>> OKAY.
GOOD MORNING.
I'M WALTER KOROSHETZ THE
DIRECTOR OF THE INSTITUTE OF
DISORDERS AND STROKE AND THIS IS
THE ALZHEIMER'S DISEASE-RELATED
DIMENTIAS SUMMIT FOR 2025.
CAN EVERYBODY HEAR ME OKAY?
THUMBS UP, GREAT.
I WANT TO THANK THE PEOPLE WHO
DID ALL THE WORK INCLUDING
PEOPLE HERE AT NINDS AND
NATIONAL INSTITUTE OF AGING AND
PARTICULARLY THE WORKING GROUPS
YOU'LL HEAR FROM TODAY WHO
BROUGHT TO YOU RESEARCH
RECOMMENDATIONS FOR YOUR
CONSIDERATION AND FOR INPUT AND
THESE WILL THEN BE PRESENTED TO
THE NINDS COUNCIL FOR FORMAL
ADOPTION AND THANKS TO DR. POZEN
SHORE CHAIRING THE WORK GROUPS
THAT LED UP TO THE SUMMIT.
SO THIS IS THE SLIDE THAT JUST
REINFORCES WHAT WE ALL KNOW THAT
THE PUBLIC BURDEN AND SUFFERING
DUE TO DEMENTIA IS INCREASING
AROUND THE WORLD AND THIS IS
FROM THE DISEASE STUDY AND THE
INCREASE IN BURDEN OF DISEASE IS
PRIMARILY DRIVEN BY THE AGING OF
THE POPULATION.
SO IF YOU LOOK AT THE AGE
STANDARD PREVALENCE IT'S FAIRLY
FLAT, SOME INCREASE BUT PRETTY
FLAT AND IF YOU LOOK ON THE
RIGHT-HAND SIDE YOU SEE THE
NUMBERS OF PEOPLE AFFECTED OVER
TIME AS THE POPULATION AGES.
SO, THAT'S TRUE GLOBALLY AND
CERTAINLY TRUE IN THE UNITED
STATES AND WHY ADDRESSING
ALZHEIMER'S DISEASE AND RELATED
DEMENTIA IS A NATIONAL PRIORITY.
THE NATIONAL PLAN TO ADDRESS
THIS BURDEN OF ILLNESS WAS
ORIGINALLY RELEASED IN 2012.
IT'S UPDATED ANNUALLY.
IT CALLS FOR ACTION TO
ACCELERATE RESEARCH AND IMPROVE
CARE IN SERVICES FOR PEOPLE
LIVING WITH DEMENTIA AND THAT'S
DEFINED FOR THESE PURPOSE AS
ALZHEIMER'S DISEASE, VASCULAR
COGNITIVE IMPAIRMENT AND LEWY
BODY DEMENTIA WHICH IS THE
CONDITION THAT AFFECTS PEOPLE
WITH PARKINSON'S WHO THEN
DEVELOP DEMENTIA.
SOME PEOPLE WITH THIS DISEASE
DEVELOP DEMENTIA EVEN BEFORE THE
PARKINSON'S SYMPTOMS AND FRONTAL
TEMPORAL DEMENTIA AND THE BURDEN
OF ILLNESS FALLS CLEARLY ON THE
PEOPLE AFFECTED BUT ALSO ON THE
FAMILIES WHO CARE FOR THESE
FOLKS.
THE NATIONAL ALZHEIMER'S ACT WAS
AUTHORIZED IN 2011 AND HELD BY
HEALTH AND HUMAN SERVICES AND IN
EVALUATION WITH NIH AND OTHER
AGENCIES CONTRIBUTING AND
INCLUDES SIX KEY GOALS COVERING
RISK REDUCTION, WHICH IS ALWAYS
THE ONE THAT'S GOING TO GIVE YOU
THE GREATEST PUBLIC HEALTH
IMPACT IN TERMS OF PREVENTION,
TREATMENT CARE SUPPORT AND
PUBLIC AWARENESS.
THE ADVISORY COUNCIL ON
ALZHEIMER'S RESEARCH CARE AND
SERVICES MEETS REGULARLY.
IT HAS 12 PUBLIC MEMBERS
REPRESENTING PATIENT ADVOCATES,
CAREGIVERS, PROVIDERS, STATE AND
LOCAL GOVERNMENT REPS,
RESEARCHERS, VOLUNTARY HEALTH
ASSOCIATION REPRESENTATIVES AND
CHAIRED CURRENTLY BY DR. MIMS
AND IT'S BEEN A PLEASURE TO WORK
WITH ADRIAN OVER THE YEARS.
YOU SEE ON THE RIGHT SIDE THE
NUMBER OF FEDERAL AGENCIES
INVOLVED IN THE ADVISORY COUNCIL
ON ALZHEIMER'S RESEARCH CARE AND
SERVICES AND FOR EACH THERE'S A
SUBCOMMITTEE THAT WORKS AS A
COMMITTEE AND PREVENTION
COMMITTEE AND RISK REDUCTION
COMMITTEE.
WHAT WE DO IS SAID THE ADRD
MILESTONES AND WE DO THAT
THROUGH PEOPLE WORKING BEHIND
THE SCENES TO DEVELOP
RECOMMENDATIONS THAT ARE THEN
VETTED AT SUMMITS SUCH AS THE
ONES WE'RE TALKING ABOUT.
THERE ARE RESEARCH SUMMITS ON
CARE AND SERVICES FOR PERSONS
WITH DEMENTIA AND THEIR
CAREGIVERS AND THEY'RE RAN BY
THE NATIONAL INSTITUTES OF AGING
AN ALZHEIMER'S RESEARCH SUMMIT
AGAIN RAN BY THE NATIONAL
INSTITUTE OF AGING AND NINDS
RUNS THE ONE WE'RE TALKING ABOUT
TODAY WHICH IS ALZHEIMER'S
DISEASE RELATED RESEARCH SUMMIT.
THE SUMMITS REFLECT CRITICAL
SCIENTIFIC PRIORITIES AS BROUGHT
TO THE FOREFRONT BY WORKING
GROUPS THAT INCLUDE SCIENTISTS,
CAREGIVERS AND HEALTH CARE
PROVIDERS.
LEADING UP TO THE SUMMIT
SUBCOMMITTEES WORK ON
PARTICULARLY DEEP DIVES INTO
AREAS THOUGHT TO BE ESPECIALLY
IMPORTANT IN THEIR SUMMITS AND
STARTING TODAY THOSE PRIORITIES
FOR THE ALZHEIMER'S DISEASE
RELATED SUMMIT WILL BE REPORTED
OUT FOR YOUR INPUT AND
CONSIDERATION.
THIS PROFESSIONAL -- THESE PLANS
ALL GO INTO DEVELOPING THE
ANNUAL ADRD PROFESSIONAL
JUDGMENT BUDGET AS WELL AS THE
2024 ADRD PROGRESS REPORT.
THAT PROFESSIONAL JUDGMENT
BUDGET GOES STRAIGHT TO HHS AND
THEN IS CONSIDERED BY THE
CONGRESS AND SET BY
APPROPRIATION OF CONGRESS AND
THEY ESTIMATE THE ANNUAL BUDGET
FUNDING NEEDED TO LEVERAGE
SCIENTIFIC OPPORTUNITIES IN
DEMENTIA RESEARCH AND THE
CONGRESS HAS BEEN EXTREMELY
GENEROUS IN TERMS OF INVESTING
IN THE FUTURE OF THIS RESEARCH
OVER THE LAST SIX OR SEVEN
YEARS.
I WOULD SAY THE ANNUAL REPORT IS
NOW AVAILABLE ON THE WEBSITE.
IN TERMS OF ALZHEIMER'S
DISEASE-RELATED DIMENTIAS WHAT
WE CONCENTRATE ON ARE THE
VASCULAR CONTRIBUTIONS AND WEAR
AND TEAR ON THE BLOOD VESSELS IN
THE BRAIN CAUSING ISSUES SUCH AS
STROK
STROKES MANY TURN OUT TO BE SUB
CLINICAL AND THEY SEEM TO BE
RELATED TO DEVELOPING RISK OF
COGNITIVE IMPAIRMENT DIM EN IS
THAT OF AGING.
THERE'S ALSO A VERY INTERESTING
CONDITION THAT'S EXTREMELY
COMMON WE CALL WHITE MATTER
DISEASE.
THIS IS USUALLY ASSOCIATED WITH
CHANGES IN THE BLOOD VESSELS BUT
THE WHITE MATTER ARE THE C
CONNECTIONS BETWEEN THE BRAIN
AREAS AND WE SEE ABNORMALITIES
IN THE AREAS THAT COMPOSE THE
WIRES.
WE DON'T UNDERSTAND EXACTLY WHAT
CAUSES THE CHANGES TO OCCUR BUT
ALSO ASSOCIATED WHITE MATTER
DISEASE WITH HYPERTENSION AND
LEAD TO COGNITIVE IMPAIRMENT.
LEWY BODY DEMENTIA ARE THE
PATHOLOGICAL HALLMARK ARE LEWY
BODIES AN AGGREGATE OF SINUCLEIN
AND THEY DEVELOP MOTOR TROUBLE
AND THE AREA OF LEWY BODY
DIMENSION.
FRONTAL TEMPORAL DEMENTIA AND
OCCUR YOUNGER AND AFFECTS PEOPLE
IN THEIR 50s AROUND 60s.
CAUSES SOCIAL DECLINE IN
BEHAVIOR AND LANGUAGE AND
THEY'LL PRESENT TO A
PSYCHIATRIST FIRST BECAUSE OF
CHANGES IN THEIR BEHAVIOR AND
ALSO SEEN IN AMYOTROPHIC LATERAL
SCLEROSIS AND CORRELATION IN THE
GENETIC FORMS AND IN THE OTHER
FORMS OF FTD.
A BIG AREA OF INVESTIGATION IS
AROUND MIXED DEMENTIAS.
WHEN SOMEONE LOOKS IN THE BRAIN
OF PEOPLE WHO HAVE DIED WHO HAD
DEMENTIA, THE OLDER YOU ARE THE
MORE LIKELY YOU WILL HAVE A MIX
OF MULTIPLE DIFFERENT CONDITIONS
GOING ON TO CAUSE DEMENTIA AND
THAT REALLY GETS THINGS
COMPLICATED BECAUSE TREATMENTS
WILL HAVE TO AFFECT ALL OR WILL
HAVE TO HAVE SPECIFIC TREATMENTS
FOR EACH OF THE DIFFERENT
ETIOLOGIES THAT GO ON TO CREATE
THE TROUBLE FOR THE PEOPLE AS
THEY AGE.
THAT'S A BIG AREA OF CONCERN AND
WE'LL TALK MORE ABOUT THAT.
WE'LL LOOK AT THE MECHANISMS
CAUSALLY RELATED TO THE
COGNITIVE IMPAIRMENT OF DEMENTIA
BY THIS TIME OF BASIC RESEARCH.
WE UNDERSTAND WHY WE CAN
INTERVENE TO TRY TO REVERSE THE
PROCESS THAT LEADS TO COGNITIVE
IMPAIRMENT AND DEMENTIA.
THAT'S ONE OF OUR BIG AREAS OF
FOCUS AT THE NIH.
BUT THE JOB IS NOT TO PUBLISH A
LOT OF PAPERS AND END IT THERE.
THE JOB IS TO MOVE FROM THE
DISCOVERY IN THE LABORATORIES TO
THE DEVELOPMENT OF THERAPEUTICS
AND THAT REQUIRES UNDERSTANDING
WHAT ARE TARGETS THAT COME FROM
THE BASIC MECHANISMS OF DISEASE
THAT COULD BE DRUGGABLE.
INCLUDES DEVELOPMENT OF
BIOMARKERS THAT CAN IDENTIFY
PEOPLE WITH PARTICULAR
ETIOLOGIES AS WE MENTIONED
BEFORE.
THERE MAY BE MULTIPLE
ETIOLOGIES.
WE NEED THE BIOMARKERS TO
IDENTIFY WHO IS GOING TO RESPOND
TO WHAT TYPE OF TREATMENT
DEPENDING ON WHAT THE TARGET OF
THAT TREATMENT IS.
IN ADDITION BECAUSE DEMENTIA
OCCURS SLOWLY OVER TIME A STUDY
TO DEFINE A TREATMENT CANNOT
RELY ON SAY LOOKING FOR SEVEN TO
10 YEARS DOWN THE ROAD TO SEE
HOW IT WORKS.
WE NEED TO MAKE DECISIONS MUCH
MORE QUICKLY IN TERMS OF WHAT
TYPE OF DRUGS, SAY, FOR INSTANCE
NEED TO GO INTO THOSE LONGER
TRIALS AND THERE WE NEED
BIOMARKERS WE CALL TARGET
ENGAGEMENT TO KNOW THE DRUG IS
DOING WHAT YOU WANT IT TO DO.
AND THAT IS REALLY CRUCIAL
PARTICULARLY NOW BECAUSE WE HAVE
SO MANY DIFFERENT TARGETS THAT
HAVE BEEN IDENTIFIED IN THE
BASIC SCIENCE.
THE BOTTLENECK IS OFTEN
IDENTIFYING WHICH ONES ARE
ROBUST ENOUGH THEY CAN REALLY
MAKE A DIFFERENCE IN PEOPLE AND
THIS IS WHERE WE NEED THE
BIOMARKERS TO MAKE THOSE EARLY
TYPE OF DECISIONS GO, NO-GO
DECISIONS BEFORE ENTERING THE
LONG CLINICAL TRIALS.
BUT THE CLINICAL TRIALS ARE
CLEARLY THE END GAME HERE IS TO
SHOW IN A RIGOROUS WAY WHETHER A
TREATMENT IS WORKING OR NOT AND
WHAT IS THE AFFECT SIZE OF THAT
TREATMENT, WHAT ARE THE RISKS
AND BENEFITS AND THEREFORE TO
INFORM THE PUBLIC ON HOW THEY
SHOULD MOVE FORWARD WITH
THEIRSELVES -- THEMSELVES OR
LOVED ONES.
THE RESEARCH SYNERGIZES WITH
OTHER NEUROLOGICAL DISORDERS.
WE MENTIONED VASCULAR COGNITIVE
IMPAIRMENT AS A KEY FEATURE OF
THE ADRDs AND THERE'S INFORMED
BY WORK ON STROKE AND
CARDIOVASCULAR DISEASE IN THE
LAST 50 YEARS.
SIMILARLY YOU'LL HEAR ABOUT
INFLAMMATION INVOLVED IN THE
DAMAGE THAT OCCURS IN THE
NEUROGENERATIVE DISEASES AND SO
RESEARCH OVER THE LAST 50 YEARS
WE LEARNED A LOT AND IN NO
INSTANCE HAVE WE LEARNED
EVERYTHING BUT WE LEARNED A LOT
ABOUT THE INFLAMMATORY RESPONSES
IN THE BRAIN AND THESE ARE ALL
CRITICALLY IMPORTANT NOW AS
FOUNDATIONS TO UNDERSTAND HOW TO
DEVELOP TREATMENTS FOR THESE
DISORDERS.
SO, THE SLIDE JUST BASICALLY
INDICATES HOW COMPLICATED THE
SITUATION IS.
PARTICULARLY WHEN YOU ARE
DEALING WITH MULTI-ETIOLOGY DIM
EN -- DEMENTIAS YOU HAVE THE
SIGNATURE OF NEURO DEGENERATIVE
DISEASES AND TAU IS A PROTEIN
THAT AGGREGATES INSIDE THE CELLS
AND COMES LATER AND SEEMS TO BE
ASSOCIATED WITH DEATH OF THE
CELLS OPPOSED TO AMYLOID ITSELF.
TAU IS ALSO A PROTEIN THAT ONE
SEES IN THE FRONTAL DEMENTIAS
AND PEOPLE ARE DIAGNOSED WITH
ALZHEIMER'S DISEASE AND SIMILAR
WE'LL SEE IN MANY PEOPLE WHO
HAVE DEMENTIA DIAGNOSES DISEASE
HAS EVIDENCE OF SYNUCLEIN
AGGREGATION AND THIS HAPPENS
OVER TIME AND WHY SOME PEOPLE
ARE RESILIENT AND HAVE THE
PATHOLOGIES BUT COGNITIVELY
NORMAL ARE INTERESTING QUESTION
TO PURSUE.
ARE THERE THINGS IN PHYSICAL
ACTIVITY, DIET OR ALCOHOL OR
DRUG USE OR ENVIRONMENTAL
FACTORS, PSYCHOSOCIAL FACTORS,
METABOLIC FACTORS THAT GO ON TO
INFLUENCE THE PROGRESSION OF
THESE DISEASES ARE AREAS OF
GREAT INTEREST AT THIS TIME.
HERE IS JUST A SLIDE TO SHOW IN
THE STUDY A RELIGIOUS ORDER
STUDY OUT OF CHICAGO.
ONE CAN SEE AND IF YOU LOOK AT
PEOPLE WHO ARE ELDERLY, FEW OF
THEM HAVE ALZHEIMER'S ALONE.
AD VASCULAR IS COMMON AND FOR
OTHER DEMENTIAS ALSO VERY
COMMON.
FOR THE MAJORITY OF FOLKS WILL
HAVE A MIX OF PATHOLOGIES IN THE
ELDERLY STATE.
SOME FOLKS DEVELOP DEMENTIA
EARLIER ON AND THEY'RE LIKELY TO
HAVE A PURER FORM OF ONE OF
THESE TYPES OF DEMENTIAS BUT THE
PUBLIC HEALTH ISSUE IS IN OUR
AGING POPULATION AND THERE WE
HAVE TO LEARN HOW TO BEST
APPROACH THE ISSUE OF
MULTIETIOLOGY DEMENTIAS.
I MENTIONED BIOMARKERS AND THIS
IS AN EXAMPLE OF THE SYNUCLEIN
BIOPSIES AND YOU CAN SEE IN THE
SPINAL FLUID AND THEY BECOME
ABNORMAL POTENTIALLY 10 YEARS
BEFORE ANYONE SHOWS SIGNS OF
THEIR NEUROLOGICAL TROUBLES.
ON ONE HAND IT'S VERY
ENCOURAGING WE HAVE TREATMENTS
WE CAN IDENTIFY PEOPLE EVEN
BEFORE THEY GET SYMPTOMS AND IF
WE CAN INTERVENE EFFECTIVELY
THERE, THEN WE'RE BASICALLY CURE
THE DISEASE.
SO THAT'S KIND OF THE HOLY GRAIL
WE'RE HOPING THESE BIOMARKERS
WHEN LINKED WITH EFFECTIVE
TREATMENT.
THIS IS AN EXAMPLE OF A PHOSPHO
TAU BIOMARKER THAT AGGREGATES
INSIDE THE CELLS AND GENERALLY
THEN KILLS THE CELLS.
THESE ARE BLOOD TESTS THE
SYNUCLEIN TEST OF SKIN OR SPINAL
FLUID AND THESE ARE BLOOD TESTS
THAT CAN LOOK AT PHOSPHORO TAU
IN FOLKS AND YOU CAN SEE IF YOU
HAVE A LOW LEVEL, THEN YOU'RE
LIKELY TO HAVE NORMAL COGNITION
OVER TIME AND IF YOU HAVE A HIGH
LEVEL, THEN YOU'RE AT RISK FOR
DECLINING OVER TIME.
SO THIS IS STARTING WITH PEOPLE
WHO ARE COGNITIVELY NORMAL AND
SHOWING THIS IS A MARKER OF
DECLINE TOWARDS DEMENTIA.
THERE ARE NEW BIOMARKERS THAT
HAVE RECENTLY BEEN DISCOVERED
AND YET TO BE VALIDATED AND HAVE
GONE TO A COMMERCIAL PROCESS AS
SOME OF THE ABETA AND TAU
BIOMARKERS HAVE ALREADY DONE.
THIS IS A STUDY SHOWING THAT
THERE ARE TWO PROTEINS.
THEY HAVE FUNNY NAMES, YWHHA IS
ONE AND THE OTHER IS MPTX2.
THE OTHER TENDS TO GO UP WITH
DEMENTIA AND THE SECOND GOES
DOWN.
SO THE RATIO OF WHAT THEY'RE
MEASURING NOW IS SHOWING -- WE
COMPARE IT TO AMYLOID AND TAU BY
ITSELF AND THIS IS MUCH MORE OF
A ROBUST MARKER.
BUT IT IS A SPINAL FLUID TEST.
JUST AN EXAMPLE OF HOW THESE
FIELDS ARE PROGRESSING AND
VALUABLE BIOMARKERS, BLOOD AND
SPINAL FLUID AND ACTUALLY I
SHOULD MENTION THE RATIO IS ALSO
ABNORMAL IN THE BLOOD AS WELL.
BUT TIME AND STUDIES IN THOUSAND
OF PEOPLE NOW VALIDATING THE
BIOMARKERS WHICH WILL BE HIGHLY
PREDICTIVE.
THE AREA OF COGNITIVE IMPAIRMENT
DUE TO DUE TO VASCULAR DISEASE.
THERE'S VASCULAR CHANGES THAT
OCCUR DUE TO DEMENTIA DUE TO THE
BREAD AND BUTTER TYPE OF SEVERAL
VASCULAR DISEASE.
WE SEE THE HYPERTENSION IN AGING
AND ALZHEIMER'S ITSELF IS
ASSOCIATED WITH CHANGES AND HOW
BLOOD FLOWS FROM THE BRAIN AND
HOW OXYGEN IS SUPPLIED.
ONE OF THE MAJOR PROGRAMS FROM
THE ADRD IS LOOKING AT THE
CHANGES IN THE BLOOD VESSELS IN
PEOPLE WHO HAVE THIS WHAT WE
CALL SMALL VESSEL DISEASE OR
WHITE MATTER DISEASE I MENTIONED
EARLIER.
AND WE CAN SEE HERE WE'RE
WORKING TO DEVELOP A MARKER THAT
WE CAN MEASURE AND CORRELATE
WITH THIS AMOUNT OF MRI
ABNORMALITY WE SEE AS WELL AS
THE COGNITIVE IMPAIRED AND THIS
SHOWS HOW BLOOD FLOW CHANGES
WHEN THE BRAIN IS ACTIVATED OR
THE BLOOD VESSELS ARE STRESSED
TO DILATE IS ABNORMAL IN FOLKS
AS THEY DEVELOP COGNITIVE
IMPAIRMENT AND THIS IS SHOWING
THE GRAPHS IN MULTIPLE DIFFERENT
INSTITUTIONS INDICATING IT'S A
FAIRLY ROBUST FINDING THAT CAN
BE REPRODUCED AT MULTIPLE
DIFFERENT PLACES.
THESE ARE THE KINDS OF THINGS WE
DEVELOP TREATMENTS TO TRY TO
IMPROVE.
KTB43 IS ANOTHER PROTEIN THAT
AGGREGATES IN SIDE THE NEURONS
IN FOLKS WITH ALZHEIMER'S
DISEASE.
AS WELL AS THE FRONTAL DEMENTIAS
AND ALS.
OF NOTE, THIS PROTEIN IS
INVOLVED IN THE SPLICING OF
MESSENGER RNA.
MESSENGER RNA IS MADE FROM THE
DNA AND PROTEINS ARE MADE OFF OF
THE INSTRUCTIONS IN THE
MESSENGER RNA AND MESSENGER RNA
IS BROKEN UP INTO PIECES TO
CAUSE THE RIGHT AMOUNT OF AMINO
ACIDS IN YOUR PROTEINS.
TDP-43 IS INVOLVED IN THE
SPLICING FUNCTION AND WHEN IT
AGGREGATES, IT CAN'T DO THAT.
SO ONE SEES PROTEINS THAT HAVE
THICK -- HAVE PIECES IN IT THAT
SHOULD BE SPLICED OUT BUT
THEY'RE NOT BECAUSE OF THE
TPD-43 DYSFUNCTION AND THESE ARE
CALLED CRYPTIC PROTEINS AND
THESE ARE POTENTIALLY GOING TO
BE VERY GOOD MARKERS OF TDP-43
IMMIGRATION IN THE BRAIN OF
PEOPLE WITH FRONTAL TEMPORAL
DEMENTIA AND PARKINSON'S AND
ALZHEIMER'S AND ALS.
AND THERE'S INTERESTING
TECHNOLOGIES ON THE RIGHT OF THE
SLIDE PEOPLE ARE USING
SOPHISTICATED GENOMIC TECHNIQUES
TO BASICALLY GET RID OF THE PATH
LOGIC ABNORMALITIES.
SO IN THIS CASE THERE'S A GROUP
WORKING WITH A PARTICULAR
ARTIFICIAL GENE THAT CAN GET IN
THE NEURONS BUT IT'S ONLY GOING
TO BE ACTIVE IN THE NEURONS THAT
HAVE TDP-43 WHERE THEY GO SPLICE
OUT A CRYPTIC PEPTIDE AND IN
THOSE NEURONS THE PEPTIDE
ARTIFICIAL GENE WILL BE ACTIVE
AND NORMALIZE THE CRYPTIC
SPLICING OF THE ABNORMALITY AND
PEOPLE CAN USE GENOMIC
TECHNIQUES IN THE LABORATORY AND
ANIMAL MODELS THAT HOPEFULLY CAN
MOVE INTO PEOPLE.
THE POWER OF THESE IS COMPARED
TO DRUGS THEY'RE ONLY ACTIVE
EXACTLY WHERE YOU WANT THEM TO
BE ACTIVE.
SO LIKELY WE CAN GET BIG EFFECT
SIZES WITH VERY FEW SIDE
EFFECTS.
AND THAT'S CERTAINLY THE TRICK.
IN TERMS OF THE GENETIC TRICKS
THE OTHER ONE IS GENE EDITING.
IN WHICH AN ABNORMAL PROTEIN CAN
BE ACTUALLY NORMALIZED BY
BASICALLY GOING IN AND CUTTING
OUT THE ABNORMAL PIECE IN AN
ALZHEIMER'S MODEL IN CUT OUT THE
AMYLOID PRECURSOR PROTEIN THAT
PREVENTS IT FROM BECOMING
PATHOLOGIC.
WE'LL SEE MORE OF THESE.
THIS IS VERY EARLY IN
DEVELOPMENT STAGE IN TERMS OF
GENE EDITING.
THERE'S A COMMON FUND PROGRAM
WE'RE INVOLVED WITH WHICH IS
BASICALLY WORKING TO GET GENE
EDITING TO THE PEOPLE IN
DIFFERENT CONDITIONS.
AGAIN, A REALLY EXCITING WAY OF
GETTING VERY PRECISE TREATMENTS
TO RECTIFY GENETIC ABNORMALITIES
FOR HEALTH.
I MENTIONED EARLIER THERE ARE
SOME REAL INTERESTING CLUES WHEN
WE LOOK AT PEOPLE TO BE VERY
LATE AGE AND DO NOT HAVE
COGNITIVE IMPAIRMENT AND THESE
ARE EXAMPLES THAT ARE REALLY
APPRECIATION IN THE SENSE THAT
WHEN YOU FIND OUT WHAT IT IS
THAT'S PROTECTING THEM, IF YOU
CAN THEN DEVELOP A DRUG OR
GENOMIC THERAPY TO MIMIC THAT
PROTECTION, YOU CAN THEN PROTECT
PEOPLE WHO HAVE ALL DIFFERENT
FORMS OF THE DISEASE.
SO, BY STUDYING THE FOUR
POPULATIONS, YOU CAN FIND
TREATMENTS THAT CAN BE
GENERALIZED TO BIG POPULATIONS.
THE TWO MENTIONED HERE ARE
REELIN A CERTAIN ISOFORM OF
REELIN FIND PEOPLE WHO HAVE A
GENETIC MUTATION THAT SHOULD
GIVE THEM ALZHEIMER'S BUT
THEY'RE COGNITIVELY NORMAL.
SOMEHOW THE REELIN ISOFORM IS
PROTECTING THEM AND THE APOE 3
IS DOING SOMETHING SIMILAR.
THE IDEA TO FIND OUT WHAT THE
APOE 3 IS DOING AND FIND PEOPLE
AT RISK FOR ALZHEIMER'S DISEASE
AND SIMILARLY WITH THE REELIN
ISOFORM.
THESE ARE CLOSE TO BEING
FOLLOWED UP FOR NEW TREATMENTS.
THE OTHER THING TO MENTION, I
BRIEFLY HIT ON THIS EARLIER IS
THAT IN ALL THE
NEURODEGENERATIONS THERE'S AN
INFLAMMATORY REACTION.
WE THINK OF INFLAMMATION WITH
INFECTION, SAY, FOR INSTANCE,
WHERE THE INFLAMMATION COMES AND
IT CONTROLS THE BACTERIA OR THE
VIRUS THAT'S CAUSING YOUR
INFECTION.
BUT IT TURNS OUT IN THE NERVOUS
SYSTEM, THE IMMUNE SYSTEM IS
ACTIVE ALL THE TIME IN RESHAPING
THE SYNAPSES BETWEEN THE CELLS
AND IN PROTECTING THE BRAIN
AGAINST BACTERIA AND VIRUSES.
BUT IN SOME INSTANCES IN
NEURODEGENERATION IT APPEARS THE
IMMUNE SYSTEM BECOMES OVER
ACTIVE AND MAY CONTRIBUTE TO THE
DAMAGE.
SO SO THERE'S A NUMBER OF
EXAMPLES.
THIS IS ONE OF THEM WHERE IT'S
BEEN FOUND THAT KEY CELLS WHICH
ARE INFLAMMATORY CELLS CAN
INVADE THE SURFACE OF THE BRAIN
SUBSTANCE CALLED THE DURA MATTER
AND PRODUCE IL17 WHICH CREATES
MACROPHAGES WHICH IS ANOTHER
MORE AGGRESSIVE INFLAMMATORY
CELL THAT CAN THEN INJURY
ADJACENT CELLS AND GIVE RISE TO
LOSS OF NEURONS AND SYNAPSES.
SO TARGETING THESE TYPES OF
CELLS IS PARTICULAR INFLAMMATORY
CELLS MIGHT BE PROTECTIVE.
AND THIS EXAMPLE AS I MENTIONED
IS ACTUALLY DRIVEN BY THE
VASCULAR ABNORMALITIES ONE SEES
IN VASCULAR COGNITIVE
IMPAIRMENT.
THERE'S ALSO RECENT STUDIES
ABOUT APOE 4 WHICH IS ONE OF THE
HIGHEST RISK FACTORS FOR
ALZHEIMER'S DISEASE AND
PROGRESSION OF ALZHEIMER'S
DISEASE.
AND THIS STUDY SHOWS THAT IN
APOE 4, MICE ONE SEES AN
ABNORMALITY IN CHOLESTEROL
METABOLISM AND CHOLESTEROL
ACCUMULATES INSIDE THE CELLS
THAT RESULTS IN INHIBITION OF
MYELIN BASED PROTEIN WHICH IS
THE PROTEIN NEEDED TO COVER THE
WIRES THAT I MENTIONED EARLIER
THAT CONNECT TO DIFFERENT BRAIN
REGIONS.
THERE'S A CONNECTION BETWEEN THE
APOE 4 GENE WHICH IS A REAL BAD
ACTOR IN ALZHEIMER'S AND
VASCULAR COGNITIVE IMPAIRMENT OR
WHITE MATTER DISEASE.
FINALLY, I WANTED TO MENTION THE
WORK YOU'LL BE HEARING ABOUT AND
I DESCRIBED GOES ON AROUND
UNIVERSITIES ACROSS THE COUNTRY.
WE ARE INDEBTED SO THE PATIENTS
AND THE SUBJECTS AND THE
CAREGIVERS WHO TAKE TIME AND
ENERGY TO PARTICIPATE IN THESE
STUDIES.
AND IT'S ONLY THROUGH THIS
COMMUNITY THAT WE HAVE BUILT
OVER THE YEARS AND CONTINUE TO
NURTURE THAT WE'RE GOING TO MAKE
ADVANCES.
SIMILARLY ACROSS THE COUNTRY WE
ALSO HAVE A PROGRAM HERE ON THE
BETHESDA BUTS THE CENTER FOR
ALZHEIMER RELATED DEMENTIAS
USING SOME REALLY INNOVATIVE
TECHNOLOGIES PARTICULARLY USING
HUMAN CELLS TAKEN FROM PEOPLE
SAY THE SKIN BIOPSY AND
DEVELOPED INTO STUDY THE ROLE OF
FACTORS IN THE PATHOLOGY THAT WE
SEE IN THE CELLS OF PEOPLE WITH
NEUROGET
NEUROGET -- NEURODEGENERATIVE
DISEASES AND AN INTERESTING
STUDY AT THE CAMPUS.
ANOTHER AREA I THINK IS
INCREDIBLY IMPORTANT NOW IS
UNDERSTANDING HOW TO IDENTIFY
PEOPLE EARLY ON AS THEY DEVELOP
NEURODEGENERATION AND THE
EARLIER SIGNS OF COGNITIVE
IMPAIRMENT.
THE GENERAL RULE THAT WE SEE
ASCRIBE TO IS THAT AS THIS
PROCESS GOES ON AND ON IT GETS
VERY HARD TO STOP IT.
THE BEST CHANCE OF MAKING A BIG
DIFFERENCE IS GOING TO BE IN
EARLY INTERVENTIONS.
THE BIOMARKER FIELD HAS
PROGRESSED WHERE SOME WILL BE
TURNING POSITIVE VERY EARLY ON
EVEN BEFORE SYMPTOMS.
SO THAT'S VERY ENCOURAGING.
WE ALSO NEED WAYS IN WHICH WE
CAN IDENTIFY PEOPLE IN
COGNITION.
THIS IS THE STUDY CALLED T THE
TECH PROGRAM TO DEVELOP A METHOD
WHEREBY PRIMARY CARE PHYSICIANS
HAVE THEIR FAMILY DOCTOR AND
THAT WILL BE THE POINT TO WHERE
THE PROBLEMS WILL BE FIRST ABLE
TO BE DETECTED.
AND SO WE NEED METHODS AND THIS
IS ONE OF THEM WHICH WAS QUITE
SUCCESSFUL AT HELPING IN THE
PRIMARY CARE SETTING TO IDENTIFY
PEOPLE WITH COGNITIVE
IMPAIRMENT.
IN THIS CASE IT SHOWED IT LED TO
IMPROVED DEMENTIA CARE.
SO EVEN WOULD THIS IDEA OF
IDENTIFYING PEOPLE FOR THESE NEW
TREATMENTS OF THE FUTURE, THESE
DIAGNOSTIC CRITERIA CAN BE
HELPFUL IN THE IMMEDIATE TIME
FRAME.
SO WHAT WE TRY TO DO IS THINK
ABOUT THE PROBLEMS THAT PEOPLE
ARE SUFFERING WITH
ALZHEIMER-RELATED DEMENTIAS AT
EVERY COMPONENT OF THESE
CONDITIONS, WE TRY TO DEVELOP
RESEARCH THAT CAN ADVANCE THEIR
TREATMENT, PREVENTION AND CARE.
I'M REALLY LOOKING FORWARD TO
HEARING FROM THE RECOMMENDATIONS
OF THE WORKING GROUPS AS THEY
HAVE REALLY TAKEN ON THE
CHALLENGE OF LOOKING AT A VERY
COMPLICATED BUT VERY IMPORTANT
AREA OF SCIENCE.
THANK YOU VERY MUCH.
NOW I'LL HAND IT OVER TO AC BER
MCCARTNEY LEADING THE SUMMIT
FROM NINDS.
>> THANK YOU, WALTER.
-- AMBER MCCARTNEY.
>> AMBER: THIS SUMMARIZES THE
PLAN TO ADDRESS ALZHEIMER'S
DISEASE.
I WANT TO MAKE ONE POINT, THAT'S
PLEASE FOCUS YOUR ATTENTION AT
THE BOTTOM OF THE SLIDE.
HERE YOU CAN SEE UNDER THE FIRST
PROFESSIONAL PLAN THERE'S AN
ACTION ITEM FOR US WHICH DIRECTS
US TO REGULARLY CONVENE A SUMMIT
ON ADRD RESEARCH.
THE SUMMIT THE PURPOSE IS TO
REVIEW PROGRESS ON
RECOMMENDATIONS AS APPROPRIATE
BASED ON RECENT SCIENTIFIC
DISCOVERIES AND THIS IS WHAT
WE'RE HERE TO DO TODAY.
TODAY WE WANT YOUR INPUT ON THE
DRAFT RECOMMENDATIONS PRESENTED
AND I WANT YOU TO KNOW WE TAKE
THIS VERY SERIOUSLY AND
ENCOURAGE YOU TO STAY INVOLVED
THROUGHOUT THE MULTI-DAY EVENT.
IN THE AGENDA YOU'LL SEE TIME
DEDICATED PUBLIC INPUT IN EACH
SESSION AND WHERE WE ENCOURAGE
YOU TO PROVIDE INPUT AND
FEEDBACK ON THE RECOMMENDATIONS.
HERE IS AN AGENDA FOR THE THREE
DAYS AND FOR EACH SESSION YOU'LL
SEE THE NAME OF THE SESSION AND
I'VE INDICATED THE NUMBER OF
RECOMMENDATIONS EACH SESSION
WILL PRESENT.
AS IN PREVIOUS YEARS,
CROSS-CUTTING SECTION SUCH AS
THE DISEASE SPECIFIC SESSION,
EACH HAVE EIGHT RECOMMENDATIONS
AND HAVE PRIORITY LEVELS 1-4.
THEY HAVE TWO NUMBER ONE AND TWO
NUMBER TWO PRIORITIES AND TWO
NUMBER THREE PRIORITIES AND TWO
NUMBER FOUR.
THE SPECIAL TOPIC SESSIONS EACH
HAVE FOUR RECOMMENDATIONS WITH
PRIORITY LEVELS 1-4.
