THIS IS KELVIN CHOI SENIOR
INVESTIGATOR WITH INTRAMURAL
RESEARCH.
HAPPY SPRING.
THE WEATHER'S GETTING NICE.
IT'S PROBABLY HOT TO STAY INSIDE
AND WATCH THE SEMINAR.
IF YOU WANT TO TAKE IT OUTSIDE
AND ENJOY THE NICE WEATHER AND
SIT UNDER A TREE, THAT WOULD BE
A NICE THING TO DO.
TODAY WE ARE FORTUNATE TO HAVE
REBECCA GOTTESMAN TO BE OUR
GUEST SPEAKER.
THE BRANCH CHIEF OF THE STROKE
BRANCH AND NEUROEPIDEMIOLOGY AT
THE NATIONAL INSTITUTE OF
NEUROLOGICAL DISORDERS AND
STROKE IN BETHESDA, MARYLAND.
SHE COMPLETED HER MEDICAL
TRAINING AT COLUMBIA UNIVERSITY
AND HER INTERNSHIP IN NEUROLOGY
RESIDENCY AS WELL AS VASCULAR
NEUROLOGY AT JOHNS HOPKINS
UNIVERSITY AND COMPLETED A Ph.D.
AT THE BLOOMBERG SCHOOL OF
PUBLIC HEATH AND IN THE
DEPARTMENT OF NEUROLOGY AT JOHNS
HOPKINS IN 2021 AND SHE JOINED
NIH.
HER RESEARCH S ON THE VASCULAR
CONTRIBUTIONS TO COGNITIVE
IMPAIRMENT, DEMENTIA AND
ALZHEIMER'S DISEASE AS WELL AS
THE CEREBRAL SMALL VESSEL
DISEASE AND POST-STROKE DEMENTIA
AND STUDIES LARGE EPIDEMIOLOGY
COHORTS WITH LEADERSHIP ROLES IN
THE ARIC STUDY AND DISCOVERY
COHORT AND USES NEURO IMAGING
RELATED TO THESE QUESTIONS.
SHE'S A FORMER SOCIETY EDITOR
FOR THE JOURNAL OF NEUROLOGY AND
WON AN AWARD FROM THE AMERICAN
HEART ASSOCIATION.
WITHOUT FURTHER ADO,
DR. GOTTESMAN, THE PODIUM IS
YOURS.
>>THANK YOU SO MUCH.
IT'S GREAT TO HAVE A CHANCE TO
MEET OTHER PEOPLE INTERESTED IN
DISPARITIES AND SOME OF THE
ISSUES IN POPULATION-BASED
STUDIES.
I'LL TALK ABOUT REDUCING
DEMENTIA IN POPULATIONS AND WHY
IT COULD BE A WAY TO FOCUS ON
PREVENTION.
I DON'T HAVE DISCLOSURES.
THIS WAS ADDED IN THE LAST
SECONDS BEFORE THE TALK KELVIN
ASKED TO E-MAIL HIM IF YOU HAVE
QUESTIONS SINCE THERE'S NOT
ANOTHER WAY TO RAISE HANDS AND
IF YOU THINK OF SOMETHING AFTER
THE TALK YOU CAN SEND IT
DIRECTLY TO ME.
HERE'S A BRIEF OUTLINE OF WHAT
I'LL TALK TO YOU TODAY ABOUT.
FIRST A BIT ABOUT THE
EPIDEMIOLOGY OF DEMENTIA OVER
ALL AND IN DISPARITY POPULATIONS
AND THEN WE'LL TALK ABOUT
VASCULAR RISK FACTORS OF
DEMENTIA AND WHY THIS IS SO
IMPORTANT NOT JUST IN
UNDERSTANDING PREVENTION AND
ETIOLOGY OF DEMENTIA AND
CONTRIBUTIONS FOR DEMENTIA AND
MECHANISMS FOR DISPARITIES WITH
SOME DISCUSSION OF DIFFERENCES
IN BIOMARKERS FOR DEMENTIA BY
RACE AND EXPLORING SOCIAL
DETERMINATES OF HEALTH AND TO
FOCUS ON THE POSSIBILITY OF
PREVENTION AND WHAT WE KNOW THUS
FAR IN POTENTIAL TARGETS OF
PREVENTION.
CERTAINLY WELL KNOWN TO MANY OF
US THAT DEMENTIA IS A GROWING
PUBLIC HEALTH EPIDEMIC AND WHAT
THE RATES OF DEMENTIA BROADLY
ARE EXPECTED TO LOOK LIKE.
IT'S AN UMBRELLA TERM AND
ALZHEIMER'S DISEASE IS THE
PRIMARY CAUSE.
IN GENERAL THERE'S FEW
SUCCESSFUL TREATMENTS.
WE NOW HAVE A COUPLE DRUGS
APPROVED FOR ALZHEIMER'S
DISEASE.
THERE'S MANY CLINICAL TRIALS
ACTIVELY EVALUATING
INTERVENTIONS.
UNTIL RECENTLY NO INTERVENTIONS
HAD BEEN SUCCESSFUL AND I DO
WANT TO POINT OUT THAT RECENT
STUDIES THOUGH WE HAVE A COUPLE
DRUGS WERE TESTED IN NON-DIVERSE
POPULATIONS WE'LL TALK BRIEFLY
AT THEN IF THERE'S TIME.
NOT ONLY ARE DEMENTIA RATES
GROWING IN GENERAL AND EXPECTED
TO GROW OVER THE WORLD BUT WE
KNOW THEY'RE HIGHER IN
MINORITIZED POPULATIONS.
HERE'S DATA FROM THE KAISER
SYSTEM SHOWING HIGH RATES WITH
AGE CROSS ETHNIC AND BLACK AND
LATINO RATES HIGHER RATES AND
THESE ARE PREVALENCE NOT
NECESSARILY INCIDENTS.
SIMILAR USING MEDICARE WE SEE
HIGHER RATES IN BLACK
PARTICIPANTS AND BLACK MEDICARE
RECIPIENTS AND HISPANIC
INDIVIDUALS AS WELL.
THE PROBLEM IS THAT DEMENTIA
RATES ARE EXPECTED TO INCREASE
OVER TIME IN MINORITIZED
POPULATIONS.
WE KNOW AND I'LL SHOW YOU DATA
IN A MOMENT SHOWING THERE'S SOME
EVIDENCE THAT DEMENTIA RATES ARE
GOING DOWN IN THE GENERAL
POPULATION BUT WE THINK THEY'RE
GOING TO CONTINUE TO GO UP.
HERE'S THE RATES LOOKING AT
WHITES AND WE THINK OVER TIME
THESE ARE GOING TO REDUCE OVER
TIME BUT IN BLACK AND HISPANIC
INDIVIDUALS THE RATES ARE
EXPECTED TO GO UP OVER TIME.
AND THERE'S SEVERAL OTHER
FACTORS THAT WE'LL CONSIDER AND
WE'LL TALK ABOUT VASCULAR RISK
FACTORS AND POSSIBLY MODIFY RISK
OF DEMENTIA AND IN OTHER STUDIES
SUCH AS THE CHICAGO HEALTH AND
AGING PROJECT BLACK VERSUS WHITE
HAVE LOWER COGNITIVE PERFORMANCE
BUT DECLINE IS SIMILAR.
SO RATE OF CHANGE IS NOT
NECESSARILY IMPACTED BY RACE BUT
MORE PREVALENT DEMENTIA IN
BLACKS VERSUS WHITES WHY WE SEE
THE INCREASE OVER TIME AND
EXPECT THEY'LL GO UP FURTHER.
A FAIR AMOUNT OF THAT DIFFERENCE
BY RACE IS EXPLAINED BY
EDUCATION DEPENDING ON THE
STUDY.
IT DEPENDS ON WHAT PROPORTION WE
THINK IS EXPLAINED BY EDUCATION
BUT CERTAINLY NOT EVERYTHING.
THIS IS SHOWING DATA FROM THE
FRAMINGHAM STUDY AND ALL CAUSE
NOT SPECIFICALLY ALZHEIMER'S
DISEASE HAVE BEEN DECREASING
OVER TIME.
THAT'S PROMISING.
THE PROBLEM IS WE DON'T
NECESSARILY SEE PARTICULAR
REDUCTION IN DEMENTIA RATES IN
DISPARITY POPULATIONS AND
FRAMINGHAM IS NOT A NON-DIVERSE
COHORT STUDY AND THINK OF WHY WE
MAY BE UNDER INFLUENCING RATES
IN DISPARATE POPULATIONS AND WHY
THEY'RE NOT GOING DOWN.
LOOKING AT THE HEALTH AND
RETIREMENT STUDY LED BY A FORMER
POSTDOC OF MINE NOW AT GEORGE
WASHINGTON AND NOW LOOKING AT
PREVALENCE OF DEMENTIA BLACK
VERSUS WHITE IS BETWEEN 1.5 AND
2 AND IF ADJUST FOR FACTORS THE
RATES ARE PRETTY FLAT OVER TIME
MEANING REGARDLESS OF WHAT'S
HAPPENING WITH WHITES THE RATES
ARE CONSISTENT OVER TIME.
WE CONTINUE TO SEE DISPARITY.
