR THAT GAP IN BETWEEN. AND THE VALUE I THINK OR THE REASON THAT IT SHOULD BE IS THAT IF YOU CAN DEFINE ANYTHING ON THE BASIS OF ONE FEATURE YOU DON'T RUN INTO AMBIGUITY SO THE GREAT VALUE HAVING BIOMARKERS IS WE MAYBE ON THE ROAD TO BE ABLE TO DO THAT. WHEN WE GET CONFLICTING INFORMATION INSTEAD OF FLOWING OUR HANDS LIKE WE USED TO DO, JUST PICK ONE ORB TRAILLY, WE CAN SAY HEY, MAYBE THERE'S MORE THAN ONE ETIOLOGY PRESENT. BY HAVING THAT KIND OF SPECIFICITY YOU CAN ALLOW CO-FEATURES TO VARY. YOU DON'T HAVE TO ARGUE THAT LEWY BODY PEOPLE, THE LEWY BODY WORLD GOT INTO IS WHETHER TO TALK ABOUT PARKINSON FIRST OR DEMENTIA FIRST AND HAVE TWO DIFFERENT NAMES FOR THOSE, SPECTRUM OF DISEASE. I THINK HAVING BIOMARKERS WILL GIVE US CONFIDENCE IN BEING ABLE TO MOVE INTO THE MULTI-ETIOLOGY WORLD TO BE ABLE TO DIAGNOSE KNOW MORE THAN ONE ETIOLOGY WITHIN THE CONTEXT OF A CLINICAL SYNDROME. SO MY LAST SLIDE ARE THE RECOMMENDATIONS THAT CAME OUT OF OUR GROUP AND YOU CAN READ THEM HERE BUT THE IDEA IS HAVING A WELL BEHAVED LEXICON THAT GIVES US WORDS THAT WORK FOR US AND THAT DON'T DISTORT OUR THINKING. THEY HAVE TO BE WORDS THAT CAN SPAN AFTER RATHER DIVERSE AUDIENCE, THE FACT IS THAT OUR FRIENDS IN THE REGULATORY WORLD HAVE DIFFERENT REQUIREMENTS AND DIFFERENT NEEDS THAN PEOPLE WHO ARE CLINICAL RESEARCHERS THAN LAY PEOPLE AND ADVOCACY GROUPS AND HOD WE'RE GOING TO BALANCE THOSE WILL TAKE WORK BUT I THINK CALLING ATTENTION TO THE FACT THAT IT'S NOT NOT A UNIFIED AUDIENCE THAT WE'RE DEALING WITH VERY IMPORTANT. AND AS ANGELA SAID, I THINK THIS JUST REPEATING, A TASK FORCE BE CONVENED TO TALK ABOUT THESE PROBLEMS AND WE'LL FIND SOMEBODY WE DONE LIKE TO BE SHARE OF IT. IT CERTAINLY IS GOING TO BE DIFFICULT. I WILL P STOP HERE. THANK YOU VERY MUCH FOR THE OPPORTUNITY TO TALK. >> WE'D LIKE THE PEOPLE TO COME UP WHO ARE ON THE PANEL FOR THE NOMENCLATURE DISCUSSION. FP >> SO I THINK WE'LL GET STARTED. >> THERE'S A CANADIAN ROCK GROUP CALLED RUSH AND THEY CLAIM IN ONE OF THEIR SONGS THAT YOU CAN BEND PERCEPTION BUS REALITY WON'T BUDGE. THE REALITY IS IN LATE COGNITIVE IMPAIRMENT, WHATEVER DIAGNOSTIC CATEGORIES WE HAVE CAPTURES A MULTIPLICITY OF INTERACTIVE PATHOLOGY. SO ONE APPROACH IS TO RE-- LET'S BRAKE DOWN INTO COMPONENT PARTS AND BUILD CRITERIA BASED ON DATA AND ADVANTAGE OF HAVING A STANDARDIZED WAY OF COLLECTING DATA, YOU CAN RELEASE IT FROM WHERE IT'S LOCKED BEHIND CRITERIA. IF U YOU ADOPT THE CRITERIA YOU DON'T KNOW WHAT THE REAL COMPONENTS, WHEREAS NOW WE CAN MEASURE THESE THINGS. THE SECOND WOULD BE THAT WE COULD HAVE TEMPORARY CATEGORIES AND WHERE THE NOMENCLATURE COME INTO BEING YOU CAN HAVE BENIGN INVENTED PROVISIONAL TERMS AND SEE HOW THEY WEIGH ON THE PUBLIC. WE CAN INVEST IN BUT MAKE THEM USER FRIENDLY. THIRDLY, IF WE DO THAT, IF WE HAVE STANDARD DATA WE CAN CO-OPT THE WHOLE WORLD IN PRODUCE DATA AND WE CAN APPLY THIS STRONG TECHNIQUES OF BIG DATA WE HAVE NOW, GENERATE A HYPOTHESIS WE CAN TEST AND CONSTRUCT NORMAL WILL HELP US LIKE TO DO IN ASTRONOMY MORE MOBILITY IS ONE GREAT ADVANCE. IN ATTEMPT TO DO THIS WAS MADE IN 2006. IT WAS ORGANIZED BRING (INDISCERNIBLE) AND MYSELF AND HAD PARTICIPANTS FROM THE SUMMIT LIKE RON PETERSEN AND DAVID HOLTZMAN. WE DID A NUMBER OF RECOMMENDATIONS BY NOW IT HAS BEEN USED IN THREE CONTINENTS AND I WONDER WHEN IT'S TIME FOR US TO REVISIT THE DESIRABILITY OF HAVING STANDARDIZED SETS OF MEASUREMENTS. SO WE CAN BUILD DATABASE CRITERIA. AND TARGET TREATABLE MECHANISMS. >> I GENERALLY AGREE WITH YOU. I SOMEWHAT RELUCTANT TO RECOMMEND TOP DOWN RECOMMENDATIONS FOR HOW WE DIAGNOSE -- MY VIEW BUT OBVIOUSLY VERY SYMPATHETIC TO WHAT YOU SAID. ANYBODY ELSE WISH TO COMMENT? >> WE HAVE OTHER PEOPLE. >> THIS MESSAGE IS TOP DOWN BECAUSE WE CAN COP OPT THEM AN ANGELA WAS ELOQUENT SAYING WE HAVE THINGS TO SAY. SO LET'S DO IT TOGETHER. THAT'S WHAT WORKS BEST. >> THANK YOU. Q. MATTHEW SHARP PROGRAM MANAGER FOR THE ASSOCIATION ON ATFTD, I WANT TO EXPRESS THE ASSOCIATION THANKS FOR BRINGING UP THIS TOPIC TO RON AND NINDS FOR TAKING THIS ON, I PARTICULARLY WANT TO SAY THANK YOU TO ANGELA TAYLOR FOR BEING THE ONE TO ASK THIS QUESTION AND OPEN THIS BOX. YOU KNOW VERY MUCH THAT WE WERE DOING WHATEVER WE CAN TO HELP. THIS IS VERY IMPORTANT ISSUE THAT NEEDS TO BE CLARIFIED ON A LOT OF FRONTS BUT ESPECIALLY THE NATIONAL PLAN. SO REFER BACK TO THE THE FIRST RECOMMENDATION B COMMUNICATION ON THIS ISSUE WITH THE NATIONAL PLAN AND THE NAPA P ADVISORY BOARD SEQUALLY IMPORTANT I DO ENCOURAGE YOU TO LOOK TO THE NATIONAL PLAN FOR AREAS THE THERE'S EASY REVISIONS AN CHANGES TO MAKE TO INCREASE THE CLARITY THEN IN THAT DOCUMENT. THANK YOU. >> THANK YOU. >> >> I'M ELAINE BARER, PROFESSOR IN NEW MEXICO AND PA TOOL THOLE GIST. I WANTED TO SAY, DR. -- PATHOLOGIST. I'M VERY EXCITED BY THE DIAGNOSTIC CRITERIA YOU ARE PROPOSING THAT ALMOST BASE OUR SORTING OF DISEASES BASED ON PATHOPHYSIOLOGY AND I HOPE WHEN YOU ARRANGE THIS RECOMMENDATION TEAM A PATHOLOGIST WILL BE INCLUDED SINCE WE ARE THE ONE WHOSE PERFORM THESE -- >> NO WAY. >> AND FINALLY I WANT TO SAY THAT -- WE HAVE THE -- I THINK NUMBER ONE RANKING OFFICE OF MEDICAL INVESTIGATOR IN THE COUNTRY IN OUR -- MEDICAL INVESTIGATORS IS HIGH RANKING TYPE OFFICE TO EXAMINE ALL DEATHSES THAT OCCUR WITHIN A 400-MILE RADIUS AROUND ALBUQUERQUE AND I HAVE HAD THE OPPORTUNITY TO EXAMINE ALL THE BRAINS THAT P COME THROUGH THAT SERVICE FOR THE LAST SIX YEARS. THERE IS A HIGH PERCENTAGE OFFER PEOPLE WHO ARE DIAGNOSED WITH ALZHEIMER'S DISEASE WHO DO NOT HAVE ALZHEIMER'S DISEASE. THE MOST COMMON IS VASCULAR DEMENTIA BUT THERE ARE MANY OTHER FORMS OF BRAIN DETERIORATION THAT SHOW UP IN AUTOPSY EXAMINATION. SO I THINK WE NEED TO THINK ABOUT FUNDING MORE AUTOPSY TYPE PATHOLOGY PACED EXAMINATIONS -- BASED EXAMINATIONS. THANK YOU. >> THANK YOU. MY -- SARCASTIC COMMENT ASIDE, WE CRITICALLY DEPEND ON NEUROPATHOLOGIST TO PROVIDE CRITICAL INSIGHT. IT IS ONE WE DIDN'T HAVE IT IN OUR RECOMMENDATIONLESS THIS TIME, BUT THE NEED TO TRAIN MORE NEUROPATHOLOGISTS INTERESTED IN DEMENTIA IS A CRITICAL ELEMENT THAT IS I WISH WE CAN DO SOMETHING ABOUT HOPEFULLY PEOPLE AT NINDS WILL HELP WAS WITH THAT. >> I KNOW NIA HAS GOTTEN IN TOUCH WITH ME ABOUT THAT. AND THEY WERE LOOKING AT FUNDING UNDER PATHOLOGY TRAINING WITH CENTERS THAT ALREADY HAVE AN ALZHEIMER'S CENTER GRANT. BUT I THINK WE HAVE TO EXPAND BEYONDS THAT. AND CERTAINLY OFFICE OF MEDICAL INVESTIGATORS WITH PROVIDE NEUROPATHOLOGY TRAINING AND WOULD BE A WONDERFUL PLACE TO FUND THAT KIND OF TRAINING. >> THANK YOU. >> I AGREE WITH THE DISCUSSION, WE JUST HAD BUT I THINK THE -- PROBABLY ELECTRONIC WHY I'M HERE ON THE PANEL IN DISCUSSION ABOUT THIS TOPIC I PUSHED ABOUT APPROACH THAT WAS COMMUNITY BASED. AND ABOUT COMMUNITY BASED PARTICIPATORY ENGAGEMENT. SO WHILE PATHOLOGY BASED CLASSIFICATION MAY WORK FOR SOME OF THE STAKEHOLDERS THAT WERE MENTIONED, IT MAY NOT WORK TO ADDRESS DIVERSE COMMUNITIES AND TO ENGAGE DIVERSE COMMUNITIES. SO MY ONLY POINT HERE IS THAT THE EFFORTS WE UNDERTAKE WITH THIS ADDRESSING NOMENCLATURE SHOULD PARTNER WITH COMMUNITYS WE'RE LOOKING TO ENGAGE. THAT IS EQUAL PARTNERSHIP WHICH WE'RE LEARNING WHAT IS IT THAT'S GOING TO ENHANCE THEIR UNDERSTANDING, THEIR WILLINGNESS TO BE IDENTIFIED S PATE IN RESEARCH. >> THANKS. >> SORRY. I HATE TO DISAGREE WITH YOU JENNIFER, I USUALLY AGREE WITH YOU BUT I DONE AGREE THESE TYPE OF APPROACHES WILL NOT WORK IN DIVERSE COMMUNITIES, IT'S VERY IMPORTANT TO GET PATHOLOGY AND THESE COMMUNITIES AS WELL, BECAUSE WE KNOW THAT THEY ARE MUCH MORE LIKELY TO HAVE MIXED DISEASE AND BECAUSE THE DRUGS ARE CURRENTLY BEING DEVELOPED BASED ON PROTUNE RESPONDING TO THE BRAIN WE DON'T KNOW WHAT'S IN THE DIVERSE COMMUNITY WE WON'T HELP THESE COMMUNITIES AS WELL. >> WE DON'T DISAGREE. >> GREAT. >> COMMENT IN REGARD TO PATHOLOGY AND MEDICAL SCIENTIFIC COMPONENT OF THIS, I THINK DAVID WHAT YOU SAID EARLIER IS CRITICAL. IMAGINE WHERE TREATMENT OF BREAST CANCER IS NOW, SOMEBODY COMES IN, DON'T CALL THIS A LUMP AND TREAT IT, WE FIGURE OUT WHAT IT IS AND DIAGNOSE IT VERY EARLY B AND EFFECT ACTIVELY USUALLY TREAT IT. FOR ALL DISEASES WE DEAL WITH THE EXCEPTION OF A FEW BIOMARKERS, WE DON'T KNOW WHAT WE'RE DEALING WITH WITH IN LIVING PEOPLE SO WE NEED WAYS TO UNDERSTAND THE PATHOLOGY IN LIVING PEOPLE HOPEFULLY BEFORE THEY BECOME SYMPTOMATIC. WE'RE MAKING PROGRESS. >> THAT'S NOT MUTUALLY EXCLUSIVE OF DEVELOPING A LANGUAGE DOING IT IN DIVERSE POPULATIONS. ABSOLUTELY. >> RON PETERSEN, MAYOR CLINIC. APPARENTLY IT'S ALL MY FOUGHT. >> YEAH. >> NOT GOING TO TRY TO DEFENDS DSM V, IT'S JANE PAULSON'S FAULT, SHE'S HERE. I WAS ON THAT COMMITTEE BECAUSE OF AFFIRMATIVE ACTION. THEY HAVE ONE NEUROLOGIST. >> ONE NORWEGIAN AMONG PSYCHOLOGISTS AND PSYCHIATRISTS. SO WHAT THE COMMITTEE TRIED TO DO WAS SEPARATE CLINICAL SYNDROME FROM THE UNDERLYING ETIOLOGY. BECAUSE IT WAS MEANT TO DEAL WITH A HOST OF DISORDERS, WE WERE INFLUENCED BY THE HIV AIDS COMMUNITY THAT THE TERM DEMENTIA WAS PEJORATIVE WHEN TALKING A 30-YEAR-OLD PERSON WITH A SEVERE DEGREE OF COGNITIVE IMPAIRMENT. SO THAT'S HOW YOU -- NEURAL COGNITIVE DISORDER, MAJOR NEUROCOGNITIVE DISORDER, IT DOESN'T ROLL OFF THE TONGUE BUT MEANT TO PUT THAT CLINICAL SPECTRUM OUT THERE OF A LEVEL OF COGNITIVE IMPAIRMENT SORT OF COMMENSURATE WITH DEMENTIA AND IN ANOTHER LEVEL THAT SORT OF COMMENSURATE WITH MILD COG ANY IMPAIRMENT AND UNDETERMINE THAT PUT -- COGNITIVE IMPAIRMENT AND UNDER THAT PUT ETIOLOGIES WITH RESPECT TO BIOMARKERS AND THE LIKE. THAT WAS THE ATTEMPT AND I GUESS THE DSM VERY IS OUT THERE, PEOPLE -- ADOPT THE IF THEY ADOPT THAT TERMINOLOGY WILL BE USED IN PARENTHESES, THERE'S STILL DEMENTIA THERE AND MILD COGNITIVE IMPAIRMENT THERE AND IF THOSE PREVAIL THOSE WILL BE THE ULTIMATE TERMINOLOGIES F. JUST A SIDE NOTE DSM V IS ARABIC FIVE NIGHT KNOT ROMAN NUMERAL FIVE BECAUSE THERE THERE MAYBE A DSM 5.1, AND .2, ET CETERA AND DIFFERENT AREAS WITHIN THE DSM NOSOLOGY MAY BE REVISED AT DIFFERENT POINTS IN TIME. EMPHASIZE SO ONE OTHER THING THAT DAVE MENTIONED WAS THE TO MILD COGNITIVE IMPAIRMENT, IT'S NOT A SALES PITCH FORB THAT BUT WHEN THE AMERICAN ACADEMY NEUROLOGY SURVEYED NEUROLOGISTS, ON THE USE OF THE TERM THE PAPER PUBLISHED IN 2010, ABILITY 80 TO 85% NEUROLOGISTS OUT THERE USED THE THE TERM MILD COGNITIVE IMPAIRMENT FOR THAT PORTION OF CLINICAL SPECTRUM. PETER (INAUDIBLE) RECENTLY DIDNA IN EUROPE SURVEYING EUROPEAN NEUROLOGISTS, GERIATRICIANS, PSYCHIATRISTS, THINKING THAT MAYBE OTHER TERMS LIKES PRODROMAL AD WOULD BE PREFERRED AND IN FACT 9 1E% OF PEOPLE SURVEYED THERE IN EUROPE THIS YEAR USED THAT TERM. SO IT MAY NOT BE THE BEST TERM BUT WE NEED THE CLINICAL SPECTRUM EYE ACROSS THE BOARD WHETHER WE USE DEMENTIA, MILD COGNITIVE IMPAIRMENT, WHATEVER THEN DECIDES UNDERLYING ETIOLOGIES BIOMARKERS AND THE LIKE. I'LL STOP THERE. >> ONE OTHER THING I HAVE DIDN'T MENTION BECAUSE I CAN ONLY KEEP SO MANY THINGS IN MY BRAIN AT ONE TIME IS THAT WE REALIZE THAT EACH STAGE HORDER GROUP HAS -- HOLDER GROUP HAS UNIQUE NEEDS. AS WE TALK ABOUT THE DIFFERENT TIERS OF DETAIL ON THE TERMINOLOGY, WE'RE GOING TO FINDS REMAY NEED TO USE DIFFERENT TERMS FOR THE SAME THING, WHEN WE TALK TO DIFFERENT AUDIENCES AND I THINK THAT'S GOING TO BE -- WITH WE HAVE TO CONSIDER THAT FROM A HEALTH DISPARITIES STANDPOINT, FROM A PUBLIC AWARE STANDPOINT ALL THE WAY DOWN TO THE NEURAL PATHOLOGIST. SO RECOGNIZE THAT WE UNDERSTAND THIS IS AN EXTRAORDINARILY COMPLEX ISSUE THAT THERE'S NOT A ONE SIZE FITS ALL SOLUTION TO. BUT HAVING SAID THAT, GO TEAM WE CAN STILL DO IT. P >> THANK YOU. >> I SAW PATIENT YESTERDAY WHO CAME TO ME AFTER HAVING SEEN ONE MIGHT HAVE WONDERFUL NEUROPSYCHOLOGIST PLEAINGS WITH THE DIAGNOSIS OF MAJOR NEUROCOGNITIVE DISORDER, WE HAVE SEEN THE TERM GET ADOPTED READILY AND THE PATIENT SAID THANKS GOODNESS I DON'T HAVE DEMENTIA. I REALLY THINK I AGREE WITH YOU, DAVE, I USE THE TERM DEMENTIA, JUST LIKE I USE THE TERM BLINDSNESS OR CONGESTIVE HEART FAIL YOU, IT CONVEYS A CLEAR LEVEL OF FUNCTIONAL IMPAIRMENT THAT STARTS DISCUSSIONS ABOUT DRIVING FINANCIAL MANAGEMENT AND SO FORTH AND UNIFIES US ALL IN THIS ROOM AND BEYOND. SO WE HAVE TO HAVE AS RON SAID THIS SPECTRUM OF OVERALL COGNITIVE IMPAIRMENT, WHAT IS THE PERSON'S FUNCTIONAL STATUS, SUBJECTIVE AS THAT IS, AND ANGELA I THINK YOUR SUMMARY OF THIS IS EXACTLY THE WAY WE DO IT WHICH IS START WITH THAT, HELP FAMILY FIGURE WHAT KINDS OF LEGAL OR OTHER DISCUSSIONS NEED TO BE HAD REGARDLESS WHAT ANYTHING UNDERNEATH THAT IS AND THEN TALK ABOUT THE CLINICAL SYNDROME. PPA PATIENTS ARE WORKING TOGETHER IN SUPPORT GROUPS OR OTHER FORUMS TO TRY TOWNS HOW TO COMMUNICATE IN SPITE OF THEIR ILLNESS THAT UNIFIES THEM. THEY DON'T CARE AT THAT LEVEL WHAT THE ONS LYING PATHOLOGY IS. -- UNDERLYING PATHOLOGY IS. I AGREE ABOUT BIOMARKERS AND ETIOLOGY WE NEED TO BE AS SPECIFIC ABOUT THAT AS WE ARE IN ONCOLOGY. SO ANGELA'S SUMMARY OF THOSE THREE LEVELS IS WHERE I'M GOING WITH MY THINKING ABILITY THIS. AND I APPLAUD YOU GUYS IN TRYING TO DIG THROUGH THE MUCK AND ALL THE TERMS. IT'S VERY CHALLENGING. >> THANKS. >> MY POINT IS HARD TO MAKE AFTER THAT COMMENT BUT RON DID MENTION THAT DEMENTIA HAS PEJORATIVE IMPLICATIONS. >> I DISAGREE, JOHN. I KNOW YOU WROTE ABOUT THAT AND I -- >> CAN I FINISH? >> SORRY. >> ALLOW ME TO FINISH MY POINT. THERE WAS A CHARACTER GIVE TOOK GREAT OFFENSE AS -- WHEN HIS WIFE WAS DIAGNOSED WITH DEMENTIA AND PERHAPS SUSAN DICKINSON CAN EXPLAIN WHY THE ASSOCIATION FOR FRONTOTEMPORAL DEMENTIA WAS CHANGE ASSOCIATION FOR FRONTOTEMPORAL DEGENERATION, A CONSIDERABLE DEGENERATION YOU WERE INVOLVED WITH. I WAS NOTS ADVOCATE, I WAS TRYING TO HELP A CAREGIVER A VOICE OBJECTIONS TO THE TERM DEMENTIA ANION A LOT OF DETAILS ABOUT THE RESEARCH BUT HYDRID POINT OUT IN JAPAN THE TERM DEMENTIA WHICH HAS SEXUAL ABUSE CONNOTATIONS WAS BANNED. NOT MAKING A CASE WE SHOULD GET RID OF THE THE TERM DEMENTIA, I USE IT TOO. BUT SUSAN, WHY DID WE CHANGE THE NAME OF AFTD. FROM DEGENERATION TO HAVE -- FROM DEMENTIA TO DE MR. JENKINS: RATION? >> I PROMISE I'LL BE FAST. THERE ARE TWO MAIN REASONS THAT ACTUALLY DON'T REFLECT TESTIFY PEJORATIVE NATURE OF THAT WORD THAT'S THERE. ONE WAS WE WANTED TO BE A PLACE TO BRING THE WHOLE COMMUNITY TOGETHER. AND WHAT WE YOU WERE WERE HEARING FROM EXPERT PES MEDICAL ADVISORY COUNCIL WHILE PEOPLE DIAGNOSE FLOWED WITH BEHAVIORAL FTD HEARING THE THE WORDS DEMENTIA, THOSE THAT WERE BEING DIAGNOSED WITH PPA PSP OR CBD WERE NEVER HEARING THE THE WORD DEMENTIA. AND THAT MAY BE BECAUSE CONSIDERED TO BE PEJORATIVE CONNOTATIONS P BUT IF WE WANT TO BE THE PLACE WE CAN BRING ALL THESE PEOPLE TOGETHER, KNOWING THAT THERE'S CROSS OVER IN ETIOLOGY OF THESE DISEASES, AND WE WANTED TO GATHER THEM IN SINGLE POPULATION WHEN WE GOT READY TO DO BIOMARKER STUDIES, WHAT HAVE YOU, WE NEEDED A NAME THESE PEOPLE WOULD RECOGNIZE WAS A HOME FOR THEM AND A PLACE THEY COULD BELONG, THEY WANTED TO PAD VOW KATE OR FUND OR PARTICIPATE IN RESEARCH. THE OTHER THING WE KNEW IS CLOSELY RELATED, THAT THE LANGUAGE, DIKE KNOW SEIZE THAT OUR PATIENTS WITH WERE HEARING, THEN, THIS IS FIVE OR SIX YEARS AGO NOW, IT WAS SOLELY A CLINICAL DIAGNOSIS. SO THOSE PEOPLE HEARING THE LANGUAGE I JUST MENTIONED P PPA BEHAVIORAL BARING FRONTOTEMPORAL DEMENTIA, PROGRESSIVE CEREBRAL POOL SY, YES LOOK FORWARD TO AND DESPERATELY WORKING FOR THE TIME TO HEAR PATHOLOGICAL DIAGNOSIS AS WELL. SO WE WANTED A NAME TO SPAN THE PRESENT TIME OF THE CLINICAL LANGUAGE TO THE FUTURE TIME OF A ETIOLOGICAL LANGUAGE AND AGAIN FUNDAMENTAL PURPOSE TO CREATE A COMMUNITY THAT COULD STAY TOGETHER THROUGH TIME AND THROUGH THOSE ADVANCES. >> ANGELA I WILL GIVE YOU A LIST OF THE ORGANIZATIONS I'M ABOUT TO MENTION BUT I THINK IN TERMS OF DISCUSSION ABILITY STAKEHOLDERS FOR THE WORK GROUP BY IDENTIFY THREE BROAD CATEGORIES UNTIL BRAD STOPS ME I'LL -- >> PLEASE DON'T. IT WON'T -- NO, NO NEW YORK CITY. WE HAVE A MINUTE. JUST MAKE YOUR POINT. >> OKAY. >> PLEASE INCLUDES SERVICES IN THE SCOPE OF THE WORK, PLEASE INCLUDES PEOPLE LIVING WITH WHATEVER WORDS WE CHOOSE TO USE. INCLUDING THOSE WHO LIKE THE VARIATION OF LIVING FULLY WITH. NOT JUST THOSE WHO SEE THEMSELVES ON A TRAJECTORY DOWN THEIR VIEWS ARE EQUALLY VALID. ALSO ENCOURAGE YOU INTO COLLUDE GOVERNMENT AGENCIES PARTICULARLY FEDERAL GOVERNMENT AGENCIES AS STAKEHOLDERS BEYOND JUST NIH. SO FDA CRITICALLY IMPORTANT, DRUG DISCOVERY BUT ALSO GETTING INTERVENTION TO MARKET AND CONSUMER YOU NEED THOSE THAT ARE INVOLVED IN PROVISION OF SERVICES AND PROTECTION OF RIGHTS, CMS DOJ, VETERANS AA FAIRS CONSUMER FINANCIAL -- >> GIVE US THE INPUT IN WRITE SOMETHING IT IS INAPPROPRIATE FOR THE OTHER PEOPLE WHO WOULD LIKE TO ASK QUESTIONS. YOU MADE YOUR POINT. THANK YOU VERY MUCH. >> MY NAME -- >> BRIEF. >> MY NAME IS JOAN SHARP I'M JUST A VOLUNTEER FOR THE LBDA BUT YOUR COMMENTS ABOUT NEEDING TERMINOLOGY FOR DIFFERENT AUDIENCES, I LOVE HEARING THAT. BECAUSE I WAS A CAREGIVER FOR P MY HUSBAND WHO HAD -- WHO WAS EVENTUALLY DIAGNOSED WITH LPDA AUTOPSY ONLY OF. NOT BEFORE THAT. BUT I COULDN'T GET HIM TO GO TO SEE A NEUROLOGIST WHEN HE AND I BOTH KNEW HE HAD SOMETHING MORE THAN SENIOR MOMENTS IN TERMS OF LOSS OF MEMORY. AND ONE OF THE REASONS WAS THE FEAR FACTOR. HE FIGURED THEY WOULD DIAGNOSE HIM WITH ALZHEIMER'S, HE KNEW THAT ALZHEIMER'S WAS A FATAL DISEASE, THERE WAS NO CURE. ET CETERA. HE WOULDN'T GO SEE A NEUROLOGIST BECAUSE HE KNEW IT WOULD DEPRESS HIM. AND HE WAS LIGHT. I KNEW HE WOULD BE AND THAT WOULD THEREFORE RUIN HIS ABILITY TO ENJOY WHATEVER LIFE HE HAD LEFT. SO I HAD TO COME UP WITH OTHER TERMS THAT WERE ACCEPTABLE AND INITIALLY IT WAS JUST MEMORY LOSS. BECAUSE HE KNEW HE HAD MEMORY LOSS SO HE WAS WILLING -- AND HE DIDN'T WANT TO GO SEE ANYONE BECAUSE HE KNEW THERE WAS NO CURE. BUT I CONVINCED HIM THAT FIRST THERE WERE MULTIPLE DEMENTIA, MAYBE IT'S NOT ALZHEIMER'S, MAYBE IT'S SOMETHING ELSE. SO YOU NEED A GENERAL TERM OF SOME KIND SO THAT THAT FEAR FACTOR DOESN'T GET IN THE WAY. BECAUSE MOST PEOPLE DON'T KNOW ABOUT THESE OTHER DEMENTIAS THEY KNOW ABOUT ALZHEIMER'S. SO THAT'S WHAT THEY'RE AFRAID OF IS ALZHEIMER'S. I CONVINCED HIM THAT THERE WERE SOME DRUGS THAT MIGHT SLOW IT DOWN. THEY DIDN'T DO IT BUT -- >> JUST IN TERMS -- >> THE FINAL THING WAS THAT ONCE I -- I EVEN WROTE TO THE NEUROLOGIST AHEAD OF TIME AND SAID DON'T TELL HIM HE HAS ALZHEIMER'S DISEASE TELL HIM HE HAS SOME KIND OF DEMENTIA. BUT THERE ARE MANY OF THEM. WHAT I FOUND TESTIFY THAT WAS SOMETHING HE ACCEPTED WITHOUT IT AFFECTING HIS DEPRESSION, SO FORTH, WAS MCI, WHEN I WOULD TALK ABOUT HIS MCI HE ACCEPTED THE FACT THAT HE HAD MILD COGNITIVE IMPAIRMENT. AS TIME WENT ON, THINGS GOT WORSE, THE WORD DEMENTIA WAS ACTUALLY BETTER THAN A SPECIFIC DISEASE. >> THANK YOU FOR YOUR INSIGHT. >> AFRAID THIS IS THE LAST QUESTION. >> GIVEN I'M MARY ANN STERLING CO-FOUNDER OF CONNECTED RESOURCES MY HUSBAND AND I HAVE THROW OF FOUR PARENT WHOSE HAVE DEMENTIA. DEPRESS PHI WANT TO MAKE A BROAD COMMENT HERE TODAY, I THINK THE MOST IMPORTANT THING WE NEED TO REMEMBER WE NEED TO BRING SCIENCE TO THE PEOPLE, WE -- ESPECIALLY WITH THIS DISEASE. AND WE CAN DO THAT IN PLAIN LANGUAGE, THAT IS A PHRASE I'M NOT HEARD MENTION YET HERE TODAY. I HOPE MAYBE LITERATOR THIS AFTERNOON. -- LATER THIS AFTERNOON BUT ENCOURAGE EVERYONE TO REMEMBER THAT PLAIN LANGUAGE IS HOW WE'RE GOING TO COMMUNICATE WITH THE PUBLIC HERE. >> THANK YOU. I REALLY WANT TO APOLOGIZE TO PEEP WHOM DIDN'T HAVE TIME, THIS IS -- THERE'S GOING TO BE MORE OPEN MIC SEX THERE'S A LONG ONE TOMORROW AFTER DR. HOLTZMAN SCIENTIFIC CHAIR SUMMARIZES THE MAJOR INPUT FROM THE METED MEETING. I ENCOURAGE PEOPLE WHO HAVE SUCH TO GIVE US INPUT IN WRITING, WE -- THIS IS THE POINT OF THE MEETING GET AS MUCH INPUT AS WE CAN AND I'M REALLY -- I APOLOGIZE, WE DO HAVE TO MOVE ON. AND BUT WE WANT YOU TO GIVE US INPUT IN WRITING, COME TOMORROW. THERE'S A LOT MORE OPEN MIC TIME TOMORROW. IT'S 40 MINUTES OR LONGER AFTER DAVE HOLTZMAN SUMMARIZES FROM THE MEETING. HAVING SAID THAT I FORGET WHAT TIME THE LUNCH BREAK ENDS. 1:30. SO WE'RE GOING START AGAIN AT 1: 306789 THERE'S A CAFETERIA HERE AT NATCHER. AND THEN AT LISTER HALL BEHIND US. SOME MAY WANT TO WALK OVER THERE. THANK YOU FOR FOR A GREAT SESSIONFUL [APPLAUSE] IT GIVES ME GREAT PLEASURE TO INTRODUCE THE CHAIR OF THE HEALTH DISPARITIES SESSION, DR. JENNIFER MANLY. SHE WAS ONE OF THE CHAIRS IN 2013 AS WELL, AND SHE WILL LEAD THIS SESSION. PLEASE WELCOME JENNIFER. [APPLAUSE] >> THANK YOU, ROD. I WANT TO THANK THE MEMBERS OF THE DISPARITIES COMMITTEE FOR THIS SUMMIT. I'M GOING TO TELL YOU ABOUT THEM RIGHT NOW SO THAT AS THEY COME UP I WON'T HAVE TO UNDERGO A LONG INTRODUCTION OF THEM. I'LL DO IT ALL AT ONCE. THEY ARE SID O'BRYANT, ASSOCIATE PROFESSOR AT UNIVERSITY OF NORTH TEXAS