GOOD MORNING.
>> I AM JONATHAN KING,
SCIENTIFIC ADVISOR AT NIA
AND THIS IS THE VERY FIRST
WEEK AT THE NIH AS A
DEPARTMENT OFFICIAL IN 2007
WAS IN FACT THE VERY FIRST
MEETING OF THE COGNITIVE
AGING SUMMIT AND IN
ADDITION, THERE HAVE BEEN
TWO OTHERS AND THIS IS THE
FOURTH AND IT HAS BEEN
REALLY GREAT BECAUSE WE HAVE
MUSED TO ROMAN NUMERALS OR
AS MY CHILD WOULD CALL THEM,
SUPER BOWL NUMBERS.
SO IN ANY CASE, I WOULD LIKE
TO INTRODUCE THE FIRST
SPEAKER THIS MORNING WHO IS
RICHARD HOTES WHO IS THE
DIRECTOR OF THE NATIONAL
INSTITUTE ON AGING.
[APPLAUSE]
>> THANK YOU JOHN, THANK YOU
EVERYONE FOR PARTICIPATING.
I WOULD LIKE TO OPEN ON A
LITTLE PERSONAL NOTE.
IT GOES BACK ABOUT 18 YEARS
NOW WHEN I GOT A PHONE CALL
FROM Dr. LEE AND I THINK
YOU ARE LISTENING BUT SORRY
YOU ARE NOT HERE BUT GREAT
TO BE PARTICIPATING WITH YOU
AGAIN.
HONESTLY I THINK I HAD NEVER
MET A MORE WARM AND SINCERE
AND CARING PERSON AND EVEN
FOLKS IN MY OFFICE WHEN THEY
KNEW THIS CONFERENCE WAS
HAPPENING TOOK A LITTLE
LONGER TO FIND OUT IN
ADDITION TO HIS WARMTH AND
PERSONALITY, HE WAS A
VISIONARY.
AND VISION STRUCK HOME
BECAUSE I THINK IT WAS VERY
MUCH WITH ALL OF US AT
NATIONAL INSTITUTE AT AGING,
NIH, ALL OF US INCLUDED NOT
ONLY TRYING TO UNDERSTAND
THE DISEASES AND PATHOLOGY
BUT ON A COMPLIMENTARY
APPROACH, THE EVENTS THAT
HAPPEN NORMALLY WITH NORMAL
AGING FOR EXAMPLE.
WE HAVE THE BEST STRATEGIES
IDENTIFYING PATHWAYS WHERE
WE CAN IDENTIFY AND INCLUDE
AND THAT IS THE CASE HERE SO
EVEN THOUGH WE SPEND A LOT
OF TIME DEALING WITH
PATHOLOGY, WE SPEND A LOT OF
TIME IN THESE SUMMITS, A LOT
OF PASSION FOR DECADES NOW
TO UNDERSTAND THE RESILIENCE
AND VULNERABILITY OF AGING
AND WHEN THERE ARE ISSUES,
WITH ROMAN NUMERALS, THE WAY
WE AGE CAN PROVIDE IMPORTANT
CLUES TO MAXIMIZE AND
OPTIMIZE THE COURSE OF
AGING.
INDIVIDUALS, RACIAL AND
EIGHT NICK GROUPS, PERSON BY
PERSON, THE APPROACH WE'RE
TAKING HERE FOR DECADES
GIVING GREAT PROMISE AND
EXCITEMENT.
SO WITH ALL OF YOU I LOOK
FORWARD TO THE NEXT COUPLE
OF DAYS.
IT IS GREAT TO BE WITH YOU
AGAIN AND LOOK FORWARD TO
IT.
NEXT?
>> NEXT UP IS JULIE
GERBERDING FROM THE
FOUNDATION OF NIH.
[APPLAUSE]
>> THANK YOU.
IT IS REALLY WONDERFUL TO BE
HERE LIVE AND IN COLOR AND
INSTEAD ON THE LITTLE SCREEN
CAMERA LIKE THE LAST TIME I
INTERACTED WITH THIS GROUP.
WHEN I WAS ON THE REDLINE
THIS MORNING COMING HERE, I
WAS THINKING ABOUT COGGIVITY
AND PARTLY BECAUSE I AM AT A
AGING STAGE WHERE THAT IS
INCREASINGLY RELEVANT BUT
PARTIALLY BECAUSE I AM
THINKING OF MY FAMILY.
I ALMOST HAVE A SIGN PAST OF
THIS PROCESS.
RECENTLY, MY UNCLE PASSED
AWAY FROM ADVANCED
PARKINSON'S AND DEMENTIA,
HAD A REALLY ROUGH CLINICAL
COURSE IN THE LAST FEW YEARS
OF HIS LIFE BUT THE OTHER
INSTANCE IS MY MOM
CELEBRATING HER 95TH
BIRTHDAY NEXT FRIDAY WHO
LIVES ALONE, A MASTER CHESS
PLAYER WHO THRIVES, GOES TO
EVERY UNIVERSITY GRADUATE
FOOTBALL AND BASKETBALL GAME
AND IS COMPLETELY INTACT
WITH THE EXCEPTION OF A CANE
THAT SHE LIKES TO TERRORIZE
US WHEN SHE DISAGREES WITH
US SO IN JUST ONE FAMILY, WE
HAVE THE GAMUT OF COGNITIVE
AGING AND TRYING TO
UNDERSTAND THE DETERMINANTS
AND WHY PEOPLE AGE
DIFFERENTLY IN THIS RESPECT.
THE FOUNDATION FOR NIH HAS A
LONG TRADITION OF
INTERACTING AND I THINK NOT
ONLY ARE WE PROUD OF THOSE
COLLABORATIONS THAT WE HAVE
BEEN ABLE TO ESTABLISH WITH
NIA AND THE McKNIGHT
FOUNDATION, ET CETERA, WE
ALSO ARE LEANING INTO SOME
NEW AREAS THAT I THINK ARE
RELEVANT TO THE TOPIC AS
WELL.
I WILL JUST MENTION ONE OF
THEM, SOUND HEALTH, AND THE
IMPORTANCE OF MUSIC AND
POTENTIAL THERAPEUTIC IMPACT
ON MUSIC WITH COGNITION AND
HEALTHY AGING.
SO LOOK FORWARD TO YOUR
WORK.
THANK YOU FOR ALL YOU ARE
CONSIDERING IN THIS REALLY
INCREASINGLY IMPORTANT SPACE
AND I HOPE YOU ENJOY THE
MEETING.
THANK YOU.
[APPLAUSE]
>> WONDERFUL AND OUR THIRD
SPEAKER TODAY, Dr. MICHAEL
DOCKERY, WHO IS CHAIR OF THE
BOARD OF TRUSTEES OF THE
McKNIGHT BRAIN RESEARCH
FOUNDATION.
>> THANK YOU, Dr. KING,
Dr. GE RBERDING, THANK YOU
FOR THIS INTRODUCTION, I
LOOK FORWARD TO THE
WONDERFUL PROGRAM AND WHAT
WILL BE HAPPENING BUT ALSO
THANK YOU TO THE STAFF WHO
ORGANIZED EVERYTHING BECAUSE
I KNOW IT WILL BE GREAT.
WANT TO START WITH A LITTLE
BIT OF HISTORY AND THE
McKNIGHT BRAIN RESEARCH
FOUNDATION WAS ESTABLISHED
IN 1991 BY EVELYN
F.McKNIGHT WHO WAS A
RETIRED NURSE AND WIFE OF
WILLIAM McKNIGHT AND HE
WAS THE CEO FOR MORE THAN 40
YEARS SO THOSE OF YOU WHO
HAVE HEARD THIS STORY, LET
ME SHARE THIS WITH THE REST.
MR.AND MS. McKNIGHT WERE
INTERESTED IN THE BRAIN AND
AGING AND MR. McKNIGHT
WOULD OFTEN SAY AFTER AN
ADDRESS WHY IS IT I CAN'T
REMEMBER THE NAME AND THEY
WOULD DRIVE AROUND LOOKING
FOR THE BRAIN INSTITUTE BUT
IN THE END, IT WAS MS.
McKNIGHT WHO LEFT HER
LEGACY TO HONOR HER HUSBAND
WITH THE McKNIGHT BRAIN
RESEARCH FOUNDATION AND WE
WERE GIVEN THE TASK TO
SUPPORT THE RESEARCH OF THE
BRAIN WITH THE LOSS OF
AGING.
NOW, THERE WAS NOTHING WRONG
WITH THEIR MEMORY AND WE
HAVE ALL HAD THESE
EXPERIENCES AS WELL BUT WE
DON'T REALLY UNDERSTAND HOW
THE BRAIN WORKS WITH MEMORY.
HOW DO WE FORM A MEMORY?
HOW DO WE STAR IT?
HOW DO WE CATALOG AND TREAT
IT?
WE DON'T UNDERSTAND THIS
VERY WELL AND THERE ARE MANY
STEPS ALONG THE WAY THIS
PROCESS CAN BREAK DOWN AND
AS WE HAVE HEARD IN OUR
AGING SOCIETY.
WE WANT TO BE SURE PEOPLE
CAN AGE WELL IN THEIR GOLDEN
YEARS.
WHILE MY FATHER, WHO WAS THE
RIDGE KNEE TRUSTEE -- I
THINK THERE SHOULD BE SOME
SLIDES WITH THIS.