THERE'S A NUMBER OF DIFFERENT
REASONS THIS MAY HAPPEN I
MENTIONED BEFORE.
WE KNOW MOST STUDIES THAT LOOK
AT CLINICAL POPULATIONS FOR
INSTANCE IN ALZHEIMER'S DISEASE
CENTERS TEND TO UNDER RECRUIT
FROM DISPARITY POPULATIONS.
WE KNOW MOST DIAGNOSTIC CRITERIA
WERE NOT DEVELOPED IN DIVERSE
POPULATIONS AND THE DATA IS NOT
DEVELOPED IN THESE POPULATIONS
AND THERE'S REDUCED ODDS OF
BEING DIAGNOSED WITH DEMENTIA AS
A BLACK ADULT AND WE MAY BE
FURTHER UNDERESTIMATING THE
DISPARITY.
LESS IS KNOWN IN HISPANIC LATINX
POPULATIONS.
THE PRESENTATION MAY LOOK
DIFFERENT IN LATINX OLDER
ADULTS.
THERE'S MORE LIKELY TO BE MOOD
SYMPTOMS IN ADDITION AND FEWER
DATA ARE AVAILABLE BUT RATES
TEND TO BE HIGHER IN LESS LIKELY
TO BE DIAGNOSED.
WHAT ABOUT THE DEMENTIA
ETIOLOGY.
THIS LEADS TO THE BULK OF WHAT
TO TALK ABOUT PREVENTION.
IF WE KNOW DEMENTIA IS A PROBLEM
AND THERE'S NOT A REDUCTION OF
DISPARITIES IN BLACK AND LATINX
INDIVIDUALS, WHY DOES ETIOLOGY
MATTER?
IF THERE'S ETIOLOGIES MODIFIABLE
OR PREVENTIBLE THAT'S AN
APPEALING TARGET ESPECIALLY IF
THOSE MODIFIABLE AND PREVENTIBLE
FACTORS ARE DISPROPORTIONATELY
RESPONSIBLE FOR THOSE RISKS IN
THOSE POPULATIONS.
THAT'S WHAT WE MORE OR LESS SEE.
HERE'S DATA FROM THE STUDY THEY
LOOKED AT INDIVIDUALS DIAGNOSED
WITH DEMENTIA POSTMOREM AND
THESE DATA ARE FROM 2015 AND
THERE'S NEWER ENTITIES ANOTHER
NEUROPATHOLOGY THIS GROUP
DESCRIBED THAT WAS NOT NOTICED
OR RECOGNIZED AS A SEPARATE
ENTITY AT THIS TIME.
THE PIES LOOK A LITTLE DIFFERENT
BUT PURE A.D. MORE COMMON IN THE
PATHOLOGY OF WHITE INDIVIDUALS
VERSUS BLACK AND MIXED
PATHOLOGY, THIS IS A MIX OF
ALZHEIMER'S AND STROKE LIKE
CHANGES WHICH IS WHAT I'LL FOCUS
ON FOR MOST MY TALK.
THIS IS LEWY BODY AND ALL THE
ABOVE.
THESE ARE INFARCTS ACCOUNT FOR A
LARGER PROPORTION OF DEMENTIA
CASES THAN IN WHITE INDIVIDUALS.
MIXED PATHOLOGY IS IMPORTANT
ESPECIALLY IN BLACKS.
YOU CAN SEE HERE AND IN GENERAL
IF YOU HAVE VASCULAR CHANGES IN
THE BRAIN YOU CAN GET AWAY WITH
LESS ALZHEIMER'S NEUROPATHOLOGY
TO GET TO EQUIVALENT LEVEL OF
DECLINE.
MANY PEOPLE WITH DEMENTIA HAVE
VASCULAR RISK FACTORS.
IT'S NOT ENTIRELY CLEAR IS THIS
BECAUSE ONE MAY CONTRIBUTE TO
THE OTHER OR COMMON.
NEURODEGENERATION IS COMMON
LEADING TO ALZHEIMER'S AND
VASCULAR RISK FACTORS SUCH AS
HIGH CHOLESTEROL WERE ALSO
COMMON.
SOME EVIDENCE SUGGESTED THEY'RE
LINKED.
THE MIXED PATHOLOGY WE SEE IN
BLACK INDIVIDUALS AND THE FACT
THERE'S ASSOCIATION WITH
DEMENTIA AND MAYBE ALZHEIMER'S
DISEASE SPECIFICALLY POINTS TO
POTENTIAL OPPORTUNITIES FOR
PREVENTION.
IF WE THINK OF MIXED DEMENTIA IN
WHITE POPULATIONS IN THIS WAY
MAYBE IN DISPARITY POPULATIONS
THERE'S A LARGER PROPORTION OF
CASES THAT ARE VASCULAR ETIOLOGY
AND MIXED WHICH MEANS THIS IS AN
AREA WE CAN TARGET OR MODIFY.
IT'S A LARGER PROPORTION OF
DEMENTIA CASES POTENTIAL LY
MODIFIABLE IN THESE POPULATIONS.
MUCH OF THE REASON MOST
TREATMENTS HAVE BEEN
UNSUCCESSFUL IS BECAUSE OF THE
LONG PERIOD.
IF YOU TREAT PEOPLE ONCE THEY
HAVE SYMPTOMS IF YOU LOOK AT
THIS VARIATION ON THE CURVE YOU
CAN SEE ONCE SOMEBODY HAS
SYMPTOMS THEIR DISEASE IS FAIRLY
ADVANCED.
THESE ARE SHOWING BIOMARKERS
THAT CHANGE IN THE DECADES
PRECEDING COGNITIVE CHANGE.
IF YOU WAIT UNTIL COGNITIVE
CHANGE STARTS WHICH IS WHEN
SOMEONE IS ENROLLED IN THE TRIAL
IT'S LATE IN THE PROCESS.
IN GENERAL THINKING OF
IDENTIFYING PEOPLE AT A
PRE-CLINICAL STAGE WHEN THEY'RE
AT RISK BUT NOTHING HAS CHANGED
IN TERMS OF BIOMARKERS WILL BE
IMPORTANT.
IT'S BEEN SPECULATED THE
VASCULAR FACTORS I MENTIONED
THERE'S OVERLAP IN PATHOLOGIES,
LOTS OF MIXED PATHOLOGY AND MANY
PEOPLE HAVE A COMBINATION
VASCULAR RISK FACTORS IN
DEMENTIA AND I'LL SHARE SOME OF
THE EPIDEMIOLOGIC DATA BUT
EVIDENCE IT MAY PROCEED THE A.D.
SPECIFIC CHANGES, THIS CURVE
SHOWS YOU CAN'T SEE THE DETAIL
BUT THE FIRST LINE IS VASCULAR
DYSREGULATION WHICH MAY PRECEDE
CHANGES IN AMYLOID AND TAU AND
COGNITION AND THE OTHER SUPPORT
FOR THE CHANGES HAPPEN EARLY IS
MOST DATA SHOW NOT ONLY ARE
VASCULAR RISK FACTORS ED WITH
COGNITIVE DECLINE BUT ASSOCIATED
FROM MIDDLE AGE AND PROBABLY
EARLIER IF WE HAD DATA SETS THAT
EXTEND FROM THAT ENTIRE TIME
PERIOD.
MIDLIFE APPEARS TO BE AN
IMPORTANT WINDOW FOR PREVENTION
AND IF WE SEE DISPROPORTIONATE
RATES OF VASCULAR ETIOLOGY IN
BLACK VERSUS WHITE INDIVIDUALS
MAY EXPLAIN DISPARITIES IN RATES
AND MAYBE AN OPPORTUNITY FOR
PREVENTION.
TO PROVIDE MORE EVIDENCE THAT
VASCULAR RISK FACTORS ARE ED
WITH COGNITIVE DECLINE AND
DEMENTIA.
THIS IS A GUIDELINE FOR THE
PREVENTION OF STROKE AND THE
RISK FACTORS WE'RE THINKING
ABOUT WHEN WE THINK OF
PREVENTING STROKE IN ADULTS AND
THE RISK FACTORS WE KNOW THAT
APPEAR TO HAVE ASSOCIATIONS WITH
COGNITIVE DECLINE IN DEMENTIA.
IN GENERAL THE SOUTHEASTERN PART
OF THE COUNTRY AS ALL OF YOU
KNOW IS CALLED THE STROKE BELT.
THIS IS AN AREA WHERE STROKE
RATES AND STROKE DEATH RATES ARE
EXCEPTIONALLY HIGH.
THIS IS THE TARGET OF STUDIES
LIKE THE REGARD STUDY TRYING TO
UNDERSTAND REASONS FOR THIS
DISPROPORTIONATE RATE OF STROKE
AND WE LOOKED AT PEOPLE IN THE
HIGH RATE MORTALITY STATE
OPPOSED TO ELSEWHERE HAD HIGHER
RATES OF DEMENTIA SO ECOLOGIC
REASONS AND THE STROKE BELT IS
WHERE WE HAVE THE HIGHEST
PROPORTION OF BLACK INDIVIDUALS
AND RESIDENTS RESIDING.
TO TELL YOU WHAT WE KNOW ABOUT
VASCULAR RISK FACTORS AND
DEMENTIA.