ALL PRIORITIES PRESENTED ARE
HIGHEST PRIORITIES FOR THE
FIELD.
YOU'LL HEAR MORE IN THE FIRST
SESSION LED BY DR. POSSIN.
THEY DECIDED TO SPLIT INTO TWO
SUBCOMMITTEES AND START OFF DAYS
ONE AND TWO.
THE FIRST SESSION WILL START
WITH INFLAMMATION AND THE SECOND
DAY IS RESEARCH.
COMBINED THEY PRESENT THE EIGHT
EXISTING RECOMMENDATIONS FOR THE
ETIOLOGY DEMENTIA SESSION FROM
2022.
I WANT TO POINT OUT IN ADDITION
TO EACH SESSION, ENDING WITH
DEDICATED MICRO PHOTI AND I'LL
TALK ABOUT THE CONTEXT AND
WHAT'S INVOLVED.
SO PLANNING STARTED SIX, SEVEN
MONTHS AGO AND THE COMMITTEES
INVOLVED OVER 120 SCIENTISTS,
PHYSICIANS, PEOPLE WITH LIVED
EXPERIENCE AND ADMINISTRATORS
AND PARTNERS AND I'LL INTRODUCE
DR. POSSIN.
SHE'LL SPEAK AFTER ME AND HOLDS
THE JOHN DOUGLAS FRENCH ENDOWED
PROFESSORSHIP IN THE DEPARTMENT
OF NEUROLOGY AT THE UNIVERSITY
OF CALIFORNIA SAN FRANCISCO AND
PREVIOUSLY SHARED THE MULTIPLE
ETIOLOGY DEMENTIA SESSION FOR
TWO PREVIOUS SESSION AND THE
LEADER IN DETECTION OF ATAXIA
I.D. AND YOU HEARD WALTER TALK
ABOUT THE PROGRAM AND A LEADER
IN NATIONAL AND INTERNATIONAL
EFFORTS TO ADDRESS DEMENTIA IN
EVERYDAY CLINICAL STUDIES WE
HAVE AN ESTEEMED STEERING
COMMITTEE OF CHAIRS AND
PROMINENT LEADERS IN THE FIELD
AND HERE AT THE SESSION AND
MEETING GOALS.
THIS SLIDE SHOWS THE NIH
RESEARCH SPENDING FOR
ALZHEIMER'S DISEASE AND
ALZHEIMER'S DISEASE RELATED
DEMENTIA RESEARCH HAS INCREASED
IN THE PAST DECADE.
THIS IS NOT A BUDGETING SLIDE
BUT ACTUAL DOLLARS SPENT ON THE
CATEGORIES OF RESEARCH AND IF
YOU'RE INTERESTED IN DETAILS FOR
THESE NUMBERS, PLEASE GO TO THE
NIH REPORTER WEBSITE THE ADDRESS
IS FOUND AT THE BOTTOM OF THE
SLIDE.
THE POINT I WANT TO MAKE IS THE
RELATED DEMENTIAS STUDIES HAVE
INCREASED AS WELL.
NINDS LEADS THE ALZHEIMER'S
DISEASE RELATED DEMENTIAS AND
WORK IN CLOSE PARTNERSHIP WITH
THE NATIONAL INSTITUTE ON AGES
AND THROUGH THE CONGRESSIONAL
PARTNERSHIP FUNDS ARE AVAILABLE
TO FUND RESEARCH.
WE USE THE ADDED FUNDS FOR
ACTIVITIES THAT RESPOND TO THE
MILESTONES IN THE NATIONAL PLAN.
THE MILESTONES THAT COME FROM
THESE SUMMITS.
IN PARTICULAR ADDED FUNDS ARE
USED FOR INCREASED INVESTIGATOR
INITIATED RESEARCH AND RESEARCH
THAT'S RESPONSIVE TO NINDS, ADRD
FUNDING OPPORTUNITIES.
THIS SLIDE IS A SUMMARY AND I
JUST WANT TO JUMP TO THE NEXT
SLIDE SO WE CAN MOVE FORWARD AND
GET TIME BACK.
BEFORE WE GET INTO SESSIONS I
WANT TO GIVE YOU A QUICK GUIDE
TO THE DRAFT RECOMMENDATIONS.
YOU CAN SEE HERE THE
RECOMMENDATION IS AN EXAMPLE AND
YOU CAN SEE IT HAS A NUMBER AND
PRIORITY AND THE PRIORITY THAT'S
IN THE BOX IS FOLLOWED BY TEXT
AND THAT TEXT IS THE TOP LEVEL
RECOMMENDATION.
SO THE DATE AT THE END IS THE
ESTIMATED YEAR TO COMPLETE OR
FULLY IMPLEMENT THE
RECOMMENDATION IF IT WERE
STARTED IN 2026.
SO THE NEXT SLIDE IS WHEN I HAND
IT OFF TO DR. POSSIN.
THANK YOU VERY MUCH FOR TODAY
AND PLEASE DO PARTICIPATE IN THE
DISCUSSION SESSIONS.
AND I THINK I'LL HAND IT OFF TO
DR. POS SCRIN.
-- DR. POSSIN.
THANK YOU.
>> DR. POSSIN: GOOD MORNING I'M
PLEASED TO KICK OFF THE ADRD
SUMMIT.
>> KATE, ARE YOU GOOD?
>> DR. POSSIN: YES, CAN YOU HEAR
ME OKAY?
ALL RIGHT, GOOD.
I HAVE NO FINANCIAL CONFLICTS TO
REPORT.
AND WE ARE HERE TODAY FOR GOOD
REASON.
A LARGE AND GROWING NUMBER OF
AMERICANS HAVE DEMENTIA.
DEMENTIA AFFECTS MORE THAN 6
MILLION AMERICANS TODAY AND 13
MILLION ARE PROJECTED TO HAVE
DEMENTIA BY 2060.
THE RISK FOR DEVELOPING DEMENTIA
FOR PEOPLE WHO LIVE INTO OLDER
AGE IS HIGH WITH ESTIMATES
RANGING BETWEEN 20% TO 40%.
AS SHOWN HERE IN THE RECENT
STUDY PUBLISHED IN NATURE AND
MEDICINE, THE RISK IS HIGHER FOR
WOMEN, FOR BLACKS AND WHITES AND
FOR PEOPLE WITH AN APOE 4
ALLELE, PARTICULARLY FOUR
ALLELES BUT IT'S HIGH FOR ALL
AMERICANS WHO LIVE INTO OLDER
AGE FROM ALL WALKS OF LIFE.
AND MANY ARE UNPAID CAREGIVERS.
DEMENTIA IS EXPENSIVE AND WILL
IMPOSE A FAST GROWING ECONOMIC
BURDEN IN THE COMING DECADES.
USING DATA FROM THE HEALTH AND
RETIREMENT STUDY, COLLEAGUES
ESTIMATED ANNUAL FORMAL CARE
COSTS, THAT IS CARE THAT'S
PURCHASED IN THE MARKETPLACE IS
CURRENTLY $200 BILLION PER YEAR.
THIS IS JUST IN THE UNITED
STATES.
THESE FORMAL CARE COSTS ARE
PROJECTED TO REACH $1.4 TRILLION
BY YEAR 2060.
IF THE COST OF INFORMAL
CAREGIVING SUCH AS FOREGONE
WAGES BY THE CAREGIVER THE COST
HIGHER.
WHILE THE PROJECTIONS ARE
ECONOMICALLY DEVASTATING THEY'RE
NOT SET IN STONE.
INVESTMENTS IN RESEARCH AND
SYSTEMS OF CARE COULD MITIGATE
THIS ECONOMIC BURDEN BY
PREVENTING OR DELAYING ONSET AND
CHANGES IN LIFE AND TREATMENTS
THAT MODIFY THE DISEASE PROCESS
AND SMART SYSTEMS OF CARE.
THAT SUPPORT THE PERSON LIVING
WITH DEMENTIA AND CAREGIVERS AND
LOWER TOTAL COST AND IT WILL
REQUIRE SMART AND EFFECTIVE
COORDINATION AND COLLABORATION
BETWEEN SCIENTISTS AND FEDERAL
AGENCIES IN THE PRIVATE CENTER.
THERE HAVE BEEN IMPORTANT RECENT
BREAKTHROUGHS IN ADRD SCIENCE.
YOU HEARD OF SOME THIS MORNING
FROM DR. KOROSHETZ.
I HAVE THE PLEASURE OF
SUMMARIZING SOME OF THE
BREAKTHROUGHS IN THE AREA OF
PREVENTION, DIAGNOSIS, TREATMENT
AND CARE.
WE CAN PREVENT DATA THROUGH
LIFESTYLE AND THERE'S EVIDENCE
UNTREATED VISION LOSS AND HIGH
HDL CHOLESTEROL ARE RISK FACTORS
FOR DEMENTIA.
THESE IMPORTANT RISK FACTORS
COMBINED WITH THOSE THEY
MODELLED PREVIOUSLY ACCOUNT FOR
45% OF DEMENTIA RISK.
WE'VE ALSO LEARNED ADDRESSING
MODIFIABLE RISK FACTORS IN
AT-RISK INDIVIDUALS CAN SLOW OR
PREVENT COGNITIVE DECLINE.
AGGRESSIVE BLOOD PRESSURE
MANAGEMENT REDUCES MILD
COGNITIVE IMPAIRMENT RISK.
IN THE FINGERS TRIAL, AN
INTERVENTION THAT TARGETED DIET,
EXERCISE, COGNITIVE AND SOCIAL
STIMULATION AND VASCULAR RISK
MONITORING IN AT-RISK
INDIVIDUALS HAD SIGNIFICANT
IMPROVEMENTS IN COGNITIVE
FUNCTION.
THE U.S. POINTER IS EXTENDING
THE WORK BY TESTING A
POTENTIALLY SCALABLE
INTERVENTION IN A LARGE GROUP OF
AMERICANS ACROSS THE UNITED
STATES.
AND TRIAL RESULTS ARE EXPECTED
THIS YEAR.
WORLDWIDE FINGERS DEMENTIA
TRIALS TO TEST STRATEGIES ACROSS
DIVERSE POPULATIONS.
BREAKTHROUGH NUMBER TWO, WE CAN
IDENTIFY DISEASE IN LIVING
PEOPLE WITH INEXPENSIVE AND
NON-INVASIVE TESTS.
PREVIOUSLY, WE COULD ONLY
IDENTIFY ALZHEIMER'S DISEASE IN
LIVING PEOPLE USING EXPENSIVE
AND INVASIVE TESTS, HEAD IMAGING
AND SPINAL TAPS.
IN THE STUDIES HERE IN SWEDEN,
WHEN THE AD PLASMA BIOMARKER TAU
217 WAS AVAILABLE, THE ACCURACY
OF DEMENTIA SPECIALISTS SHOWN IN
BLUE AND PRIMARY CARE PROVIDERS
IN A AND B WERE IDENTIFYING
ALZHEIMER'S DISEASE PATHOLOGY
IMPROVED SUBSTANTIALLY TO 91%.
YOU HEARD FROM DR. KOROSHETZ HOW
SUBSTANTIAL BREAKTHROUGH BEING
MADE IN BIOMARKERS FOR
PARKINSON'S DISEASE AND LEWY
BODY DEMENTIA.
ALPHA SYNUCLEIN CAN BE MEASURED
IN BLOOD, SALIVA AND SKIN AND
PLASMA AND OTHER SCALABLE
BIOMARKERS EXTEND ACCESS TO
ACCURATE DIAGNOSIS AND HAVE
FACILITATED A MOVEMENT TOWARDS
BIOLOGICAL STAGING OF DISEASE.
THESE ADVANCES PROVIDE
GROUNDBREAKING NEW OPPORTUNITIES
TO IMPROVE CARE AND FIND CURES.
BUT NEXT WE NEED TO MOVE TOWARDS
STANDARDIZED DIAGNOSTIC PATHWAYS
THAT INCORPORATE THESE MARKERS
WITH OTHER CLINICAL DATA.
WE NEED TO REDUCE VARIABILITY
DUE TO HOW THE SAMPLES ARE
HANDLED AND PROCESS AND ADJUST
RESULTS BASED ON PATIENT
COMORBIDITIES THAT IMPACT
RESULTS.
AND THE NEXT POINT WILL BE A BIG
FOCUS OF THE SUMMIT.
WE NEED TO ADVANCE BIOMARKERS TO
THE OTHER BIOLOGICAL MARKERS OF
ADRD INCLUDING SYNUCLEIN AND
THERE'S A MULTI-SITE NATIONAL
CONSORTIUM TO CONSOLIDATE AND
IDENTIFY BIOMARKERS USED IN
DEMENTIA CLINICAL TRIALS.
THE BIOMARKERS HAVE UNDER GONE
INSTRUMENTAL VALIDATION AND NOW
UNDERGOING CLINICAL VALIDATION.
BREAKTHROUGH NUMBER THREE, WE
CAN IMPROVE DIAGNOSIS OF
DEMENTIA IN PRIMARY CARE.
YOU HEARD A BIT OF THIS FROM
DR. KOROSHETZ.
AND THERE'S BEEN FUNDING WHERE
PAIR DIMES HAVE BEEN DEVELOPED
AND IMPLEMENTED IN PRIMARY CARE
AND IMPROVED DETECTION AND
DIAGNOSIS.
THREE LARGE PRAGMATIC CLUSTER
TRIALS ARE UNDERWAY WITH RESULTS
EXPECTED IN 2027.
I ALSO HIGHLIGHT ON THE SLIDE
OTHER IMPORTANT INITIATIVES WITH
THE SAME GOAL THIS IS SO
IMPORTANT.
IF WE DON'T DETECT AND DIAGNOSIS
PEOPLE EARLY IN CARE WE CAN'T
CHANGE CARE.
AND TWO AMYLOID THERAPIES ARE
APPROVED FOR ALZHEIMER'S
DISEASE.
WHEN WE LAST HELD THE SUMMIT IN
2022, OUR FIELD DID NOT HAVE ANY
DISEASE MODIFYING THERAPIES TO
OFFER PATIENTS.
NOW, TWO THERAPIES THAT TARGET
AMYLOID ARE APPROVED FOR THE
TREATMENT OF EARLY STAGE
ALZHEIMER'S DISEASE.
PATIENTS MUST BE DIAGNOSED AT
THE EARLY STAGE TO QUALIFY.
THE DECLINE IN FUNCTION IS ABOUT
27% TO 40% SLOWER WHEN ON
TREATMENT WHICH MEANS PATIENTS
CAN STAY INDEPENDENT AND HOLD ON
TO WHAT MATTERS MOST TO THEM FOR
SEVERAL MONTHS LONGER THAN THEY
COULD WITHOUT THE TREATMENT.
HOWEVER THIS TREATMENT AFFECT IS
MODEST AND THE TREATMENT POSES A
RISK AND EXTENSIVE SCREENING IS
REQUIRED TO DETERMINE IF THE
PATIENT IS APPROPRIATE FOR THE
TREATMENT AND MOST DO NOT
QUALIFY.
WE NEED TO MOVE TOWARDS MORE
EFFECTIVE AND PERSONALIZED
TREATMENT FOR PATIENTS TAILORED
TO EACH PATIENT'S RISKS AND
BIOMARKERS AND PROGRESS IS BEING
MADE AND TAU THERAPIES IS
EXCITING AND TAU AGGREGATION IS
MORE LINKED TO COGNITIVE
DECLINE.
PROMISING GENE THERAPY APPROACH
OR REDUCING THE IMPACT OF APOE 4
GENE AND INCREASING THE
PROTECTIVE VARIANT AND REDUCING
THE PRODUCTION OF AMYLOID BETA.
WE KNOW THERE'S MULTIPLE
PATHOLOGIES IN MOST PATIENTS AND
WE'LL BE MOVING TOWARDS
COMBINATION THERAPIES.
IN SUMMARY, TO THE TREATMENT
AFFECT OF THE ANTIAMYLOID
THERAPIES IS MODEST BUT
REPRESENT AN IMPORTANT STEP
FORWARD AND WE MUST KEEP OUR
FOOT ON THE GAS TO HAVE MORE
TREATMENTS AVAILABLE FOR
PRECISION TREATMENT OF ADRD.
NIH FUNDS A WIDE RANGE OF
CLINICAL TRIALS FOCUSSED ON THE
TREATMENT OF ADRD.
THERE'S BEEN A SHIFT FROM 36% OF
CLINICAL TRIALS WITH
PHARMACOLOGIC AGENTS TARGETING
AMYLOID IN 2013 TO 2023, 15%.
ALSO YOU CAN SEE THERE'S BEEN
SUBSTANTIAL INVESTMENT IN WILL
NON-PHARMACOLOGIC APPROACHES.
BREAKTHROUGH NUMBER 5, WE HAVE
DEMENTIA CARE THAT ADDRESSES
PATIENT AND CAREGIVER NEEDS.
MEDICARE'S GUIDE PAYMENT MODEL
RELEASED IN 2024 IS MEDICARE'S
FIRST PAYMENT MODEL THAT
INCLUDES SERVICES AND SUPPORTS
FOR THE CAREGIVER.
A TRUE BREAKTHROUGH.
THERE'S A COLLABORATIVE CARE
MODEL SPECIFICALLY DESIGN FOR
DEMENTIA.
YOU SEE IN THE INFOGRAPHIC FROM
CMS THE REQUIRED COMPONENTS AND
WHEN DEMENTIA CARE ADDRESSES NOT
ONLY THE MEDICAL AND SOCIAL
NEEDS OF THE PATIENT BUT ALSO
THE SUPPORTS THE CAREGIVER, IT
IMPROVES QUALITY OF LIFE FOR THE
PATIENT, REDUCES BURDEN ON THE
CAREGIVERS AND SAVES MEDICARE
MONEY BY PREVENTING UNNECESSARY
EMERGENCIES.
WITH COLLABORATIVE CARE FAMILIES
SHIFT TOWARDS A MORE PROACTIVE
AND STABLE EXPERIENCE OF
DEMENTIA.
THIS BREAKTHROUGH HAS BEEN MADE
POSSIBLE BY EFFECTIVE
COORDINATION BETWEEN
RESEARCHERS, POLICY LEADERS AND
FEDERAL AGENCIES.
STILL, MUCH MORE WORK REMAINS TO
OPTIMIZE AND WIDELY IMPLEMENT
QUALITY DEMENTIA CARE AND THE
MECHANISMS OF ITS EFFECTIVENESS.
YOU'LL HEAR MORE IN THE NEXT
SESSION TODAY.
SO NOW I WILL BRIEFLY SHARE WITH
YOU THE TOP PRIORITY
RECOMMENDATIONS FROM EACH OF THE
SESSIONS.
STARTING WITH SESSIONS ON THREE
CATEGORIES OF DISEASE.
FRONTAL TEMPORAL DEMENTIA,
VASCULAR COGNITIVE IMPAIRMENT
AND LEWY BODY.
TO HELP KEEP US ON TIME I WON'T
READ THESE TO YOU AND URGE YOU
TO SNAP A PICTURE.
THESE ARE THE TOP
RECOMMENDATIONS AND TWO THAT ARE
TOP PRIORITY AND THE SESSION IS
LED BY DR. KARCH AND IRWIN.
THEY'LL BE PRESENTING LATER
TODAY.
VASCULAR COGNITIVE IMPAIRMENT
AND DEMENTIA.
THIS SESSION LED BY DR. BASATI
AND DR. LU.
NEXT, OUR SESSION ON LEWY BODY
DISEASE ALSO HAS TWO PRIORITY 1
RECOMMENDATIONS LED BY DR
DR. GALVIN AND POSTIN.
NEXT, WE HAVE THREE SESSIONS ON
SPECIAL TOPICS AND POST DBI AND
THESE ARE SESSIONS THAT WERE
FIRST INTRODUCED IN 2019 AND
CONTINUE TO BE FEATURED AT THE
SUMMIT.
THEY EACH HAVE FOUR
RECOMMENDAT
RECOMMENDATIONS.
AND THEN A SESSION ON THE
EXPOSOME.
THIS HAS EVOLVED SINCE 2022.
WE HAD A SESSION POST-COVID.
DR. LOOKIN AND KIPNIS ARE THE
CHAIRS.
WE ALSO HAVE THREE SESSIONS ON
CROSS-CUTTING THEMES.
WE HAVE A BASIC ON BASIC AND
CLINICAL DISCOVERY RESEARCH THAT
WILL KICK OFF OUR DAY TOMORROW.
THEY HAVE FOUR RECOMMENDA RECOM
THIS ACAN CHAIRED BY DR. IADECOL
AND CARLSSON AND THOSE AT RISK
LIVING WITH AD/ADRD YOU'LL HEAR
THIS ON THE THIRD DAY CHAIRED BY
DR. GLYMOUR AND THEN THE CROSS
CUTTING THEMES WILL BE NEXT IN
JUST A MOMENT.
SO, I'LL JUMP IN I THINK.
WE'LL LAUNCH OUR FIRST SESSION
OF THE ADRD SUMMIT, 2025 WITH
THE SESSION ON MULTIPLE ETIOLOGY
DEMENTIA RESEARCH FOR
IMPLEMENTATION OF DISCOVERIES
INTO PRACTICE.
AND THIS IS A NEW SESSION FOR
THE 2025 SUMMIT.
YOU'LL BE HEARING TODAY FROM MY
CLOSE COLLEAGUES WHO WILL
PRESENT WITH ME.
DR. WOOD WITH FROM THE AMERICAN
ACADEMY OF FAMILY PHYSICIANS,
DR. HAGERTY-LINGLER FROM THE
UNIVERSITY OF PITTSBURGH AND
DR. SNYDER FROM THE ALZHEIMER'S
ASSOCIATION.
I'LL START BY SAYING AGAIN I
HAVE NO FINANCIAL DISCLOSURES.
ALL RIGHT.
SO WE HAVE THIS NEW SESSION FOR
THIS SUMMIT.
THIS IS CALLED RESEARCH FOR
IMPLEMENTATION OF DISCOVERIES
INTO PRACTICE.
THE FIRST GOAL OF THE NAPA
NATIONAL PLAN IS TO PREVENT AND
EFFECTIVELY TREAT AD/ADRD BY
2025.
THIS IS A MOMENT TO REFLECT ON
WHAT NEEDS TO BE DONE TO GET THE
BREAKTHROUGHS INTO PRACTICE TO
BENEFIT PATIENTS, FAMILIES AND
SYSTEMS OF CARE.
BECAUSE THE RECENT ADVANCES ARE
NOT YET AVAILABLE TO MOST
INDIVIDUALS AT RISK FOR OR
LIVING WITH AD/ADRD.
SESSION 1 IS FOCUSSED ON
IDENTIFYING KEY AREAS OF
RESEARCH NEEDED TO CAPITALIZE ON
THE BREAKTHROUGHS AND ENSURE
THEY REACH PATIENTS, FAMILIES,
HEALTH CARE PROVIDERS AND HEALTH
SYSTEMS.
WE PRESENT FOR YOUR
CONSIDERATION FOUR
RECOMMENDATIONS THAT ARE
IMPORTANT ACROSS ALL STAGES OF
BRAIN HEALTH.
OUR PRIORITY 1 RECOMMENDATION IS
FOCUSSED ON IMPROVING DETECTION,
DIAGNOSIS AND LINKAGES TO CARE.
OUR PRIORITY 2 IS FOCUSSED ON
IMPROVING ACCESS TO QUALITY CARE
WHICH IS PARTICULARLY IMPORTANT
AROUND THE DIAGNOSIS AND INITIAL
TREATMENT PERIOD.
OUR PRIORITY 3 RECOMMENDATION IS
ON DEMENTIA CARE AND PRIORITY 4
IS ON PRIMARY AND SECONDARY
PREVENTION.
MOST THE RESEARCH THAT WE'RE
RECOMMENDING USES THE METHODS OF
IMPLEMENTATION AND DISSEMINATION
SCIENCE WITH THE GOAL TO IMPROVE
PATIENT OUTCOMES AND ENHANCE
CARE QUALITY.
THIS TYPE OF RESEARCH IS BEST
CONDUCTED AS A COLLABORATION
BETWEEN SCIENTISTS AND
PRACTITIONERS WITH
BI-DIRECTIONAL LEARNING
THROUGHOUT THE INTEGRATION
PROCESS.
PRIMARY CARE PLAYS A CRUCIAL
ROLE IN THE RESEARCH RECOMMENDED
BY THE SESSION.
MOST PCPs FEEL THEY'RE IN THE
FRONT LINES OF PROVIDING
DEMENTIA CARE YET NOT PREPARED
TO PROVIDE THIS CARE.
I WANT TO THANK MY INCREDIBLE
COMMITTEE MEMBERS WORKING WITH
ME TO PREPARE THE
RECOMMENDATIONS WE PRESENT TODAY
FOR YOUR INPUT.
I'LL PRESENT NOW OUR
RECOMMENDATION ON CARE.
WE RECOMMEND TO CONDUCT RESEARCH
TO ENHANCE THE EFFICIENCY AND
EFFECTIVENESS OF EVIDENCE-BASED
AND EVIDENCE-INFORMED
COLLABORATIVE CARE MODELS THAT
SUPPORT THE NEEDS OF PATIENTS
AND CARE PARTNERS AT KEY POINTS
IN THE AD/ADRD CARE JOURNEY FROM
DIAGNOSIS TO END OF LIFE
INCLUDING POPULATIONS MOST AT
RISK FOR POORER OUTCOMES.
AND A PATIENT SAID HIS HEART
DISEASE WAS TOUGH BUT THINGS
REALLY FELL A PART WHEN HIS
MEMORY STARTED TO GO AND I FELT
STUM IN HIS ENDLESS CYCLE ER
VISITS AND HOSPITAL STAYS AND I
WAS EXHAUSTED TRYING TO FIGURE
IT OUT ON MY OWN WITH NO ONE
HELPING ME FIGURE IT OUT.
I FELT ALONE JUST TRYING TO KEEP
MY DAD SAFE.
THIS SESSION'S RECOMMENDATION ON
CARE IS FOCUSSED ON
COLLABORATIVE CARE FOR DEMENTIA
THIS USES MULTI-DISCIPLINARY
NEEDS TO MEET THE PSYCHOSOCIAL
NEEDS AND EMPHASIZES CARE
NAVIGATION AND SUPPORT.
THIS TYPE OF CARE HAS BEEN SHOWN
TO IMPROVE QUALITY OF LIFE FOR
PEOPLE LIVING WITH DEMENTIA,
CAREGIVER WELL BEING AND REDUCED
EMERGENCY ROOM VISIT AND REDUCED
TOTAL COST OF CARE AND REDUCING
POLY PHARMACY.
THERE'S BEEN SUBSTANTIAL HARD
WORK AND PROGRESS TOWARDS BETTER
DEMENTIA QUAR -- CARE FOR ALL.
AND THERE WERE COLLABORATIVE
DEMENTIA CARE MODELS.
THE 2019 ADRD SUMMIT INTRODUCED
A RECOMMENDATION FOR ADVANCED
DEMENTIA CARE AND NIH
SUBMISSIONED REVIEWS TO EVALUATE
THE DEMENTIA CARE AND THE
RESULTING WHITE PAPERS CONCLUDE
THE EVIDENCE WAS SUFFICIENT TO
IMPLEMENT COLLABORATIVE CARE
MODELS IN WITH EVALUATION
CONDUCTED TO CONTINUE EXPANDING
THE EVIDENCE BASE.
THIS INSPIRED IMPORTANT POLICY
WORK BY THE ALZHEIMER'S
ASSOCIATION AND IMPACT MOVEMENT
AND OTHERS WHICH LED TO THE
COMPREHENSIVE CARE FOR
ALZHEIMER'S ACT.
INTRODUCED IN THE HOUSE AND
SENATE WITH STRONG BUY --
BIPARTISAN SUPPORT AND WE HAVE
THE MODEL AND THIS BRINGS US TO
THE ADRD SUMMIT OF 2025 WHERE WE
RECOMMEND THE NEXT CRUCIAL STEPS
IN RESEARCH TO MOVE US TOWARDS
BETTER DEMENTIA CARE FOR ALL.
THE SUBSTANTIAL PROGRESS TOWARDS
BETTER DEMENTIA CARE REFLECTS
EFFECTIVE COORDINATION BETWEEN
FEDERALLY FUNDED RESEARCH,
POLICY WORK, FEDERAL AGENCIES
AND BIPARTISAN LEGISLATORS BUT
WE STILL HAVE A WAYS TO GO.
CHALLENGES REMAIN.
THE EFFECT SIZES ARE SMALL AND
SOME TRIALS HAVE BEEN NEGATIVE.
AFFECT SIZES CAN VARY
SUBSTANTIALLY FROM DIFFERENT
TYPES OF PATIENTS AND CAREGIVERS
WHICH MAY HELP EXPLAIN THE SMALL
EFFECT SIZES WITHIN AND ACROSS
STUDIES.
WE NEED TO █DO A BETTER JOB
UNDERSTANDING THE RIGHT CARE FOR
THE RIGHT PATIENT AT THE RIGHT
TIME AND NEED TO ADAPT CARE
MODELS TO MEET THE NEEDS OF
PATIENTS WHO LIVE ALONE OR
WITHOUT AN ENGAGED CAREGIVER.
THE CARE MODELS TEND TO HAVE
MANY COMPONENTS OF CARE JUST
LIKE GUIDE BUT WE DON'T ALWAYS
KNOW WHICH ARE THE COMPONENTS
THAT DRIVE EFFECTIVENESS.
WE NEED TO ADAPT OUR CARE MODELS
TO MEET THE NEEDS OF PATIENTS
DURING VULNERABLE POINTS IN
THEIR JOURNEY AND CARE TEAMS
IMPLEMENTING SCIENCE-BASED CARE
MODEL FACING CHALLENGES
INFIDELITY AND INTEGRATING THE
MODELS WITH ROUTINE CARE.
THIS COULD BE ADDRESSED IN PART
WITH A.I.-BASED TOOLS.
SO, THIS IS THE FULL TEXT OF
THIS RECOMMENDATION.
WE WANT TO PUSH FORWARD RESEARCH
THAT ADDRESSES VULNERABLE POINTS
IN THE CARE JOURNEY.
WE WANT TO MEET THE NEEDS OF
INDIVIDUALS IN THE HETEROGENEOUS
POPULATION INCLUDING PEOPLE WHO
LIVE ALONE.
IN COOPERATE DECISION SUPPORT
TOOLS, GENERATIVE A.I.
APPROACHES TO DRIVE EFFICIENCIES
AND ADHERE TO BEST PRACTICES.
IDENTIFY THE CORE COMPONENTS OF
CARE THAT DRIVE EFFECTIVENESS
AND FOR WHOM.
AND ADVANCE WORK ON THE
AVAILABILITY OF COMMON DATA
ELEMENTS TO FACILITATE
EVALUATION OF REAL-WORLD
SETTINGS.
THANK YOU AND NEXT.
I'D LIKE TO INTRODUCE NOW JULIE
WOOD WHO WILL SPEAK ON OUR NEXT
RECOMMENDATION.
>> JULIE WOOD: THANK YOU FOR
JOINING US.
I'M JULIE WOOD A FAMILY
PHYSICIAN AND JOINING FROM THE
AMERICAN ACADEMY OF FAMILY
PHYSICIANS THAT REPRESENTED
ABOUT 28,000 FAMILY PHYSICIANS
FROM ACROSS THE UNITED STATES.
MY -- I'M GOING TO COVER
PRIORITY 1 A RECOMMENDATION ON
DIAGNOSIS.
I DON'T HAVE ANYTHING TO
DISCLOSE.
I'M GOING TO READ THIS FOR YOU
AS WELL.
OUR RECOMMENDATION ON DIAGNOSIS,
CONDUCT IMPLEMENTATION AND
DISSEMINATION RESEARCH ON
EVIDENCE-BASED INTERVENTIONS TO
DETECT AND DIAGNOSIS COGNITIVE,
BEHAVIORAL OR FUNCTIONAL
IMPAIRMENTS ASSOCIATED WITH
AD/ADRD, COMMUNICATE RESULTS TO
PATIENTS AND CARE PARTNERS AND
LINK THEM TO QUALITY CARE IN
PRIMARY HEALTH CARE SETTINGS.
SO ONE OF THE THINGS THAT WE
WANTED TO EMPHASIZE IS WHY THIS
IS SO IMPORTANT TO DIAGNOSIS
MILD COGNITIVE IMPAIRMENT.
OFTEN THIS CAN DEMONSTRATE THAT
WE CAN HELP TREAT SOMETHING
THAT'S REVERSIBLE.
THIS MAY BE A CONDITION WHERE WE
TREAT SOMETHING LIKE A MEDICAL
PROBLEM THAT IS ACTUALLY A
REVERSIBLE PROBLEM.
WE CAN ALSO OPTIMIZE MEDICATION.
THIS CAN HELP INFORM TREATMENT
DECISIONS FOR OTHER CONDITIONS
THAT A PERSON MAY HAVE.
WE ALSO WANT TO HELP CONNECT
PEOPLE TO OTHER SERVICES AS WELL
AS THE CAREGIVERS AND THIS IS
MUCH OF WHAT THE GUIDE MODEL IS
BASED ON YOU HEARD ABOUT
EARLIER.
IT GIVES A PATIENT AND THEIR
FAMILY THE OPPORTUNITY TO MAKE
DECISIONS ABOUT PARTICIPATING IN
CLINICAL TRIALS OR OTHER
RESEARCH THAT'S AVAILABLE.
AND A REALLY IMPORTANT ONE IS
STARTING TO TALK ABOUT QUALITY
OF LIFE AND GOALS FOR THE
PATIENT AND THEIR FAMILY.
AND TALK ABOUT SAFETY ISSUES.
AND TALK TO THE PATIENT AND
THEIR FAMILY ABOUT PLANNING
AHEAD FOR THEIR CARE AND HAVING
CONVERSATIONS ABOUT WHAT ARE THE
GOALS.
IMPORTANTLY, TALKING ESPECIALLY
NOW AS YOU HEARD EARLIER TALKING
ABOUT NEW AND EMERGING
THERAPIES.
IT'S IMPORTANT TO HAVE METHODS
IN PLACE TO FIND PEOPLE EARLIER
TO HELP WITH THE INTERVENTIONS
THAT ARE SO IMPORTANT.
THERE'S ALSO DISPARITIES IN
MEDICALLY UNDER SERVED
COMMUNITIES AND MINORITIES,
PEOPLE IN RURAL AREAS LIKE WHERE
I PRACTICE AND DIFFERENT SOCIAL
DISADVANTAGES AND WE KNOW THE
DIFFERENT RESOURCES ON THE SLIDE
BELOW.
SO IN PRIMARY CARE THERE'S A LOT
OF BARRIERS.
THERE'S A DEFINITE INTEREST
AMONG PRIMARY CARE PHYSICIAN TO
DO THIS BUT IT COULD BE A BIT
OVERWHELMING.
TIME WAS GIVEN AS THE TOP
FACTOR.
THERE WAS AN INTEREST AND A
KNOWLEDGE OF THE NEED AND AS YOU
HEARD EARLIER FROM THE PREVIOUS
PRESENTATION 82% OF PRIMARY CARE
DOCS CONSIDER THEMSELVES THE
FRONT LINE.
HOWEVER, AN ALMOST EQUAL CONCERN
AND BARRIER.
ONE THING WE WANTED TO POINT OUT
IS THERE WAS A STUDY DONE BY THE
JOURNAL OF INTERNAL MEDICINE,
GENERAL INTERNAL MEDICINE THAT
CAME OUT IN 2022 THAT LOOKED AT
TIME AND THEY ACTUALLY FOUND OUT
IF PRIMARY DOCS DID EVERYTHING
RECOMMENDED IT WAS IMPORTANT FOR
ALL KINDS OF GUIDELINES IT WOULD
TAKE A PRIMARY CARE PHYSICIAN
26.7 HOURS A DAY TO DO ALL
THOSE.
WE WANT TO DO ALL THOSE AND
PROVIDE GOOD CARE BUT THE KEY IS
WE HAVE TO FIND GOOD WAYS TO DO
THAT AND HAVE THE RIGHT CARE AT
THE RIGHT TIME SO WE CAN WORK IN
TEAMS AND A LOT OF OUR
RECOMMENDATIONS TODAY ARE BASED
ON THAT.
WE ALSO FOUND WITH SURVEYS
INCLUDING ONE FROM MY
ORGANIZATION AND --
>> YOU HAVE A TWO-MINUTE
WARNING.
>> JULIE WOOD: THAT GETTING
CONFIDENCE IN TRAINING IS THE
MOST IMPORTANT THING TO THEM AND
REDISCOVERED ORGANIZATIONS
GETTING INFORMATION ON
EVIDENCE-BASED CARE WAS KEY.
WE RECOMMEND TO GO WITH
COGNITIVE SCREENING.
THIS IS AN EXAMPLE OF FACTORS
THAT CAN CONTRIBUTE TO
RISK-BASED SCREENING AND
COGNITIVE CARE IN PRIMARY CARE
CLINICS THAT CAN ALLOW IT TO GO
MUCH QUICKER.
THE NEXT SLIDE IS A DIAGRAM THAT
WAS DONE AT A CONFERENCE OF
MULTI-DISCIPLINARY SCIENTISTS ON
HOW THE RISK STRATIFICATION CAN
OCCUR OFFSITE AND BUILD INTO THE
WELLNESS VISIT.
I WANTED TO MENTION IT'S VERY TO
KNOW THERE'S CLINICAL TRIALS
ONGOING AND THE MILESTONE
SHOWING THE PARADIGMS IS VERY
IMPORTANT AND THERE'S RESEARCH
ON THE WAY.
YOU HEARD ABOUT ONE OF THEM.
I WON'T REITERATE THAT BECAUSE
WE HAD A GREAT SUMMARY BEFORE.