WE HAVE NOW EXPAND ED TO
EIGHT TRUSTEES AS SHOWN HERE
ON THE SLIDE AND IN OUR 20TH
ANNIVERSARY THIS YEAR, WE'RE
EXCITED TO LAUNCH AN
AWARENESS CAMPAIGN TO PEOPLE
UNDERSTAND WHAT AGING ON THE
BRAIN IS AND SOME HEALTH
MODIFICATIONS THAT CAN HELP
BRAIN HEALTH ACROSS THE
LIFESPAN.
WE'RE KICKING OFF A BRAIN
WORKS ACROSS THE SPAN
PROGRAM AND STARTING FRIDAY
IF YOU VISIT OUR WEBSITE, McKN.
ORG/BRAIN WORKS.
SINCE THE 25 YEARS OF THE
CHARGE, WE KNEW THIS
CHALLENGE WOULD REQUIRE
COLLABORATION AND THEREFORE
WE HAVE ESTABLISHED
PARTNERSHIPS WITH FOUR
INSTITUTES AT THE UNIVERSITY
OF ALABAMA BIRMINGHAM,
UNIVERSITY OF ARIZONA,
UNIVERSITY OF FLORIDA AND
UNIVERSITY OF MIAMI.
WE ALSO HAVE A RESEARCH
PROGRAM THROUGH THE NIH AND
FOUNDATION OF THE NIH AND AS
THIS SLIDE NOTES, OVER
$200 MILLION SPECIFICALLY
TARGETING AGING, MEMORY
DECLINE AND MEMORY LOSS WITH
GREAT CONTRIBUTIONS AS WELL
AS STRATEGIC PARTNERSHIPS
INCLUDING THE BRAIN
INSTITUTE, NATIONAL
INSTITUTE OF AGING AT NIH,
AMERICAN BRAIN RESEARCH AND
BRAIN FOUNDATION.
WE HAVE HOSTED THREE
COGNITIVE SUMMITS AND TODAY
IS OUR FOURTH.
THE CHALLENGE WE HAVE IS TO
EDUCATE THE PUBLIC AND
SCIENTIFIC COMMUNITY TO
DIFFERENTIATE COGNITIVE
AGING AND AGE RELATED
COGNITIVE DECLINE FROM THE
OTHER COGNITIVE DISORDERS.
NOW, YOU ALL ARE SCIENTISTS
IN THE FOREFRONT OF YOUR
COLLEAGUES.
WHO BETTER TO HELP US
IDENTIFY THE AREAS OF
CRITICAL NEED, INTEREST AND
OPPORTUNITY ON WHICH WE
SHOULD FOCUS OUR COLLECTIVE
EFFORT?
WHICH ITEMS HOLD THE BEST
PROMISE AND WHAT ARE THE NEW
CUTTING EDGE CONCEPTS THAT
NEED TO BE BE EXPLORED AND
DEVELOP ?
WHO IS THAT PERSON INSIDE
YOUR INSTITUTE WHO CAN HELP
US GROW AND COLLABORATE.
SO THANK YOU FOR STEPPING
FORWARD IN THIS CHALLENGE.
[APPLAUSE]
>> AND NOW THE LAST SPEAKER,
Dr. MADHAV THAMBISETTY,
VICE-CHAIR BOARD OF TRUSTEES
AT McKNIGHT.
>> THANK YOU, MICHAEL.
MY DAY JOB, I AM THE SENIOR
INVESTIGATOR ON AGING OF THE
BRAIN PROGRAM AND I THINK I
AM THE ONLY ONE IN THE ROOM
WHO HAS AN IMPORTANT REASON
TO CELEBRATE TWO
ANNIVERSARIES, THE 25TH
ANNIVERSARY OF THE
McKNIGHT FOUNDATION AND
THE 50TH ANNIVERSARY ON THE
NATIONAL INSTITUTE OF AGING.
SO WHAT I WOULD LIKE TO DO
TODAY IS TAKE YOU THROUGH
WHERE WE HAVE COME FOR IN
TERMS OF THE COGNITIVE AGING
SUMMIT.
I KNOW SOME OF YOU ARE HERE
FOR THE VERY FIRST TIME AND
SOME OF YOU HAVE BEEN HERE
FOR ALL FOUR MEETINGS SO A
BRIEF SUMMARY OF WHERE WE
BEGAN AND WHERE WE ARRIVED.
SO THE FIRST COGNITIVE AGING
SUMMIT WAS 2007 AND JOHN, I
DIDN'T KNOW THAT WAS WHEN
YOU CAME TO THE NIA BUT WHEN
I CAME TO THE NIA AS WELL.
THE IMPORTANT ESTABLISHES
THE McKNIGHT BRAIN FORUM
HAS ESTABLISHED WHICH IS THE
COGNITIVE AGING AND NIA.
A RECOGNITION IN 2007 LED TO
THE ESTABLISHMENT OF THIS
PARTNERSHIP IN 2009 AND LED
TO THE DEPLOYMENT OF
$28 MILLION IN FEDERAL
RESEARCH FUNDS OVER FIVE
YEARS TO ESTABLISH NEURAL
AND BEHAVIORAL PROFILES OF
COGNITIVE AGING AND TO BE
ABLE TO PUSH TRANSLATIONAL
RESEARCH FORWARD THROUGH
PILOT HAVE INTERVENTION
STUDIES OF AGE-RELATED
COGNITIVE DECLINE.
THE SECOND SUMMIT HAPPENED
THREE AND A HALF YEARS AND
OF ALL THE IMPORTANT
OUTCOMES OF THE SUMMIT, THIS
IS MY FAVORITE.
THIS IS THE STUDY THAT MOLLY
AND JOHN AND MY COLLEAGUES
AT NIA PUBLISHED IN THE
JOURNAL OF GERONTOLOGY WHICH
WAS TO UNDERSTAND
AGE-RELATED COGNITIVE
IMPAIRMENT AS DISTINCT FROM
THE NEUROLOGICALLY DEFINED
CLINICAL SYNDROMES.
THIS IS ANOTHER ARTICLE FROM
THE SAME COLLECTION OF
ARTICLES DONE IN JOURNAL OF
GERONTOLOGY AND IN MANY
WAYS, LOOK AT THE FUTURE,
STUDYING INDIVIDUAL
DIFFERENCES AND PERHAPS THAT
MAY LEAD TO INDIVIDUALIZED
INTERVENTION FOR AGE-RELATED
COGNITIVE AGING.
JOHN AND MOLLY HAVE A
FANTASTIC NKNACT FOR
WRITING NOT ONLY FANTASTIC
ARTICLES BUT ALSO IN THE
SUMMIT, HIGHLIGHTING THE
INCREASING IMPORTANCE OF
THESE CONCEPTS UNDERSTANDING
BOTH AGE RELATED AS WELL AS
PATHOLOGY RELATED CHANGE AND
HIGHLIGHTED IMPORTANT GAPS
IN OUR SHARED UNDERSTANDING
OF HOW TO CHARACTERIZE TERMS
SUCH AS RESERVE, RESILIENCE
AND MAINTENANCE.
WONDERING IF WE WEREN'T
SPEAKING THE SAME LANGUAGE,
WE WOULD BE LOST IN
TRANSLATION.
AND ONE OF THE KEY OUTCOMES
OF THAT MEETING WAS THE
COGNITIVE RESERVE, BRAIN
MAINTENANCE AND BRAIN
RESERVE.
THERE WERE 12 PILOT STUDIES
OF THAT INITIATIVE, MY
FAVORITE CALLED SITARRRS LED
BY MY COLLEAGUE Dr. PETER
AT NIH AND ONE OF MY
FAVORITE STUDIES, THE
COGNITIVE RESEARCH PROVIDING
NEUROLOGICAL DATA, IMAGING
SCANS AND BIOSPECIMENS FOR
THE WIDER SCIENTIFIC
COMMUNITY AND IDENTIFIED AS
A DIRECT RESPONSE TO A NEED
FOR AGING SUMMIT IN 2017.
THESE ARE PICTURES FROM THE
INSTALLATION OF THE MAGNET
FOR THE STARRRS INITIATIVE.
PETERY CLIENT TO SEND A
PICTURE BECAUSE HE DIDN'T
WANT HIS GOOD LOOKS TO BE A
DISTRACTION OF THIS MEETING
BUT FOR THOSE WHO WILL
ATTEND, THE INSTITUTIONAL
MEETING AT THE UNIVERSITY OF
FLORIDA, I AM DELIGHTED THAT
PETER WILL BE GIVING ONE OF
THE KEYNOTE TALKS WHERE I AM
SURE YOU WILL LEARN A LOT
ABOUT THIS INITIATIVE WE ARE
VERY EXCITED ABOUT.
IN FACT, JUST A COUPLE OF
DAYS BACK, I LOOKED AT THE
SCANS FROM THE STARRRS
INITIATIVE AND I THINK THIS
WILL BE A GREAT RESULT FOR
THE COMMUNITY AT LAST.
AND THE FOURTH THEME OF THIS
COGNITIVE AGING SUMMIT WHICH
IS THE RECOGNIZED
DIFFERENCES AND PRESUMPTION
OF AGE COGNITIVE DECLINE AND
THE SESSIONS ARE GROUPED IN
FOUR THEMATIC GROUPS
FOCUSING ON THE ENVIRONMENT
ALL THE WAY TO CLINICAL
TRIALS.