I HAVE AN ASSOCIATION WITH THE
ARIC STUDY AND IT'S THE
ATHEROSCLEROSIS RISK IN
COMMUNITY STUDY STARTED IN THE
LATE 1980s, NEARLY 16,000 ADULTS
45 TO 64 AT STUDY ONSET.
THIS SAYS VISIT SEVEN.
WE'RE CURRENTLY ON VISIT 10.
I'M SHOWING YOU THROUGH VISIT 7
BECAUSE THAT'S THE DATA I'LL
SHARE UP THROUGH AND THE HOPE IS
TO CONTINUE TO SEE THESE ADULTS
WHO ARE NOW IN THEIR 85 PLUS AGE
RANGE BUT IMPORTANTLY THEY'VE
BEEN FOLLOWED CONTINUOUSLY AND
HAD A NUMBER OF IN-PERSON VISITS
AND HAD ANNUAL AND NOW SEMI
ANNUAL PHONE CALLS TO LEARN
ABOUT HOSPITALIZATION AND OTHER
EVENTS AND HAD COGNITION EVENTS
AND AT VISIT 5 THAT THE AN
INF
INFORMANTIN INTER --
AND WE HAVE STROKE SCREENING AND
WE HAVE CS VISITS CONTINUING TO
GO ON WHERE THERE'S MORE
DETAILED COGNITIVE ASSESSMENT.
A SUBSET OF PARTICIPANTS HAVE
HAD BRAIN MRI WHICH WILL BE
IMPORTANT WHEN I TALK ABOUT
MECHANISM AND CONTINUE TO GET
MRI AT CURRENT VISITS AND
FURTHER SUBSET AT THIS PET THAT
BINDS TO AMYLOID FLORBETAPIR AND
SCANNED PARTICIPANTS AT THE ARIC
PET STUDY VISIT AND REPEAT IN
THE SUBSET AND NOW WE'RE GETTING
MORE SCANS NOW IN OUR CURRENT
VISITS.
AND TO POINT OUT ARIC IS THESE
AREAS AND ALL FOUR SITES
REPRESENT A COMBINATION OF
RURAL, URBAN, BLACK, WHITE
PARTICIPANTS PRIMARILY.
WHEN I TALK ABOUT COGNITIVE
CHANGE WHICH I'LL MENTION
SHORTLY I'LL TALK ABOUT CHANGE
IN COGNITION OVER TIME AS WELL
AS INCIDENT DEMENTIA EVENTS.
AND I WON'T HAVE TIME TO GO INTO
DETAIL BUT WE CONSIDER ATTRITION
AND WE USE BOTH INVERSE RATING
AND SOME STUDIES AS WELL AS
MULTIPLE CHANGE EQUATIONS TO TRY
TO ACCOUNT FOR THE ATTRITION
HIGHLY ASSOCIATED WITH OUR RISK
FACTORS OF INTEREST AND WITH
LIKELIHOOD OF DROP OUT RELATED
TO COGNITIVE CHANGE OVER TIME.
FIRST, WHAT ABOUT STROKE?
I TOLD YOU THE STROKE BELT
PEOPLE BORN IN THE STROKE BELT
HAT HIGHER RATES OF DEMENTIA.
I MENTIONED I'M FOCUSSING ON
STROKE RISK FACTORS AS POSSIBLE
WAYS TO MODIFY RISK OF DEMENTIA.
FIRST IS STROKE ITSELF RELATED
TO DEMENTIA?
YES, IT IS.
WE LOOKED AT STROKE AS WELL AS
STROKE SEVERITY AT PEOPLE IN THE
A K
ARIC SCALE AND THEY SHOWED
HIGHER NUMBERS MORE SEVERE
STROKES AND PEOPLE WITH MORE
SEVERE STROKES HAD A GREATER
RISK OF DEMENTIA.
ADDITIONALLY IF YOU HAD
RECURRENT STROKE AND ONE WAS A
SEVERE STROKE THE RISK WENT UP
FURTHER.
THIS IS ADJUSTED FOR RISK
FACTORS, MEDICATION USE,
ETCETERA AND YOU CAN SEE WE SEE
A DOSE RESPONSE TYPE OF
RELATIONSHIP IF YOU HAVE ONE
MINOR STROKE, RISK GOES UP
NEARLY DOUBLING OVER TRIPLED IF
YOU HAVE ONE SEVERE STROKE
COMPARED TO PEOPLE WITH NO
STROKE AND MULTIPLE STROKES THE
RISK CONTINUES TO GO UP IF ONE
WAS SEVERE.
WHAT HAD WHAT ABOUT DISPARITIES?
WE FOUND IN BLACK VERSUS WHITE
PARTICIPANTS HAVING AT LEAST ONE
MODERATE TO SEVERE STROKE
INCREASED RISK OF DEMENTIA MORE
SO THAN IN WHITE PARTICIPANTS.
MILD STROKE WAS SIMILARLY
INCREASED FOR BLACK AND WHITE
INDIVIDUALS.
THE HAZARD RATIOS AND SIMILAR
RELATIVE TO THOSE WHO DIDN'T
HAVE BUT IF ONE STROKE WAS
MODERATE TO SEVERE AND COULD
HAVE BEEN YOU ONLY HAD ONE
STROKE THE RISK WENT UP HERE
FOURFOLD INCREASE RISK IF YOU
WERE BLACK PARTICIPANT WHO HAD A
MODERATE TO SEVERE STROKE
COMPARED TO NOT HAVING A STROKE
AT ALL VERSUS IF YOU ARE WHITE
AND THE INCREASE BUT NOT
COMPARED TO WHITE INDIVIDUALS
AND DON'T SEE RACE DIFFERENCES
IN THE MILD TO MODERATE STROKES
MORE IN THE NUMBER OF STROKES
ALONE.
THE NUMBER OF STROKES HAS A
SIMILAR AFFECT BY RACE FOR
DEMENTIA.
WHAT ABOUT VASCULAR RISK FACTORS
AND STROKE IS A FACTOR BUT NOT
THE ONLY TARGET FOR PREVENTION.
WE WANT TO PREVENT DEMENTIA BY
PREVENTING STROKE.
STROKE ITSELF CONTRIBUTES TO
DEMENTIA BUT THE RISK FACTORS TO
DEMENTIA RISK.
ANDREA SCHNEIDER DID THIS ATT
JOHNS HOPKINS IN HYPERTENSION
AND FOUND PEOPLE WITH HIGH BLOOD
PRESSURE IN MIDDLE AGE HAD
STEEPER COGNITIVE DECLINE OVER
THE DECADES COMPARED TO PEOPLE
WHO HAD NORMAL BLOOD PRESSURE
AND THOSE ON MEDICATIONS WERE IN
BETWEEN.
THESE ARE MODELS LOOKING AT
CONTINUOUS BLOOD PRESSURE WE
LOOKED AT BLOOD PRESSURE AND SEE
THE SAME BASIC BUT WHEN YOU LOOK
AT LATE LIFE BLOOD PRESSURE IS
NOT AS IMPORTANT FOR SUBSEQUENT
COGNITIVE OUTCOMES.
AND THEY LOOKED AT DIABETES AND
HEMOGLOBIN A1C AND IN DIABETICS
THE HIGHER THE GREATER THE
COGNITIVE DECLINE WHEN SHE
LOOKED AT GLYCEMIC CONTROL IN
MIDLIFE WAS ASSOCIATED WITH
WORSE COGNITIVE CHANGE, STEEPER
DECLINE OVER THE DECADES.
THESE ARE PAIRS OF ESTIMATES ARE
TO SHOW YOU THE EFFECT OF
ACCOUNTING FOR ATTRITION.
WE DID THINGS -- THINGS LOOK
WEAKER IF YOU DON'T CONSIDER THE
ATTRITION PEOPLE WITH DIABETES
AT MIDLIFE ARE LIKELY NOT TO
MAKE IT TO A LATER VISIT AND
PEOPLE WITH COGNITIVE CHANGE ARE
MOST LIKELY NOT TO MAKE IT TO A
LATER VISIT.
MAY LOSE THAT POTENTIAL IF YOU
DON'T ACCOUNT FOR THAT
ATTRITION.
WHAT ABOUT DEMENTIA THEMSELVES
ARE THESE VASCULAR RISK FACTORS
ED?
YES.
WE LOOKED AT DEMENTIA SEVERAL
WAYS I WON'T GET IN TREMENDOUS
DETAIL WE HAVE THE PEOPLE WE SAW
IN PERSON AND HAVE DETAILED
INFORMANT INTERVIEW AND PEOPLE
IDENTIFIED THROUGH PHONE
INTERVIEWS AND HOSPITALIZATION
CODES.
WE HAVE A MODEL I'LL SHOW THE
RESULTS OF HERE.
A NUMBER OF VASCULAR RISK
FACTORS ARE ASSOCIATED WITH
DEMENTIA WHEN WE ADJUST FOR
THEM.
CURRENT SMOKERS HAVE HIGHER RISK
OF DEMENTIA, INDIVIDUALS WITH
DIABETES, HAZARD OF 1.77 ARE
RISK OF DEMENTIA.
THESE ARE MIDLIFE VASCULAR RISK
FACTORS LOOKING AT DEMENTIA RISK
OVER THE 25 YEARS.