YOU SAW THE SLIDE OF SEVERAL
MENTIONED.
THESE ARE BEING IMPLEMENTED IN
PRIMARY CARE SETTINGS FOR EARLY
DETECTION AND DIAGNOSIS.
SO, WE WANT TO MAKE SURE WE'RE
HAVING SETTINGS AND FRAGMENTED
RESEARCH CONTINUED AND THAT'S
OUR RECOMMENDATION.
I WILL LEAVE IT THERE FOR YOU TO
SEE AND SINCE I'M OUT OF TIME,
THANK YOU.
I READ THE BEGINNING.
THANK YOU FOR YOUR ATTENTION.
I'LL TURN IT OVER TO DR
DR. LINGLER.
>> DR. LINGLER: IT'S AN HONOR TO
PRESENT ON BEHALF OF OUR WORKING
GROUP.
MY DISCLOSURES IS PAID
COMPENSATION AND WE HAVE
STRATEGIES TO IMPROVE ACCESS TO
HIGH QUALITY AD/ADRD CARE
INCLUDING DIAGNOSTIC EVALUATIONS
AND BIOMARKER TESTING,
PHARMACOLOGIC AND
NON-PHARMACOLOGIC TREATMENTS AND
PALLIATIVE CARE AND HOSPICE
CARE.
RECOGNIZING THE EARLIEST PROCESS
INCLUDES STRATEGY TO INCREASE BE
OPPORTUNITIES FOR BRAIN HEALTH
RESEARCH PARTICIPATION.
THE ACCESS RECOMMENDATION IS NEW
THIS YEAR.
IT'S GROUNDED IN A ROBUST BODY
OF EVIDENCE SUGGESTING MANY
BREAKTHROUGHS HIGHLIGHTED
THROUGH THE INTRODUCTION ARE NOT
BENEFITING ALL FAMILIES IMPACTED
BY DEMENTIAS.
I'LL PROVIDE THE RATIONALE FOR
THE RECOMMENDATION.
BEAR IN MIND THE RECOMMENDATION
IS COMPREHENSIVE IN SCOPE
SPANNING THE DIAGNOSTIC AND CARE
CONTINUUM SO VIEW THIS AS A HIGH
LEVEL OVERVIEW FOR CHALLENGES TO
HIGH QUALITY CARE ALONG A
PERSON'S DEMENTIA TRAJECTORY.
A RECENT SYNTHESIS OF PUBLISHED
LITERATURE SHOWS A PATTERN THAT
THOSE WHO ARE FROM GROUPS NOBODY
TO EXPERIENCE MORE AD/ADRD TURN
OUT TO BE THE LEAST LIKELY TO
RECEIVE TIMELY AND ACCURATE
DIAGNOSIS AND RECEIVE TREATMENT
WITH INHIBITERS AS THE DISEASE
PROGRESSES THE PATTERNS OF LOWER
QUALITY CARE PERSIST OFTEN IN
THE FORMS OF CARE.
LET'S TAKE A CLOSER LOOK AT THE
PATTERNS BEGINNING WITH
DIAGNOSTICS.
YOU HEARD THE DIAGNOSES OF
AD/ADRD.
ON THE PANEL TO YOUR LEFT WE
HIGHLIGHT CLAIMS DATA
DEMONSTRATING MISSES AND DEVIL
RAYS IN DEMENTIA DIAGNOSES ARE
PROGRAMATIC WITH DELAYS FOR
HISPANIC INDIVIDUALS AND LONGER
FOR THOSE IN THE HISPANIC AND
NON-HISPANIC GROUPS.
A STUDY DOCUMENTED HIGHER
PREVALENCE OF AD/ADRD AMONG
RURAL POPULATIONS BUT NOTED
CONSISTENT DELAYED DIAGNOSIS AND
LACK OF ACCESS TO PROFESSIONALS.
AND AS WAS ALLUDED TO, THE
IMPLICATION MATTER TODAY BUT ARE
SALIENT WHEN WE CONSIDER THE
ELIGIBILITY WINDOW FOR NOVEL AND
EMERGING THERAPEUTICS.
AS THE FIELD MOVES FORWARD TO AN
ERA OF BIOMARKER INFORMED
DIAGNOSIS THERE'S EARLY EVIDENCE
IN THE ABSENCE OF THE DEDICATED
EFFORT THOSE AT HIGHEST RISK
FROM AD/ADRD MAY BE LESS LIKELY
TO UNDER GO BIOMARKER TESTS.
HERE THE STUDY SHOWS ACCESS TO
AMYLOID PET WAS UNEVEN ACROSS
RACIAL AND ETHNIC GROUPS AND IF
YOU PAN TO THE RIGHT, A REVIEW
OF STUDIES ON THE TURN OF
BIOMARKER TESTS RESULTS TO
PATIENTS AND FAMILIES SHOWS A
NEED OF PARTICIPANTS FROM BLACK
AND BROWN COMMUNITIES SO IT
INFORMS BEST PRACTICES FOR THE
RESPONSIBLE RETURN OF THE
SENSITIVE INFORMATION.
IN TERMS OF ACCESS TO PHARMACO
THERAPIES IT'S ESSENTIAL TO NOTE
CARE ENCOMPASSES NOT ONLY THE
TIMELY INITIATION OF FDA
APPROACHED ANTI-DEMENTIA
MEDICATIONS BUT EXTENDS TO
INAPPROPRIATE PRESCRIBING FOR
MOOD AND BEHAVIORAL SYMPTOMS AND
COMORBID SYMPTOMS.
AS HIGHLIGHTED INDIVIDUALS FROM
RURAL COMMUNITIES ARE
PARTICULARLY IMPACTED BY THE
LATTER.
THE LAST EXAMPLES IDENTIFY
STRATEGY TO IMPROIF ACCESS TO
HIGH QUALITY CARE IN THE FINAL
STAGES OF AD/ADRD.
AS THE TEXT ON THE LEFT
HIGHLIGHTS MEDICARE
BENEFICIARIES IDENTIFYING AS
BLACK AND/OR HISPANIC RECEIVE
MORE BURDENSOME AND COSTLY CARE
AT THE END OF LIFE.
SIMILAR TO OTHER ASPECTS OF CARE
WE SEE OPPORTUNITIES TO IMPROVE
ACCESS TO HIGH QUALITY CARE FOR
LATER STAGE INDIVIDUALS WITH THE
PUBLICATION HIGHLIGHTING LOWER
RATES OF DOCUMENTS GOALS OF CARE
INCLUDING DEMENTIA PATIENTS
RECEIVING HOSPICE.
IN SUM, ADVANCES IN AD/ADRD CARE
FOR DIAGNOSTIC PRECISION TO END
OF LIFE CARE HAVE NOT BENEFITTED
ALL WHO ARE IMPACTED BY THE
CONDITIONS IT'S CRITICAL TO
ACCELERATING THE TRANSITION OF
EFFECTIVE DIAGNOSIS OF CARE AND
REACHING REACH THOSE WITH WHO
EXPERIENCE THE GREATEST BURDEN
OF AD/ADRD.
THE WORK GROUP RECOMMEND TO
IDENTIFY AND NAVIGATE PEOPLE TO
QUALITY CARE WITH A FOCUS ON
POPULATIONS EXPERIENCING HEALTH
DISPARITIES.
THESE INTERVENTIONS SHOULD TAKE
A SYSTEMS APPROACH AND
APPROACHES SHOULD INCORPORATE
PROVIDER EDUCATION AND TRAINING
AND LINK PATIENTS WITH THE CARE
THAT'S RIGHT FOR THEM.
AND LASTLY TO EXAMINE ETHICAL
ISSUES AND EVALUATE PATHWAYS IN
EVERYDAY CLINICAL SETTINGS AND
SHOULD INCLUDE HELPING PROVIDERS
TO INTERPRET AND COMMUNICATE THE
RESULTS IN A WAY THAT OPTIMIZE
AGENCY AND REDUCES POTENTIAL
HARM.
WITH THAT I'LL TURN IT OVER TO
DR. SNYDER AND LOOK FORWARD TO
THE DISCUSSION.
>> DR. SNYDER: GOOD MORNING,
EVERYBODY.
I'M TRYING TO TURN ON MY CAMERA
AND IT'S NOT LETTING ME SO I'LL
KEEP GOING AND HOPEFULLY
SOMEBODY CAN FIGURE THAT OUT.
IT'S A PLEASURE TO PRESENT ON
BEHALF OF THE WORK GROUP AS WE
THINK ABOUT THE FOURTH
RECOMMENDATION.
AND THESE ARE MY DISCLOSURES.
AS WE GET TO BACK TO MIXED
ETIOLOGY DEMENTIA THE PRIMARY
AND SECONDARY PREVENTION IT'S
ABOUT THE PREVENTION OF
COGNITIVE DECLINE OR THE
CONTINUED DECLINE OF AN
INDIVIDUAL ONCE THEY'RE
EXPERIENCING COGNITIVE CHANGES
FOR THEMSELVES.
IN THINKING ABOUT PREVENTION,
THIS GETS YOU TO OUR NEXT SLIDE
RECOMMENDATION WHICH IS TO
EVALUATE THE IMPLEMENTATION
EFFECTIVENESS OF INTERVENTIONS
THAT MITIGATE THE RISK OF
COGNITIVE DECLINE IN PRIMARY
CARE AND COMMUNITY SETTINGS.
THE IDEA OF ACCESS WITH A STRONG
FOCUS ON POPULATIONS
EXPERIENCING DISPROPORTIONATE
AD/ADRD BURDEN.
SO THE WORK GROUP TALKED ABOUT
THE POTENTIAL AND EXAMPLES OF
HOW IN PARTICULAR PRIMARY CARE
COULD BE IMPLEMENTED.
THE IDEA AS WE THINK ABOUT THE
NEED FOR RESEARCH THAT FOCUSES
ON IMPLEMENTATION, STRATEGIES,
PERSONALIZED INTERVENTIONS BASED
ON THE PATIENT'S RISK AND CAN BE
DELIVERED WITHIN PRIMARY CARE
COMMUNITY.
WHAT YOU SEE HERE IS AN EXAMPLE
THAT CAME FROM DR. WOOD WHO
PREVIOUSLY SPOKE FROM THE AAFP
THINKING ABOUT ALCOHOL USE AND
SCREENING AND CESSATION PROGRAMS
DELIVERED IN PRIMARY CARE.
IN USING A SIMPLE BASIC
SCREENING TOOL DELIVERED
THROUGHOUT PRIMARY CARE, YOU CAN
SEE A SIGNIFICANT IMPACT ON BOTH
THE CONVERSATION HAPPENING IN
PRIMARY CARE, AWARENESS OF THE
THIS AS A POTENTIAL ISSUE AND A
CHANGE IN BEHAVIOR.
AGAIN, REALLY LEADING TO IF WE
CAN HAVE THE KINDS OF
CONVERSATIONS AS IT APPLIES TO
COGNITIVE DECLINE AND WE CAN
IDENTIFY THE PRACTICES OR
INTERVENTIONS FOR DELAYING OR
SLOWING AN INDIVIDUAL'S RISK OF
COGNITIVE DECLINE, THEN THIS MAY
ALLOW US TO MOVE FORWARD AND
THINKING OF THE IDEA OF PRIMARY
OR SECONDARY PREVENTION IN THE
PRIMARY CARE OR IN THE
COMMUNITY.
SO WE LOOK AT PHYSICIANS OR
PRIMARY CARE PHYSICIANS, ONE OF
THE THINGS WE HEAR AND THIS CAM
CAME FROM THE ALZHEIMER'S
ASSOCIATION S AND FIGURES IN
2020, 71% PHYSICIANS SAY THEY'RE
ASKED ONCE A WEEK ABOUT DEMENTIA
AND IN THINKING ABOUT TOOLS AND
IDENTIFYING WHERE AND WHEN WE
MAY BE ABLE TO INTERVENE WE NEED
TO THINK ABOUT PREPARING OR
SUPPORTING THESE CONVERSATIONS
WITH INFORMATION, ACCURATE
INFORMATION AND GOING INTO THE
PRIOR THREE RECOMMENDATIONS THAT
WE'VE HEARD ABOUT IN THINKING
ABOUT TREATMENT AND THINKING
ABOUT DETECTION AND DIAGNOSIS IN
THE FACTS AND FIGURES REPORT
PUBLISHED TODAY, 68% OF
INDIVIDUALS TALK ABOUT THEIR
DESIRE TO HAVE THIS INFORMATION
IN THINKING ABOUT MAKING
BEHAVIORAL CHANGES.
85% THAT OF INDIVIDUALS FIRST
DIAGNOSED BY NON-DEMENTIA
SPECIAL
>> USISTS AND THEY THE
INITIAL DEMENTIA DIAGNOSIS.
85% OF PERSONS DIAGNOSED WERE
WERE DIAGNOSED BY A NON-DEMENTIA
SPECIALIST AND EVEN AFTER FIVE
YEARS AROUND 23.5% OF
BENEFICIARIES HAD A DIAGNOSIS OF
AN UNSPECIFIED DEMENTIA AND
LOWER WITH THOSE WHO RECEIVED
DEMENTIA SPECIALIST HEALTH CARE
AND OVER FIVE YEARS LESS THAN
HALF OF ALL PERSONS WITH
DEMENTIA RECEIVED AN AD
DIAGNOSIS.
AGAIN, IDENTIFYING THAT THROUGH
PRIMARY CARE AND THERE'S A PATH
IN THINKING ABOUT PRIMARY AND
SECONDARY PREVENTION.
DR. POSSIN TALKED ABOUT THE
LANCET COMMISSION REPORT IN
THINKING ABOUT THE DEMENTIA RISK
AS A CONSOLATION OF ACCUMULATORS
ACROSS A PERSON'S LIFE AND BY
UNDERSTANDING THAT THROUGH THE
POTENTIAL CONTRIBUTORS TO A
PERSON'S RISK, THIS CAN AID IN
THE CONVERSATION WITH THE HEALTH
CARE PROVIDER.
AND AS WE THINK OF BUILDING OUT
THE CONVERSATIONS AND TOOLS AND
TESTS AND STUDIES THAT CAN ALLOW
US TO HAVE THE INFORMATION,
THERE'S A NEED FOR US TO
TRANSLATE THIS TYPE OF
INFORMATION TO TOOLS THAT WILL
IDENTIFY THOSE MOST AT RISK FOR
TE DISEASE OR MOST AT RISK FOR
COGNITIVE DECLINE IN A SCALABLE
ACCURATE WAY.
>> TWO-MINUTE WARNING.
>> THANK YOU.
THERE'S A RESEARCH IN THINKING
ABOUT DETECTION AND EARLY
DETECTION IN SOME OF THESE
EXAMPLES.
THESE ARE HIGH-LEVEL EXAMPLES.
WE HEARD A LITTLE BIT MORE ABOUT
THINKING ABOUT TAX AD AS
EXAMPLES IN HOW TO DETECT THE
EARLIEST CHANGES.
WHEN WE LOOK AT THIS IN THINKING
ABOUT THERE'S A NUMBER OF
STUDIES THAT HAVE BEEN DONE IN
DELIVERY OF SPECIFIC
INTERVENTIONS WHETHER IT BE
LOOKING AT EXERCISE IN A
POPULATION OF PEOPLE THAT MAY BE
EXPERIENCING MILD COGNITIVE
IMPAIRMENT OR COGNITIVE TRAINING
IN INDIVIDUALS ACROSS THE BOARD.
OR LOOKING AT THINGS TRYING TO
UNDERSTAND THE UNDERLYING
BIOLOGY IN AN INDIVIDUAL SO WE
CAN EXPAND OUT THE TYPES OF
INTERVENTIONS IN THE
PERSONALIZED APPROACH.
OR LOOKING AT MULTIMODAL
INTERVENTIONS LOOKING AT
MULTIPLE RISK REDUCTION
STRATEGIES AND THEY'RE TIED INTO
RESEARCH EFFORTS IN THINK ABOUT
DISCOVERY VALIDATION AND
IMPLEMENTATION ACROSS ALL THE
SPECTRUMS OF DISCOVERY AND
INTERVENTION IN CLINICAL CARE
THAT CAN BE DELIVERED THROUGH
PRIMARY CARE.
AND SO THINKING ABOUT THE
SPECIFIC RECOMMENDATIONS OF OUR
WORK GROUP AND EVALUATING THE
IMPLEMENTATION AND EFFECTIVENESS
OF INTERVENTIONS THAT PROMOTE
BRAIN HEALTH AND MITIGATE THE
RISK OF PRIMARY CARE SETTINGS
WITH A STRONG FOCUS ON
POPULATIONS EXPERIENCING
DISPROPORTIONATE AD/ADRD BURDEN
AND TOOLS TO IDENTIFY HIGH RISK
INDIVIDUALS AND THINKING OF
PRIMARY AND SECONDARY
INTERVENTIONS THAT ARE LOOKING
AT THOSE DIFFERENT FACTORS,
THINKING ABOUT PROMOTING BRAIN
HEALTH, REDUCING RISK OF
COGNITIVE DECLINE AND
INTERVENTIONS THAT MAY INCLUDE
GUIDANCE ON PERSONALIZED
INTERVENTION STRATEGIES BASED ON
A PATIENT'S RISK PROFILE.
SO THIS BRINGS US TO THE SECTION
CLOSE WHERE WE'VE GONE THROUGH
THE FOUR RECOMMENDATIONS THAT
YOU SEE LISTED HERE.
WHETHER WE'RE THINKING ABOUT
THAT ENTIRE SPECTRUM OF
IMPLEMENTATION AND DISSEMINATION
RESEARCH ON EVIDENCE-BASED
INTERVENTIONS TO DETECT AND
DIAGNOSIS COGNITIVE IMPAIRMENT
AND THINKING ABOUT EVALUATION
STRATEGIES TO IMPROVE ACCESS TO
CARE PATIENTS AND PARTNERS TO
QUALITY CARE.
THINKING OF CONDUCTING RESEARCH
FOR THE ADVOCACY AND
EFFECTIVENESS OF EVIDENCE-BASED
RESEARCH AND THINKING ABOUT THE
OPPORTUNITY FOR PRIMARY AND
SECONDARY PREVENTION AS WE GO
FORWARD.
SO THANK YOU VERY MUCH AND I'LL
TURN IT BACK TO THE SESSION
CHAIR.
>> THANK YOU.
I WANT TO THANK THE PRESENTERS.
I ALSO WANT TO THANK ALL OF THE
COMMITTEE MEMBERS THAT WORKED
TOGETHER FOR THE RECOMMENDATIONS
AND INVITE THEM ALL TO TURN ON
THEIR CAMERAS THEY'RE ABLE TO
JOIN US TODAY.
WE ARE VERY EAGER TO HEAR
COMMENT.
SO, I THINK YOU CAN USE THE
RAISE HAND FEATURE IF YOU'D LIKE
TO SHARE A COMMENT OR QUESTION
FOR THE PANELISTS.
I SEE THE FIRST HAND IS RAISED.
PLEASE TURN ON YOUR CAMERA IF
YOU'RE COMFORTABLE AND TELL US
WHAT YOU HAVE TO SAY.
>> ANYONE WHO WANTS TO ASK A
QUESTION USE THE RAISE HAND
FEATURE.
SO ENABLE YOUR CAMERA AND
MICROPHONE AND THEN YOU CAN TURN
IT OFF.
WE DON'T HAVE ALL THE NAMES.
I'M GOING TO TRY TO COME BACK TO
THIS.
>> CAN YOU HEAR ME?
>> YES.
THANK YOU.
>> YEAH, HI.
THANKS FOR THE VERY INTERESTING
PRESENTATIONS IT MAY BE NAIVE TO
THINK WE CAN DISCUSS POLITICIANS
AND DO YOU THINK IT WILL AFFECT
AND SEEMS LIKE IT COULD BE SEEN
AS A DEI EFFORT SO CAN YOU
COMMENT ON HOW POLITICS CAN
AFFECT SOME MUCH THESE?
>> THANK YOU FOR THAT VERY
IMPORTANT QUESTION.
I THINK DR. KOROSHETZ MAY BE
ABLE TO SPEAK THAT.
>> DR. KOROSHETZ: DEMENTIA IS A
POLITICAL PROBLEM.
LET'S GET THAT ON THE TABLE
FIRST.
HEALTH DISPARITIES ARE PROGRAMS
THAT EVERYONE, HEALTH CARE AND
EVERYONE HAS TO WRESTLE WITH.
HEALTH DISPARITIES ARE NOT
INCLUDED IN THE GOVERNMENT'S DEI
ADMINISTRATIONS AT THE CURRENT
TIME.
ALL INDICATIONS TALKING TO THE
NIH DIRECTOR WHO HAS MADE IT
VERY CLEAR, HEALTH DISPARITIES
AND DEI ARE COMPLETELY DIFFERENT
ISSUES ACCORDING TO THE
ADMINISTRATION'S DEFINITION.
WE REALLY DO NEED TO RECOGNIZE
AND MORE THAN RECOGNIZE, DEVELOP
INTERVENTIONS THAT WILL REDUCE
HEALTH DISPARITIES WITH REGARD
TO DEMENTIA AND DEMENTIA CARE IN
THE U.S. AND THAT'S REALLY
IMPORTANT FOR THE SUMMIT.
WE'RE GOING TO HEAR ON JUNE 2
PARTICULARLY ON THE ISSUE.
VERY IMPORTANT.
I'M GLAD TO GET THAT CLEARED UP.
>> SORRY TO PUSH FOR THE
FOLLOW-UP CAN I ASKED ABOUT THE
PROPOSED 44% DECREASE IN NIH
BUDGET FOR NEXT YEAR.
DO YOU THINK IT'S LIKELY TO
AFFECT NIA AND NINDS?
>> DR. KOROSHETZ: THE BUDGETS
COME OUT IN DIFFERENT STAGES AND
GET WORKED ON BY THE SENATE AND
HOUSE.
WE HAVE NO IDEA WHAT THE
BUDGET'S GOING TO BE.
SO, WE CAN'T REALLY COMMENT
BECAUSE WE DON'T KNOW WHAT THE
BUDGET IS.
>> SHOULD WE TRY AGAIN?
AFTER THAT WE'LL SEE DALE
LESINA.
IT LOOKS LIKE THERE'S A BLOCK
SIGN.
LET'S GO FORWARD WITH DALE FOR
NOW.
DALE, PLEASE, SHARE YOUR
COMMENTS.
WE CAN'T QUITE HEAR YOU YET.
ARE YOU ABLE STO -- TO UNMUTE?
WE CAN SEE YOU.
WE CAN'T HEAR YOU YET.
ARE YOU ABLE TO UNMUTE?
NO, CAN'T UNMUTE.
I WISH WE COULD HEAR YOUR
COMMENT.
HMM.
WHILE THE TEAM IS TROUBLE
SHOOTING LET'S SEE IF ANOTHER
PERSON CAN UNMUTE.
WE'LL COME BACK TO YOU DALE.
HOPEFULLY WE CAN FIX THIS.
ERIC, I THINK ALSO NOT ABLE TO.
WE'LL TRY ONE MORE PERSON
OTHERWISE THIS SEEMS TO BE A
PROBLEM ON OUR END.
>> I THINK SO.
CAN YOU HEAR ME?
>> YES.
>> ALL RIGHT.
>> DR. KOROSHETZ: PENNY, HOW
DID YOU DO THAT?
>> MAGIC.
I THINK SOMEONE ENABLED IT
BECAUSE IT WASN'T POSSIBLE FOR
ME AND SEEMS TO BE FINE SOMEONE
ON YOUR I.T. SIDE ENABLED IT BUT
I THINK THE PEOPLE HERE HAVE
BEEN TRYING SO I CAN'T ANSWER
THAT FOR YOU, WALTER.
I WILL COMMENT ON A QUESTION.
NUMBER ONE, THANK YOU TO ALL OF
YOU FOR YOUR EXCEPTIONAL WORK
AND I WANT TO THANK THE NIH AND
ALL THE ACADEMIC RESEARCH
LEADERS WHO ARE BEHIND THE
BREAKTHRO
BREAKTHROUGHS THAT BROUGHT OUT
TO THE CONVERSATION TO HOW TO
ACCESS AND YOU HAVE PEOPLE WITH
PARKINSON'S DISEASE THAT DEVELOP
LEWY BODY DISEASE AND DISORDERS
ACTUALLY FTD INITIALLY DIAGNOSED
WITHIN THE PARKINSON CLINICS.
WE HAVE THE VARIANT FORMS THAT
MAY NOT MANIFEST IN THE SAME
WAY.
IN THE WORK YOUR RECOMMENDING
AND HOW TO IMPROVE ACCESS TO
DIAGNOSIS, CAN YOU TALK ABOUT
HOW TO INCORPORATE THAT
COMPLEXITY PEOPLE CAN BE SHOWING
UP WITH DIFFERENT TYPES OF
SYMPTOMS, IT'S NOT ALWAYS
MODERATE COGNITIVE IMPAIRMENT.
HOW DO WE GET BETTER ACCESS TO
EVERYBODY FACING ONE OF THE
ALZHEIMER'S DISEASE OR
ALZHEIMER'S DISEASE RELATED
DEMENTIAS?
>> THANK YOU, PENNY, FOR THAT.
I'LL GIVE A BRIEF ANSWER AND IF
ANYBODY ELSE WANTS TO SPEAK, I
WANT TO SAY WE'RE NOTING THIS
DOWN AND CAN MAKE SURE OUR
RECOMMENDATION INCLUDES
EVALUATION FOR NOT ONLY THE
TYPICAL SIGNS OF EARLY DISEASE
BUT THE LESS TYPICAL SIGNS SUCH
AS BEHAVIORAL SYMPTOMS.
I'M NOTING THIS AS A COMMENT FOR
US TO INCORPORATE.
THANK YOU.
SHOULD WE TRY AGAIN?
>> IN THE TEAMS PLATFORM AT THE
TOP THERE'S A CAMERA ICON.
WE ENABLED TO USE THE BUTTONS.
SO YOU CLICK ON IT AND IT SHOULD
UNMUTE YOU.
I CAN SEE DALE YOU STILL
[INDISCERNIBLE]
>> IT LOOKS LIKE ERIC IS
UNMUTED.
>> THANK YOU.
YES AND THANK YOU DR. KONKWLO.
LET'S HEAR FROM YOU.
>> IT KIND OF GOES BACK AND
FORTH BETWEEN A MUTE AND BLOCKED
SIGN WHICH MAKES ME THINK IT'S
NOT JUST --
>> I'M TRYING TO MUTE AND UNMUTE
BUT FOR WHATEVER REASON IT'S NOT
ABLE TO [INDISCERNIBLE]
>> HI, DR. MCCARTNEY.
MAYBE IT'S THAT WHEN LLOYD IS
DOING IT I THINK THE USER IS
SIMULTANEOUSLY TRYING TO UNMUTE
THEMSELVES.
IT MAY CAUSE A PROBLEM.
WE ALSO HAVE A LINK ON VIDEOCAST
WHERE YOU CAN SUBMIT WRITTEN
COMMENTS.
WE'LL BUT THAT INFORMATION ON
THE SLIDE SO EVERYONE CAN SEE
IT.
THIS IS REALLY THE IMPORTANT
PART OF THE MEETING AND WHAT I
CARE ABOUT MOST IS GETTING INPUT
FROM ALL OF YOU.
SORRY FOR THE TECHNICAL
PROBLEMS.
>> IS IT POSSIBLE TO UNLOCK THE
CHAT?
>> RAUL, DO YOU WANT TO ASK A
QUESTION?
>> THANK YOU FOR THE WONDERFUL
QUESTIONS COMMENT ON THE
NEUROPSYCHIATRIC SYMPTOMS IN
THIS POPULATIONS AND CURRENT
MEDICATIONS.
>> I THINK THE QUESTION IS CAN
WE COMMENT ON THE
NEUROPSYCHIATRIC SYMPTOMS.
I THINK IT'S A NICE POINT THAT
WE NEED TO MAKE SURE THAT WHEN
WE'RE EVALUATING PATIENTS IN
PRIMARY SETTING WE'RE LOOKING
FOR THOSE SYMPTOMS.
ANYONE ELSE IN THE SESSION WANT
TO COMMENT?
>> I WOULD JUST OFFER IT'S ALSO
IMPORTANT IN TERMS OF
COORDINATED CARE TO IDENTIFY THE
SYMPTOMS AND HAVE A COORDINATED
APPROACH TO CLINICAL AND
NON-CLINICAL INTERVENTIONS FOR
THE SYMPTOMS.
SO THE DRUG THERAPIES AS PERHAPS
LAST RESORT BUT KNOWING THERE'S
A LOT OF NON-DRUG INTERVENTIONS
NON-EMERGENCY SITUATIONS ARE
TRIED INITIALLY AND IN MANY
CASES ARE ENTIRELY SUCCESSFUL
BUT JUST KNOWING WE NEED TO
CONTINUE ADVANCING THE RESEARCH
ABOUT THE NON-PHARMACOLOGIC AND
PHARMACOLOGIC INTERVENTIONS AND
THE CLINICIANS AND INDIVIDUALS
WITH COGNITIVE EXPERIENCES HAVE
A FULL COMPLEMENT TO ADDRESS THE
INCREDIBLY SERIOUS AND COMPLEX
MANIFESTATIONS OF COGNITIVE
IMPAIRMENT FROM INDIVIDUALS.
>> THAT DOVETAILS NICELY WITH
DR. SNYDER'S PRESENTATION FOR
TREATING AND DIAGNOSING AND
PROVIDING CURES TO THESE
DISORDERS.
IT'S A NICE WAY TO TIE THEM
TOGETHER.
>> MAYBE JUST TO ADD -- SORRY, I
CAN'T TURN ON MY CAMERA.
MAYBE JUST TO ADD THE ONE PIECE
AS WE THINK ABOUT THE SPECTRUM
OF SYMPTOMS THAT AN INDIVIDUAL
MY EXPERIENCE.
WE WERE INTENTIONAL IN TALKING
AROUND PRIMARY AND SECONDARY
PREVENTION AND DISEASES IS
POTENTIALLY SOMETHING VERY
DIFFERENT AND WE MADE THAT
DISTINCTION WITHIN OUR
DISCUSSIONS AND THINKING ABOUT
BEHAVIORAL CONSIDERATIONS A
PERSON MADE PART OF THAT AS WE
THINK ABOUT THE PRIMARY AND
SECONDARY PREVENTION.
OF COURSE THE FULL SPECTRUM OF
THE RECOMMENDATION.
>> WONDERFUL.
AND I'D JUST ENCOURAGE DALE AND
AN I'LL TURN NOW TO SARA
DELANEY.
>> AND IN TREATING DEMENTIA FOR
PEOPLE WHO DON'T HAVE A
CAREGIVER OR SOCIALLY ISOLATED.
I WONDERED IF THAT WAS PART OF
THAT.
>> THIS IS EXPLICITLY PART OF
OUR RECOMMENDATIONS FOR
IMPROVING COLLABORATIVE DEMENTIA
CARE TO MEET THE NEEDS OF PEOPLE
WITHOUT AN INVOLVED CAREGIVER
THAT LIVE ALONE.
SOMETHING WE SHOULD THINK ABOUT
ACROSS ALL FOUR OF OUR
RECOMMENDATIONS SO I'M NOTING
THIS.
>> THANK YOU.
>> LET'S TRY MIA.
>> HI, THANK YOU ALL.
I'M ONE OF THE PARTICIPATING
GUIDE SITES.
ONE THING I WANTED TO BRING UP
IS THAT THE NUMBER OF FOLKS WHO
ARE ELIGIBLE FOR GUIDE IS
SMALLER THAN POTENTIALLY
ELIGIBLE BECAUSE IT'S ONLY FOLKS
WITH TRADITIONAL MEDICARE.
I'M WONDERING IF THE PRESENTERS
HAVE ANY SUGGESTIONS OR ADVOCACY
ON THE PART OF ASKING MEDICARE
ADVANTAGE PROGRAMS TO ALSO
CONSIDER A COLLABORATIVE
DEMENTIA CARE MODEL BECAUSE THAT
IS THE MAJORITY OF THE MARKET IN
MANY PARTS OF THE COUNTRY.
>> DO YOU WANT TO TAKE THIS OR
SHOULD I?
>> I'LL GIVE IT A TRY.
THANKS FOR YOUR QUESTION.
SO, TWO POINTS, IS ONE, YES, THE
ADVOCACY COMMUNITY AND OTHERS
ARE WORKING HARD TO EXPAND
ACCESS BEYOND PARTICIPANT SITES
FOR THE OTHER 7 MILLION NOT
ELIGIBLE TO ENSURE SHAY HAVE
ACCESS AND THERE ARE MANY OTHER
AVENUES TO IMPROVE DEMENTIA CARE
OUTSIDE OF THIS MODEL FROM CMS.
ON A RECOMMENDATION SITE YOU SAW
REFERENCE TO HCVS.
AND IT'S COMMUNITY-BASED
SERVICES.
MANY ARE UNCOORDINATED THROUGH
VARIOUS SERVICE PROVIDERS AND WE
WANT TO SEE GREATER COORDINATION
BETWEEN NOT ONLY CLINICAL
PROVIDERS BUT NON-CLINICAL
SUPPORT PROVIDERS.
THAT CAN HAPPEN THROUGH THE
GUIDE MODEL AND THROUGH
MEDICARE.
WE WANT TO MAKE SURE THAT'S
ACCESSIBLE TO PEOPLE NOT PART OF
THE MODEL AND WANT TO TRY TO
PUSH MEDICARE TO DEVELOP THE
EVIDENCE THROUGH THE GUIDE MODEL
AS QUICKLY AS POSSIBLE HOPEFULLY
FASTER THAN THE MODEL AND GET
THIS TO A FULL MEDICARE BENEFIT
BOTH FOR TRADITIONAL MEDICARE
AND MEDICARE ADVANTAGE
PARTICIPANTS HOPEFULLY SOONER
THAN EIGHT YEARS.
>> WE HAVE TIME FOR ONE MORE
QUESTION AND THEN AFTER THAT
PLEASE STAY ON AND AMBER
MCCARTNEY WILL GIVE GUIDANCE ON
PROVIDING WRITTEN COMMENTS AND
SUPPORT ON THE MICROPHONE
ISSUES.
WE HAVE A COMMENT OR QUESTION.
>> AS THE BEEN WONDERFUL TO
LISTEN TO ALL THE PRIORITIES.
I'M JUST FOLLOWING UP ON AN
EARLIER QUESTION IN TERMS OF
DIAGNOSES.
I WORK WITH CARE PARTNERS OF
PEOPLE WITH LEWY BODY DEMENTIA.
ONE COMMENT THAT COMES UP FROM
SPOUSES AND SINCE MANY ARE WOMEN
AND OLDER ADULTS, BECAUSE OF THE
FLUCTUATIONS IN COGNITION IN
LEWY BODY DEMENTIA IS SOMETHING
THAT SOMETIMES BECOMES TRICKY.
PRIMARY CARE PHYSICIANS MAY NOT
NOTICE IT WHEN THEY SEE THE
PATIENT, THEY THINK THE PATIENT
IS FUNCTIONING PERFECTLY FINE
AND RESPONDING TO QUESTIONS
PERFECTLY FINE WHILE THE SPOUSE
AT HOME IS SEEING THE
FLUCTUATION.
NOTING THE FLUCTUATIONS IS ONE
THING TO COMMENT ON AS THE
DIAGNOSTIC IMPORTANCE.
>> YES, OF COURSE.
I WANTED TO INVITE JULIE OR I'LL
NOTE THE IMPORTANT COMMENT THAT
WE NEED TO MAKE SURE TO INCLUDE
DETECTION AND DIAGNOSIS IN
PRIMARY CARE AND THIS IS
SOMETHING THEY KNOW ABOUT AND
THEY'RE LOOKING FOR.
WITH THAT WE'LL LEAVE COMMENTS
AND I WANT TO ENCOURAGE THOSE
WHO HAD A COMMENT AND WEREN'T
ABLE TO SHARE IT, PLEASE PROVIDE
IT IN WRITING.
WE'RE GOING TO GO THROUGH EVERY
ONE OF THE COMMENTS AND THINK
HOW TO INTEGRATE THEM IN THE
RECOMMENDATIONS.
THIS IS WHY WE'RE HERE TODAY.
I'M GOING TO TURN IT OVER --
ACTUALLY, YOU HAVE A BREAK FOR
ONLY 11 MINUTES.
WE'RE GOING TO COME BACK AT THE
HOUR FOR OUR NEXT SESSION ON FRONTAL TEMPORAL DEMENTIA AND
COME BACK ON FOR GUIDANCE ON COMMENTS OR USING YOUR MICROPHONE.
>> WE'RE GOING TO GET STARTED
AND LINDE JACOBS WILL BE ON I
INTRODUCE YOU.
THANK YOU TO EVERYBODY WHO
WORKED ON THE SETTINGS.
I HOPE IT'S GOING TO WORK
BETTER.
FRANK, ARE YOU READY?
>> IT'S MY PLEASURE TO INTRODUCE
LINDE JACOBS WHO SERVED ON OUR
SUBCOMMITTEE AND HAS BEEN A
WONDERFUL ADVOCATE FOR FTD AND
SOMEONE WHO I LEARNED A LOT
FROM.
>> THANK YOU FOR THE
INTRODUCTION.
GOOD MORNING.
MY NAME IS LINDE JAKESCOBS IT'S
PRIVILEGE AND HONOR TO SPEAK TO
YOU AT THE 2025 ALZHEIMER'S
DISEASE-RELATED DIMENTIAS
SUMMIT.