HEALTH SCIENCE CENTER, MARIA GLYMOUR, ASSOCIATE PROFESSOR AT UCSF, VIRGINIA WADLEY, PROFESSOR OF MEDICINE AT UAB, UNIVERSITY OF ALABAMA, AND HECTOR GONZALEZ, MICHIGAN STATE UNIVERSITY, AND THROUGHOUT OUR TIME IN FORMING THESE RECOMMENDATIONS WE RECEIVED A LOT OF HELP FROM PEOPLE AT NIH LIKE IRENE, CARL HILL AND NINA SILVERBERG. THIS IS AN OUTLINE OF MY SHORT INTRODUCTION, I'M GOING TO TALK ABOUT DISPARITIES POPULATIONS, AND THE EMPIRICAL EVIDENCE FOR DISPARITIES IN A.D. AND ADRD, SOCIETAL BURDEN OF DISPARITIES, I'LL SUMMARIZE PROGRESS SINCE 2013 AND OVERVIEW AND RECOMMENDATIONS COMPARED TO LAST TIME AND EXPLAIN SOMETHING THAT YOU'VE HEARD ABOUT THIS MORNING, THE RECOMMENDATIONS APPLY NOT JUST TO ADRD BUT ALSO ALZHEIMER'S DISEASE. THIS IS A LIST OF THE NIH-DEFINED DISPARITIES POPULATIONS. THEY INCLUDE PEOPLE FROM MINORITY, RACIAL AND ETHNIC GROUPS, SOCIOECONOMICICALLY DISADVANTAGED AND RURAL POPULATIONS. THERE ARE DIFFERENT DEFINITIONS OF DISPARITIES, BUT THEY ALL CONVERGE AND AGREE WITHOUT ADDRESSING THE UNDERLYING CAUSES OF STARK DIFFERENCES IN HEALTH, THE CYCLE OF INEQUITY AND DISPARITY AND INEQUALITY IN HEALTH WILL REMAIN FOR GENERATIONS. HERE ARE SOME QUICK AND A FEW EXAMPLES, DATA TAKEN FROM THE HEALTH AND RETIREMENT SURVEY, DEPICTING RATES OF COGNITIVE IMPAIRMENT BY AGE AND RACE AND ETHNICITY. IN BLUE AND RED AFRICAN-AMERICANS AND HISPANICS ARE AT MUCH HIGHER RISK AT ALL AGE GROUPS. THIS IS A RECENT STUDY FROM KAISER PERMANENTE. SORRY, I CAN'T SAY IT, HEALTHCARE SYSTEM IN NORTHERN CALIFORNIA. IT'S A INTEGRATED HEALTHCARE SYSTEM AND THEY SURVEYED LONGITUDEALLY MEMBERS 60 AND OLDER COMPARING INCIDENCE CASES OF DEMENTIA USING ICD-9 CODES, ALL CASES. ASIAN-AMERICANS DEPICTED IN THIS LINE GRAPH IN BLACK WERE LEAST LIKELY TO DEVELOP DEMENTIA, A REFERENCE GROUP. AFRICAN-AMERICANS 65% MORE LIKELY TO DEVELOP INCIDENT CASES THAN ASIAN-AMERICANS, AMERICAN INDIANS AND ALASKA NATIVES WERE 32% MORE LIKELY COMPARED TO ASIAN-AMERICANS. THE DISPARITIES, RACIAL AND ETHNIC DISPARTIES WERE WIDER AMONG MEN, LIFETIME RISK WAS HIGH FOR ALL GROUPS, SO THE EFFECT WAS ABOUT AGE OF ONSET. THE SOCIETAL BURDENS OF DISPARITIES ARE HIGH. I WANT TO POINT OUT THAT AMONG PEOPLE WHO ARE DIAGNOSED WITH DEMENTIA, THE MINORITY GROUPS AND DISPARITIES GROUPS ARE OFTEN DIAGNOSED LATER, AT LATER STAGES OF THE DISEASE. AND THIS RESULTS IN HIGHER MEDICAL COSTS FOR THESE INDIVIDUALS. AND HIGHER PREVALENCE OF NEUROPSYCHIATRIC SYMPTOMS. SINCE 2013, THERE'S ACTUALLY BEEN A TREMENDOUS AMOUNT OF WORK IN THE DISPARITIES AREA. WE RECEIVED AN UPDATE AND A PROGRESS REPORT, AND WE'VE BEEN LEVERAGING EXISTING STUDIES OF DIVERSE COHORTS TO INCLUDE COGNITION AND ADDING ALZHEIMER'S DISEASE AND BIOMARKERS, STUDIES THAT MAY NOT HAVE BEEN ORIGINALLY INTENDED TO MEASURE COGNITION OR ADRD AS OUTCOMES. WE'VE BEEN LEVERAGING LOCAL EXISTING EXPERTISE TO REACH OUT TO DIVERSE COMMUNITIES AND EVALUATE ADRD AND DEVELOPING OUR ADAPTING ASSESSMENT TOOLS AND INVESTIGATING POTENTIAL MECHANISMS OF DISPARITIES. I LIST THE SOME HERE. IT'S AN IMPRESSIVE LIST OF STUDIES GOING ON, AND MOST OF YOU KNOW NOW OF THE PROGRAM ANNOUNCEMENTS THAT NIA PUT OUT TO LOOK AT DISPARITIES AND ALZHEIMER'S DISEASE IN RO1 AND RO3. CHANGES FROM 2016, WE REALLY WANTED TO CLARIFY SOME ISSUES. WE HAD TWO FOCUS AREAS IN 2013, ADVANCING TREATMENT AND PREVENTION STRATEGIES AND RECRUITMENT. WE HAVE NOW WITHIN THE RECRUITMENT DOMAIN EMPHASIZED EQUAL COMMUNITY PARTNERSHIPS AND PULLED OUT RECOMMENDATIONS AND EXPANDED ON THEM TO GET AT ASSESSMENT AND ALSO MONITORING CHANGES IN ADRD, SO THESE ARE TRACKING CHANGES AND IN ADDITION TO RESEARCH ON MECHANISMS OF DISPARITIES AND LIFE COURSE PATHWAYS, WE'RE ALSO EMPHASIZING IN OUR RECOMMENDATIONS ACCOUNTABILITY. AND I WANT TO POINT OUT SOMETHING THAT IS REALLY SIMILAR TO THE TALKS WE HEARD EARLIER THAT THESE RECOMMENDATIONS, THESE DISPARITIES RECOMMENDATIONS, ARE RELEVANT TO ADRD AND ALZHEIMER'S DISEASE. WE HAVE AN EMPHASIS ON RESEARCH ON TREATMENT AND PREVENTION AND MECHANISMS. WE FOCUS ON MODIFIABLE RISKS. THERE'S OBVIOUSLY OVERLAP IN THE ASSESSMENT TOOLS WHICH HAVE TO BE APPROPRIATE FOR DIVERSE POPULATIONS. WE HAVE AN AWARENESS OF THE ROLE OF THE SETTING IN WHICH WE GET PARTICIPANTS, MAGNITUDES AND TRENDS, AND BOTH SETS OF DISORDERS WHICH MAY NOT BE SO SEPARATE COMMUNITY PARTNERSHIPS AND ENGAGEMENT ARE CRITICAL. OKAY. SO I'M NOW GOING TO INTRODUCE DR. SID O'BRYANT, HE'S GOING TO SPEAK TO US ABOUT THE RECOMMENDATIONS IN FOCUS AREA 1 AND HE WILL GO RIGHT INTO PROGRESS HIGHLIGHT ON MECHANISMS, BIOLOGICAL MECHANISMS OF HEALTH DISPARITIES. >> THANK YOU, JEN. THANKS, ROD, FOR ALSO HAVING ME HERE. AND TO THE COMMITTEE FOR ALL THE WORK PUT INTO THIS. I'M GOING TO TALK ABOUT RECOMMENDATION 1, FOCUS AREA 1, THE TWO RECOMMENDATIONS CONTAINED THEREIN. AS GENERAL BACKGROUND INFORMATION, I AM CONSTANTLY SURPRISED BY THE LACK OF AWARENESS OF THE NEED TO CONSIDER DISPARATE POPULATIONS WHEN LOOKING AT NEURODEGENERATIVE DEGENERATIVE AND NEUROLOGICAL DISEASE AND COMPLICATIONS. IF YOU SPEND TIME IN ONCOLOGY SPACE READING LITERATURE, OR CARDIOVASCULAR SPACE, THE INFECTIOUS DISEASE SPACE AS WELL AS ENDOCRINOLOGY SPACE THESE ARE SIMPLY UNDERSTOOD, KNOWN AND STUDIED EXTENSIVELY. AND IN PRECISION MEDICINE EMPHASIS HEADED TOWARDS BEING PUSHED FORWARD THIS IS VERY IMPORTANT. HOWEVER, IN THE ADRD SPACE, EVEN IN THE ALZHEIMER'S SPACE TO A CERTAIN EXTENT THERE'S STILL LIMITED INFORMATION REGARDING PREVALENCE, INCIDENCE, RISK FACTORS. AND THE BIOLOGY OF THESE HEALTH DISPARITIES AMONG DISPARATE POPULATIONS WHEREAS LIKE I SAID A MOMENT AGO IF YOU GO INTO ENDOCRINOLOGY AND DIABETES, WELL, THERE ARE WELL-DOCUMENTED DIFFERENCES IN PREVALENCE, RISK FACTORS, THERE'S BEEN SUGGESTION FOR DIFFERENT IMPLEMENTATION OF BIOMARKER CUT SCORES AND THEY KNOW THERAPIES DIFFER DEPENDING ON WHICH GROUP YOU'RE LOOKING AT IN TERMS OF IMPLEMENTATION AND THERAPEUTIC INTERVENTION. FOR US, IN THIS AREA OF RECOMMENDATION 1, I'LL GET MORE IN DETAIL, SEEKING TO ADDRESS EXISTING GAPS IN KNOWLEDGE, TAKE INTO ACCOUNT SOCIAL, ENVIRONMENTAL, BIOLOGICAL FACTORS, AND RECOMMENDATION 2 SEEKS TO LEVERAGE A HUGE INFRASTRUCTURE THAT'S ALREADY IN PLACE IN LITERATURE THAT'S ESTABLISHED THAT HAS LED TO MANY, MANY EPIDEMIOLOGICAL STUDIES AS WELL AS INTERVENTIONS. SO LET'S PUT SOME PERSPECTIVE TO THINGS, AND I WANT TO HIGHLIGHT THE LIMITED SUCCESS AT ENROLLING DISPARATE POPULATIONS INTO CLINICAL TRIALS OF NEUROLOGICAL DISEASE. I'M GOING TO -- TWO EXAMPLES, BECAUSE THESE ARE ALMOST THE ONLY TWO WHERE YOU CAN READILY GET THE DATA. ALZHEIMER'S AND PARKINSON'S DISEASE, THIS IS A 2007 ARTICLE THAT REVIEWED OVER 12,000 PATIENT RECORDS THAT COMBINED ACDS AND INDUSTRY-SPONSORED CLINICAL TRIALS. THESE WERE THE CLINICAL TRIALS THAT LED TO EVERY SINGLE FDA APPROVED INDICATION FOR ANY ALZHEIMER'S THERAPEUTIC THAT'S CURRENTLY ON THE MARKET. WHEN YOU LOOK AT THE NUMBERS, YOU SEE THAT OVER IN THE ADCS TRIAL, ADCS HAS DONE MUCH BETTER THAN INDUSTRY. IN ADCS YOU HAVE 90 PERCENT CAUCASIAN, IN INDUSTRY YOU HAVE LESS 1/2 OF 1% OF HISPANIC. IN THE PARKINSON'S SPACE A 2009 ARTICLE THAT REALLY RESEMBLES THE ALZHEIMER'S SPACE, 93% ENROLLED WERE NON-HISPANIC WHITE, THE LARGEST NEXT CATEGORY WAS EITHER OTHER OR AND/OR NOT REPORTED. YOU CAN GUESS WHICH OF THOSE ARE THE MAJORITY IN THAT SUBGROUP. AND THEN LESS THAN 1% WERE ENROLLED REPORTED AS AFRICAN-AMERICAN OR HISPANIC OR ASIAN. NOW, THIS BARRIER I THINK LEADS TO OPPORTUNITY. I THINK THERE'S TREMENDOUS OPPORTUNITY WITHIN THE FIELD TO WORK WITH OTHER FIELDS WHO ARE DOING THIS QUITE SUCCESSFULLY. DEMENTIA STUDIES AND EPIDEMIOLOGICAL STUDIES FROM A DEMENTIA STANDPOINT, AGING STANDPOINT, HAVE -- THIS IS THE BULLET, IT'S JEN'S, NOT MINE, I STOLE IT, CAN ELOQUENTLY DETECT AND DISCRIMINATE THE CLINICAL PHENOTYPES OF VARIOUS DEMENTIA SYNDROMES, WHEREAS THE CARDIOVASCULAR FIELD CAN VERY, VERY SUCCESSFULLY RECRUIT DISPARATE POPULATIONS INTO NOT ONLY EPIDEMIOLOGICAL STUDIES BUT ALSO CLINICAL INTERVENTION TRIALS. THERE MAY BE A MISSED OPPORTUNITY HERE. WHAT I DID WAS SURVEYED AND LOOKED AT JUST A FEW. THESE ARE NOT ALL, JUST A FEW OF THE RECENTLY STARTED ONGOING OR PUBLISHED CARDIOVASCULAR DISEASE TRIALS. NOW, THESE ARE ONLY FOCUSING ON BLOOD PRESSURE RELATED, COULD BE IN COMBINATION WITH DIABETES, BUT WHAT YOU SEE IS THAT ANYWHERE FROM 10 TO 30% OF THESE POPULATION ENROLLED ARE STATISTIC MINORITY SUBGROUPS, IN THE SPRINT STUDY IT'S ACTUALLY EVEN LARGER. THEN THERE'S THE ACCORD STUDY AND THE ACCORD MIND AND SPRINT MIND STUDIES, THE SANDS TRIAL, SANDS TRIAL RECRUITED NATIVE AMERICAN, THE OTHER ONLY AFRICAN-AMERICAN. YOU SEE A VERY IMPRESSIVE CAPACITY TO RECRUIT FROM DISPARATE POPULATIONS, BUT ON THE OTHER SIDE, THE FLIP SIDE, MOST DO NOT EVEN HAVE COGNITIVE MEASURES. THOSE THAT HAVE COGNITIVE MEASURES ARE VERY BRIEF. AND THEY MAY NOT BE, MANY IN THIS ROOM WOULD ARGUE, CANNOT DISTINGUISH SUBTYPES OF NEURODEGENERATIVE DISEASES. THIS IN MY OPINION IS A WONDERFUL OPPORTUNITY TO WORK WITH CARDIOVASCULAR STUDIES, AND ON OUR PANEL IS DR. GONZALEZ, HECTOR GONZALEZ, WHO DID JUST THAT WITH THE INCA STUDY UP AND RUNNING, THE SOUL STUDY TO DO A COGNITION STUDY, ALSO DONE IN THE ATHEROSCLEROSIS STUDY, THERE'S LARGE SCALE EPIDEMIOLOGICAL STUDIES OF HEART DISEASE THAT CAN BE LEVERAGED IN ORDER TO MEET SUCCESS. SO WITH REGARDS TO ASSESSING EPIDEMIOLOGY AND MECHANIC IN THIS PARTICULAR PATHWAYS, WHAT OUR GROUP FELT IS OF TREMENDOUS IMPORTANCE IS FOR US TO SIMPLY UNDERSTAND THE PREVALENCE, THE INCIDENCE, THE RISK FACTORS, BUT ALSO THE MECHANISMS. WHAT ARE THE BIOLOGICAL CORRELATES AS WELL AS UNDERLYING MECHANISTIC PATHWAYS FOR THESE HEALTH DISPARITIES? IT'S NOT SUFFICIENT TO SIMPLY SAY THAT THERE ARE DISPARITIES AND THESE DISPARITIES ARE RELATED SIMPLY, SIMPLY IN QUOTES, TO SOCIAL OR OTHER FACTORS. WE ACTUALLY HAVE TO STUDY EMPIRICALLY THE BIOLOGICAL MECHANISMS. THE INTERRELATIONS BETWEEN SOCIAL, ENVIRONMENTAL AND BIOLOGICAL MECHANISMS ARE OF EXTREME IMPORTANCE. THERE HAVE BEEN RECENT STUDIES TO SHOW GENE ENVIRONMENT INTERACTIONS AND COGNITION THAT ARE QUITE COMPLEX AND THEN WHEN YOU OVERLAY ETHNIC DIFFERENCES THEY BECOME MORE COMPLEX, BUT WE WILL NEVER UNDERSTAND OR BE ABLE TO HAVE EFFECTIVE THERAPIES IF WE DO NOT UNDERSTAND THE COMPLEXITIES. ANOTHER RECOMMENDATION IS TO INVOLVE THE EXPERTS IN TRIAL DESIGN WHEN CREATING NEW EPIDEMIOLOGICAL STUDIES. OFTENTIMES WHAT YOU SEE IS YOU HAVE A BEAUTIFULLY DESIGNED EPIDEMIOLOGY STUDY OF AGING OF HEART DISEASE OR WHATEVER BUT FINDINGS ARE NOT TRANSLATABLE TO INTERVENTION AND WE FELT IF WE COULD MERGE THESE EXPERTISE TO HELP CREATE BETTER TRIAL DESIGNS, EPIDEMIOLOGICAL DESIGNS, THEN TRANSLATION ACROSS WOULD BE MUCH EASIER AND TAKE A SHORTER TIME FRAME TO DO SO. ALSO WE NEED TO LEVERAGE SOCIAL AND BIOLOGICAL EVIDENCE TO IDENTIFY POLICIES, SYMPTOMS AND INTERVENTION TO REDUCE THESE DISPARITIES. THE NEXT ONE IS LEVERAGING CURRENTLY AVAILABLE INFRASTRUCTURE SO ENHANCED DESIGN TO IMPROVE APPLICATION TO AGING AND DIVERSE POPULATIONS. AS I SHOWED PREVIOUSLY THERE ARE LARGE SCALE TRIALS ONGOING, AND I REALLY LIKE DAVID'S TWO SLIDES WHERE HE SAYS EPIDEMIOLOGY STUDIES SHOWS LINK BETWEEN HEALTH DISEASE AND COGNITION, HEALTH ABC, PHASE III SHOWS BLAH, BLAH, BLAH. THAT'S WHAT HEART DISEASE HAS DONE. THEY HAVE DONE LARGE SCALE EPIDEMIOLOGY STUDASE THAT LEAD TO LARGE SCALE STUDIES AND IN THE NEURODEGENERATIVE WE NEED TO DO THE SAME THING F WE CAN CREATE STANDARDIZED ASSESSMENTS TALKED ABOUT IN SESSIONS PRIOR TO THIS ONE, THESE WOULD BE OF TREMENDOUS IMPORTANCE TO THE DESIGN OF THESE FUTURE TRIALS. SO NOW I FINISHED IT, LIKED YOU SAID. YOU TOLD ME TO FINISH EARLY AND MOVE TO THE SECOND TALK. OKAY. NOW I'M GOING TO TALK ABOUT RESEARCH ON MECHANISMS OF HEALTH DISPARITIES, AND THE NEURODEGENERATIVE SPACE. I'M GOING TO HIGHLIGHT SOME WORK DONE BY OTHERS AND FOCUS ON SOME STUFF WE'VE DONE OVER THE LAST SEVERAL YEARS AND I'LL EXPLAIN HOW WE GOT HERE FROM THERE. I DON'T KNOW HOW THIS JUST HAPPENED. SO SIT WASN'T MY FAULT FOR THE FIRST -- I'M HAVING A GROUNDHOG DAY EXPERIENCE. [LAUGHTER] ME AND BILL MURRAY. I'M CAUGHT IN A CIRCULAR LOOP OF DEATH, I THINK IT'S TWILIGHT ZONE OR GROUNDHOG DAY OR SOMETHING. THEY ARE GOING TO FIX SOMETHING THAT FOR A CHANGE WASN'T MY FAULT. YOU GOT TO TELL MY WIFE THAT, BY THE WAY. SHE WILL NEVER BELIEVE SOMETHING WASN'T MY FAULT. ALL RIGHT. SO WE'RE GOING TO TALK ABOUT MECHANISMS OF HEALTH DISPARITIES. SO THIS IS SOMETHING I CAN GET PASSIONATE ABOUT. IF I START FLAILING HANDS, YOU'LL HAVE TO FORGIVE ME. HOWEVER, I'M GOING TO DO SOME BACKGROUND AND GET SOME VERY EASY EXAMPLES. SOMEONE ELSE IN A PRIOR SESSION ACTUALLY TALKED ABOUT KIDNEY DISEASE, CKD, AS A TREATABLE RISK FACTOR FOR COGNITIVE LOSS. YEAH. ABSOLUTELY. WE JUST PUBLISHED SOME WORK ON THIS SHOWING THAT CKD, EVEN MILD CKD IS RELATED TO COGNITIVE LOSS. INTERESTINGLY ENOUGH IF YOU GO TO QUEST OR LAB CORPS AND YOUR PRIMARY CARE DOC RUNS YOUR STANDARD CBC, ET CETERA, THE EGFR LEVELS ARE STRATIFIED BY EITHER AFRICAN-AMERICAN OR NON-AFRICAN-AMERICAN. THIS HAS BEEN THERE FOR AT LEAST A DECADE THAT WE KNOW THAT THIS BIOMARKER ABSOLUTELY VARIES BY ETHNICITIES, AND EGFR LEVELS ARE A BIOLOGICAL OUTCOME FOR CLINICAL TRIALS. THIS IS A LOW HANGING FRUIT, IF YOU WANTS AN EXAMPLE OF WHY WE SHOULD CONSIDER MECHANISMS OF HEALTH DISPARITIES. AND WORK WE DID WITH NEPHROLOGISTS RECENTLY WE FOUND THE PROTEOMIC PROFILE OF CKD-RELATED COGNITIVE LOSS, MILD COGNITIVE IMPAIRMENT, WAS COMPLETELY DIFFERENT THAN THAT OF SOMETHING NOT RELATED TO CKD, WHICH LOOKED LIKE AN ALZHEIMER'S TYPE NCI, A DIFFERENT SOMETHING SPECIFICALLY AMONG MEXICAN AMERICANS. ONCE YOU GET INTO PRECISION MEDICINE, PERSONALIZED MEDICINE, WHICH IS REALLY AN ENTIRE AREA OF HEALTH CARE THAT'S DOMINATED BY ONCOLOGY, THERE IS NOTHING IN THE NEUROLOGY SPACE IN THIS AREA, AND VERY LITTLE OTHER THAN INFECTIOUS DISEASE. THERE ARE WELL-ESTABLISHED BIOMARKERS THAT ARE GOING TO IMPACT THERAPEUTIC RESPONSE. FOR EXAMPLE, CYTOCHROME P 440 IS WELL KNOWN TO IMPACT DRUGS CYP IMPACTS THE RATE OF METABOLISM, YOU CAN BE A FAST OR SLOW METABOLIZER DEPENDING ON THIS GENETIC POLYMORPHISM. THESE POLYMORPHISMS ARE NOPE TO VARY BY ETHNIC GROUPS. WELL, THE DRUGS IMPACTED BY THIS POLYMORPHISM INCLUDE PLAVIX, NEXIUM, ET CETERA, INCREDIBLY COMMON, THERE'S A POLYMORPHISM THAT AFFECTS COUMADIN LEVELS, AND I WORK WITH PRIMARY CARE A LOT, AND UNDERSERVED POPULATIONS ESPECIALLY FQHCs, AND NONE OF THEM ARE DOING THIS. THEY HAVE A HELL OF A TIME GETTING THEIR PATIENTS STABILIZED ON COUMADIN OFTENTIMES AND IT'S BECAUSE OF THIS. HER AND TRIPLE-NEGATIVE BREAST CANCER IS ANOTHER EXAMPLE. INTERESTINGLY ENOUGH, THAT IS A BIOMARKER OF THERAPEUTIC INTERVENTION. IF YOU'RE HER POSITIVE TRIPLE POSITIVE -- SORRY, TOO MANY TRIPLE-NEGATIVE AND HER POSITIVE THAT TELLS YOU A VERY SPECIFIC CHEMOTHERAPY. WELL, WE ALSO KNOW THAT THESE GENETIC MARKERS VARY BY ETHNICITY. ANOTHER EXAMPLE, SAME THING WITH CYP 2D 6, THIS MARKER IMPACTS THERAPEUTIC TREATMENT RESPONSE, DRUGS THAT ARE VERY COMMON IN THE PSYCHIATRY AND NEUROLOGY SPACE, IF YOU LOOK AT THAT LIST. SO LET'S TAKE THIS A LITTLE STEP FURTHER AND TALK ABOUT WHY STUDY THESE HEALTH DISPARITIES, THE BIOLOGICAL MECHANISMS OF HEALTH DISPARITIES AMONG ADRDs. WELL, CYP 2D 6 VARIES BY ETHNICITY, RELATED TO PREVALENCE OF PARKINSON'S DISEASE. PARKINSON'S DISEASE VARIES BY ETHNICITY, DEMONSTRATED PREVIOUSLY. IF YOU LOOK AT THE ALZHEIMER'S SPACE, APOE4 GENOTYPE, APOE4 IS THE SINGLE STRONGEST RISK FOR ALZHEIMER'S DISEASE AND THERE ARE GENETIC DIFFERENCES IN THE APOE4 PRESENCE. THERE'S A LATITUDE EFFECT TO MULTIPLE SCLEROSIS WHICH LEADS TO HAVING LATINOS AT HIGHER PREVALENCE RATES. DR. BARNES WHO APPEARS TO BE ON EVERY COMMITTEE OF THIS TASK FORCE RECENTLY PUBLISHED SOME WORK SHOWING THE DIFFERENTIAL COMORBIDITY RATES WHICH DAVE BENNETT HIGHLIGHT THE PREVIOUSLY. I'M GOING TO JUMP INTO WORK WE'VE BEEN DOING AMONG MEXICAN AMERICANS. WHY FOCUS ON MEXICAN-AMERICAN COGNITIVE AGING? APPROXIMATELY HALF OF THE INCREASE IN THE U.S. POPULATION BETWEEN 2000 AND 2010 WAS GROWTH IN THE HISPANIC COMMUNITY. THE NUMBERS OF THOSE 65 AND ABOVE HISPANICS WILL TRIPLE. IF YOU LOOK AT THE GRAPH HERE YOU'LL SEE THAT THE INCREASED AGING PERCENTAGE OF THE POPULATION IS GROWING MOST RAPIDLY AMONG HISPANIC ELDERS. HISPANIC ELDERS ARE THE FASTEST GROWING SEGMENT OF THE ELDERLY POPULATION. THERE'S A WEALTH OF LITERATURE SUGGESTING THAT MEXICAN AMERICANS MAY BE AT INCREASED RISK FOR ALZHEIMER'S AND MCI, SOME SAY EQUIVALENT, SOME SAY INCREASED. THE LITERATURE IS CLEAR ON LATER STAGES OF DISEASE PROGRESSION WHICH WAS COVERED EARLIER ALSO, BUT ALSO DATA SUGGESTING DIAGNOSED AT YOUNGER AGES, EARLIER AGE OF ONSET. LESS LIKELY TO SEE FORMAL DEMENTIA CARE, LONGER DELAYS IN RECEIPT TO CARE, ET CETERA, AND MULTIPLE COMORBIDITIES WHICH AS SEVERAL PRESENTATIONS, NEIL AND DAVID AND OTHERS HAVE SHOWN. COMORBIDITIES OF IMPORTANCE TO CONSIDER. WHEN WE STARTED THIS LINE OF WORK WE STARTED BY DOING THE EPIDEMIOLOGY, THE PREVALENCE AND RISK FACTORS. SO ONE OF THE THINGS THAT WE STUMBLED ACROSS VERY EARLY WHEN DOING COMMUNITY-BASED RESEARCH, WHICH IS THOSE POPULATIONS LOOK VERY DIFFERENT THAN YOUR CLINIC BASED POPULATIONS, SO WE RECRUITED FROM RURAL LOCALES AS WELL AS URBAN BASED SPECIFICALLY TARGETING HISPANICS. IN THAT SETTING WHAT WE FOUND WAS THE AGE OF EARLIEST IDENTIFICATION OF COGNITIVE LOSS WAS SIGNIFICANTLY YOUNGER IN HISPANICS AND MEXICAN-AMERICAN COHORT COMPARED TO NON-HISPANIC WHITES. TEN YEARS SO; THE COMMUNITY BASED SAMPLE DIAGNOSIS WITH MCI. THAT TEN YEAR GAP IS THE SAME GAP FOR EARLIER AGE OF ONSET OF TYPE 2 DIABETES AMONG MEXICAN AMERICANS COMPARED TO NON-HISPANIC WHITES. WE STARTED LOOKING AT MEDICAL COMORBIDITIES, DIABETES AND BLUE BAR DEPRESSION, AND OBESITY, AND WHAT YOU SEE AMONG MEXICAN AMERICANS DIAGNOSED WITH MCI COMPARED RIGHT NEXT TO THEM NON-HISPANIC WHITES, DRASTIC DIFFERENCES WITH REGARDS TO PREVALENCE OF THESE CONDITIONS. BUT THEN WHAT WE ALSO FOUND IS SIGNIFICANTLY OTHER EIGHTS OF APOE4, YOUNGER AGE OF ONSET, COMPARABLE OR INCREASED RISK OF COGNITIVE IMPAIRMENT, AND DECREASED GENETIC RISKS WITH THE ICE OF APOE4. WHAT'S GOING ON? WHY? SO WE STARTED LOOKING AT ALL OF THE RISK FACTORS, YOU GET TO THE ODDS OF HAVING MILD COGNITIVE IMPAIRMENT, THE ONLY THING CONSISTENT ACROSS ALL COHORTS WAS AGE. EDUCATION HAS NEVER FOR US BEEN A CONSISTENT RISK OR PROTECTIVE FACTOR, WHAT WE THINK OUR EDUCATION RAIN GOES FROM 0 TO, 20% OF POPULATION HAS 0-3 YEARS OF EDUCATION. WE'RE STARTING TO LOOK AT INFLECTION POINT OF WHEN DO YOU GO FROM RISK, NO RISK TO PROTECTION WITH REGARDS TO EDUCATIONAL LEVELS? IF YOU MAKE A METABOLIC RISK SCORE, IT APPEARS TO BE INCREASED RISK FOR HISPANICS, NOT NON-HISPANIC WHITES. SO THEN WE DOVE INTO -- I THOUGHT I HAD EXTRA TIME BECAUSE I WENT FAST BEFORE? YOU'RE KILLING ME HERE. SORRY. SO WE START -- WE'VE CREATED A BLOOD TEST FOR SCREENING, THAT'S FOR OUR USE IN PRIMARY CARE FOR REFERRAL, THINGS DISCUSSED EARLIER. WHEN YOU GET INTO BIOMARKER DEVELOPMENT, IT REQUIRES TO YOU LOOK AT ETHNIC IMPACT ON YOUR BIOMARKERS. IF YOU WANT TO GET TO CLINIC. SO WE CAN FIND COMPARABLE DIAGNOSTIC ACCURACY OF A BLOOD TEST AMONG HISPANICS, SAME WITH NATIVE AMERICANS AND AFRICAN-AMERICANS, YOU FIND RELATIVE IMPORTANCE OF BIO, MAKERS VARIES DRASTICICALLY. SAME PANEL, BUT WHAT YOU FIND IS INFLAMMATION IN VASCULAR DYSFUNCTION. AMONG MEXICAN AMERICANS IT'S METABOLIC. FATTY ACID BINDING PROTEIN, GLUCAGON, UPON CREATIC POLY POLYPEPTIDE, THE DRIVING FORCE OF THE PROTEOMIC PROFILE IS METABOLIC IN NATURE, ALTHOUGH THE ACCURACY IS THE SAME. WE CREATED A SUBGROUP OF METABOLIC DYSFUNCTION, VERY SPECIFIC GROUP, AND WHEN YOU LOOK AT THE SUBGROUP OF METABOLICALLY DYSFUNCTIONING MCI AND A.D., THE PREVALENCE OF THAT IN THE PHENOTYPE IS THREE TIMES HIGHER IN MEXICAN AMERICANS THAN IT IS NON-HISPANIC WHITES, AND THAT IN THE PHENOTYPE SPECIFICALLY PREDICTS PROGRESSION AMONG THAT GROUP OF INDIVIDUALS SO IT TELLS YOU, OR ME, THAT YOU MAY WANT TO GET A GUIDED INTERVENTION TAILORED TO THE SPECIFIC POPULATION. AND BASICALLY THIS GETS AT RON'S POINT EARLIER IS YOU HAVE THESE RISK FACTORS BUT WHAT I'M TAKING IT A STEP FURTHER SAYING THE RELATIVE WEIGHT OF THE BIOLOGICAL AND MECHANIC MECHANISTIC FACTORS VARIES BY ETHNICITY, WE NEED TO LOOK AT METABOLIC IN MEXICAN AMERICANS MORE CLOSELY, THIS IS A SCHEMATIC, HOW THEY VARY BY ETHNICITY. OKAY. [APPLAUSE] >> GREAT. THAT WAS GREAT. THANK YOU VERY MUCH, SID. MARIA GLYMOUR IS HEADED UP. SHE'S GOING TO DISCUSS OUR FOCUS AREA 2, WHICH IS MONITORING CHANGES IN ADRD DISPARITIES. >> THANK YOU. IT IS A LITTLE BIT EERIE TO SEE EVERYTHING MOVE ON THE SCREEN WITHOUT YOU TOUCHING ANYTHING. IT'S KIND OF FABULOUS. I WISH IT WAS MORE COMMON IN MY