HYPERTENSION AND THESE ARE OLDER
DEFINITIONS WHAT'S CALLED
HYPERTENSION IS CALLED STAGE 1
AND WHAT IS HYPERTENSION THERE
IS NOW STAGE 2 AND INCREASED
RISK WITH EITHER ENTITIES AND
BMI AND CHOLESTEROL FOR THIS
PARTICULAR STUDY WE DID NOT FIND
ASSOCIATIONS FOR MIDLIFE BMI OR
RISK OF DEMENTIA INDEPENDENT OF
THE OTHER RISK FACTORS AND
DEMOGRAPHICS.
AND APOE THE STRONGEST RISK
FACTOR FOR GENETIC DISEASE WAS
ASSOCIATED WITH DEMENTIA AND THE
AFFECT SIZE FOR HAVING AT LEAST
ONE APOE ALLELE IS NOT THAT FAR
OFF WITH WHAT WE SEE WITH
DIABETES.
THIS IS PREVENTIBLE AND
COMPELLING IN TERMS OF THE
EFFECT SIZE WE SEE FOR DIABETES.
AND THEN IMPORTANTLY WHAT ABOUT
THE DIFFERENCES BY RACE.
AS I MENTIONED, WE KNOW RATES OF
DEMENTIA ARE HIGHER IN BLACKS.
WE KNOW MIXED DEMENTIA IS MORE
PREVALENT THAN BLACKS AND WHITES
SO THESE RISK FACTORS AFFECT
BLACK AND WHITES DIFFERENTLY AND
FOR SMOKING IN PARTICULAR WE SEE
SMOKE IS NOT A RISK FACTOR IN
BLACK PARTICIPANTS BUT IT IS IN
WHITES AND IN GENERAL MANY VERY
FEW BLACK PARTICIPANTS IN ARIC
SMOKE.
FOR DIABETES AND HYPERTENSION
THE RISK IS SIMILAR, MEANING, IF
YOU'RE DIABETIC AND MIDDLE ABLE
AND BLACK VERSUS WHITE YOUR
INCREMENTAL RISK OF DEMENTIA
WILL BE SIMILAR IN EITHER
GROUPS.
SAME FOR HYPERTENSION BUT IT
DOESN'T ACCOUNT FOR DIFFERENCES
AND PREVALENCES OF THE RISK
FACTORS WHICH CAN ACCOUNT FOR
LARGER PROPORTION AND HAVING THE
RISK FACTOR DOESN'T INCREASE THE
RISK IT'S INCREASED IN BOTH
GROUPS.
THE APOE E4 ALLELE IS A STRONGER
KNOWN GENETIC RISK FACTORS IN
WHITES THAN BLACKS.
WE FOUND SUPPORT FOR THAT AND
IMPORTANT IN BLACKS BUT NOT AS
STRONG FOR WHITES.
THIS MAY ACCOUNT FOR THE MIXED
DEMENTIA LOOKING AT ALL-CAUSE
DEMENTIA.
SO KEEN ON WALKER DID THIS WORK
FOR ME AND WHEN HE LOOKED AT
CHANGE OVER THE LIFE COURSE AND
BLOOD PRESSURE IN PARTICULAR.
I TOLD YOU MIDLIFE WAS IMPORTANT
AND WAS IMPORTANT IN PREVENTION
AND EARLY CLINICAL CHANGES IN
ALZHEIMER'S DISEASE AND
EPIDEMIOLOGIC DATA SHOWS
STRONGER ASSOCIATIONS FOR MID
LIFE AND ASKED WHAT IF PEOPLE
HAVE CHANGES OVER THEIR LIFE
COURSE DOES THAT AFFECT THEIR
LIKELIHOOD OF DEVELOPING
DEMENTIA AND FOUND PEOPLE WITH
HYPERPENSION FOLLOWED BY LATE
LIFE HYPOTENSION AND LOW BLOOD
PRESSURE AND MEANING DIASTOLIC
BELOW 60 AND HYPERTENSION
FOLLOWED BY HYPOTENSION WAS
ASSOCIATED WITH THE GREATEST
RISK OF DEMENTIA AND
HYPERTENSION FOLLOWED BY LATE
LIFE HYPOTENSION AND THIS
PATTERN WAS PROBLEMATIC AND MOST
INDIVIDUALS WERE ON
BLOOD-PRESSURE LOWERING
MEDICATIONS AND EXCLUDED PEOPLE
WITH EARLY COGNITIVE CHANGES AND
WE SEE THE SAME RELATIONSHIP.
IN RACE STRATIFIED MODELS WE
DIDN'T SEE PARTICULAR
DIFFERENCES IN THE EFFECTIVE
BLOOD PRESSURE OVER TIME.
BUT WE DON'T SEE THE
HYPERTENSION FOLLOWED BY
HYPOTENSION PARTICULARLY
PROBLEMATIC IN BLACKS VERSUS
WHITES.
WHAT ABOUT POTENTIAL MECHANISMS
OF VASCULAR IMPACT OF DEMENTIA?
I HOPE I CONVINCED YOU SOMEWHAT
VASCULAR RISK FACTORS ASSOCIATED
WITH COGNITIVE CHANGE AND
DEMENTIA.
WHAT ARE THE POTENTIAL REASONS
THAT MAY BE?
IN EPIDEMIOLOGY WE TEND TO USE
BIOMARKERS WHETHER IMAGING OR
BLOOD BASED TO HELP US
UNDERSTAND MECHANISMS.
CERTAINLY ONE POTENTIAL
MECHANISM IS IF YOU HAVE
VASCULAR RISK FACTORS AND
DEVELOPED STROKE THAT CAN
CONTRIBUTE TO COGNITIVE DECLINE
AND DEMENTIA.
HERE'S AN EXAMPLE OF AN MRI AND
ACUTE STROKE AND SEE THESE
INDEPENDENT OF CLINICAL STROKE.
WHAT ABOUT SUBCLINICAL CHANGES?
PEOPLE WITH VASCULAR RISK
FACTORS ACCUMULATE A FAIR NUMBER
OF THE IS KEEMIC -- ISCHEMIC
INFARCT AND MICROBLEED AND
PEOPLE CAN HAVE VASCULAR RISK
FACTORS AND HAVE LOSS IN THE
BRAIN OVER TIME WHICH MAY
ATTRIBUTE TO COGNITION AND IT'S
TRUE VASCULAR RISK FACTORS MORE
DIRECTLY TO CONTRIBUTE TO
ALZHEIMER'S NEUROPATHIC CHANGES
AND WE LOOK AT THE ALZHEIMER'S
CHANGE AND THE PET IS A WAY TO
LOOK AT AMYLOID BURDEN BRAINS OF
INDIVIDUALS WHO DID NOT HAVE
DEMENTIA AND UNDERSTAND HOW
VASCULAR RISK FACTORS RELATE TO
THE FINDING THIS IS A POSITIVE
AMYLOID PET SCAN.
WHAT'S THE POTENTIAL FOR THESE
BEING LINK BETWEEN VASCULAR RISK
FACTORS AND COGNITIVE DECLINE
>>MISSISSIPPI UNIVERSITY
MEDICAL CENTER LOOKED AT THE
CHANGES I SHOWED HERE AND SILENT
INFARCTS AND THE COMBINATION OF
THEM AND PARTICULARLY THE
COMBINATION WAS ASSOCIATED WITH
STEEPER COGNITIVE DECLINE OVER
TWO DECADES.
IN ADDITION, MELINDA POWER AT
G.W. FOUND THE HAVE MORE LOSS OF
WHITE MATTER INTEGRITY USING
DIFFUSER TENSION IMAGING AND THE
PATTERN OF HIGH BLOOD PRESSURE
FOLLOWED BY LOW PRESSURE MAY
CONTRIBUTE TO BRAIN VOLUME LOSS
AND THEY TEND TO HAVE LESS
COGNITION OVER TIME AND PEOPLE
WITH MORE PROGRESSION OF THESE
CONDITIONS HAVE ASSOCIATIONS AND
PHYSICAL ACTIVITY SHOWS
DIFFERENCES AFFECTING REGIONS WE
KNOW ARE IMPORTANT IN
ALZHEIMER'S.
SOME EVIDENCE LINKING VASCULAR
RISK FACTORS TO THESE IMAGING
MARKERS AND LINKING THEM TO
COGNITION.
WHAT ABOUT THE AMYLOID
HYPOTHESIS?
I EXPLAINED THAT AMYLOID IS A
LEADING HYPOTHESIS IS FELT TO
CAUSE ALZHEIMER'S DISEASE AND
WHAT MECHANISTICALLY LINK TO
DEMENTIA ONE IS DO THEY DIRECTLY
CONTRIBUTE TO AMYLOID DEPOSITION
IN THE BRAIN AND WE LOOKED AT
VASCULAR RISK FACTORS IN MIDDLE
AND LATER AGE AND FOCUSSED ON
MIDDLE AGE WITH THE HYPOTHESIS
VASCULAR RISK FACTORS IN MIDDLE
MAY BE ASSOCIATED WITH AMYLOID
DEPOSITION LATER IN LIFE
INDEPENDENT OF FACTORS AND IN
PARTICULAR WE LOOKED AT NUMBER
OF VASCULAR RISK FACTORS HERE.