I COME TO THIS MEETING NOT ONLY
AS A PARTICIPANT SERVING ON THE
FTD SUBCOMMITTEE BUT I'VE BEEN
AFFECTED BY FAMILY DESTROYED BY
FRONTAL TEMPORAL DEMENTIA AND
THESE GUIDELINE CURATED TO
DETERMINE WHO, WHAT AND WEAR
APPRECIATION FUNDING ALLOCATIONS
WILL BE SLOTTED AND IF CHOSEN
INCORRECTLY WILL WILL DICTATE
WHETHER THERE'S SOMETHING FOR ME
IN THE NEXT YEAR AND IF I TOO
WILL SUCCUMB TO THE MISCODING IN
MY GENOME.
I WAS ASKED TO SHARE MY STORY
WITH FTD AND HOW TO IT'S CREATED
AN OPPORTUNITY TO SERVE AS A
PERSON WITH LIVED EXPERIENCE ON
A SCIENTIFIC SUBCOMMITTEE.
BEING THE VOICE FOR MY COMMUNITY
AND ADVOCATING FOR THOSE WHO
WORK THIS PATH ALONG SIDE.
YOU'LL NOTICE I LACK
CREDENTIALS.
THERE'S NO Ph.D. OR EVEN A
MASTER'S DEGREE.
I DON'T HOLD HIGHLY REGARDED
ACRONYMS THAT FALL ON MY NAME.
IT'S STRANGE I FIND MYSELF
SPEAKING TO INDIVIDUALS WITH THE
HIGHEST OF I.Q.s AND CREDENTIALS
AND RESUMES.
IT'S NOT THE CROWD I ENVISIONED
I'D BE IN.
I WANT TO SEE CHANGES IN THE
FIELD TO GET FTD FROM A PLACE OF
TERMINAL DISEASE TO DIAGNOSIS
WITH OPTION TO TREAT OR CURE
BEFORE MY BRAIN SUCCUMBS IT'S
IMPERATIVE I TALK ABOUT MY
FAMILY BECAUSE IT'S MY FUTURE.
I'M THE FUTURE FACE OF FTD AND
THE SUBJECTS IN THE GRANTS AND
THE PATIENTS IN THE PRIORITIES.
WHAT WE DECIDE HERE BECOMES MY
LIFE LINE.
I HAVE NO DISCLOSURES TO REPORT.
I'M A WIFE AND MOTHER TO YOUNG
YOUNG DAUGHTERS AND HAVE BEEN A
REGISTERED NURSE WORKING IN A
VARIETY OF SETTINGS AND WORK IN
AMBULATORY SURGERY.
BEING IN THE COMPANY OF THOSE IN
HEALTH CARE IS SOMETHING I'M
WELL ACCUSTOMED TO BUT I
INTENTIONALLY CHOSE NOT TO
OBTAIN AN ADVANCED NURSING
DEGREE.
I WAS A CAREGIVER FOR MY MOTHER
STARTING AT THE AGE OF 22 AFTER
I GRADUATED COLLEGE UNTIL SHE
PASSED IN AUGUST OF 2021.
I WILL BE THE THIRD KNOWN
GENERATION IN MY FAMILY AFFECTED
BY BEHAVIORAL VARIANT FTD AS A
KNOWN MAP 2 MUTATION CARRIER.
FOLLOWING MY GENERATION, THERE
ARE SIX CHILDREN IN THE NEXT WHO
ARE NOW ALL FACING 50/50 ODDS OF
BEING FLAGGED, IN OTHER WORDS,
GENETIC FTD WILL CONTINUE TO
DESTROY GENERATIONS OF FTD UNTIL
THERE'S SOMETHING DONE TO STOP
IT.
FTD HAS BEEN A CURSE ON MY
FAMILY SINCE THE TIME I WAS
BORN.
MY GRANDMOTHER STARTED
EXHIBITING SYMPTOMS OF FTD AND
LANGUISHED FOR THE DISEASE WITH
15 YEARS UNTIL 2006.
JUST THREE YEARS AFTER MY
GRANDMOTHER PASSED, MY MOTHER,
ALLISON'S BRAIN STARTED TO
CHANGE AT THE AGE OF 50.
DESPITE A FAMILY HISTORY AND
DAUGHTER WORKING IN THE MEDICAL
FIELD, IT TOOK US EIGHT YEARS TO
GAIN A DIAGNOSIS OF FTD IN 2018.
MY MOTHER PASSED IN 2022 AFTER
12 YEARS OF THIS DISEASE.
TO DATE MY GRANDMOTHER BEVERLY
AND ALL FOUR OF HER CHILDREN
RECEIVED DIAGNOSIS OF BEHAVIORAL
VARIANT FTD WITH CONFIRMED
GENETIC PINNINGS.
ONCE MY MOTHER AS A FIGHT ENDED,
I RECEIVE D MY RESULTS AND GOT
CONFIRMATION THE FAMILIAL CURSE
LIVES IN ME AND NOW POSSIBLY
BOTH OF MY DAUGHTERS.
I WAS TOO LATE TO SPARE THEM.
MY SISTERS THEN PROCEED WITH
THEIR OWN GENETIC TESTING
THEREAFTER AND THEIR RESULTS
MATCHED MINE.
POSITIVE.
WHICH MEANS ALL SIX OF THOSE
CHILDREN IN THE PICTURES ON THE
LEFT ARE ALL FACING THE GENETIC
COIN TOSS THAT COMES WITH
AUTOSOMAL DOMINANT DISEASES.
THE CHILDREN ARE ABOUT WHAT
GIVES ME THE TIRELESS ENERGY TO
CONTINUE TO FIGHT.
SOMETIMES I WONDER IF IT WOULD
BE EASIER TO PRETEND I DON'T
KNOW WHAT THE FUTURE LOOKS LIKE
AND IT'S THE DECISIONS WE MAKE
TODAY TO FUND TOMORROW TO
DETERMINE THEIR FUTURE.
THERE'S MORE TO DO SO IT'S
EASILY RECOGNIZED AND DIAGNOSED
WITH THOSE FIRST COMING INTO
CONTACT WITH PATIENTS.
HETEROGENEITY MAKES IT
DIAGNOSTICALLY CHALLENGING IT
TAKES OVER THREE YEARS AFTER
SYMPTOMS START TO GAIN A CORRECT
DIAGNOSIS.
WHICH MEANS THE ATROPHY HAD
ALREADY BEEN OCCURRING THREE
YEARS PRIOR TOE THAT FOR FIRST
SYSTEM.
WITH FTD BEING A YOUNGER ONSET
DISEASE AFFECTING A PERSON IN
THE PRIME OF THEIR ADULT LIFE,
THERE'S SIGNIFICANT CHALLENGES
THE PERSON AND FAMILY FACES.
LEGAL ISSUES WITH GAINING PROPER
CONTROL OVER THE INDIVIDUAL
WHILE STILL MAINTAINING THEIR
AUTONOMY, ECONOMIC ISSUES WITH
ASSETS, THE IMPACT ON THE ENTIRE
FAMILY AS SOMEONE TYPICALLY
RAISING DEPENDENT CHILDREN AND
PROVIDING INCOME FOR THEIR
FAMILY.
THERE'S A VERY APPARENT LACK OF
AWARENESS IN THE PUBLIC EYE AND
EVEN WITH MANY HEALTH
PRACTITIONERS, STATING SYMPTOMS
LIKE EXECUTIVE REASONING
IMPAIRMENT, DISINHIBITION AND
OTHER SYMPTOMS NO ONE KNOWS AND
HARD TO DESCRIBE WITHOUT SHOWING
AN EXAMPLE AS EACH SPECIFIC
PERSON OWN DISINHIBITION MAY NOT
LOOK THE SAME AS SOMEONE ELSE'S.
SO WE ON THE FTD SUBCOMMITTEE
FOR THE NEXT SET OF MILESTONES
HAVE A HUGE UNDERTAKING FOR
CONSIDERATIONS.
IT'S NOT JUST NEEDING DIAGNOSTIC
MEASURES AND TREATMENTS, WE ALSO
HAVE TO FIGURE OUT WHAT'S
CAUSING THE DISEASE.
WHERE'S IT HAPPENING AND WHAT
TYPES OF THERAPIES A PERSON CAN
BE A PART OF.
ARE THEY SEEING THE CORRECT
PRACTITIONER AS WELL AS FINDING
WAYS TO UNDERSTAND THE DISEASE
TO THEN IMPLEMENT THE MILESTONES
TO BE SUCCESSFUL.
AT THIS TIME I WANTED TO GIVE A
SPECIFIC MENTION OF GRATITUDE
AND THANKS FOR ALL THE THINGS
THE NIA, NIH AND NINDS HAS
FUNDED.
I'VE BEEN GIVEN THE GIFT OF
BEING ABLE TO PARTICIPATE IN
RESEARCH THE LAST FOUR YEARS.
THAT'S FOUR YEARS OF IMAGING
I'VE BEEN ABLE TO OBTAIN WITHOUT
COST.
THESE STUDIES HAVE PROVIDED ME
THE OPTION TO GET A BASELINE MRI
STARTING AT THE AGE OF 32.
THE ONE PIECE THAT COULD HAVE
DRASTICALLY ALTERED GETTING MY
MOM DIAGNOSED SOONER AND TESTING
AND COGNITIVE TESTING AND
FURTHER IMAGING.
EVERY TIME GIVING ME THE
VALIDATION THINGS ARE STABLE
RIGHT NOW.
IT'S TERRIFYING THE STUDIES ARE
IN JEOPARDY.
THERE WAS LACK OF SCIENTIFIC
DISCOVERY HOWEVER, AFTER THE
LAST THREE YEARS OF TRYING TO
UNDERSTAND EVERYTHING DISCOVERY
ENTAIL I'VE CHANGED FROM
FRUSTRATION TO AWE.
LEARNING HOW EACH RESEARCHER'S
WORK PROVIDES A PIECE TO THE
PUZZLE TO DISCOVERY CREATED
PROFOUND GRATITUDE FOR THE WORK
EVERYONE ON THE CALL IS DOING.
THIS IS A COMMUNITY FIGHT.
NOT A SINGLE INDIVIDUAL'S QUEST.
I REALIZE HOW MANY ALLIES ARE
FIGHTING FOR WHAT I'M FIGHTING,
AN END TO THESE DISEASE.
THANK YOU FOR YOUR TENACITY AND
DETERMINATION.
I FEEL HONORED TO BE A MEMBER OF
THIS GROUP.
WHEN I WAS FIRST ASKED TO SERVE
AS THE PWLE ON THE COMMITTEE I
WAS QUITE TERRIFIED TO BE THE
SOLE VOICE OF MY COMMUNITY.
I HAD SEVERE IMPOSTER SYNDROME
AND QUESTIONED IF I WAS THE
RIGHT CHOICE.
I KNEW IF I HAD TO ENSURE THAT
MY VOICE SERVED AS THE VOICE AND
REPRESENTATIVE OF THE WHOLE FTD
COMMUNITY.
WITHIN MY ADVOCACY WORK, I
TYPICALLY HAVE A TARGETED FOCUS
ON GENETIC FTD BUT THIS REQUIRED
ME TO HAVE A UNIFIED VOICE,
FAMILIAL, SPORADIC AND GENETIC
AND I SENT MULTIPLE E-MAILS IN
THE FTD COMMUNITY TO MAKE SURE I
UNDERSTOOD MY ROLE AND GET
FEEDBACK FOR TOP PRIORITIES AND
MILESTONES.
THOUGH MY VOICE WAS THE ONE
HEARD IN THE DISCUSSIONS IN THE
LAST MONTHS, I WAS THE MEGA
PHONE FOR OUR COMMUNITY MEMBERS.
ONE OF THE BLARING SHARED
MESSAGE IS WE NEED DIAGNOSTIC
TOOLS AND BIOMARKERS AND
TREATMENTS AND THERAPIES AS THE
FIRST, HIGHEST, TOP PRIORITY.
AS SOMEONE WHO WATCHED THE
DEBILITATING DISEASE DESTROY A
PERSON'S LIFE I WAS IN ABSOLUTE
AGREEMENT.
AS A COMMUNITY, WE NEED TO
DEVELOP WAYS TO MORE EASILY
DIAGNOSIS FTD AND THE SUB TYPES
AND WAYS TO DETERMINE WHICH
UNDERLYING PATHOLOGY WE'RE
WORKING WITH AND THEN WE NEED TO
FIND A WAY TO TREAT THIS DISEASE
WHETHER IT'S CURATE OR SYMPTOM
MANAGEMENT BUT TRYING TO SOLVE
THE PROBLEM IS OF THE HIGHEST
PRIORITY.
BECAUSE ISN'T THAT TRULY WHAT
WE'RE ALL TRYING TO ACCOMPLISH?
AREN'T WE HERE TO FORMULATE WAYS
TO CURE THESE DISEASES?
I REORGANIZED THE MILESTONES OF
RENOWN CLINICIANS TO VOICE AN
OPINION I DIDN'T FEEL I HAD
EARNED.
AFTER SUGGESTING A REORDERING TO
SET A PRECEDENT OF DIAGNOSTICS
AND TREATMENTS AS THE HIGHEST
PRIORITY, DO WANT TO KNOW WHAT
HAPPENED?
THEY LISTENED.
NOT ONLY DID THEY LISTEN, THEY
AGREED AND THEY TOOK ACTION.
NOW, THE MILESTONES FOR FTD FOR
THE NEXT THREE YEARS REFLECT
THIS, NUMBER ONE, ACCELERATE THE
EVALUATION OF NOVEL FTD
TREATMENTS AND NUMBER TWO,
ADVANCE DEVELOPMENT OF AN ARRAY
OF STANDARDIZED BIOMARKERS IN
DIGITAL HEALTH TECHNOLOGY FOR
SCREENING.
THAT MOMENT WAS SOMETHING I WILL
NEVER FORGET.
TO BE VALIDATED IN A WAY THAT
BOLDLY DEMONSTRATED MY VOICE, MY
OPINION AND MY POSITION WITHIN
THIS SUBCOMMITTEE WAS JUST AS
VALUED AS EVERYONE ELSE'S.
FOR THAT I REALLY WANT TO THANK
THOSE WHO SERVE ON THE FTD
SUBCOMMITTEE FOR GIVING ME THE
OPPORTUNITY AND FOR YOUR
SUPPORT.
IT'S STILL MISUNDERSTOOD AND
UNDER DIAGNOSED AND UNDER FUNDED
AND FOR MANY STILL A MYSTERY.
WE NEED MOMENTUM IN SCIENCE,
CARE AND COMMUNITY AND EARLIER
DETECTION AND MORE TRIALS AND
SUPPORT FOR THE CAREGIVERS AND
ACCESS TO SPECIALISTS AND
THERAPIES THAT REFLECT THE
COMPLEXITY OF THIS DISEASE.
THIS HOPE IS WHAT DRIVES ME TO
PUSH BOUNDARIES AND SEEK ANSWERS
AND SUPPORT OTHERS ON THE
JOURNEY.
IT IS A HOPE ROOTED IN SCIENCE,
NURTURED BY COMMUNITY AND
PROPELLED BY UNWAVERING
DETERMINATION.
HOPE IS THE FIGHT.
THE RELENTLESS PUSH FORWARD
UNTIL THERE'S NOTHING LEFT TO
PUSH.
I'M AWARE OF THE REALITY THERE'S
NO GUARANTEE THERE WILL BE A
TREATMENT IN TIME TO SAVE ME BUT
WITH THE INTELLIGENCE AND
DETERMINATION I SAW IN THIS
COMMITTEE, I KNOW THAT MY
DAUGHTERS WILL BE GIVEN OPTION
AND AN OPPORTUNITY FOR A
DIFFERENT FUTURE.
ONE THEY WON'T HAVE TO FIGHT SO
HARD FOR.
MAY WE ALL CONTINUE TO KEEP
FILING FOR THE NEXT GENERATION.
THANK YOU.
-- FIGHTING FOR THE NEXT
GENERATION.
THANK YOU.
>> DO YOU WARRANT TO -- WANT TO
TAKE US IN THE NEXT SESSION?
>> I'D LIKE TO WELCOME YOU ALL
ON BEHALF OF MY CO-CHAIR, I'M
CELESTE KARCH.
WE JUST HEARD BEAUTIFULLY FROM
LINDY ABOUT THE REAL JOURNEY AND
COMPLEX DIAGNOSIS.
WHEN WE THINK OF FRONTAL
TEMPORAL DEMENTIA WE'RE THINKING
ABOUT THE COMPLEX SET OF
SYMPTOMS THAT CAN PRESENT IN
THREE MAJOR WAYS AND THEY'RE
MEDICAL TERMS AND WHAT WE SEE IS
THAT THE REAL WAY IN WHICH
PATIENTS ARE COMING INTO THE
CLINICS IS WITH CLINICAL
PRESENTATIONS MORE COMPLEX THAN
THESE THREE VERY BROAD
CATEGORIES OF CLINICAL
PRESENTATIONS THAT BOTH
INCORPORATE THE KEY FEATURES AS
WELL AS CAPTURE ASPECTS OF
PARKINSON'S OR ALZHEIMER'S
DISEASE OR EVEN ALS.
AND SO THIS COMPLEX CLINICAL
PRESENTATION OF FTD REALLY
REQUIRES WE PUT FORTH INNOVATIVE
APPROACHES TO DIAGNOSE AND
MONITOR THE PROGRESSION OF
DISEASE AND FIGURE OUT WHICH
TREATMENT BEST FOR WHICH FORMS
OF DISEASE.
NOT JUST IN THE CLINIC BUT IF WE
GO BACK TO THE MOLECULAR CAUSES
OF DISEASE WE'RE REMINDED FTD IS
AN UMBRELLA TERM THAT REPRESENTS
SEVERAL DIFFERENT SUB TYPES.
THEY'RE INITIATED BY A NUMBER OF
DIFFERENT GENES IN FAMILIAL
FORMS LIKE T THESE AND ULTIMATEY
WHETHER SPORADIC OR FAMILIAL IT
CAN LEAD TO DIFFERENT TYPES OF
PATHOLOGY THAT ACCUMULATES IN
DISEASE AND IN THE BRAIN.
SO WE MUST CONSIDER THESE AS
WE'RE DEVELOPING THE TREATMENTS
AND EVEN THE DIAGNOSES TO DEFINE
IN THE CLINIC WHICH SUB TYPE AN
INDIVIDUAL PRESENTS ITSELF AS.
ULTIMATELY THE RECOMMENDATIONS
YOU'LL HEAR ABOUT IN THE SESSION
ARE REALLY BUILDING OFF THE
URGENT NEEDS TO BE ABLE TO
DIAGNOSIS FTD AND TO UNDERSTAND
OF THE SUB TYPES AND EFFECTIVELY
MANAGE AND ASSIGN THE BEST
TREATMENT FOR THE SUB TYPES.
AND IN ORDER TO DO THIS WE STILL
NEED TO UNDERSTAND THE
FUNDAMENTAL MECHANISMS THAT
DRIVE DISEASE AND WORK ACROSS
THE MODALITIES FROM THE PATIENT
POPULATIONS ALL THE WAY INTO OUR
MODEL SYSTEMS AND BACK AGAIN.
AND THESE MILESTONES AND
RECOMMENDATIONS ARE REALLY BUILT
OFF WHAT IS AN EXCEEDINGLY
EXCITING TIME IN THE FTD FIELD
WHERE WE'RE GETTING AT NEW
BIOMARKERS, NEW MECHANISMS, NEW
MODELS AND THOSE I THINK ARE ALL
A REFLECTION OF THE SUPPORT THAT
CAME FROM THE LAST SUMMIT'S
RECOMMENDATIONS AND THESE NEW
RECOMMENDATIONS YOU'LL HEAR ARE
REALLY A REFLECTION OF WHERE
WE'RE AT AND WHERE WE CAN GO TO
MEANINGFULLY TREAT THIS
DEVASTATING DISEASE.
I'LL STOP THERE.
WE CAN GO ON TO DR. BOXER.
>> DR. BOXER: THANK YOU FOR
INVITING ME TO SPEAK TODAY.
I'M GOING TO TALK TO YOU ABOUT
THE FIRST AND FIFTH
RECOMMENDATIONS.
HERE'S MY DISCLOSURES.
SO THE FIRST RECOMMENDATION THAT
OUR COMMITTEE CAME UP WITH IS TO
ACCELERATE THE EVALUATION OF
NOVEL FTD TREATMENTS BY BOTH
CAPITALIZING ON EXISTING
EVIDENCE, INFRASTRUCTURE AND
RESOURCES AND ON THE DEVELOPMENT
OF FTD SPECIFIC DESIGNS AND NEW
PREVENTION AND TREATMENT TRIALS
REPRESENTATIVE OF THE
U.S. POPULATION AND IT'S TOP
PRIORITY AND YOU HEARD FROM
LINDE JACOBS JUST NOW HOW
IMPORTANT IT IS TO OUR
COMMUNITIES.
SO IMPORTANT TO MENTION THERE
ARE NO APPROVED TREATMENTS FOR
FTD IN ANY FORM.
AND RIGHT NOW WE'RE LIMITED AS
PHYSICIAN TO USE
NON-PHARMACOLOGIC APPROACHES AND
SYMPTOMATIC TREATMENTS WITH
PSYCHIATRIC MEDICATIONS BUT
DON'T HAVE ANYTHING TO SLOW THE
INEXTRICABLE COURSE OF THIS
DISEASE TOWARDS SEVERE
DISABILITY AND DEATH IN MANY
PEOPLE.
DESPITE THIS AN EXCITING TIME
FOR THE DEVELOPMENT OF TREATMENT
FOR NEURAL DEGENERATIVE DISEASES
AND SEEN IN SOD 1 ALS IT'S
POSSIBLE TO DEVELOP DISEASE
MODIFYING DRUGS TO SLOW
PROGRESSION OF DISEASE AND HAVE
AN IMPORTANT IMPACT OF SURVIVAL.
WE CAN LEARN FROM THE EXPERIENCE
AND BRING THIS TO FTD.
WE'RE ALSO SEEING IN OTHER
DISEASES TAU AND TDP43
TREATMENTS ARE BEING DEVELOPED
TO INTO AND THE CLINIC AND MAY
BE WE CAN ALSO TEST THEM FOR
OVED.
THEY MAY ALSO WORK BETTER THAN
FOR OTHER NEUROGENE RATIVE
DISEASES.
I WANT TO ACKNOWLEDGE THE
SUPPORT FROM THE NATIONAL
INSTITUTE ON AGING AND
NEUROLOGICAL DISORDERS AND
STROKE FOR THE ALL FTD RESEARCH
NETWORK AND THE FTD DISORDERS
REGISTRY WHICH HAS BUILT THE
INFRASTRUCTURE THROUGHOUT NORTH
AMERICA TO SUPPORT THE NEXT
GENERATION OF FTD TRIALS.
THIS IS A BIT OF A BUSY CHART
AND WANT TO ILLUSTRATE TO YOU
USING ALZHEIMER'S DISEASE AND
SOD-1 RELATED ALS AS DISEM
PARTICULARS -- EXEMPLARS AND
IT'S PROVEN VIABLE FOR THE
INDICATIONS.
IN FRONTOTEMPORAL DEMENTIA WHAT
YOU CAN SEE IS THERE ARE REALLY
TWO FORMS.
THOSE LINKED TO GOOD MORNINGS OR
FAMILIAL FTD AND SPORADIC FORMS
OF FRONTOTEMPORAL DEMENTIA
DEGENERATION.
YOU CAN SEE IN THE RIGHT IN BLUE
ARE HOW FAR DRUG DEVELOPMENT HAS
MADE IT IN CLINICAL TRIALS FOR
THESE VARIOUS DIFFERENT FORMS OF
FTD.
AND HOPEFULLY WHAT YOU CAN
NOTICE IT'S THE AVAILABILITY OF
BIOMARKERS AND YOU'LL HEAR ABOUT
THIS IN IN THE NEXT
RECOMMENDATION THAT'S REALLY
ALLOWED THE DEVELOPMENT OF THESE
CLINICAL TRIALS.
AS WE THINK OF THE NEXT FIVE
YEARS OF THE FTD NETWORK WE'RE
FOCUSSING ON PREPARING FOR
CLINICAL TRIALS AND DEVELOPING
MORE BIOMARKERS AND MORE TOOLS
TO DO CLINICAL TRIALS THROUGHOUT
THE FIRST SPECTRUM OF FTD.
SO WHAT OTHER ADVANCES HAVE
HAPPENED SINCE THE LAST SUMMIT?
IMPORTANTLY WE'RE EXCITED THE
FIRST TRIAL RESULTS WERE
REPORTED EARLIER THIS YEAR AND
THIS WAS WITH A SYMPTOMATIC
AGENT THAT REALLY SEEMS TO HAVE
AN IMPORTANT IMPACT ON THE
SYMPTOMS OF BEHAVIORAL VARIANT
FTD.
THIS IS INTRANASAL OXYTOCIN FOR
FTD.
WE'VE ALSO SEEN IN PROGRANULIN
RELATED FTD THAT GENE THERAPY
WITH INTRAFECALLY ADMINISTERED
VIRAL VECTOR PROGRANULIN CAN
CORRECT THE CHEMICAL ASSOCIATED
WITH A PROGRANULIN MUTATION AND
AWAITING THE RESULTS OF THE
TRIALS.
THERE'S OTHER THERAPIES OTHER
WAY.
OUR CLINICAL TRIAL PROGRAMS
UNDERWAY.
AND AGAIN I JUST WANT TO REMIND
YOU THAT WE ARE BUILDING UPON
AND STARTING TO BRING SOME DRUGS
FROM OTHER INDICATIONS INTO FTD
AND I'LL TELL YOU ABOUT THIS IN
A MINUTE.
ONE IDEA AND THIS IS NOW
HAPPENING IN ALS BECAUSE WE KNOW
CERTAIN FORMS OF FTD INDIVIDUALS
HAVE MUTATIONS THAT PUT THEM AT
RISK FOR DISEASE, WE MAY BE ABLE
TO DESIGN PREVENTION TRIALS
WHERE WE INITIATE TREATMENT
PRIOR TO THE ONSET OF SYMPTOMS.
OVER THE PAST YEAR, RESEARCHERS
FROM THE ALS AND FTD COMMUNITIES
HAVE MET TO BEGIN PLANNING THE
FIRST PREVENTION TRIALS OF FTD.
>> TWO-MINUTE WARNING.
>> WE ALSO ARE TAKING THE IDEA
OF PLASTER PROTOCOLS NEW TRIAL
DESIGN AND FUNDED BY THE
NATIONAL INSTITUTES OF HEALTH.
WE'RE BEGINNING LATER THIS YEAR
A NEW PLATFORM TRIAL FOR
PROGRESSIVE SUPER NUCLEAR
POLICY.
THE IDEA OF A PERFORM TRIAL IS A
COST AND RAPID WAY TO TEST NEW
TREATMENT OR TO DEVELOP NEW
TREATMENTS FOR A DISEASE.
WHAT YOU SEE IS THE DESIGN OF
THE NEW PSP TRIAL PLATFORM.
IN THIS TRIAL WE WILL BE TESTING
THREE DIFFERENT DRUGS FOR PSP
SIMULTANEOUSLY.
INDIVIDUALS WILL BE RANDOMIZED
TO ONE OF THE THREE DRUG
REGIMENTS AND WITHIN EACH
REGIMENT, THEY ARE HAVE A 3-1
CHANCE OF RECEIVING THE DRUG.
ONE OF THE EFFICIENCIES IS WE
CAN PULL THE PLACEBO SO WE CAN
TEST DRUGS MORE QUICKLY WITH
FEWER PATIENTS HAVING TO BE
EXPOSED TO PLACEBO AND THIS WILL
CREATE A NEW RESOURCE FOR OTHER
INVESTIGATORS AROUND THE COUNTRY
TO DEVELOP NEW TREATMENTS AND
NEW BIOMARKERS FOR PSP.
NOW I'M GOING TO END WITH THE
FIFTH RECOMMENDATION,
RECOMMENDATION NUMBER 5, WHICH
IS TO UNDERSTAND FTD
MANIFESTATIONS AND HOW DISEASE
FACTORS LIKE HETEROGENEITY AND
SEX AND EXPOSOME AFFECT DISEASE
RISK AND CLINICAL MANIFESTATIONS
AND THE LIVED EXPERIENCE OF FTD.
IT'S IMPORTANT TO MENTION THE
CLINICAL DIAGNOSTIC CRITERIA WE
USED ARE BASED ON STUDIES OF
INDIVIDUALS WITH ACCESS TO
SPECIALIZED CARE MOSTLY IN NORTH
AMERICA AND IN EUROPE.
BUT WHAT WE'RE LEARNING IS THAT
THERE ARE SPECIFIC GENETIC
AFFECTS THAT MAY BE IMPORTANT
FOR CAUSING FTD.
SO FOR THE MAJOR AUTOSOMAL
DOMINANT FOR FAMILIAL GENE WE
THINK THIS AROSE IN SCANDINAVIA
AND PROGRANULIN IN MEDITERRANEAN
FAMILIES AND OTHER CAUSES FOR
EXAMPLE IN EAST ASIA ANXA11
MUTATION A MORE IMPORTANT CAUSE
OF FTD.
THEY'RE ALL IMPORTANT AND
POTENTIALLY IMPORTANT BIOMARKER
TO DEVELOP NEW TLAPIES.
WE ALSO KNOW FOR TAUOPATHIES
THERE'S A GENETIC FACTOR RELATED
TO TAU CALLED THE H2 ALLELE
WHICH PROTECTS BUT IS A RISK
FACTOR FOR ANOTHER DISEASE.
IT'S NOT PRESENT IN ASIAN
ANCESTRIES.
AGAIN, IT'S SOMETHING THAT
SUGGESTS WE SHOULD BE
UNDERSTANDING THE EPIDEMIOLOGY
AND GENETICS OF FTD THROUGHOUT
THE WORLD BECAUSE IT MAY HELP
DEVELOP NEW TREATMENTS.
FINALLY AGAIN, WE ARE
INCREASINGLY COLLABORATING WITH
OUR ALS COLLEAGUES IN THE ALL
ALS RESEARCH NETWORK.
ONE THING WE LEARNED FROM ALS IS
THE EXPOSOME SO THE
ENVIRONMENTAL RISK FACTORS AND
POTENTIALLY TOXIN IN THE
ENVIRONMENT ARE LIKELY TO BE
IMPORTANT FOR ALS AND
INCREASINGLY WE'RE LEARNING IT'S
IMPORTANT FOR FTD SO WE NEED TO
FOCUS ON THIS IN COLLABORATION
WITH OUR ALS COLLEAGUES IN THE
FUTURE.
THANK YOU.
>> THANK YOU.
GOOD AFTERNOON, EVERYONE.
DAVID IRWIN FROM THE UNIVERSITY
OF PENNSYLVANIA.
I'LL BE PRESENTING ON BEHALF OF
THE SUBCOMMITTEE ON THE
ADVANCING FTD BIOMARKERS TO
DISENTANGLE THE FTD CLINICO
PATHOLOGICAL HETEROGENEITY.
TO START, THE VAST HETEROGENEITY
OF FTD FROM A CLINICAL AND
PATHOLOGICAL PERSPECTIVE POSES A
SIGNIFICANT OBSTACLE IN TERMS OF
NOMENCLATURE AND BIOLOGICAL
CLASSIFICATION OF FTD AND THE
DESIGN AND IMPLEMENTATION OF THE
MECHANISTIC AND TREATMENT
STRATEGIES WHICH IS THE FOCUS OF
OUR SUBCOMMITTEE AS WE HEARD
FROM THE POWERFUL TALK BY LINDE.
WHAT THERE'S PHOTO MICROGRAPHS
OF THE ASSOCIATED PATHOLOGIES
CAN BE FOUND MICROSCOPICALLY
POSTMORTEM BY THE PROTEINS THAT
AGGREGATE IN THE BRAIN CELLS AND
THERE'S TAU PROTEINS AND FTLD
AND OTHER PROTEINOPATHIES AND
PRIMARY ALZHEIMER'S DISEASE
CHANGE CAN PRESENT WITH FOCAL
CLINICAL SYNDROME WITHIN THE FTD
SYNDROME.
SO SUPER IMPOSING THE
PATHOLOGIES WE CAN SEE THE MAIN
FTD SYNDROMES COLOR CODED BY THE
FREQUENCY OF THE VARIOUS
PATHOLOGIES BELOW AND WHAT WE
SAW IN A PRIOR SLIDE.
YOU CAN SEE SOME SYNDROME SUCH
AS SUPRAPROGRESSIVE PALSY IS
PREDICTIVE AND THE VARIANT OF
FTD HAS VARIOUS TAU AND
PATHOLOGY COULD BE THE
UNDERLYING CAUSE.
AND WHAT WE SAW FROM DR. KARCH
EARLIER IS THESE SYNDROMES CAN
OVERLAP WITH EACH OTHER.
IT SETS THE RECOMMENDATION TO
ADVANCE THE DEVELOPMENT OF AN
ARRAY OF BIOMARKERS AND DIGITAL
HEALTH TECHNOLOGIES FOR MULTIPLE
USES TO AFFECT THE MAIN GOAL AND
PROBLEM OF THE CRITICAL
IMPORTANCE OF AN EARLY AND
ACCURATE DIAGNOSIS OF FTD.
THIS IS IMPORTANT FOR SCREENING
INDIVIDUALS AT RISK TO OBTAIN
RISKS AND IDENTIFYING BIOLOGICAL
CHANGES TO PREDICT
PHENOCONVERSION TO MANIFEST FTD
AND IN THE CONTEXT OF CLINICAL
TRIALS AND THE IMPORTANCE OF
DISEASE MONITORING, PATIENT
STRATIFICATION TO BIOLOGICAL SUB
GROUPS WITH HOMOGENEOUS BIOLOGY
AND ENHANCE POWER AND TOOLS TO
DETECT TARGET ENGAGEMENT FOR
ASSOCIATED PATHOLOGIES AS THE
OVER ALL RECOMMENDATION.
WE PRIORITIZE LOW COST AND
NON-INVASIVE MODALITIES.
THEY HELP FACILITATE SCREENING
AND DIAGNOSIS, PARTICULARLY IN
REMOTE AREAS THAT MAY NOT HAVE
ACCESS TO TERTIARY CARE TO HELP
EXPAND OUR ABILITY TO DIAGNOSE
EARLY AND REDUCE THE DELAY.
EMPHASIZE NATURAL HISTORY
STUDIES TO UNDERSTAND THE
BIOLOGY OF FTD AND THE
IMPORTANCE OF BRAIN DONATION TO
VALIDATE MARKERS TESTED AND
DEVELOPMENT AND PET IMAGING
MODALITIES TO HELP ACCELERATE
OUR ABILITY TO CROSS VALIDATE.
WE OBSERVED IN ALZHEIMER'S
DISEASE WHERE AUTOPSIES ARE THEN
TO ABLE CROSS-VALIDATE EMERGING
BIO FLUID BIOMARKERS RATHER THAN
TO RELY ON AUTOPSY ALONE.
AS WE MAKE GAINS IN THE AREAS
ACCORDING TO THE RECOMMENDATION
WE CAN PREPARE FOR BIOLOGICAL
FRAMEWORK AND CONSIDER HOW
BIOMARKER CLASSIFICATION EXISTS
WITH EXISTING AND EMERGING
STRATEGIES FOR ALZHEIMER'S
DISEASE AND SYNUCLEIN MYOPATHIES
AND THE INITIATIVE.
TO BRIEFLY HIGHLIGHT SOME OF THE
ADVANCES SINCE THE LAST SUMMIT.
SOME HAVE BEEN IN BLOOD BRAIN
BARRIER BIOMARKERS AND
NEUROFILAMENT LIGHT CHAIN TO
DETERMINE EARLY BIOLOGICAL
CHANGES FOR INDIVIDUALS AT RISK
OF DEVELOPING CLINICALLY
MANIFESTING FTD AND UNDER GO
QUALIFICATIONS FOR THE USE IN
THE CONTEXT OF FAMILIAL FTD.
IN TERMS OF DIAGNOSING BIOLOGY
AND IDENTIFYING THOSE LIKELY TO
HAVE TAU OR TPD43 AND COMBINING
FILAMENT LIGHT WITH OTHER
BIOMARKERS SHOW PROMISING EARLY
RESULTS.
PHOSPHORYLATED TAU EPITOPES TO
DETECT PATHOLOGY IN THE CONTEXT
OF FTD WHICH IS IMPORTANT AND
ALSO IMPORTANT TO NOTE THE NEED
FOR FTD SPECIFIC BIOMARKERS TO
COMPLEMENT THESE IN THE ERA OF
AMYLOID THERAPIES.
NEWER TECHNIQUES SUCH AS MASS
SPEC TROSSCOPY TO LOOK AT
PRAGMENTS OF TAU AND PROTEOMIC
TECHNIQUES AND DERIVED EXTRA
CELLULAR VESICLES AND PET
TRACERS FOR FTLD FORMS OF TAI
AND TDP43 ARE UNDERWAY.
AND THE WAY TO INTEGRATE
BIOLOGICAL INDEXES AND
BIOMARKERS AND BUILD STATISTICAL
MODELS OF PROGRESSION ARE AN
IMPORTANT ADVANCE AND HELP GUIDE
CLINICAL TRIAL END POINTS AS
WELL.
A COMPLEMENTARY RECOMMENDATION
IS RECOMMENDATION 7 SO IDENTIFY
THE SHARED AND DISPARATE
MECHANISMS UNDERLYING THE
CLINICAL AND MOLECULAR SUB TYPES
INCLUSION OF CO-PATHOLOGIES AT
THE MOLECULAR, CELLULAR, CIRCUIT
AND TISSUE LEVELS.
THIS RECOMMENDATION IS FOCUSSED
ON COMPARATIVE STUDIES USING
HUMAN TISSUE AND DATA AND
TRANSLATE THE MECCISTIC STUDIES
WE'LL HEAR ABOUT IN CLINICAL
APPLICATION WITH AN EMPHASIS ON
IMPROVING AND INFORMING
RECRUITMENT STRATEGIES TARGETING
MOLECULAR MECHANISMS OF FTD.