WHAT WE SHOWN INTERVENTION
OF THESE TEAMS WILL LEAD TO
COST CUTTING AND
INTERVENTIONARY WORK THAT
MAY BRING US CLOSER TO
INTERVENTION FOR COGNITIVE
IMPAIRMENT AND COGNITIVE
AGING.
I WOULD LIKE TO REMIND
MYSELF THAT A FOCUS ON THE
INDIVIDUAL IS NOT A
REDUCTIONIST APPROACH.
WE HOPE THAT THIS WILL BRING
US CLOSER TO AN
UNDERSTANDING OF THE
UNIVERSAL PROBLEM AND I AM
REMINDED OF ONE OF MY
FAVORITE QUOTES FROM CARL
ROGERS SAYING WHAT IS MOST
PERSONAL IS MOST UNIVERSAL
SO WELCOME EVERYONE AND I
HOPE YOU HAVE A GREAT
SUMMIT.
THANK YOU VERY MUCH.
[APPLAUSE]
>> WELL THANK YOU VERY MUCH.
THIS WAS JUST THE FIRST
SESSION OF A VERY, VERY FULL
PROGRAM SO LET ME TAKE THE
OPPORTUNITY RIGHT HERE TO
REMIND SPEAKERS AND GUESTS
THAT WE ARE GOING TO
MAINTAIN A COMPLETELY
ON-TIME PERFORMANCE, SO
ALTHOUGH WE'RE GOING TO GET
A FEW EXTRA MINUTES HERE
BECAUSE OF THE REMARKS BEING
QUICK, I WILL TO POINT OUT
THE TIMER, THEY CAN SEE IT
FROM THERE, I CAN SEE IS
FROM HERE, I AM NOT A SHY PERSON BUT THERE WILL BE A
ROBUST TIME TO DISCUSS THE SESSIONS.
SO NOW WE HAVE A BREAK TILL 8: 45:00 A.M. SEE YOU THEN.
>> GOOD MORNING EVERYONE,
LIKE TO HAVE THE REST OF YOU
START MAKING YOUR WAY
TOWARDS YOUR SEATS, WE'LL
ACTUALLY GET STARTED WITH
THE FIRST SESSION OF REALLY
EXCITING SCIENCE.
SO GOOD MORNING, MY NAME IS
SAUL VILLEDA FROM THE
UNIVERSITY OF CALIFORNIA-SAN
FRANCISCO.
TO REMIND EVERYONE, WE WILL HAVE A PANEL OF FOUR TALKS
AND AT THE END OPEN QUESTIONS FROM EVERYONE SO
PLEASE WRITE DOWN YOUR FAVORITE QUESTION BECAUSE I
WILL COME BACK TO YOU AT THE END OF THE PANEL.
SO WE WANT TO TALK ABOUT
THIS IDEA OF BLOOD,
METABOLISM AND SYSTEMIC
ENVIRONMENT, TARGETING THE
PERIPHERY AS A WAY TO DELAY
AND REVERSE COGNITIVE AIMING
SO WITH THAT I WILL
INTRODUCE THE SPEAKERS, EACH
ONE AS THEY COME.
SO FIRST I WOULD LIKE TO
INTRODUCE Dr. TARA WALKER
WHO IS COMING TO US FROM THE
UNIVERSITY OF QUEENSLAND IN
AUSTRALIA AND REALLY LOOKING
FORWARD TO YOUR TALK.
SO PLEASE HELP ME IN
WELCOMING YOU AND REALLY
EXCITED YOU ARE HERE.
[APPLAUSE]
>> THANK YOU, SAUL, HAPPY TO
BE HERE.
OKAY, THE BRAIN HAS A
REMARKABLE ABILITY TO
MAINTAIN SPEECH THROUGHOUT
OUR LIVES AND ONE OF THE
WAYS IT DOES THIS IS ADULT
NEUROGENESIS.
SO I WILL SHOW THIS AS THE
PARTICULAR AREA OF THE BRAIN
FROM WHERE MEMORY COMES.
SO NEUROGENESIS DECREASES
ARE AGE AND WITH THE VARIOUS
NEUROGENESIS REDUCTIONS.
THE MAIN CONTRIBUTOR TO THIS
IS AGE BUT IT CAN DECLINE
FROM A NUMBER OF STRUCTURES
AND ONE OF THE WAYS WE CAN
INCREASE NEUROGENESIS IS BY
PHYSICAL EXERCISE.
SO THIS WAS DISCOVERED
ALMOST 20 YEARS AGO NOW THAT
WHEN MICE ARE GIVEN FREE
ACCESS TO THE WHEEL, THEY
LOVE TO RUN AND THIS
INCREASE IN NEUROGENESIS,
INCREASE IN SYNAPTIC POLICE
'TISY AND INCREASE IN
LEARNING AND MEMORY.
HOWEVER THROUGHOUT 20 YEARS
OF RESEARCH, WE STILL DON'T
UNDERSTAND THE MECHANISM BY
WHICH EXERCISE INCREASES
NEUROGENESIS.
SO THE MAJOR FOCUS OF MY LAB
THE LAST YEAR HAS BEEN TO
UNDERSTAND HOW EXERCISE
INCREASES NEUROGENESIS IN
THE BRAIN.
SO WITH THAT WE ASK TWO
QUESTIONS, WHAT IS THE
UNDERLYING MECHANISM BY
WHICH EXERCISE BOOSTS
NEUROGENESIS AND CAN WE
INCREASE THAT.
SO THE FIRST STUDY WAS A
BLOOD-BORNE LOOK AT FACTORS
CIRCULATING IN THE BLOOD
ABLE TO MEDIATE BOTH
NEUROGENESIS AND COGNITIVE
ABILITIES.
SO WE HYPOTHESIZED, GIVEN
THE NATURE OF HOW DISEASE
WORKS, THAT MAYBE IT IS THE
SAME, THAT EXERCISE IS ABLE
TO REFORM NEUROGENESIS.
SO WE TOOK THIS VERY SIMPLE
EXPERIMENT, WHERE WE LOOKED
AT THE BLOOD-BORNE
NEUROGENESIS IN MICE AND WE
LOOKED AT THE BLOOD SERUM
WITH EXERCISE AND IF IT WAS
ABLE TO GENERATE THE
NEUROSEVERE.
SO WHAT ARE THE FACTORS?
WE AGAIN LOOKED AT THE BLOOD
OR SERUM IN THE MICE AND
NUMBER OF PROTEINS
UPREGULATED IN THE BLOOD DUE
TO EXERCISE.
AND A RIF REANALYSIS
REVEALED THAT PLATELET
ACTIVATION MAY BE A
SIGNIFICANT PORTION OF THIS
AND WE IDENTIFIED ONE IN
PARTICULAR CALLED PLATELET
FACTOR 4.
SO PLATELETS ARE CELLS FOUND
IN THE BLOOD BUT THEY HAVE
MANY FUNCTIONS BEYOND THEIR
ROLE OF THE COWAG LAKES AND
ARE ALSO ASSOCIATED WITH
MANY NEUROGENESIS DISORDERS.
WHAT IS EXCITED ABOUT
PLATELETS IS THEY ARE ALSO
SHOWN TO CONTAIN A WIDE
PLETHORA OF BIOACTIVE
MOLECULES.
THERE ARE HUNDREDS OF
BIOACTIVE MOLECULES FOUND IN
PLATELETS AND FOUND TO HAVE
EXCITING ROLES IN BLOOD
THERAPY.
SO WE FIRST HAVE TO
DETERMINE HOW THEY ARE
PRODUCED IN EXERCISE SO WE
LOOKED AT THE BLOOD OF THE
MICE AND FOUND THAT AS
LITTLE AS ONE DAY OF
EXERCISE WAS ENOUGH TO
GENERATE PLATELETS.
TO DETERMINE IF THE EXERCISE
WAS REQUIRED FOR THE
RESPONSE BY PLATELETS, WE
LOOKED AT THE PLATELETS IN
THE MICE USING THE
ANTIPLATELET SERUM OVER A
1-DAY PERIOD AND AS WE
EXPECTED, THE PLATELETS IN
DEPLETED MICE, THIS RESPONSE
DUE TO EXERCISE WAS LOST,
THE MEDIATED RESPONSE OF
NEUROBEN SIS.
THE OTHER MENTION, PLATELETS
ARE ACTIVATED BY EXERCISE
AND RELEASE A NUMBER OF
FACTORS INTO THE BLOOD FOR
THIS RESPONSE AND ONE OF THE
MAJOR FACTORS THAT WE
IDENTIFIED WAS PLATELET
FACTOR 4.
WE CONFIRMED THIS RESULT
USING THE RESTING PLATELET
AND THE EXPERIMENTS WAS TO
SEE IF EXERCISE INDUCED
PLATELETS COULD BE
GENERATED.
SO AS YOU CAN SEE HERE,
COMPARED TO THE CONTROL
WHICH IS THE DOTTED LINE,
THERE WAS A SIGNIFICANT
INCREASE IN THE NUMBER OF
NEUROSPHERES GENERATED.
IT ALSO LED TO THE PLATELET
INCREASE OF PLATELET FACTOR
4 AND ITS POTENTIAL.
SO THE WE INFUSED FACTOR 4
INTO THE BRAIN OF MICE.
THIS LED TO A SIGNIFICANT
INCREASE OF NEWBORN
PLATELETS GENERATED IN THE
HIPPOCAMPAL AREA OF THE
BRAIN IN THE MICE.