WE TALLIED HOW MANY OF HIGH
BLOOD PRESSURE AND CHOLESTEROL,
OBESITY, SMOKING AND DIABETES
AND HOW MANY RISK FACTORS YOU
HAD AND PEOPLE WITH MORE OF THE
RISK FACTORS COMPARED TO PEOPLE
WHO HAD NONE THAT PEOPLE WHO HAD
MORE OF THE RISK FACTORS HAD A
GREATER AMYLOID IN THEIR BRAIN
IF YOU HAD ONE RISK FACTOR YOU
HAD IN BETWEEN.
A DOSE RESPONSE AND THE ACTUAL
NUMBERS ARE SHOWN IN THE TABLE
HERE AND AS WE GET TO LATER
VISITS, MEANING LESS MIDLIFE AND
LATER IN LIFE AND MORE
CONCURRENT WITH AMYLOID SCAN WE
DON'T SEE THE SAME RELATIONSHIP
SHOWING THE IMPORTANCE OF LIFE
COURSE IN VASCULAR RISK FACTORS
AND A LINK TO AMYLOID DEPOSITION
THAT CAN LEAD TO ALZHEIMER'S
DISEASE OR AT LEAST IS A MARKER
OF ALZHEIMER'S DISEASE.
AND KEENON WALKER LOOKS AT THESE
CARDIOVASCULAR RISK FACTORS AND
PEOPLE WITH THESE HAD MORE MORE
AMYLOID DEPOSITION AND SAW
STRONGER RELATIONSHIPS IN BLACK
PARTICIPANTS COMPARED TO WHITE.
THE AMOUNT OF QUARTILES OF RACE
AND FOUND HIGHER AMYLOID
DEPOSITION IN BLACK INDIVIDUALS
WITH THESE AND I HOPE YOU
PROVIDED VASCULAR RISK FACTORS
ARE ASSOCIATED DEMENTIA AND MAY
BE AN APPEALING TARGET FOR
PREVENTION BECAUSE OF THE MIXED
CASES WE SEE IN DEMENTIA IN
BLACK VERSUS WHITE INDIVIDUALS
AND WHAT EVIDENCE IS THERE IN
THE LITERATURE AND FOCUSSING ON
THE EPIDEMIOLOGIC LITERATURE
THAT SHOWS DIFFERENCES IN RACE
AND WHAT MIGHT THE MECHANISMS
BE?
ONE THING TO LOOK AT IS HOW THE
BIOMARKERS FOR ALZHEIMER'S
DISEASE DIFFER BY RACE.
IS THERE A DIFFERENCE IN THE
DISEASE PROCESS AND IN THE
INDIVIDUALS WE ENROLL FOR
STUDIES?
THE ANSWER IS PROBABLY YES TO
BOTH AND TO THE LATTER.
THE ARIC STUDY WAS FROM THREE
COMMUNITIES.
WE FOUND INDEPENDENT OF AGE,
SEX, EDUCATION, APOE, WHITE
MATTER HYPERINTENTION TI AND
BRAIN VOLUME IF PEOPLE HAD MILD
IMPAIRMENT OR NOT WE SEE HIGHER
AMYLOID IN BLACK VERSUS WHITE
AND NO STUDIES THAT WERE
RECRUITING PEOPLE FOR AMYLOID
IMAGING HAD DIVERSE POPULATIONS
AT ALL.
NO ONE HAD SHOWN ANYTHING LIKE
THIS AND WE WERE SURPRISED BY
THE FINDING AND NOT SURE WHAT TO
MAKE OF IT.
IT WAS NOTHING WE HYPOTHESIZED
AT THE POINT BUT WE THINK OF
DEFINING DISEASE BY THESE
IMAGING BIOMARKERS WE NEED TO
UNDERSTAND HOW THEY MIGHT DIFFER
ACROSS RACE ETHNIC GROUPS AND
WHAT THE REASONS FOR THE
DIFFERENCE MIGHT BE.
INTERESTINGLY, SINCE THAT STUDY
CAME OUT, THESE ARE OUR DATA
AGAIN 2016 SHOWING HIGHER RATES
OF AMYLOID IN BLACKS VERSUS
WHITES REGARDLESS OF WHAT APOE
LEVEL YOU'RE LOOKING AT.
HERE'S HIGHER AMYLOID IN BLACKS
VERSUS WHITES.
AS THE NOT EXPLAINED BY THE APOE
DIFFERENCE WE SEE WITH DEMENTIA
IN THE CLINICAL DEMENTIA EVENTS.
THIS IS A STUDY WHERE YOU SEE
ALMOST THE SAME TABLE PUBLISHED
YEARS AGO LOOKING AT A CLINICAL
TRIAL RECRUITING PEOPLE CALLED
THE A4 STUDY AND THEY FOUND THE
OPPOSITE THE NON-HISPANIC BLACK
PARTICIPANTS THE ORANGE BAR WERE
CONSISTENTLY AT LOWER AMYLOID
LEVELS COMPARED TO OTHER GROUPS
ON PET SCAN.
ON A SIMILAR SCAN DEFINING
THINGS IN A SIMILAR WAY THEY SEE
A VERY DIFFERENT FINDING.
THIS IS THE CLINICAL TRIAL
POPULATION.
THEY TRIED HARD AND BEEN
SUCCESSFUL AND HAD A DIVERSE
POPULATION BUT IT'S NOT A
COMMUNITY-BASED COHORT AND WE
NEED TO CONSIDER THAT.
IN THE WORK IN THE ALZHEIMER'S
DISEASE CENTER THEY FOUND
SIMILAR AMYLOID ON BLACK AND
WHITE AND LOWER LEVELS OF CSF
TAU WHICH WE DON'T HAVE THAT
WORK IN OUR DATA YET.
WE HAD INCONSISTENT RESULTS AND
LEADS TO CONFUSION IN THE FIELD
BUT AN EMPHASIS WE NEED TO THINK
ABOUT BIOMARKER LEVELS AND HOW
THEY MAY DIFFERENT BY RACE
ETHNIC GROUPS AND WHY THEY MAY
DIFFER AND WHAT THAT SAYS ABOUT
OUR RECRUITMENT AND POTENTIAL
SELECTION BIAS.
HERE'S SOME POSSIBLE
EXPLANATIONS FOR WHAT WE SAW AND
REASONS FOR THESE INCONSISTENT
-- INCONSISTENCIES AND THERE'S
MORE MIXED PATHOLOGY IN PEOPLE
THAT PRESENT.
IF YOU LOOK AT A COGNITIVELY
IMPAIRED POPULATION YOU MAY SEE
THIS AND WE RECRUIT FROM PEOPLE
WHO DIDN'T HAVE DEMENTIA AND MAY
EXPLAIN THE FINDING AND I SHOWED
VASCULAR RISK FACTORS ARE
ASSOCIATED WITH AMYLOID.
IS IT POSSIBLE THE RELATIONSHIP
COULD REFLECT IN HIGHER LEVELS
OF AMYLOID BECAUSE THERE'S MORE
VASCULAR RISK IN BLACK VERSUS
WHITE INDIVIDUALS AND THE
EMPHASIS.
IT DEPENDS HOW YOU CONSIDER THE
POPULATION, A CLINICAL TRIAL
POPULATION, PEOPLE MOTIVATED
COME IN TO BE PART OF A CLINICAL
TRIAL OR ALZHEIMER'S DISEASE
CENTER WHICH IS A
DISPROPORTIONATELY HIGHER
EDUCATED POPULATION AND MAY BE
LESS RISK AND WE HAVE TO LOOK AT
DIVERSE POPULATIONS AND BUT IT'S
IMPORTANT TO UNDERSTAND IT IF
POTENTIAL THERAPEUTICS ARE GOING
TO BE IMPACTFUL IN DIVERSE
POPULATIONS BECAUSE IF WE'RE
SCREENING PEOPLE BASED ON
IMAGING, BIOMARKER LEVELS,
ETCETERA, WE MAY GET A DIFFERENT
STORY DEPENDING ON WHO WE
RECRUITED FOR THE STUDY AND HOW
WE DEFINE POSITIVITY, ETCETERA.
TO WRAP UP IN THINKING OF
MECHANISM AND WRAP UP THE TALK
IN GENERAL BEFORE WE TALK
BRIEFLY ABOUT WHAT WE KNOW ABOUT
PREVENTION, WHAT ABOUT SOCIAL
DETERMINATES OF HEALTH.
WE TALKED ABOUT RACE AND NEED TO
THINK OF UPSTREAM FACTORS AND
WHAT MAY HAVE CONTRIBUTED.