FOR EXAMPLE COMPARING FEATURES
WITH FTD SUB TYPES WITH THE
COMMUNITY TO UNDERSTAND THE
BASIS FOR THE VARIOUS CLINICAL
EXPRESSION OF TDP43
PROTEINOPATHIES.
AND MORE CLEAR MECHANISMS AND
HOW THEY MAY RELATE TO THE
BIOLOGY OF SPORADIC OVEDs IS
ANOTHER HIGH PRIORITY.
AND PARTS OF THE BRAIN THAT
CONTRIBUTE TO LANGUAGE AND
SOCIAL BEHAVIOR AND STUDY THIS
IN THE CONTEXT OF HUMAN DISEASE
WE PRIORITIZE STANDARDIZING NEW
APPROACHES OF PATHOLOGY AND
INTERROGATE HUMAN BRAIN TISSUE
AND HOW TO INTEGRATE THESE TO
STUDY THE BIOLOGY IN THE CONTEXT
OF THE HUMAN BRAIN CONNECTOME
AND INTEGRATE OTHER MODEL
SYSTEMS FROM HUMAN DERIVED DATA
AND TISSUES.
THE OVER ALL ARCHING GOAL OF THE
PRIORITY WHICH IS A LONGER TERM
GOAL IS TO IDENTIFY THE NEURAL
SUBSTRATES AND MODULATING FACTOR
FOR DIFFERENT FTD SUB TYPES TO
IDENTIFY THERAPEUTIC TARGETS AND
OPTIMIZE THERAPEUTIC CLINICAL
TRIAL RECRUITMENT STRATEGIES.
I'LL BRIEFLY SUMMARIZE EXAMPLES
OF RECENT BIOLOGICAL SUB TYPES
DEPICTED ARE FINDING OF TDP43
TYPE C HAVING CONSISTENT ANXA11
PROTEINOPATHY AND A UNIQUE
FEATURE IS FILAMENT STRUCTURE.
AND EXCITING WORK LOOKING AT
CRYPTICEX -- CRYPTIC AM AXON
AND FLUIDS IN THE VARIOUS FORMS
OF PROTEINOPATHIES SHOW
POTENTIAL MECHANISMS AND FURTHER
UNDERSTANDING OF THE CELLULAR
AND TRANSCRIPTIONAL SUB TYPES
AND HOW THEY RELATE ARE
IMPORTANT.
USING DIGITAL PATHOLOGY TO
INTERROGATE BRAIN TISSUE AND
LOOKING AT CLINICALLY DEFINED
GROUP AND BEHAVIORAL VARIANT OF
FTD WE CAN STUD
NEURODEGENERATION IN BRAIN
PATTERNS AND CONNECTIVITY AND
FINALLY FINDINGS OF PROGRANULIN
AND HAPLO INSUFFICIENCY SUGGEST
AD/ADRD AND I'D LIKE TO THANK
OUR PATIENTS AND FAMILIES WHO
PARTICIPATE IN RESEARCH.
>> I'M BACK.
THIS IS CELESTE KARCH IN
ST. LOUIS AND I'LL BE SHARING
OUR RECOMMENDATIONS AND MODELS
AND MY DISCLOSURES ARE HERE.
I BRING YOU BACK TO THIS IDEA OF
THE WRESTLING WITH THE UMBRELLA
TERM WHILE KNOWING THERE'S BIG
CLEAR GENETIC CAUSE DIFFER
ACROSS THE DIFFERENT FTD SUB
TYPES AND AMONG THE NON-GENETIC
FORMS THE SPORADIC FORMS THERE'S
DIFFERENT AS RESPECTS OF
MOLECULAR PATHOLOGY THAT AFFECTS
THE PHENOTYPE WE SEE WHEN
PATIENTS COME REPORT IING ISSUE.
AS WE THINK OF MODELLING
DISEASE, PERHAPS THE TRADITIONAL
THOUGHT IS SORT OF TO MODEL THE
CELL BASIS OF DISEASE AND WHILE
THAT'S IMPORTANT THE COMMITTEE
WANTED TO EMPHASIZE THAT MODELS
REALLY WILL BE VALUABLE TO
CAPTURE EVERY LEVEL OF THE
ASPECTS OF FTD FROM THE GENETIC
AND PATH LOGIC FEATURES AND ALSO
THINKING ABOUT WAYS TO
EFFECTIVELY MODEL THE CLINICAL
PRESENTATIONS.
I WANT TO SHOW THE RECENT WORK
IN THE LITERATURE THAT SHOW THE
VALUE OF MODELS AND THE VALUE OF
INTEGRATIVE MODELS AND I
APOLOGIZE FOR THE BLURRINESS OF
THIS PICTURE AND WHAT'S EMERGED
FROM STUDIES FROM TWO
INDEPENDENT ROLES IS THERE'S A
ROLE FOR TDP43 IN ALTERING
SPECIFIC TRANSCRIPTS THAT
PRODUCE WHAT IS TERMED CRYPTIC
AXON WE HEARD FROM DR. IRWIN
THAT CAN TELL US ABOUT THE
BIOLOGY OF DISEASE AND
POTENTIALLY SERVE AS BIOMARKERS.
WHAT THE COMPANION PAPERS SHOWED
US IS WE CAN GET AT THE IDEAS
THROUGH VERY DIFFERENT
APPROACHES TO MODELS.
IN THE FIRST STUDY STEM CELL
MODELS WERE USED WHERE A WELL
CHARACTERIZED POTENT STEM CELL
LINE WAS MANIPULATED TO REMOVE
TDP43 AND SUBSEQUENT ANALYSIS OF
THE NEURONS REVEALED THIS CHANGE
IN IN A PARTICULAR GENE IN 13A
WHICH HAD ALTERED CRYPTIC AXONS.
IN A PARALLEL APPROACH
INVESTIGATORS WERE ABLE TO TAKE
HUMAN BRAIN TISSUE FROM PEOPLE
WHO HAVE FTD AND WERE ABLE TO
ISOLATE NEURONS FROM THE BRAINS
AND ASK WHAT'S THERE, WHAT'S
DIFFERENT AND HOW DOES THAT
COMPARE TO NORMAL CONTROL BRAINS
AND AGAIN THEY WERE ABLE TO SEE
THIS CHANGE IN A GENE ONC 13A IN
GENERATIONS IN THE SPLICING.
SO THIS REALLY HIGHLIGHTED THE
ADDED VALUE OF MOILING FROM
DIFFERENT PERSPECTIVES AND
DIFFERENT LEVELS.
IN DISCOVERY OF FUNDAMENTAL
MECHANISMS AND TO REVEAL NEW
BIOMARKERS AND THERAPEUTIC
TARGETS.
ANOTHER AREA OF MASSIVE GROWTH
HAS BEEN ABLE TO LEVERAGE CELLS
IN WAYS AND WHILE THE PRIOR
STUDY USED SYSTEM MODELS TO
REMOVE A GENE, THERE ARE EFFORTS
FOCUSSED ON TAKING CELLS FROM
PEOPLE WHO CARRY MUTATIONS THAT
CAUSE DISEASE LIKE THOSE LINDE
DESCRIBED AND TO MAKE THEM INTO
CELL TYPES IN THE BRAIN SUCH AS
BRAIN ORGANOIDS THAT DEVELOP IN
A MANNER THAT LOOKS LIKE THE
DEVELOPING BRAIN.
AND THEN TO TRACK HOW THESE
CHANGES OCCUR ORE HOW SPECIFIC
CHANGES OCCUR OVER TIME AND HOW
THEY COMPARE TO CELLS WHERE THE
GENETIC MUTATION HAS BEEN
CORRECTED.
ULTIMATELY THE EFFORTS HAVE LED
TO A REALLY BEAUTIFUL SET OF
PHENOTYPES THAT ARE CHANGING
OVER TIME AND CAN BE TARGETED.
IN ADDITION TO THAT THERE'S A
LOT OF GROUPS THAT HAVE MADE
HUGE HEADWINDS IN MAKING
FIBROBLASTS FROM PEOPLE WHO
CARRY DIFFERENT MUTATIONS OR ARE
CLINICALLY DIAGNOSED WITH FTDs
AND CONVERT THOSE FROM A SKIN
CELL INTO A NEURON AND THOSE ARE
ENABLED US TO BE ABLE TO BEGIN
TO VISUALIZE PROTEIN AGGREGATS
IN A WAY WE HAVEN'T BEFORE.
THIS ALLOWS US TO UNDERSTAND THE
BIOLOGY AND AGGREGATES IN WHICH
THEY ARE FORM AND HAVE TOOLS
NOW, CELL LINES WE CAN SCREEN
FOR COMPOUNDS THAT BLOCK OR
REDUCE THE FORMATION OF THE
AGGREGATES THAT CAN BE MOVED
INTO TRIALS.
WITH OF THE MANY EXAMPLES I'VE
SHOWN ARE REALLY ON EFFECTS
WITHIN NEURONS AND THE FTD FIELD
IS SEEING A LEVEL OF COMPLEXITY
ACROSS THE CELL TYPES THAT ARE
FOUND IN THE BRAIN THAT ARE
LIKELY CONTRIBUTING TO FTD AND
MODELS ARE BEGINNING TO POINT US
IN THIS DIRECTION BUT REMAINS AN
IMPORTANT AREA OF GROWTH AND
EMPHASIS IN THE COMING YEARS.
RECOMMENDATION 3 IS FOCUSSED ON
A NEED TO ESTABLISH AND VALIDATE
PRECLINICAL AND TRANSLATIONAL
MODELS BECAUSE WE THINK THESE
ARE ESSENTIAL TO UNDERSTAND
BASIC CELLULAR MECHANISM AND TO
GET TO THERAPEUTICS.
AND WHEN WE TALK ABOUT MODELS I
WANT TO EMPHASIZE THAT WE'RE
DEFINING MODELS QUITE BROADLY.
IN FACT BECAUSE OUR MODELS ARE
ONLY AS GOOD AS THE DISEASE THAT
WE'RE ABLE TO UNDERSTAND.
WE NEED TO UNDERSTAND WHAT THE
PATIENT POPULATION LOOKS LIKE
AND HOW THE DIFFERENT SUB TYPE
MANIFESTING IN THE BRAIN AND IN
OTHER FEATURES LIKE IN IMAGING
AND FLUID BIOMARKERS AND TAKING
AN UNBIASSED APPROACH
INTEGRATING A.I. TO DEFINE THE
WAYS IN WHICH THE GROUPS ARE
SIMILAR AND DISCREPANT SO OUR
MODELS IN CELLS AND IN MICE CAN
ULTIMATELY REFLECT THOSE
INDIVIDUALS.
IN ORDER TO DO THIS WE REALLY
SEE A NEED TO WORK IN
PUBLIC-PRIVATE PARTNERSHIPS TO
AGGREGATE THE DATA AND HARMONIZE
THE RESOURCES AND REALLY ENABLE
OUR UNDERSTANDING OF DISEASE AND
IN DOING THIS, WE THINK THAT
THERE'S A SPECIAL NEED TO ALSO
FOCUS ON MODELLING THE SPORADIC
FORMS OF DISEASE, WHICH IS
PRESENTED AS A MAJOR CHALLENGE
IN THE PAST.
SO I'LL STOP THERE AND THANK
EVERYONE FOR THEIR ASSISTANCE IN
DEVELOPING THESE
RECOMMENDATIONS.
>> THANK YOU.
I APPRECIATE THE OPPORTUNITY TO
PRESENT HERE AT THIS ADRD
SUMMIT.
I'LL TALK ABOUT RECOMMENDATION
NUMBER SIX WHICH IS PRIORITY
THREE AND THERE'S A LOT OF
WORDS.
RECOMMENDATION SIX IS TO
ELUCIDATE THE CELL AUTONOMOUS
AND UNDERSTANDING SELECTIVELY
VULNERABILITIES AND THERE BE
IDENTIFYING NEW TARGETS FOR
THERAPEUTIC DEVELOPMENT.
THE BULLETS ARE BASICALLY AN
OUTLINE OF HOW I'M GOING TO GO
THROUGH THIS BUT IT'S IMPORTANT
FOR FOLKS TO KNOW AS DR. KARCH
PRESENTED THE BRAIN REGIONS
VULNERABLE AND FTD ARE
DISTINCTIVE FROM ALZHEIMER'S
DISEASE AND OTHER ALZHEIMER'S
DISEASE-RELATED DIMENTIAS AND
THEY COME IN GLIA AND IMMUNE
CELLS AND ENDOTHELIAL CELLS I'LL
UNPACK IN A MOMENT.
IF WE CAN GAIN DEEPER
MECHANISTIC INSIGHT WHETHER
THEY'RE STARTING OR PROGRESSING
IN NEURON OR NON AUTONOMOUS OR
NON-NEURONAL CONTRIBUTIONS WILL
HELP DEVELOP BETTER THERAPIES.
THE PROCESSES THAT INVOLVE
NEURONS AND OTHER CELLS
INCLUDING NEURAL INFLAMMATION
AND SENESCENCE AND VASCULAR
DYSFUNCTION, ETCETERA.
THE HEADLINE HIERE IS WE KNOW
THROUGH THE COURSE OF SCIENTIFIC
RESEARCH AND EFFECTIVE THERAPIES
DEVELOPED TO DATE IF WE BETTER
UNDERSTAND DISEASE MECHANISMS
WE'RE GOING TO GET BETTER
THERAPIES AND TO THIS I'LL ADD
WHAT DR. IRWIN TALKED ABOUT IS
BETTER BIOMARKERS AND DR. BOXER
SAID WE NEED THEM TO DO BETTER
THERAPIES.
THE BRAIN REGIONS AFFECTED ARE
THE FRONTO TEMPORAL LOBES AND
EACH BRAIN REGIONS HAVE
DIFFERENT CELLS.
NEURON THERE AND THERE'S ASTRO
GLIA WHICH ARE THE PARENTS OF
NEURONS, THE COUSINS OF NEURONS
OR SIBLINGS RATHER THAN JUST A
GLUE CELL.
MICROGLIA WHICH ARE IMPORTANT TO
THE IMMUNE SYSTEM AND APPENDMEL
CELLS AND ADREN DROE SITES AND
MAY CONTRIBUTE TO THE DISEASES
AND NEED TO BE STUDIED AND
UNDERSTOOD.
ALSO THE GENETICS OF THE GENES
FOUND TO BE ASSOCIATED WITH FTD
ARE NOT ALWAYS EXPRESSED IN THE
NEURONS.
THE VAST MAJORITY ARE EXPRESSED
IN MOST CELLS.
SOMETIMES FOR PROGRANULIN IT'S
EXPRESSED MORE IN MICROGLIA THAN
IN NEURONS AND TO TAKE AN
EXAMPLE FROM ALZHEIMER'S DISEASE
THERE'S GENES SUCH THAT ARE OATH
EXPRESSED IN MICROGLIA AND NOT
IN NEURONS AT ALL.
IT'S IMPORTANT AS WE THINK ABOUT
THE GENETICS WE THINK ABOUT
WHERE THE GENE MUTATION IS
ACTING.
IN ADDITION, I THINK FOR A LONG
TIME I THOUGHT THE AGGREGATES
IMPLICATIONS THE TDP43 AND TAU
AGGREGATE ONLY FOUND IN NEURONS
WE KNOW NOW IN SUPRANUCLEAR
PALSY YOU CAN SEE THEM IN ASTRO
GLIA AND ADRENDOCYTES AND WE AS
WE UNDERSTAND DISEASE MECHANISMS
IT WILL LEAD TO APPROPRIATE
THERAPIES THAT PERHAPS TARGET
MORE THAN NEURONS.
AS A CORRELATE WHAT I SHOULD
HAVE ADDED IS AS WE UNDERSTAND
MECHANISM, WE CAN BETTER
UNDERSTAND WHAT WE NEED TO
DEVELOP AS BIOMARKERS.
SO TOGETHER THESE MAKE UP THE
CELL AUTONOMOUS VERSUS
NON-AUTONOMOUS MECHANISMS.
SO SELECTIVE VULNERABILITY IS
THE CONCEPT CERTAIN NEURONS OR
CERTAIN CELLS IN DIFFERENT BRAIN
AFFECTED IN DIFFERENT DISEASES.
THIS TERM HAS BEEN AROUND FOR
OVER 20 YEARS.
I REMEMBER READING REVIEWS ABOUT
THIS IN THE EARLY 2000s BUT THE
ADVANCES WE HAVE MADE HAVE COME
FROM UNDERSTANDING THERE'S A LOT
OF GENETIC MUTATIONS ASSOCIATED
WITH THE DIFFERENT DISEASES.
SOMETIMES THEY'RE OVERLAPPING,
SOMETIMES THEY'RE NOT AND
THEY'RE HIGHLIGHTED IN THE
PURPLE BOX.
IN ADDITION, WE NOW KNOW THAT
THERE ARE DIFFERENT CELL TYPES
THAT MAY BE AFFECTED, FOR
EXAMPLE, LAYER TWO VERSUS LAYER
SIX IN BRAIN STEM VERSUS
CORTICAL AND THEY'VE BEEN VERY
IMPORTANT IN UNDERSTANDING
SELECTIVE VULNERABILITY.
THE BOTTOM LINE IS WE DON'T
UNDERSTAND WHAT MAKES CERTAIN
BRAIN REGIONS AND CELL TYPES
VULNERABLE.
SO THIS IS A KEY AREA WE NEED TO
PUSH FORWARD IN TERMS OF
DEVELOPING INSIGHT.
AMONG THE REASONS FOR MOVING
BEYOND THE NEURON CENTRIC VIEW
ARE THE DISTRIBUTION OF
AGGREGATES, THE RELATIVE GENE
EXPRESSION AND CELL
NON-AUTONOMOUS MECHANISMS I'VE
MENTIONED.
THESE THREE THINGS ALSO LEAD US
TO FOCUS ON DIFFERENT PROCESSES
FOR INVESTIGATION.
SO NEURAL INFLAMMATION WE KNOW
IS A BIG CONTRIBUTOR IN FTD
BECAUSE WE SEE EXPANSION OF
GLIAL CELLS AND THERE'S THE
INABILITY TO CLEAR PROTEINS AND
LIPID METABOLISM IS IMPORTANT
AND METABOLISM AND SENESCENCE
AND THE SPREADING OF TOXIC
PROTEINS AND VASCULAR
DYSFUNCTION AND APOE
MUTATIONS -- VARIANTS LEADING TO
INCREASED RISK FOR FTD ALONG
WITH ALZHEIMER'S DISEASE AND
SLEEP DYSFUNCTION, STRESS AND
AGING WHICH IS THE SINGLE MOST
IMPORTANT RISK FACTOR FOR ALL
THE NEURAL DEGENERATIVE
DISORDERS.
SO, THE NEXT QUESTION IS WHAT IS
NEEDED TO ADVANCE THE
RECOMMENDATION?
YOU CAN GO AHEAD AND PRESS
THROUGH THESE.
FIRST IS CELL BIOLOGICAL TOOLS
AND APPROACHES.
BY CELL BIOLOGICAL I MEAN THESE
APPROACHES THAT WE DON'T YET
KNOW AND MOST OF US DOESN'T KNOW
WE NEEDED SMARTPHONES AND CELL
PHONES AND NOW WE CAN'T LIVE
WITHOUT THEM AND IN TERMS OF
SCIENTIFIC TOOLS ARE THE CRISPR
EDITING AS WELL AS CRISPR
INHIBITION AND ACTIVATION THAT
HAVE NOT JUST BEEN THOUGHT OF IN
TERMS OF THERAPEUTIC APPROACHES
BUT TRANSFORMED OUR ABILITY TO
DO SCIENCE IN THE LAB.
AS DR. KARCH TALKED ABOUT THE
STEM CELL AND ORGANOID MODELS
ARE INCREDIBLY IMPORTANT AND
AS
ASEMBLOIDS ARE BEING DEVELOPED.
THE ANIMAL MODELS WE HAVE IN C.
ELEGANS AND MICE ARE IMPORTANT
AND BECAUSE FTD AFFECTS HIGHER
BRAIN FUNCTIONS SUCH AS SOCIAL
COGNITION, ETCETERA, IT'S
IMPORTANT TO HAVE MODELS WHERE
WE CAN STUDY BEHAVIORS AND ONE
EXAMPLE I LOVE TO SITE IS THE
PRAIRIE FOLDS WHICH FALL IN LOVE
AND EXHIBIT PAIR BONDING FOR A
LIFE TIME IS IMPORTANT FOR
UNDERSTANDING DISEASES AND
MODELS TO STUDY AGING IN.
CELL TYPE SPECIFIC OMICS ARE
IMPORTANT.
I THINK RNA SEQ HAS BEEN AT THE
FOREFRONT AT FIGURING OUT WHAT
CELLS ARE EXPRESSING WHAT BUT
PROTEOMICS ARE ALSO GOING TO BE
IMPORTANT.
CELL TYPE SPECIFIC PROTEOMICS.
LIPID OMICS, METABOLOMICS ARE
ALL REALLY IMPORTANT.
IF WE HAVE THE DATA WE NEED DATA
ANALYSIS AND SHARING PIPELINES
TO DECONVOLUTE THE DATA TO FIND
THE SECRETS THE DATA IS TRYING
TO TELL US.
REALLY IMPORTANTLY IT IS
IMPORTANT TO KEEP BRINGING A
PIPELINE OF SCIENTISTS IN
TRAINING... THE NIH HAS BEEN A
HUGE PROPONENT AND PUBLIC
PRIVATE PARTNERSHIP WHICH
SUPPORT THIS AND ADVOCATES SUCH
AS JACOBS. TOGETHER, ALL THESE
THINGS CAN LEAD US TO
MECHANISTIC INSIGHTS, NEW
TARGETS, NEW BIO MARKER,
THERAPIES IN PRECISION MEDICINE.
WITH THAT, I'LL FINISH.
>> ALL RIGHT. HI, EVERYONE.
I'M BETH FROST, DIRECTOR OF
SENSORS FOR ALZHEIMER'S BROWN. I
WILL COVER TWO ISSUES INCLUDING
MODIFIERS OF FRONTAL TEMPORAL
DEMENTIA RISK AND ACCELERATING
THERAPEUTIC DISCOVERY. WE
RECOMMEND TO DEFINE GENETIC AND
MOLECULAR MODIFIER OF GENETIC
AND SPORADIC FTD INCLUDING
COHORTS OF THE U.S. POPULATION
ALONG WITH MOLECULAR AND
CELLULAR MECHANISMS OF ACTION.
NEXT SLIDE. SO OVER HALF OF
FRONTAL TEMPORAL DEMENTIAS ARE
SPORADIC, MEANING THEY DON'T
FALL WITHIN A FAMILY THAT IS
AFFECTED. THERE ARE ABOUT 15% OF
FAMILIAL CASE WHERES WE KNOW S
/* -- CASES WHERE WE KNOW WHAT
IS CAUSING THE FTD. THESE ARE
CAUSED BY THREE MUTATIONS. THIS
EXPANSION AND C972 MUTATION AND
PROGRANULIN AND GENE THAT EN
COALS TA, MAP T, WHICH AFFECTS
WENDY AND HER GROUP. THEIR GENES
HAVE BEEN IDENTIFIED THAT CAUSE
ABOUT -- CONTRIBUTE TO THAT 15%
OF FTD CAUSED BY A KNOWN
MUTATION. HOWEVER A BIG CHUNK OF
FAMILIAL CASES ARE DUE TO
VARIANTS AND MUTATIONS WE DON'T
KNOW WHAT THEY ARE OR
POTENTIALLY OTHER FACTORS THAT
MAY UNDERLIE DEVELOPMENT OF FTD
WITHIN A CERTAIN FAMILY. SO WE
NEED TO UNDERSTAND HOW THESE
MUTATIONS ACTUALLY DRIVE DISEASE
AT A MOLECULAR AND CELLULAR
LEVEL AND UNDERSTAND WHAT CELL
TYPES ARE AFFECTED BY THESE
MUTATIONS. DR. GA NICELY COVERED
THE IMPORTANCE OF UNDERSTANDING
WHENEVER THESE DEPOSIT WHAT CELL
TYPES THEY ARE DEPOSITING IN AND
HOW THAT MIGHT AFFECT
NEIGHBORING CELLS. SO
UNDERSTANDING WE ARE EACH A
CONSTELLATION OF GENES, SOME OF
WHICH MAY EXACERBATE OR PROTECT
AGAINST DISEASE-CAUSING
MUTATIONS WE NEED TO UNDERSTAND
HOW DIFFERENT THE BACKGROUNDS
AFFECT THE RISK AND RESILIENCE
FOR INDIVIDUALS CARRYING THESE
MUTATIONS. GOING THROUGH THE
SLIDES, AHEAD OF ME THERE, BUT
FOR -- IN UNDERSTANDING HOW
GENETIC BACKGROUND AFFECTS RISK
WE NEED TO KNOW HOW THESE
MUTATIONS IN DIFFERENT POP LAYS
AFFECT RISK, AGE OF ONSET AND
HOW QUICKLY THESE PROGRESS. WE
NEED TO SUPPORT AND DEVELOP CORE
SERVICES INCLUDING GENE KNOW
TYPING AND CELLULAR MODELS AND
BUILD AND SUPPORT COHORTS FOR
INDIVIDUAL WHO'S CARRY THESE. AN
EXAMPLE HOW THIS WORKS WELCOMES
FROM THE ALZHEIMER'S DISEASE
FIELD, MENTIONED IN THE INTRO.
WHILE MUTATIONS INCREASE 1,
NORMALLY SUFFICIENT TO CAUSE
ALZHEIMER'S, A STUDY OF COHORT
IN COLUMBIA WHO CARRY A MUTATION
THAT WOULD NORMALLY CAUSE
ALZHEIMER'S FOUND A SUBSET WERE
RESISTANT TO DEVELOPING
ALZHEIMER'S, DESPITE CARRY ING
THAT MUTATION. SO IT WAS
DISCOVERED THESE PEOPLE CARRY
THE CHRIST CHURCH MUTATION THAT
PROTECTS THEM. THIS TYPE -- WE
NEED MORE THOF WORK IN FRON-- M
WORK IN FRONTAL TEMPORAL WORK AS
WELL. UNDERSTANDING WHY THERE IS
THIS HUGE FRACTION WHERE THEY
DON'T RUN IN FAMILIES, OCCUR
SPORADICALLY, WE NEED TO FOCUS
ON UNDERSTAND ING WHAT
ENVIRONMENTAL FACTORS MIGHT BE
CONTRIBUTING THERE. NEXT SLIDE
SO RECOMMENDATION 8 IS PRIORITY
4 FOCUSING ON PRE-CLINICAL
DISEASE MODIFYING -- BACK ONE
SLIDE, I DON'T HAVE IT
MEMORIZED. IN FRONTAL TEMPORAL
DEMENTIA BUT DEF RAJING KNOWN
PATHWAYS OR MECHANISM-AGNOSTIC
APPROACHES SUCH AS HIGH
THROUGHPUT SCREENING. WE KNOW
THE PROTEINS THAT DEPOSIT IN
FRONTAL TEMPORAL DEMENTIA. THESE
ARE TA, TDP43 AND FUS. THESE ARE
TARGETS WHETHER TAN BO IT /* AN
UNDERSTANDING OF FACTORS THAT
MAY CONTRIBUTE TO DEPOSITION OF
SOME OF THESE PATHOGENIC PREE
PROTEINS FOR DEVELOPMENT. WE ARE
BEGINNING TO UNDERSTAND HOW
THESE ARE CAUSING NEURAL
DENEUDENEWURO
DENEURODEGENERATION AND NEEDS TO
UNDERSTAND ACROSS THE SPECTRUM,
WE NEED TO RECOGNIZE THAT
INDIVIDUALS ARE MAYBE NOT GOING
TO BE -- THEY GOING TO NEED
DIFFERENT DRUGS DEPENDING WHICH
STAGE THEY ARE IN. WE NEED TO BE
ABLE TO DIAGNOSE PEOPLE AND KNOW
WHERE THEY ARE IN THE SPECTRUM
SO WE CAN DEVELOP -- GIVE THEM
THANK YOU, MR. PR
THERAPEUTICS FOR THE STAGE THEY
ARE IN AND UNDERSTAND HOW THEY
AFFECT DIFFERENT CELL TYPES, AS
DR. GAL MENTIONED, NEXT SLIDE. A
EXAMPLE HOW THIS HAS WORKED
WELL. SO WE AND OTHERS HAVE
FOUND THAT PATHOGENIC FORMS OF
TA AND TDP43 DRIVE
NEURODEGENERATIVE THROUGH
ACTIVATION OF RETRO TRANSPOSONS,
MAKE UP ABOUT 45% OF THE HUMAN
GENOME. WHEN THESE ELEMENTS GET
ACTIVATED THROUGH TA OR TDP43
THEY ARE TRANSCRIBED INTO RNA,
SOMETIMES PROTEIN-CODING. THOSE
PROTEINS CAN ACT TO MAKE A NEW
COPY OF D.N.A. AND THAT CAN
INSERT SOMEWHERE ELSE IN THE
GENOME. OVER THE COURSE OF RETRO
TRANSPOSON ACTIVATION THEY CAN
JUMP, REFERRED TO AS JUMPING
GENES. THE PRODUCTS MADE OVER
THE COURSE OF THE ACTIVATION CAN
LOOK LIKE A VIRUS TO THE CELL.
WE FOUND THAT AN ANTI VIRAL
NORMALLY PRESCRIBED FOR HIV CAN
BLOCK THE TRANSCRIPTION OF
R.N.A. INTO D.N.A. WE FOUND THIS
WAS EFFECTIVE IN TA MODELS, FLY
MODELS, TEL O
DIFFERENT MOUSE WORKS. WE
FINISH ED A PHASE 2 TRIAL AT UT
HEALTH BEFORE I MOVED TO BROWN
FOR ALZHEIMER'S DISEASE USE ING
THIS HIV DRUG. A DIFFERENT HIV
DRUG IS TESTED AT BROWN IN
ALZHEIMER'S. BECAUSE THIS IS A
TA-BASED IT CAN BE EXPANDED TO
NON-ALZHEIMER'S TELOPATHY. A
RECENT PHASE 2A WAS FINISHED FOR
HIV AND PARTICIPANTS WITH SUPER
NUCLEAR PAL SI WITH GOOD
RESULTS. SIMILARLY FINISHED A
TRIAL IN ALSFTD AND PLANNING FOR
PHASE 3. THOR LIGHTHOUSE TRIAL
IN ALS HAD NICE RESULTS FROM
PHASE 2, IN A PHASE 3 OPEN
ROLLOVER BASED ON RESULTS FROM
THAT TRIAL. THIS IS ONE EXAMPLE
OF THERAPEUTICS THAT TARGET
INFLAMMATION ASSOCIATED WITH
DEMENTIA AND RECOMMEND OTHER
POTENTIAL KNOWN TARGETS BE
PURSUED IN PRE-CLINICAL AND
CLINICAL STUDIES AS WELL AS
APPROACHES AGNOSTIC AS HI
THROUGHPUT COMPOUND SCREENING.
BACK TO THE ORGANIZERS.
>> I JUST WANT TO THAN TK FTD
COMMITTEE MEMBERS WHO WERE
REALLY ESSENTIAL IN DEVELOPING
THESE RECOMMENDATIONS AND WHO
SOUGHT ADVICE OF PATIENT
POPULATIONS, OF ADVOCATES, OF
THEIR COLLEAGUES AND THANK YOU
ALL. LOOKING FORWARD TO THE
QUESTIONS.
>> RAISE YOU HAND IF YOU'D
LIKE TO ASK A QUESTION. WE ARE
MONITORING QUESTIONS COMING IN
LIVE FROM VIDEO CASTS. OUR FIRST
QUESTION HAS A HAND RAISED,
GENE.
>> YES, THANK YOU SO MUCH.
THANK YOU, EVERYONE, FOR
SPEAKING. I WANT TO ZERO IN ON
DRUG DISCOVERY AND USE
THERAPEUTICS TO PREVENT OR TREAT
FTD. THE DOCTOR HAD A NICE CHART
TO CONSIDER THIS. IF WE CONSIDER
THIS, WE SHOULD ALSO REALLY
CONSIDER THE NOT DRAMATIC AFFECT
OF RELASAL IN ALS. THOSE NOT
AWARE, 72, MY FAMILY SIMILAR
PACTED BY, THE MOST COMMON CAUSE
OF GENETIC FTD AND GENETIC ALS.
IF SOMEBODY HAS BFCT AND GET
DIAGNOSED ALS THEY WILL BE
PRESCRIBED (?) AS
DISEASE-MODIFYING THERAPY. YET
IF THE CAUSE OF THE DISEASE IS
CNR72 AND WORKS FOR ALS, WHY
WOULDN'T IT WORK FOR FTD. IF WE
ARE CONSIDERING
DISEASE-MODIFYING THERAPIES WE
SHOULD -- WHY ARE WE NOT
CONSIDERING RENASAL. ALSO I SO
APPRECIATE EVERYONE'S ATTENTION
THAT THERE'S DRUGS IN TRIAL FOR
ALS THAT MIGHT BE USEFUL IN FTD.
JUST TO BRING IT BACK, HOW ARE
WE GOING TO ENSURE THE CRYPTIC
AXON ANTI OLIOGO NUCLEOTIDE
THERAPIES IN TRIALS FOR ALS OR
SOON TO BE IN TRIAL, SHOW AFFECT
IN ADVANCED ALS, HOW WILL WE BE
SURE THOSE DRUGS MIGHT ONLY WORK
EARLIER IN THE DISEASE AND
PEOPLE WHO ARE PREDISPOSED TO
DEVELOPING ALS AND FTD. SO IT IS
NOT JUST THAT WE ARE WILLING TO
SEE A HOME RUN BUT HOW DO WE
GUARD AGAINST THESE DRUGS
WORKING EARLIER IN THE DISEASE
AND WITH URGENCY BECAUSE IF WE
DISCARD THOSE THERAPIES WITHOUT
AFFIRMING THEY MIGHT ONLY WORK
EARLIER, THEN HOW WILL WE EVER
KNOW? SO THANK YOU SO MUCH.
>> ADAM, WOULD YOU LIKE TO
RESPOND?
>> YEAH, WELL THANK YOU,
JEAN. THANK YOU FOR YOUR MANY
CONTRIBUTIONS TO EVERYTHING I
TALKED ABOUT FOR THOSE WHO DON'T
KNOW, THIS HAS BEEN PART OF
THESE DISCUSSIONS AND COME UP
WITH MANY FANTASTIC IDEAS WE ARE
TRYING TO INCORPORATE INTO OUR
FUTURE WORK. I COMPLETELY AGREE
WITH PRETTY MUCH EVERYTHING YOU
SAID. I WANTED TO HIGHLIGHT THE
STRENGTH OF THE PUBLIC-PRIVATE
PARTNERSHIP THAT IS FUNDED
THROUGH THE NATIONAL INSTITUTES
OF HEALTH THROUGH ALL FTD,
THROUGH THE NEW PSP PLATFORM
TRIAL AND WHAT WE HOPE TO DO
MORE IN FUTURE BECAUSE TO ANSWER
MANY OF THE THERAPEUTICS
QUESTIONS THAT YOU BRING UP, WE
REALLY NEED NOT JUST INDUSTRY
SUPPORT BUT WE NEED THE NIH TO
HELP US TO REALLY BRING THESE
TREATMENTS INTO SCENARIOS THAT
MAY NOT BE AS ATTRACTIVE TO
INDUSTRY TO DO ON THEIR OWN.
THIS IS WHERE THIS PARTNERSHIP
IS SO IMPORTANT BETWEEN YOU AND
US AT THE NIH ACADEMIC
INVESTIGATORS, THE COMMUNITY AND
INDUSTRY SO THANK YOU SO MUCH.
>> I DON'T KNOW IF THERE IS
ANY -- SORRY, OKAY. SINCE THE
QUESTION FROM VIDEO CAST IS
SINCE AM LLOYD PLAQUE AND TA
NERVE TREATMENTS ONLY PROVIDE
MODEST SYMPTOM REDUCTIONS WITH
SEVERE SIDE EFFECTS WHAT GOOD
COULD THEY DO FOR FTD.
>> MAYBELY TAKE THAT ONE TOO.
I DIDN'T MEAN TO SUGGEST AM
LLOYD TREATMENTS BE USED FOR FTD
BECAUSE THERE IS NO AM LLOYD IN
FTD. I DON'T AGREE THEY PROVIDE
MODEST BENEFITS. I THINK FOR THE
RIGHT PEOPLE THEY CAN BE QUITE
IMPACTFUL. BUT WHAT I WAS TRYING
TO ALLUDE TO IS THE IDEA THAT IN
ALZHEIMER'S DISEASE THE NIH
SUPPORTED THE DEVELOPMENT OF
MANY BIO MARKERS SUCH AS BRAIN
SCANS AND BLOOD TESTS WE CAN
USE. THESE ARE VERY INSTRUCTIVE
FOR US. WE ARE BRINGING THESE
TECHNOLOGIES INTO FTD. WE THINK
THAT REGARDLESS ABOUT HOW YOU
FEEL ABOUT THE ALZHEIMER'S
THERAPIES, THEY DO PAVE THE WAY
AND PROVIDE REALLY A ROAD MAP
THAT WE WILL ACCELERATE THE
DEVELOPMENTS.
>> YOU CAN GO AHEAD WITH THE
NEXT QUESTION. I WILL JUST --
ONLINE ALREADY --
>> OKAY, GREAT. I THINK THE
NEXT QUESTION IS STEVEN HAD HIS
HAND OUT.