AND THEN THIS SHOWS THE
SIGNIFICANT DECREASE IN THE
PLATELET AND NEUROFILLS.
IN THE ABSENCE OF PF4, THE
MICE HAD A NEUROGENIC
RESPONSE TO EXERCISE.
SO AS I MENTIONED BEFORE,
THE NEUROGENESIS
SIGNIFICANTLY DECREASES WITH
AGE SO WE WANTED TO SEE
WHETHER THE PF4 TREATMENT
COULD RESCUE THIS NEURO
GENERATIVE LOSS DURING
AGING.
SO WE TOOK 20-MONTH-OLD MICE
AND TREATED THEM TO A TAIL
INJECTION OF PF4 AND AS YOU
CAN SEE, THERE WAS A
PROLIFERATION OF PF4 AND
ASSOCIATED NEURONS.
THEN WE WANTED TO SEE IF WE
COULD ENHANCE THESE NEURONS.
COMPARED TO THE CF4 KNOCKOUT
MICE, THIS ENHANCED THE
DENDRITIC NEURONS.
WITHOUT THE EXERCISE, THIS
LEADS TO A SPECIFIC TYPE OF
COGNITIVE DECLINE AND MEMORY
DYSFUNCTION.
SO WE TOOK AGED MICE WITH
CF4 AND PUT THEM TO THE
FACIAL MEMORY TASKS.
FIRST THERE WAS AN AVOIDANCE
TASK IN WHICH THE MICE ARE
PLACED ON A ROTATING
PLATFORM AND HAVE TO USE
FACIAL RECOGNITION TO AVOID
SHOCK.
SO THE MICE WITH CF4 WERE
SHOWN TO HAVE SIGNIFICANT
ENHANCED LEARNING ABILITY
COMPARED TO THOSE MICE WHO
WERE DECREASED AND SHOCKED.
SO WE TREATED THE AGED MICE
WITH PF4 AND SEPARATED THE
TASKS.
AS YOU CAN SEE IN THE NUMBER
OF LOCATION TASKS, THE MICE
MET SIGNIFICANTLY MORE TIME
EXPLORING THE OBJECT AND IN
THE SUBJECTIVE FREE TEST,
THE MICE SHOWED MORE PF4
SHOWING IT ENHANCED
COGNITION IN AGING.
SO WE WANTED TO SEE IF THIS
WAS DEPENDENT NEUROGENESIS
SO WE TESTED THIS IN THE
AGED MOUSE MODEL.
THESE MICE BASICALLY HAVE
THE DETERIORATING RECEPTOR
AT THE CONTROL OF THE NEURON
MOTOR CORTEX SO WHEN WE
TREAT THESE MICE, EFFECTIVE
NEUROGENESIS IS LOW.
SO WE TREATED THE MICE WITH
PF4 AND AS YOU CAN SEE HERE,
AS EXPECTED, THE PF4 IN
UNTREATED MICE SHOW A
SIGNIFICANT IMPROVEMENT WITH
MEMORY AND FUNCTION BUT THIS
IS LOST IN THE --
[INDISCERNIBLE]
-- INDICATING THIS ONGOING
NEUROGENESIS IS REQUIRED FOR
THE PF4 RECOGNITION.
SO OVERALL THIS HAS SHOWN
PLATELETS ARE REQUIRED FOR
THE EXERCISE RESPONSE,
NEUROGENIC RESPONSE AND THAT
ONE SECTOR ALONE, PF4 CAN BE
USED TO REJUVENATE THE
COGNITIVE FUNCTION IN AGED
MICE.
SO THIS ARTICLE WAS
PUBLISHED IN NATURE AGING
WHICH CAME TO THE SAME
IDENTIFICATION OF PF4 AS A
FACTOR INVOLVED IN
REJUVENATION IN AGING AND
WE'RE VERY FORTUNATE TO BE
ABLE TO PUBLISH OUR RESEARCH
ALONGSIDE EACH OTHER AT THE
SAME TIME IN THREE SEPARATE
ARTICLES.
SO GIVEN THE EXCITING
FINDINGS WE FOUND, NOW
TAKING THIS INTO THE MOUSE
MODELS WITH DISEASE TO SEE
IF WE CAN REDUCE THE
COGNITIVE DECLINE OF
ALZHEIMER'S DISEASE.
SO THIS IS JUST THE FIRST
SECTION AND WE ARE VERY
EARLY IN THIS RESEARCH BUT
BASICALLY WE HAVE TAKEN THE
MOUSE MODEL AND TREATED THEM
WITH PLATELET FACTOR 4 AND
AS YOU CAN SEE HERE, AND AS
EXPECTED, THIS IS THE
SPECIAL LEARNING AND MEMORY
TASK AND AS YOU CAN SEE
HERE, THE MICE TREATED WITH
SALINE HAVE A DIFFERENCES
SIT IN THIS TASK AND THIS
COULD BE RESCUED BY PLATELET
FACTOR 4.
SO WE WILL WATCH FOR FURTHER
DATA ON PLATELET FACTOR 4
GOING FORWARD.
SO WITH THIS I WILL CONCLUDE
AND THANK MY LAB.
MOST OF THIS WORK WAS DONE
BY MY POST-DOC WHO PERFORMED
ALL THE PF4 STUDIES AND THE
COLLABORATORS THROUGH THE
YEARS THAT HAVE CONTRIBUTED
AND OUR FUNDING INCLUDING
THE NIH.
SO THANK YOU VERY MUCH.
[APPLAUSE]
>> OKAY, PERFECT SO WE ARE
NOW GOING TO BE MOVING FROM
CIRCULATING BLOOD FACTORS
MORE INTO THE BORDER AND
DECODING SIGNALS ACROSS THE
BLOOD AND BRAIN.
SO WITH THAT WE HAVE ANDREW
YANNUAL NG WHO WILL BE
SHARING WITH US THE WORK ON
THE BBB.
>> THANK YOU, SAUL,
DELIGHTED TO BE HERE.
I AM AN ENGINEER,
NEUROSCIENTIST AND WILL TALK
ABOUT HOW RECENT
NEUROLOGICAL RESPONSES
ACROSS THE BLOOD BRAIN
BARRIER AND DECODING SIGNALS
ACROSS THAT.
WHAT THE MOLECULES ARE, HOW
THEY MAY DIFFER ACROSS THE
LIFESPAN.
THEY MAY EXPAND AND ANO
MALIES TO HEALTHY BRAIN
SIGNALS.
SO WE WANT TO UNDERSTAND HOW
DOES THE BODY --
[INDISCERNIBLE]
TO BEGIN, WE START WITH THE
SYMPATHETIC, THE BLOOD BRAIN
BARRIER IS IMPORTANT.
NEURONAL FUNCTION DEPEND ON
VASCULAR FUNCTION AND THE
MILLIONS OF NEURONS THAT
WILL BE CREATED THROUGHOUT
LIFE ARE A SIGNAL TO WHO WE
ARE AND ONE OF THE PROCESSES
IS WHAT WE CALL THE BLOOD
BRAIN BARRIER, DISCOVERED
OVER A CENTURY AGO.
THEY TOOK A DYE, A TEXTILE
DYE AND INJECTED IT
THROUGHOUT THE ORGANISMS AND
THAT DYE SPREAD THROUGHOUT
THE BRAIN.
THIS WAS OUR FIRST INKLING
SOMETHING SPECIAL WAS GOING
ON IN THE BRAIN AND
ESTABLISHED THAT THERE WAS A
BARRIER.
THE WAY I SEE IT, THE BLOOD
BRAIN BARRIER IS THE SPECIAL
HOME FOR THE BRAIN AND
DYNAMIC SENSING AND LIFE.
[INAUDIBLE] SO NOWADAYS, AND
I ALSO THINK MAYBE MORE
THOUGHTFULLY, IF THE BRAIN
IS GETTING OLD AND DAMAGED,
LIKE YOU DON'T JUST FIX UP
THE INTERIOR OF A OLDER HOME
AND THE SAME PRINCIPLES ARE
TRUE FOR THE BLOOD BRAIN
BARRIER.
SO IN OUR LAB, UNDERSTANDING
THESE BUILT-IN PATHWAYS AND
HOW THE BODY FEEDS THE BRAIN
ALL THE TIME THROUGHOUT
LIFE.
SO ONE OF THEM IS HOW DO
VIABLE BLOOD PROTEINS INVADE
THE BRAIN.
WE ARE ALSO INTERESTED IN
THE RESERIOUS ACTION, HOW
THEY USE THEM TO MOBILIZE TO
BE BRAIN HEALTH.
OR MAYBE CERTAIN FORMS OF
AGING AND THE PATHOLOGY.
SO TODAY I WANT TO GIVE A
QUICK CONCEPT OF ONE OF
THESE VALUES, TO TRY TO
BUILD A CATALOG IN TERMS OF
UNDERSTANDING WHAT ARE THE
PROTEINS OF THE BRAIN, WHAT
ARE THE RULES OF ENTRY, WHAT
DO THEY DO.
AS I MENTIONED, THE WAY WE
APPROACHED THIS IS TO TAKE
ONE OF THESE DYES AND INJECT
THEM ONE BY ONE.
A RECENT REVIEW BY SAUNDERS
SUMMARIZED THIS APPROACH.
WE TAKE THESE DYES, PLANT
PROTEIN AND INJECT THEM AND
THEN ASK THE QUESTION IS
THERE A LEAKAGE OR NOT.