CHRISTEN GEORGE LED THE STUDY
AND WE LOOKED AT LIFE COURSE AND
EDUCATION FACTORS AND THERE'S A
NUMBER OF WAYS WE DEFINE LIFE
COURSE SES IN CHILDHOOD AND
YOUNG ADULTHOOD AND ONLY STARTED
SAYING PARTICIPANTS 45 AND UP SO
A LOT OF THIS IS BY INFORMATION
WHERE THEY LIVED AND WE HAVE
INFORMATION ABOUT PARENTAL
EDUCATION BY INTERVIEW AND WHAT
SHE FOUND IS PEOPLE WHO HAD A
HIGHER LIFE COURSE SOCIO
ECONOMIC STATUS AND INDIVIDUAL
SOCIO ECONOMIC STATUS AND SOME
NEIGHBORHOOD LEVEL ECONOMIC
STATUS HAD A LOWER RISK OF
DEMENTIA BUT THERE'S EXCITING
WORK BEING DONE WITH THE AREA
DEPRIVATION INDEX AND A SUMMER
STUDENT LED WORK LOOKING AT
WHETHER THE RACE DIFFERENCE WE
SAW IN THE ARIC PET STUDY COULD
BE EXPLAINED BY OTHER SOCIO
ECONOMIC FACTORS, OTHER SOCIAL
FACTORS.
WE ADJUSTED FOR EDUCATION AND
VASCULAR RISK FACTORS AND WHITE
MATTER, AND DIDN'T SEE THE
DIFFERENCE AMYLOID EFFECTS WERE
GREATER IN BLACKS THAN WHITES
AND THIS IS SHOWING WHAT THE
ESTIMATES ARE IF WE ADJUST FOR
THE OTHER FACTORS.
AGE, SEX, APOE, HYPERTENSION,
DIABETES, SMOKING, BODY MASS,
EDUCATION.
THIS IS SHOWING A CONSISTENTLY
HIGH ODDS OF AMYLOID FOR BLACKS
VERSUS WHITES AND WHEN WE ADDED
ANNUAL INCOME FACTORS AND
PRIVATE INSURANCE STATUS YOU CAN
SEE WE'RE STARTING TO CHIP AWAY
AT THE AFFECT OF THE RACE
DIFFERENCE ON AMYLOID.
IT'S HIGHLY LIKELY THERE ARE
SUFFICIENT SOCIAL FACTORS THAT
COULD EXPLAIN THE RACE
DIFFERENCE WE SEE CLEARLY IN
GENERAL FOR THESE STUDIES WE'RE
NOT DOING A GOOD ENOUGH JOB OF
CAPTURING WHAT THE FACTORS ARE
AND THAT'S TRUE ACROSS THE
BOARD.
WHAT WE FOUND IS 8% OF THE RACE
EFFECT ON AMYLOID POSITIVITY IS
M
MEDIATED BY INCOME AND 10% BY
INSURANCE STATUS.
THERE'S STILL A GREAT DEAL WE
DON'T KNOW WHY IS THERE BUT
STILL NEED TO THINK OF OTHER
SOCIAL FACTORS.
THERE'S OTHER SOCIAL FACTORS.
OLIVIA MANUAL A POST-BAC WITHME
IS LOOKING AT LOW BIRTH WEIGHT
AND FOUND PEOPLE WITH A
SELF-REPORTED LOWER BIRTH WEIGHT
ARE A LOWER RISK BUT NOT BIG.
HIGH BIRTH WEIGHT IS ASSOCIATED
WITH A HIGHER RISK OF DEMENTIA
ONLY IN BLACK BUT NOT WHITE
PATIENTS.
THIS IS ABOVE 9 POUNDS.
INDEPENDENT OF OTHER BASIC
DEMOGRAPHIC AND EDUCATION RISK
FACTORS BUT WE'RE STILL IN THE
PROCESS OF DELVING INTO OTHER
SOCIO ECONOMIC FACTORS TO TRY TO
EXPLAIN THE DIFFERENCES.
SO TIMELY WHAT ABOUT
OPPORTUNITIES FOR PREVENTION?
IN GENERAL, I TOLD YOU THAT
THESE RISK FACTORS ARE IMPORTANT
SO POTENTIALLY COULD BE
SOMETHING THAT IS A TARGET FOR
PREVENTION.
I WANT TO EMPHASIZE THESE ARE
ESTIMATES OF OPTIMAL
CARDIOVASCULAR HEALTH ACROSS THE
DIFFERENT MEASURES AND SHOWING
YOU IN NON-HISPANIC BLACKS AND
WHITES AND MEXICAN-AMERICAN
INDIVIDUALS AND THESE ARE
STATISTICS IF YOU LOOK AT BMI,
THIS BLUE IS IDEAL, RED IS
INTERMEDIATE.
LOWER RATES OF IDEAL AND
INTERMEDIATE IN BLACK AND
HISPANIC INDIVIDUALS AND SIMILAR
NUMBERS IN DIET AND BLOOD
PRESSURE AND LOWER RATES OF
CARDIOVASCULAR HEALTH IN
MINORITIZED POPULATIONS.
THERE'S A TREMENDOUS
OPPORTUNITIES FOR PREVENTION
BECAUSE WE'RE NOT DOING A GOOD
JOB AT ACHIEVING THE TARGETS.
AND I'M NOT GOING TO GO INTO
THIS IN DETAIL AND I SUSPECT
EVERYONE ON THE MEETING COULD
TEACH ME ABOUT THIS BETTER THAN
I UNDERSTAND IT MYSELF BUT I
WANT TO MAKE THE POINT THAT ALL
OF THESE IMPORTANT SOCIAL
FACTORS WE THINK ABOUT
INDIVIDUAL LEVEL, NEIGHBORHOOD
LEVEL, SOCIETY LEVEL, COMMUNITY
LEVEL CAN INFLUENCE HEALTH TO
THE POINT THEY INFLUENCE BIOLOGY
AND CAN INFLUENCE THE RISK
FACTORS.
SEEING DIFFERENCES IN RISK
FACTOR PREVALENCE DOESN'T MEAN
THEY'RE NOT INFLUENCED BY SOCIAL
FACTORS BUT THERE'S MANY WAYS IN
WHICH SOCIAL FACTORS CAN
INFLUENCE RISK OF DEMENTIA AND
THEREFORE POTENTIALLY BE TARGETS
FOR PREVENTION.
SO JUST TO WRAP UP IN WHAT WE
KNOW ABOUT PREVENTION SO FAR.
SO MARK LEED USED ARIC DATA
TRYING TO UNDERSTAND THE
PROPORTION OF PREVENTIBLE CASES
FOCUSSING ON THE MODIFIABLE RISK
FACTORS IDENTIFIED.
BASED ON THE DATA SOME I SHARED
AND SOME FROM OTHER COHORTS,
THEY TARGETED THESE PRIMARY
FACTORS THEY FELT WERE
MODIFIABLE RISK FACTORS FOR
DEMENTIA.
THIS IS OVER THE LIFE COURSE AND
WHY THE LIFE COURSE IS IMPORTANT
AND HIGH BLOOD PRESSURE,
OBESITY, THEY PUT DIABETES IN
LATER LIFE BUT WE THINK IT'S
PARTICULARLY IMPORTANT IN
MIDLIFE AS WELL.
THESE RISK FACTORS, WE LOOKED AT
THEM TO SEE WHAT PROPORTION OF
DEMENTIA CASES THEY ACCOUNTED
FOR.
WE FOUND 41% OF DEMENTIA CASES
IN THE U.S. WERE ATTRIBUTABLE TO
THE 12 RISK FACTORS PARTICULARLY
HYPERTENSION AND PHYSICAL
INACTIVITY IF EACH RISK FACTORS
WAS REDUCED IT REDUCED THE RISK
BY 7% AND HIS -- THIS WAS
HIGHER IN OTHER POPULATION AND
WE AT ALZHEIMER'S TREATMENTS.
RECENT THERAPIES HAVE BEEN IN
RELATIVE NON-DIVERSE
POPULATIONS.
HERE'S AN EDITORIAL TALKING
ABOUT THE STUDY AND THEY WERE
SELF-REPORTED FOR LECANEMAB AND
BECAUSE IT WAS A RANDOMIZED
TRIAL ONLY 6 WERE BLACK AND
THERE'S A NEW NEWER THERAPEUTIC
WITH HIGHER RATES OF HISPANIC
INDIVIDUALS BUT STILL LOWER
RATES OF BLACK PARTICIPANTS AND
THIS ALLOWED RISK FACTORS AND
OTHER TRIALS HAVE A PURE
ALZHEIMER'S POPULATION SO THEY
OFTEN EXCLUDE VASCULAR RISK
FACTORS WHICH IS WHY THEY'RE
SHOOTING THEMSELVES IN THE FOOT
WITH LESS DIVERSE POPULATIONS.
OTHER RISK TRIALS, PRINT MIND
WHICH LOOKED AT AGGRESSIVE BLOOD
PRESSURE CONTROL DID A BETTER
JOB AT RECRUITING MORE DIVERSE
POPULATIONS AND FOUND EVIDENCE
MORE AGGRESSIVE VERSUS LESS
AGGRESSIVE BLOOD PRESSURE
CONTROL WAS ASSOCIATED WITH LESS
MCI BUT NOT DEMENTIA
SPECIFICALLY WHICH WAS THE
PRIMARY HYPOTHESIS.
THE STUDY OF ASPIRIN AND WAS
NEGATIVE FOR DEMENTIA ONLY HAD
5% BLACK PARTICIPANTS.
MULTI-MODAL INTERVENTIONS ARE
NOW A NEW DIRECTION.