LIFE. WE HAVE A NICE LONG OPEN MIC PLANNED THAT'S QUICKLY DISSIPATING INTO NOT SO LONG BUT WE PLANNED 30 MINUTES OF DISCUSSION AND I HOPE THAT WE CAN RETAIN THAT. THAT'S WHY I'M RUSHING SPEAKERS, LOOKING FORWARD TO A DISCUSSION AND SO EVERYONE WHO HAS QUESTIONS AND COMMENTS, JUST MAKE SURE AND WRITE THEM DOWN AND GET UP TO THE MICS EARLY, GET TO THE EDGES SO THAT WE KNOW HOW MANY PEOPLE WE HAVE LINED UP FOR QUESTIONS AND WE CAN PLAN ACCORDINGLY. >> IT'S REALLY A PLEASURE TO BE HERE AND BE ABLE TO TALK ABOUT MONITORING CHANGES IN DISPARITIES. I GUESS PART OF WHAT'S AMAZING ABOUT BEING HERE, EVEN THOUGH WE CAN'T ALL AGREE APPARENTLY ON NOMENCLATURE, WE DO SHARE A VISION OF REALLY ELIMINATING THE BURDEN OF THIS INTERLOCKING SET OF DISEASES ON PUBLIC HEALTH THE QUESTION IS IN PARTICULAR HOW WOULD WE KNOW IF WE'VE SUCCEEDED, AND SO THE GOAL OF THE RECOMMENDATION AREA IS THAT WE REALLY DEVELOP -- FOCUS ON DEVELOPING A SYSTEM TO MONITOR MAGNITUDE AND TRENDS IN DISPARITIES AND INCIDENCE OF ADRD. THIS IS A VERY AMBITIOUS GOAL. IT COULD TAKE UP TO 8 YEARS TO ACHIEVE A FUNCTIONAL SYSTEM BUT WE CAN START RIGHT AWAY. I WANT TO TALK ABOUT WHY WE NEED THIS, WHY THIS IS CRITICAL AND HOW WE THINK STRATEGICALLY IT CAN BE DONE. SO EVERYONE AGREES THAT PROGRESS TOWARDS ELIMINATING DISPARITIES IS REALLY ESSENTIAL, BUT HOW WILL WE EVEN KNOW IF WE'VE ARRIVED WITH THE CURRENT DATA INFRASTRUCTURE? IF WE CREATE STRONG SYSTEMS TO MONITOR DISPARITIES, THIS WILL EXPEDITE PROGRESS TOWARDS ELIMINATING DISPARITIES, BUT IT WILL ACCELERATE RESEARCH ON TREATMENT AND PREVENTION AND ALLOW US TO MEASURE OUR SUCCESS. SO WE KNOW WHEN WE HAVE MADE PROGRESS. THE REALITY IS THAT PROGRESS IS DRIVEN BY DATA, BY EVIDENCE, AND FOR EXAMPLE IF YOU CONSIDER CARDIOVASCULAR DISEASE COMMUNITY IT'S ONE OF THE PLEASURES OF BEING ON THE AMERICAN HEART ASSOCIATION E-MAIL LIST WHEN THEY NOTIFY ME THEY HAVE MORE PROGRESS THAT ACTUALLY MORTALITY RATES HAVE GONE DOWN, IT MAKES ME BELIEVE IN PUBLIC HEALTH. THIS IS JUST A PICTURE SHOWING THE TRENDS IN MORTALITY FROM HEART DISEASE ACROSS THE LAST 60 YEARS. YOU CAN SEE A 70% DECREASE IN MORTALITY FROM HEART DISEASE, HOW CAN WE DRAW A PICTURE FOR ADRDs AND DISPARITIES IN PARTICULAR? WE DON'T HAVE THE DATA TO KNOW WHAT THE PICTURE LOOKS LIKE ON A NATIONAL BASIS WITH RESPECT TO DIVERSE POPULATIONS. WE RELY ON DATA FROM A HANDFUL OF COHORTS, REGISTRIES IN LOCAL AREAS, AND PASSIVE DATA SOURCES WHICH REALLY RELY ON ADMINISTRATIVE DATA. MOST OF THESE DATA SOURCES ARE NOT REPRESENTATIVE OF RACIAL/ETHNIC MINORITIES, RURAL AMERICANS AND PROBABLY UNDERREPRESENT LOW SOCIOECONOMIC STATUS INDIVIDUALS. MANY MOST IMPORTANT COHORTS THAT PROVIDE US INCREDIBLY IMPORTANT INFORMATION ARE NOT REPRESENTATIVE SAMPLES AND THEY CAN'T TELL US ANYTHING ABOUT TRENDS. THEY CAN'T TELL US WHETHER WE MADE PROGRESS IN PUBLIC HEALTH. ALL OF OUR STUDIES AS WE'VE TALKED ABOUT TREMENDOUSLY CHALLENGES AND COMPREHENSIVE MEASUREMENT OF ADRDS. SO THE ISSUE OF REPRESENTATIVE SAMPLES HAS BEEN CONTROVERSIAL IN EPIDEMIOLOGY RECENTLY, THOSE WHO ARE NOT EPI-WONKS MAY NOT BE AWARE OF THE LIVELY DEBATE BUT THERE'S A DEBATE WHEN YOU NEED REPRESENTATIVE SAMPLES AND WHEN YOU DON'T. THERE'S A CLASSIC STORY ABOUT WHY WE NEED REPRESENTATIVE SAMPLES WHICH IS IF YOU'RE GOING TO SAY ANYTHING ABOUT NATIONAL TRENDS, YOU REALLY NEED TO HAVE A REPRESENTATIVE SAMPLE. THIS IS THE FAMOUS EXAMPLE FROM THE 1936 ELECTIONS IN WHICH THE MAJOR MAGAZINES GOT THE PREDICTION WRONG BY 20 PERCENTAGE POINTS, THEY PREDICTED PRESIDENT LANDON WINNING BECAUSE THEY DIDN'T HAVE REPRESENTATIVE SAMPLES. IF OUR GOAL IS REALLY TO ADDRESS PUBLIC HEALTH PROGRESS, WE NEED REPRESENTATIVE SAMPLES. ANOTHER MAJOR CHALLENGE IS ACTUALLY SIMPLY DIVERSITY, ACTUALLY DIVERSITY, NOT REPRESENTATIVENESS. STUDIES INCLUDE 1, 2 OR 3 RACIAL/ETHNIC GROUPS, WHITES AND AFRICAN-AMERICANS, IT'S MORE DIVERSE THAN WHITES AND AMERICANS OR WHITES AND LATINOS. THE CHALLENGES OF INTEGRATING DATA IS EXACERBATED BECAUSE DIAGNOSTIC RATES ARE SENSITIVE TO DIAGNOSTIC CRITERIA. WE CAN'T DIFFERENTIAL ACROSS STUDIES, HOW THE DIAGNOSTIC CRITERIA ARE IMPLEMENTED ACROSS STUDIES. THIS IS ONE ILLUSTRATION. THIS IS A SLIDE OF ELIZABETH MAYEDA'S, WE TRYING TO UNDERSTAND THE RELATIONSHIP WITH ETHNICITY AND DEMENTIA, THE SALSA STUDY INCLUDES MEXICAN AMERICANS, THE WHICAP STUDY IN NEW YORK INCLUDES MORE CARIBBEAN LATINOS. SALSA HAS ONLY LATINOS. WE SEE DIFFERENT RACIAL/ETHNIC PATTERNS, THAT THAT BECAUSE ONE IS CALIFORNIA AND ONE IS NEW YORK AND THERE MIGHT BE OTHER REASONS FOR CALIFORNIA AND NEW YORK TO DIFFER? IS THAT BECAUSE PEOPLE IMPLEMENTING HAD DIFFERENT STRATEGIES? OR THEY REALLY HAVE DIFFERENT RISK FACTORS? WE CAN'T ANSWER THE QUESTIONS NOW. WHAT HAPPENS WHEN WE DON'T HAVE A REALLY RIGOROUS NATIONAL SYSTEM IS THAT WE BASICALLY RISK ERODING PUBLIC COMMITMENT. THIS WAS A BEAUTIFUL STUDY THAT CAME OUT OF FRAMINGHAM, THEY HAVE UNUSUALLY HIGH QUALITY DATA FOR TEMPORAL TRENDS, AND THEY DESCRIBED WHAT HAS HAPPENED OVER TIME AND SHOWED DECLINES IN DEMENTIA RISK OVER TIME IN THEIR COHORTS. ALTHOUGH IT WAS IN FACT DESCRIBED WITH APPROPRIATE CAUTION I THINK IN THE PRIMARY PAPER AND EVEN IN MUCH OF THE POPULAR LITERATURE, WELL COVERED IN THE "NEW YORK TIMES" FOR EXAMPLE, COMMON INTERPRETATIONS WERE NOT PROBABLY WHAT WE WANTED TO HEAR, THIS IS FROM A BLOG THAT IS ON THE DMJ SITE, SO THE COMING EPIDEMIC MAY NOT HAPPEN AT ALL ON THE SCALE FORECAST BY SINGLE ISSUE LOBBYISTS REGARDS WILL OF BRITISH BREAKTHROUGHS. THIS IS REALLY NOT THE IMPLICATION THAT WE WANT PEOPLE TO TAKE AWAY FROM THE EPIDEMIOLOGIC EVIDENCE. WE WANT PEOPLE TO TAKE AWAY PROGRESS IS POSSIBLE, PRIORITIZE GOOD RESEARCH. SO WE NEED DATA SETS THAT ARE DIVERSE, WE NEED REPRESENTATIVE SAMPLES, WE NEED WELL MEASURED OUTCOMES, WE NEED LONGITUDINAL DATA AND LARGE SAMPLES. I CAN FEEL EVERYONE IN THE ROOM WHO THOUGHT ABOUT BUDGETS IS GASPING. WE'RE NOT GOING TO HAVE ONE SINGLE COMPREHENSIVE DATA SOURCE. WE'RE GOING TO HAVE TO INTEGRATE DATA, BUT THE TECHNICAL TOOLS ARE AVAILABLE, JUST MATHEMATICAL TOOLS, IF WE HAVE A COMPREHENSIVE SYSTEM FOR INTEGRATING EVIDENCE FROM MULTIPLE SOURCES WE CAN DO IT. WE NEED TO INCLUDE INFORMATION FROM BOTH COMMUNITY BASED COHORTS WHICH TEND TO HAVE MANY ADVANTAGES WITH RESPECT TO MEASUREMENT AND PASSIVE SURVEILLANCE SOURCES WHICH HAVE BETTER ADVANTAGES WITH RESPECT TO REPRESENTATIVENESS AND DIVERSITY. THE GOAL IS TO ESSENTIALLY QUANTIFY BIASES IN EACH TYPE OF STUDY AND INTEGRATE INTO THE OTHER TYPES OF STUDIES. SO A FEASIBLE MONITORING SYSTEM WOULD DEVELOP AND VALIDATE DATA STANDARDIZATION PROTOCOLS. WE HAVE TO UNDERSTAND HOW MUCH WITHIN DATA SOURCE UNDERSTATEMENTS, OVERESTIMATES COMPARED TO ANOTHER DATA SOURCE. THERE WILL BE ONGOING SMALL STUDIES TO VALIDATE AND HARMONIZE, INFRASTRUCTURE TIED TO PASSIVE DATA SOURCES, HAVING THE ADVANTAGE OF HAVING LARGE POPULATION BASES TO MONITOR DISPARITIES IN RARE DISEASES AND POPULATIONS THAT ARE NOT COMMON IN SMALLER DATA SETS. AND WE NEED A REALLY GOOD INFRASTRUCTURE TO COLLECT, CLEAN AND MERGE THE DATA. IT TAKES TIME AND MANPOWER, HUMAN POWER, AN IMPORTANT SKILL SET. I WANT TO CONTRAST THREE CATEGORIES OF STUDIES THAT ARE IMPORTANT SOURCES, ILLUSTRATIVE OF TYPES OF STUDIES. KAISER, JEN MANLY MENTIONED WORK COMING OUT OF KAISER WHERE THEY HAVE COMPARED BASED ON ICD CODES. WHAT'S REMARKABLE IS THEY HAVE ESTIMATES FOR THESE GROUPS, NO PLACE ELSE CAN WE GET THESE DATA. DESPITE THE MANY STRENGTHS OF KAISER THERE ARE MAJOR CONCERNS ABOUT REPRESENTEDNESS. WE CAN GO TO A LARGER COHORT, H RS IS GREAT, LARGE, LONGITUDINAL, BLACKS, WHITES, LATINOS, BUT THERE ARE POTENTIAL ISSUES WITH MORTALITY AND MEASUREMENT QUALITY. THE STUDY TYPE THAT'S BEEN OUR CORE, WHICAP IS FAMILIAR TO PEOPLE BECAUSE IT HAS BEEN SO INFLUENTIAL, WHAT ARE THE ISSUES, IT ONLY HAS ONE LOCATION AND THAT MEANS THAT IT CAN'T TELL US ABOUT NATIONAL TRENDS. THESE STUDIES HAVE OFFSETTING LIMITATIONS, AND WE CAN INTEGRATE EVIDENCE ACROSS THE STUDIES, ONLY WITH CAREFUL PLANNING. THESE ARE THE STEPS WE CONSIDER IMPORTANT TO MOVE FORWARD. WE NEED TO FORM A MONITORING PROGRESS WORKING GROUP DRAWING ON LEADERS OF ACTIVE AND PASSIVE DATA SOURCES. EVERYBODY HAS THEIR FAVORITE DATA SOURCE. LIVE WITH THE LIMITATIONS AND FIGURE OUT HOW OTHER DATA SOURCES CAN STRENGTHEN YOUR DATA SOURCE. WE NEED TO IDENTIFY DATA SOURCES WITH THE GREATEST BREADTH, IDENTIFY CENTRAL DAT INTEGRATION AND MONITORING SITES, DEVELOP DATA PROTOCOLS TO STANDARDIZE AND INTEGRATE EVIDENCE, AND WE NEED ONGOING SERIES AND A FUNDING STRUCTURE TO PROVIDE STABLE RESOURCES FOR EACH CONTRIBUTING DATA SOURCE FOR DATA COLLECTION, CLEANING AND MERGING. WITH THAT WE MIGHT GET TO KNOW IF WE SUCCEEDED IN THE GOALS WE LAID OUT TODAY. THANK YOU. [APPLAUSE] >> THANK YOU, MARIA. I'M GOING TO TAKE ON FOCUS AREA 3, WHICH WE HAVE NAMED ASSESSMENT. AND I'M GOING TO JUSTIFY THE RECOMMENDATIONS THAT WE MADE IN THIS AREA, WE MADE TWO. AND ASSESSMENT TOOLS ARE IMPORTANT FOR ALL OF US HERE INTERESTED IN DEMENTIA. THE ISSUE I THINK IS PARTICULARLY IMPORTANT WHEN WE'RE LOOKING AT DISPARITIES. DEVELOPMENT OF ASSESSMENT TOOLS THAT WORK AND WORK THE WAY WE WANT THEM TO AMONG DISPARITIES POPULATIONS IS GOING TO ACCELERATE RESEARCH KNOWLEDGE IN THIS AREA. IT'S CRITICAL FOR THAT. I THINK THAT DISPARITIES RESEARCH BECAUSE THESE POPULATIONS THAT WE'RE SETTING ARE SO DIVERSE, THERE'S SOME THORNY ISSUES AND CHALLENGES THAT TAKE UP THE DISPROPORTIONATE AMOUNT OF OUR TIME WHEN WE'RE DOING THIS KIND OF RESEARCH, BUT HAPPILY MODERN PSYCHOMETRIC TECHNIQUES AND TESTING WE HEARD ABOUT FROM SANDY THIS MORNING, WE DID NOT COORDINATE BUT SOME SLIDES ARE ALMOST IDENTICAL, THIS IS WHERE I THINK THERE'S A LOT OF PROMISE. WE HAVE A CHALLENGE. I'M A NEUROPSYCHOLOGIST SO IT'S REALLY HARD FOR ME NOT TO TALK ABOUT COGNITION, ALTHOUGH YOU HEARD FROM US IN OUR PRIOR TALKS THAT OUTCOME ASSESSMENT IS NOT THE ONLY ISSUE HERE FOR RESEARCH ON DISPARITIES AND ADRD. WE'RE TALKING ABOUT PREDICTORS AS WELL. AND MEASURES OF BOTH BIOLOGICAL AND SOCIAL MECHANISMS. SO THESE MEASUREMENT ISSUES APPLY ON THE OTHER SIDE EQUATION AS WELL. OUR COGNITIVE -- I WILL USE COGNITIVE MEASURES AS AN EXAMPLE. THEY HAVE REDUCED SPECIFICITY AMONG DISPARITIES POPULATIONS SO WE OVERDIAGNOSE COGNITIVE IMPAIRMENT IN PEOPLE NOT PART OF THE MAINSTREAM GROUP. WE KNOW THAT WE NEED TO HAVE CONSTRUCT AVAILABILITY ACROSS POPULATIONS, NOT BEEN DONE IN RESEARCH STUDIES. PEOPLE RESPONDED BY COMING UP WITH DEMOGRAPHICALLY ADJUSTED NORMS THAT ARE LOCAL NORMS, BUT THIS IS EXPENSIVE, NOT EVERYONE HAS THE MONEY, THE SUPPORT, THE ABILITY TO RECRUIT LARGE NUMBERS OF NORMAL PEOPLE, COGNITIVELY NORMAL PEOPLE FROM THESE DISPARITIES POPULATIONS TO ESTABLISH NORMS. AND THEY ARE NOT ULTIMATE SOLUTION BECAUSE EVEN IF YOU HAVE NORMS, CROSS-SECTIONAL STUDIES ARE PARTICULARLY VULNERABLE TO MISDIAGNOSIS, EVEN STUDIES OF CHANGE OVER TIME IF WE DO NOT UNDERSTAND DEMOGRAPHIC TO PRACTICE EFFECTS, IF WE'RE CATCHING PEOPLE AT DIFFERENT TIMES, SELECTION BIAS AND MORTALITY AMONG DISPARITIES POPULATIONS MEAN THAT WE MAY HAVE DIFFERENT EFFECTS ACROSS DIFFERENT -- EVEN IN LONGITUDINAL STUDIES. SO I'M GOING TO USE THE BATTERY AS AN EXAMPLE OF HOW WE CAN DO THIS RIGHT. THIS IS DAN MUNGUS' WORK, HE'S AT UC DAVIS. HIS ISSUE WAS THAT HE HAD SPANISH SPEAKERS IN THE NORTHERN CALIFORNIA REGION HE HAD TO GET A COGNITIVE ASSESSMENT ON. HE DID NOT HAVE ADEQUATE INSTRUMENTS TO DO SO. SO HE KNEW THAT IF HE JUST TRANSLATED THE ITEMS FROM HIS COGNITIVE TEST OVER TO SPANISH, THAT WOULD NOT ADDRESS COMPARABILITY, THAT WOULDN'T MAKE THEM EQUALLY SENSITIVE AND SPECIFIC, AND ALSO THAT WOULD NOT ADDRESS CONSTRUCT VALIDITY. SO IN A NUMBER OF STUDIES HE LET US KNOW HOW HE DID THIS. HE USED ITEM RESPONSE THEORY TO CREATE MATCHED NEUROPSYCHOLOGICAL INSTRUMENTS AND MEASURE A NUMBER OF COGNITIVE DOMAINS. HE DEVELOPED 12 ENTIRELY NEW SCALES AND YOU CAN SEE HERE THEY WERE IN THE AREAS OF CONCEPTUAL THINKING, MEMORY, ATTENTION, SPATIAL ABILITY AND VERBAL ABILITIES, AND HE DEVELOPED FOR MANY OF THOSE DOMAINS VERBAL AND NON-VERBAL MEASURES. AND THE MOST DIFFICULT PART OF THIS, THERE'S A LOT OF DIFFICULT PARTS OF WHAT HE DID, BUT ONE OF THE DIFFICULT PARTS, ITEM RESPONSE THEORY REQUIRES YOU TO DEVELOP A LOT OF ITEMS FOR EACH SCALE, AND THEN FIGURE OUT WHICH ONES ARE THE BEST IN EACH OF YOUR GROUPS. HE DID THAT. HE USED TRANSLATION, BACK TRANSLATION IN CULTURALLY AND LINGUISTICALLY APPROPRIATE STAFF TO HELP HIM DEVELOP THOSE ITEMS. AND HE USED ITEM RESPONSE THEORY TO SELECT SMALLER GROUP OF ITEMS FOR FURTHER TESTING, AND HE REQUIRED BOTH MEASURES IN SPANISH AND ENGLISH BE SENSITIVE TO LOW AND HIGH ABILITY. ONE OF THE FIGURES FROM HIS PAPER, HE SHOWED INFORMATION CURVES. THE DASHED LINE IS THE 3MS, IN SPANISH AND ENGLISH, SOLID LINE IS NEW OBJECT NAMING. ON THE Y AXIS THEY CONVEY PRECISION OF MEASUREMENT ALONG WHAT'S ON THE X AXIS, THE ABILITY CONTINUUM FROM HIGH TO LOW. SO YOU CAN SEE THE 3MS LIKE ANY OTHER SCREENING MEASURE THAT WE'RE FAMILIAR WITH HAS HIGH INFORMATION AND LOW ABILITY, BUT TERRIBLE INFORMATION IN THE HIGH ABILITY SO THE GOAL IS TO GET PRETTY MUCH A FLAT LINE HERE WHERE YOU WANT YOUR ITEMS TO GIVE YOU THE MOST INFORMATION YOUR TEST CONSISTING OF DIFFERENT ITEMS TO GIVE YOU THE MOST INFORMATION ALONG THE CONTINUUM, EQUAL ACROSS SPANISH AND ENGLISH MEASURES. WHAT HE HAD TO DO WAS CHOOSE DIFFERENT ITEMS FOR ENGLISH SPEAKERS, DIFFERENT ITEMS FORESPANISH SPEAKERS TO ACHIEVE THE SAME AMOUNT OF PRECISION. COMPUTERIZED ADAPTIVE DING IS BASED ON THE SAME PRINCIPLE, SANDY TALKED ABOUT THIS BEFORE. CAN YOU DO THIS QUICKLY. THIS IS A FANTASTIC APPROACH FOR CROSS CULTURAL ASSESSMENT. THEY USED IT IN THE TOOL BOX. IT'S GREAT FOR SOME COGNITIVE DOMAINS, OTHERS YOU CAN IMAGINE IT DOESN'T MAKE SENSE, TRAIL MAKING OR DRAWING, YOU CAN'T USE IRT FOR THOSE SORTS OF THINGS. BUT IT'S ALSO BEEN USED TO DO PSYCHOSOCIAL ASSESSMENT, MEASURES OF ANXIETY, DEPRESSION AND STRESS WHICH ALSO HAVE CULTURAL LOAD. WE USED -- WE COULDN'T DO WHAT DAN DID, CREATE ITEMS, THE BATTERY IS ALREADY DONE. WE HAD TO SHOW IT WAS VALID AND MEASURING THE SAME THING ACROSS ENGLISH AND SPANISH SPEAKERS. KAREN SIEDLECKI DID THIS TO LOOK AT WHETHER THE STRUCTURE OF THE BATTERY WAS EQUIVALENT ACROSS DIFFERENT ETHNIC AND LANGUAGE GROUPS AND FOUND THAT THIS WAS THE STRUCTURE OF THE BATTERY WE HAD FACTORS FOR MEMORY, LANGUAGE, VISUAL, SPATIAL ABILITY AND SPEED, AND THAT THIS STRUCTURE WAS EQUIVALENT ACROSS OUR SPANISH AND ENGLISH SPEAKERS, SO THAT GIVES US ONE PIECE OF STRONG EVIDENCE THAT OUR MEASURES ARE LOOKING AT THE SAME THING ACROSS THESE DIFFERENT LANGUAGE GROUPS. SO YOU CAN MANAGE WHEN YOU HAVE A DIVERSE COHORT, YOU REALLY HAVE TO THINK ABOUT WHAT YOUR MEASURES MEAN IN THIS COMMUNITY. SO WE'RE ALL ACCUSTOMED TO ASKING PEOPLE ABOUT INCOME, BUT IN DISPARITIES POPULATIONS, SEVERAL RESEARCH STUDIES FOUND THE MORE RELEVANT VARIABLES TO HEALTH ARE THINGS THAT MEASURE WEALTH, ASSETS AND DEBT. SO IT'S HARDER TO ASK ABOUT, IT DOESN'T -- IT'S NOT AS QUICK, BUT IT'S MUCH MORE MEANINGFUL THAN SOMETHING LIKE INCOME. IN OTHER WORDS, THE DOLLAR GOES FURTHER IN SOME COMMUNITIES THAN OTHERS. AND THAT HAS HEALTH IMPLICATIONS. WE FOUND THAT WAS CERTAINLY TRUE WHEN WE BEGAN TO TALK ABOUT QUALITY OF EDUCATION, COMPARED TO YEARS OF EDUCATION, AND I'LL GO OVER THAT A LITTLE BIT MORE IN THE NEXT TALK, BUT EDUCATIONAL EXPERIENCE IS NOT EQUIVALENT ACROSS DIFFERENT ETHNIC AND RACIAL GROUPS, AND THIS HAS IMPLICATIONS FOR COGNITIVE AGING, AND FOR DEMENTIA. ACULTURATION CAN HELP, ANOTHER SIDE IS THE CULTUREATIVE STRESS THAT CAN NEGATIVELY AFFECT HEALTH. WE HAVE TO TAKE BOTH SIDES INTO ACCOUNT. LANGUAGE PRO EFFICIENCY PROFICIENCY AFFECTS OUTCOMES, AND THE WILLINGNESS OF PEOPLE TO COME FORWARD WITH FUNCTIONAL OR MEMORY COMPLAINTS AND THE WAY THEY EXPRESS THEM ARE VERY DIFFERENT SO OUR MEASURES HAVE TO ACCOMMODATE THAT AS WELL. I'M INVOLVED IN STUDIES NOW MORE OFTEN THAT ARE MEASURING PERCEIVED DISCRIMINATION ACROSS DIFFERENT ETHNIC AND RACIAL GROUPS AND IT'S REALLY FASCINATING TO SEE WHAT THE MEASURES MEAN ACROSS DIFFERENT ETHNIC AND RACIAL GROUPS, THE SAME WORD, DISCRIMINATION, DESCRIBES VASTLY DIFFERENT EXPERIENCES ACROSS THESE DISPARITIES POPULATIONS. SO BASICALLY WHAT I'M TRYING TO SAY HERE IS CULTURAL KNOWLEDGE AND COMMUNITY PARTNERS ARE REALLY CRITICAL IN DEVELOPING INSTRUMENTS. SO OUR RECOMMENDATION IS TO IMPROVE TOOLS FOR ASSESSMENT OF DISPARITIES AND RISKS, PRE-CLINICAL DISEASE CHARACTERISTICS, AND COSTS OF ADRD AMONG DISPARITIES POPULATIONS. I ALSO WANT TO SAY IN PROVIDING THE RATIONALE FOR OUR NEXT RECOMMENDATION THAT IN TRIALS THAT ARE LOOKING AT INTERVENTIONS TO REDUCE THE BURDEN OF COGNITIVE IMPAIRMENT IN DEMENTIA, OR TO TREAT SOME OF THE RISK FACTORS FOR DEMENTIA, THESE SOCIAL AND BIOLOGICAL FACTORS MAY MODERATE THE OUTCOME, SO THIS IS DATA FROM THE ACTIVE TRIAL WHERE AFRICAN-AMERICANS AND WHITES WERE INCLUDED. THIS WAS AN INTERVENTION THAT SOUGHT TO IMPROVE COGNITIVE FUNCTION BY GIVING PEOPLE COMPUTER-BASED TASKS AND HAVING THEM PRACTICE THEM OVER AND OVER AGAIN, AND ONE OF THE INTERVENTIONS WAS A REASONING INTERVENTION. AFRICAN-AMERICANS DID NOT BENEFIT FROM TRAINING AS MUCH AS WHITES DID IN THE ACTIVE TRIAL. THAT RACIAL DIFFERENCE IN BENEFIT WAS MEDIATED BY EXTERNAL LOCUS OF CONTROL. IF YOU HAVE MORE EXTERNAL LOCUS OF CONTROL THAT'S WORSE. IT'S ASSOCIATESSED WITH WORSE HEALTH OUTCOMES. AFRICAN-AMERICANS WHO EXPERIENCED MORE DISCRIMINATION HAVE A HIGHER EXTERNAL LOCUS OF CONTROL, THE BELIEF THAT YOU DON'T HAVE AS MUCH CONTROL OVER YOUR CIRCUMSTANCES. SO IN OTHER WORDS WHAT I'M SAYING HERE IS SOCIAL VARIABLES SHOULD BE MEASURED WITHIN OUR INTERVENTIONS BECAUSE THEY MAY MODERATE BENEFIT. HERE ARE -- I LIST HERE POTENTIAL SOCIAL MECHANISMS OF DISPARITIES, I'LL TALK MORE ABOUT THOSE IN A MINUTE, BUT YOU CAN SEE HOW THEY REALLY SPAN THE RANGE OF CIRCUMSTANCES THAT DISPARITIES POPULATIONS LIVE IN AND SOME OF THE EXPERIENCES THEY MAY HAVE. SO OUR FIFTH RECOMMENDATION IS INCREASE UTILIZATION OF CULTURALLY AND LINGUISTICALLY APPROPRIATE TOOLS WITHIN ONGOING AND NEWLY GENERATED STUDIES AND VASCULAR HEALTHS INTERVENTION TRIALS, DECIDE WHETHER INTERVENTIONS THEMSELVES ARE CULTURALLY SENSITIVE, ASSESS A BROAD RANGE OF FACTORS, AND IT WOULD BE GREAT IF WE HAD A REPOSITORY OF ASSESSMENT TOOLS THAT HAVE ALREADY BEEN VALIDATED FOR USE AMONG DISPARITIES POPULATIONS. THANK YOU. [APPLAUSE] I'M GOING TO RESERVE THE REST OF MY TIME TO THE NEXT SPEAKER, WHO IS ME [LAUGHTER] OKAY. SO I'M GOING TO TALK ABOUT -- THIS IS THE PARTNER TALK TO SID'S, WHERE HE TALK ABOUT THE BIOLOGICAL MECHANISMS OF ALZHEIMER'SS DISEASE AND ADRD DISPARITIES. I'M GOING TO BACK TO THE TITLE SLIDE BECAUSE VIRGINIA AND MARIA AND I COLLABORATED ON THIS TALK. KNOWN HOW I ENDED UP BEING SPEAKER BUT I'M HAPPY TO DO IT AND HOPE THAT I REPRESENT THEIR WORK AND THEIR CONTRIBUTION WELL BECAUSE IT WAS A PLEASURE TO WORK WITH THEM ON THIS. WE MADE PROGRESS LOOKING AT SOCIAL MECHANISMS OF DISPARITIES. I WILL GO OVER SOME EVIDENCE THAT SUPPORTS CAUSAL ASSOCIATION BETWEEN SOCIAL FACTORS AND ALZHEIMER'S'S DISEASE AND ADRD, MOSTLY ALZHEIMER'S DISEASE. I WILL GO OVER THE MODIFIABILITY OF POTENTIAL MECHANISMS OF DISPARITIES. I WANT AS I GO THROUGH THE FACTORS, NOTICE HOW EACH IS A MODIFIABLE MECHANISM AND I'LL DISCUSS WAYS TO DOES GAPS IN KNOWLEDGE ABOUT CONTRIBUTION OF SOCIAL FACTORS TO DISPARITIES IN ADRD. HERE IS MY LIST OF SOCIAL MECHANISMS AGAIN. WE KNOW FROM SEVERAL STUDIES, THIS IS JUST A COUPLE OF EXAMPLES THAT SOCIOECONOMIC STATUS AND DISPARITIES IN SOCIOECONOMIC STATUS ARE RELATED TO INCIDENT DEMENTIA. SO IN ONE STUDY THAT DEFINES PSYCHOSOCIAL SOCIOECONOMIC PRECARIOUSNESS, THIS CONDITION CONFERRED 36% GREATER RISK OF DEVELOPING DEMENTIA OVER 25 YEARS OF FOLLOW-UP. AND IN THE HEALTH ABC STUDY, THIS IS CHRISTINE'S GROUP, FOUND THAT SOCIOECONOMIC DISPARITIES CONTRIBUTED TO HIGHER RATES OF DEMENTIA IN AFRICAN-AMERICANS. AND MARIA LOOKED AT CDC DATA WITH SHE RELATED PLACE OF BIRTH TO DEMENTIA MORTALITY, AND HERE I WANT YOU JUST TO NOTICE THAT THE DARKER COLORS WHICH REPRESENT HIGHER MORTALITY RELATED TO DEMENTIA ARE IN THE STROKE BELT. THERE'S GEOGRAPHIC CONTRIBUTIONS TO THESE PATTERNS THAT WE NEED TO UNDERSTAND BETTER. EVEN WITHIN STATE WE CAN USE COUNTY LEVEL DATA TO UNDERSTAND SOME OF THE EARLY LIFE MECHANISMS FOR LATER LIFE COGNITIVE DYSFUNCTION. SO THIS IS ALABAMA. AND I LEARNED FROM THIS SLIDE WHEN VIRGINIA GAVE IT TO ME THAT IT IS THE HEART OF THE DEEP SOUTH, I DIDN'T KNOW THAT BEFORE. BUT THE ORANGE BLOB IN THE MIDDLE IS WHERE BIRMINGHAM IS, AND IT INCLUDES ONE OF THE NATION'S TENTH WEALTHIEST COMMUNITIES AND YET THERE ARE MANY COMMUNITIES WITHIN ALABAMA THAT ARE VERY POOR. PEOPLE LIVING