>> YEAH, THANKS FOR ALLOWING
ME TO ASK ANOTHER ONE. SORT OF
ON THE TOPIC OF THE LAST FEW
QUESTIONS. A WAY TO IMPROVE BOTH
IS BRAIN PENETRATION OF DRUG AND
DIFFUSE TO OTHER ORGANS. IS IT
OF INTEREST TO THIS GROUP TO
FORMALLY SUPPORT STUDY OF THE
BLOOD BRAIN BARRIER INCLUDING
APPLIED IN BASIC RESEARCH SO WE
CAN WORK ON THAT?
>> I DON'T MIND JUMPING IN
AND ADDRESSING THAT. SO GLAD YOU
BROUGHT THAT UP. I DID MENTION
END THEEL YELL CELLS WHICH MAKE
UP THE BLOOD BRAIN BARRIER. I
ALMOST ED THAT IDEA LIKE A
HELMET SURROUNDING THE BRAIN
THAT PREVENTED CELLS AND
BIOLOGICS AND DRUGS FROM GETTING
IN. IN FACT, , THE BARRIER IS
THE END THEEL YELL CELLS THAT
HELP. WE KNOW THE BLOOD BRAIN
BARRIER BECOMES LEAKY AND IS A
BIG PART OF THIS DISEASE SO IT
IS CRITICAL TO STUDY BLOOD BRAIN
BARRIER. THERE IS A GREAT LAB AT
STANFORD THAT'S STUDIED THIS IN
CONTEXT OF BRAIN MUTATIONS. I'M
ORGANIZING A RESEARCH CONFERENCE
FOR NEXT YEAR ON FRONTAL
TEMPORAL DEMENTIA. WE ARE
PUTTING TOGETHER THE PROGRAM
NOW. ONE OF THE SESSIONS IS
GOING TO BE DEVOTED TO VASCULAR
BLOOD BRAIN BARRIER WORK TO LOOK
FORWARD TO ADVANCE ING THAT
AREA.
>> THANK YOU.
>> CONGRATULATIONS TO THE
NDINS AND ALL YOU. I THINK THE
RECOMMENDATIONS YOU HAVE COME UP
WITH, I THINK ARE IMPORTANT
TOUCHSTONES FOR THE FIELD TO BE
PAYING ATTENTION. THEY ARE JUST
WELL PUT TOGETHER AND ALSO
REFLECT THE HOPE THAT COMES FROM
THE INCREDIBLE PROGRESS THAT HAS
BEEN ENABLED LARGELY FROM
NIH-FUNDED TO ACADEMIC RESEARCH
CENTERS IN THE UNITED STATES. I
THINK IT BRINGS SO MUCH HOPE TO
FAMILIES AND COMMUNITIES THEY
SUPPORT. I NEED TO ASK ONE
QUESTION WHICH IS FAMILIES WE
SUPPORT DON'T JUST COME FROM
COGNITIVE BEHAVE YOUR OR
NEUROLOGY CLINICS. THE FIELD HAS
DONE SO MUCH WHERE THE NETWORK
IS TAPPING INTO THE ALZHEIMER'S
INFRASTRUCTURE, LIKE NICK READ
FOR EXAMPLE, FOR BIOSAMPLE
REPOSITORIES AND THE NAC CENTERS
AND ADRCs. OUR PATIENTS AND
FAMILIES ARE SEEN IN PARKINSON'S
CLINICS AND ALS AND ALZHEIMER'S
CLINICS, NOT TO MENTION IF THEY
HAVE BEEN MISDIAGNOSE ED IN
PSYCHIATRIC CLINICS. A LOT OF
THE RESEARCH INVOLVES BRINGING
IN BIOSAMPLES AND UNDERSTANDING
THE EPIDEMIOLOGY AND ALL OF
THESE DIFFERENT RESEARCH
NETWORKS TENDS TO HAVE LARGE
INFRASTRUCTURE THAT IS
INDEPENDENT OF ONE ANOTHER AND
THE FTD FIELD TENDS TO TRY TO
BRIDGE ACROSS THEM. CAN YOU
COMMENT ON HOW WE CAN DO BETTER
AT THAT? IS THIS RELYING ON DATA
SCIENCE AND AI TO FIND WHAT DATA
IS WHERE? IS IT ON THE
DIAGNOSTIC TOOLS, MINIMAL DATA
SET S SO WE CAN HAVE SOME
ABILITY COMBINE OR BETTER
ABILITY TO COMBINE DATA ACROSS
DISPARATE PLACES? IT IS A HARD
PROBLEM TO SOLVE BUT FOR FTD
FAMILIES IT IS WHAT WE ARE GOING
TO NEED.
>> THANK YOU, RESA. A REALLY
CRITICAL POINT THAT WAS
SOMETHING THAT CAME UP OVER AND
OVER IN OUR DISCUSSIONS AROUND
SORT OF HOW -- TO BREAK DOWN
BARRIERS, HOW TO INTEGRATE AND I
THINK THE GROUP TRIED TO THINK
ABOUT THIS IN A FEW WAYS THAT I
CAN MENTION. ONE IS TO ENCOURAGE
THE USE OF ENGAGEMENT WITH
PUBLIC PRIVATE PARTNERSHIPS THAT
HAVE BEEN SO SUCCESSFUL FOR DATA
REPOSITORIES AND INTEGRATED
STUDIES. YOU KNOW, TARGET ALS.
SO BRIDGING THOSE UNDER SIMILAR
-- POTENTIALS TO BRING THOSE
UNDER A SIMILAR PLATFORM HAS THE
POTENTIAL TO CONNECT INDIVIDUALS
AND SAMPLES AND GET AT SOME OF
THESE QUESTIONS BUT I THINK THIS
IS ALSO WHERE DR. IRWIN TALKED
ABOUT SORT OF INEXPENSIVE, YOU
KNOW, BIO MARKERS, TESTS THAT
CAN BE DONE, ENABLED ACROSS
DIFFERENT CENTER TYPES. I THINK
THIS IS AN AREA OF GREAT
IMPORTANCE. IF ANYONE ELSE WANTS
TO COMMENT, PLEASE DO.
>> MAYBE I'LL BRIEFLY ECHO
THAT AND SAY THE BIOLOGICAL
CHARACTERIZATION NOMENCLATURE
CLASSIFICATION, THOSE EFFORTS I
THINK WILL HELP ACCELERATE AS
THE DEMENTIA NOMENCLATURE
INITIATIVE. ONE OF THE FEEDBACK
FROM THAT GROUP WAS THAT IN THE
RESEARCH REALM, REQUESTING
SAMPLES AND WHAT TERMS WE USE
CAN SOMETIME BES S BE A BARRIER.
THE MORE WE DEVELOP BIOLOGICAL
CAN HARMONIZE AND BETTER
COMMUNICATE ACROSS DISCIPLINES
OF NEUROLOGY AND OTHER FORMS OF
MEDICINE AND RESEARCH.
>> SUSAN.
>> I WANTED TO FOLLOW UP. ON
ALL THE DIFFERENT FORMS OF
DEMENTIA WE WILL BE DISCUSSING
OVER THE COURSE OF THIS SUMMIT,
ALTHOUGH WE DON'T KNOW THE
PREVALENCE OF FTD, AS YOU
APPROPRIATELY ADDRESS IN
RECOMMENDATION, WE CAN BE SURE
THIS IS PROBABLY, BY FAR, THE
LEAST PREVIOUS LE PREF /* --
PREVALENT. I WANTED TO CALL OUT
HOW MUCH THE COMMUNITY
APPRECIATES THE NIH'S INVESTMENT
IN FTD AND HOW WE RECOGNIZE THAT
IT IS STUDIES THAT NIH HAS
BACKED, ALONG WITH THE PASSION
OF THIS COMMUNITY. IT HAS LED TO
ADVANCES AND SPECIFICALLY TO
BIOPHARMA'S ADVANCEMENT IN FTD.
IT IS GOING TO TAKE, AS YOU HAVE
ALLUDED TO, THE PUBLIC PRIVATE
PARTNERSHIPS TO GET US THROUGH
THE FIRST THERAPEUTICSES. A NOTE
OF APPRECIATION FOR ALL-TIME YOU
HAVE PUT IN, AS WELL AS REALLY
THE DECADES BASIC AND
TRANSLATIONAL RESEARCH THAT HAS
GOTTEN US AS FAR AS WE ARE. AND
WILL GET US TO THOSE APPROVED
THERAPEUTICSES.
>> THANK YOU. COMMENTS OR
QUESTIONS?
>> I HAVE ONE COMMENT THAT
CAME IN ONLINE I CAN READ AND
MAYBE TAKE -- END AND MAYBE TAKE
A TWO-MINUTE BREAK AND TRY TO
START BACK UP AS QUICK AS WE
CAN. THERE'S ONE -- I WILL READ
THIS QUICK. NOT A QUESTION, JUST
COMMENT. FTD IS UNIQUELY CRUEL
BECAUSE IT OFTEN AFFECTS PERSON
IN PRIME OF THEIR CAREER AND
COST OF LOST PRODUCTIVITY,
INCOME IS HUGELY IMPACTFUL FOR
FAMILIES, OFTEN BOTH PATIENT AND
CAREGIVER ARE FORCED TO LEAVE
CAREERS AND STUCK FOR MANY TOR
YEARS. NIH, HELP US END FTD.
>> THANK YOU. BRANDON. UNMUTE
YOUR CAMERA AND MICROPHONE.
>> HE'S OPEN.
>> MAYBE WHILE BRANDON IS
TRYING TO UNMUTE, I JUST WANT TO
TAKE THIS OPPORTUNITY AGAIN TO
THANK THE COMMITTEE AND ALSO
THE, YOU KNOW, THAT OUR WORK
COULDN'T BE DONE WITHOUT THE
PATIENT ADVOCACY GROUPS, PEOPLE
WITH LIVED EXPERIENCES.
INCREDIBLE AND POWERFUL AND
REALLY REVEALING HOW, YOU KNOW,
HOW REAL THESE -- THIS DISEASE
IS AND HOW BROAD THE IMPACT IS
AND HOW URGENT IT IS TO TREAT
THESE DISEASES.
>> I THINK WE WILL TAKE A
TWO-MINUTE BREAK AND COME BACK
WITH THE NEXT SESSION. SORRY,
BRANDON, FOR TECHNOLOGY NOT
WORKING FOR YOU.
>> WELCOME BACK, A SHORT
BREAK. WE ARE ABOUT EIGHT
MINUTES BEHIND AND TRY TO MAKE
THAT UP IN THE BREAK. APOLOGIES
FOR NOT HAVING A LONGER BREAK.
KRISTIN, ARE YOU ABLE TO TURN ON
YOUR CAMERA?
>> I JUST HAD IT ON. DO YOU
NOT SEE ME?
>> IT MAY BE ON ME THAT. IS
GREAT. I HEAR YOU, THANK YOU.
>> GREAT. CAN I GET STARTED?
>> YEP, DEFINITELY.
>> GREAT, THANK YOU. THANK
YOU EVERYONE FOR STICKING WITH
US. I KNOW THESE DAYIES CAN FEEL
LONG. I'M SO HONORED TO BE ABLE
TO HAVE THIS OPPORTUNITY TO
SHARE OUR SUBCOMMITTEE'S
RECOMMENDATION ON POST-TRAUMATIC
BRAIN INJURY NEURODEGENERATION
AND ALZHEIMER'S AND RELATED
DISORDERS. I HAVE NO
DISCLOSURES. WE JUST WANTED TO
ACKNOWLEDGE THAT WE USED
SPECIFIC PROGRAM TO GENERATE
OTHER FIGURES IN THIS
PRESENTATION. THIS SLIDE SHOWS A
CONDENSED OVERVIEW OF OUR FOUR
RECOMMENDATIONS WHICH REALLY
EMPHASIZED THE NEED TO INVEST IN
INFRASTRUCTURE AND WHAT IS STILL
A RELATIVELY NEW AREA OF
RESEARCH. WE HAVE MADE SOME
RAPID ADVANCEMENTS AND TO
CONTINUE ON THIS TRAJECTORY WILL
REQUIRE INTER DISCIPLINARY
COLLABORATION ACROSS TBI AND
DEMENTIA COMMUNITIES,
MULTI MODAL AND TRANSLATION OF
KNOWLEDGE INTO CLINICAL SETTINGS
AS WELL AS SHARING KNOWLEDGE.
TBI IS A MAJOR HEALTH PRIORITY.
NOTE THAT ALSO TBI IN OLDER
ADULTS IS EXCEEDING POPULATION
GROWTH AND MILLIONS OF TRAUMATIC
BRAIN INJURIES ARE NOT COUNTED
IN THESE ESTIMATES INCLUDING
INJURIES SUSTAINED IN MILITARY
COMBAT, THOSE FOR WHICH CARE IS
NOT SOUGHT OR RECEIVED AND
INJURIES THAT ARE INTENTIONALLY
CONCEALED, SUCH AS INJURIES
SUSTAINED IN CONTEXT OF INTIMATE
PARTNER VIOLENCE. WE WANT TO
CLARIFY TERMS RELEVANT, SO
REPETITIVE HEAD IMPACT, RHI
REFERS TO REPEATED IMPACTS TO
THE HEAD INCLUDING CONTACT
SPORTS, PERHAPS SIMILAR TO
EXPERIENCE ED IN MILITARY BLAST
EXPOSURE OR IN CONTEXT INVOLVING
PARTNER VIOLENCE. THESE HITS TO
THE HEAD DO NOT RESULT IN
SYMPTOMS OF A TRAUMATIC BRAIN
INJURY. ON THE OTHER HAND
TRAUMATIC BRAIN INJURY IS AN
ISOLATED BLOW OR INJURY TO THE
HEAD OR NECK THAT RESULTS IN
LOSS OR ALTERATION OF
CONSCIOUSNESS. NEXT SLIDE. THE
ACUTE AND CHRONIC SYMPTOMS OF
TBI CAN RANGE CONSIDERABLY SO
MOST PEOPLE WITH A MILD TBI
RECOVER COMPLETELY AND I WILL
NOTE THAT ONGOING NIH AND NINDS
EFFORTS TO IMPROVE TDI SEVERITY
CLASSIFICATION INDICATES IT
DOESN'T ALWAYS ALIGN WITH TBI
SEVERITY. MILD TBI HAS BEEN
ASSOCIATED WITH DEMENTIA RISK IN
SOME STUDIES. NEXT, RHI, WHICH I
SHOULD NOTE IS ALSO PRESENT AND
-- ADVANCE, THERE WE GO. IS ALSO
PRESENT IN SUBSTANTIAL
PROPORTION OF PEOPLE WHO
SUSTAINED A SINGLE TBI, ABOUT
HALF AND SOME OF OUR STUDIES
HAVE SUSTAINED EXTENSIVE
EXPOSURE TO RHI, WHICH DOES NOT
ITSELF RESULT IN IMMEDIATE
SYMPTOMS IN MOST CASES BUT
COMPELLING EVIDENCE DOES SUGGEST
A SUBSET OF THOSE WITH RF RHI
EXPOSURE DEVELOP DECLINE LATER
IN LIFE. THIS IS JUST A SNAPSHOT
OF FIVE-YEAR OUTCOMES FROM THE
NIDLER-FUNDED TBI SYSTEMS WHERE
YOU CAN SEE AMONG SURVIVORS OF
MODERATE TO SEVERE TBI, NEARLY A
THIRD DECLINE WITHIN FIVE YEARS,
BUT OVER A QUARTER CONTINUE TO
IMPROVE. WE NEED TO KNOW WHAT IS
DRIVING THESE HETEROGENOUS
CHRONIC TRAJECTORIES. NEXT.
ANOTHER QUICK NOTE ON KN
NOMENCLATURE AND WORDS WE ARE
USING IN OUR PRESENTATION TODAY,
WHEN WE ARE TALKING ABOUT
POST-TBI, ADRD, ALSO REFERRED TO
AS POST-TRAUMATIC
NEURODEGENERATION OR PTRD, WE
ARE NOT TALKING ABOUT ACUTE
SYMPTOMS THAT HAPPEN AFTER TBI;
WE ARE REFERRING TO A SUBSEQUENT
PATTERN OF DECLINE THAT IS
EXPERIENCED FOLLOWING RECOVERY
IN A SUBSET OF CHRONIC TBI
SURVIVORS. NEXT SLIDE. THIS
IMAGE IS FROM A PAPER WE WROTE
AFTER THE 2019ADRD SUMMIT. I
HAVE INCLUDED IT BECAUSE IT
REALLY EMPHASIZES THAT PTND IS
INDISPUTEDLY A MULTIPLE ETIOLOGY
DEMENTIA. TBI IS ONE OF MANY
THINGS IN A LIFETIME THAT CAN
INFLUENCE DEMENTIA RISK. TBI HAS
UNIQUE PATHOLOGICAL FOOT PRINTS
WE ARE JUST NOW BEGINNING TO
EXPLORE. JUST BRIEFLY GROWING
EVIDENCE SUGGESTS HEAD TRAUMA OF
DISTINCT ETIOLOGIES MAY HAVE
DISTINCT FOOTPRINT S SO CTE HAS
A WELL-DEFINED LESION THAT
APPEARS TO BE UNIQUE TO RHI.
THEN WE HAVE EVIDENCE THAT
SUGGESTS THAT BLAST EXPOSURE MAY
HAVE A UNIQUE PATTERN OF -- WE
CALL IT INTER FACE ASTRO GLIAL
SCARRING. NEXT INTIMATE PARTNER
VIOLENCE, WHICH IS A PATTERN
OFTENTIMES OF BRAIN INJURY THAT
CAN INVOLVE REPETITIVE HEAD
IMPACTS, AGNOSTIC OR HIGH POHIC
INJURY IN AN INDIVIDUAL. BASED
ON VERY FEW CASES STUDIED TO
DATE. BUT WE HAVE NOT FOUND MUCH
CTE IN IPV, SUGGESTING THIS IS
NOT A PRIMARY PATHOLOGY OF IPV.
FINALLY ISOLATED TRAUMATIC BRAIN
INJURY SEEMS TO RESULT IN WIDE
RANGE OF DISTINCT AND
OVERLAPPING PATHOLOGIES
INCLUDING TISSUE TEARS AND NEW
EVIDENT EVIDENCE IS SUGGESTING
IT MAY BE AMPLIFIED BY OR
PROXIMAL TO TRAUMATIC LESIONS.
NEXT. WE WANT TO ALSO
ACKNOWLEDGE THAT WE HAVE HAD
TREMENDOUS PROGRESS SINCE EVEN
JUST THE LAST SUMMIT IN 2022.
THE NIH HAS FUNDED SEVERAL
AWARDS TO ADVANCE
RECOMMENDATIONS WITH A
PARTICULAR EMPHASIS ON
MULTI MODAL INVESTIGATIONS INTO
TBI AS A MULTIPLE ETIOLOGY
DEMENTIA EMPHASIZING
MULTI DISCIPLINARY COLLABORATION
AND FACILITATING DATA SHARING.
NEXT.
>> TWO MINUTES.
>> WE HAVE CHANGED OUR TIME
ALLOCATION, JUST SO YOU KNOW.
NEXT. PRIORITY ONE IS -- I'M
GOING TO GO THROUGH EACH OF OUR
PRIORITIES. I'M GOING TO START
WITH PRIORITY ONE THEN HAVE SOME
SLIDES THAT JUST ILLUSTRATE SOME
OF THE SUB COMPONENTS OF
PRIORITY ONE. LET'S GO TO THE
NEXT SLIDE. SO PRIORITY ONE IS
REALLY ABOUT LONGITUDINAL
MULTI MODAL STUDIES, THE NEED TO
DEVELOP THIS INFRASTRUCTURE TO
STUDY THE LONG-TERM IMPLICATIONS
OF TBI AND INTERSECTIONS WITH
ADRDs SO FOUNDATIONAL TO THIS
EFFORT IS FURTHER VALIDATION AND
STANDARDIZATION OF METHODS TO
QUANTIFY TBI AND RHI.
SELF-REPORT IS OFTEN BEST OPTION
FOR LIFETIME EXPOSURE
CHARACTERIZATION. IDEALLY IT IS
SUPPLEMENTED BY MEDICAL RECORDS
WHICH CAN GIVE SNAPSHOTS OF
INJURIES THAT HAVE RECEIVED CARE
AND EACH HAS STRENGTHS AND
WEAKNESSES THERE ARE ONGOING
EFFORTS TO QUANTIFY RHI IN
CONTACT SPORTS AND MILITARY
SETTINGS. NEXT. IMPORTANTLY,
GROWING EVIDENCE SUGGESTS
READILY REPORTABLE INDICES SUCH
AS DURATION OF EXPOSURE TO
CONTACT SPORT S HAVE A DOSE
RELATIONSHIP WITH FOR EXAMPLE
CTU NEURAL PATHOLOGY, NEXT.
OKAY. NEXT. THERE GO. NEXT. SO A
DIAGNOSIS OF POST-TRAUMATIC
NEURO DEGENERATION DURING LIFE,
WHEN WE CAN STILL INTERVENE, IS
OF HIGH PRIORITY. THIS REQUIRES
LONGITUDINAL STUDY IN COHORTS
WILLING TO UNDERGO MULTI MODAL,
CLINICAL AND BIO MARKER
EVALUATIONS TO DISTINGUISH THE
STABLE POST TBI SYMPTOMS AND
CRITERIA UNDERLYING DISEASE
PROCESSES. NEXT AGAIN TRAUMATIC
BRAIN INJURY IS AN ADRD RISK
FACTOR WITH A TIME ZERO WHICH
MEANS TBI SURVIVORS ARE A RISK
POPULATION THAT MAY SUPPORT
IDENTIFICATION OF THE EARLIEST
BIOLOGICAL SIGNS OF DEMENTIA
RISK. IT IS ESSENTIAL TO
RECOGNIZE THAT MOST INDIVIDUALS
WITH RHI EXPOSURE AND WITH TBI
WILL NOT DEVELOP ADRDs. WE NEED
ASYSTEMATIC INDIVIDUALS WITH
THESE EXPOSURES WITH RHI AND T
BIV TO BE INCLUDED IN OUR
LONGITUDINAL STUDIES SO WE CAN
ALSO IDENTIFY PROTECTIVE
FACTORS. NEXT. WE NEED
BIO MARKERS OF PTMD. TPI
BIOMARKER DISCOVERIES HAVE
FOCUSED ALMOST EXCLUSIVELY ON
ACUTE CARE TRIAGING. OUR
COLLEAGUES MEANWHILE WHO ARE
STUDYING AD AND ADRDs HAVE MADE
REALLY IMPORTANT DISCOVERIES IN
IMAGING AND FLUID BIOMARKERS OF
DEMENTIA SO IN SEARCHING FOR
BIO MARKERS OF POST TBI ADRD WE
HAVE FOCUSED SO FAR ON THOSE WE
KNOW TO BE PERTURBED BY ACUTE
TBI AND KNOWN RELEVANT TO ADRDs.
WE MAY BE MISSING IMPORTANT PTND
SPECIFIC BIOMARKERS AND NEED TO
BROAD INTO IDENTIFY OTHER
NON-INVASIVE BIOMARKERS THAT CAN
PREDICT AND MONITOR DISSEEDS
PROGRESSION OVER TIME AND
IDENTIFY THE PATHOLOGIES THAT
UNDERLIE CLINICAL DECLINE. NEXT.
A GROWING UNDERSTANDING OF
INJURY BIOMECHANIC NICK S IS
HELPING US UNDERSTAND HOW
DIFFERENT TYPES IN HEAD TRAUMA
CAN RESULT IN PATHOLOGICAL
PROCESSES. WHAT WE DON'T KNOW IS
HOW TBI SPECIFIC PATHOLOGIES CAN
INTER ACT WITH AD AND OTHER ADRD
PATHOLOGIES OR WITH CLINICAL
SYMPTOMS, OR SPECIFICALLY HOW
ESTABLISHED AD BIO MARKERS ARE
INFLUENCED BY A TBI. WE NEED TO
BETTER UNDERSTAND WHETHER HEAD
TRAUMA INFLUENCES THE RESPONSE
TO DISEASE MODIFYING TREATMENTS
WITH EXISTING APPROVED
THERAPIES. NEXT. FINALLY OUR
SUBCOMMITTEE HAS EMPHASIZED THE
IMPORTANCE OF COLLECTING COMMON
DATA ELEMENTS. CAN WE GO TO THE
NEXT SLIDE. THERE WE GO. COMMON
DATA ELEMENTS, SO THIS IS A
RECOMMENDATION TO INCLUDE
SIMILAR MEASURES IN STUDIES EVEN
ONGOING STUDIES OF TRAUMATIC
BRAIN INJURY, WHICH MAY IN SOME
CASES MEAN COLLECTING ADDITIONAL
DATA TO OPTIMIZE OVERLAP BETWEEN
TBI STUDIES AND DEMENTIA STUDIES
SPECIFICALLY, NEXT, PROVIDE THE
FOUNDATIONS THAT WE NEED FOR
CROSS-STUDY COMPARISONS AND DATA
SHARING IN PUBLIC REPOSITORIES.
I'M GOING TO TURN IT OVER NOW TO
MY COLLEAGUE, WHO IS GOING TO
PRESENT RECOMMENDATION TWO,
THANK YOU.
CAN WE UNMUTE, DR. GRAHAM?
>> WONDERFUL, THAT COMING
THROUGH? THANKS, I WANT TO THANK
THE ORGANIZERS AT NIH FOR
PUTTING TOGETHER THIS AND
BRINGING TOGETHER THESE
RECOMMENDATIONS, I THINK ARE
REALLY IMPORTANT. AND, YOU KNOW,
ARE GOING TO BE VERY IMPACTFUL A
MOMENT OF OPPORTUNITY FOR OUR
FIELD. SO, YOU KNOW, AS WE SET
OUT WE HAVE MADE A GREAT DEAL OF
PROGRESS SO FAR IN TERMS FROM MY
PERSPECTIVE, BIOMARKERS OF
INJURY, GAVE ME A MECHANISTIC
UNDERSTANDING BUT LOTS FOR US TO
DO. IF WE COULD ADVANCE TO THE
NEXT SLIDE, PLEASE .
THE RECOMMENDATION I WANTED TO
SHARE WITH YOU, WHICH WE HAVE
PUT TOGETHER, IS ABOUT LINKING
UP THE ALZHEIMER'S AND TBI
FIELDS TO GAIN SOME KIND OF
SCALE AND LEVERAGE EXISTING
INVESTMENT IN SKILLS, EXPERIENCE
PRESENT IN EACH OF THOSE IN
ORDER TO HAVE THE SCALE TO KIND
OF MAKE THE BREAKTHROUGHS
NECESSARY IF WE ARE GOING TO
TRANSLATE INTO PATIENT CARE. FOR
EXAMPLE IT IS CLEAR TBI IS A
VERY HETEROGENOUS DISEASE AND
UNDERLYING BASIS, FOR INSTANCE,
NEED LARGE SAMPLE SIZES. THIS IS
WHAT OUR RECOMMENDATION TWO
FOCUSES ON. I CAN GIVE YOU SOME
KIND OF DETAIL OF WHAT WE ARE
GOING TO DO. THE FIRST CHUNK, IF
WE CAN ADVANCE TO THE NEXT
SLIDE, PLEASE, IS ABOUT
CONVENING A WORKING GROUP OF
STAKEHOLDERS FROM TBI AND ADRD
COMMUNITIES TO EVALUATE EXTENT
WHAT WE KNOW CAN MR. APPLIED TO
STUDY OF TBI AND VICE VERSA AND
DEVELOP A FORUM KNOWLEDGE
EXCHANGE WHICH WOULD INCLUDE
BASIC SCIENCE, TRANSLATIONAL AND
CLINICAL RESEARCH, WHICH WOULD
HOPEFULLY GIVE BIDIRECTIONAL
COMMUNICATION. I THINK THIS
WOULD HELP US TO HIGHLIGHT
CLINICAL DISCOVERIES THAT REVEAL
GAPS WHERE GAINIES CAN BE MADE
AND HIGHLIGHT BASIC SIZE
DISCOVERIES THAT MIGHT INFORM
DEVELOPMENT OF CLINICALLY
ACCESSIBLE BIOMARKERS AND
INTERPRETATION OF FACTORS
RELEVANT TO PATHOLOGY. THIS IS
DONE YET WE DON'T HAVE SOMETHING
THAT BRINGS TOGETHER THESE
FIELDS. CERTAINLY WITHIN TBI WE
HAVE A STRONG INTERNATIONAL
RESEARCH COMMUNITY THROUGH INBIR
BUT I THINK THERE IS POTENTIALLY
MORE THAT CAN BE DONEN. SOME
WAYS THIS IS LOW HANGING FRUIT
ABOUT WORKING TOGETHER. IF WE
COULD HAVE THE NEXT SLIDE, THE
SECOND SUBPART OF THIS
RECOMMENDATION IS AROUND, YOU
KNOW, HARMIZATION. WHAT WOULD WE
NEED TO DO TO ACHIEVE THESE KIND
OF GAINS. YOU KNOW, WE STRONGLY
PROMOTE HARMONIZATION OF
EXISTING DATA THAT'S ALREADY
BEEN DONE INCLUDING DATA IN
FEDERAL REPOSITORIES FOR
RIGOROUS AND REPRODUCIBLE
RESEARCH. THAT MAY MEAN DATA
STRUCTURE TO SUPPORT HARMIZATION
AND ESTABLISHING SPECIFIC CODE
BOOKS, FUNDING USABILITY STUDIES
TO SIMPLIFY AND SHARING
REQUIRING PROSPECTIVE DATA
COLLECTION USING STANDARDIZED
ELEMENTS AND MINIMUM DATA
ELEMENTS, IMPORTANT FROM OUR
PERSPECTIVE. LAST IS ABOUT
FOSTERING COLLABORATION.
SPECIFICALLY TO BUILD TOWARDS
THE GOAL OF GAINING REGULATORY
SUPPORT FOR DIAGNOSTICS AND
ASSESSMENT METHODS, LOOKING AT
SAFETY AND EFFICACY IN CLINICAL
TRIALS. FROM OUR PERSPECTIVE WE
WANT BETTER COLLABORATION BUT WE
WANT TO DO SO WITH A VERY CLEAR
PURPOSE THAT WE ARE AIMING
ULTIMATELY TO OVER COME BARRIERS
THE FIELD HAS HAD TOWARD
DEVELOPING NEW THERAPEUTICSES.
WE ARE HOPING THAT, YOU KNOW,
KIND OF PRECISION DIAGNOSTIC
APPROACH TO PATIENTS THAT IS
GOING TO YIELD SUCCESS IN
TRIALS. SO THAT WRAPS UP
RECOMMENDATION NUMBER TWO TO OUR
NEXT PRESENTER, THANK YOU.
>> YES, GOOD MORNING. I TOO
WOULD LIKE TO ECHO MY THANKS TO
NINDS AND NIH IN GENERAL,
CERTAINLY ALL THE SUBCOMMITTEE
MEMBERS I HAVE HAD THE PRIVILEGE
OF WORKING WITH. I HAVE THE
PRIVILEGE OF INTRODUCING
RECOMMENDATION 3. IF I COULD
HAVE THE NEXT SLIDE. I HAVE
NOTHING TO DISCLOSE. NEXT SLIDE.
NEXT SLIDE, THANK YOU. SO
RECOMMENDATION 3 REALLY IS TO
CROSS-LINK MODELS AND CONDUCT
BASIC AND TRANSLATIONAL RESEARCH
WITH HUMAN SPECIMENS AND
EXPERIMENTAL MODELS FOR THE POST
TISSUE RESPONSE, IE IDENTIFY
MECHANISTIC PATHWAYS AND
ELUCIDATE PATHWAYS AGAINST
PROGRESSION OF POST TBI, ADRDs.
UNDERNEATH THIS RECOMMENDATION
WERE SORT OF THE FIVE SUB
RECOMMENDATIONS, IF YOU WILL. I
WILL TOUCH ON THAT BRIEFLY AS WE
GO THROUGH THIS TALK. NEXT
SLIDE, PLEASE. I JUST WANTED TO
REMIND EVERYONE THAT POST TBI
AND ITS PROGRESSION TO ADRD IS A
CONTINUUM. THE LEFT PANEL IS
SUMMARY, ALBEIT A LITTLE
SIMPLIFIED, OF HOW A TBI MIGHT
THEN SLOWLY SPIRAL DOWN TO
COGNITIVE IMPAIRMENT TYPE
PATHOLOGY AND KEY WORDS ARE
AD-LIKE PATHOLOGY BUT IT IS
IMPORTANT TO NOTE THIS LITTLE
SCHEMATIC INCLUDES FEATURES
PREVALENT IN AD, INCLUDING BETA
AM LLOYD, VASCULAR DIGITAL ET
CETERA. EMERGING EVIDENCE IN THE
FIELD INCLUDING THIS MANUSCRIPT
FROM GRAHAM AND COLLEAGUES IN
2023, WHERE IN THE TOP PANEL YOU
CAN SEE BRAIN REGIONS THAT ARE
IMPACTED, BOTH GRAY MATTER,
WHITE MATTER, CSF, IMPACTS A
LARGE SWATH OF VARIOUS BRAIN
REGIONS. IN THE MIDDLE PANEL YOU
CAN SEE TBI SIMILARLY HAS OTHER
REGIONS ALSO CO -EMERGED AS WITH
THE ADRD PATIENT SUGGESTING
THERE ARE POTENTIAL COMMON
MECHANISMS. HOWEVER AS THESE
PROCESSES ARE DIFFERENT BETWEEN
THE TBI AND ADRD AND THEY ARE
DISTINCT BUT IT IS ALSO
IMPORTANT TECHNOLOGY THAT
CONSIDERABLE OVERLAP EXISTS.
NEXT SLIDE, PLEASE. AS NOTED
EARLIER, AS NOTED EARLIER BY DR.
OH C OH CONNOR, SOME HAVE BEEN
FUNDED. THIS IS A NEW HOPE TBI
STUDY, WHERE THEY ARE EXPANDING
A LARGE NETWORK OF WELL
CHARACTERIZED BRAIN DONORS
LOOKING AT NEURAL IMAGING,
BEHAVIORAL MEASURES AND
IDENTIFYING SIGNATURES FROM
THESE DATA TYPES, INCLUDING
QUANTITATIVE NEURO PATHOLOGY TO
BETTER INFORM FUTURE RESEARCH
AND ONGOING TREATMENTS FOR
PATIENTS INCLUDING VASCULAR
PATHOLOGY. THE END GOAL, OF
COURSE, IS TO PROVIDE A
LONG-TERM REPOSITORY THAT
RESEARCHERS AND CLINICIANS CAN
NOW START TO VACCINATE FUTURE
RESEARCH DIRECTIONS. IF I CAN
HAVE THE NEXT SLIDE, PLEASE. SO
THE NEXT RECOMMENDATION, ONE OF
THE SUB RECOMMENDATIONS WAS
REALLY TO START TO STRENGTHEN
THIS LINKAGE OF HUMAN SPECIMENS
TO CHARACTERIZE POST TBIADRD. IN
THIS SUMMARY FROM SMITH AND ALL,
THIS REVIEW PAPER, WHERE YOU
HAVE SINGLE TO MODERATE SEVERE
TBI OR REPETITIVE T BIV,TBI, WH
STRENGTHENED INCLUDING TA,
INFLAMMATION, A BETA, LONG-TERM
DEVELOPMENT OF ATROPHY. IN LATE
EFFECTS OF TBI STUDIES, WHERE
THEY ARE DOING HIGH RESOLUTION 7
TESLA ANATOMICAL IMAGING,
COMBINING THAT WITH VARIOUS
NEURO PA LOGICAL STAINS AND
SHOWN HERE IN C, YOU CAN SEE A
VASCULAR STRUCTURE SURROUNDED BY
A BETA STAINING, SUGGESTING A
VASCULAR ETIOLOGY, SO
CHARACTERIZING THESE IN MORE
DETAIL IS CERTAINLY A HIGH
RECOMMENDATION OF THIS
SUBCOMMITTEE. NEXT SLIDE,
PLEASE. OF COURSE THE EVALUATION
OF -- NEXT SLIDE. THE EVALUATION
OF CLINICALLY RELEVANT ANIMAL
MODELS THAT MAY ACCELERATE ADRD
IS VERY IMPORTANT. IN THE LEFT
PANEL HERE YOU CAN SEE SORT OF
CLASSICAL INDUCTION MODELS OF
TRAUMATIC BRAIN INJURY AND
INCLUDING HERE IN THE MIDDLE
REPEATED HEAD INJURY OR CLOSE
HEAD INJURY. MANY OF THESE ARE
USED TO STUDY THE ACUTE TYPE OF
TBI BUT NOW WE ARE STARTING TO
BE USED TO STUDY LONG-TERM
EVENTS IN TBI. THE USE OF
ENCEPHALOPHIC MODELS, STUDIES
OVER 16 WEEKS IN A FERRET MODEL,
ONE CAN SEE INCREASING
FRACTIONAL SIGNATURES STARTING
TO EMERGE, PARTICULARLY AT THE
GRAY MATTER WHITE MATTER
BOUNDARIES IN THESE. SO
DEVELOPMENT OF THESE MODELS AND
FOLLOWING THEM OVER LONG-TERM
LIFE SPAN STUDIES IS VERY
IMPORT
IMPORTANT. A FINAL
RECOMMENDATION IS IDENTIFY MORE
CLEARLY FACTORS THAT CAN CONFER
RESILIENCE SUSCEPTIBILITY AFTER
TBI. MOST IMPORTANTLY, USE THOSE
FACTORS TO GUIDE PATIENT CARE.