THE FINGER TRIAL SHOWED EVIDENCE
IN FINLAND THAT A MULTIMODAL
INCLUDING COGNITIVE STIMULATION
AND PHYSICAL ACTIVITY AND
HEALTHY DIET WHICH WAS A HEALTHY
NORDIC DIET CONTRIBUTED TO A
HEALTHIER LIFESTYLE AND THEY'RE
LOOKING TO RECRUIT DIVERSE
POPULATIONS AND PLANNING TO
STUDY A SIMILAR MULTIMODAL
INTERVENTION.
IN CONCLUSION WE SEE HIGHER
RATES IN BLACK AND HISPANIC
INDIVIDUALS IN THE U.S.
VASCULAR RISK FACTOR A GREAT
OPPORTUNITY FOR PREVENTION WE
HAVE A CLEAR ASSOCIATION FOR
OUTCOME.
THEY MAY BE IMPORTANT AT AN
EARLY STAGE OF DISEASE AND VERY
COMMON IN DISPARITY POPULATIONS.
THERE MAY BE SOME DIFFERENCES IN
THE RISK FACTORS IN BLACKS
VERSUS WHITES AND STILL NEED TO
UNDERSTAND MORE WHY THAT'S THE
CASE AND WE NEED TO THINK
CAREFULLY ABOUT BIOMARKERS WHEN
WE DESIGN TRIALS AND INTERPRET
TRIAL RESULTS AND MAKE SURE THE
STUDIES HAVE DIVERSE STUDY
POPULATIONS.
THE MORE WE TRY TO TRACE BACK
THE MECHANISMS WE NEED TO THINK
OF SOCIAL DETERMINATES AND NEED
TO DO A BETTER JOB OF STUDYING
THEM IN LARGE COHORT CLINICAL
TRIAL STUDIES BUT MAY NOT
ELIMINATE WHAT IMPACTS HEALTH
OUTCOMES.
WE'RE CONTINUING TO DO A LOT OF
THE WORK LOOKING AT ARIC AND
MODIFIABLE RISK FACTORS AND
INTERACTIONS BETWEEN VARIOUS
OMICS AND SOCIAL DETERMINATES OF
HEALTH AND THOSE WHO CAN ACHIEVE
RELATIVE NORMAL HEALTH THAT HAVE
PATHOLOGY AND LOOKING AT THE
LIFE COURSE AND THE DISCOVERY
COHORT WHICH IS AN ONGOING
DETAILED STUDY LOOKING AT
POST-STROKE DEMENTIA IN
DISPARITY POPULATIONS FOCUSSING
ON THE YOU HAVE A VULNERABLE
BRAIN WITH A STROKE AND THAT
IMPACTS THE RISK AND WE HAVE
P.I.s AT MASS GENERAL AND A LEAD
THE STATISTIC CORPS.
WE'RE RECRUITING 8,000 PEOPLE
WITH ISCHEMIC STROKE AT 30 SITES
FOCUSSING ON DIVERSE POPULATIONS
AND FOCUSSING ON COGNITIVE
IMPAIRMENT AND DEMENTIA AFTER
STROKE.
WITH THAT I'D LIKE TO
ACKNOWLEDGE ALL OF MY MANY
INCREDIBLE COLLABORATORS AND OUR
FUNDING SOURCES AND MY FUNDING
SOURCE IN THE INTRAMURAL
RESEARCH PROGRAM AND WITH THAT I
WILL STOP AND IF THERE'S
QUESTIONS THROUGH KELVIN OR IF
HE CAN ASK THEM OR FEEL FREE TO
REACH OUT BY E-MAIL.
THANKS SO MUCH.
>>THANK YOU, DR. GOTTESMAN.
VERY INTENSIVE BODY OF WORK THAT
REALLY SHOWCASES THE
RELATIONSHIP BETWEEN RACE AND
ETHNICITY AND SOCIAL
DETERMINATES AND THE BIOLOGICAL
MECHANISM WITH IMPAIRMENT OF
DEMENTIA.
IT'S BLIND BLOWING THE WORK
BEING DONE.
IT'S VERY IMPRESSIVE.
I HAVE A FEW QUESTIONS AND YOU
CAN SEND AN E-MAIL AND ASK THE
QUESTIONS OF YOU.
ONE OF WHICH IS THAT I FOUND
SOME OF THESE STUDIES THAT HAVE
CONDUCTED IN THE PAST STARTING
MORE WITH LATE LIFE AND LATER ON
AND KNOWING THE PREMATURE
MORTALITY IN CERTAIN POPULATIONS
IT POSES A CHALLENGE OF
UNDERSTANDING SOME FACTORS MAY
HAVE LED TO PREMATURE MORTALITY
AND COMPARED TO CAUSE OF DEATH
AND HAVING THE OUTCOME.
I UNDERSTAND YOU TRIED TO DO
SOME OF THE PROJECTS TO ACCOUNT
FOR THOSE BUT IT STILL SEEMS TO
BE A BIG CHALLENGE THERE.
IS THAT CORRECT?
>>YOU'RE RIGHT.
WE CLEARLY SEE DISPROPORTIONATE
ATTRITION IN MORTALITY IN BLACK
INDIVIDUALS IN ARIC.
NO QUESTION.
JACKSON IN PARTICULAR THERE'S
ONGOING THERE WAS A WHOLE WATER
DISASTER THE PAST YEAR.
THERE'S CURRENT THREATS TO
HEALTH OF INDIVIDUALS IN JACKSON
AND WE KNOW WHEN WE LOOK AT THE
ATTRITION OF OUR COHORT OVERTIME
IT'S DISPROPORTIONATE IN JACKSON
IN PARTICULAR WE HAVE BLACK
PARTICIPANTS FROM JACKSON AND
WINSTON AND SALEM.
WE TRY TO ACCOUNT FOR THAT
ATTRITION KNOWING THE
INDIVIDUALS MOST AT RISK FOR THE
OUTCOME ARE LEAST LIKELY TO MAKE
IT IN.
THE IDEA IS YOU UPWEIGHT THOSE
LESS LIKELY TO MAKE IT TO A
LATER VISIT TO COME UP TO A
PSEUDO POPULATION IF THEY HADN'T
HAD THE ATTRITION BUT YOU CAN'T
UPWEIGHT PEOPLE THAT DON'T
EXIST.
THERE'S THAT CONSIDERATION.
WE LOOK AT COMPETING RISK OF
DEATH IN OUR ANALYSES AS A
SECONDARY ANALYSIS TO HELP US
UNDERSTAND HOW THAT AFFECTS OUR
ASSOCIATIONS AND MOST OF WHAT I
SHOWED YOU HAS SIMILAR
ASSOCIATIONS WHEN WE LOOKED AT
COMPETING RISK OF DEATH AS WELL.
THE PROBLEM IS THAT EVERY STUDY
OF AN AGING POPULATION, EVEN IF
YOU RECRUIT PEOPLE AT AGE 70 IS
GOING TO BE A SURVIVAL
POPULATION.
THAT'S THE DEFINITION OF
RECRUITING PEOPLE IN OLDER AGE
OR WE FOLLOW THEM TO OLDER AGE.
THE ADVANTAGE WE KNOW WHO WE
HAVE AND DON'T HAVE BUT ANY
STUDY THAT STUDIES AGING IS
GOING TO HAVE A SURVIVORSHIP
ISSUE AND WE THINK OF THIS A LOT
ESPECIALLY FOR OUR ARIC PET
STUDY IN PARTICULAR WAS ONLY
PEOPLE WITHOUT DEMENTIA.
.
WE SOMETIMES HAVE FOUND
UNEXPECTED ASSOCIATIONS WHERE WE
SAW A RISK FACTOR WE THOUGHT
WOULD INCREASE AMYLOID BUT IS
PROTECTIVE BECAUSE WE THINK THE
PEOPLE THAT MADE IT THIS FAR IF
YOU HAD THAT RISK FACTOR AND HAD
AMYLOID INTO OUR BRAIN YOU WOULD
PROBABLY NOT MAKE IT IN OUR
STUDY BECAUSE WE EXCLUDE PEOPLE
SO IT'S TRICKY TO THINK OF
SURVIVORSHIP AND WE ACKNOWLEDGE
IT'S A LIMITATION BUT I THINK
ANY STUDY OF OLDER PEOPLE YOU'LL
ENCOUNTER THAT ISSUE.
>>AND ALSO THINK BACK TO SOME
OF THE WHEN YOU SHOW THE SLIDE
FOR THE LANCET REPORT SOME
THINGS MENTIONED LIKE ONLY ONE
BEING MENTIONED IS EDUCATION AND
EIGHT OF THINGS ARE MIDLIFE AND
LATER IN LIFE.
IS THAT BECAUSE OF THE
AVAILABILITY OF THE DATA AND NOT
BECAUSE THEY'RE NOT INFORMED OF
EARLIER STAGE OF LIFE BUT NOT
ENOUGH DATA AND WE SHOWCASE THE
IMPACT.
>>YES, 300%, YES.
IF ANYONE HAS A PEDIATRIC COHORT
THAT WANTS TO EXTEND -- THIS IS
MY FANCY TO FOLLOW PEOPLE FROM
EARLIER AGE.
I DON'T THINK MIDLIFE IS
IMPORTANT BUT IF YOU ARE NOT
EXPOSED BY SOMETHING YOU'RE SAFE
AND PROBABLY HYPERTENSION IN
MIDDLE AGE YOU'RE BEING EXPOSED
AT A CRITICAL PERIOD AND
PROBABLY REFLECTED OF DURATION
OF EXPOSURE.