IN POVERTY, EVEN WITHOUT ADEQUATE PLUMBING, SO IT HAS THE LOWEST RANK IN 50 STATES AMONG CAREGIVER SUPPORT. YOU CAN EXPLOIT THIS COUNTY LEVEL DATA TO TELL US MORE ABOUT THE EARLY LIFE INFLUENCES ON DEMENTIA SO MICHAEL CROWE A WHILE BACK LOOKED AT COUNTY LEVEL DATA ON SCHOOL QUALITY, HISTORICAL VARIABLES, TEACHER-STUDENT RATIO, SCHOOL YEAR LENGTH AND EXPENDITURES. TWO OF THOSE THREE VARIABLES WERE ASSOCIATED WITH BASELINE COGNITIVE FUNCTION IN THE LONGITUDINAL STUDY. AND THIS WAS INDEPENDENT OF OTHER FACTORS THAT WERE OBVIOUSLY RELATED TO WHERE YOU WERE BORN AND RAISED LIKE EDUCATION LEVEL, INCOME, READING ABILITY, VASCULAR RISK FACTORS, SOMETHING ABOUT WHERE YOU GREW UP IN ALABAMA THAT MAKES A BIG DIFFERENCE IN YOUR COGNITIVE LEVEL WHEN YOU REACH THE AGE OF 65. BUT THIS WAS NOT ASSOCIATED WITH CHANGE IN COGNITIVE FUNCTION, ONLY LEVEL. I THINK THAT WE'RE ALL INTERESTED IN COGNITIVE DECLINE, AND THAT IS IMPORTANT, I THINK THAT UNDERSTANDING DIFFERENCES IN THE RELATIONSHIP OF THESE VARIABLES WITH LEVEL AND CHANGE IS CRITICAL. MICHAEL ALSO FOUND THE ASSOCIATIONS OF THESE SCHOOL-BASED HISTORICAL VARIABLES WERE STRONGER IN THOSE WITH LOWER LEVELS OF EDUCATION. AND SO AS I SAID BEFORE, EDUCATIONAL ATTAIN. IGNORES TREMENDOUS VARIABILITY IN QUALITY SCHOOLING, HAS A LOT TO DO WITH DISPARITIES BY RACE, GEOGRAPHIC REGION AND SECULAR CHANGES IN RISK OF COGNITIVE DECLINE AND DEMENTIA THAT WE'RE SEEING. THESE ARE DATA I'VE SHOWN IN THE ROOM A COUPLE OF TIMES BUT THIS IS LENGTH OF SCHOOL YEAR IN DIFFERENT STATES ACROSS THE YEARS FROM 1919 TO 1951. NEW YORK IS THE BLACK ONE ON TOP, AND THE PURPLE ONE AT THE BOTTOM IS SOUTH CAROLINA FOR AFRICAN-AMERICANS IN SEGREGATED SCHOOLS, SO ONE YEAR SCHOOL IN SOUTH CAROLINA MEANT YOU WERE GOING -- YOU WERE IN THAT CLASSROOM, IF YOU ATTENDED, YOU WERE IN THE CLASSROOM FOR HALF THE TIME AS YOUR COLLEAGUING IN NEW YORK, AND THE LENGTH OF SCHOOL YEAR WAS SHORTER FOR WHITES IN SOUTH CAROLINA AS WELL BUT NOT QUITE AS SHORT AS IT WAS FOR BLACKS. WE'RE TALKING ABOUT COMPLETELY DIFFERENT THINGS WHEN WE SAY 8 YEARS OF SCHOOL IN THE SOUTH VERSUS 8 YEARS OF SCHOOL IN THE NORTH, 8 YEARS OF SCHOOL FOR A BLACK VERSUS WHITE, AFRICAN-AMERICANS IN SEGREGATED SCHOOLS MUCH MORE LIKELY TO ATTEND ONE-ROOM SCHOOLS AND THIS MAKES A BIG DIFFERENCE FOR COGNITIVE OUTCOMES. SAM, MARIA, CHRIS AND I DID A STUDY ON LOOKING AT COGNITIVE DISPARITIES USING HEALTH AND RETIREMENT STUDY DATA AND FOUND THAT THE DISPARITIES, THE SIZE OF RACIAL DISPARITIES BETWEEN BLACKS AND WHITES DIFFERED DEPENDING ON BIRTH PLACE, AND IT ALSO DIFFERED WITH RESPECT TO COGNITIVE DOMAINS. YOU CAN SEE THAT THE BARS HERE ON THE MEMORY WHICH IS IN THE LOWER LEFT-HAND CORNER, A LITTLE BIT SMALLER THAN THE BARS FOR VOCABULARY WHICH IS JUST TO ITS RIGHT OR OVERCOGNITIVE OVERALL COGNITIVE STUDIES. GREATER THAN FOR PEOPLE BORN AND RAISED IN THE NORTH, REGARDLESS OF WHERE THEY LIVE NOW. AND THOROUGH IMPORTANT STEWEDY THAT USED SOCIAL VARIABLES TO GET AT HEALTH DISPARITIES IS JUST COMING OUT. IT'S AGAIN MARIA, JESS, STEPHAN AND JAKE WHO LOOKED AT AFRICAN ANCESTRY IN HEALTH AND RETIREMENT SURVEY, RELATIONSHIP TO HYPERTENSION RISK. I WILL TELL YOU WHAT IT IS THEY MEAN. THEY LOOKED AT -- THEY COMPARED RESPONDENTS IN HRS WITH HIGHEST QUARTILE OF AFRICAN ANCESTRY, 8 PERCENTAGE POINTS HIGHER IN PREVALENCE HYPERTENSION, BUT AFTER ADJUSTED FOR CHILDHOOD AND INCOME, IT WAS 1/3. WE LOOK AT GENETIC ANCESTRY, WE NEED TO REMEMBER THIS IS RELATED TO SOCIAL DISADVANTAGE AND THAT THIS MAY BE A REALLY GOOD MARKER FOR SOCIAL DISADVANTAGE AND NOT NECESSARILY SAYING ANYTHING ABOUT GENETIC CAUSES OR GENETIC EXPLANATION FOR DISPARITY. THIS MODEL IS BASICALLY HERE TO ASK -- TO REMIND ME TO TELL YOU ABOUT THE IMPORTANCE MUCH A LIFE COURSE APPROACH IN STUDYING SOCIAL DETERMINANTS OF COGNITIVE FUNCTION AND DEMENTIA THAT THERE'S A CUMULATIVE PATHWAY ALONG THE LIFE COURSE BEGINNING WITH EARLY LIFE FACTORS, GOING INTO MID-LIFE FACTORS, AND ENDING IN LATER LIFE FACTORS, AND THESE ARE RISK AND RESILIENCY FACTORS THAT INTERACT AT EACH OF THESE LIFE STAGES. THEY INCLUDE GEOGRAPHICS, SOCIOECONOMIC, PSYCHOSOCIAL, BIOLOGICAL AND GENETIC CAUSES THAT INTERACT WITH EACH OTHER, AND IT'S IMPORTANT TO DRAW AND TEST A MODEL WITH DIFFERENT COHORTS BECAUSE WE WANT TO KNOW WHEN PREVENTION IS POSSIBLE AND WHEN THE MOST EFFECTIVE TIMES ARE TO REDUCE DISPARITIES. WE NEED STUDIES DESIGNED TO ELUCIDATE CAUSAL MECHANISMS. ONE GREAT WAY TO GET AT THAT ARE NATURAL EXPERIMENTS USING INSTRUMENTAL VARIABLES. SO FOR EXAMPLE WHEN COMPULSORY SCHOOL LAWS CHANGED, MARIA EXPLOITED THIS TO LOOK AT THE RESULT OF THAT POLICY CHANGE ON LATER LIFE COGNITIVE FUNCTION, HEALTH AND RETIREMENT SURVEY, FOUND AN EFFECT OF THESE POLICY CHANGES BUT THESE ARE REALLY HARD TO FIND. SO IN THE MEANTIME WE CAN USE GREAT LONGITUDINAL DATA AS LONG AS WE MEASURE POTENTIAL SOCIAL MEDIATORS AND MODERATORS. WE NEED LIFE CORE STUDIES WITH VALID INFORMATION ABOUT EARLY LIFE CONDITIONS, WE CAN ASK ABOUT EARLY LIFE CONDITIONS WHEN PEOPLE ARE OLDER. WE JUST TO MAKE SURE WE'RE DOING THAT IN A VALID WAY. AND WE NEED TO REMEMBER THAT WE CAN BUILD INTO OUR ANALYSES ABOUT MECHANISMS, ABOUT MEDIATORS, WAYS TO EVALUATE THE POTENTIAL IMPACT OF UNMEASURED CONFOUNDERS AND THERE'S SOME GREAT TOOLS, BIOSTATISTICAL TOOLS TO DO THAT NOW. WE NEED LONGITUDINAL STUDIES WITH BASELINE PRIOR TO DEVELOPMENT OF DEMENTIA AND REPEAT COGNITIVE ASSESSMENT. THERE ARE INTERVENTIONS GOING ON, ON SOCIAL FACTORS. IT WOULD BE GREAT IF WE COULD IMBED COGNITIVE MEASURES, LARGE SCALE THINGS LIKE THE EARNED INCOME CREDIT OR OTHER NATIONAL POLICIES THAT PUT MORE MONEY IN THE POCKETS OF PEOPLE, I KNOW KIM NOBLE AT COLUMBIA UNIVERSITY IS PUTTING MORE MONEY IN THE POCKETS OF WOMEN WHO ARE MOTHERS AND TESTING EFFECT ON THE BRAIN DEVELOPMENT OF THEIR CHILDREN AND SO WE NEED TO GET COGNITIVE OUTCOMES IN THESE KINDS OF STUDIES. THE MOVING TO OPPORTUNITY STUDY IS ONE EXAMPLE WHERE THEY IMPROVED NEIGHBORHOOD AND HOUSEHOLD AND LOOKED AT LATER LIFE OUTCOMES, COGNITION WAS NOT ONE OF THOSE. AND THERE'S SOME REALLY COMPELLING RESEARCH NOW ON REDUCING IMPACT OF STEREOTYPE THREAD, ADMINISTRATION VALUES AFFIRMATION. IT'S REALLY VERY EFFECTIVE IN SCHOOL AGE KIDS AND IN ADULTS AND WE SHOULD LOOK AT THE EFFECT ON COGNITIVE FUNCTION IN OLDER PEOPLE. OKAY. AND FINALLY, THERE IS A FRAMEWORK THAT JUST CAME OUT IN AN IOM REPORT THIS MONTH, FROM THE NATIONAL ACADEMY OF SCIENCES FOR EDUCATING HEALTH PROFESSIONALS TO ADDRESS THE SOCIAL DETERMINANTS OF HEALTH. AND WE KNOW THAT HISTORICALLY THERE'S A GAP BETWEEN MEDICAL CARE AND RESEARCH ON SOCIAL DETERMINANTS OF HEALTH, BUT THERE'S AN INCREASED RECOGNITION OF THE INTERPLAY BETWEEN THE TWO. THE CLINICAL SETTING HAS TO BE AWARE OF SOCIAL DETERMINANTS OF HEALTH TO BETTER TREAT PATIENTS AND TO KEEP THE COMMUNITY HEALTHY, SO THIS FRAMEWORK AND IT'S A GREAT DOCUMENT, I RECOMMEND IT, IT'S AVAILABLE ONLINE, THAT ENCOURAGES INFORMATION ABOUT SOCIAL DETERMINANTS OF HEALTH TO BE PASSED ON EARLY IN TRAINING IN IDENTIFICATION OF THE HEALTH CARE WORKFORCE AND THE COLLECTION OF SOCIAL DETERMINANT DATA IN THE MEDICAL RECORD INCLUDING HELPING US UNDERSTAND HOW COMMUNITY PARTNERSHIPS CAN HELP REDUCE DISPARITIES. THANK YOU. [APPLAUSE] >> VIRGINIA WADLEY IS ON HER WAY UP TO DISCUSS COMMUNITY PARTNERSHIPS, RECRUITMENT AND RETENTION. I WANTED TO SAY WHEN WE WERE HERE IN 2013, THERE WAS A BIG EMPHASIS ON RECRUITMENT WITHIN THE DISPARITIES GROUP. AND WE FEEL THAT THAT IS INCREDIBLY IMPORTANT BUT WE ALSO WANTED TO EMPHASIZE THE SCIENCE OF DISPARITIES, NOT JUST THE RECRUITMENT BARRIERS. THERE'S A SCIENCE OF RECRUITMENT AS WELL, AND I LOOK FORWARD TO HEARING MORE ABOUT THAT FROM VIRGINIA. >> THANK YOU, JEN. I'D LIKE TO LOOK AT EXAMPLES OF INCLUSION OF COMMUNITIES AFFECTED BY HEALTH DISPARITIES IN ALZHEIMER'S DISEASE AND ADRD RESEARCH, REVIEW BARRIERS TO INCLUES, LOOK AT EVIDENCE-BASED GUIDELINES ON COMMUNITY PARTNERSHIPS, RECRUITMENT AND RETENTION OF DISPARITIES POPULATIONS, OUTLINE PLANS AND RECOMMENDATIONS TO ADDRESS GAPS BY ESTABLISHING A HEALTH DISPARITIES TASK FORCE THAT'S OUR FIRST RECOMMENDATION, AND DEVELOPING COMMUNITY PARTNERSHIPS AS OUR SECOND RECOMMENDATION. AND THIS IS GOING TO ECHO WHAT SID SAID AND WHAT SAID AND WHAT JEN HAS SAID, BUT WE DON'T KNOW MUCH ABOUT ADRDs, AND COMMUNITIES AFFECTED BY DISPARITY, LEWY BODY DISEASE, VASCULAR, MIXED ETIOLOGY DEMENTIA, NOT THAT MUCH ABOUT A.D. EITHER IN THESE POPULATIONS. SOME RESEARCH HAS SHOWN IN SPITE OF THE OBSTACLES TO RESEARCH PARTICIPATION AND THE FEARS THAT SOME DISPARITIES POPULATIONS HAVE FOR GOOD REASON, RESEARCH DOES SUGGEST HISPANIC AND BLACK POPULATIONS REPORT BEING INTERESTED IN TRIAL PARTICIPATION, BUT THEY WERE NEITHER ASKED NOR ELIGIBLE, AND WHY IS THAT? IT'S REALLY BECAUSE SO MUCH OF OUR RESEARCH IN OUR FIELD HAS BEEN CLINIC BASED. FOR EXAMPLE, A GREAT STUDY THAT WE'VE HEARD ABOUT TODAY, ADNI, IS ENTERING PHASE III. THEY ENROLLED 822 PARTICIPANTS INITIALLY, LATER THERE WOULD BE DRUG DISCOVERY TRIALS WHICH WOULD REQUIRE PURE CLEAN HOMOGENOUS SAMPLES. SAMPLES TEND TO BE HIGHLY EDUCATED IN THIS STUDY, 61% WAS COLLEGE GRADUATES, MOSTLY NON-HISPANIC WHITE, BECAUSE OF THE NEED FOR PURE SAMPLES OR AT LEAST WHAT WE THOUGHT WERE PURE SAMPLES, COMORBIDITIES EXCLUDED, AFFECTING DISPARITIES GROUPS, STROKE AND HISTORIES OF STROKE AND SUBSTANCE ABUSE, ALSO REQUIREMENT OF A STUDY PARTNER CAN NEGATIVELY AFFECT THE RECRUITMENT OF DISPARITIES POPULATIONS WHO ARE MORE LIKELY TO NOT HAVE A PARTNER. THERE ARE PARTICIPANTS FROM 29 NIA-FUNDED ALZHEIMER'S DISEASE CENTERS SINCE 1999, 25,000, 14% AFRICAN-AMERICAN, 2% ASIAN, LESS THAN 1% AMERICAN INDIAN/NATIVE ALASKAN. FOCUS IS ALZHEIMER'S DISEASE BUT SOME CENTERS COLLECT DATA ON ADRD, VASCULAR DEMENTIA, LEWY BODY DEMENTIA AND FTD AND HAVE IDENTIFIED OVER 1000 CLINICAL FTD CASES NOT TOPSY IN THE NACC SINCE THE UNIFORM DATA SET WAS INTRODUCED, 95% OF THOSE CASES ARE WHITE BUT THERE ARE VARIATIONS IN RECRUITMENT METHODS ACROSS THE ALZHEIMER'S DISEASE CENTERS. SOME ARE CLINICAL REFERRALS. SOME ARE COMMUNITY REFERRALS, SELF REFERRALS, SOME ARE RECRUITED THROUGH COMMUNITY EDUCATION AND OUTREACH EFFORTS, AND SOME -- MOST ALZHEIMER'S DISEASE CENTERS ALSO RECRUIT COGNITIVELY NORMAL CONTROLS WHO TEND TO BE HIGHLY EDUCATED. SO, YOU KNOW, THIS JUST -- AND THEN ALSO THE AUTOPSY REQUIREMENT OF SOME CENTERS HAS BEEN A NOTORIOUS BARRIER FOR MINORITIES, FOR PEOPLE OF LESS THAN COLLEGE EDUCATION ON ARE ANY COLLEGE EDUCATION, RESIDENTS OF THE SOUTH, DEEP SOUTH WHERE I LIVE. THE NACC DATA DON'T LEND THEMSELVES TO ESTIMATES OF PREVALENCE OR INCIDENCE JUST LIKE MARIA POINTED OUT OF DEMENTIA OF VARIOUS SUBTYPES. THAT'S ONE OF THE THINGS WE HAVE TO ADDRESS. SO SOME OF THE BARRIERS TO RECRUITMENT OF DISPARITIES COMMUNITIES INCLUDE INADEQUATE CONNECTION WITH HEALTH SYSTEMS OF PEOPLE WHO ARE IMPOVERISHED, ILLITERATE, MINORITY GROUPS, AND THEN THE LACK ON THE PART OF THE RESEARCHERS IN REALLY ENGAGING IN COMMUNITY BASED PARTICIPATORY RESEARCH, THERE'S A LACK OF ENGAGEMENT AND PARTNERSHIP BETWEEN RESEARCHERS AND COMMUNITIES AFFECTED BY DISPARITIES. THE DISTRUST OF RESEARCH THAT'S A LEGACY OF THE TUSKEGEE SYPHILIS STUDY THAT I'M SURE YOU ALL KNOW ABOUT, BUT JUST AS A REMINDER THIS STUDY WAS IN TUSKEGEE, ALABAMA, SO IT AFFECTS OUR STATE BUT IT OF COURSE HAS INTERNATIONAL EFFECTS ON ETHICS. WHERE AFRICAN-AMERICAN MEN IN MACON COUNTY, ALABAMA, PRIMARILY SHARE CROPPERS, IMPOVERISHED, ALSO TO NO SCHOOLING, RECRUITED BY THE U.S. GOVERNMENT-FUNDED RESEARCH ON THE NATURAL HISTORY OF SYPHILIS, BEGAN IN 1932, DID NOT END UNTIL 1972, AND IN 1947 WHEN PENICILLIN BECAME THE STANDARD OF CARE THEY WERE NOT TOLD ABOUT AVAILABILITY, COULD NOT READ ABOUT AVAILABILITY OF PENICILLIN AND WERE NOT GIVEN TREATMENT, RESULTING IN 299 MEN WHO HAD SYPHILIS AT ENROLLMENT, SO THEY DIED THE NATURAL COURSE OF SYPHILIS IN MOST OF THOSE CASES. THEIR SEXUAL PARTNERS WERE AFFECTED. THERE WERE 19 CHILDREN BORN WITH SYPHILIS BECAUSE OF THE LACK OF TREATMENT. IT WAS A TRAVESTY THAT'S CHANGED A LOT OF THINGS IN HUMAN SUBJECTS PROTECTION, BUT THIS IS SOMETHING THAT LIVES IN THE MINDS OF THE COMMUNITIES THAT HAVE BEEN AFFECTED BY THIS TYPE OF GROSS TRAVESTY. ANOTHER BARRIER IS JUST ALTERNATIVE HEALTH BELIEFS. THERE ARE DIFFERENCES IN WHAT SYMPTOMS ARE ACCEPTED IT'S AS NORMAL OR NOT NORMAL. SOMEONE EARLIER AT THE MICROPHONE SAID I HAVE MAJOR NEUROCOGNITIVE DISORDER AND NOT DEMENTIA. WE HEAR, WELL, NO, HE HAS DEMENTIA BUT YOU DOESN'T HAVE ALZHEIMER'S DISEASE. THE CONNOTATIONS OF THESE WORDS DO MATTER AND THEY ARE DIFFERENT IN DIFFERENT POPULATIONS. ALSO THE RELIGIOUS DIFFERENCES. YOU KNOW, LIVING IN THE SOUTHEASTERN STROKE BELT IT'S ALSO THE BIBLE BELT, AND THERE ARE A LOT OF RELIGIOUS BARRIERS TO AUTOPSY, FOR EXAMPLE. SO THERE WAS A NICE STUDY THIS BOISE STUDY THAT CAME OUT, WILL MY SOUL GO TO HEAVEN IF THEY TAKE MY BRAIN? THAT WAS A PREVALENT BELIEF SYSTEM ACROSS ETHNIC GROUPS, SO THAT'S ANOTHER THING WE HAVE TO TAKE INTO ACCOUNT WHEN WE'RE REACHING OUT TO COMMUNITIES. DAVID KATZ PUBLISHED THIS REALLY NICE SUMMARY OF THINGS TO DO IF YOU'RE GOING TO ATTEMPT TO DO COMMUNITY-BASED PARTICIPATORY RESEARCH. IT TAKES TIME AND IT TAKES MONEY. SO YOU BEGIN WITH QUESTIONS RATHER THAN SOLUTIONS. YOU DON'T GO IN SAYING YOU HAVE SOMETHING TO TEACH. YOU ALSO HAVE SOMETHING TO LEARN. YOU HAVE TO LEARN WHAT MATTERS TO THE COMMUNITY. RECOGNIZE THE GAP BETWEEN MEASURING DIFFERENCES IN DISPARITIES GROUPS, AND MAKING A DIFFERENCE IN THOSE GROUPS. THAT'S, YOU KNOW, VERY IMPORTANT. SHARING CONTROL OVER FINANCIAL RESOURCES AND DECISIONS, YOU KNOW, WHAT MATTERS AND WHERE SHOULD THE MONEY BE INVESTED. AND COMMIT TO A WORKING RELATIONSHIP THAT'S BUILT ON TRUST AND EQUITY. THERE WERE UNIVERSITY OF MARYLAND AND SEVERAL PARTNER ORGANIZATIONS IN THEIR AREA CONDUCTED 20 FOCUS GROUPS. THEY CAME OUT WITH SOME SIMILAR RECOMMENDATIONS. THIS WAS 160 PARTICIPANTS THAT THEY INCLUDED IN THESE 20 FOCUS GROUPS, THEY INCLUDED LOW INCOME AFRICAN-AMERICAN PATIENTS, LOW INCOME BILINGUAL SPANISH-ENGLISH SPEAKING PATIENTS, PATIENTS FROM AN AFRICAN-AMERICAN CHURCH, BLIND AND VISUALLY IMPATIENT PATIENTS, DEAF AND HEARING IMPAIRED, WITH MOBILITY PAIRMENTS, CAREGIVERS AND PHYSICIANS AND NURSES WHO TREAT HARD TO REACH PATIENTS. SO TRYING TO GET AT ALL THE GROUPS THAT WOULD BE AFFECT THE BY RESEARCH AND THEIR RECOMMENDATIONS WERE TO ALLOW A PERIOD OF PRE-ENGAGEMENT BEFORE RECRUITING PARTNERS AND PARTICIPANTS, INVOLVE THE FULL SPECTRUM OF THOSE AFFECTED BY RESEARCH, BRING THE RESEARCH WHERE THE PEOPLE LIVE, KEEP THE PARTICIPANTS POSTED DURING RESEARCH, PROVIDE A SUMMARY OF FINDINGS THEY SUGGESTED AN END OF STUDY CELEBRATION, AND GIVE BACK TO THE COMMUNITY. RESEARCHERS, THERE WAS A STUDY BASED ON 93 STROKE RESEARCHERS WHO WERE INTERVIEWED AND SURVEYED REGARDING RECRUITMENT AND RETENTION OF UNDERREPRESENTED GROUPS, AND RESEARCH, AND THEIR BEST PRACTICES INCLUDED TRAINING RESEARCH AND RESEARCH STAFF IN CULTURAL COMPETENCY AND COMMUNICATION, DEVELOPING AND FOSTERING COMMUNITY PARTNERSHIPS AND CONSULTING COMMUNITY PARTNERS ABOUT TRIAL DESIGN, THIS IS A THEME THAT, YOU KNOW, PARTNERSHIP AND EQUITY IN ALL PHASES OF RESEARCH AND THEN REALISTIC BUDGETING WITH THIS LITTLE CARTOON SAYING THIS PERSON WANTS TO FIND OUT ONCE AND FOR ALL WHETHER THERE'S TRUTH IN THE BELIEF MONEY CAN'T BUY HAPPINESS. I THINK A MODEL OF EFFECTIVENESS HAS BEEN CARRIED OUT AT RUSH UNIVERSITY AND OTHER STUDIES, SO THEY HAVE RATHER THAN JUST MEETING THE THRESHOLD OF A REPRESENTATIVE SAMPLE WHICH IN THE CHICAGO AREA WOULD BE ROUGHLY 20% OF PARTICIPANTS, THEY HAVE OVERSAMPLED WHICH I THINK IS SOMETHING THAT'S REALLY IMPORTANT FOR POWER AND FOR A LOT OF OTHER REASONS. SO THEY HAVE OVER A THOUSAND MINORITY PARTICIPANTS IN ADC AS OF 2012, 350 COGNITIVELY NORMAL OLDER ADULTS, 94% AFRICAN-AMERICANS, A MINORITY RESEARCH STUDY WITH 450 AFRICAN-AMERICAN ADULTS AND TWO OTHERS. HOW DO THEY DO IT? DR. LISA BARNES, WHO IS HERE, WAS QUOTED AS SAYING GIVE BEFORE YOU GO ASKING FOR SOMETHING AND EMPHASIZED ONGOING ENGAGEMENT WITH THE COMMUNITY, ESTABLISHING A RELATIONSHIP BEFORE RECRUITMENT, ENGAGING COMMUNITY LEADERS IN ALL PHASES OF THE RESEARCH, AND RECRUITING WHEN READINESS IS ESTABLISHED. RETAINING PARTICIPANTS ALSO HUGELY IMPORTANT AND A BIG CHALLENGE, TIED TO THE NEEDS OF SPECIFIC COMMUNITIES. SO FOR EXAMPLE AT RUSH TRANSPORTATION IS ONE OF THE BARRIERS TO CONTINUING PARTICIPATION AND RETENTION. THEY PROVIDE ANNUAL EXAMS IN THE PARTICIPANTS' HOMES, THEY HAVE A MULTI-DISCIPLINARY TEAM THAT GOES TO THEIR HOMES TO GATHER DATA AT THEIR ANNUAL VISITS. FOR IMAGING THEY SEND A CAR AND PROVIDE A SNACK ON THE WAY. IMAGING IN THEIR COMMUNITY HAS BEEN VIEWED AS A SERVICE BY PEOPLE WITH LIMITED ACCESS TO HEALTH CARE, UNLIKE SOME OF THE RESEARCH THAT'S FOUND IMAGING TO BE ONE OF THE THINGS THAT'S NOT UNDERSTOOD AND TRUSTED. AND THEN THEY TOO EMPHASIZE YOU PRESENT THIS STUDY RESULT TO THE COMMUNITY, VERY IMPORTANT FOR LEADERSHIP OF THE STUDY TO GO BACK AND PRESENT RESULTS AND CONTINUE ENGAGEMENT WITH COMMUNITY GROUPS. AND DAVID BENNETT WENT OVER AND SO DID SID SOME OF THE IMPORTANT FINDINGS THAT ARE MADE POSSIBLE BY INCLUSION OF DISPARITIES GROUP INCLUDING THESE DIFFERENCES IN MIXED ETIOLOGY IN PEOPLE WITH CLINICAL A.D. AT ALWAYS. TWO NATIONAL STUDIES THAT HAVE BEEN SUCCESSFUL INCLUDING DISPARITIES POPULATION, THE SPRINT STUDY ON THE LEFT WHICH SID REFERRED TO HAS OVER 100 CLINICS IN THE UNITED STATES AND PUERTO RICO, THEY HAVE BEEN ABLE TO -- THEY'VE GOT 9361 PARTICIPANTS, 30% AFRICAN-AMERICAN, 1% ASIAN, 58% WHITE, 11% HISPANIC, AND SPRINT WAS DESIGNED TO SEE IF INTENSIVE BLOOD PRESSURE CONTROL WAS PROTECTIVE AGAINST CARDIOVASCULAR INCIDENT DISEASE AND MORTALITY, THAT QUESTION HAS BEEN ANSWERED AND THE DATA SAFETY MONITORING BOARD STOPPED THE STUDY EARLY BECAUSE IT WAS SUCH A POSITIVE EFFECT OF LOWERING TO 120 SYSTOLIC ACROSS RACIAL/ETHNIC AND AGE GROUPS. BUT WE HAVE NOT YET ANSWERED THE QUESTION ABOUT INCIDENT, COGNITIVE IMPAIRMENT AND COGNITIVE DECLINE AND INCIDENT DEMENTIA WHICH IS ONGOING, NOR HAVE WE ADDRESSED THE PROGRESSION OF CHRONIC KIDNEY DISEASE. THE OTHER -- TIME TO STOP? OKAY. 30 SECONDS. OKAY. AND THEN REGARDS RACIAL AND ETHNIC -- EXCUSE ME, RACIAL AND GEOGRAPHIC DIFFERENCE IN STROKE OVER 30,000 PEOPLE, 42% AFRICAN-AMERICAN, THE REST NON-HISPANIC WHITE, AND LOOKING PROSPECTIVELY AS INCIDENT STROKE, COGNITIVE DECLINE, WE'LL BE GETTING AT INCIDENT DEMENTIA, THAT'S BEEN GOING ON 13 YEARS, AMAZING RESOURCE, THAT'S AN EPI STUDY. FIRST RECOMMENDATION TO GENERATE A TASK FORCE TO HELP US PROVIDE GUIDANCE IN MEETING THESE GOALS AND THE SECOND IS TO DEVELOP NOVEL AND ALREADY EVIDENCE-BASED COMMUNITY ENGAGEMENT AND OUTREACH METHODS. THANKS. >> THANK YOU, VIRGINIA. STAY UP HERE. VIRGINIA, STAY UP HERE BECAUSE NOW IT'S TIME FOR OUR OPEN MIC. SO COME ON UP, EVERYONE FROM THE DISPARITIES COMMITTEE ASK YOUR QUESTION WHILE PEOPLE ARE MAKING THEIR WAY UP. >> I'M JERRY SHOTTEN FROM PITH PITTSBURGH. I WANT TO CONGRATULATE YOU ON THE FASCINATING AND IN MANY WAYS DEPLORABLE EVIDENCE YOU HAVE. ONE POINT THAT I DIDN'T HEAR EXPLICITLY DISCUSSED WAS ADRD SCIENTISTS AND PRACTITIONERS FROM DIVERSE COMMUNITIES, YOU KNOW, SO OFTEN WE FEEL MOST COMFORTABLE WITH PEOPLE WHO ARE SIMILAR TO US AND IN FACT IF YOU LOOK AT THIS ROOM, IT'S VERY MUCH LIKE THE P.I.s OF THE NIH. IT'S STALE PALE MALES, OLD WHITE GUYS. IF YOU GO OUTSIDE YOU SEE REAL AMERICA, DIFFERENT THAN HERE. IN MANY WAYS WE NEED OUR PRACTITIONERS, CLINICIANS, RESEARCHERS REPRESENTATIVE OF THE FULL AND RICH DIVERSITY OF AMERICA AND SO I THINK WE HAVE TO HAVE PROGRAMS TO RECRUIT, TO MENTOR AND TO RETAIN INVESTIGATORS OF DIVERSITY. >> WELL, THANK YOU FOR THAT COMMENT. I'M ALWAYS LOOKING AT THE ROOM, THE WAY YOU DESCRIBED, I'M GLAD YOU MENTIONED IT. IN THE HALLWAY I WAS TALKING TO HEATHER SNYDER FROM THE ALZHEIMER'S ASSOCIATION. IN AN EARLIER SESSION MENTION THE THE SHIFT THAT THE MEDICAL AND SCIENTIFIC ADVISORY BOARD TAKEN TO EMPHASIZE EARLY CAREER BUT ALSO CALLING OUT THREE SEPARATE AWARDS TO ENHANCE DIVERSITY OF RESEARCHERS IN ALZHEIMER'S DISEASE. SO THERE ARE TWO AWARDS, ONE FOR A RESEARCH FELLOWSHIP, AND ONE A CLINICAL FELLOWSHIP FOR PEOPLE AT POSTDOC AND EARLY CAREER LEVELS BUT ALSO A DIVERSITY AWARD FOR SENIOR PEOPLE WHO DON'T NEED A MENTOR. THOSE LETTERS OF INTENT ARE DUE ON FRIDAY. BUT YOU STILL HAVE TIME TO TALK TO ME OR TALK TO HEATHER SNYDER, IF YOU KNOW OF ANYONE WHO IS DOING RESEARCH THAT WOULD BE RELEVANT TO ALZHEIMER'S DISEASE I JUST CONVINCED SID IN THE BREAK TO GET ONE OF HIS POSTDOCS DOING COGNITION IN KIDS WITH RELEVANT SKILLS FOR A HISPANIC POSTDOC TO ADDRESS ALZHEIMER'S DISEASE WITH HIM AS MENTOR, SO THANK YOU FOR