SO IN THE VIN DIAGRAM ON THE
LEFT YOU CAN SEE PRE-INJURY,
FACTORS INCLUDING GENETIC
SUSCEPTIBILITY, INJURY RELATED
FACTORS SUCH AS SEVERITY AND
LOCATION, POST INJURY AND MOST
IMPORTANTLY POST INJURY FACTORS
SUCH AS CO. MORBID DEFICITS AND
REHABILITATIONS ALL CAN GUIDE
OUR CARE AND IDENTIFY BETTER
WAYS TO TREAT PATIENTS. IN THE
SCHEMATIC FROM 2022 THEY
ACKNOWLEDGE WE HAVE MADE GREAT
PROGRESS IN BIOMARKERS AND MRI
FOR TRIAGING AND UNDERSTANDING
PROGRESSION AND MANAGEMENT OF
TBI. AS THEY ALSO POINT OUT
THERE ARE SIGNIFICANT GAPS,
PARTICULARLY IN HOW TO TREAT
OLDER POPULATIONS OF WHICH FORM
A CONSIDERABLE NUMBER OF TBI
PATIENTS. SO THESE
RECOMMENDATIONS AND SUB
RECOMMENDATIONS REALLY ARE TO
GUIDE ENHANCE BASIC AND
TRANSLATIONAL RESEARCH TO
ELUCIDATE MECHANISMS AND
TREATMENT TARGETS FOR POST TBI,
ADRD. WITH THAT I WILL HAND IT
OVER THE MY OTHER COLLEAGUES.
>> WE CAN'T HEAR YOU. I SEE
-- MONIQUE, YOU HEAR SNUS WE
CAN'T HEAR YOUF YOU ARE TRYING
TO USE YOUR MICROPHONE.
>> CAN YOU HEAR ME NOW?
>> IT IS VERY QUIET. ADJUST.
>> BETTER?
>> THANK YOU.
>> GREAT. JUST WANTED TO ECHO
JUST THANKING NINDS AND NIH FOR
THIS OPPORTUNITY. THE NEXT
SLIDE, PLEASE. NO DISCLOSURES.
( POOR AUDIO)
>> FOR THIS FOURTH
RECOMMENDATION THE POINT WE WANT
TO BEIPOINT TO ACKNOWLEDGE IT TS
YEARS FOR SCIENTIFIC DISCOVERIES
AND ADVANCES TO BE IMPLEMENTED,
SO WE ACKNOWLEDGE WE NEED TO BE
ABLE TO SHARE INFORMATION.
THERE'S CHALLENGES WITH BEING
ABLE TO SHARE KNOWLEDGE AND
INFORMATION TO ALL INTER TESTED
PARTIES, ESPECIALLY INDIVIDUALS
WHO WOULD RECEIVE SUCH
INFORMATION SUCH AS PEOPLE WITH
TRAUMATIC BRAIN INJURY AS WELL
AS FAMILIES AND COMMUNITY. WE
HAVE FOUR SUB RECOMMENDATIONS
RELATED TO THIS TOPIC. THIS IS
ABOUT DIVERSIFYING -- HAVING A
DIVERSE TEAM, ADVANCING
FINDINGS, MAKING SURE THERE IS
SHARING TO OPTIMIZE ENGAGEMENT
WITH RESEARCH AND MAXIMIZE
CLINICAL TRANSLATABILITY. NEXT
SLIDE, PLEASE. SO FOR THIS FIRST
SUB RECOMMENDATION, AGAIN, TO
THE LEFT IS THIS IDEA OF MAKING
SURE WE HAVE ALL INTERESTED
PARTIES THAT ARE INCLUDED,
ESPECIALLY INDIVIDUALS WITH
LIVED EXPERIENCES AND THEIR
FAMILY. YOU KNOW , THE PRINCIPAL
OF NOTHING ABOUT US WITHOUT US,
MAKING SURE THEY ARE INCLUDED IN
EVERY PROCESS, FROM PLANNING,
IMPLEMENTATION, AS WELL AS
DISSEMINATION OF SUCH RESEARCH
AND INCLUDING OTHER INDIVIDUALS
AT THE TABLE, RIGHT. CLINICIAN,
RESEARCHERS, ADDITIONAL
COMMUNITY PARTNERS. AND, OF
COURSE W THE NEW FIELD OF
IMPLEMENTATION SCIENCE, YOU
KNOW, INCLUDING IMPLEMENTATION
SCIENTISTS IN ORDER FOR US TO BE
ABLE TO DEVELOP AND CREATE,
CO -CREATE SIGNATURE ROUSE
RESEARCH, TO REDUCE THIS BURDEN
OF POST-TBI, ADRD. SO NO LONGER
WORKING IN SILOS. TO THE RIGHT,
THE POINT TO EMPHASIZE IS AFTER
HAVING A TRAUMATIC BRAIN INJURY
THERE COULD BE SINGLE TRAUMATIC
BRAIN INJURY THAT IS SEVERE.
OBVIOUSLY THERE ARE A VARIETY OF
DIFFERENT PATHWAYS OR -- THAT
CAN HAPPEN AFTER AN INJURY. THEN
FROM RESILIENCE WHERE
INDIVIDUALS MAY BE -- RESUME
BACK TO FULL RECOVERY, WHEREAS
OTHERS MAY EXPERIENCE
PROGRESSIVE NEURO DEGENERATION.
AT THE LOWER END IS RELATED TO
INDIVIDUALS THAT MAY HAVE
REPEATED MILD TRAUMATIC BRAIN
INJURIES. SO WHAT IS REALLY AS
IMPORTANT IS WE HAVE TO
CO -CREATE OPPORTUNITIES AND
INTERVENTIONS AND PROGRAMMING TO
HELP HOW CAN WE PREVENT OR AT
LEAST DELAY THE PROGRESSION OF
POST TBIADRD. NEXT SLIDE.
>> TWO MINUTES.
>> THEN IN THE SECOND
SUBCOMMITTEE SETUP
RECOMMENDATION IS ABOUT
INCLUDING ALL OF THE DIFFERENT
TYPES OF RESEARCH, FROM
PRECLINICAL TO CLINICAL, BOTH IN
THE ADRD AND TBI SPACES AND
USING THESE -- THIS KNOWLEDGE TO
BE ABLE TO DEVELOP, VALIDATE,
TRANSLATE AND OBVIOUSLY
IMPLEMENT INTO CLINICAL
PRACTICE, USING DIFFERENT TYPE
OF DIAGNOSTIC APPROACHES AND
HOLISTIC INTERVENTIONS SO WE
CAN, AS I MENTIONED BEFORE, BE
ABLE TO PREVENT OR DELAY
POST-TBIADRD. NEXT SLIDE. THEN
THE THIRD SUB RECOMMENDATION,
RIGHT, IS, AGAIN, CREATING THIS
SPACE, RIGHT, A PRECOMPETITIVE
SPACE WHERE YOU HAVE A VARIETY
OF DIFFERENT INDIVIDUALS THAT
ARE COLLABORATING, SHARING
KNOWLEDGE, TRYING TO IDENTIFY
SOLUTIONS, SHARING DATA. YOU
KNOW, HELPING TO GUIDE DIFFERENT
METHODOLOGIES OR DEVELOPMENTS
AND JUST ENCOURAGING THIS SPACE
WITH NUMEROUS REGULATORY
PARTNERS, INDUSTRY PARTNERS,
HOSPITAL CLINICIANS, PEOPLE WITH
LIVED EXPERIENCE, MAKING SURE
EVERYONE IS AT THE TABLE TO BE
ABLE TO CONTRIBUTE AND HELP US
WITH PROMOTING THE INNOVATION
AND FURTHER DEVELOPING NEW
TECHNOLOGIES OR METHODOLOGIES
AND TREATMENTS EARLY BY WORKING
TOGETHER TO SOLVE SUCH PROBLEMS.
NEXT SLIDE. THEN I WILL ITERATE
WE HAVE TO BE ABLE TO TRANSLATE
OUR FINDING INTO CLINICAL
PRACTICE, HOW DO WE DO THAT. HOW
DO WE SHARE IN THE BEST WAY TO
SHARE INFORMATION. BOTH
RECIPROCAL, RIGHT, INDIVIDUALS
THAT INDIVIDUALS WITH LIVED
XHEE
EXPERIENCE MAY SUPPORT THE
RESEARCH PROCESS AND PROMOTE
FURTHER ENGAGEMENT. INCLUDING A
VARIETY OF DIFFERENT PARTNERS,
SPECIAL INSTITUTIONAL
THOSE WITH THE BRAIN INJURY
ASSOCIATION OF AMERICA AGAIN NOT
WORKING IN SILOS BUT WORKING
TOGETHER WITH A VARIETY OF
DIFFERENT PARTNERS ENSURING THAT
WE HELP PROMOTE AND SHARE THE
KNOWLEDGE AND ALL THE FINDINGS
THAT WE HAVE BASED OFF THE
RESEARCH THAT WE'RE DOING AND
THAT MAKES THE RESEARCH, BETTER,
RIGHT.
HOW CAN WE ENGAGE ALL
INDIVIDUALS IN THE PROCESS TO
HELP IMPROVE CLINICAL PRACTICE
AS WELL AS INFORM -- MAKING SURE
INDIVIDUALS ARE AT THE RECEIVING
END AND MAKING SURE THAT THERE
ARE DIVERSE INDIVIDUALS.
SO JUST INCLUDING A VARIETY OF
DIFFERENT INTERESTED PARTIES OR
STAKEHOLDERS IN THE PROCESS.
>> THANK YOU, MONIQUE AND
EVERYONE TO PARTICIPATED ON THE
SUBCOMMITTEE.
WE HAVE A FEW MINUTES NOW FOR
DISCUSSION.
>> WE'RE RUNNING A LITTLE LATE
SO WE'LL HAVE 15 MINUTES FOR
DISCUSSION.
>> THANK YOU.
AMBER, I CAN'T SEE HANDS RAISED
SO IF YOU DO --
>> RIGHT NOW I DO NOT SEE HANDS
RAISED.
LET ME CHECK VIDEOCAST.
>> I SEE PENNY.
PENNY ARE YOU ABLE TO UNMUTE?
>> WORKING ON IT.
TOOK A MINUTE.
SORRY.
YOU GUYS HAVE DONE A WONDERFUL
JOB.
THANK YOU FOR PULLING THIS
TOGETHER.
MY QUESTION IS THERE WERE A
COUPLE TIMES IN THE DISCUSSION
WHERE IT HEARD THE REFERENCE
BETWEEN TBI AND ALZHEIMER'S AND
A KNOWLEDGE SHARING BETWEEN THE
TBI AND ALZHEIMER'S FIELD AND
YET TBI IS NOT JUST RELATED TO
ALZHEIMER'S IT'S RELATED TO THE
COMPLEX IDEOLOGY AND BEHIND
HAVING NOT JUST ALZHEIMER'S BUT
ALSO THE PLACE WHERE FTD AND ALS
IS WELCOME.
WELCOME HOW THE TBI FIELD AND
HOW YOUR RECOMMENDATIONS ARE
THINKING ABOUT THE HOLISTIC
CAUSES OF DEMENTIA AND HOW HEAD
IMPACT AND TBI AND FORGIVE ME
BECAUSE I'M PROBABLY GET YOUR
TERMINOLOGY LONG, I KNOW IT'S
COMPLICATED.
HOW DO THEY RELATE TO DIFFERENT
FORMS OF DEMENTIA?
I'LL STOP.
>> THANK YOU, PENNY.
IT'S A GREAT QUESTION.
IT ACKNOWLEDGES THE EVOLUTION OF
SCIENCE IN THE SPACE.
FOR DECADES WE WERE ALL TAUGHT
TRAUMATIC BRAIN INJURY WAS THE
GREATEST ENVIRONMENTAL RISK
FACTOR FOR ALZHEIMER'S DISEASE
IN PARTICULAR.
IN THE ENSUING DECADES WE HAVE
COME TO APPRECIATE THAT WE
ACTUALLY DO NOT SEE ALZHEIMER'S
DISEASE NEUROPATHOLOGY AS
COMMONLY AS WE WOULD HAVE
EXPECTED IF THAT WERE
EXCLUSIVELY TRUE.
TRAUMATIC BRAIN INJURY AND
POST-TRAUMATIC BRAIN IS A
DEMENTIA AND INHERENT THAT A
TRAUMATIC BRAIN INJURY IS ONE OF
LIFE EXPOSURES OVERLAID TO OTHER
EXPOSURES THAT MAY HAVE IMPACTED
DEMENTIA RISK IN A GIVEN
INDIVIDUAL.
DR. GRANT, IT WOULD BE GREAT IF
YOU'D BE WILLING TO TOUCH ON
THIS TOO.
I KNOW WE SPENT TIME THINKING
THROUGH THIS IN OUR MEETINGS ON
THE IMPORTANCE OF UNDERSTANDING
HOW A NEW ONSET TRAUMATIC BRAIN
INJURY MY IMPACT DISEASES AND
DIAGNOSES AND USE OF EXISTING
TREATMENT.
>> THANKS FOR THE QUESTION.
IT'S THE QUESTION AND I DON'T
WANT TO OVEREMPHASIZE THE LINK.
THERE'S A VERY GOOD EXAMPLE OF A
COMMUNITY THAT WORKS WELL AND
THEY COVER LOTS OF ETIOLOGIES.
WE NEED TO BE TALKING TO A VERY
WIDE RANGE OF SPECIALIST GROUPS
AND TRYING TO BRIDGE ACROSS
THESE BECAUSE THERE ARE
INTERESTING AND SCIENTIFICALLY
INFORMATIVE OVERLAPS BETWEEN
WHAT YOU SEE AND TBI.
IT TOUCHES ON OUR IGNORANCE OF
THE GENERAL HIGH LEVEL THINGS
LIKE AGING.
IT'S NOT CLEAR WHAT TBI DOES TO
YOUR NEURODEGENERATIVE
TRAJECTORY AND MIGHT ACCELERATE
WHAT WOULD HAVE HAPPENED ANYWAY.
THERE'S A LOT OF WORK TO BE DONE
AND WE'RE THINKING INCREASINGLY
OPEN MINDED AND IT'S CHALLENGING
AS A CONDITION TO TREAT BECAUSE
CO-PATHOLOGY IS SO COMMON OR
POLY PATHOLOGY AND IN THE
SPORTING CONTEXT THERE'S A GREAT
DEAL OF TALK WITH CTE AND IT'S
ALMOST A BRANDING
BUT OF COURSE WE INCREASINGLY
RECOGNIZE CO-PATHOLOGIES ARE
EXTREMELY COMMON AFTER HEAD
IMPACTS AND EVEN IF YOU WERE TO
TREAT THE CTE PATHOLOGY IN ALL
THOSE GROUPS THEN YOU'D PROBABLY
FIND THERE'S STILL A GREAT DEAL
OF DEMENTIA VARIANTS KIND OF
UNTREATED.
IT'S A GREAT CONDITION I'D ARGUE
TO MEASURE INFLAMMATION AND
PATHOLOGY AND TARGETING
DIFFERENT THINGS BUT WORKING AT
AN INDIVIDUAL LEVEL WHAT'S
HAPPENING.
THAT'S MY TAKE ON IT BUT THERE'S
LOTS OF WORK THAT NEEDS TO BE
DONE.
>> I WORK FOR THE ASSOCIATION
FRONTOTEM
FRONTOTEMPORAL DEGENERATION AND
HEAD IMPACT WAS UP BUT LITTLE IS
KNOWN FROM IT BUT FROM A
THEORETICAL SIDE THAT NO REASON
TO THINK IT WOULDN'T HAVE A
SIGNIFICANT RELATIONSHIP.
>> IT'S IMPORTANT TO RECOGNIZE
OUR RECOMMENDATIONS ARE STRIVING
TO FY WHAT ARE THE UNIQUE
PATHOLOGIES OF DISTINCT IT HEAD
TRAUMA EXPOSURES SUB TYPES AND
HOW DO THEY INTERACT WITH THE
PATHOLOGIES OF BETTER KNOWN
ADRDs?
THIS IS THE HALLMARK OF WHAT
WE'RE TRYING TO PRIORITIZE
ACROSS OUR RECOMMENDATIONS.
AND WE ALSO TRY TO EMPHASIZE
THAT RECOGNIZE THE RELATIVE
INFANCY OF OUR RESEARCH AND THIS
HAS BEEN STUDIED FOR CENTURIES.
AND SO WE WANT TO LEARN FROM OUR
COLLEAGUES WHO HAVE BEEN AT IT
LONGER AND USE THE TREMENDOUS
WORK THAT'S ALREADY BEEN DONE AS
A STARTING POINT AND CONTINUE
COLLABORATION SO WE CAN
ACCELERATE KNOWLEDGE AS QUICKLY
AS POSSIBLE.
I SEE A QUESTION FROM NICOLE
BR --BJORKLUND.
>> WHEN WE KNOW ABOUT THE
PARTNER VIOLENCE AND WE DON'T
KNOW WHAT THE IMPACT OF THAT IS
COMPREHENSIVELY BUT ONE QUESTION
I HAD WAS CONSIDERING WHAT
YOU'RE STUDYING IT SEEMS LIKE
THERE SHOULD BE MORE WORK WITH
THE AND DOD, ARE THERE
POSSIBILITIES OF INCORPORATING
OR MESHING WITH THEM IN TERMS OF
DATA AND BIO SPECIMENS?
>> I THINK WE HAVE SOMEONE TO
SPEAK TO THIS.
>> EVERYTHING WE DO IS IN
PARTNERSHIP AND WITH NINDS AND
DOD AND V.A. AND DR. HOFFMAN IS
A WORKING MEMBER ON THIS
COMMITTEE.
IF YOU HAVE SOMETHING TO ADD
TOO.
>> YOU'RE ON MUTE.
DOES SOMEONE NEED TO ENABLE YOUR
MICROPHONE.
>> NOW IT'S ON.
EVERYONE CAN HEAR ME?
>> YES.
>> YEAH.
THE LONG-TERM ISSUES IS A
PRIORITY FOR THE V.A. BECAUSE
UNLIKE DOD AROUND MANY OF THE
HOSPITAL SYSTEMS OUT THERE, WE
DON'T TREAT ACUTE TBI.
WE GET THE PERSON AFTER THEY
HAVE HAD LIFE TIME BRAIN
INJURIES.
SO WE TRY TO WORK BACK THAT.
WE HAVE TWO LONGITUDINAL STUDIES
THAT ARE ONGOING.
ONE IS STARTING FROM 2010 AND
THE OTHER ABOUT 2013 THE V.A. IS
NOW GOING TO CARRY IT ON FOR THE
FORESEEABLE FUTURE.
AND WE'RE ACTUALLY HARMONIZING
THE DATA BETWEEN THE TWO THAT
WILL HELP US TO UNDERSTAND
CRITICAL BIOMARKERS FOR
DIAGNOSTIC PURPOSES AND PERHAPS
ALLOW US TO EVEN APPROACH HOW TO
MAYBE DEVELOP TREATMENTS THAT
ARE MECHANISTIC IN THE FUTURE
FOR SOME OF THESE MORE
PROGRESSIVE PROCESSES.
LIKE YOU ASKED, IT IS A MAJOR
PRIORITY AND WE DO COLLABORATE
ESPECIALLY AT POLY TRAUMA
CENTERS COLLABORATE WITH THE TBI
MODEL SYSTEMS AND SO OUR MODEL
SYSTEM IS CONSIDERS THE CIVILIAN
VERSION A CRITICAL PARTNER WE'VE
BEEN TEAMING UP WITH WELL OVER
10 YEARS.
THIS IS THE IMPORTANT PART, TBI
AS CMS, CENTERS FOR MEDICAID --
SORRY, I DON'T REMEMBER ALL THE
CMS INITIALS.
I'M FORGETTING ON THE SPOT HERE,
BUT THEY HAVE NOW RECOGNIZED
SOMETHING THAT THE V.A. HAS
RECOGNIZED SINCE 2011 THAT TBI
IS A CHRONIC CONDITION.
SO WE IN OUR FEDERAL PARTNERS
AND NIH AND DOD, THIS ASPECT IS
A HIGH PRIORITY SO THANK YOU FOR
THE QUESTION.
>> THANKS.
I ALSO WANTED TO ADD THAT WE
HAVE THE BIO REPOSITORY WHERE
WE'RE NOW LINKING THE TISSUE AND
FLUIDS BIO SAMPLES WITH THE DATA
FROM THE CLINICAL STUDIES AS
WELL AS THE BRAIN BANKS.
SO THERE'S DEFINITELY A LOT OF
ADDITIONAL INFORMATION THAT WE
GET WHEN WE HAVE A COMPREHENSIVE
COALITION OF ALL THE DATA AND
WE'RE EXCITED TO SEE HOW THINGS
WILL MOVE FORWARD AND I ALSO
WANTED TO GIVE TIME FOR SARAH
FONTANE THE DOD PARTNER, IF YOU
HAVE ANYTHING TO ADD.
>> I WANTED TO ADD IN THAT
THERE'S OFTEN A STIGMA THE DOD
WORKS WITH AND WHILE THERE CAN
BE, THERE'S MANY RESEARCHERS
WITHIN THE DOD WILLING TO WORK
ON THIS LONG TERM EFFECT OF WHAT
IS HAPPENING WITH THE TISSUES,
WITH THE BIO SAMPLES WE HAVE
BANKED.
WE'VE GOT COLLABORATIVE FOLKS.
THE WHOLE POINT IS TO LOOK AT
THE DEGENERATION AND RELATED
DEMENTIAS BECAUSE WE SIMPLY
DON'T HAVE ENOUGH INFORMATION IN
THE AREA OF THE FIELD TO BE ABLE
TO DISTINGUISH WHAT, IF ANY, IS
THE LIKELY POST TBI PATHOLOGY
WE'LL END UP WITH WE'RE
INCLUSIVE THERE BUT THERE'S A
WHOLE RESEARCH PROGRAM THAT I
MANAGE THAT FOCUSES PRIMARILY ON
THAT.
SO, THANK YOU.
>> I JUST WANT TO ADD ONE MORE
THING.
THE V.A. ALSO THROUGH THE WORK
OF DR. PUGH HAS A DATA SET FOR
VETERANS GOING BACK TO THEIR
MILITARY SERVICE AND THAT NUMBER
IS ABOUT OVER 2 MILLION.
AROUND AND LOOKING AT THEIR
HEALTH CURRENTLY.
WHETHER IT'S DEMENTIA OR OTHER
ASPECTS OF BRAIN HEALTH, WE HAVE
THAT MILITARY DATA SET THAT'S
AVAILABLE.
>> THANK YOU ALL.
YOU CAN SEE OUR SUBCOMMITTEE IS
LUCKY TO HAVE OUR FEDERAL
COLLEAGUES WEIGH IN AND NICOLE,
GREAT QUESTION, THAT ALLOWS US
TO UNDER SCORE THE THEME ACROSS
OUR RECOMMENDATION WE NEED TO
BREAK DOWN BARRIERS AND
COLLABORATE AND WORK ACROSS
AGENCIES.
THANK YOU FOR THAT.
I SEE IAN KREMER.
>> I APOLOGIZE IF I MISSED THIS
BUT I LOST CONNECTIVITY EARLIER
IN THE TALK.
DO THE RESEARCH RECOMMENDATIONS
ADDRESS ONE OR BOTH OF THE
FOLLOWING POSSIBILITIES.
ONE IS LOOKING AT OTHER FORMS OF
DEMENTIA THAT HAVE HIGH INCI
INCIDENTS OF FALLS AS POTENTIAL
DRIVERS OF TBI AND THEREFORE AS
RISK REDUCTION POSSIBILITIES AND
THE OTHER IS THE RESEARCH
RECOMMENDATIONS ADDRESS
OPPORTUNITIES TO COLLABORATE
WITH THE INTERNATIONAL RESEARCH
COMMUNITY PARTICULARLY COUNTRIES
WITH EXTENSIVE HISTORIES DURING
WARTIME TO STUDY TBI IN THE
NON-U.S.-BASED POPULATIONS.
>> THAT'S A GREAT QUESTION AND
KEEP IN MIND PART OF THE MAIN
GOALS OF THE DAY TOGETHER IS TO
SOLICIT INPUT ON OUR
RECOMMENDATIONS.
AND MAKING SOME NOTES, THESE ARE
GREAT IDEAS.
HEATHER SNYDER ARE YOU STILL
WITH US TO SPEAK TO THE QUESTION
PERTAINING TO FALLS AND
RELATIONSHIPS WITH POST-TBI
DEMENTIAS?
>> I DON'T THINK SO.
>> IT'S SUCH AN IMPORTANT AREA
OF RESEARCH.
A LOT OF STUDIES HAVE EXAMINED
ASSOCIATIONS OF FALLS WITH
DEMENTIA RISK AND MANY ASSUMED
TRAUMATIC BRAIN INJURY IS THE
CONFOUNDER AND A COUPLE STUDIES
FOUND THAT AND THE NOTION THAT A
FALL MAY BE A HARBINGER OR AN
EARLY SIGN OF A
NEURODEGENERATIVE PROCESS I
THINK REQUIRES INVESTIGATION AND
SPANS BEYOND OUR SUBCOMMITTEE.
THERE'S A NEED TO UNDERSTAND HOW
NUANCED THE TRAUMATIC BRAIN
INJURY, IN LATE LIFE, FOR
EXAMPLE, INTERACTS WITH OTHER
NEURODEGENERATIVE PROCESSES AND
MAY HAVE RESULTED FROM LATE LIFE
FALLS WHICH IS A CRITICAL TARGET
FOR PREVENTION.
>> FOR THE SECOND QUESTION ABOUT
COUNTRIES THAT HAVE HIGHER
INCIDENTS DUE TO CONFLICTS OR
OTHER ENVIRONMENTAL REASONS.
AS PART OF THE ALZHEIMER'S
RESEARCH PROGRAM WE'RE ALLOWED
TO FUND INVESTIGATORS IN THOSE
COUNTRIES AND COLLABORATING WITH
SOME OF THOSE AND WE ACTUALLY DO
HAVE SEVERAL STUDIES RIGHT NOW
WHERE WE'RE LOOKING AT THE
FOLLOW-UP FROM POPULATIONS WHO
HAVE A HIGH LEVEL OF TRAUMATIC
BRAIN INJURIES EVEN COMPARED TO
THE UNITED STATES DUE TO
MILITARY SERVICE AND G
GEOPOLITICAL COMPLEX AND CAN ADD
THAT TO THE KNOWLEDGE BASE GOING
FORWARD.
>> HOPEFULLY THE FOGARTY CENTER
WILL CONTINUE TO EXIST.
>> I BELIEVE THAT CONCLUDES OUR
TIME.
>> WE'LL SKIP THE SCHEDULED
BREAK AND KEEP GOING WITH THE
LAST SESSION OF THE DAY IF THAT
WORKS FOR EVERYBODY.
WE CAN TAKE A MINUTE WHILE OUR
TEAM BRINGS UP THE SLIDES AND
SESSION 4 SPEAKERS, PLEASE GET
READY TO PRESENT.
THANK YOU.
>> ALL RIGHT.
THANK YOU FOR TUNING INTO OUR
SESSION LATE AND I'M FROM
BRIGHAM AND WOMEN'S HOSPITAL AND
LATE WAS NAMED IN 2019 DEFINED
BY THE IMMIGRAAGGREGATION IN A
ENTER SERVICE AND IT WAS FOUND
IN THE FRONTAL GYRUS AND THE
CLINICAL SYNDROME IS A COGNITIVE
DECLINE.
WHY DO WE CARE ABOUT LATE?
IT'S SENIOR AND PATHOLOGICAL
SENSE SO IT'S AN IMPACTFUL
PATHOLOGY THE THIRD TYPE OF
DEMENTIA PRESENTATION AND
FOLLOWS ALZHEIMER'S DISEASE AND
VASCULAR IMPAIRMENT TO ATTRIBUTE
TO THE RISK IN OLDER ADULTS.
ONE IN EVERY FIVE WITH TAU
PATHOLOGY HAVE A PURE FORM OF
LATE NC CAN BE FOUND IN OVER AGE
75 WITH SOLE PROGRESSION BUT
PRETTY MUCH FROM CLINICAL
PRACTICE STANDPOINT IT'S
DIFFICULT TO DISTINGUISH FROM
ALZHEIMER'S DISEASE AND YOU HAVE
TO RELY ON BIOMARKERS TO
DISTINGUISH AND THE BIGGER
IMPLICATIONS COME FROM THE MIX
PATHOLOGY AND ALZHEIMER'S
DISEASE AND LATE LIKES TO
COMMINGLE.
MORE THAN HALF CASES WITH AD
PATHOLOGY HAVE LATE NC AND THEY
HAPPEN IN THE BACKGROUND OF
ALZHEIMER'S DISEASE AND THIS
COMBINED PATHOLOGY IS NOT ONLY
THE MOST COMMON BUT THE MOST
PROGRESSIVE AND SHOWS RAPID V
VOLUME LOSS AND HAS A GREAT
PUBLIC HEALTH IMPACT AND
ESPECIALLY PROBATIC IN
ANTI-AMYLOID ANTIBODIES BECAUSE
IT CAN BE A MAJOR CONFOUNDER OF
RESPONSE AND THE CLINICAL COURSE
IN THE SETTING OF COMBINED
PATHOLOGY.
LAST BUT NOT LEAST, THE PUBLIC
HEALTH IMPACT ASSOCIATED WITH
LATE IS ONLY EXPECTED TO
INCREASE OVER TIME.
IT'S PREDOMINANTLY FOUND IN THE
OLDEST OLD POPULATION AND THE
RAPIDLY EXPANDING SEGMENT AND
OVER 80 AND 90 THE IMPACT IS
GREATER THAN ALZHEIMER'S DISEASE
ITSELF AS SHOWN BY THE 90 PLUS
STUDY FROM THE UNITED STATES AND
THE STUDY FROM FINLAND.
GIVEN THE SIGNIFICANCE THE
SUBCOMMITTEE WAS ESTABLISHED IN
2019 AND MADE RECOMMENDATIONS IN
2022 AND GOALS WE SET WERE
SUMMARIZED HONING THE DEFINITION
OF LATE AND HOW TO BETTER
DIAGNOSIS THIS IN VIVO AND LOU
TO STUDY MECHANISMS OF LATE
PATHOGENESIS.
I'M GLAD TO REPORT THERE'S BEEN
SIGNIFICANT PROGRESS IN THE PAST
THREE YEARS.
WE NOW HAVE INITIAL CLINICAL
CRITERIA TO USE IN THE CLINIC.
FOR EXAMPLE, THIS IS THE OUTLINE
OF THE CLINICAL KROO CRITERIA TO
DEFINE AS A PRIMARY DIAGNOSIS.
IF SOMEONE PRESENTS WITH
COGNITIVE DECLINE WITH OTHER
DOMAINS RELATIVELY PRESERVES AND
HIPPOCAMPAL ATROPHY AND
BIOMARKERS THAT CASE IS
DIAGNOSED AS PROBABLE LATE MEANS
LATE NEUROLOGICAL CHANGES ARE
LIKELY THE PRIMARY DRIVER OF THE
CLASSIFICATION.
IF THEY HAVE A POSITIVE A BETA
BIOMARKER WE CHECK TAU
BIOMARKERS IN THE MEDIAL
TEMPORAL LOBE AND IF IT'S
NEGATIVE IT CAN BE DIAGNOSED AS
POSSIBLE AND THERE'S MRI AND PET
PATTERNS ASSOCIATED WITH THE
PATHOLOGICAL CHANGE.
HOWEVER, THERE'S STILL REMAINING
GAPS AND ONE BIG LIMITATION IS
CLINICAL DATA SETS FOR OUR
ABILITY TO PERFORM TARGET
DISCOVERY EFFORTS.
WE HAVE A NEUROPATHOLOGY
CRITERIA FOR LATE CHANGE AND
DETAILS HOW TO DEFINE IT FOR
EACH STAGE ALSO BETTER WAYS TO
DISTINGUISH IT FROM OTHER TDP
AGGREGATION DISORDERS AND ALS.
CLARIFYING THE RELATIONSHIP WITH
THE HIPPOCAMPUS IS CLOSELY
RELATED HISTOLOGICAL FINDING
NEEDS MORE WORK.
THERE'S BEEN PROGRESS IN
MECHANISTIC STUDIES.
THE GENOME WIDE STUDY HAS BEEN
PERFORMED AND CONFIRMED
PREVIOUSLY IDENTIFIED GENETIC
RISK FACTORS SUCH AS APOE 4 AND
VARIANTS AS WELL AS GRANULIN
VARIANT AND OTHER CANDIDATE
MARKERS THAT CAN BE FOLLOWED UP
IN THE FUTURE STUDIES.
AND SPLICING EVENTS COMPARED TO
OTHER OPATHTIES AND THEY NEED
MORE WORK.
BASED ON THE GAPS AND OTHERS,
OUR SUBCOMMITTEE HAS A DRAFT FOR
RECOMMENDATIONS AND THESE WERE
PRESENTED AND I'LL TOUCH ON
RECOMMENDATION ONE BECAUSE TWO
TO FOUR WILL BE COVERED BY MY
COLLEAGUES FOLLOWING THIS
PRESENTATION.
SO RECOMMENDATION ONE IS TO
DEVELOP AND EXPAND THE PHENOTYPE
COHORTS WITH CHARACTERIZATION
INCLUDING POSTMORTEM DATA WITH
THE GOAL TO UNCOVER UNIQUE
FEATURES OF LATE VERSUS OTHER
PATHOLOGY TO INFORM DIAGNOSIS
AND THERAPIES.
AND ALSO INFORM HOW TREATMENT
AFFECTS LATE NC AND SO ON.
FINALLY, IT'S CRITICALLY
IMPORTANT TO SUPPORT
INFRASTRUCTURE FOR CROSS-TALK
BETWEEN THE FIELDS WITH ALS
FIELDS THAT STUDY PATHOLOGIES
AND ENHANCE THE FOR ALL THE
DISORDERS.
AND EXPANDING AWARENESS IN THE
PUBLIC CLINICIANS AND OTHER
STAKEHOLDERS ARE IMPORTANT FOR
THE COMMON UNDER STUDIED
DISORDER.
THIS IS ALL I HAVE.
THANK YOU FOR YOUR ATTENTION.
I'LL TURN IT OVER TO THE NEXT
SPEAKER, KONSTANTINOS.
>> I HAVE NOTHING TO DISCLOSE.
THE SECOND RECOMMENDATION IS TO
AND VALIDATE IN VIVO MODIFIERS
AND RISK CLASSIFIER FOR LATENCY
AND THEY MUST HAVE GOOD
PERFORMANCE AS WELL AS IN
PERSONS WITH LATE LIFE DEMENTIA
SYNDROMES.
DIAGNOSIS IS ONLY VIABLE IN
AUTOPSY AND IT'S A MAJOR STEP
FORWARD IN TERMS OF LATE
DETECTION.
HOWEVER, WITHOUT THE MARKER
WE'RE LIMITED.
THEREFORE THERE'S AN URGENT NEED
FOR MOLECULARLY SPECIFIC
MARKERS, CLASSIFIERS AND RISK
PROIFIER FOR LATE TO ALLOW
PARTICIPANT SELECTION OF LATE
AND ABRB BECAUSE LATE IS OFTEN
MIXED WITH OTHER
NEUROPATHOLOGIES.
THEREFORE SUPPORT DRUG DISCOVERY
AND TREATMENT AND HAVING ACCESS
TO ACCURATE MARKERS WILL ENHANCE
ALL OTHER RESEARCH ON LATE.
WE KNOW LATE IS RELATED TO
MEMORY LOSS AND DEFICIT AND MORE
COMMON IN INDIVIDUALS OLDER THAN
75 YEARS OF AGE.
WE ALSO KNOW THERE ARE A NUMBER
OF GENES LINKED TO LATENCY.
HOWEVER WE NEED TO REFINE OUR
UNDERSTANDING OF THE COGNITIVE,
BEHAVIORAL AND GENETIC FEATURES
ASSOCIATED WITH LATENCY.
BY DOING THAT WE MAY IMPROVE
DETECTION OF LATE AND IF WE HAVE
A MARKER OF LATE, IT MAY HELP US
UNDERSTAND BETTER THE COGNITIVE
BEHAVIOR AND GOOD MORNING
FEATURES OF LATE.
SO, THIS IS A TWO-WAY STREET.
BY COMBINING IN VIVO OR EX VIVO
MRI WE'VE BEEN ABLE TO SHOW
LATENCY ASSOCIATED WITH THE
TEMPORAL LOBES AND OTHER LOBES
AND INSULA AND WE HAVE SHOWED
LATENCY HAS A STRONGER IMPACT ON
THE HIPPOCAMPUS THAN
ALZHEIMER'S.
WE'VE BEEN ABLE TO MAP THE
PATTERN OF OUR ABNORMALITIES
ASSOCIATED WITH LATENCY AND TO
DEMONSTRATE THE MAIN CONNECTIONS
IN THE BRAIN THAT ARE IMPLICATED
HERE ARE TEMPORAL CONNECTIONS,
TEMPORAL BASAL GANGLION
CONNECTIONS.
IN ADDITION, WE'VE BEEN ABLE TO
SHOW THE PROGRESSION OF THE
ABNORMALITIES IS FOLLOWING THE
PROGRESSION OF LATENCY.
ALSO WE HAVE PATHOLOGY MAPPED
PATTERN OF ABNORMALITIES IN THE
BRAIN ASSOCIATED WITH LATENCY.
ADDITIONALLY, BY COMBINING EX
VIVO MRI PATHOLOGY WE HAVE DEM
VATE D -- DEMONSTRATED LATENCY
FOLLOWS THE SPREAD CONSISTENT
WITH THE SPREAD OF THE PATTERN.
OVER THE LAST FEW SLIDES I HOPE
IT BECOMES CLEAR THAT MRI IS
SENSITIVE TO THE BRAIN
ABNORMALITIES ASSOCIATED WITH
LATE NC AND FUTURE STUDIES COULD
USE THESE AND OTHER FEATURES TO
TRAIN MRI BASED CLASSIFIERS OF
LATENCY.