IF YOU HAVE IT IN MIDLIFE YOU
HAVE IT FOR LONGER.
I THINK CARDIA IS LOOKING AT
EARLIER ADULTHOOD BUT THEY'RE
NOT OLD ENOUGH YET AND SEE
ASSOCIATIONS WITH COGNITION.
SOME PEDIATRIC COHORTS IN THE
YOUNG FIN STUDY IN FINLAND
SHOWING ASSOCIATION BETWEEN
OPTIMAL CARDIOVASCULAR HEALTH
AND COGNITION IN THE 20s BUT WE
DON'T KNOW WHAT THAT MEANS FOR
LONGER TERM OUTCOMES AND
CERTAINLY NOT FOR ANY OF THE
BIOMARKERS THAT TAKE DECADES TO
DEVELOP.
SO YOU'RE ABSOLUTELY RIGHT
THERE'S CLEARLY OTHER IMPORTANT
FACTORS THAT OCCUR EARLIER IN
THE LIFE COURSE.
MANY ARE CO-LINEAR WITH
EDUCATION AND BIRTH WEIGHT WE
SEE INDEPENDENT ASSOCIATIONS
WITH EDUCATION AND EDUCATION
ACCOUNTS FOR MUCH OF THESE BUT
NOT EVERYTHING.
SO MUCH IS NEEDED TO BE DONE TO
LOOK EARLIER IN THE LIFE COURSE
BECAUSE IF WE'RE REALLY
FOCUSSING ON PREVENTION AND
REDUCING IF THE POINT IS SOCIAL
FACTORS CONTRIBUTE TO CHANGES IN
BIOLOGY BUT CONTRIBUTE TO
CHANGES IN DEMENTIA RATES THEN
OBVIOUSLY THE EARLIER YOU TARGET
THOSE PREVENTSIVE OF PREVENTIVE
STUDIES THE MORE THEY'LL IMPACT
THE BIOLOGICAL CHANGES.
>>PARTICULARLY WHEN YOU RAISE
THE FINDING ABOUT BIRTH WEIGHT
AND BLACK INDIVIDUALS AND HIGH
BIRTH WEIGHT ASSOCIATED WITH THE
MORE SIGNIFICANT DECLINE I'M
WONDERING DOES IT HAVE ANYTHING
TO DO WITH GESTATIONAL DIABETES
HIGHER AMONG BLACK WOMEN
ACCORDING TO SOME DATA.
>>YOU'RE ABSOLUTELY -- I AGREE
IT'S HIGHLY LIKELY IT REFLECTS
HEALTH OF THE MOTHER BUT ANY
BIRTH WEIGHT MEASUREMENT WILL
REFLECT HEALTH OF MOTHER BUT
PARTICULARLY IN THAT CASE IT'S A
REFLECTION OF A DIABETIC MOTHER.
WE HAVE SOME PARENTAL
INFORMATION AND PARENTAL
EDUCATION AND OCCUPATION AND BUT
NOT MUCH OTHER IN TERMS OF THEIR
HEALTH MEASURES.
BUT THAT'S THE POINT OF A LOT OF
THESE FINDINGS IS EVEN IF WE CAN
LOOK WITHIN ONE GENERATION FOR
EXAMPLE AND TRY TO EDUCATE FOR
EVERY FACTOR WE THINK IS
PRESENT, IF YOU HAVE DECADES OF
SYSTEMIC RACISM ALTERING THE WAY
HEALTH IS DEALT WITH AND HEALTH
MAY AFFECT OTHER OUTCOMES YOU'RE
NOT REALLY GOING TO BE ABLE TO
ACCOUNT FOR THOSE UNLESS YOU
HAVE MULTI-GENERATIONAL STUDIES.
YOU'RE RIGHT, THAT'S PROBABLY A
KEY DRIVER OF SOME OF THE
FINDING IN BLACK INDIVIDUALS IN
PARTICULAR.
>>YEAH.
AND I THINK ONE OF THE -- YOUR
CALL FOR MORE DIVERSE POPULATION
IN THE STUDIES AND ONE POINT I
WANTED TO RAISE WITH YOU IS THE
HETEROGENEITY WITH THE ETHNIC
RACIAL GROUPS AND PARTICULARLY
WHEN WE THINK ABOUT BLACK
INDIVIDUALS AND WE HAVE A
SIGNIFICANT PROPORTION OF THEM
WE SEE AN INCREASING NUMBER OF
AFRICAN IMMIGRANT OR AFRO
CARIBBEANS AND WHEN WE EXTEND
THAT TO THE ASIAN POPULATIONS
YOU SEE A MIXED GROUP OF PEOPLE
SO I THINK IS THERE ENOUGH DATA
TO EVEN LOOK AT THAT
HETEROGENEITY WITHIN THE RACIAL
GROUPS?
>>DEFINITELY NOT IN OUR STUDY.
SO ONE FREQUENT CRITICISM WHICH
WE FULLY ADMIT WE CAN'T TOTALLY
OVERCOME IS HOW MUCH OF WHAT WE
SEE IS BECAUSE OF JACKSON,
MISSISSIPPI.
HOW MUCH IS COMMUNITY-SPECIFIC.
THE DISCOVERY COHORT WHICH IS
RECRUITING PEOPLE THAT HAVE
STROKE AND LOOKING AT
POST-STROKE DEMENTIA IS
RECRUITING FROM 30 DIFFERENT
SITES ACROSS THE U.S. WHICH
DOESN'T ADDRESS MORE GLOBAL
DIVERSITY AND WE'VE BEEN VERY
CAREFUL TO MAKE SURE NOT ONLY DO
WE HAVE SITES WITH DIVERSE
POPULATIONS AND NOT ONLY
RECRUITING MEXICAN AMERICANS BUT
IN TERMS OF DIVERSITY OF OUR
DISPARITIES POPULATIONS.
AND AS WE THINK ABOUT THE DATA
MAKING SURE WE HAVE DATA FROM
PEOPLE THAT ARE GEOGRAPHICALLY
DIVERSE SO NOT JUST REPRESENTING
ONE COMMUNITY FOR EXAMPLE.
SO MESA IS ANOTHER COHORT STUDY
INCLUDING BLACK POPULATION,
LATINX AND ASIAN POPULATION AND
WHITE POPULATION.
I'M PRETTY SURE THEY'RE ALL
CHINESE INDIVIDUALS FROM SAN
FRANCISCO BECAUSE THERE'S LINKS
CERTAIN COMMUNITIES TO CERTAIN
GROUPS OF POPULATIONS AND
INEVITABLY YOU'LL LIKELY TO
CONSIDER THAT ISSUE AND
SOMETHING TO CONSIDER IF WE
OBSERVE X IT DOESN'T HAVE MUCH
MEANING IS X ISN'T WELL DEFINED
AND THE POPULATION THAT HAS THAT
OBSERVATION ISN'T WELL DEFINED.
>>I'M LOOKING TO THE DATA WHERE
WE HAVE A DIVERSE POPULATION TO
LOOK AT THE HETEROGENEITY WITHIN
EACH GROUP AND WHEN YOU TALK
ABOUT THE RISK FACTORS RELATED
TO STROKE AND DEMENTIA FOR A
PARTICULAR RACIAL GROUP THEY'RE
VARY GREATLY WITH BEING A
SPECIFIC RACIAL GROUP AND I CAN
SAY I STUDY SMOKING WHEN YOU
LOOK AT ASIAN, THERE'S A
PREFERENCE BUT DIFFERENT WHEN
YOU LOOK AT CHINESE AMERICAN AND
JAPANESE AMERICAN VERSUS
JAPANESE IMMIGRANT VERSUS OTHERS
AND YOU LOOK AT FILIPINOS AND
THERE'S A HIGHER RATE OF SO THE
RATE OF CONTRIBUTION OF THE RISK
FACTOR IN THE SUBPOPULATION
COULD BE QUITE DIFFERENT AND
BRING BACK TO THE POINT OF
TAILORING THE PREVENTION
STRATEGY KNOWING THE
HETEROGENEITY WILL BE QUITE
IMPORTANT.
>>THAT'S A GREAT POINT.
THANK YOU FOR BRINGING THAT UP.
>>SO UNFORTUNATELY WE'RE RIGHT
UP TO OUR WONDERFUL CONVERSATION
ABOUT THE TOPIC OF DISPARITY IN
STROKE AND COGNITIVE IMPAIRMENT.
AS DR. GOTTESMAN PUT THERE'S
MORE WORK THAT NEEDS TO BE DONE
AND THAT'S WHY WE'RE HERE TO DO
THE RESEARCH AND HOPEFULLY MAKE
AN IMPACT IN REDUCING THE BURDEN
OF STROKE AND DISABILITY WITHIN
THE POPULATION ALSO DISPARITY OF
IT.
LOOKING FOR MORE OF THE WORK
YOU'RE GOING TO DO,
DR. GOTTESMAN AND WHEN YOU DO
WE'LL INVITE YOU BACK.
>>THANK YOU SO MUCH.
THANKS FOR HAVING ME.
BYE.
>>TAKE CARE, EVERYONE.