GIVING ME THE OPPORTUNITY TO TALK ABOUT THAT IN THIS ROOM. >> I WANT TO -- I'M HECTOR. I WANT TO ECHO THINGS THAT WERE MENTIONED HERE. I THINK IT WAS MENTIONED THAT THERE'S BEEN A LARGE GAP IN FUNDING IN ALZHEIMER'S DISEASE AND RELATE THE DEMENTIA IN THE PAST AND NOW THINGS ARE BETTER. GLAD OF THAT. IF THERE'S A DIP IN THE AVAILABILITY OF SENIOR SCIENTISTS IN THE FIELD, THERE'S A REAL NEED FOR JUNIOR POSTDOCS, TRAINEES TO BRING UP, YOU KNOW, I'M IN THE UNFORTUNATE POSITION -- WELL, FORTUNATE BUT UNFORTUNATE POSITION TO HAVE FUNDING TO SUPPORT TRAINEES, AND IT'S BEEN A REAL STRUGGLE TO FIND FOLKS OUT THERE. SO THAT'S A PLUG TO SEND THEM MY WAY. AND THEN SECONDLY I THINK THESE INITIATIVES ARE NEEDED AND BECAUSE THE DEMOGRAPHY IS CHANGING, AND SO EXCELLENT POINT. THANK YOU >> I'M ELAINE, PATHOLOGIST FROM UNIVERSITY OF NEW MEXICO. I HAD A PAPER OUT TWO WEEKS AGO ABOUT SOMETHING THAT I'M MISSING HERE AT THIS MEETING, I THINK IT DOES DISPROPORTIONATELY AFFECT LOW INCOME GROUPS, AND THOSE IN MEXICO ARE NUMEROUS SINCE WE HAVE 850,000, ALMOST HALF OUR POPULATION, ON THE NEW AFFORDABLE CARE ACT INSURANCE. SO WE HAVE A HUGE DISPARITY PROBLEM IN NEW MEXICO, AND IT'S PARTLY ETHNIC SINCE WE HAVE A LARGE -- OVER 61% HISPANIC. OUR HISPANIC POPULATION IS PROBABLY QUITE DIFFERENT FROM THE ONE YOU'RE STUDYING IN TEXAS, SINCE MANY HISPANICS CAME IN THE 16th CENTURY TO NEW MEXICO THEY ARE NOT RECENT 'EM GRANTS FROM MEXICO. THEY THINK OF THEMSELVES AS SPANISH. WE HAVE CENTRAL AMERICANS COMING IN ALL THE TIME. SANTA FE IS A SANCTUARY CITY, IMMIGRANTS CANNOT BE THROWN OUT. WE HAVE THAT MAJOR BURDEN OF UNFUNDED SOCIALLY ECONOMICALLY DEPRIVED PEOPLE IN OUR STATE WHICH COULD BE PART OF THE REASON WHY A LOT OF THE AUTOPSIES I LOOK AT ARE DIAGNOSED OR QUOTE UNQUOTE CALL THEMSELVES ALZHEIMER'S DISEASE AND ARE NOT BECAUSE THEY DON'T HAVE MEDICAL CARE. BUT THERE'S A BIG ISSUE MISSING THAT WE'RE NOT DISCUSSING, AND I THINK IT HAS SOMETHING TO DO WITH SOCIAL DETERMINANTS, BUT INFECTIOUS DISEASE IS MORE COMMON AGAINST THE POOR POPULATION OF RURAL PEOPLE AND INNER CITY PEOPLE WHO LIVE IN VERY COMPROMISED CIRCUMSTANCES IN TRAILER PARKS AND MANY EVEN WITHOUT ANY SHELTER. MY PAPER WAS CALLED "MICROBES AND ALZHEIMER'S DISEASE" AND I THINK AT SOME POINT WE NEED TO OVERCOME RESISTANCE TO THE YESTERDAY THAT INFECTIOUS DISEASE MIGHT PLAY SOME ROLE IN EXACERBATING ALZHEIMER'S, AFFECTING VASCULAR INTEGRITY AND INFLAMMATORY PROCESSES WE'VE DESCRIBED AS BEING PART OF ALZHEIMER'S AND OTHER DEMENTIAS, BUT WE HAVEN'T ADDRESSED UNDERLYING ISSUE, WHY IS THERE INFLAMMATION, WHERE DOES IT COME FROM? MANY OF THE INFECTIOUS DISEASES WE SEE, I'VE SEEN THESE IN BRAINS I TEST FOR PATHOGENS, THERE'S A LOT OF THEM THERE, IN FACT IT'S ALMOST IMPOSSIBLE TO FIND A BRAIN THAT DOESN'T HAVE A PATHOGEN IN IT AT DEATH. SO I THINK IT'S SOMETHING WE NEED TO START THINKING A LITTLE BUILT MORE CLEARLY ABOUT. >> THANK YOU. >> I THINK YOUR POINT IS WELL TAKEN, AND I WON'T SPEAK TO INFECTIOUS DISEASE PATHOGENS BUT I WILL SPEAK TO ANOTHER TOPIC, KNOWING AND LOVING ALBUQUERQUE VERY WELL, THAT THE SOUTH VALLEY WHERE A LOT OF YOUR POPULATION WILL COME FROM OF ALBUQUERQUE IS ALSO A SUPERFUND SITE, AND SOMETHING THAT DID NOT COME UP TODAY BUT I WILL JUST MENTION IN PASSING, THERE'S SOME ENVIRONMENTAL FACTORS, THERE'S BEEN VERY NICE WORK IN THE SOCIAL EPIDEMIOLOGY WORLD THAT HAVE LOOKED AT WHAT IT MEANS TO BE BROKE, BROWN AND LIVING IN THE WRONG PART OF TOWN. AND SOME OF THOSE MAP VERY SADLY ONTO ENVIRONMENTAL SUPERFUND SITES AND THE LIKE, SO IT'S A VERY COMPLEX SITUATION INDEED. >> AND ONE OF THE FUNDED STUDIES IN OUR PROGRESS REPORT WAS ON AIR POLLUTION, AND COGNITIVE OUTCOMES, AND I KNOW THAT WORK IS EXPANDING, SO HAPPY TO REPORT THAT THERE'S SOME WORK, THERE'S SOME THINGS IN THE WORKS TO TAKE A LOOK AT SOME OF THOSE FACTORS. >> SO FOR THE MICROBIAL MICROBES AND ALZHEIMER'S -- SORRY. >> (INAUDIBLE). >> JUST ONE MORE SENTENCE. IF YOU GOOGLE MICROBES AND ALZHEIMER'S YOU CAN FIND SCIENTIFIC AMERICAN COMMENTARY ABOUT IT. >> HI. THIS IS (INDISCERNIBLE) FROM UNIVERSITY OF ROCHESTER, HEALTH DISPARITIES IS VERY INTERESTING AND IMPORTANT RIGHT NOW. AND AS THE SPEAKERS THIS MORNING MENTIONED, THE SOCIOECONOMIC POPULATIONS MIGHT BE MORE LIKELY TO UNDERREPORT OR UNDERDIAGNOSE, SO I THINK WHEN YOU STUDY HEALTH DISPARITIES, CENTERS NEED TO TAKE INTO CONSIDERATION TO DEVELOP MORE ACCURATE RESULTS. THANK YOU. >> I DIDN'T UNDERSTAND THE LAST PART OF YOUR QUESTION. COULD YOU SAY IT ONE MORE TIME. >> OH, YEAH, WHEN YOU STARTED THE HEALTH DISPARITIES DID YOU CONSIDER FACTORS SUCH AS UNDERREPORTING OR UNDERDIAGNOSE, IT SEEMS LIKE SOCIOECONOMIC DISADVANTAGED POPULATIONS AND RURAL POPULATIONS MORE LIKELY TO UNDERREPORT. >> OKAY. SO I'LL JUST -- THAT'S A GOOD QUESTION. I'M GLAD YOU ARE ASKING FOR CLARIFICATION. THERE'S DIFFERENCE BETWEEN CLINIC BASED STUDIES AND COMMUNITY BASED STUDIES. SO WHEN YOU GO OUT INTO THE COMMUNITY AND DON'T ASK PEOPLE TO IDENTIFY THEMSELVES AS HAVING DEMENTIA YOU FIND THESE DISPARITIES THAT WE SHOWED THE STUDY, IN THE KAISER STUDY, BUT WHEN YOU WORK IN A CLINIC YOU SEE VERY FEW DISPARITIES POPULATIONS PRESENT THEMSELVES AS HAVING MEMORY DISORDERS SO AND THOSE PEOPLE IN THE CLINIC ARE USUALLY HAVING NEUROPSYCHIATRIC PROBLEMS, MORE SEVERE IN THEIR DISEASE, SO THERE'S REALLY A DIFFERENCE IN THE CHARACTERISTICS OF THE DISPARITIES POPULATIONS DEPENDING ON THE SETTING OF YOUR RESEARCH STUDY. >> ONE THING TO ADD TO THAT IS FOR SOME REASON THINK THERE'S A MISCONCEPTION THAT COMMUNITY BASED PARTICIPATORY RESEARCH MEANS IT'S SURVEYED QUESTIONS. THAT'S NOT NECESSARILY THE CASE. CBPR IS AN APPROACH TO ENGAGING THE COMMUNITY TO DO A RESEARCH PROJECT. IN OUR WORK, WE RECRUIT FROM A COMMUNITY OF 700 MEXICAN AMERICANS, EVERYONE HAS FULL CLINICAL LABS. WE DON'T ASK ABOUT DIABETES DIAGNOSIS, 30% WE'VE GIVEN A DIABETES DIAGNOSIS. YOU GIVE SOMETHING BACK TO THE COMMUNITY, I DON'T KNOW IF WE HIGHLIGHTED, SO THAT EVERYONE WHO COMES THROUGH OUR RESEARCH AND NOT JUST OURS, OTHER PEOPLE UP ON HERE AND OTHER COHORTS, IT'S NOT JUST ABOUT SAYING HERE, BE PART OF RESEARCH AND YOU'LL NEVER HEAR BACK FROM US. IF WE DO MRIs WE GIVE BACK THE CLINICAL REPORTS TO PRIMARY CARE PHYSICIANS. IF WE DO CLINICAL LABS THEY GET A COPY. IF WE DETECT COGNITIVE DYSFUNCTION THEY GET AN IN-PERSON FEEDBACK AND PRIMARY CARE PHYSICIANS CAN CONTACT ME AND I WILL HELP THEM. THAT RELATIONSHIP IS ESSENTIAL AND REQUIRED SO YOU CAN GET AROUND SOME OF THESE SELF REPORT VERSUS OBJECTIVE, WE HAD SOMEONE THE OTHER DAY A CASE THAT CAME IN TO THANK US BECAUSE THEY DIDN'T KNOW THEY HAD DIABETES BECAUSE THEY HAD HIV, THEY HAD BEEN TRACKED SO TIGHTLY FOR EVERYTHING ELSE THE PRIMARY CARE DOC DIDN'T TRACK FOR DIABETES. THESE THINGS ARE INCREDIBLY IMPORTANT AND YOU HAVE TO -- IF YOU DON'T DO THIS YOU MISS A LOT. >> STANDING THERE THAT'S ON EVERY COMMITTEE, LISA. >> FUNNY. LISA BARNES, I HAVE A COMMENT AND QUESTION. WE PUBLIC I PUBLISHED A STUDY, CYTOMEGALOVIRUS, IT INCREASED RESERVOIR OF ALZHEIMER'S TWO-FOLD, AFRICAN-AMERICANS IN THE STUDY MORE LIKELY TO HAVE CYTOMEGALOVIRUS INFECTION, THE RELATIONSHIP WITH ALZHEIMER'S WAS NOT DIFFERENT. I DON'T THINK YOU CAN ALWAYS NATURALLY ASSUME BECAUSE RISK FACTOR IS GREATER IN ONE POPULATION THAT IT WILL HAVE A DIFFERENT RELATIONSHIP WITH THE OUTCOME. IT COULD BE MORE COMPLICATED YES. MY OTHER QUESTION, MY ACTUAL QUESTION, YOU ALREADY ANSWERED, SID. IT WAS HOW DO WE ENCOURAGE STUDIES AND P.I.s WHO DON'T HAVE EXPERTISE IN COMMUNITY BASED PARTICIPATORY RESEARCH TO GO BEYOND JUST GOING TO THE COMMUNITY, HOW DO WE ENCOURAGE THEM TO HIRE THOSE PEOPLE, GO OUT THERE AND GET THE DATA TO DO CBPR WITH THE COMMUNITY AND NOT ON THE COMMUNITY. >> THE EXCEPTIONAL THING TO UNDERSTAND WHEN YOU DO CBPR, IT'S REALLY NOT THAT HARD. IT'S NOT A DIFFICULT WAY. RECRUITMENT OF GETTING INTO A MINORITY OR RURAL POPULATION TO DO RESEARCH IN MY EXPERIENCE HAS NOT BEEN DIFFICULT, IT JUST REQUIRES A DIFFERENT EFFORT. YOU HAVE TO BECOME PART OF THE COMMUNITY. YOU HAVE TO HIRE PEOPLE FROM THE COMMUNITY TO BE PART OF YOUR RESEARCH TEAM. AND YOU DON'T JUST SHOW UP AND TAKE QUESTIONS AND LEAVE. YOU GIVE BACK TO THE COMMUNITY. IT'S JUST A DIFFERENT APPROACH. IT'S NOT MORE DIFFICULT. IT'S NOT MORE COSTLY. BUT IT'S INCREDIBLY SUCCESSFUL AND IT'S BEEN SUCCESSFUL ACROSS THE DISEASES, HIV, HEP C, ALCOHOL USE, CARDIOVASCULAR DISEASE, ENDOCRINOLOGY, ONCOLOGY, PEDIATRICS, EVERYTHING. AND THAT'S THE POINT OF ONE OF THE RECOMMENDATIONS OF THIS GROUP FOR THAT TASK FORCE, BUT IT'S I THINK FROM MY STANDPOINT IT'S IMPORTANT FOR PEOPLE, SCIENTISTS, TO REALIZE IT'S NOT THAT IT'S INCREDIBLY DIFFICULT AND COMPLEX WAY TO DO, JUST A DIFFERENT WAY OF THINKING ABOUT IT. IT'S INCREDIBLY SUCCESSFUL. >> I WAS JUST GOING TO ADD ALSO A MOTIVATING FACTOR IS JUST THE SCIENTIFIC GAP, AND THE MERIT OF THAT RESEARCH, YOU KNOW, IS ALSO GREAT REASON. >> THANK YOU. >> I THINK THIS IS A VERY IMPORTANT SESSION. UNFORTUNATELY THE WAY I HEARD IT, QUITE A BIT OF THE PSYCHOSOCIAL FACTORS ARE CONFOUNDED WITH THE BIOLOGICAL UNDERPINNINGS OF THE DISPARITY ISSUE. I THINK IT'S THAT IMPORTANT TO SEPARATE THOSE TWO FACTORS SO THAT WE COULD DEAL WITH EACH ONE INDEPENDENTLY. I KNOW IT'S VERY DIFFICULT YET VERY IMPORTANT. THE REASON FOR SEPARATING IS THAT IT'S BECOMING INCREASINGLY APPARENT THAT THE DISEASE IS VERY HETEROGENEOUS AND HETEROGENEITY IS BASED ON EVOLUTIONARY TRENDS, GENETIC UNDERPINNINGS WHICH MEANS IN ORDER TO DO ADEQUATE CLINICAL TRIALS WE NEED TO COME UP WITH BETTER WAYS OF STRATIFYING CLINICAL TRIALS WHICH MEANS SLICING THE POPULATION INTO SMALLER AND SMALLER SECTIONS, WHICH MEANS WE'RE GOING TO REQUIRE VERY, VERY LARGE POPULATIONS TO DO CLINICAL TRIALS. THAT'S GOING TO BE VERY COSTLY. SO I THINK IT'S VERY IMPORTANT TO SORT THESE OUT. HOW DO WE GET INTO THE NITTY-GRITTY OF THE UNDERLYING BIOLOGY THAT CAN ACCOUNT FOR THE DISPARITIES. SOMETHING AKIN TO WHAT ALAN ROSEN'S WORK IS SHOWING, DIFFERENCE BETWEEN THE VARIOUS AFRICAN-AMERICAN, HISPANIC POPULATIONS. >> I THINK THAT PROBABLY EVERYBODY ON THE PANEL HAS SOMETHING TO SAY TO THAT. MY OWN PERSPECTIVE IS THAT VERY OFTEN WE STOP WITH BIOLOGICAL EXPLANATIONS WITHOUT LOOKING TO HOUSE SOCIAL FACTORS, MAY BE THE UNDERLIKE CAUSES OF BIOLOGICAL EXPLANATION. YOU SO SOCIAL INEQUALITIES IN HEALTH THERE'S A BIOLOGICAL NECK MECHANISM, HEALTH IS BIOLOGICAL, SO IF YOU SEE EDUCATION PREDICTS OUTCOME THERE'S A BIOLOGICAL BASES, WHAT IS LINKING A SOCIAL EXPERIENCE OUTSIDE THE BODY TO SOMETHING THAT IS ESSENTIALLY A PHYSICAL EXPERIENCE INSIDE THE BODY. AND THAT SID REALLY LAID OUT THE ARGUMENTS FOR UNDERSTANDING THAT. IF WE FAIL TO ACCOUNT APPROPRIATELY FOR THE SOCIAL DETERMINANTS WE JUST GET THE BIOLOGICAL ANSWERS WRONG AND THE KEY QUESTION TO ME IS THE PLACE WHERE YOU STOP ACTUALLY IS WHAT COULD WE INTERVENE ON, WHAT WOULD ACTUALLY GUIDE US IN PREVENTION AND TREATMENT, AND VERY OFTEN THE SOCIAL FACTORS WHICH GETS EASY TO DISMISS AS KIND OF FUZZY, NOT AMENABLE, SOCIAL FACTORS ARE MODIFIABLE, SO MUCH EASIER TO ADDRESS. SO I DO THINK IT'S REALLY IMPORTANT TO CONSIDER THE INTERSECTION BETWEEN THE SOCIAL AND BIOLOGICAL AND TO ASK VERY OFTEN IF YOU SEE A BIOLOGICAL DIFFERENCE, IS THAT REALLY A SOCIAL PHENOMENON MASQUERADING AS A BIOLOGICAL DIFFERENCE? >> JOHN, YOU'RE THE LAST PERSON TO ASK A QUESTION IN OUR SESSION. >> THANK YOU VERY MUCH. THIS MAY BE A VERY NAIVE QUESTION BUT IT FOLLOWS WHAT WAS JUST DISCUSSED -- >> SPEAK UP PLEASE. >> WHETHER YOU CAN TEASE OUT THE BIOLOGICAL EFFECTS OF HEALTH DISPARITIES IN ANIMAL MODELS OF DISEASE. WE KNOW THAT EXERCISE WILL REDUCE PLAQUE, COGNITIVE STIMULATION, I DON'T KNOW A LOT ABOUT THE LITERATURE OF OBESITY AND DIABETES IN ANIMAL MODELS, IT WOULD BE POWERFUL TO TAKE IT TO THE NEXT STEP, WITH RESPECT TO OTHER POSSIBLE HEALTH DISPARITIES FACTORS AND EXAMINE OR INTERROGATE THOSE IN ANIMAL MODELS. I DON'T KNOW IF PEOPLE ARE DOING THAT, AND IF IT'S POSSIBLE TO DO THAT. >> I KNOW THERE ARE SOME PEOPLE WHO ARE DOING THINGS LIKE THAT, EXPOSING ANIMALS -- DID YOU WANT TO SAY SOMETHING, LISA? YES, RIGHT. SO EXPOSING ANIMALS TO STRESS, TO CERTAIN DIETS, AND LOOKING AT THE OUTCOMES, BEHAVIORAL OUTCOMES, THE COGNITIVE OR BIOLOGICAL OUTCOMES, THERE ARE WAYS OF MANIPULATING CONDITIONS IN BASIC SETTINGS WITH ANIMAL MODELS THAT CAN -- THAT BASICALLY TAKING THE EPI FINDINGS AND TRANSLATING IT TO THAT RESEARCH. >> COOL. >> WE'RE GOING TO HAVE TO STOP THERE. I'M SORRY. PLEASE PROVIDE IN AN E-MAIL OR COME UP TO THE FRONT AND TALK. WE'LL HAVE A 20 POINTS -- WE'LL HAVE A WE'RE GOING TO GET STARTED WITH THE LEWY BODY DEMENTIA SESSION, CHAIRED BY DR. DENNIS DICKSON AND DR. KARAN MARDER, DR. DICKSON WILL GET US STARTED. >> I WANT TO ACKNOWLEDGE THERE ARE TWO MEMBERS OF OUR COMMITTEE THAT MADE VITAL CONTRIBUTIONS THAT FOR REASONS BEYOND THEIR CONTROL UNABLE TO BE HERE, ANDY SINGLETON, HE PROVIDED SLIDES ON GENETICS AND DR. TANNER WILL BE PRESENTING HIS SLIDES AND THEN IAN McKEE HAS BEEN A LEADER IN THE FIELD IN TERMS OF LEWY BODY DEMENTIA, HE ALSO HAS CONTRIBUTED TO OUR MODIFICATION OF RECOMMENDATION AND ESTABLISHING WHAT WE CONSIDER TO BE OUR SUCCESS CRITERIA. SO IF WE COULD BEGIN WITH THE FIRST SLIDE, OUR PRIORITIZED RECOMMENDATIONS BUILD ON THE 2013 RECOMMENDATIONS, AND THE NUMBER ONE AREA IS TO DEVELOP LONGITUDINAL COHORTS THAT HAVE COMMON MEASURES, CLINICAL BIOMARKERS, ET CETERA, AT LEAST A SUBSET COME TO AUTOPSY FOR CONFIRMATION OF FINAL DIAGNOSIS. THE SECOND IS DISEASE MECHANISMS USING A VARIETY OF PROFILING METHODS TO CHARACTERIZE BRAIN TISSUE OF WELL CHARACTERIZED PATIENTS AS WELL AS GENETIC METHODS. THE THIRD MAIN FOCUS AREA IS ON BIOMARKERS AND WE MEAN BIOMARKERS IN THE BROADEST SENSE TO INCLUDE BIOLOGICAL MARKERS THAT ARE PREDICTIVE OR DIAGNOSTIC OF THE LEWY BODY DEMENTIAS, AND IMAGING BIOMARKERS, AND THE FOURTH AREA IS TO DEVELOP MODELS OF THE DISEASE PROCESS, WITH THE EVENTUAL GOAL OF USING MODELS TO DEVELOP DISEASE MODIFYING THERAPIES. THERE HAS BEEN A WHOLE SESSION ON TERMINOLOGY, AND I WOULD JUST -- OR NOMENCLATURE, AND I BRIEFLY GO OVER SOME TERMS WE USE IN OUR GROUP. WE DON'T -- WE'RE NOT TALKING ABOUT PARKINSON'S DISEASE BUT MOST PATIENTS WITH LEWY BODY DEMENTIA HAVE SOME DEGREE OF PARKINSONISM, RIGIDITY, BRADY KINESIA AND TREMOR, FEATURES LIKE AS ASYMMETRY OR RESPONSE TO LEVADOPA. AND DEMENTIA WITH LEWY BODIES, DEMENTIA IS THE PREVAILING CLINICAL FEATURE, OFTEN BEFORE ANY DEGREE OF PARKINSONISM OR IN SOMETIMES IN THE ABSENCE OF PARKINSONISM. THE OTHERS ARE HALLUCINATIONS, FLUCTUATION AND SOME DEGREE OF PARKINSONISM. FROM THE RECOMMENDATIONS WHEN WE USED THE ABBREVIATION LBD IN THIS AREA WE REFER TO THE LEWY BODY DEMENTIAS PLURAL, THAT INCLUDES PARKINSON'S DISEASE AND DEMENTIA WITH LEWY BODY, THE LATTER TWO BEING THE DIFFERENT CLINICAL SYNDROMES DESCRIBED. WHEN WE TALK ABOUT LEWY BODY DISEASE, AN OVERARCHING TERM THAT DESCRIBES ALL THE PATHOLOGY, BECAUSE OF THE AM AMBIGUITY, WE RECOMMEND LEWY PATHOLOGY TO BE CLEAR IT'S A PATHOLOGIC PROCESS AND NOT TO USE LBD TO MEAN LEWY BODY DISEASE BUT TO REFER TO LEWY BODY DEMENTIAS. THE LEWY RELATED PATHOLOGY IS DIVERSE THROUGHOUT THE NERVOUS SYSTEM AND CAN BE SUBCLASSIFIED OR STAGED, IN LEARNING LEWY RELATED PATHOLOGY CAN BE LOCALIZED IN THE BRAIN, IN ALZHEIMER'S DISEASE FROM 60 TO 80% OF PATIENTS WILL HAVE LEWY RELATE THE PATHOLOGY IN THE AMYGDALA. THEY HAVE EOSINOPHILIC, IN PIGMENT NEURONS IN THE NIGRA AND AFFECT NON-MELANIN CONTAINING NEURONS. THE BULLS EYE APPROACH THAT ANGELA TAYLOR PRESENTED WOULD BE TO THINK OF THESE AS SYNUCLEIN OPATHY. I MENTIONED THE BROCK STAGING, THIS IS A SCHEME IN WHICH THE SYNUCLEIN PATHOLOGY IS SEEN IN OLFACTORY AND LOWER BRAIN STEM AND PROGRESSES TO HIGHER CORTICAL AREAS. AND BRIEFLY THERE'S HETEROGENEITY IN TERMS OF CLINICAL AND PATHOLOGY, IN THIS PAPER BUILDING ON THE LONGITUDINAL STUDY I WOULD FOCUS ON THE THE TWO HIGHLIGHTED GROUPS AS THOSE IN WHICH COGNITIVE IMPAIRMENT IS A CHARACTERISTIC FEATURE OR VARIABLE, THESE TWO FORMS OF LEWY BODY RELATED DISORDERS ARE ASSOCIATED WITH DEMENTIA WITH LEWY BODY AND PARKINSON DISEASE DEMENTIA WHERE YOU SEE IN DLB IT'S A DISEASE OF ELDERLY INDIVIDUALS, DEMENTIA PRESENT AT ONSET, AT THE END STAGE IT'S A MIXED DEMENTIA WITH ALZHEIMER'S PLAQUES, TANGLES AND WIDESPREAD LEWY BODIES. EVENTUALLY IT PROGRESSES TO DEMENTIA AND IN END STAGE MAY BE ASSOCIATED WITH AMYLOID PLAQUES, CORTICAL LEWY BODIES. AND IN TERMS OF -- WE MENTIONED LEWY RELATED COGNITIVE DISORDER, DLB, I WANT TO MENTION AN INTERNATIONAL CONFERENCE IN FORT LAUDERDALE IN DECEMBER, REVISIONS TO THE CLINICAL CRITERIA BEING WORKED ON AT PRESENT BUT THERE HAVEN'T YET BEEN FORMULATED OR PUBLISHED 69 THERE'S A MINOR MODIFICATION IN PATHOLOGY. AND WITH THAT I WANT TO MOVE ON TO JENNIFER GOLDMAN WHO IS GOING TO GIVE A PRESENTATION ON OUR FIRST PRIORITIZED RECOMMENDATION ON LONGITUDINAL COHORTS, AS AN ASIDE, THE NUMBER ONE RECOMMENDATION IN TERMS OF OUR PRIORITIES IN THIS IS TO DEVELOP SYMPTOMATIC THERAPIES, AND THIS GREW OUT OF THE 2013 RECOMMENDATION FROM THE FLOOR FROM THE PATIENT ADVOCACY GROUPS WHO THOUGHT THAT THE NUMBER ONE RESEARCH PRIORITY FOR LEWY BODY DEMENTIAS SHOULD IN FACT BE TREATMENTS. TREATMENTS THAT CAN BE OFFERED TO PATIENTS NOW. >> OKAY. GOOD AFTERNOON. THANK YOU, DENNIS. THANK YOU TO IT THE ORGANIZERS FOR ALLOWING ME TO PRESENT AN UPDATE ON THE CLINICAL TRIALS ON THIS PRIORITIZED RECOMMENDATION. SO THE FIRST SLIDE WE'RE GOING TO DIVIDE THIS AND TALK ABOUT TRIALS FOR DLB AND TURN TO PDD USING THE OUTLINE THAT DENNIS JUST PRESENTED GIVEN THE SYMPTOMATOLOGY FOR THE CONDITIONS. THIS IS PROGRESS IN DLB SINCE 2013, AND TO SHARE WITH YOU THAT THERE HAVE BEEN FOUR CLINICAL TRIALS IN DLB PATIENTS COMPLETED SINCE 2013. THESE HAVE BEEN MOSTLY OPEN LABEL STUDIES OR OPEN LABEL EXTENSION STUDIES AS YOU CAN SEE HERE IN 2013, AS WELL AS 2015. TO DATE THERE'S BEEN ONLY ONE RANDOMIZED DOUBLE BLIND PLACEBO CONTROLLED TRIAL WHICH IS IKEDA IN 2015. MOSTLY THESE HAVE FOCUSED ON DRUGS REPURPOSED, DRUGS THAT WE KNOW OF THAT HAVE BEEN APPROVED AND USED IN ALZHEIMER'S DISEASE, CHOLINESTERASE INHIBITORS. OVER THE PAST THREE YEARS THERE HAVE BEEN SMALLER RECENTLY COMPLETED TRIALS STARTING TO USE NOVEL AGENTS, LOOKING BEYOND CHOLINESTERASE INHIBITORS OR MMDA ANTAGONIST, INCLUDING ARMODAFINIL, A COUSIN, AND NILOTINIB, ONE IN DLB, ONE IN DLB AND PDD AS WELL, SMALL STUDIES ON THE SCALE OF 10 TO 20 PATIENTS OR SO, SO I THINK WE NEED TO HEAR MUCH MORE ABOUT THESE COMPOUNDS BUT JUST TO HIGHLIGHT SOME OF THE PROGRESS. THERE'S ALSO BEEN A GROWING INTEREST IN NEW TYPES OF PRIMARY OUTCOME MEASURES FOR COGNITION, MUCH OF THE OUTCOME MEASURES HAVE BEEN FOCUSED ON WHAT'S BEEN USED IN ALZHEIMER'S STUDIES, SO STARTING TO LOOK AT PRIMARY OUTCOME MEASURES FOR COGNITION, SUCH AS THOSE USING COMPUTERIZED BATTERY TESTING, AS WELL AS INCORPORATION OF BIOMARKERS SUCH AS THE THE NILOTINIB STUDY. OTHERS ARE IMPORTANT TO KNOWB SEVERAL ARE RECENT TRIALS UNDERWAY, THEY HAVE BEEN LOOKING AT NOVEL APPROACHES SO GOING BEYOND MEDICATIONS, THERE'S A SMALL PILOT STUDY LOOKING AT DEEP BRAIN STIMULATION WHICH WE TYPICALLY THINK OF FOR MOTOR FEATURES OF PARKINSONISM BUT STIMULATING THE AREA THAT'S HIGHLY IMPLICATED IN ATTENTION LEARNING AND MEMORY AND HAS BEEN STUDIED IN ALZHEIMER'S DISEASE. THERE'S SEVERAL UPCOMING DLB CLINICAL TRIALS, AND THESE ARE LOOKING AT NOVEL COMPOUNDS. I HIGHLIGHT HERE THE HEADWAY DLB TRIAL WITH R.V.T-101, FOCUSED ON COGNITION IN DLB SPONSORED BY AXOVANT, PHASE IIB STUDY, LOOKING AT A LARGE POPULATION, OVER 200 PATIENTS IN MULTI-CENTERS, AND I CAN SAY HEADWAY IS NOW UNDERWAY, AND LOOKING AT THIS FOR DLB. IN ADDITION, NELOTANSERIN, A 5HT 2A AGONIST STUDIED LOOKING AT DLB PATIENTS EXPERIENCING VISUAL HALLUCINATIONS, ONE OF THE FEATURES POINTED OUT BEFORE, AS WELL AS REM SLEEP BEHAVIOR DISORDER IN DLB, LOOKING AT COGNITIVE ASPECTS DISABLING TO PATIENTS BUT SOME BEHAVIORAL ASPECTS AS WELL. TURNING TO PARKINSON'S DISEASE DEMENTIA SPECIFICALLY, THIS IS SOME OF THE PROGRESS THAT'S BEEN MADE SINCE 2013, IN THIS PATIENT POPULATION. THERE HAVE BEEN THREE CLINICAL TRIALS IN PDD PATIENTS COMPLETED SINCE 2013. THESE HAVE INCLUDED A FEW NEW FOCUS AREAS, ONE LOOKING AT PERHAPS DRUG FORMULATION, THIS IS A STUDY THAT COMPARED RIVASTIGMINE PATCH VERSUS ORAL PILL, RIVASTIGMINE IS THE ONLY FDA APPROVED MEDICINE CURRENT FOR PARKINSON'S DISEASE DEMENTIA, A LONG-TERM STUDY LOOKING AT 76 WEEKS OF THERAPY. THERE WAS A SECONDARY ANALYSIS OF AMENTINE TRIAL LOOKING AT CARE FIRST, LOOKING AT EXPERIENCES THAT ARE QUITE SIGNIFICANT IN THESE DISORDERS. AND LASTLY TURNING TO THE BEHAVIORAL COMPLICATIONS, A RECENT STUDY FOCUSED ON PSYCHOSIS IN PARKINSON'S DISEASE, THIS STUDY WAS A RANDOMIZED DOUBLE BLIND TRIAL WITH