USING PET STUDIES HAVE SHOWN
LATENCY IS ASSOCIATED WITH MORE
PRONOUNCED HYPERMETABOLISM IN
THE MEDIAL TEMPORAL LOBE AND THE
PATTERN IS TRUE FOR ALZHEIMER'S.
THEREFORE THE STUDY HAS
SUGGESTED
SUGGESTED IT MAY BE A MARKER FOR
LATENCY.
FURTHER WORK IS NEEDED TO TEST
THE CLASSIFIERS OF LATENCY.
AND THERE'S FEATURES AND
ADDITIONAL FEATURES AND FOR NOW
WE NEED TO TEST THE CLINICAL
CRITERIA USING LONGITUDINAL
OBSERVATIONS AND NEUROIMAGING
MARKERS AND NEUROPATHOLOGY.
IN THE FUTURE WE NEED TO UPDATE
THE CRITERIA BASED ON
DEVELOPMENTS IN THE FIELD.
AND HIGHER LEVELS OF TDP43 IN
THE PLASMA DERIVED EXTRA
CELLULAR VESICLES WITH THOSE
WITH TDP AND IN ADDITION LOSS OF
TDP43 AND PROTEINOPATHY IS
LINKED TO THE EXPRESSION OF THE
AND RECENT STUDIES SUGGESTED THE
PLASMA OR CSF HAS POTENTIAL AS A
MARKER FOR LATE.
ADDITIONAL WORK IS NEEDED TO
DEVELOP AND TEST BIOFLUID
MARKERS OF LATENCY.
ALSO EXCITING FINDINGS COME FROM
THE FIELD OF PET MARKERS OF
TDP43 WHERE RELATIVELY RECENTLY
NEW PET LIGAND HAS SHOWN
PERFORMS PERFORMANCE IN THE
SAMPLES AND IN ANIMAL TESTS.
AS FAR AS I KNOW THIS IS
CURRENTLY BEING TESTED IN HUME
CANS HAVE AND ADDITIONAL WORK IS
NEEDED TO TEST LATENCY.
IN CONCLUSION THERE'S AN URGENT
NEED FOR MARKERS OR CLASSIFIERS
THAT SHOW GOOD DISCRIMINATION OF
PATHOPHYSIOLOGY AND COULD BE
NEUROIMAGING OR BIO FLUID OR IN
COMBINATION.
IN ORDER TO ACCOMPLISH THE ABOVE
AWAY NEED COHORTS TO JOIN
MARKERS WITH DATA AND PATHOLOGY
AND EX VIVO MRI.
IN ADDITION WE NEED TO REFINE
OUR UNDERSTANDING OF THE
COGNITIVE AND GENETIC FEATURES
ASSOCIATED WITH LATENCY AND WE
ALSO NEED TO TEST THE CLINICAL
CRITERIA AND UPDATE THIS
CRITERIA IN THE FUTURE DEPENDING
ON NEW DEVELOPMENTS IN THE
FIELD.
THANK YOU.
>> THANK YOU.
I'LL CONTINUE LOOKING AT THE
CAUSES AND THERAPEUTIC
OPPORTUNITIES.
AND LOOK AT CAUSES AND THROUGH
HUMAN STUDIES AND ENVIRONMENTAL
MODELS AND AGING AND
PATHOLOGICAL AND MOLECULAR AND
STRUCTURAL PATHOLOGIES WITH THE
FOCUS ON DEVELOPING AND TESTING
TARGETS FOR THERAPEUTICS.
THE FIRST ASPECT IS DESIGN AND
DEVELOP MODELS OF LATE NC.
IN MANY SLIDES I'M USING
EXAMPLES FROM OTHER ALZHEIMER'S
DISEASE RELATES DEMENTIAS
BECAUSE IT'S THE MODELS LACKING
IN LATE NC SPECIFIC MODELS.
SO HUMANS SEEM TO HAVE THIS
UNIQUE SUSCEPTIBILITY TO LATE NC
HOWEVER, WE DON'T HAVE GOOD
MODELS OF LATE NC IN MISSING OR
OTHER ANIMAL MODELS.
WHAT WE'RE LOOKING FOR IS
DEVELOP MODELS OF DYSFUNCTION
NOT JUST IN ALS THAT ALREADY
EXIST BUT WHERE WITH HAVE
PHENOTYPES IN THE MODELS.
ADDITIONALLY IN THE MODELS WED
LIKE TO CHARACTERIZE GLIAL AND
NEURAL INFLAMMATORY
CONTRIBUTIONS TO TDP ADENOPATHY
AND THERE'S MOLE MODELS OF THIS
IN ALS AND WOULD LIKE TO
TRANSLATE THE MODELS IN LATE.
WE'RE ALSO TRYING TO LOOK AT
DEVELOPING CELLULAR NOLDES AND
HOW TO MODEL LATE NC PATHOLOGY
IN INDUCED PLURIMOW --
PLURIPOTENT MODELS AND IN THE
CULTURE SYSTEM OR USED PATIENT
DERIVED HAVE LATE WILL THOSE
REPRESENT ANY PHENOTYPES SEEN IN
LATE AS SUGGESTED BY SOME FOR
ALS.
AND OBSERVE WHAT'S BEEN IN
PATIENT GLIAL CELLS AND THIS IS
IMPORTANT TO DEFINE THE LOSS OF
FUNCTION AND GAIN OF CYTOPLASMIC
CYTOPLASMIC FUNCTION AND WHAT
CAN WE DO TO MODEL LATE NC IN
CELLS TO STUDY THIS CONDITION IN
DETAIL.
AND TO GO FURTHER TOWARDS
STRUCTURALLY SPECIFIC AND IN
VITRO MODELS WHERE WE NEED TO
UNDERSTAND LATE SPECIFIC ULTRA
STRUCTURE OF TDP43 ITSELF WHEN
IT'S DEPOSITED AND POTENTIAL
CO-DEPOSITED PROTEINS IN
ORGANISM MODELS AND BIO CHEMICAL
MODELS AND WOULD LIKE TO
UNDERSTAND THE STRUCTURE OF
TDP43 AND HAS BEEN DISCOVERED BY
WORK IN A LAB IN THE U.K. AND
WHAT IS THE MOLECULAR STRUCTURE
IN LATE?
THAT BRINGS UP AN IMPORTANT
QUESTION.
ANOTHER ASPECT OF OUR
RECOMMENDATION IS TO LOOK AT THE
TDP43 STRUCTURE DIRECTLY AND TRY
TO UNDERSTAND THE PRIMARY
STRUCTURAL AND POST
TRANSLATIONAL MODIFICATIONS AND
THE IMPORTANCE OF COMPOSITION OF
CO-DEPOSITED PROTEINS.
FOR EXAMPLE IN FTLD IS THAT THE
CASE IN THE LATE AND WE DO SEE
OTHER PROTEINS CODEPOSITED IN
LATE.
IMPORTANTLY WE'D LIKE TO
UNDERSTAND HOW THE PATHOLOGICAL
INCLUSION FORMED.
WHAT IS THE ASSEMBLIES FORMED
AND CAN WE PREVENT THE FORMATION
OF THESE ABHORRENT STRUCTURES
AND WHAT DOES IT LOOK LIKE
INITIALLY BEFORE DEPOSITION AND
EITHER OF THESE THINGS, THESE
TOXIC OR POTENTIALLY TOXIC
INCLUSIONS THAT ARE STRUCTURES
ON THE LEFT OR THESE FUNCTIONAL
ASSEMBLIES OF THE SAME REGION OF
TDP43 IN THE CENTER MAY BE
TARGETS FOR THERAPEUTIC
MODULATION.
THERE'S CO-DEPOSITED PROTEINS
AND WHAT ARE THESE MOLECULAR
CONSEQUENCE OF THE PATHOLOGIES?
WE ALSO NEED TO DESIGN MODELS
THAT INCORPORATE NOT JUST TDP43
PATHOLOGY BUT CO-PATHOLOGIES AND
IF THERE'S SYNUCLEIN PATHOLOGIES
AND ORGANISM MODELS AND IF IT
COEXISTS WITH OTHER PATHOLOGIES
WE FEED TO UNDERSTAND HOW THEY
ARE INTERACT.
WE NEED TO STUDY THE MECHANISTIC
BASIS OF DISEASE INITIATION.
HOW DO THE DISEASE START AND HOW
ARE NEURONS LOST?
HOW ARE BRAIN REGIONS TARGETED
FOR DEGENERATION SPECIFIED IN
LATE AGE RELATED PROGRESSION IS
PRIMARILY IMPORTANT.
WE NEED TO UNDERSTAND HOW THAT
WORKS.
CAN WE DEVELOP MODELS THAT
INCORPORATE AGE-RELATED
PROGRESSION AND HOW IS
PROGRESSION ACROSS THE BRAIN
AREAS INCLUDED.
WE ALSO NEED TO DISCOVER GENETIC
CAUSATIVE FACTORS FOR LATE.
SO SEVERAL HAVE BEEN SHOWN AS OR
DISCOVERED AS SHOWN HERE.
WILL WE BE ABLE TO CONFIRM THESE
BY REPLICATION AND WILL WE FIND
NEW GENES CAUSATIVE FOR LATE AND
OTHER TDP43 PROTEINOPATHIES BE
CAUSATIVE FOR LATE.
WE NEED TO STUDY THE LATE
PATHOPHYSIOLOGY.
WHAT ARE THE SPLICING CHANGES WE
HEARD ABOUT.
THERE WAS A RECENT STUDY SHOWN
JUST LAST WEEK THAT THE AMYLOID
PRECURSOR PROTEIN IS PROCESSED
IN THE CYTOPLASMIC GAIN OF
FUNCTION AND IT WOULD BE
INTERESTING TO STUDY WHAT ARE
THE CORRECTIBLE CHANGES THAT
COULD BE TARGETED.
>> WE'RE AT TIME.
>> WE NEED TO GEAR UP TO STUDY
THESE IN MODELS.
WE NEED TO TAKE ACTION ON THESE
POTENTIAL THERAPEUTIC
TECHNOLOGIES BECAUSE WE KNOW IN'
SENSE ALOGOES CAN BE SUCCESSFUL
TREATMENT AND WE'VE HAD
THERAPEUTICS IN SPINAL ATROPHY
AND WE NEED MODELS TO TEST THESE
THERAPIES IN TDP43.
I'LL LEAVE IT THERE.
THANK YOU VERY MUCH.
>> WE'LL GO STRAIGHT TO
DR. NELSON'S TALK.
>> THANK YOU TO THE ORGANIZERS.
I APPRECIATE IT.
IT'S WONDERFUL TO BE PART OF
THIS EXCELLENT SUMMIT.
I HAVE NOTHING TO DISCLOSE.
I'M TALKING TODAY ABOUT
RECOMMENDATIONS RELATED TO
HIPPOCAMPAL SCLEROSIS OF AGING
AND I CAN SAY BASICALLY IT
BREAKS DOWN TO TWO THINGS.
NUMBER ONE, IMPROVING OUR
CLASSIFICATION AND DIAGNOSIS AND
TWO, IMPROVING OUR UNDERSTANDING
OF THE MECHANISM TO PROVIDE
TARGETS FOR FUTURE THERAPIES.
SO WHAT IS HIPPOCAMPUS SCLEROSIS
IT'S LOSS IN THE MEDIAL TEMPORAL
GLOBE AND THE NORMAL HIPPOCAMPUS
ON THE RIGHT.
YOU SEE THE SHRIVALLED
HIPPOCAMPUS WITH CELL LOSS AND
GLIOSIS.
THIS IS A COMMON PATHOLOGY.
10% LIFE TIME RISK AND AFFECTED
25% OF PEOPLE WITH DEMENTIA.
IT DOESN'T AFFECT PEOPLE EQUALLY
ALONG THE HUMAN AGING SPECTRUM.
HERE YOU SEE THE NEXT SLIDE.
GO BACK TO THE LAST SLIDE.
THIS SHOWS YOU ON THE X AXIS IS
AGE AND THE Y AXIS IS PATHOLOGY.
THE BLACK TRACE SMOOTHED BY
MEASURES IS ALZHEIMER'S DISEASE
AND HIPPOCAMPAL SCLEROSIS
PATHOLOGY IS THE RED TRACE AND
UNLIKE ALZHEIMER'S HIPPOCAMPAL
SCLEROSIS THAT FOCUSES MOSTLY ON
THE OLDEST OLD.
HOWEVER IT'S A SOMEWHAT
CONFUSING TEAM AND OFTEN LINKED
TO EPILEPSY.
TO DESCRIBE THIS WE DID A SURVEY
AT THE UNIVERSITY OF KENTUCKY
WHICH IS A UNIVERSITY THAT HAS A
VERY GOOD FAMILIARITY WITH THE
CONDITION.
WE DID THE SURVEY TWICE.
IN 2018 AND 2015 TO SEE WHAT WAS
THE EFFECT OF THE NEW
NOMENCLATURE AND THIS WAS PART
OF THE PART -- PART PASSION --
PARTICIPATION AND 80% OF THE
RESPONDENTS SAID IT WAS AN
EPILEPSY DISORDER TERM AND WE
THOUGHT IT WOULD BE BETTER IN
2025.
BUT REGRETTABLY IT'S NOT THE
CASE.
IT'S STILL NOT REALLY THE TERM
THAT PEOPLE THINK OF WHEN THEY
THINK OF HIPPOCAMPAL SCLEROSIS
THEY THINK OF A DIFFERENT
PATHOMECHANISM OF HIPPOCAMPUS
SCLEROSIS DIFFERENT FROM THAT
WHICH AFFECTS DEMENTIA AND IT'S
MORE COMMON.
SO WE CONCLUDE THAT WE NEED MORE
TERMINOLOGY FOR HIPPOCAMPAL
SCLEROSIS OF AGING.
THE GOLD STANDARD DEFINITION
WHICH IS A PATHOLOGY NEEDS TO BE
STANDARDIZED AND OPTIMIZED IN A
DATA-DRIVEN WAY.
SO IT'S STRONGLY ASSOCIATED WITH
LATE NC BUT NOT SYNONYMOUS.
ON THE RIGHT YOU SEE THE VEN
DIAGRAM THAT SHOWS A MEANINGFUL
CONCEPTUALIZATION OF HIPPOCAMPAL
SCLEROSIS OF AGING IS THE MORE
SEVERE SUB TYPE OF LATE NC AND
THAT COULD BE CONNECTED TO THE
PATHOGENIC PROGRESSION THAT'S
HYPOTHESIZED FROM NO LATE TO
LATE WITH NO PATHOLOGY AND THE
ORANGE ARROW GOES TO LATE WITH
HS MAYBE THE QUESTION IS YOU SEE
THE STRONG HIPPOCAMPUS AND IT'S
LOGICAL YOU THINK IT WOULD BE
BAD FOR YOU BUT WE AND OTHERS
AROUND THE WORLD FOUND THIS
PROGRESSION FROM LATE TO LATE
NC-HS IS ASSOCIATED WITH WORSE
PROGRESSION BUT NOT SEIZURES OR
AD PATHOLOGY BUT LATE NC STAGES.
SO THE WAY YOU DETECT IT IN THE
CLINIC IS BY MRI AT THIS POINT.
THIS IS MY PICTURE OF AN
INDIVIDUAL WHO PASSED AT THE AGE
OF 93 AND HAS THESE NICE
POSTMORTEM IMAGES TAKEN BUT THAT
IS TO UNDER SCORE SOME THINGS
THAT WAS SAID THE HIPPOCAMPAL
ATROPHY AND SCLEROSIS IS WORSE
THAN WHAT YOU SEE WITH
ALZHEIMER'S DISEASE.
WE NEED SPECIFIC CUT POINTS AND
UNDERSTAND THE MECHANISM FOR HOW
THIS DEGENERATION OCCURS.
AND IT'S NOT JUST ABOUT LATE NC.
SO WHY DO SOME SUBSET OF PEOPLE
WHO HAVE LATE AND NOT OTHERS
DEVELOP HS AND THESE MECHANISTIC
INSIGHTS CAN BE TRANSLATABLE.
SO LABS AROUND THE WORLD THAT
FOUND EVIDENCE OF POSSIBLE
PATHOGENETIC MECHANISMS
VASCULAROPATHY AND MORE
INFLAMMATION AND WE NEED MORE
SYSTEMS TO GENERATE TRANSLATABLE
MECHANISMS.
THESE MECHANISTIC INSIGHTS GIVES
US STRATEGIES.
I WANT TO GIVE AN EXAMPLE OF A
SPECIFIC CLINICAL RESEARCH ARM
THAT HAS LED DIRECTLY TO A
CLINICAL TRIAL AIMED AT
PREVENTING DEMENTIA IN OLD
PEOPLE AND HAS NOTHING TO DO
WITH ALZHEIMER'S AND DAVID FARDO
GENERATED THIS AND THERE WAS A
DRUG THAT A COLLEAGUE OF MINE AT
THE UNIVERSITY OF KENTUCKY ARE
USING IN THE FIRST CLINICAL
TRIAL FOR LATE HS.
AND TO GIVE YOU AN IDEA OVER ALL
IDEA OF WHAT IS GOING ON THERE,
IT'S THERE'S A NEW STANDARD OF A
PATIENT WHO'S COGNITION IS
SLIPPING AND THERE'S A BIOMARKER
MANIFESTING.
AND IF THERE'S ABETA AMYLOIDOSIS
NOTICED BY BIOMARKER EVIDENCE
THERE'S HOPE.
IT'S NOT 100% PERFECT BUT NO --
>> DR. NELSON, TIME IS UP.
>> I'M ALMOST DONE.
AND COHORTS COGNITIVE IMPAIRED
AND SOME HAVE THIS TYPE OF
AMYLOIDOSIS AND IF YOU HAVE THE
IMPAIRMENT AND IF YOU HAVE THIS
MRI PICTURE THEN HOPEFULLY WE
CAN DEVELOP NEW REMEDIES AND A
CLINICAL TRIAL SUBJECT TO
PERHAPS PREVENT FURTHER
DEGENERATION.
AND THANK YOU AND I'VE GOT IT.
>> THANK YOU SO MUCH.
>> SO WE'LL HAVE 15 MINUTES FOR
QUESTIONS.
>> THANK YOU TO THE COMMITTEE
AND THE WHOLE GROUP AND
OBVIOUSLY NINDS FOR SUPPORTING
THIS.
I'M CHAIRING THE SESSION.
I GUESS I DID WANT TO START FROM
ONE COMMENT FROM WITHIN OUR
PANEL AN INDIVIDUAL, DEIDRE AND
HER LIVED EXPERIENCE AND GIVE
HER AN OPPORTUNITY TO SAY A FEW
WORDS.
>> YES, MY PAST YEAR MY MOTHER
WAS DIAGNOSED LATE.
OUR JOURNEY TO LATE BEGAN WITH
THE DIAGNOSIS IN 2018 OF MILD
COGNITIVE IMPAIRMENT DUE TO
ALZHEIMER'S.
SHE WAS 81.
WE WERE BRACING FOR THE
PROGRESSION TO DEMENTIA AND
AFTER THE DIAGNOSIS OF MILD
COGNITIVE IMPAIRMENT SHE
REMAINED AT THAT LEVEL WITHOUT
FURTHER DEFICIT WHICH WAS
SURPRISING AND THEN WE WERE TOLD
SHE HAD LATE OR TDP43.
WE LEARNED IT WAS SLOWER MOVING
THAN ALZHEIMER'S AND WOULD
AFFECT HER ABILITY TO LEARN NEW
THINGS AND HAD A PET SCAN TO
CONFIRM NO AMYLOID PLAQUE AND
WERE TOLD HER CEREBRAL CORTEX
WAS INTACT.
IT'S THE FIRST TIME AS A FAMILY
WE FELT HOPE BECAUSE A DIFFICULT
PART FOR ME WAS TALKING TO MY
MOM AND EACH TIME WONDERING WILL
THIS BE THE LAST TIME SHE KNOWS
WHO I AM AND NOW WITH THE NEW
DIAGNOSIS IT'S EDUCATING ALL
THOSE WHO ASSIST HER TO THIS
CONDITION AND WE HAD A FAMILY
WITH HER 24/7 SO SHE WOULDN'T
GET LOST IN THE ENVIRONMENT AND
HAD TO EDUCATE ALL THE DOCTORS
AND NURSES ON THE DIAGNOSIS AND
WEREN'T AWARE OF LATE AND WERE
THANKFUL AND IT DOES MAKE A
DIFFERENCE IN THE CARE AND I
CAN'T STRESS ENOUGH TO GET THE
INFORMATION OUT TO FAMILIES TO
NAVIGATE LATE AND ASSIST HEALTH
CARE PROVIDERS AND THEIR
APPROACH TO THE PATIENTS AND I
KNOW THERE'S RECENT CRITERIA
ABOUT TO BE PUBLISHED WHICH IS
WONDERFUL AND HOPEFULLY THERE'LL
BE CARE GUIDELINES TAILORED TO
LATE BECAUSE RIGHT NOW AS A
FAMILY WE IS HAVE TO EDUCATE
THOSE AROUND US HOW BEST TO
SUPPORT MY MOTHER AND AT THE END
IT REALLY WAS A GAME CHANGER TO
FIND OUT HER ACTUAL DIAGNOSIS
AND IT'S HEARTENING TO KNOW
THERE'S TEAMS LIKE AT PENN
MEDICINE TO CARE ENOUGH TO
PROVIDE ANSWERS TO THOSE WHO
DON'T EXHIBIT THE TYPICAL
MANIFESTATIONS OF ALZHEIMER'S
AND GIVES PEOPLE A SENSE OF
WHAT'S GOING ON.
AGAIN, GETTING THE WORD OUT IS
EVERYTHING AND THANK YOU SO MUCH
AND THANK YOU FOR GIVING ME SOME
TIME TO SPEAK.
>> THANK YOU, DEIDRE, IN THE
ADDITION OF DIAGNOSIS THERE'S
DEMYSTIFYING THE CONDITION AND
THE ABILITY TO DESCRIBE LATE IS
CRITICALLY IMPORTANT.
>> I HAVE MANY QUESTIONS BUT IN
THE INTEREST OF TIME I HAVE ONE
FOR THE HIPPOCAMPAL SCLEROSIS
THE ELEPHANT IN THE ROOM AND
WHEN IT COMES TO THIS DIAGNOSIS
THERE'S A LOT OF INCONSISTENCY
LEADING TO AGREEMENT BETWEEN
DIFFERENT GROUPS.
I DON'T SEE A LOT OF EFFORT IN
TRYING TO UNIFY THE DIAGNOSIS OR
SET OF RECOMMENDATIONS TO HELP
US TALK THE SAME LANGUAGE WHEN
WE SAY HIPPOCAMPUS SCLEROSIS OF
AGING AND THE OTHER DOWN THE
LINE IS MOVING AWAY FROM A
BINARY DIAGNOSIS AND COMING UP
WITH AT LEAST AN ORGANAL
CRITERIA LIKE WITH OTHER
PATHOLOGIES.
>> YOUR POINT IS WELL TAKEN.
WE NEED BETTER CRITERIA FOR HOW
WE THRESHOLD OUR DIAGNOSES IN
THE PATHOLOGICAL AND STRUCTURAL
IMAGING CONTEXT.
WE NEED THAT AND ONE OF THE
STRONG RECOMMENDATIONS THAT WE
MADE IS THAT BOTH FOR IS THE
BIOMARKER OF OPATHY WE NEED
GROUPS TO COME TOGETHER AND MAKE
THE CALLS.
>> AND COME UP WITH HARMONIZED
PROTOCOLS WITH HOW PATHOLOGISTS
SPEAK ABOUT HIPPOCAMPAL
SCLEROSIS AND MOVE IT TO CLINIC.
>> I WANT TO RAISE UP WHEN IT
COMES TO ALZHEIMER'S
DISEASE-RELATED DIMENTIAS ARE
DIFFERENT THAN LATE NC EVEN TO
THIS DAY PEOPLE WILL THINK
THEY'RE BEING IMPACTED BY
ALZHEIMER'S DISEASE AND IN YEARS
PAST BEFORE ALL THE WORK YOU
GUYS HAVE DONE SO NEATLY HAS
SHOWN MORE WHAT THE DISEASE IS.
AND TO THAT END, TDP43 HAS BEEN
ON THE BACK FOOT AND HOW CAN WE
OVERCOME THE INJUSTICE OF THAT
VERY IMPORTANT THING AND
FAMILIES EVEN SAYING IT'S
ALZHEIMER'S DISEASE AND TALKING
TO PEOPLE BUILT AND NOT KNOWING
IT'S AMYLOID AND TAU IMPLICATED
AND THAT'S A BIG PICTURE
QUESTION AND THERE'S WORK
SHOWING TDP43 IS SHOWN
DYSFUNCTIONALLY IN OTHER BODY
PARTS AND THE GUT WHICH COULD BE
A WAY THAT IT'S TRANSMITTED I
GATHER.
SO, ARE YOU LOOKING AT THAT OR
ANY THOUGHTS ABOUT IT?
THANK YOU SO MUCH.
>> I'LL TAKE THE FIRST PART OF
OF THAT QUESTION AND TURN TO
OTHERS IF YOU WANT TO TALK MORE
ABOUT OUTSIDE THE BRAIN.
I THINK WE NOW KNOW ALZHEIMER'S
DISEASE HAS MULTIPLE PATHOLOGIES
AND THERE'S THE IMPORTANCE OF
UNDERSTANDING THE ROLE OF TDP
AND LATE WITHIN THE CONTEXT OF
ALZHEIMER'S DISEASE AND ABLE TO
IDENTIFY THE INDIVIDUALS WITH
ALZHEIMER'S DISEASE WHO HAVE THE
CO-PATHOLOGY BECAUSE IT'S ALMOST
CERTAIN THERE'S MECHANISTIC
DIFFERENCES THAT CAUSE ONE
INDIVIDUAL TO HAVE CON COMBINANT
TDB AND WHEN WE'RE ENGAGED WITH
THERAPEUTICS FOR ALZHEIMER'S
DISEASE WE'RE GOING TO BE
NEEDING TO FIGURE OUT WHO HAVE
THE CO-PATHOLOGIES AND HOW IT
AFFECTS OUTCOMES AND OF WHAT
OTHERS STRESSED AND WE NEED GOOD
BIOMARKERS TO TELL US MORE
DEFINITIVELY ABOUT THE PRESENCE
OF DETERMINING AND HAVING BETTER
BIOMARKERS IS IMPORTANT AND YOU
MENTIONED THE IMPORTANCE OF
EDUCATING THE COMMUNITY ABOUT
THAT AND A -- THERE'S STATEMENTS
OF MORE COMMUNITY OUTREACH IN
UNDERSTANDING THE CONDITION
WHICH IS KEY BECAUSE MANY
NEUROLOGISTS LET ALONE PRIMARY
CARE DOCTORS HAVE NEVER HEARD OF
THE DIAGNOSTIC ENTITY.
I DON'T KNOW IF ANYONE WANTS TO
COMMENT OUT SIDE THE BRAIN IN
TERMS OF TDP43 FUNCTION AT ALL.
NO TAKERS?
ONE THING WE STRESSED IN THE
RECOMMENDATIONS IS TO
COLLABORATE AND WORK WELL WITH
THE BROADER TDP43 COMMUNITY AND
ALS AND IF FTD WAS THERE'S LOTS
OF WISDOM FROM MANY YEARS OF
WORK THIS FIELD CAN GAIN FROM
AND CERTAINLY I THINK
COLLABORATION IS CRITICAL.
>> I HAVE TWO QUESTIONS ON THE
VIDEOCAST.
THEY'RE ABOUT DETECTING TDP43 IN
LATE AND IF YOU HAVE THE ABILITY
TO DISTINGUISH IT FROM
ALZHEIMER'S DISEASE.
WHAT IS THE IMPACT ON TREATMENTS
AND CLINICAL BIOMARKERS AND THE
OTHER IS A MORE TECHNICAL
QUESTION ABOUT WHAT IS NEEDED TO
DETECT TDP43 DEPOSITS.
DO WE NEED DEVELOPMENT OF
NON-AMINO HISTOCHEMISTRY METHODS
TO BE ADVANTAGEOUS TO DETECT OR
IS IT DIFFERENT SPECIES OF TDP43
BOTH ON THE TECHNICAL DETECTION
AND THE IMPACT.
>> THOSE ARE GREAT QUESTIONS.
I DON'T KNOW, KONSTATINOS DID
YOU WANT TO SAY A FEW WORDS?
>> WE KNOW LATE NC IS MIXED WITH
OTHER PATHOLOGIES COMMONLY.
THIS MEANS IF WE HAVE A MARKER
FOR LATE NC WE'RE NOT GOING TO
BE ONLY HELPING CLINICAL TRIALS
IN THE DIAGNOSIS OF LATE BUT
ALSO GOING TO BE HELPING
CLINICAL TRIALS IN TREATMENT FOR
OTHER PATHOLOGIES FOR THE SIMPLE
REASON IF YOU HAVE THE
SUCCESSFUL ALZHEIMER'S DRUG BUT
TESTING ON PEOPLE THAT HAVE
LATE, THESE PEOPLE MAY PROGRESS
AND HAVE DEMENTIA AT SOME POINT.
IT DOESN'T MEAN THE ALZHEIMER'S
DRUG DID NOT WORK.
IT'S VERY IMPORTANT TO BE ABLE
TO IDENTIFY NOT ONLY FOR
DIAGNOSING AND TREATING BUT
ATTACKING ADRD.
THEN THE SECOND QUESTION WAS YOU
SAID --
>> MORE AROUND THE QUESTION
ABOUT DETECTION OF -- TECHNICAL
BARRIERS.
>> AT THIS POINT I THINK IT'S
WISE WE DO IT THIS WAY AND
ATTACK IT FROM ALL ASPECTS.
THERE BLOOD BASED MARKERS AND
TRACERS TO DETECT THE PATHOLOGY
AND SPECIFIC MARKERS AND EVERY
ASPECT.
I THINK THERE ARE VERY HOPEFUL
SIGNS FROM EACH ONE OF THEM EVEN
THE CLINICAL CRITERIA ALREADY
INCLUDES INFORMATION WITH KNEW
KNOWLEDGE GENERATED FROM THE
BIOMARKER POINT OF VIEW.
I FEEL THE CLINICAL CRITERIA
WILL ABSORB THE INFORMATION AND
INCORPORATE THEM.
I THINK WE'RE SEEING VERSION ONE
OF THE CLINICAL CRITERIA RIGHT
NOW WHICH IS A HUGE STEP FORWARD
BUT WE NEED TO GO TO VERSION
TWO.
>> A QUICK POINT.
THE POINTS MADE BY THE PATIENT'S
DAUGHTER WERE IMPORTANT TO ME
AND THIS PERVADES TO EVERYTHING
WE HEARD TODAY AND NOT JUST WITH
LATE OR AD BUT THE DEMENTIA
FIELD NEEDS TO LEARN FROM THE
CANCER FIELD SOME OF THE
CULTURAL ADVANCES THEY HAVE
ACHIEVED THAT HAVE BEEN
TRANSLATED TO SCIENTIFIC
ADVANCES AND NOT BE AFRAID OF
COMPLEXITY.
CANCER GRAPPLES WITH DEEP
COMPLEXITY AND HAS COME UP WITH
IT ON THE UPPER HAND IN MANY
WAYS.
WE HAVE BEEN VERY AVERSE TO IT
AND WE TEND TO DICHOTOMIZE
THINGS AS YES, NO, YES, NO.
IT'S NOT A YES, NO SITUATION.
THERE'S FACTORS AND GENETIC AND
ENVIRONMENTAL.
THE COMPLEXITY, NUMBER ONE,
NUMBER TWO, WE NEED TO GET TO
THEIR ASSESSMENTS.
THE BIOMARKERS WORK AND THERE
USED TO BE A CULTURE WHERE THERE
IS IN CANCER AND NOT CURRENTLY
IN DEMENTIA TREATMENT AND CARE.
AND WE NEED TO GET PEOPLE TO
KNOW WHAT TO SCREEN THEM FOR AND
WHAT THEY'RE AT RISK FOR AND TO
THEN GIVE THEM OPTIONS.
IT'S NOT TELLING THEM THEY HAVE
TO DO THIS OR THAT BUT PEOPLE
ARE SCARED OF DEMENTIA AS MUCH
AS THEY'RE SCARED AS CANCER AND
WE'VE ACTED AS THOUGH BEING
INTERVENTIONISTS ARE BAD AND
IT'S NOT IT'S GIVING PEOPLE
CHOICES AND DECISIONS ON THEIR
OWN AND THOSE ELEMENTS OF CANCER
CULTURE WE CAN LEARN A LOT FROM.
>> AND THERE'S A MORE PRECISION
MEDICINE APPROACH AND IN THE
CONTEXT OF ALZHEIMER'S BUT IN
THE CONTEXT OF OTHER
NEURODEGENERATIVE CONDITIONS IN
ITS OWN RIGHT.
DEVELOPING BIOMARKERS WILL HAVE
THAT IMPACT.
>> IF I CAN ADD TO THE ANSWER.
SPEAKING SPECIFICALLY ABOUT THE
TDP43 PATHOLOGY DETECTION WITHIN
THE LDP SPACE THERE'S MULTIPLE
PATHOLOGY.
WITHIN THE ALS SPACE AND FTD
SPACE AND LATE SPACE, THERE'S A
SENSE WHERE THE DIRECTION OF
PATHOPHYSIOLOGY HAS BEEN
DIFFICULT AND HARDER TO DETECT
COMPARED TO OTHER FORMS OF
PATHOLOGY BUT THE ABSENCE OF
TDP43 ACTION THROUGH THE KRY
KRYPTONS MAY BE EASIER TO DETECT
AND AS DR. NELSON SAID EXTREMELY
WELL, WE ALSO NEED TO THINK OF
OPPORTUNITIES TO COME UP WITH
TOOLS THAT WILL NOT END UP
HAVING BANKRUPT OUR SOCIETY TO
BE BLUNT AND BE AT THE
INTERSECTION AND NOT LOOKING FOR
EACH INDIVIDUAL FORM OF
PHOSPHORYLATED TDP43 BUT LOSS OF
FUNCTION THAT COULD BE
APPLICABLE ACROSS BECAUSE IT
WILL BE A LOT LESS EXPENSIVE FOR
OUR SOCIETY.
>> THOSE ARE ALL EXCELLENT
POINTS.
I THINK TRYING TO SEE WHERE OUR
BIOMARKERS OVERLAP VERSUS WHERE
THEY'RE DISTINCTIVE.
PET TRACERS MAY DIFFERENTIALLY
BIND TO AGGREGATE FORMS OF TDP43
AND THE CONTEXT OF LATE VERSUS
OTHER CONDITIONS.
I SEE ANOTHER HAND UP.
I THINK IT'S MITCH.
>> HI.
THANK YOU VERY MUCH.
I WANTED TO AMPLIFY SOME RECENT
COMMENTS ABOUT COMPLEXITY AND
BUT IN STUDIES WITH TESTING OF
COGNITION IN TERMS OF THAT TYPE
OF BIOMARKER TO LOOK AT WEATHER
THERE IS A CHARACTERISTIC OF
CO-OCCURRING AD PATHOLOGY WITH
MULTI-DOMAIN TESTING AND SEE
WHAT HAPPENS FIRST AND LATER ON.
A CORRELATION TO THAT IS
ASSOCIATION OF COGNITION IMPROVE
THE PRECISION OF THAT TYPE OF
COGNITIVE BIOMARKER GOING
FORWARD.
>> I'LL JUST -- THOSE ARE GREAT
QUESTIONS, MITCH.
THERE HAVE BEEN A NUMBER OF
ANTI-MORTEM, POSTMORTEM STUDIES
LOOKING AT COGNITION OVER TIME.
THERE'S BEEN A RUSH GROUP THAT'S
DONE BEAUTIFUL WORK LOOKING AT
COGNITIVE CHANGES AND THE
SEQUENCES OVER TIME BUT I ARGUE
DEFINING PEOPLE IN VIVO IS
CRITICAL TO GET MORE NUANCED
UNDERSTANDING OF COGNITION IS
YOUR NOT RELIANT ON PREVIOUSLY
COLLECTED STANDARDIZED DATA AND
IMPLEMENT DIGITAL BIOMARKERS.
THAT'S WHY THE FIRST
RECOMMENDATION REALLY STRESSES
THE IMPORTANCE OF DEEPLY
PHENOTYPED COHORTS WHERE WE'RE
FOLLOWING INDIVIDUALS AND
CLASSIFYING THEM LONGITUDINALLY
HOPEFULLY TO AUTOPSY AND LINK
WHAT WE SEE PATH LOGICALLY TO
WHAT WE'RE SEEING IN VIVO.
>> I AGREE.
THANK YOU.
>> GO AHEAD WITH YOUR QUESTION.
OKAY.
SO WE'LL ALSO HAVE TIME AGAIN AT
THE END OF DAY TWO TO TAKE
ADDITIONAL QUESTIONS AND
COMMENTS FROM ANY OF THE
SESSIONS FROM THE TWO DAYS.
>> SOME PEOPLE COULDN'T BE HERE.
I WANT TO SAY THANKS FOR JULIE
SNYDER A LEADER HERE AND
DRDR
DR. GIFFIN AND HAS BEEN A TREAT
TO WORK WITH ALL OF YOU.
>> THANK YOU, PETE.
>> THANK YOU SO MUCH.
AND GREAT JOB.
SORRY FOR RUNNING A LITTLE BIT
OVER BUT WE HAVE AFTER MEETING
SLIDES THAT WILL COME UP AND
WE'LL ADJOURN FOR THE DAY.
>> THANK YOU VERY MUCH.
THANK YOU ALL.