AND THESE ARE VERY IMPORTANT
STUDIES, DON'T GET ME WRONG,
IN WHICH WE HAVE LEARNED A
LOT OF HALLMARKS OF THE
BRAIN.
WE ALSO RECOGNIZE SOME OTHER
HALLMARKS INVOLVING THE
LUMEN AND IT STARTS WITH HOW
CAN WE SEE MORE, RIGHT?
RATHER THAN INJECTING JUST
ONE DYE AT A TIME, THE BLOOD
HAS BEEN AROUND MILLIONS OF
YEARS AND IF WE CAN PATH AND
TRACK AND VISUALIZE THE
MOVEMENT OF THESE BLOOD
PROTEINS, WE MIGHT RECOGNIZE
ISSUES WITH IT BECAUSE AFTER
ALL, THE BLOOD HAS FIGURED
OUT A WAY TO DO THIS.
SO WE TOOK NONAGEK, DISEASED
BRAIN TO UNDERSTAND THE
PATHWAYS AND SELECTIVE
CHEMICAL LABELING.
THE FIRST THING THAT STRUCK
US IS WE SAW THE NEW
PROTEINS IN THE BRAIN
VANNUAL SCULATURE.
SO YOU CAN SEE HERE, THE
UNEXPECTED DEGREE OF
VESICULAR BBB TRANSPORT TO
BRAIN CELLS.
AND ON THE RIGHT YOU SEE THE
HIPPO CAMPUS AND THE BLOOD
AND WE WENT ON TO SHOW HOW
THIS WORKS WITH THE ARRAY OF
RECEPTORS ON THE BRAIN
RECEPTORS.
AND THERE IS A CODE HERE
WHERE THE
CLATHRIN-TRANSCYTOSIS IS
ENGAGED AND BECOMES VISIBLE
DEPENDING ON THE INJECTED TRAC.
SO [INAUDIBLE].
SO LEARNING THE LANGUAGE OF
THE PROTEIN TRANSPORT ACROSS
THE BLOOD BRAIN BARRIER, IT
WAITS FOR THE PERMEABLE
PROTEINS TO ENTER THE BRAIN,
THEN WE HARVEST THE BRAIN OF
ALL THE BLOOD AND ISOLATE
THE NEURONS.
AND THEN WHAT YOU CAN DO IS
TAKE THOSE CELLS ANDING BAIT
THEM WITH A PARTICULAR
PROBLEM PROTEIN.
YOU CAN CATALOG ALL OF THESE
AND WHAT HAPPENS IS THEY
WON'T BE IN ANYONE ELSE.
KIND OF LIKE WHEN YOU GO TO
A BAR, YOU WON'T TALK TO
ANYONE ELSE BUT YOUR FRIEND
AND THAT IS HOW THIS WORKS.
YOU FISH OUT THE PROTEINS
THAT ARE PERMEABLE AND
ENTERING THE BRAIN WITH THE
BLOOD AND THEN IDENTIFY WHAT
THOSE ARE ON MASS
EXPECTITOMETRY.
SO AFTER A WHOLE SERIES OF
OPTIMIZATION THAT TOOK TWO
YEARS AND ALL THE CONDITIONS
THAT MADE THIS WORK, AND
JUST TO SHOW YOU WHY THIS IS
FRUITFUL, YOU CAN SEE THE
PROTEIN ON THE LEFT AND IT
TURNS OUT CHEMISTRY MATTERS.
YOU CAN SEE SO MUCH MORE IN
THE SENSITIVITY, BETTER MAP
OF THE BRAIN.
JUST TO SHOW ANOTHER CONCEPT
THAT WE CAN TAG HUNDREDS OF
PROTEINS IN THE BLOOD
PLASMA, ACROSS DIFFERENT
CLASSES, TISSUES, SO WE FEEL
LIKE WE ARE READY TO GO AND
UNDERSTAND WHAT ARE THOSE
FACTORS.
SO FIRST THERE IS THIS UP
EXPECTED DEBRIS, SIMILAR TO
A SPONGE SO WHEN WE DO THIS
MASS SPECTOMETRY ANALYSIS,
AND I APOLOGIZE THAT SOME OF
THE DATA IS MISSING HERE,
BUT WE FIND THAT THERE ARE
187 PROTEINS BEING TAKEN UP
BY THE BRAIN ALL THE TIME SO
IT IS NOT SO MUCH A BARRIER
BUT INITIALING ALONG THE
PLASMA AND SENSING WHAT IS
GOING ON WITH THE BLOOD.
BASED ON THE IMAGING, WE
HAVE SHOWN THAT UNKNOWN
PROTEINS ENTERING THE BRAIN.
YOU CAN TAG THEM AND WHAT WE
HAVE FOUND IS THEY CONTAIN
UNKNOWN CIRCULATING PROTEINS
AND UNDER MASS SPECTOMETRY
EVALUATION, WE CAN IDENTIFY
THESE HUNDREDS OF PROTEINS
SO THE QUESTION IS WHAT DO
THEY DO AND WHY DOES OUR
BRAIN NEED PROTEINS?
SO THROUGH ANALYSIS, SEEMS
LIKE THERE ARE CERTAIN
PROTEINS THE BRAIN WORKS
INCLUDING CARRIER PROTEINS
BUT THERE ARE MANY OTHER
FACTORS SUCH AS PROTEASE
INHIBITORS AND THEN OF
COURSE GROWTH FACTORS.
THESE PROTEINS ARE EXPECTED
TO COME FROM THE LIVER, THE
HEART AND BONE MARROW AND OF
COURSE WITH EVERY NEW
TECHNOLOGY, YOU WANT TO
CHECK, WELL, IS THIS
WORKING, RIGHT?
SO I WANT TO GIVE A COUPLE
OF EXAMPLES IN THE WAY THIS
IS TRUE.
SO ONE WAY WE GO ABOUT THIS,
IF WE SEE A PROTEIN IN THE
CATALOG, IT HAS BEEN THERE
BUT NOT EXPRESSED BY ANY RNA
THAT IT ENTERED THE BRAIN.
YOU LOOK HERE, NEITHER ARE
EXPRESSED IN THE BRAIN BUT
YET WHEN YOU TAG THEM AND
INJECT THEM IN THE
BLOODSTREAM, YOU CAN SEE THE
PROTEINS IN THE VASCULATURE
AND WHERE THE NEURONS ARE,
COMPLETELY TRANSPARENT.
SO YOU SEE HERE IN THE
GREEN, THE VASCULATURE IS
SOAKED UP WITH THESE PRETTY
TONS.
AND WHAT THEY DO, THAT WILL
BE SHOWN IN ONGOING WORK.
BUT I THINK IT IS OBVIOUS
THERE ARE CLEAR CLASSES OF
PROTEINS, A MEANING TO THIS.
IT SEEMS LIKE THIS IS NOT
JUST ONE OUTLIER BUT THAT IT
IS TRUE THE BRAIN HAS MANY
OTHER CARRIER PROTEINS AND
WHAT IS REALLY FASCINATING
FOR US HAS BEEN THE PRIOR
WORK SHOWING US THE KNOCKOUT
OF DIFFERENT PROTEINS HAS
THE NEUROLOGICAL
CONSEQUENCES IN AGED MICE
AND WE'RE FOLLOWING UP ON
THAT.
AND THEN THIS IS EARLY DAYS
BUT WE'RE REALLY INTERESTED
TO KNOW WHAT HAPPENS IN
AGING AND THAT IS BECAUSE IN
OUR PRIOR WORK, WE FOUND
THERE ARE DRAMATIC CHANGES
IN THE BRAIN BARRIERS WITH
NORMAL AGING AND DISEASE
AGING.
FOR ONE, THERE IS THIS SHIFT
IN THE RECEPTOR TRANSPORT,
THE RIGHT CELL ENTERING THE
RIGHT PART OF THE BRAIN BUT
RATHER A KIND OF FREE FLOW,
INSTEAD OF THE PROTEIN
ENTERING IN A CERTAIN WAY,
IT SORT OF LEAKS THROUGH.
SO ON THE LEFT WE HAVE THE
SES KELS IN THE YOUNG
VASCULATURE, THEN AS YOU
TURN ON THE AGE, IT LOOKS
LIKE THE BRAIN IS LOSING ITS
VASCULARIZATION.
SO WHAT DOES THIS MEAN FOR
THE INDIVIDUAL PROTEINS
ENTERING THE BRAIN?
WHAT WE CAN SEE NOW IS IT
SEEMS LIKE THERE ARE SOME
THAT ARE MORE INFLAMMATORY
ENTERING THE BRAIN, THERE IS
A LOSS OF THESE HEALTHY
PROTEINS.
WE BEGIN TO VALIDATE SOME OF
THIS.
FOR EXAMPLE, YOU CAN STAIN
FOR HEMOGLOBINS VASCULARLY
AND SEE THESE.
SO THOUGHT PUSHING, IT IS
MORE THAN JUST VASCULATURE
AND LEAKY.
IF YOU THINK OF THE BRAIN AS
A SPONGE, SOAKING UP THE
RIGHT PROTEINS IN THE BLOOD,
MONITORING WHAT IS GOING ON
WITH THE BLOOD AND THAT CAN
BE VERY INDIVIDUAL DEPENDING
ON THE LIFESTYLE.