PIMAVANSERIN, PUBLISHED BY CUMMINGS, COMPARED TO PLACEBO, DEMONSTRATING SIGNIFICANT EFFECT ON PSYCHOSIS AND PARKINSON'S USING NOVEL SCALE CALLED THE SAPPD THAT LOOKED AT HALLUCINATION AND DELUSION, CHANGE IN CDIC, CURRENT BECAUSE THE FDA IS MEETING AS WE SPEAK. THERE'S SEVERAL ONGOING PDD INTERVENTION STUDIES. THESE HAVE FOCUSED ON SOME SEROTONINERGIC DRYINGS, THE , ILLUSTRATING A PARTNERSHIP WITH BIOTIE, MICHAEL GEORGIA FOX FOUNDATION AND STUDY GROUP LOOKING AT PDD PATIENTS LOOKING AT SYN120. THERE'S A STUDY OUT OF KOREA THAT'S BEEN LOOKING AT INCREASED DOSES OF DONEPEZIL, THERE'S A 23-MILLIGRAM DOSE THAT'S AVAILABLE FOR ALZHEIMER'S BUT HAS NOT YET BEEN STUDIED IN PARKINSON'S DISEASE DEMENTIA. THE SAME GROUP LOOKING AT THE SMALL PILOT STUDY DEEP BRAIN STIMULATION IS ALSO LOOKING AT A PDD GROUP. ONE OF THE AREAS THAT WAS DISCUSSED EARLIER IN THE SESSIONS TODAY WAS THAT OF MILD COGNITIVE IMPAIRMENT, AND THIS HAS BEEN A GROWING AREA OF INTEREST IN THE PARKINSON'S FIELD PDMCI, AS BEING AN AREA THAT MAY REPRESENT AN EARLIEST PHASE OF COGNITIVE CHANGES AND POTENTIAL PRODROME, A NEW AREA FOR EMERGING THERAPEUTIC, TREATING SYMPTOMS OF COGNITIVE IMPAIRMENT, SINCE 2013 THERE HAVE BEEN FOUR COMPLETED TRIALS LOOKING AT PDMCI POPULATIONS, THIS HAS BEEN AN EVOLVING AREA IN THE FIELD IT'S BEEN DEFINED IN A NUMBER OF DIFFERENT WAYS, WITH DIAGNOSTIC CRITERIA PUT FORTH BY THE MOVEMENT DISORDER SOCIETY IN 2012. THESE COMPLETED CLINICAL TRIALS HAVE LOOKED AT A VARIETY OF DIFFERENT TYPES OF DRUGS THAT INCLUDE THE INHIBITORS AND TWO AGENTS THAT WORKED ON OTHER SYSTEMS AND NOREPINEPHRINE REUPTAKE MEDICATION. PRODROMAL WE'VE HEARD ABOUT TODAY, DENNIS ALLUDED TO THIS EMERGING CONCEPT, THIS IS AN AREA THAT HAS NOT HAD CLINICAL TRIALS YET. THIS SUMMARIZES WITH THE EXISTING NETWORK INFRASTRUCTURE, ONE OR MORE FDA APPROVED DRUGS FOR IMPROVEMENT OF CLINICAL FEATURES. THERE HAVE BEEN SEVERAL PROGRAMS TO DATE FOCUSING ON BIOMARKER STUDIES IN PARKINSON'S AND ALZHEIMER'S. SEVERAL ARE LISTED HERE, INCLUDING THE BIOMARKER PROGRAM, PPMI AND PPMI STUDY THAT WAS MENTIONED FOR PRODROMAL. THERE ARE A NUMBER OF INDIVIDUAL MEDICAL CENTERS. I'D LIKE TO HIGHLIGHT EURO DLB INITIATIVE WHICH INCLUDES A NUMBER OF EUROPEAN COUNTRIES WITH OVER A THOUSAND PATIENTS WITH DLB LEWY BODY DISORDERS ACROSS MULTIPLE PATIENT POPULATIONS TO COME UP WITH PROSPECTIVE TRIALS AND BIOMARKER RESOURCES. TO DATE THERE HAVE BEEN VERY FEW LONGITUDINAL DLB COHORTS THAT FOLLOW FROM THE CLINICAL BIOCAL IMAGING FROM THE EARLY STAGES TO AUTOPSY. SUPPORTS HYPOTHESIS DRIVEN CLINICAL RESEARCH TO DISCOVERY BIOMARKERS FOR THE LEWY BODY DEMENTIAS. THE SUCCESS CRITERIA WOULD INCLUDE AT LEAST ONE NEW STUDY THAT LEVERAGES ONE OR MORE EXISTING COHORTS TO DEVELOP AND ESTABLISH RESEARCH TOOLS THAT WE CAN HAVE TO STUDY DLB AND PDD TO UNDERSTAND BIOMARKERS AND DEVELOP THERAPEUTICS FOR THESE PATIENTS. THE OTHER IS TO COLLECT AND SHARE DATA FROM THOSE INDIVIDUALS WITH POTENTIAL EARLY MANIFESTATION OF DISORDERS. AND WITH THAT I WILL CLOSE. >> THANKS FOR THE OPPORTUNITY TO GIVE THE UPDATE. THE GOAL WAS TO DEVELOP A COMPLEMENTARY MODULE THAT WILL GO WITH THE UNIFORM DATA SET, THAT'S WERE THE NIADC PROGRAMS. THE GOAL IS A FRAMEWORK AND HARMONIZE WITH STUDIES BY THE MOVEMENT DISORDER SOCIETY AND SOME UDALL CENTER. THE IDEA WAS A COMPANION MODULE, HARMONIZE EFFORTS, WE WANTED TO EVALUATE BOTH DLB AND PDD PATIENTS AND DATABASE THEM. WHAT WE STARTED OUT FIRST BY DOING IS TAKING OUR LARGER COMMITTEE AND DEVELOPING SUBCOMMITTEES WHO HAD A TASK TO DO, BECAUSE WE HAD TO CREATE A MODULE, WE PUT PEOPLE INTO LITTLE GROUPS. SUBCOMMITTEES WERE ALLOWED TO INVITE TWO AD HOC MEMBERS, WE GOT OPINIONS FROM PEOPLE AROUND THE NORTH AMERICA. SOME ACTION STEPS, WE CHOSE SOME INSTRUMENTS AND MEASUREMENTS. WE ADDED ADDITIONAL CONSULTANTS, AND THEN WE TRIED TO IDENTIFY SOME DEFICIENCIES IN WHAT WAS CURRENTLY AVAILABLE IN THE EXISTING MODULE, WE WANTED TO TAP INTO BOTH MOTOR AND NON-MOTOR FEATURES, HOW WE COULD CAPTURE EVOLUTION IN THE PRODROMAL PHASE, AN EXCITING CONCEPT TO DIVE AND EXPAND. WE WANTED TO CAPTURE AUTONOMIC FEATURES AND TRY TO HARMONIZE SOME THINGS THAT WOULD BE COMMON. ON THE SLEEP SIDE, WE CAPTURED RELATED PHENOMENON, AND WHILE THE UDS HAS SOME YES-NO QUESTIONS IT'S NOT SURE HOW PEOPLE CAPTURE THOSE SYMPTOMS. THERE'S NO STANDARDIZED WAY OF DATA COLLECTION CURRENTLY OTHER THAN PRESENT OR ABSENT. THE IDEA OF GLOBAL TOOLS, HOW COULD CAPTURE FUNCTIONING AFFECTING PEOPLE'S QUALITY OF LIFE, AND SO AGAIN WE WANTED TO DO THIS FROM A CAREGIVER OR PATIENT PERSPECTIVE. ON THE NEUROPSYCH WE WANTED TO HAVE TESTS THAT WOULD CAPTURE DOMAINS EARLY AFFECTED IN LEWY BODY DISORDERS, PARTICULARLY IN ATTENTION AND TASKS. WE WANTED TO BE LEAN AND MEAN. WITH THE BIO, MAKERS SINCE THERE'S NO ADDITIONAL FUNDING TO DO THIS WE WEREN'T GOING TO ASK THEM TO COLLECT ADDITIONAL BIOMARKERS, RATHER WE WANTED A BETTER RECORD OF CURRENT BIOMARKERS. THE IDEA WAS WE WANTED TO TAP INTO EXISTING TOOLS THAT ARE AVAILABLE. WE DIDN'T WANT TO CREATE THINGS IF WE DIDN'T HAVE TO, SO FOR THE MOVEMENT DISORDER SOCIETY SYMPTOMS WE CHOSE TO USE THE MDS UPDRS, PART 2 AND 3 WOULD ALLOW US TO CAPTURE EXPERIENCES OF DAILY LIVING AND MOTOR SYMPTOMS, WE COULD USE THE NMS TO LOOK AT NON-MOTOR SYMPTOMS AND THE AUTONOMIC SYSTEMS. SLEEP AND ATTENTION, LUCKILY BRAD WHO WAS LEADING THIS SUBCOMMITTEE, HIS GROUP HAD DEVELOPED A NUMBER OF TASKS, WE DECIDED TO TAP INTO THAT INCLUDING THE MAYO FLUCTUATION QUESTIONNAIRE AND MAYO SLEEP QUESTIONNAIRE. FOR BEHAVIOR AND MOOD NPIQ WAS COLLECTED SO WE DECIDED JUST TO EXPAND UPON THE NPI SCREENING QUESTIONNAIRE, TAPPING INTO THESE FOUR SYMPTOMS, THE DELUSIONS, AND COMMON BEHAVIORS ON THE LEWY BODY SIDE. WE TALKED ABOUT ADDING GLOBAL TOOLS, ULTIMATELY THE MDS CAPTURES EXPERIENCE OF DAILY LIVING SO WE DECIDED TO GO WITH THAT AND NOT ADD ADDITIONAL TASKS WHICH WILL MAKE THE CLINICAL CORE LEADERS AT THE ADCs QUITE HAPPY. WE TRIED TO THINK ABOUT NOVEL TASKS TAPPING INTO LEWY BODY DEMENTIA. THE SECOND IS VISUAL ALEUTIANS THAT DLB PATIENTS EXPERIENCE ARE THAT THEY SOMETIMES SEE THINGS THAT AREN'T THERE AND DON'T SEE THINGS THAT ARE THERE. THIS WAS DEVELOPED BY A JAPANESE INVESTIGATOR, A VERSION OF INK BLOTS, HOPEFULLY YOU CAN SEE THE FACE. COMPLEMENTARY ARE TASKS WITH INK BLOTS THAT DO NOT HAVE A FACE. LEWY BODY PATIENTS START TO SEE A FACE WHERE THERE'S NOT A FACE AND SOMETIMES DON'T SEE THE TEST THERE. IT TAKES UP TO 20 MINUTES, MOST PEOPLE TAKE 10-15 MINUTES TO DO IT. THERE ARE 40 BLOTS, MORE THAN ONE ILLUSION, AND IT IS SENSITIVE. WHO DIDN'T SEE THE FACE THERE? ANYBODY? [LAUGHTER] WITH THE BIOMARKERS, THE IDEA WAS TO CATALOG THEM. WE'RE NOT ASKING PEOPLE TO COLLECT ANYTHING NOVEL. WE WANT TO KNOW WHAT THEY ARE COLLECTING. SO THAT AGAIN THE POSSIBILITY OF DATA SHARING, SO THIS IS SIMILAR TO WHAT'S SET UP FOR A.D. BIO, MAKERS, WE WANT TO UNDERSTAND IF ANYBODY IS DOING GENETICS, AND THERE'S NOT VERY MANY PEOPLE DOING A DATA MIBG AT THE MOMENT BUT IF THESE INCREASE WE WANT TO BE ABLE TO CHARACTERIZE THEM. SO OUR NEXT STEPS, WE'RE TRYING TO PULL THE ADCs, SO WE HAVE A PARTIAL RESPONSE FROM THE ADCs, THERE'S ONLY ONE THAT ACTUALLY HAS A DLB COHORT, AND THERE'S ONLY THREE THAT ARE COLLECTING ANY DLB-RELATED INSTRUMENTS, WE'RE ALSO INTERESTED IN COLLECTING SO THERE CLEARLY IS A NEED TO CREATE STANDARDIZED MODULE TO DO LONGITUDINAL STUDIES IN DLB. THAT'S A PARTIAL RESPONSE BECAUSE THERE ARE 29 CENTERS, ONLY 10 CLINICAL COURSE THAT RESPONDED, TYPICAL FOR PEOPLE RESPONDING TO A QUESTIONNAIRE SURVEY. WE'RE GOING TO PRESENT AT ADC MEETING. WE'VE GOTTEN A LOT ACCOMPLISHED, THE TELECONFERENCE WAS IN SEPTEMBER OF 2015, WE HAVE A DRAFT MODULE TO BE SHOWN IN APRIL OF 2016, WE'RE ABLE TO DO THIS EFFICIENTLY. I WANT TO THANK THE COMMITTEE MEMBERS WHO DID A GREAT JOB OF WORKING TOGETHER >> THE GOAL IS TO CHARACTERIZE LEWY BODY DEMENTIA PATHOLOGY, USING GENOMICS, METABOLOMICS, PROTEOME ICS AND TALK ABOUT THE PROGRESS TO DATE. I'M TODD GOLDE. I'M SUPPOSED TO TALK ABOUT AN EXAMPLE USING BAD, OMIC DATA IN AN INTEGRATED WAY TO SET THE STAGE FOR WHAT ARE COULD BE DONE IN ANY OTHER DEMENTIA. A COUPLE DISCLOSURES, FIRST A SHOUT OUT TO SUSANNA FOR PROVIDING A LOT OF THE SLIDES, SHE'S THE PROGRAM OFFICER FOR THIS PROGRAM WHICH MANAGES SIX FUNDED GRANTS, AND SHE PROVIDED A LOT OF THE SLIDES FOR THIS. SECOND TO A DISCLAIMER, I'M NOT A SYSTEMS BIOLOGIST, I'M MAYBE A MOLECULAR NEUROBIOLOGIST, BUT I BUT THAT GIVES ME A UNIQUE PERSPECTIVE. THIS IS PART OF THE ACCELERATING MEDICINE PARTNERSHIP, AND WHEN WE TALKED THIS MORNING ABOUT THE NOVEL ACADEMIC N.G.O. PARTNERSHIPS, THIS IS ONE OF THESE THAT'S COME OUT OF THE DIRECTOR'S OFFICE, THIS INVOLVES THE NIA, NINDS, FOUNDATION FOR NIH AND THEN FOUR COMPANIES AND SEVERAL NON-PROFIT ORGANIZATIONS. TODAY I'LL TALK ABOUT THE TARGET DISCOVERY AND PRE-CLINICAL VALIDATION PROGRAM, THERE'S ALSO A PARALLEL BIOMARKERS INITIATIVE THAT'S LEVERAGING THE SECONDARY PREVENTION TRIALS THAT ARE UNDERWAY, I'LL JUST MENTION IT HERE BUT WON'T TALK ABOUT IT. WHAT I WILL TALK ABOUT IS THE SIX ACADEMIC TEAMS FUNDED UNDER THE NIA GRANTS, IN THIS PRE-CLINICAL VALIDATION AND TARGET DISCOVERY PROGRAM. THESE ARE THE SIX PROGRAMS, PHIL AND DAVID LEAD THE ONE FROM BROAD RUSH, ERIC AND BEN FROM MOUNT SINAI, AND NATHAN PRICE AT THE INSTITUTE FOR SYSTEMS BIOLOGY LEADS ONE OF THE PROGRAMS, ALAN LEVY FROM EMORY AND THEN THERE'S A DUKE GROUP FOCUSING ON METABOLOMICS, AND BRUCE FROM HARVARD AND M.I.T. , THE GOAL TO GET TO TARGET IDENTIFICATION OF NOVEL THERAPIES, AND THERE'S A WHOLE BUNCH OF PRE-CLINICAL VALIDATION STEPS. BUT MOSTLY I'M GOING TO FOCUS ON THE DATA GENERATION AND WHAT TYPE OF DATA REGENERATING AND HOW WE'RE HANDLING IT TODAY. THIS IS A SLIDE GIVEN TO ME BY PHIL, AND DAVID THAT DESCRIBE THE DATA, AND ALSO MINING THE RICH DATA SET THAT COMES FROM THE CLINICAL DATA OF THIS PROSPECTIVE COHORT FROM THE ROSS MAP STUDY, MANY OF THE OTHER GROUPS HAVE OUR UNIQUE CONTRIBUTIONS, USING BRAINS FROM DENNIS DICKSON'S BRAIN BANK, FOCUSING ON PSP AND PRODROMAL AND AGING, OTHER GROUPS HAVE OTHER CRITERIA. THIS GIVES AN IDEA OF THE SCOPE OF DATA THAT'S BEING GENERATED. THIS IS ALSO FROM ALAN LEVY, WHO IS THE ONLY GROUP FOCUSED ON PROTEOMES, AND PROTEOME IS, DOING DISCOVERY PROTEOMICS. AS THIS WENT ON, THESE GRANTS HAVE EVOLVED INITIALLY THERE WAS PROTEOMICS GOING TO BE DONE ON A CERTAIN SET OF SAMPLES. AS CONSORTIUM CAME TOGETHER, NOW THE PROTEOMIC SAMPLES FROM ALL THE GROUPS ARE BEING ANALYZED BY ALAN AND COLLEAGUES AT EMORY, SO THERE WILL BE A SYSTEMATIC ANALYSIS AT LEAST AT A PROTEOMICS LEVEL OF THESE. THE OTHER THING THAT WAS INCREDIBLY USEFUL AND IMPORTANT AND CHALLENGING WAS THE FACT THAT THERE WAS NO PUBLICATION EMBARGO ON THE DATA AND THERE WERE QUARTERLY DATA RELEASES, THE DAT IS IS PUT IN THE COLLABORATIVE WORKSPACE, ACCESSED BY VIRTUALLY ANY QUALIFIED INVESTIGATOR WITH MINIMAL REQUIREMENTS, AND THIS IS HOSTED BY LAURA AT SAGE AND UNDER THE SYNAPSE WEBSITE SO YOU COULD SEE THE DATABASE HERE. YOU COULD ACCESS THIS DATA NOW FROM ALL THE GROUPS AND AS MORE DATA IS ADDED IT WILL BE THERE AND SO THIS IS A VERY NOVEL WAY OF SHARING THE DATA LOCK BEFORE IT'S PUBLISHED AND IT'S THERE FOR PEOPLE TO USE AND PUBLISH ON INDEPENDENTLY. THERE ARE MILESTONES, DEVELOP MODELS OF AD, CARRY OUT COMPARATIVE ANALYSIS, TARGET NOMINATION SELECTION AND CHARACTERIZE EXPERIMENTAL VALIDATION MODELS AND ASSESS RELEVANCE THROUGH COMPARATIVE ANALYSIS WITH HUMAN NETWORK MODELS AND FINALLY A CONSORTIUM-WIDE VALIDATION OF UP TO SIX NOVEL TARGETS. IT'S INTERESTING TO POINT OUT THESE GRANTS WERE INITIALLY -- THE RFA WAS FOR THESE TO BE RO1 GRANTS, THERE WAS NO -- WE DID NOT HAVE TO COLLABORATE, THESE HAVE BEEN TURNED TO UO1 GRANTS, COLLABORATING WITH DATA GENERATION AND TALKING ABOUT HOW WE'RE GOING TO USE THIS DATA AND MOVE IT FORWARD IN THE BEST POSSIBLE WAY. THIS IS A WORK IN PROGRESS AND OMIC TECHNOLOGIES ARE CHANGING AND RAPIDLY EVOLVING. THESE WILL CONTINUE TO EVOLVE. SEQUENCING METHODS, THESE COULD ALL INFLUENCE YOUR DATA THAT COMES OUT. THEY WERE NOT STANDARDIZED UP FRONT INTEGRATION OF DATA SOURCES ARE EVOLVING, WE WOULD LIKE TO INTEGRATE THIS WITH EXOME SEQUENCING OR WHOLE GENOME SEQUENCING SO YOU HAVE A COMPLETE DATA SET. THIS IS GOING TO BE INFORMATIVE AND ALSO IMPORTANT WHEN WE CONSIDER EXPANDING INTO OTHER DISEASES, WHAT REGION OF THE BRAIN ARE YOU GOING TO TAKE? IS IT GOING TO MESH WITH THE REGIONS THAT HAVE BEEN ANALYZED? OTHERWISE YOU CAN'T CROSS COMPARE. WE TOOK CEREBELLAR CORTEX AND I'LL SHOW DATA FROM THAT IN ONE SNAPSHOT, THE RESULTS ARE QUITE SURPRISING. THERE'S AN ONGOING DISCUSSION OF THE IMPORTANCE OF CELL ANALYSIS, WHEN YOU GRIND A BRAIN YOU LOSE INFORMATION ABOUT ZIP CODES OF WHAT CELLS ARE DOING WHAT COMPUTATIONAL METHODS COULD HELP, AND THERE ARE SOME NEW TECHNOLOGIES EMERGING THAT SUGGEST YOU CAN DO SINGLE CELL ANALYSIS. WE GENERATED MOUSE MODEL RNA-SEQ DATA AND WE'LL BE DOING -- I WOULD RECOMMEND THAT WHETHER OR NOT THIS SHOWS HOW GOOD OR BAD THE MODELS ARE, INCLUDING THAT IN SOME ASSESSMENT WOULD BE IMPORTANT. AND THEN I THINK THE REAL CHALLENGE COMES ONCE YOU GENERATE THIS DATA, HOW DO YOU VALIDATE IT, ALL I'LL SAY HERE IS THAT THERE'S NO CONSENSUS ON VALIDATION STEPS AND EACH GROUP WILL TAKE SOME DIFFERENT APPROACHES BUT THAT'S IMPORTANT. I THINK I WON'T SHOW DATA BECAUSE IT'S NOT HERE. THE SUCCESS CRITERIA PROPOSED ARE TO ESTABLISH AN INVENTORY AND REPORT ON EXISTING AUTOPSY SAMPLES WITH CLINICALLY WELL CHARACTERIZED BRAINS WITH ANTI-MORT 'EM DIAGNOSIS. THIS REPORT WILL COMMENT ON QUALITY AND AVAILABILITY OF THESE SAMPLES, A LITTLE LESS FREQUENT THAN THE ALZHEIMER'S DISEASE CASES SO I THINK ALSO IMPORTANT THIS BE SYNERGIZED UP FRONT SO THAT WHEN WE DO THIS IT'S DONE AS EFFICIENTLY AS POSSIBLE. ALL OF THIS OMIC TECHNOLOGY AND APPLICATION OF IT IS NOT INEXPENSIVE. TO HOLD A PLANNING WORKSHOP INFORMED BY THE LBD PATHOLOGY CAL TO DETERMINE AND PROPOSE AN OPTIMIZE IMPLEMENTATION PLAN FOR CHARACTERIZING BRAIN CHANGES USING SAMPLES DATAENED AND OTHER RESOURCES DATA AVAILABLE. NOW WE HAVE CARLIE TANNER. >> THIS IS LIKE AN ANXIETY EXAM DREAM. I'M GOING TO TALK ABOUT THE PROGRESS AND OUR NEW DIRECTIONS, THE GOAL BEING NOVEL COMMON AND RARE GENETIC VARIANTS, EPIGENETIC CHANGES AND ENVIRONMENTAL INFLUENCES THAT IMPACT RISK FOR CLINICAL FEATURES OF LBD. SO THERE'S BEEN QUITE A BIT OF PROGRESS SINCE LAST MEETING, AND THE GENETICS AREA IN PARTICULAR, SO THE PUBLICATION OF ONE STUDY AND ANALYSIS OF HERITABILITY, LOOKING AT PATHOLOGYICALLY PROVEN CASES, THE FIRST ANALYSIS WAS SOMEONE AT POSTMORTEM CATEGORIZED INTO THE PARTICULAR POPULATION. AND SOME OF THE DATA SHOW AN OVERLAP IN THE GENETICS OF PARKINSON'S DISEASE, DLB AND ALZHEIMER'S DISEASE, SO WHEN YOU LOOK AT THE DISORDERS YOU CAN SEE THERE'S ABOUT A SIMILAR AMOUNT OF OVERLAP OF DLB WITH PD, ON ONE HAND, AD ON THE OTHER HAND IN TERMS OF LOOKING AT THE GENETIC LOCI. AND ALSO EVIDENCE THAT SUPPORTS LYSOSOMAL DYSFUNCTION AS MECHANISM OF DISEASE, INTERESTING AS THAT'S ALSO BEEN SEEN FOR EXAMPLE IN PARKINSON'S DISEASE. SECOND STUDY ALSO GENOME-WIDE ANALYSIS LOOKING AT GENETIC CORRELATION, DEMENTIA LEWY BODY, FOUND THAT ONCE APOE WAS PULLED OUT OF THE ANALYSIS, THERE WAS A FAIRLY SIMILAR GENETIC CORRELATION BETWEEN DLB AND PD AND DLB AND AD, 30% CORRELATION. IN PROGRESS STILL TO COME BUT IN PROGRESSES ARE LARGE WHOLE GENOME ASSOCIATIONS, TARGETED RESEQUENCING STUDIES AS WELL. MORE TO COME IN THE FUTURE IN THE AREA OF GENETICS. THESE ARE LOOKING AT POPULATIONS OF ABOUT SEVERAL HUNDRED, 600 OR SO INDIVIDUALS IN EACH GROUP, AND I WILL SAY BACK TO THE DISCUSSION EARLIER THIS AFTERNOON ON DISPARITIES ANOTHER GAP THAT I THINK NOT WELL ADDRESSED IS DISPARITIES POPULATIONS. CRITICAL NEEDS FOR SUPPORT, INFRASTRUCTURE AND SHARING, MORE INDIVIDUAL SAMPLE THAT CAN BE PULLED, THE MORE THAT BE UNDERSTOOD ABOUT DIFFERENCES, LARGE NUMBERS OF PATIENTS WILL BE NEEDED FOR DISCOVERY AND REPLICATION. AS WE START FOCUSING LESS ON JUST DESCRIPTION OF STATE OF DIAGNOSIS AND START FOCUSING MORE ON PROGRESSION LONGITUDINAL DATA BECOMES IMPORTANT. ADDING THIS GENETIC COMPONENT AND COMBINING IT BECOMES INCREASINGLY IMPORTANT. TO PUT THIS TOGETHER AN IDEA WOULD BE TO HAVE A COORDINATING CENTER, TO FACILITATE CLINICAL INFORMATION, DISTRIBUTION OF NEURO PATHOLOGICAL SAMPLES AND ALLOWING RESEARCH TO PROCEED MORE RAPIDLY AND A CENTRAL DATA REPOSITORY THAT WOULD HARMONIZE WITH THE OTHER ONGOING STUDY. WE'VE HEARD ABOUT HOW SOME OF THE OTHER GROUPS HAVE TALKED ABOUT EFFORTS FOR THAT TO BE ONGOING, BUT PERHAPS THERE CAN BE MORE THAT REACH OUT TO STUDIES LIKE PTMI TO ENCOURAGE THAT HARMONIZATION. THE NEWER FOCUS THAT CAME UP FOR THIS TOPIC IS TO ALSO LOOK AT THE RELATIONSHIP BETWEEN ENVIRONMENTAL INFLUENCES AND DLB AND PDD. AND THIS IS AN AREA WHERE THERE HAVE BEEN FEWER STUDIES AND IN PART THERE IS IT VERY LITTLE DATA ABOUT THE ENVIRONMENT THAT CAN BE COMBINED WITH THE CLINICAL OR GENETIC OR PATHOLOGIC STUDIES THAT HAVE BEEN ONGOING. A FEW STUDIES CONDUCTED IN THE LAST FEW YEARS, DISPARATE TYPES OF POPULATIONS, NOT EASILY COMPARED AMONG THEMSELVES, AND CRITERIA HAVE VARIED WITHIN THE DIFFERENT POPULATIONS. SO ONE GROUP LOOKED AT COMPARISON OF PEOPLE WITH LBD AND PEOPLE WITHOUT DEMENTIA, AND FOUND THAT NOT SURPRISINGLY AGE, CONDITIONS, FAMILY HISTORY, LOW USE OF ALCOHOL AND LOW USE OF CAFFEINE WERE RISK FACTORS AND LOW CAFFEINE FOR EXAMPLE HARKS BACK TO SOMETHING OBSERVED IN PARKINSON'S DISEASE, COMPARED TO PEOPLE WITH ALZHEIMER'S DISEASE, INTERESTINGLY GIVEN THE EARLIER CONVERSATION ABOUT INFECTIONS AND THINGS LIKE THAT, FOUND THAT ANTECEDENT INFECTION OR LIVING IN ENVIRONMENTS WITH REDUCED SANITATION, THIS WAS A STUDY FROM BRAZIL SEEMED TO BE ASSOCIATED WITH HIGHER RISK OF DEVELOPING LBD. AND THEN IN A POPULATION OF INDIVIDUALS AT HIGH RISK TO HAVE A NEURODEGENERATIVE DISORDER INCLUDING LBD, LOW OR NO CAFFEINE USE WAS ASSOCIATED WITH A HIGHER RISK OF CONVERTING TO LEWY BODY DEMENTIA. SO THIS IS THE PROGRESS WE'VE MADE TO DATE. THIS IS REPRESENTING SEVERAL HUNDRED INDIVIDUALS BUT NOT AS MANY AS HAVE BEEN STUDIED FOR OTHER DISORDERS, AND AS WE AGAIN DISCUSSED IN THE SESSION BEFORE, IDENTIFYING MODIFIABLE RISK FACTORS SHOULD BE A NO BRAINER BECAUSE FOR MANY CHANGES CAN BE IMPLEMENTED QUICKLY AND WE MAY HAVE SOMETHING TO DO TO MAKE A BIG DIFFERENCE. I'M GOING TO GIVE A COUPLE EXAMPLES TO HIGHLIGHT RISK FACTORS. PESTICIDES HAVE BEEN ASSOCIATED WITH HIGHER RISK OF PARKINSON'S DISEASE, AND THIS SLIDE REPRESENTS SOME WORK THAT WAS LOOKED AT IN THE AGRICULTURE HEALTH STUDY, A POPULATION OF FARMERS WHO USED PESTICIDES ROUTINELY, IT'S LOOKING AT -- THEREFORE YOU HAVE GOOD EXPOSURE INFORMATION AND ALSO GENE INFORMATION, AND THESE ARE PEOPLE WHO HAD A NORMAL METABOLIC GENE THAT HELPS TO BREAK DOWN EXPOSURE, THESE PEOPLE HAVE INACTIVE OR MUTANT FORM OF THAT GENE, THIS IS THE RISK OF DEVELOPING PARKINSON'S DISEASE IN THIS CASE, SO IF YOU HAVE THE NORMAL GENE RISK IS NOT INCREASED RISK. IF YOU HAVE THE MUTANT, YOU'RE NOT GOOD AT BREAKING DOWN THIS PESTICIDE AND YOU'RE EXPOSED TO THE PESTICIDE YOUR RISK IS 13 TIMES HIGHER, AN EXAMPLE OF GENE ENVIRONMENT INTERACTION. IF YOU DON'T KNOW ABOUT THE ENVIRONMENTAL EXPOSURE, JUST KNOWING ABOUT THE GENE DOESN'T GET YOU VERY FAR. AND THIS IS AN EXAMPLE AGAIN FROM THE SAME AGRICULTURE HEALTH STUDY OF FARMERS THAT GIVES A THE PLAUSIBILITY, LOOKING AT THE POSSIBILITY OF PREVENTING DISEASE, THIS IS JUST LOOKING AT THE VERY SIMPLE THINGS, IF PEOPLE MIX OR APPLY PESTICIDES DO THEY USE PROTECTION, DO THEY WEAR GLOVES, WASH IF THERE'S A SPILL AND HOW DOES THIS RELATE TO THEIR DISEASE RISK? PRIMARY PREVENTION YOU TRY TO REMOVE CAUSATIVE FACTORS, THE DISEASE PROCESS ISN'T INITIATED. AND HERE IS WHAT WE SEE. FARMERS WHO WERE EXPOSED IN THEIR WORK AND USED GLOVES HAD NO RISK OF DISEASE. WELL, FARMERS WHO DID NOT USE GLOVES HAD ALMOST A FOUR-FOLD INCREASED RISK OF DISEASE. SIMILARLY, FARMERS WHO WERE EXPOSED TO PERMETHRI, IN OUR CAMPING CLOTHES, LOTS OF PEOPLE HAVE EXPOSURE, WHO DID NOT USE GLOVES HAD A 4 1/2-FOLD INCREASED RISK OF DISEASE. THIS IS A VERY SIMPLE INTERVENTION, YOU COULD GO OUT AND ENCOURAGE PEOPLE TO TAKE PRECAUTIONS WHEN USING PESTICIDES, NOT JUST FARMERS, BUT PEOPLE DOING HOME GARDENING, MAY HAVE A VERY SIGNIFICANT PUBLIC HEALTH CONSEQUENCE. MODIFIABLE RISK FACTORS, THERE MAY BE MANY OF THESE BUT WE NEED TO LOOK FOR THEM. THIS IS AN EXAMPLE IN ALZHEIMER'S DISEASE FROM THE WASHINGTON HEIGHTS PROJECT AGAIN, SO THIS IS A COMMUNITY-BASED POPULATION LOOKING LONGITUDINAL COHORT, 65 YEARS AND OLDER, WE'RE LOOKING AT AN AREA OF EVOLVING INTEREST, THE MICROBIOME. SO INTERESTING, A LOT OF DIFFERENT NEURODEGENERATIVE DISORDERS, SOMETHING THAT WOULD BE OF RELEVANCE TO STUDY HERE, THIS IS LOOKING AT THE RELATIONSHIP BETWEEN LEVELS TO SEVERAL DIFFERENT PERIODONTAL PATHOGENS AND GOING FORWARD AFTER BLOOD LEVELS WERE DETERMINED ADJUSTED FOR DETERMINANTS OF RISKS FOR ALZHEIMER'S DISEASE, AND ONE OF THESE IS ASSOCIATED WITH AN INCREASED HAZARD OF DISEASE, ANOTHER WITH A REDUCED HAZARD OF DISEASE, SUGGESTING THAT THINGS LIKE MICROBIOME, THESE ARE ASSOCIATED WITH GINGIVITIS, MAYBE WITH INFLAMMATION, THERE'S A PROCESS YOU CAN WORK OUT HERE, IN PARKINSON DISEASE PEOPLE ARE INTERESTED IN THE INTESTINAL MICROBIOME, THESE ARE AREAS OF IMPORTANCE RELEVANT TO STUDY HERE. THIS LEADS US TO NEXT STEPS, STUDYING ENVIRONMENT AND INTERACTION. WE FEEL HAVING PROSPECTIVE STUDIES OF CLINICALLY WELL DEFINED POPULATIONS, COLLECTING INFORMATION WILL BE IMPORTANT TO EVALUATE THE RELATIONSHIP OF THESE FACTORS AND TO EXPLAIN PERHAPS SOME OF THE UNEXPLAINED DETERMINANTS OR PEOPLE WHO HAVE GENETIC RISK BUT YET DO NOT MANIFEST DISEASE, AT LEAST SOME PART OF THAT IS PROBABLY DUE TO ENVIRONMENT AND NOT JUST OTHER GENETIC MODIFIERS. ALSO TO ADDRESS THIS, LOOKING AT WHAT WE KNOW BIOLOGICALLY ABOUT MECHANISMS OF DISEASE, LOOKING AT EXPOSURES THAT MAY BE OF RELEVANCE TO P.D. AND A.D., GENETIC ASSOCIATIONS THERE, IT MAKES SENSE THERE MAY BE ENVIRONMENTAL FACTORS, USING THESE AS PART OF OUR WAY OF TARGETING FACTORS TO EXPLORE MORE FULLY, ALSO LOOKING AT BIOMARKERS THAT WILL MAY BE OF RELEVANCE, NOT JUST COLLECTING HISTORY OF EXPOSURES, SO THE MICROBIOME, INFLAMMATORY AND EXPOSURE MARKERS, MARKERS THAT WOULD MEASURE EXPOSURE TO A PESTICIDE, BLOOD LEVELS, FOR EXAMPLE, OR LOOKING AT POSTMORTEM SAMPLESELS. OUR CRITERIA FOR SUCCESS FOR THIS WOULD BE FIRST OF ALL LOOKING FOR THE GENETICS WITHIN FAMILIES WITH AFFECTED MEMBERS FOR GENOMIC ANALYSES, DEFINITIVE ASSESSMENT OF IN WELL CHARACTERIZED PATIENTS, CONVENING A WORKSHOP TO LOOK AT METHODOLOGIC ISSUES NEEDED TO EXPLORE GENE ENVIRONMENT INTERACTION AND THIS LONG WORDY PARAGRAPH IMPLEMENTING METHODS FOR ASSESSING ENVIRONMENTAL DETERMINANTS. HERE BASIC SCIENCE AND EPIDEMIOLOGISTS SHOULD WORK TOGETHER WHERE WE KNOW GENOTYPE AND CLINICAL FEATURES AND ADDING IN ENVIRONMENT, TAKING POPULATIONS WHERE WE KNOW CLINICAL FEATURES AND MAY KNOW SOME ENVIRONMENTAL EXPOSURES ADDING IN GENES AND LOOKING AT GENETIC FACTORS SO WE CAN REALLY PUT TOGETHER GENE ENVIRONMENT INTERACTION AND THEN FINALLY LOOKING AT OTHER SOURCES OF EXPOSURE INFORMATION, FOR EXAMPLE GEO CODING TO INFER EXPOSURES, SOMEBODY TALKED ABOUT AN AIR POLLUTION STUDY THAT WAS HAPPENING FOR EXAMPLE LOOKING AT SUPERFUND SITES, TO EXPLORE THE POSSIBLE RELATIONSHIP OF THESE AND INTERESTING NOTE WAS MADE IN THE LAST SESSION ABOUT HOW AGAIN DISPARITY POPULATIONS MAY BE A PARTICULAR -- AT PARTICULAR RISK FOR ENVIRONMENTAL EXPOSURE. I DON'T KNOW WHO IS NEXT. OH, JOEL. THANK YOU. [APPLAUSE] >> I'M JOEL PERLMUTTER. AND WE'RE GOING TO TALK ABOUT THE IMAGING COMPONENTS, AND CLEMENS IS GOING TO TALK ABOUT THE BIOMARKERS, IN MY PERSPECTIVE IMAGING IS BIOLOGICAL BUT WE'LL KEEP IT THAT WAY. THAT I RECOMMENDATION WAS TO DETECT LATENT AND PRODROMAL AND MONITOR DISEASE PROGRESSION. WHAT I'M GOING TO DO IS GIVE YOU A LITTLE BIT OF WHAT'S BEEN DONE SINCE THE LAST SYMPOSIUM. NORMALLY WE TALK ABOUT THIS AND THAT METHOD. I'M GOING TO TALK ABOUT THIS PROBLEM AND THAT PROBLEM AND THE NEXT PROBLEM, A LITTLE BIT MORE PROBLEM ORIENTED. SO IN TRYING TO DISTINGUISH P.D. FROM DEMENTIA, FROM ALZHEIMER'S DISEASE FOR EXAMPLE, AND WE ALREADY KNOW THAT'S FAILED BECAUSE THERE'S MULTIPLE PATHOLOGIES GOING ON IN A LOT OF THESE PEOPLE, THIS STUDY LOOKED AT CHOLINESTERASE ACTIVITY, IN PEOPLE WITH DLB COMPARED TO ALZHEIMER'S, WHICH IS CONSISTENT WITH WHAT'S BEEN KNOWN ABOUT THE AND GREATER CHOLINERGIC DEFICIT SEEN IN VIVO. THIS FIGURE HAS NOTHING TO DO WITH THAT, TO KEEP YOU ON YOUR TOES. IN ADDITION PEOPLE HAVE USED AMYLOID IMAGING TO TRY TO DISTINGUISH PARKINSON'S DEMENTIA FROM PEOPLE WITH ALZHEIMER'S. THIS STUDY DONE BY MEGAN CAMPBELL IN OUR CENTER, WE DID A PRINCIPLE COMPONENTS ANALYSIS OF THE DISTRIBUTION OF AMYLOID IN PEOPLE WITH PARKINSON'S, THAT'S WHAT THIS FIGURE IS, SO PEOPLE IN GREEN HERE ARE ALZHEIMER'S, PEOPLE IN BLUE ARE WITH PARKINSON'S, AND THERE WAS A CLEAR SEPARATION, THIS IS JUST PRINCIPLE COMPONENT ONE VERSUS TWO, LOOKING AT THE DISTRIBUTION OF THE IMAGING AGENT, AND YOU CAN SEE A NICE SEPARATION. THERE'S SOME OVERLAP BUT IT'S FAIRLY DISTRICT PATTERNS. THE AMYLOID THAT WE CAN DETECT WITH PIB IS DIFFERENT IN DISTRIBUTION IN PEOPLE WITH PARKINSON'S FROM THOSE WITH ALZHEIMER'S, THAT'S TRUE EVEN WHEN WE LIMITED THIS TO PEOPLE WHO HAVE COMPARABLE COGNITIVE IMPAIRMENT. THERE'S ONGOING STUDY AT THE UNIVERSITY OF MICHIGAN WHERE THEY ARE COMBINING THREE DIFFERENT IMAGING MODALITIES, SO DOPAMINE TRANSFORTER, VEST LARGE ANIMAL MONO AMINE TYPE 2 THAT MARKS PRESYNAPTIC VEST TELLS, AND COMBINING THOSE IN A LONGITUDINAL STUDY, I DON'T THINK THEY PUBLISHED THIS YET, I'M NOT SURE THIS IS OUT. AND IT LOOKS LIKE THEY CAN VERY CLEARLY DO A BETTER JOB PREDICTING AUTOPSY DIAGNOSIS THAN CLINICAL DIAGNOSIS SO USING THIS IMAGING THEY CAN DISTINGUISH DLB FROM AD BETTER WITH THE IMANNUALING THAN CLINICALLY. THERE IS NOT NECESSARILY SUCH A GREAT DISTINCTION WITH THE OTHER DEMENTING ILLNESSES BUT THESE TWO SEEM TO BE WELL DISTINGUISHED. GOING TO A DIFFERENT KIND OF PET METHOD, FCG, AND IT'S CLEAR USING A SPATIAL CO-VARIANCE METHOD DIFFERENT FROM WHAT DAVID IDLEBERG DOES, THEY CAN -- THIS GROUP HAS DISTINGUISHED CLEARLY ALZHEIMER'S FROM PEOPLE WITH PARKINSON'S BUT THEY WERE NOT AT ALL ABLE TO DISTINGUISH PDD FROM DLB. THOSE TWO THINGS LOOK ENTIRELY THE SAME WITH THE DISTRIBUTION AGAIN OF THE FDG. WHEREAS THIS GROUP HAS USED SPM T MAPS, TAKING THE FDG IMAGE, COMPARING TO CONTROL, ASKING HOW DOES THE VOXEL BASED APPEARANCE DIFFER FROM ALZHEIMER'S TO NON-ALZHEIMER'S DEMENTIA AND THEY ARE ABLE TO DO THAT PREDICTION. THIS IS WHAT THEY ARE SHOWING HERE, THEY TAKE PEOPLE FOR EXAMPLE WITH PDMCI AND THEN LOOK AT THE IMAGE HERE AND THEN DETERMINE WHETHER THEY HAVE AN ALZHEIMER'S TYPE PAT HE WERE IN THE IMAGE OR NON-ALZHEIMER'S OR PARKINSON'S, NEGATIVE PATTERN FOR ALZHEIMER'S, THEY WILL BE ABLE TO PREDICT WHO IN FOLLOW-UP WILL THEN BE MORE LIKELY TO DEMEANT. IF THE PERSON WITH MCI HAD ALZHEIMER'S PATTERN THEY WERE MORE LIKELY TO FOLLOW UP, THE NUMBERS ARE SMALL. THESE GROUPS ARE IN GROUPS OF LIKE 8, SO IT'S SMALL PRELIMINARY STUDY. ANOTHER THING THAT'S COMING DOWN THE ROAD TO HELP DISTINGUISH PARKINSON'S DEMENTIAS FROM LEWY BODY DEMENTIAS FROM ALZHEIMER'S IS TAU IMAGING, AND SO THIS HASN'T BEEN DONE YET. NOTHING PUBLISHED IN PARKINSON'S COMPARING ALZHEIMER'S BUT THIS IS THE KIND OF THING THAT'S GOING ON, THERE MAY BE HIGHER UPTAKE OF TAU, THAT'S THE NOTION, COMPARED TO THE PEOPLE WITH ALZHEIMER'S, IT MAY VARY DEPENDING UPON SPECIFIC PATHOLOGICAL UNDERPINNINGS HERE. FURTHERMORE, RESTING STATE FUNCTIONAL CONNECTIVITY, TAKING PEOPLE LYING IN AN M.R. SCANNER, BOLD IMAGING, LOOKING AT THE RELATIONSHIPS OF DIFFERENT REGIONS AND THEIR BOLD ACTIVITY, THERE'S STANDARDEST ARING STATE NETWORKS, GREATER LOSS IN NETWORKS. THERE'S A LOT OF FUNKY DETAILS IN THIS STUFF. SO REALLY CAREFUL ATTENTION TO DETAILS HOW ONE CORRECTS FOR SLIGHT MOVEMENTS IN THE HEAD CAN MAKE HUGE DIFFERENCES IN THE INTERPRETATION OF THESE DATA. AND SO WHAT I'M GOING TO TELL YOU IS A LITTLE BIT OF DISCREPANCY DATA, INCREASING RIGOR IN CORRECTING FOR THESE THINGS AND THE BEHAVIOR OF SOMEBODY DURING THE SCAN CAN MAKE A HUGE DIFFERENCE. THE THINGS THAT HAVE BEEN SEEN, RECENT STUDY LOOKING AT THE LOSS OF THE CONNECTIVITY OF THE DEFAULT MODE NETWORK, RESTING STATE DIFFERS IN DLB VERSUS A.D. THESE SEEM TO BE MUCH LESS POTENT IN THIS PARTICULAR STUDY, ONLY IN THE PEOPLE WITH DLB COMPARED TO THOSE WITH ALZHEIMER'S, AND IN THIS STUDY THEY SAW GREATER CONNECTIVITY WITH BASAL GANGLIA. IN ANOTHER STUDY, BOTH USED INDEPENDENT COMPONENTS ANALYSIS, AS OPPOSED TO SEED BASED APPROACH, THIS PARTICULAR STUDY FOUND NO CHANGES IN THESE CORTICAL NETWORKS BUT RATHER FOUND INCREASED PUTAMEN CONNECTIVITY, ONE THING THAT'S ENTIRELY CONSISTENT BETWEEN THE TWO STUDIES IS THAT IN PEOPLE WITH DLB COMPARED TO A.D. THEY HAVE AN INCREASED CONNECTIVITY WITH CERTAIN BASAL GANGLIA STRUCTURE, THAT'S FAIRLY CONSISTENT. AND DLB VERSUS PDD ON THE OTHER HAND, THERE'S SWITCHING OVER TO PET, AGAIN ONE CAN LOOK AT POSITIVITY ON AMYLOID IMAGING, THAT'S WHAT'S REVIEWED WELL RECENTLY, SHOWING THAT PEOPLE WITH DLB HAVE A HIGHER RISK OF HAVING THE KIND OF UPTAKE YOU SEE IN ALZHEIMER'S DISEASE VERSUS PEOPLE WITH PDD WHO SEEM TO BE LOWER AND THAT'S ACROSS MULTIPLE STUDIES, NOT EVERY STUDY HAS HAD THAT FINDING, SOME DON'T, BUT THAT WOULD BE CONSISTENT WITH SOME OF THE PATHOLOGY. JUST TO MAKE A SMALL COMMENT BECAUSE PEOPLE DO TRY TO USE DAT IMAGING TO DISTINGUISH FROM ALZHEIMER'S -- DAT IMAGING CAN BE NORMAL. YOU HAVE TO BE CAREFUL WITH SOME OF THOSE. I'M ALMOST DONE. THEN THE OTHER POINT AGAIN CAN WE USE THIS TO LOOK AT MCI OR COGNITIVE DECLINE? AND HERE IS ANOTHER RESTING STATE M.R. STUDY LOOKING AT FUNCTIONAL CONNECTIVITY AND THEY FOUND IN PEOPLE WITH MCI THAT THEY HAD REDUCED STRENGTH OF BILATERAL PREFRONTAL CORTEX CONNECTIONS IN THE FRONT PARIETAL NETWORK AND THIS IS JUST SHOWING LEFT AND RIGHT FRONTAL PARIETAL CONNECTIVITY HERE, AND THIS IS SHOWING DIFFERENCE, SO IT WAS FOUND HERE. I'M GOING TO JUMP DOWN TO HERE, SIMILARLY FOUND REDUCED DORSAL ATTENTION NETWORK CONNECTIVITY IN PEOPLE WITH MCI AS WELL AS FRONTAL INSULAR, ANOTHER NAME FOR WHAT'S UP HERE, VERY CONSISTENT. THIS STUDY ACTUALLY TRIED TO LOOK OR DID LOOK AT LONGITUDINAL STUDIES WHERE THEY FOUND THAT FUNCTIONAL CONNECTIVITY REDUCED WITH COGNITIVE DECLINE, THESE WERE PEOPLE AS THEY ARE DEMENTING, THERE WAS LOTS OF CHANGES THROUGHOUT CORTICAL AREAS, NOT FOUND IN ANY OF THESE OTHER STUDIES. THIS PARTICULAR STUDY WHICH I'M FOUND OF BECAUSE IT'S FROM OUR CENTER LOOKED AT PEOPLE WITH NON-DEMENTED PARKINSON'S PATIENTS AND COMPARED THOSE PEOPLE WHO HAD MCI VERSUS THOSE WHO DID NOT HAVEMCI FOLLOWED THEM, THOSE PEOPLE WHO HAD MCI HAD NORMAL DORSAL ATTENTION NETWORK. THOSE WHO DID NOT HAVE AT BASELINE HAD ABNORMALLY ELEVATED NETWORK, WHEN REPEATED AT VISIT 2 THE PEOPLE SPLIT, THOSE WHO WERE THEN IN VISIT 3 BECOME MORE COGNITIVELY IMPAIRED, WEREN'T MORE COGNITIVELY IMPAIRED HERE, HAD THE NETWORK COME DOWN TO WHAT THE OTHERS WITH MCI HAD, WHICH IS IN FACT NORMAL, SUGGESTING THERE WAS A COMPENSATORY ACTIVITY THAT IS LOST THAT PREDATES ADDITIONAL COGNITIVE IMPAIRMENT. RESTING STATE STUDY MAY GIVE IS ANTECEDENT INFORMATION ABOUT SUBSEQUENT COGNITIVE IMPAIRMENT. SO OUR PRIORITIZE THE RECOMMENDATIONS, SUCCESS CRITERIA, CONVENE A WORKSHOP OF EXPERTS AND RELATED DISCIPLINES IN WHICH WE CAN DISCUSS ANALYTIC APPROACHES AND STANDARDIZATION, WE CAN FIND VERY HIGHLY STATISTICALLY SIGNIFICANT STUFF THAT'S NOT REPRODUCIBLE BECAUSE OF METHODOLOGICAL DIFFERENCES AND BEGIN ONE STUDY FOR THE DIFFERENTIAL DIAGNOSIS OF LEWY BODY DEMENTIAS COMPARED TO OTHER DEMENTING ILLNESSES IN LONGITUDINALLY FOLLOWED COHORTS CONFIRMED BY AUTOPSY ULTIMATELY. IF THEY ARE NOT CONFIRMED WE HAVEN'T LEARNED MUCH IS MY OPINION. INCLUDE EMERGING TECHNOLOGIES INCLUDING FUNCTIONAL MRI, MOLECULAR IMAGING OR INCLUDING ALPHA SYNUCLEIN, AND WE THANK MICHAEL FOX, EFFORTS ARE ONGOING, IT HASN'T COME THROUGH YET. THANK YOU. AND NOW CLEMENS WILL TALK ABOUT THE BIOLOGICAL ASPECTS. [APPLAUSE] >> THE SECOND PART OF THIS ABOUT BIOMARKERS. THE IMPORTANCE OF BIOMARKERS HAS BEEN A TOPIC THROUGHOUT THIS DAY. IT'S IMPORTANT TO KEEP IN MIND THAT FOR BOTH PDD AND DLB WE DON'T JUST NEED ONE BIOLOGIC MARKER BUT WE NEED A TOOL BOX OF DIFFERENT BIOMARKERS. WE NEED BIOMARKERS FOR EARLY DIAGNOSIS, FOR TRACKING THE PROGRESSION OF PDD, MEASURING DISEASE RESPONSE TO THERAPIES, AND WE ALSO NEED MARKERS FOR DIFFERENTIAL DIAGNOSIS. SIMILARLY FOR DLB WE NEED MARKERS THAT CAN IDENTIFY PRODROMAL CHANGES, PERHAPS PRE-CLINICAL STAGES OF DLB AND THEN MARKERS THAT CAN TRACK THE COURSE, PROGRESSION OF DISEASE SEVERITY AND RESPONSE TO THERAPEUTICS. WE NEED MARKERS SPECIFICALLY LINKED TO MECHANISTIC PROCESSES, AND IT'S VERY REICHLY SOME MARKERS CAN FULFILL SEVERAL OF THESE CRITERIA BUT AT THE END OF THE DAY WE'LL LIKELY END UP WITH A TOOL BOX OF MARKERS. WE'RE FORTUNATE THAT THERE IS A FULL PIPELINE OF BIOMARKERS BUILDING UP FOR ALZHEIMER'S DISEASE AS WELL AS PARKINSON'S DISEASE THAT ARE HIGHLY RELEVANT AND CAN INSPIRE BIOMARKER DEVELOPMENT FOR LEWY BODY DEMENTIAS AND ACTUALLY SINCE THE I LAST SHOWED THIS SLIDE IN 2013 SEVERAL NEW CANDIDATES WERE MOVED TO THE FRONT OF THE PACK, AT LEAST FOR PARKINSON'S DISEASE. I WILL BRIEFLY TOUCH ON SOME HIGHLIGHTS, STUDIES THAT I'M PARTICULARLY INTERESTED IN. BUT THE BIG PICTURE IS THAT SINCE 2013 THERE HAVE BEEN AT LEAST SIX BIOMARKER STUDIES FOR PDD AND AT LEAST 4 FOR DLB, AND THERE ARE INTERESTING THEMES EMERGING, PDD BIOMARKER STUDIES ARE GETTING LARGER, TEND TO BE LONGITUDINAL OR PERSPECTIVE. THE DLB STUDIES ARE STILL RELATIVELY SMALL, TYPICALLY PATIENT POPULATION OF 30 DLB PATIENTS VERSUS 30 CONTROLS, AND CROSS-SECTIONAL AND THAT REFLECTS THE UNDERLYING NEED FOR LARGER LONGITUDINAL BIOBANKS ESPECIALLY FOR DLB. HERE IS ONE OF THE LONGITUDINAL BIOMARKER STUDIES FOR COGNITIVE DECLINE IN PARKINSON'S DISEASE. THAT'S FROM OUR GROUP. WE LOOKED AT THREE LONGITUDINAL STUDIES, HARVARD BIOMARKER STUDY, THE PARKINSON'S DISEASE STUDY GROUP PROBE STUDY AND MICHAEL J. FOX STUDY, 800 PATIENTS AND CONTROLS. FIRST IN THE CROSS-SECTIONAL ANALYSIS WE FOUND THAT SYNUCLEIN mRNA LEVELS ARE REDUCED 20% IN BLOOD OF PARKINSON'S PATIENTS, TREATED OR NOT TREATED, THIS WAS CONFIRMED TWO DIFFERENT PLATFORMS, PHYSICAL GENE EXPRESSION ANALYSIS IN THE PPMI STUDY SHOWING 27% REDUCTION OF SYNUCLEIN IN DE NOVO PARKINSON'S'S PATIENTS, DIFFERENT ISOFORMS OF TRANSCRIPTS DETECTED, PARTICULARLY THE LONG-3 UTR APPEAR TO BE DOWN REGULATED, INTERESTING BECAUSE THERE'S SOME EVIDENCE SUGGESTING THAT THE LONG FREE TIME TAIL ADDRESSES THIS TRANSCRIPTS MITOCHONDRIA. HOW IS THIS RELEVANT? WELL, IF THE GROUP, THE PARKINSON'S PATIENTS, INTO THOSE WITH THE HIGHEST LEVELS OF SNCA EXPRESSION IN BLOOD AND 25% WITH THE LOWEST EXPRESSION LEVELS, LOOK AT LONGITUDINAL DECLINE AND IMPAIRMENT MEASURED BY SCORES COLLECTED OVER FIVE YEARS, THE SYNUCLEIN EXPRESSERS SEEM TO HAVE A MORE RAPID COGNITIVE DECLINE COMPARED TO THE THE HIGH EXPRESSERS, WHICH ARE VIRTUALLY STABLE. AND THIS WAS SIGNIFICANT IN THE HARVARD BIOMARKER STUDY. IT WAS NOT SIGNIFICANT BUT SHOWED THE SAME TREND IN APPROACH STUDY, HERE THE LONGITUDINALLY FOLLOWED CASES WERE SMALL IN SAMPLE SIZE, IN THE META ANALYSIS ACROSS TWO STUDIES IT WAS SIGNIFICANT, AN INTERESTING LEAD AND MUCH MORE WORK NEEDS TO BE DONE IN OTHER COHORTS. ANOTHER INTERESTING LONGITUDINAL STUDY CAME OUT LOOKING AT CSF MARK MARKERS OF 99 PARKINSON'S PATIENTS LONGITUDINALLY FOLLOWED FOR UP TO TEN YEARS, AND EXCITINGLY WHAT HE FOUND IS THAT PATIENTS WITH LOW LEVELS OF CSS A-BETA 132 AT BASELINE HAD A FASTER DECLINE SO THEY HAD HIGHER RATE OF -- HIGHER RISK, HIGHER HAZARD RATIO OF PDD OVER TIME COMPARED TO INDIVIDUALS WITH HIGH CSF A-BETA LEVELS. THIS MAKES SENSE WITH WHAT WE HAD BEFORE WITH LOW A-BETA, MIGHT BE AN INDICATOR OF A.D. PATHOLOGY CONTRIBUTING TO PDD IN THESE FOLKS. THE TWO OTHER MARKERS THAT HE LOOKED AT ARE ALSO INTERESTING, CSF, NEUROFILAMENT LIGHT CHAINS, CSF HEART FATTY ACID BINDING PROTEIN, BOTH MARKERS HAD PREVIOUSLY BEEN FOUND TO BE ASSOCIATED WITH DLB IN CROSS-SECTIONAL STUDIES AND NOW IN THE LONGITUDINAL STUDY HE ADDED AN INTERESTING TWIST THAT COMPLETELY CONSISTENT WITH THE CROSS-SECTIONAL STUDY, PARKINSON'S PATIENT WITH HIGH NEUROFILAMENT LEVELS AT BASELINE HAD A HIGHER HAZARD RATIO OF PDD COMPARED TO THOSE WITH LOW NEUROFILAMENT LEVELS AT BASELINE, THE SAME FOR HEART FATTY ACID PROTEIN, BOTH NEUROFILAMENT AND HEART FATTY ACID BINDING PROTEIN ARE PROBABLY MARKERS OF NEURONAL INTEGRITY THAT CAN BE MEASURED IN CSF. THERE WAS SEVERAL OTHER INTERESTING LONGITUDINAL STUDIES, FOR EXAMPLE TAKING ADVANTAGE OF THE DATA THOUGHTS LONGITUDINAL CSF COLLECTION INDICATING THAT HIGH CSF AND RATIO OF A-BETA 42 IS ASSOCIATED WITH MORE RAPID COGNITIVE DECLINE IN PARKINSON'S DISEASE. AND I'LL FINISH UP WITH JUST HIGHLIGHTING THREE SNAPSHOTS IN THE DLB BIOMARKERS AREA, THESE STUDIES ARE SMALLER AND THEY ARE REALLY IN NEED OF FURTHER REPLICATION, BUT ALSO SOME INTERESTING TRENDS ARE EMERGING, FOR EXAMPLE CSF ALPHA SYNUCLEIN, LEWY BODY DEMENTIAS IN PARTICULAR, SPECIFICALLY DLB COMPARED TO HEALTHY CONTROLS AS WELL AS PDD COMPARED TO HEALTHY CONTROLS AND THIS WAS AGAIN CONFIRMED IN ONE STUDY BUT NOT IN THE OTHER, AND SO WHAT'S SHOWN HERE, IN THE LEWY BODY DEMENTIAS ALPHA SYNUCLEIN LEVELS WERE LOWER COMPARED TO ALZHEIMER'S DISEASE AND WHEN THEY PULLED THE LEWY BODY DEMENTIAS TOGETHER OVERALL THERE WAS REDUCTION COMPARED TO THE HEALTHY CONTROLS. IN ADDITION TO THIS MARKERS EMERGING, ESSENTIALLY THAT HAVE EMERGED FROM PARKINSON'S AND ALZHEIMER'S, THERE ARE NEW CANDIDATES ON THE HORIZON PARTICULARLY ONE STUDY FROM HENRIETTA NEILSEN'S GROUP FROM SWEDEN IDENTIFIED THAT SOLUBLE PROTEOGLYCAN NG 2 WAS DECREASED IN DLB COMPARED TO HEALTHY CONTROLS BUT AGAIN SMALL SAMPLE SIZES, 30, 40 PATIENTS, SIMILARLY NEUROCIN, A PROTEASE WHICH MIGHT BE -- WAS DECREASED COMPARED TO HEALTHY CONTROLS AS WELL AS TO ALZHEIMER'S PATIENTS. AND NOT SO MUCH HAS BEEN GOING ON ON THE UNBIASED OMICS DISCOVERY OF NEW MARKERS BUT AT LEAST ONE STUDY HAS ATTEMPTED TO USE SERUM PROTEOMICS TO FIND 11 NEW POTENTIALLY INFORMATIVE PEP SIDES ASSOCIATED WITH SERUM. SO WE -- OUR RECOMMENDATION NUMBER 6 LARGELY UNCHANGED FROM 2013, TO USE NEW OR EXISTING LONGITUDINAL CASE CONTROL STUDIES OF INDIVIDUALS WITH DLB AND PDD AND LONGITUDINAL COHORT STUDIES, TRACKING COGNITIVE DECLINE AND STUDIES CAPTURING INCIDENT CASES OF LEWY BODY DEMENTIAS, TO DEVELOP BIOMARKERS FOR RELATED TO PATHOLOGIC CHANGES RELATED TO DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS AS WELL AS DISEASE PROGRESSION AND THERAPEUTICS RESPONSE. THIS IS SUCCESS CRITERIA, RECOMMEND TO IDENTIFY EXISTING COLLECTIONS OF TISSUE AND BIOFLUID SAMPLES, AND FROM READILY AVAILABLE STUDIES INCLUDING CLINICAL TRIALS WITH WELL ANNOTATED CLINICAL DATA AND BEST PRACTICE SAMPLE COLLECTION PROCEDURES, WHAT WE ADDED BASED ON COMMUNITY FEEDBACK IS THE PARTICULAR EMPHASIS ON THE MICROBIOME, THERE WAS SOME GOOD FEEDBACK AND THAT'S CERTAINLY A VALUABLE AVENUE AS WELL. AND IN ADDITION TO ANALYZING EXISTING BIOBANK ALSO RECOMMENDATION IS TO INITIATE AT LEAST ONE NEW LARGE STUDY TO DEVELOP AND VALIDATE NORMAL BIO, MAKERS USING WELL CHARACTERIZED LEWY BODY DEMENTIA SAMPLES. THERE IS IT FOR RECOMMENDATION NUMBER 6. MY PLEASURE TO ANNOUNCE A MAN WHO DOES NOT NEED ANNOUNCING. [APPLAUSE] >> THANK YOU VERY MUCH. HOW ARE YOU DOING? I THINK WE'RE A LITTLE BIT LATE SO I'LL TRY TO BE BRIEF AND SO WE CAN MOVE ON TO THE LAST SECTION OF THE PROGRAM. SO I'M GOING TO REVIEW RECOMMENDATIONS 7 AND 8. THIS IS WORK THAT WAS DONE TOGETHER WITH THE COMMITTEE AND IN PARTICULAR I WAS WORKING WITH LAURA AND I WANTED TO THANK THE ORGANIZERS FOR INVITING ME TO BE PART OF THIS IMPORTANT SUMMIT. SO RECOMMENDATIONS 7 AND 8 RELATE TO THE CREATION OF NEW ANIMAL MODELS OF IN VITRO AND IN VIVO ANIMAL MODELS FOCUSING ON ALPHA-SYNUCLEIN AND TO TRY TO CAPTURE COMPLEXITY OF DISEASE, RECOMMENDATIONS WERE SLIGHTLY REVISED TO INCLUDE THINGS SUCH AS UNDERSTANDING THE SELECTIVE NEURONAL VULNERABILITY AND SOME MECHANISMS OF NEURONAL DYSFUNCTION AND DISEASE PROGRESSION THAT WERE NOT WELL KNOWN AND ALSO SINCE OF TIME OF RECOMMENDATIONS QUITE A BIT OF PROGRESS HAS BEEN MADE ON DEVELOPING MODELS BASED ON THE CONCEPT OF TRANSMISSION AND PROPAGATION SO THIS IS ALSO AN IMPORTANT COMPONENT OF THE REVISED MATERIAL, AND THE SECOND PART RELATES TO THE IN VITRO MODELS THAT THERE WERE VERY ALSO CHANGES HERE BUT AGAIN THE IDEA OF DEVELOPING IN VITRO MODELS IN PARTICULAR UTILIZING iPS CELLS OR OTHER TYPES OF CELLS OBTAINED FROM HUMAN MATERIAL THAT WILL INCLUDE THE COMPLEXITY OF THE GENETICS OF THE DISEASE AND ALSO THE BIOMARKER AND CLINICAL ASPECTS OF IT. THERE HAS BEEN A TREMENDOUS PROGRESS IN DEVELOPING NEW EXPERIMENTAL MODELS AS I MENTIONED BEFORE, IN PARTICULAR MODELS RELATED TO THE USE OF SEEDS AND PROPAGATION, A LOT OF WORK DONE BY VIRGINIA LEE, JOHN AND A NUMBER OF OTHER INVESTIGATORS, AND THE BOTTOM LINE IS THAT SYNUCLEINS HAVE BEEN INJECTED INTO WILDTYPE AND LOW EXPRESSER NEUTRIGENIC ANIMAL MODELS, DIFFERENTIAL PATTERNS OF NEUROPATHOLOGY HAVE BEEN DEVELOPED UTILIZING FIBRILS, EITHER SYNTHETICALLY MADE OR DERIVED FROM PATIENTS, DIVERSE POPULATIONS RECOLLECTION PATTERNS OF DISEASE CAN BE REPRODUCED IN THE ANIMAL MODELS THAT COULD MIMIC