BUT IN THE AGING, THE BRAIN
IS NO LONGER GETTING WHAT IT
NEEDS AND THIS COULD BE
EXPOSURE TO CAN DO INS AND
PATHOGENS.
SO TO SUMMARIZE, THE BRAIN
BARRIER IS ALIVE, MONITORING
WHAT IS GOING ON, THERE ARE
HUNDREDS OF THINGS GOING ON
ALL AT THE SAME TIME WITH
THE PROTEINS AND THESE SHIFT
WITH BRAIN ALONG WITH
CHANGES IN THE BLOOD BRAIN
BARRIER.
SO MY THOUGHT, IT SOUNDS
CRAZY BUT IS THERE A
MOLECULAR MOWIVE?
JUST LIKE WE KNOW THERE ARE
AMINO ACIDS THAT UPHOLD
PROTEINS WITHIN THE CELL,
THERE MIGHT BE PATTERNS
ENRICHED IN THE BBB
PERMEABLE PROTEINS INFORMING
NEW DELIVERY AVENUES TO
TARGET BRAIN AGING.
YOU MAY NOT HAVE TO HAVE THE
PATHOGEN ENTER THE BRAIN FOR
IT TO BE ABLE TO MODULATE
IT.
SO IN SHORT LEARNING THE
RULES OF ENGAGEMENT AND HOW
THE BODY SPEAKS TO THE BRAIN
MIGHT BE A REALLY IMPORTANT
ADVENT AND OPEN NEW
OPPORTUNITIES FOR
UNDERSTANDING THE AGING
ISSUE AND PROMOTE HEALTHY
TISSUE.
SO WITH THAT, I WANT TO
THANK SAUL AND OTHERS AT
U.S. F.
THANK YOU FOR YOUR TIME AND
LOOK FORWARD TO YOUR
DISCUSSION.
[APPLAUSE]
>> OKAY, GOING TO THE NEXT
ONE, SORRY, THERE WE GO.
SO YOU SEE KIND OF THE TRIP
WE'RE TAKING, WE ARE DOING
BLOOD, WENT TO THE BARRIER
BUT OF COURSE WE CAN'T THINK
OF THAT INTERFACE BETWEEN
THE PERIPHERY AND BRAIN
WITHOUT GOING INTO THE OTHER
PLAYERS, HORMONES AND
METABOLISM AS WELL.
SO WE WILL START TO LEARN A
LITTLE MORE THAT GOES IN
THAT DIRECTION AND WE HAVE
EMILY JACOBS FROM THE
UNIVERSITY OF
CALIFORNIA-SANTA BARBARA TO
TALK TO US ABOUT THAT.
>> THANK YOU FOR HAVING ME
AND PUTTING THIS PANEL
TOGETHER.
I WILL TALK ABOUT THE
ENDOCRINE MODULATION OF THE
NERVOUS SYSTEM BUT BEFORE I
GET IN THE SCIENCE, I WANT
TO TAKE A STEP BACK AND
CONSIDER WOMEN'S HEALTH
BECAUSE ARGUABLY, WE ARE 20
YEARS BEHIND WHERE WE SHOULD
BE.
MOST OF US KNOW ABOUT THE
DISEASE ON THE BODY AND
THERE IS A WHOLE HISTORY OF
THAT THAT I HAVE GIVEN
ENTIRE LECTURES ON BUT NOT
TODAY, 70 PERCENT OF THESE
DISEASE CASES ARE WOMEN, TWO
OUT OF THREE WHO SUFFER FROM
DEPRESSION ARE WOMEN.
THERE ARE SOME CONDITIONS
THAT ONLY PEOPLE WITH A
UTERUS WILL DISCOVER LIKE
POSTPARTUM BLUES OR PERRY
MENOPAUSAL BRAIN FOG.
THESE ARE CONDITIONS THAT
AFFECT WOMEN AND MORE MEN
THAN WOMEN GARNER FUNDING
AND THAT BOOSTING OF
INVESTMENT COULD REAP BIG
REWARDS.
SO I HAVE THE DISTINCT HONOR
MONDAY KAY IN THE WHITE
HOUSE JOINING THE PRESIDENT
AND FIRST LADY WHERE
PRESIDENT BIDE TEN SIGNED AN
EXECUTIVE ORDER PUSHING FOR
$12 BILLION IN NEW FUNDING
TO TRANSFORM WOMEN'S HEALTH
RESEARCH.
THIS COULD NOT COME QUICK
ENOUGH.
ELIMINATING THE GENDER DATA
GAP WILL REDUCE $1 TRILLION
RETURN ON THE INVESTMENT AND
THAT IS ANNUALLY.
SUFFICE IT TO SAY, WE CAN'T
AFFORD TO IGNORE WOMEN'S
HEALTH ANY LONGER, OR AS HAS
BEEN SAID, WE CANNOT SUCCEED
WHEN HALF OF US ARE LEFT
BEHIND.
WE HAVE A LOT OF WORK TO DO
AND TO PUT REAL NUMBERS ON
THAT PROBLEM, I WANT TO CULL
FROM AN EXAMPLE THAT HITS
CLOSE TO HOME, COMES FROM MY
OWN WORLD OF HUMAN BRAIN
IMAGING.
TECHNOLOGY FIRST ENTERED THE
MAINSTREAM IN THE MID TO
EARLY 90s AND GAVE
NEUROSCIENTISTS
UNPRECEDENTED ACCESS TO THE
LIVING HUMAN BRAIN.
AND SINCE THAT TIME, THERE
HAS BEEN OVER 50,000
ARTICLES THAT HAVE BEEN
PUBLISHED USING BRAIN
IMAGING TECHNOLOGIES,
REPRESENTED BY THIS BLUE
WAVE AND THEN IF YOU SQUINT
REALLY HARD, YOU CAN SEE
THIS SORT OF THIN BLACK LINE
AT THE BOTTOM BUMPING AROUND
ITS AXIS.
YOU HAVE TO PULL OUT A
MICROSCOPE.
THAT IS EVERYTHING WE KNOW
ABOUT HOW THE BRAIN RESPONDS
TO PREGNANCY, MENOPAUSE,
MENSTRUAL CYCLE, HORMONAL
DON'T SESSION CONTRACEPTION
ALTOGETHER.
SO OF THOSE TOGETHER, LESS
THAN 1 PERCENT FOCUSES ON
HEALTH FACTORS OF WOMEN.
OR TO PUT IT ANOTHER WAY,
THE CONDITION AFFECTS HALF
OF ALL THOSE IN THE WORLD.
SO I THINK WE HAVE TO ASK
WHOSE BODY DOES IT SERVE?
AND HERE IS THE THING, THESE
TOPICS ARE UNKNOWN BUT
KNOWABLE AND BY LOOKING AT
THESE MAJOR FACTORS, WE ARE
ALMOST CERTAINLY MISSING
CRITICAL CLUES THAT CAN TELL
US ABOUT THE BRAIN HEALTH
OVER THE LIFE COURSE.
I WILL USE THE IMAGING WHICH
I HAVE BEEN DOING THE LAST
SEVERAL YEARS AND ONE THING
I WANT YOU TO KEEP IN MIND
IS AS THIS COMES TOGETHER IN
ANIMAL AND HUMAN MODELS, THE
TISSUES ARE MORE REGULATED
BY HORMONES AND ACROSS HE IS
LIFE EVENTS BUT OVERLAP WITH
CIRCUITS THAT REGULATE
DEPRESSION AND ALZHEIMER'S
DISEASE.
SO THE QUESTIONS IN MY LAB
IS WHAT ARE THE
PHYSIOLOGICAL PROPERTIES
THAT MAKE THESE SO PRONE TO
DAMAGE?
SO I WOULD BE REMISS NOT
THOUGH THROW THIS SLIDE IN.
THIS IS A BEAUTIFUL WORK
FROM KATHERINE WOOLEY FROM
THE 90s AND SHE REALLY
SHINED THE SPOTLIGHT ON
STERIHORMONES, NOT THE
GLAND, NOT FOCUSING ON OVERT
BEHAVIORS, SHE SHOWED THE
POTENT MODULATORS IN THE
REGION OF THE HIPPO CAMPUS,
ZOOMED IN TO LOOK AT THE
DENDRITES AND DENDRITIC
SPINES BY ESTRO-CYCLE STAGE
IN THE FEMALE LAB MICE AND
WHEN YOU LOOK AT WHAT THIS
LOOKS LIKE, YOU GET THIS
MASSIVE PROLIFERATION OF THE
SPINES AND THEN 24 HOURS
LATER WHEN ESTROGEN COMES
DOWN, YOU GET THIS SPINING.
THIS IS BEAUTIFUL WORK EVEN
THOUGH IT WAS KIND OF
REJECTED AS THE FIELD WAS
NOT READY FOR THIS KIND OF
SCIENCE BUT IT IS ALL
CROSS-SECTIONAL, BASED ON
HISTOLOGY.
SO ONE QUESTION THAT I HAVE
IS CAN WE USE TODAY'S
TECHNOLOGY TO SEE THESE SAME
PULSES IN THE BRAIN?
WE HAVE THESE ABILITIES TO
PEER INTO THE ANIMAL NOW
WITH MORE MICROSCOPY USING
2-PHOTO TON IMAGING AND WITH
THE MOUSE BRAIN FLIPPED
UPSIDE DOWN, YOU CAN SEE
THIS RESOLUTION IN THE AWAKE
BEHAVING ANIMALS.