EITHER PD OR DLB OR EVEN MULTIPLE SYSTEMS ATROPHY. IN TERMS OF TRANSGENERAL IT MODEL, A LOT OF THE MODELING IT'S OF PDD VERSUS DLB OR PD DEPENDS ON THE TIME OF PROMOTERS USED, EITHER THE PDGF, PRP, ET CETERA, AND AS YOU CAN SEE HERE WITH THE PDGF PROMOTER WE TEND TO SEE A PATTERN OF THE DISTRIBUTION OF ALPHA-SYNUCLEIN REMINISCENT OF DLB WITH CORTICAL AND LIMBIC PATTERN WHILE WITH THE PSY 1 AND PRP PROMOTER THERE'S A MORE WIDESPREAD DISTRIBUTION OF SYNUCLEIN MORE REMINISCENT OF PDD OR OTHER PD. THERE HAS ALSO BEEN TREMENDOUS PROGRESS NOT ONLY ON A UTILIZING SMALL MICE, DEVELOPING RAT MODELS OF NEURODEGENERATIVE DISORDERS, IN PARTICULAR RECENT PUBLICATION, THIS IS WHAT I WOULD THINK IS A VERY EXCITING MODEL, UTILIZING ALPHA ALPHA-SYNUCLEIN, IT'S A RAT, CORTICAL AND LIMBIC REGIONS, REMINISCENT OF DLB BUT THE ANIMALS ALSO DEVELOP SYNUCLEINOPATHY, WITH LOSS OF CHOLINERGIC -- SORRY, LOSS OF DOPAMINERGIC FIBERS, AND THE ANIMALS BECAUSE OF SIZE AND CHARACTERISTICS COULD BE IMAGING IN MICRO PET AND LOSS COULD BE DETECTED AND THEY SHOW LONGITUDINAL CHANGES THAT COULD BE CORRELATED WITH BEHAVIORAL DEFICITS IN THE ANIMALS. HERE WE MAINLY CHARACTERIZE MOTOR PHENOTYPE, ANIMALS ALSO DEVELOP CORTICAL PHENOTYPE WITH ACCUMULATION OF SIGN NUCLEIN AGGREGATES. THERE HAS BEEN A LOT OF ADVANCES DONE BASED ON THE GENETICS INDICATING THAT A LOT OF THE GENES ASSOCIATED IN ADDITION OF BEING ALPHA-SYNUCLEIN, A LOT ARE LYSOSOMAL GENES SUCH AS GBA AND OTHER GENES, SO THE EFFORT HAS BEEN COMBINING I SYNUCLEINOPATHY ANIMAL MODELS WITH GBA AND LYSOSOMAL GENES. I'LL MENTION ONE EXAMPLE, THERE'S A NUMBER OF LYSOSOMAL GENES COMBINED WITH SYNUCLEIN ANIMALS. THE GROUP DEVELOPED BY ROBERT SHOW AUGMENTATION OF SYNUCLEIN PATHOLOGY IN THE MUTANT ANIMAL MODEL, THE KNOCKDOWN OF THE GBA EXPRESSING THIS MUTANT, IT'S REALLY INTERESTING THAT IN OLDER ANIMALS THEY CAN SHOW PROGRESSIVE ACCUMULATION OF PHOSPHORYLATED SYNUCLEIN IN MULTIPLE BRAIN REGIONS INCLUDING REGIONS THAT ARE AFFECTED IN DLB SUCH AS LIMBIC SYSTEM. AND ANOTHER INTERESTING MODEL AND AGAIN QUITE A BIT OF PROGRESS BOTH BACTERO AGAINIC, COMBINATION MODEL, UTILIZING VIRAL VECTOR IN THIS WORK BY THE GROUP OF YORKLAND, THEY UTILIZE ALPHA-SYNUCLEIN BUT THIS TIME WHAT THEY DID IS THEY INJECTED IT IN THE FOREBRAIN OF THE ANIMALS, THE TRADITIONAL MODELS UTILIZING VIRALLORS, INJECTED ALPHA ALPHA-SYNUCLEIN AND DEMONSTRATED CORTICAL LOSSES OF NEURONS IN TICKLES REDUCTION ON CAT NEURONS, WITH ACCUMULATION OF SYNUCLEIN IN REGIONS RELEVANT TO SUCH AS OLFACTORY STRIATUM AND OTHER CORTICAL BRAIN REGIONS. AND FINALLY AS I MENTIONED AT THE BEGINNING A TREMENDOUS PROGRESS HAS BEEN MADE, MAINLY BY JOHN AND VIRGINIA ON MODELS UTILIZING SEEDS AND FIBRILS AND THIS IS MORE RECENT MODEL THAT LAURA VOLPICELLI WAS DEVELOPING WHERE SHE USED SONICATED FIBRILS FROM RECOMBINANT SYNUCLEIN FROM MOUSE AND INJECTED IT INTO MULTIPLE BRAIN REGIONS INCLUDING THE STRIATUM BUT THE INTERESTING THING IS THAT SYNUCLEIN PATHOLOGY WAS DETECTED IN CORTICAL REGIONS IN THE HIPPOCAMPUS AND IN PARTICULAR IN THE AMYGDALA, YOU CAN SEE SOME OF THE SYNUCLEIN PATHOLOGY IN THIS REGION, LIMBIC REGION, WHICH IS RATHER STRIKING AND THIS IS THE TYPE OF LIMBIC SYNUCLEIN PATHOLOGY WE SEE IN DLB AND EVEN IN ALZHEIMER'S DISEASE SO I THINK IT'S QUITE AN INTERESTING MODEL. OF COURSE, I THINK WE NEED TO DO MORE WORK IN INJECTING THESE DIFFERENT TYPES OF FIBRILS IN DIFFERENT BRAIN REGIONS AND I KNOW FROM RECENT ADLER FOUNDATION MEETING AND OTHER MEETING THAT JOHN AND VIRGINIA ARE WORKING ON INJECTING ALPHA ALPHA-SYNUCLEIN IN THE HIPPOCAMPUS AND OTHER BRAIN REGIONS TO MODEL DLB AS WE KNOW FROM THE WORK OF DENNIS DICKSON AND ALSO JOHN, THERE ARE A NUMBER OF DIFFERENT TYPES OF LEWY BODY DISTRIBUTION AND REALLY DLB IS A TERATOGENIC DISORDER, THIS HETEROGENEITY MIGHT BE A MODEL BY INJECTING DIFFERENT TYPES OF FIBRILS IN DIFFERENT BRAIN REGIONS. I THINK THE OTHER THING THAT WE STILL NEED TO CONSIDER AND THAT MORE WORK IS NEEDED IS IN COMBINING SOME OF THESE MODELS OF SYNUCLEINOPATHY WITH TOXINS, SOME WORK HAS BEEN DONE WITH PARAQUAD BUT MORE WORK IS NEEDED. WE NEED TO DO MORE WORK IN EXPRESSING ALPHA-SYNUCLEIN IN SELECTED NEURONAL POPULATIONS TO EXPLORE HOW SELECTIVELY EXPRESSING SYNUCLEIN OR INJECTING SYNUCLEIN IN CERTAIN NEURONS IS INVOLVED IN VULNERABILITY, DIDN'T HAVE MUCH TIME TO TALK ABOUT IPS BUT THIS IS WORK THAT IS COMING UP AND FINALLY MODELS SHOULD HAVE TRACTABLE BOUGH MARKERS THAT COULD BE USED FOR DEVELOPING OF CLINICAL TRIALS AND IN THIS REGARD AS I MENTIONED SOME OF THE LARGER TRANSGENIC MODELS THAT CAN BE USED FOR PET IMAGING FOR EXAMPLE IF A SYNUCLEIN PET IMAGING TOOL COULD BE DEVELOPED, I MEAN, ANIMALS LIKE THE RAT MODEL COULD BE REALLY FANTASTIC TOWARD DEVELOPING PRE-CLINICAL MODEL WITH A TRACTABLE BIOMARKER THAT COULD BE USED AS AN EXAMPLE TOWARD CLINICAL TRIALS. SO HERE IS THE SUCCESS CRITERIA FOR THE MILESTONE NUMBER 7, THE HOPE IS ADDITIONAL MODELS WILL BE DEVELOPED THAT WILL NOT ONLY BE FOCUSED ON ALPHA ALPHA-SYNUCLEIN BUT INTERACTIONS WITH A BETA, WITH TAU, TDB-43, ET CETERA, AND ALSO AGAIN THAT THESE MODELS COULD BE USED FOR THERAPEUTICS AND THERAPEUTICS, DISEASE-MODIFYING THERAPEUTICS IS THE LAST RECOMMENDATION, NUMBER 8, DEVELOP DISEASE MODIFYING INTERVENTIONS BASED ON BIOMARKERS AND ANIMAL MODELS AND SO O ALL THE ANIMAL MODELS, WE DESCRIBED HIGHLY USEFUL, THEY DON'T TRULY REPRESENT THE WHOLE SPECTRUM OF THE DISEASE, PROBABLY THEY DEVELOP SOME PORTION OF THE SPELL SPECTRUM, SOMEWHAT NARROWER, SOME WIDER, AT THE END OF THE DAY RELATIVELY NARROW SPECTRUM OF DISEASE. SOMED MY BE USEFUL FOR PREVENTING THERAPEUTIC, DEPENDING ON WHICH PART OF THE WINDOW WE ARE LOCATED IS HOW THE ANIMAL MODELS SHOULD BE UTILIZEDS, TAR GETTING SYNUCLEIN MAY BE MORE PREVENTIVE WHILE TARGETING NEUROTROPHIC FACTOR AND STEM CELLS MIGHT BE MORE ON THE THERAPEUTICAL ASPECT. HERE BIO, MAKERS THAT ARE MORE RELEVANT THAT ARE TRACTABLE AND REFLECTED IN THE ANIMAL MODELS ALSO HAVE BEEN CONSIDERABLY DEVELOPED, IN THIS PARTICULAR ANIMAL MODEL WE DEVELOPED SEVERAL YEARS AGO THIS IS A PSY 1 ALPHA-SYNUCLEIN MODEL, THERE ARE DATA IN RECENT STUDIES THAT HAVE SHOWN THE ANIMALS NOT ONLY DEVELOP MOTOR DEFICITS BUT THEY DEVELOP COGNITIVE AND BEHAVIORAL ALTERATIONS LIKE THE WORK OF MARIA, THEY DEVELOP CARDIOVASCULAR AND DYNAMIC ALTERATIONS, THEY DEVELOP SLEEP DISORDERS, SOMETHING SIMILAR TO RBD, AND IN A VERY RECENT AND VERY INTERESTING PUBLICATION BY THE GROUP OF LEONARD MOOKIE SHOWED THAT THESE TRANSGENIC ANIMAL MODELS DEVELOPED EEG ALTERATION, IF WE CAN MODIFY IN ANIMAL MODELS WITH DISEASE-MODIFYING DRUGS, THIS KIND OF BIOMARKERS, WE CAN TEST SIMILAR HYPOTHESIS IN VIVO IN PATIENTS WITH TRANSLATABLE BIOMARKERS AND I THINK THIS IS RATHER EXCITING. SO THERE HAS BEEN A NUMBER OF THERAPEUTICS, DISEASE MODIFYING THERAPEUTICS DEVELOPED, TARGETING ALPHA-SYNUCLEIN, POP GRATING ALPHA SUE NUCLEIN, NEURON TO NEURON, NEUROTO CLIA CELLS USING IMMUNOTHERAPY OR DRUGS THAT DIMINISH INFLAMMATION THAT IS TRIGGERED BY THE SYNUCLEIN PROPAGATING TO ASTRAL GLIAL AND MACRO GLIAL CELLS, THE IDEA IS TO DEVELOP THERAPEUTICS TARGETED FOR THE DISEASE STAGE BUT THAT ALSO TAKE INTO CONSIDERATION WHAT WE HAVE LEARNED ABOUT THE GENETICS, AS I MENTIONED, SEVERAL GENETIC MARKERS ARE LYSOSOMAL MARKERS, SEVERAL INCLUDE GBA, SYNUCLEIN, TAU, ET CETERA, SO TO DEVELOP THERAPEUTICKICS BASED ON WHAT WE KNOW ON THE GENETICS AND FINALLY THE IDEA OF DEVELOPING THERAPEUTICS USING STEM CELL IS ALSO PRETTY HOT TOPIC AND I JUST WANT TO BRING THIS PAPER THAT JUST CAME UP VERY RECENTLY UTILIZING HUMAN NEURONAL STEM CELLS GRAFTED INTO OUR ALPHA-SYNUCLEIN MODEL WITH LEWY BODIES, SHOWING IT PROTECTS IN NEUROGENIC PATHOLOGY AND RESCUE THE BEHAVIORAL DEFICITS. THIS IS MY LAST SLIDE AND I THINK AGAIN THAT THERE HAS BEEN CONSIDERABLE PROGRESS MADE ON DISEASE MODIFYING THERAPEUTICS, SPECIFICALLY TARGETING ALPHA-SYNUCLEIN. THERE'S PHASE 1 CLINICAL TRIAL COMPLETED BY ROCHE, A HUMANISED MONOCLONAL ANTIBODY TARGETING THE C TERMINUS OF ALPHA-SYNUCLEIN, MOVING INTO PHASE II, MICHAEL J. FOX DEVELOPED A VACCINATION THAT'S NOW MOVING INTO PHASE II AND THIS HAS BEEN BOTH IN PD PATIENTS AS WELL AS MSA, BUT I THINK AS THESE NEW COHORTS OF ARE READY FOR CLINICAL TRIALS BECOME AVAILABLE AND TRANSLATABLE TOOLS BECOME AVAILABLE, A LOT OF THESE IMMUNOTHERAPY DRUGS THAT HAVE BEEN DEVELOPED COULD PROBABLY BE USED IN PDD AND THERE IS A LOT OF INTEREST ALSO TO USE THEM IN DLB, ALSO THERAPIES IN COMBINATION WITH UCB FUNDED BY THE MICHAEL J. FOX DEVELOPED THE SMALL MOLECULE THAT IS AN ALPHA-SYNUCLEIN STABILIZER FOR USE IN PD AND PDD THAT HAS ALREADY BEEN SHOWN TO BE SAFE IN PHASE 1 CLINICAL TRIALS AND WILL BE MOVING FORWARD. THERE ARE A NUMBER OF OTHER COMPANIES ALSO DEVELOPING THERAPEUTICS TARGETING SPECIFIC ALPHA-SYNUCLEIN. AS COHORTS ARE READY FOR CLIMBS BECOME AVAILABLE, I THINK IN THE NEXT COUPLE OF YEARS WE'RE GOING TO SEE A LOT OF PROGRESS AND AS I MENTIONED ONE OF THE SUCCESS CRITERIA WOULD BE TO HAVE THESE SORT OF CLINICAL TRIALS UNDERGOING IN THE FUTURE. THANK YOU. [APPLAUSE] SO I THINK THAT NEXT WE HAVE THE PANEL. WE HAVE STILL A FEW MINUTES I GUESS FOR THE PANEL DISCUSSION. >> ROD HAS GIVEN US 15 MINUTES BUT DON'T FEEL COMPELLED TO STAY. I WANT TO THANK DEB AND BETH-ANNE WHO HAVE BEEN TERRIFIC, WE WOULD NOT HAVE BEEN HERE WITHOUT THEM. LET'S START WITH SOME QUESTIONS. WE'RE LIMITED SO TRY TO BE SUCCINCT. WHO WOULD LIKE TO START? >> I'M MARY MILLER PROGRAM DIRECTOR FOR THE GENETICS OF ALZHEIMER'S DISEASE AT THE NATIONAL INSTITUTE ON AGING. THREE QUICK BULLETS. THIS IS TWO DR. THANER, WE HAVE BEEN ENGAGED IN A WHOLE GENOME SEQUENCE PROJECT AS WELL AS WHOLE EXOME SEQUENCE PROJECT, HUNDREDS OF WHOLE GENOMES AND HOUSE AND THOUSANDS OF WHOLE EXOMES. I WOULD RECOMMEND YOU MOVE TO GET MORE BANG FOR YOUR BUCK. IT'S GOING TO GO DOWN MORE. YOU'LL GET MUCH MORE INFORMATION AND WE FOUND NOT SO MUCH IN THE EXOMES. IF YOU'RE COMPARING LEWY BODY DISEASE OR ANY OTHER DEMENTIAS TO ALZHEIMER'S DISEASE, LOOKING AT THE EXOMES IS MAYBE NOT THE BEST PLACE TO START. THE SECOND THING IS I WOULD URGE YOU STRONGLY TO LOOK AT ENDOPHENOTYPES, THE THINK WE'RE GOING TO HAVE TO DO THIS THE OPPOSITE WAY WE THOUGHT WE WERE GOING TO DO IT, STACK UP THE GENES FIRST AND THEN LOOK AND SEE WHAT THE GENES TELL US ABOUT THE ENDOPHENOTYPE RATHER THAN LOOKING TO FIGURE OUT WHAT THE GENES ARE. THE THIRD THING IS THAT WE SPEND A LOT OF TIME AND ENERGY AND MENTAL PERTURBATION TO GET A PRETTY GOOD SYSTEM FOR DATA COORDINATION. I'D STRONGLY RECOMMEND THAT YOU START WITH YOUR DATA COORDINATION CENTER AT FIRST RATHER THAN LAUNCHING INTO A SEQUENCING PROJECT AND NOT KNOWING WHERE YOU'RE GOING TO PUT YOUR DATA. WE WERE LUCKY BECAUSE WE LAUNCHED BOTH OUR SEQUENCING PROJECT AND DATABASE AT THE SAME TIME AND HAD WE NOT DONE THAT WE WOULD HAVE BEEN IN THE REAL PROBLEM A YEAR LATER. THAT'S MY POINTS. >> THANK YOU. >> HI. MIKE PETROCEK FROM SCRIPPS, A QUESTION ABOUT VALIDATION OF BIO, MAKERS, BIOMARKERS OF CHANGE, WHAT YOU WANT IS A BIO, MAKER THAT IF YOU FIX IT THAT THAT'S TELLING YOU THAT YOUR DRUG IN THE FUTURE IS WORKING. SO ANY INSIGHT HOW TO VALIDATE THOSE? >> UNTIL WE HAVE EFFECTIVE THERAPIES WE'RE CAUGHT IN A CIRCULAR ARGUMENT FOR A.D. OR P.D. OR ANYTHING. I THINK IT'S CHALLENGING THAT YOU COULD SAY THAT THIS IS A PREDICTIVE BIOMARKER OF RESPONSE BUT UNTIL YOU HAVE A PROVEN DRUG THAT MODIFIES DISEASE COURSE YOU'RE NOT GOING TO HAVE THAT. >> TO JUMP IN, IT'S A CO-EVOLUTION OF BIOMARKERS AND DRUGS, FOR GBA WORKING HAND IN HAND WITH A COMPANY DEVELOPS DIRECTED DRUGS TRYING TO BUILD BIOMARKERS AND DO THIS IN PARALLEL IN HUMANS AND IN MICE SO I THINK THE SAME THING WILL HAPPEN IN THE OTHER AREAS. >> I WOULD ADD THAT YOU HAVE TO BE CAREFUL WITH BIOMARKERS BECAUSE YOU HAVE TO UNDERSTAND WHAT THE PURPOSE OF THE INDIVIDUAL BIOMARKER IS. SO BIOMARKER WHICH CAN REFLECT AND UNDERLYING PROCESS MAY NOT BE RELEVANT FOR SPECIFIC INTERVENTION. INTERVENTION MECHANISM DOESN'T GO THROUGH THAT PARTICULAR PATHOLOGY IT'S NOT GOING TO GIVE YOU TARGET ENGAGEMENT. AND JUST TO FOLLOW THAT UP, ALSO I WOULD BE VERY CAUTIOUS ABOUT EVER USING A BIOMARKER AS A SURROGATE ENDPOINT, FREQUENTLY IT WON'T SHOW TOXICITY. GREAT FOR TARGET ENGAGEMENT BUT BE CAREFUL. >> ROSEMARY DAWSON, CARE PARTNER EMERITA, I MODERATE ONLINE SUPPORT GROUP FOR 500 OR SO SPOUSES OF PEOPLE LIVING WITH LEWY BODY. I HAVE TWO COMMENTS. THE FIRST IS THAT A MAJOR CONCERN AMONG THE MEMBERS OF OUR GROUP WITH SPOUSES RELATES TO NEXUS BETWEEN THE FIRST TWO RECOMMENDATIONS AND FOCUS AREA 1, AND THAT IS THE IMPORTANCE OF EARLY DIAGNOSIS FOR SO MANY REASONS BUT PARTICULARLY FOR THE CORRECT TREATMENT AND AS AN EXAMPLE IS THE SIGNIFICANT PROBLEM OF WHEN SOMEONE WHO HAS NOT BEEN OFFICIALLY DIAGNOSED YET ALTHOUGH IT HAPPENS EVEN AFTER DIAGNOSIS IS ADMINISTERED AN ATYPICAL OR A TYPICAL ANTIPSYCHOTIC AND HAS A SIGNIFICANT NEUROLEPTIC SENSITIVITY, IT WOULD BE GREAT IF THERE WOULD BE SOME KIND OF SCREENING FOR NEUROLEPTIC, IF THERE'S SOME WAY TO AVOID THOSE KINDS OF PROBLEMS WHEN PEOPLE DO HAVE SOMETIMES VERY LONG LASTING SEVERE REACTIONS TO NEUROLEPTICS. THE SECOND, IT'S RECOGNIZED NON-PHARMACOLOGICAL APPROACHES ARE VERY EFFECTIVE WITH BEHAVIORAL AND PSYCHOLOGICAL SYMPTOMS, WITHOUT THE ADVERSE SIDE EFFECTS, I DIDN'T SEE IT IN PRINT THAT THOSE KINDS OF TREATMENTS ARE GOING TO BE PART OF THE RECOMMENDATION ALTHOUGH DR. GOLDMAN DID MENTION THOSE IN THE SUCCESS CRITERIA. >> WELL, I WANT TO COMMENT BACK THAT PART OF THE EFFORT THAT WE TALKED ABOUT IN THE BEGINNING WAS TO TRY TO PROVIDE A PLATFORM TO BETTER CHARACTERIZE WHICH CAN LEAD TO BETTER DIAGNOSTIC TOOLS, AND I THINK WE TALK ABOUT RECOMMENDATION BUT WE'RE INCLUDING NON-PHARMACOLOGICAL RECOMMENDATIONS IN THE BROADER CATEGORY OF SYMPTOMATIC APPROACHES. >> VLADIMIR, NEUROLOGIST, LONDON ONTARIO. CSF TURNS OVER THREE TIMES. HAS ANYONE STUDIED IN PARKINSON'S DISEASE RELATIONSHIP BETWEEN PHYSICAL ACTIVITY, CSF TURNOVER AND CONCENTRATION BIOMARKERS BECAUSE OF DECREASED MOBILITY MAY BE HIGH CONCENTRATION RELATED TO ACTIVITY AND NOT BRAIN ACTIVITY. >> I THINK IT'S AN EXCELLENT THOUGHT. I'M NOT AWARE OF ANYBODY HAVING ADDRESSED THIS QUESTION PRECISELY BUT THE MICHAELJ FOX FOUNDATION CREATED A RESOURCE AVAILABLE TO YOU AND EVERYBODY, COLLECTED CSF OVER THE COURSE OF 24 HOURS OR 48 HOURS, EVERY OTHER HOUR, AND SO ALSO YOU DON'T HAVE THE EFFECT OF EXERCISE THAT YOU CAN GET A BETTER SENSE OF VARIATION AND STABILITY OF YOUR MARKERS. >> I BELIEVE IT'S AN IMPORTANT QUESTION. IF THERE'S THE RELATIONSHIP WITH INTERNAL CONCENTRATION, MAY BE LESS MOBILE THAN BIO, MAKERS, IF IT'S NOT BEEN ADDRESSED I WOULD ASK THIS BE A PRIORITY BECAUSE IT APPLIES ACROSS ALL THE COGNITIVE IMPAIRMENTS. >> I MEAN, IT'S A GOOD QUESTION. I THINK ALSO WHAT'S PERHAPS MITIGATING THIS ISSUE IS MANY OF THE STUDIES AND MANY COLLECTIONS ARE FROM NEWLY DIAGNOSED DE NOVO PATIENTS, PARTICULAR LEVELS NOT EXPECTED TO BE ANY DIFFERENT FROM CONTROL. >> ON THE OTHER HAND, THE VERY SAME PEOPLE WHO ARE RELATIVELY NORMAL, DETERIORATE, LESS ACTIVE, THIS IS HAPPENING IN THE BRAIN, PART MAY REFLECT THE DECREASED TURNOVER. IT'S A QUESTION THAT I'M ASKING TO BE ADDRESSED AS IMPORTANT. >> WE'LL NOTE THAT. THANK YOU. >> HI, IT'S JOAN SHARP AGAIN. ALTHOUGH YOU DISCUSSED MANY OF MY CONCERNS IN THE EXCELLENT PRESENTATIONS ALL DAY TODAY, AND PROGRESS THAT YOU'RE MAKING IS IMPRESSIVE, THERE WERE A NUMBER OF PROBLEMS THAT I SAW THAT I WOULD LIKE TO MAKE YOU FOLKS AWARE OF IN HOPES THAT MAYBE SOME THEM AT LEAST CAN BE CORRECTED. I'M SORRY. THANK YOU. YES, THANK YOU. MY NUMBER ONE PROBLEM WAS FINDING DEMENTIA NEUROLOGISTS WHO WERE ALSO EXPERTS IN LBD. THEY ARE ALMOST NON-EXISTENT. THEY KNEW WHAT LBD WAS. THEY KNEW WHAT THE MOST COMMON SYMPTOMS WERE, BUT BEYOND THAT IT WAS VERY HARD TO FIND ANYONE AND I LIVE IN THE NEW YORK CITY AREA SO WE HAVE ALL THESE WONDERFUL RESEARCH HOSPITALS AND IN 2014 DR. GALPIN WAS THERE BUT IT TOOK ME A WHILE TO FIND HIM. WHEN HE LEFT, THERE'S NOBODY WHO HAS REAL EXPERTISE IN LBD. >> I'LL GIVE YOU MY CARD. >> I'M SORRY, WHAT WAS THAT? >> I'LL GIVE YOU MY CARD. I'M IN NEW YORK STILL. >> YOU'RE IN NEW YORK CITY? WONDERFUL. THANK YOU. THE SECOND PART OF MY -- I'LL TELL YOU SOME OF THE THINGS I FOUND IT HARD TO GET ANSWERS FOR, THE SECOND PART OF MY PROBLEM WAS THAT WHEN I REALIZED I WASN'T GETTING THE RIGHT ANSWERS WHEN I ASKED THEM OF MY NEUROLOGIST, WHO IS A VERY KNOWLEDGEABLE DEMENTIA NEUROLOGIST BUT DIDN'T KNOW MORE ABOUT LBD AFTER I DID RESEARCH, THERE'S NO LIST THAT TELLS YOU WHO ARE THE DOCTORS WITH THE EXPERTISE YOU'RE LOOKING FOR. WE NEED A LIST. SOMEBODY NEEDS TO PUT TOGETHER A LIST. AND THESE HOSPITAL SEARCH ALGORITHMS THAT ALLOW YOU TO TELL WHAT SPECIALTY YOU'RE LOOKING FOR, THEY GIVE YOU THE NAME OF A DOCTOR, WELL, LBD IS NOT ONE OF THE THINGS. SO YOU CAN'T SEARCH THE HOSPITALS FOR SOMEBODY WHO KNOWS SOMETHING ABOUT IT. WE NEED A SUBSPECIALTY FOR NEUROOLOGISTSES. >> I WONDER IF ANGELA COULD ADDRESS THAT. THE LBD ASSOCIATION HAS PLANS TO DEVELOP SUCH A PHYSICIAN -- LIKE CENTERS OF EXCELLENCE SO YOU COULD GO TO THE LBDA WEBSITE AND IDENTIFY PHYSICIANS. >> ANGELA? MAYBE YOU WANT TO -- >> I MENTIONED THAT TO NORMA. I WAS HOPING YOU WERE COMING. >> I WILL SAY THAT IT'S CERTAINLY A PRIORITY TO IDENTIFY CENTERS WHERE THERE IS EXPERTISE, WHERE THERE'S A FOCUS ON PATIENT RECRUITMENT, ENGAGEMENT, WE'RE WORKING ON IDENTIFY ACTIVELY AND HOPE IN THE COMING YEAR WE'LL HAVE MORE INFORMATION. >> I WOULD ALSO JUST ADD TO MAKE SURE THAT THAT NOT EVERYBODY ENDS UP AT THE LBDA TO COLLABORATE WITH THE OTHER NOT FOR PROFITS SO THEY ARE LINKED AND CROSS REFERENCING WITH ALZHEIMER'S ASSOCIATION AND OTHER THINGS WOULD BE GREAT. >> YEAH, THANK YOU. BY THE TIME I FOUND DR. GALPIN IT WAS TOO LATE TO GET ASSISTANCE, HE DID DO A WONDERFUL PRESENTATION, OR A SESSION. BUT A COUPLE OTHER THINGS -- >> EXCUSE ME, WITH KEY CAN WE GET A LIST? THERE ARE TWO PEOPLE BEHIND YOU. >> ONE LAST REQUEST, BAN THE TERM PROBABLE A.D., PROBABLY ALZHEIMER'S BECAUSE IT NEEDS TO BE SOMETHING MORE SPECIFIC THAN THAT AS A DIAGNOSIS AND THE DIAGNOSIS NEEDS TO BE CHANGED IF THE SYMPTOMS CHANGE. IT GETS LEFT THERE. >> THANK YOU. >> DAVID KLEINFELT, UC SAN DIEGO. A QUESTION THAT CAME UP THIS MORNING AND AGAIN DURING THE PRESENTATION USING RESTING STATE fMRI, FOLLOW-UP STUDIES, FOLLOW-UP HISTOLOGICAL AND ANATOMIC STUDIES. WHAT YOU WOULD LIKE TO HAVE WHITE MATTER, YOU KNOW, AMAT ANATOMY TO FOLLOW UP, BOTH RESTING STATE, THEY BOTH GIVE YOU INFORMATION ABOUT CONNECTIVITY, PERHAPS A LOT OF INTERPRETATION IS INVOLVED IN RESTING STATE. ALL THE IMAGES SHOWN ARE TRANSVERSE ACROSS SECTIONS, SINGLE PICTURES, THERE DIDN'T SEEM TO BE A PUSH TOWARD LARGE SCALE RECONSTRUCTION OF WHITE MATTER IN HUMANS IN ORDER TO MAKE A CONNECTION WITH WHAT YOU SEE WITH DIFFUSION SENSOR IMAGING, THAT'S ALWAYS BEEN A CRITICISM. IS THIS SOMETHING THAT'S ON THE PLATE OR TOO EXPENSE OR INVOLVED? >> THE QUESTION IS ABOUT RESTING STATE VERSUS DIFFUSION IMAGING, OTHER STRUCTURAL MRI TECHNIQUES, AND SO RESTING STATE SHOWS FUNCTIONAL CONNECTIVITY BUT DOESN'T NECESSARILY REQUIRE ANY DIRECT ANATOMICAL CONNECTION. YOUR POINT, ARE PEOPLE CURRENTLY LOOKING AT RESTING STATE AND COMPARING IT WITH BOTH DIFFUSION MEASURES, TRACTOGRAPHY AND THE ANSWER IS YES, THAT'S BEING DONE. THERE ARE A NUMBER OF STUDIES DOING THAT. >> THE QUESTION IS WHETHER AT THE END YOU'RE GOING TO DO A ANATOMY ON CADAVER TISSUE TO GET A GOLD STANDARD IN ORDER TO INTERPRET EITHER. >> SURE, IN FACT WE'RE DOING THAT TWO WAYS. IN OUR STUDIES WE FOLLOW PEOPLE TILL THEY NO LONGER NEED THEIR BRAINS, AND THEN WE ACTUALLY EXAMINE THEIR BRAINS. AND THE SECOND THING WE ARE DOING IS WE LOOK IN NON-HUMAN PRIMATES WHERE WE CAN VALIDATE BIOMARKERS, RESTING STATE OR PET IMAGING, AND THEN LOOK IN THE BRAIN AND SEE EXACTLY WHAT IT IS WE'RE MEASURING BECAUSE SOMETIMES WHAT WE THINK WE'RE MEASURING IS NOT WHAT WE'RE MEASURING, WE HAVE A SERIES OF PAPERS DOING VALIDATION OF THOSE KINDS OF STUDIES. THAT'S VERY IMPORTANT I THINK. >> LAST QUESTION. >> YOU KNEW YOU WOULDN'T GET AWAY WITHOUT ME AM COME TOCK THE MICROPHONE. ANGELA TAIOR, LEWY BODY ASSOCIATES. THANK YOU FOR THE INFORMATION SINCE THE LAST SUMMIT. I WOULD LIKE TO ENCOURAGE YOU TO LOOK AT MILESTONES AS I LISTEN TO THE PROGRESS THAT'S BEEN MADE ONE OF THE THINGS THAT STRIKES ME IS ABOUT PROGRESS, I WANT TO ENSURE THREE YEARS FROM NOW WE'RE SEEING EQUAL PROGRESS ON THE DLB SIDE, MILESTONES, A LOT OF THEM SAY EITHER/OR. WE HAVE TO HAVE HAVE MORE CONCERTED FOCUS TO ENSURE WE DON'T -- THAT WE -- IT'S HARD TO SAY THIS WITHOUT COMING ACROSS THE WRONG WAY. I'M JUST GOING TO SAY MAKE SURE THAT WE PRIORITIZE DLB ON THE SAME LEVEL AS WE DO PDD, WHERE THE SCIENCE ALLOWS US TO