SO TAKING FEMALE MICE,
IMAGING THEM WITH 2-P EVERY
12 HOURS FOR 8 DAYS WHICH
RESPONDS TO TWO COMPLETE
ESTRO-CYCLES, DOING VAGINAL
CYTOLOGY WITH THE SCHORR
STAIN AND SURE ENOUGH, WHAT
DOES SHE FIND?
THESE BEAUTIFUL PULSES, THIS
ESTROUS CYCLE.
AND YOU CAN SEE THE SPINES
EBB AND FLOW THROUGHOUT TIME
AND SEE WHAT THE CYCLE
OCCURRENCE WAS.
SO NOW COMES THE CRITICAL
QUESTION.
WHY IS THE BRAIN ORGANIZED
IN THIS WAY?
WHY ARE THESE RHYTHMS
HAPPENING AND I DON'T HAVE
TIME TO GET INTO THE NEURAL
PORTION OF THAT BUT I CAN
TELL YOU THAT THROUGH TIME,
WE KNOW THROUGH PROESTUS
THERE IS SOMETHING THAT
HAPPENS TO THE IMMUNE CELL
RESPONSES IN WHICH THEY
BECOME BOTH MORE STABLE SO
WHEN YOU PUT THE ANIMAL IN
TRACK A, YOU GET THESE
WONDERFUL PLACE CELLS ON THE
CIRCULAR TRACK IN BLUE.
ANOTHER INITIATION INTO THAT
TRACK AT A LATER TIME, THOSE
RESPONSES BECOME REALLY HIGH
FIDELITY.
THE CELLS ALSO BECOME MORE
FLEXIBLE.
SO THERE ARE TWO SIDES TO A
DIFFERENT COIN SO CLEARLY
THESE MORPH LOGICAL CHANGES
DRIVEN BY ACTIVITY HAVE AN
EFFECT ON THE CIRCUITS AND
THEN WE ADD IN CERTAIN
FACTORS TO UNDERSTAND IT A
LITTLE MORE.
SO NOW MY PART, CAN WE SEE
THESE CHANGES IN THE HUMAN
BRAIN OVER A RAPID TIME
SCALE?
THIS IS A STUDY THAT WOULD
NOT HAVE HAPPENED WERE IT
NOT FOR THE PANDEMIC.
OUR COMMUNITY WAS SHUT DOWN
BUT WE COULD SCAN OURSELVES
SO I HAD ONE INDIVIDUAL WHO
VOLUNTEERED TO PUT HERSELF
IN THE SCANNER, WE DID A
SCAN EVERY 24 HOURS,
COMPLETED THE CYCLE, DID IT
AGAIN.
WHY DID WE PULL THIS OFF?
IT SEEMS A CRITICAL FEATURE
OF THE ENDOCRINE SYSTEM IS
THERE ARE THESE EBBS AND
FLOWS FOR WOMEN THROUGH MOST
OF OUR TIME AND DRIVE THE
PROPERTIES THROUGHOUT THE
BODY BUT NOBODY KNEW HOW TO
SHAPE THE BRAIN.
AT BEST WE HAD
CROSS-SECTIONAL STUDIES OR
TWO-POINT STUD IES BUT THAT
DOESN'T GET AT THE DYNAMIC
HORMONE SECRETION.
SO WE DID THIS AND WE GET
THE PEAK IN PROGESTERONE AND
THE FIRST OBSERVATION WE
MADE USING TIME LAG ANALYSIS
THERE IS STRONG ANALYSIS
THAT INCREASES IN ESTRADIOL
OVER TIME DRIVE INCREASES IN
FUNCTIONAL CONNECTIVITY
ACROSS THE CORTICAL MANTLE
WITH SOME BEING MORE
RESPONSIVE THAN OTHERS.
SO WE GO TO THE GRAPH
LOOKING AT THE NETWORK
PROPERTIES AND ONE REALLY
POPPED OUT.
SO AT THE BOTTOM, THESE ARE
HORMONE LEVELS AND YOU YOU
CAN SEE WHEN ESTRADIOL
LEVELS PLUNGE, SO TOO IS THE
CENTRIC.
SO AT THIS POINT DURING THE
PANDEMIC, WE ARE STARING AT
THIS DATA AND TEAMED UP WITH
THE LAB WITH JEAN, JOSH AND
LAURA.
AND JOSH WAS LOOKING AT THE
THE COMMUNITY DETECTION AND
LOOKING AT NETWORK
FLEXIBILITY AND AT THE TOP
JUST GROUPING THE STAGE AT
THE MENSTRUAL CYCLE, THERE
IS SOMETHING DIFFERENT THAT
HAPPENS IN OVULATION.
THESE NETWORKS BECOME MORE
FLEXIBLE.
YOU SEE THIS TIME SERIES AT
THE BOTTOM AND WHAT I AM
HIGHLIGHTING IN THE BAR ARE
THE SPIKES OF ESTRADIOL IN
POPULATION SO THE BRAIN
INCREASES THIS THROUGHOUT
TIME AND SOME OF THIS IS
SHOWN IN THE NETWORKS, A LOT
OF BRAIN PHENOMENA THERE.
I DO WANT TO MAKE A LIVING
POINT.
THESE HORMONES ARE NOT
EXCLUSION SIEVE TO WOMEN.
THAT IS A MYTH THAT HAS BEEN
USED TO EXCLUDE WOMEN
THROUGHOUT THE LAST 50 YEARS
OF FUNDING.
BUT THAT IS NOT TRUE.
MEN HAVE THESE HORMONES,
TOO.
THIS DONE THROUGH 28 AND HE,
EVER 12 TO 24 HOURS, 40
SESSIONS AND HERE WE'RE
TARGETING THAT DIURNAL
FLUCTUATIONS THAT INCREASE
IN THE MORNING, DIP IN THE
EVENING AND THEN THE WHOLE
BRAIN FUNCTION OF COHERENCE
IN THE SAMPLE MALES AND THE
MAGNITUDE OF THESE EFFECTS
ARE VERY SIMILAR BETWEEN THE
MALE AND THE FEMALE.
IF ANYTHING, IT IS JUST THAT
THE EFFECTS ARE DIFFERENT,
RIGHT, WHERE MALES AND
FEMALES HAVE THE DIURNAL
RHYTHM BUT WOMEN HAVE THIS
SEPARATE RHYTHM.
SO WE KNOW THEY EBB AND FLOW
OVER TIME SO WE LOOK AT
THESE BRAIN STRUCTURAL
CHANGES IN SYNC WITH THE
CYCLE AND WHAT WE LEARNED IS
THE ESTRADIOL IN THE BLUE,
WHEN THE PARTICIPANT
COMPLETED THE EXPERIMENT A
YEAR LATER, THERE WAS ONE
WRINKLE TO THAT EXPERIMENT I
DIDN'T MENTION.
SHE WAS ON A DRUG THAT
SELECTIVELY SUPPRESSED
PROGESTERONE.
NOTICE THAT BLUE WAVE WAS
MISSING IN THE SECOND GRAPH
AND WHEN WE REMOVED THAT, WE
ABOLISHED THAT NATURAL
CYCLING RHYTHM.
SO WHAT ABOUT THE OTHER
ENDOCRINE CONDITIONS?
WE KNOW ENDOCRINE CHANGES
THAT OCCUR ACROSS THE
MENSTRUAL CYCLE CAN MORECH
COMPARED TO THOSE ACROSS
PREGNANCY, THIS WORK DONE
WITH CASTLE WHO IS IN THE
AUDIT KWR-PBS BUT THIS IS
PRECISION IMAGING OF THE
MATERNAL BRAIN AND YOU CAN
SEE THERE IS THIS WAVE OF
HORMONE PRODUCTION THAT
OCCURS ACROSS THE
GESTATIONAL PERIOD AND DROPS
PRECIPITOUSLY AT MATURATION,
WE HAVE PRECONCEPTION SCANS,
SCANS DURING GESTATION THAT
OCCURRED APPROXIMATELY EVERY
TWO WEEKS AND THEN GOING UP
TO TWO YEARS POSTPARTUM.
WHAT DO WE FIND?
THERE ARE THESE SWEEPING
CHANGES IN GRAY MATTER BRAIN
VOLUME, THE PARALLEL
EXPANSION WITH CSF IN
FILLING UP THE CAVITY WHICH
MAKES SENSE AND THEN THERE
ARE THESE REALLY INTERESTING
NONLINEAR MEASURES THAT PEAK
AND TOUCHDOWN BASELINE.
IN THE FOUR OR FIVE STUDIES
THAT LOOKED AT THE BRAIN
THROUGH PRE- AND POST, THE
ANALYSIS DONE BY SUSANNAH
AND OTHERS IN EUROPE, ONE
THING THAT IS MISSING AND I
THINK THIS PRECISION I
IMAGING STUDY BRINGS TO BEAR
IS THERE ARE ALL KINDS OF
SESSIONS DURING PREGNANCY
THAT WE MISS.
THIS IS PRETTY UBIQUITOUS
WITH THE CHANGE IN BRAIN
FUNCTION BUT SOME BUCK THE
TREND AND THAT WILL BE A
THREAD I WILL WANT TO PULL
ON.
THESE GRAY MATTER VOLUMES
FOR EXAMPLE, THE NODES
WITHIN THE DEFAULT NETWORK,
YOU CAN SEE THESE GRAY
MATTER VOLUME UNFOLD IN THE
DIFFERENT WEEKS.
THE PRECONCEPTION IN PINK
AND THEN THE FIRST, SECOND
AND THIRD TRIMESTER, THE
DECLINE AND DECREASE AND
THEN THERE IS NO REBOUND.
THESE ARE LIKE PERMANENT
ETCHINGS IN THE BRAIN TILL
AT LEAST TWO YEARS
POSTPARTUM.
SO WE REALLY START TO THINK
OF THIS EXTENDED PERIOD IN
THE ADULT BRAIN THAT COULD
GIVE US CLUES ON HOW THE
BRAIN IS AGING LATER IN
LIFE.
WE KNOW YOU CAN KEEP THE
BRAIN RESPONSIVE TO ESTROGEN
INCLUDING NEUROGENESIS AND
AGING IN RATS AND IN THE 42
SECONDS I HAVE LEFT, I WANT
TO JUST SAY ONE WORD ABOUT
THIS.
OUR GOAL IS TO TAKE WOMEN'S
BRAIN HEALTH THROUGH TIME.
SOME OF THE EVIDENCE IS
KNOWN IN MEN'S BRAIN HEALTH
BUT WE WANT TO MAKE IT
INCLUSIVE BOTH IN TERMS OF
WHO GETS TO ASK THE
QUESTIONS AND GET THE
ANSWERS.
SO WE HAVE GENERATE THE
DATA, BUILD THE
INFRASTRUCTURE TO SHARE THE
DATA AND THEN DEVELOP AI
TOOLS TO ANSWER THE
QUESTIONS OF WOMEN'S BRAIN
HEALTH.
WE HAVE ONE OF THESE CENTERS
AT THE INSTITUTE AND ONCE WE
COLLECT THE DATA, WE GIVE IT
ALL AWAY.
OPEN ACCESS TO BRAIN
DISCOVERY SHOULD NEVER STOP.
SO WITH THAT I WANT TO THANK
THE BRILLIANT SCIENTISTS WHO
DO THE HARD WORK, I JUST GET
THE PLEASURE OF SPEAKING
ABOUT IT.
THANKS.
[APPLAUSE]
>> AWESOME, THAT WAS
FANTASTIC AND WE WILL
DEFINITELY BE VISITING SOME
OF THOSE TOPICS DURING THE
DISCUSSION SO GET READY,
JUST A HEADS-UP.
OKAY FOR OUR LAST SPEAKER,
WE ARE GOING TO CONTINUE
MOVING FORWARD WITHIN THE
REALM OF THE HUMAN CONDITION
LOOKING TOWARD THERAPEUTICS
AND INTERVENTIONS WE CAN DO
AND IN THIS CASE LOOKING AT
THE METABOLISM SO REALLY
EXCITED TO LOOK AT THE WORK
BY Dr. ROBERTA DIAZ
BRINTON.
>> FIRST OFF I WANT TO THANK
MOLLY WAGNER AND THE
COMMITTEE FOR PRESENTING THE
WORK THEY ARE INVOLVED IN
THIS MORNING AND ALSO A
SHOUTOUT TO THE NATIONAL
INSTITUTE OF AGING WHO HAS
BEEN FUNDING WOMEN'S HEALTH
RESEARCH FOR DECADES AND
KUDOS TO THEM, BECAUSE THEY
ARE LEADING THE FIELD.
OKAY, SO THIS IS PRETTY
SIMPLE.
SO I WILL BE TALKING ABOUT
THIS MID-LIFE AGING
TRANSITION AND OUR
DISCOVERIES ABOUT HOW THAT
MIDLIFE AGING TRANSMISSION
IN THE FEMALE BRAIN HAS
IMPLICATIONS FOR BRAIN
METABOLISM AND ULTIMATELY
FOR BRAIN HEALTH AND
RESISTANCE -- RESILIENCE.
THESE ARE ME DISCLOSURES.
SO ONE OF THE THINGS I HAVE
LEARNED A GREAT DEAL ABOUT
OVER THE SEVERAL DECADES OF
THIS RESEARCH IS THE WAY WE
THINK ABOUT AGING.
AND WE TYPICALLY THINK ABOUT
AGING AS A, YOU KNOW, LINEA
PROGRESSION FROM WE ARE
ALIVE AND THEN WE ARE DEAD.
WHAT STUDYING THE FEMALE
BRAIN HAS TAUGHT ME, IS THAT
THE BRAIN ACTUALLY UNDERGOES
MULTIPLE TRANSITIONS STATES.
AND SO TO UNDERSTAND THESE
TRANSITION STATES, IT IS
NECESSARY TO REALLY LOOK AT
SYSTEMS BIOLOGY THROUGHOUT.
AND THE IMPORTANCE OF THIS
IS UNDERSTANDING THESE
TRANSITION STATES GIVES US
AN OPPORTUNITY TO SUSTAIN
BRAIN HEALTH, TO DELAY
TRANSITIONS TO DISEASE AND
THE POTENTIAL TO RESTORE.
SO LET'S THINK ABOUT THIS
TRANSITION STATES.
SO IT CAN SPAN YEARS.
WE KNOW IN THE CASE OF
ALZHEIMER'S DISEASE, THE
TRANSITION STATE,
PRECLINICAL STATE CAN LAST
10-20 YEARS.
THERE IS A SEQUENTIAL
ACTIVATION AND DEACTIVATION
OF REGULATORY PATHWAYS AND
THAT PREDISEASE IS AT THE
TRANSITION OF NORMAL.
SO WHEN WE THINK ABOUT WHAT
THE NORMAL RANGE IS, IS THE
PERSON AT THE HIGH END OR
LOW END OF THAT NORMAL
CURVE?
AND THAT SMALL PERTURBATIONS
CAN UNMASK EXISTING
VULNERABILITIES AND THIS IS
PARTICULARLY TRUE IN THE
TRANSITION STATES.
THIS IS A CRITICAL SLOWING
OF THE SYSTEM AND IMPORTANT
FOR REPAIR.
TRANSITION STATES ARE
UNSTABLE AND POTENTIALLY VIS
VERSABLE.
THEY ARE HOWEVER TIME
LIMITED AND COMPLEX SYSTEMS
LIKE THAT IN THE BRAIN HAVE
CRITICAL THRESHOLDS, OR WHAT
I CALL TIPPING POINTS.
OUR STUDY OVER A NUMBER OF
DECADES, OUR ANALYSES OVER A
NUMBER OF DECADES HAVE
TAUGHT US THERE ARE THREE
TRANSITION STATES IN THIS
AGING PROCESS.
LIKELY MORE, BUT TODAY WE
HAVE CATEGORIZED THEM INTO
THREE.
THE FIRST IS EARLY
CHRONOLOGICAL AGING AND THAT
IS THE AGING YOU DON'T EVEN
KNOW IT HAPPENING, BUT IT
IS.
AND THAT EARLY CHRONOLOGICAL
AGING PRECEDES THE
ENDOCRINOLOGY CALL AGING.
AND WHEN WE LOOK AT THE
EARLY ENDOCRINOLOGICAL AGING
AND THE TRANSCRIPTION, MORE
IN THE HYPO THALAMUS AND
VERY FEW IN THE HIPPO
CAMPUS.
BUT THEN YOU LOOK AT THIS
TRANSITION, THE
ENDOCRINOLOGICAL, VERY FEW
IN THE HYPO THALAMUS AND
LESS IN THE HIPPO CAMPUS.
NOW THE BRAIN HAS CHANGED
AND YOU CAN SEE THE
PREDOMINANCE OF CHANGES IN
TRANSCRIPTION ARE HAPPENING
IN THE-THOUGH THALAMUS AND
THAT THE HIPPO CAMPUS HAS
CHANGED.
SO WHEN WE LOOK AT MIDLIFE
AGING IN THE FEMALE AND
THINK ABOUT THE PERRY
MENOPAUSE TO MENOPAUSAL
TRANSITION OF THE FEMALE
BRAIN, THE MIDLIFE
NEUROLOGICAL TRANSITION, WE
SEE COINCIDENT WITH THE
DECLINE IN BRAIN GLUCOSE
METABOLISM THAT HAPPENS
EARLY IN THIS PROCESS AND
DURING THE PER
PERIMENOPAUSAL TRANSITION,
THERE IS A RISE IN THE
BRAIN.
BUT IF YOU LOOK AT THE
SYMPTOMS OF THIS TRANSITION,
THEY HAVE NOTHING TO DO WITH
PRODUCTIVE SYNESCENS.
MANY WOMEN WILL COMPLAIN OF
DEPRESSION SIEVE DISORDERS,
CHANGES IN THE BRAIN, MOOD
CHANGES, ALL OF THESE
SYMPTOMS ARE ACTUALLY
NEUROLOGICAL SYMPTOMS.
WE HAVE STUDIES IN THE
IMPACT OF ESTROGEN
REGULATION OF OUTCOMES IN
THE BRAIN FOR MANY YEARS
BECAUSE OF THE CHANGE THAT
OCCURS IN BRAIN LEVELS OF
ESTROGEN.
WE KNOW THAT ESTROGEN, I
CALL THE QUEEN OF DARLING,
SHE HAS LEFT NOTHING TO
CHANCE.
ESTROGEN PROMOTES THE UPTAKE
OF GLUCOSE IN THE BRAIN, THE
METABOLISM OF GLUCOSE
ULTIMATELY INTO ADP.
SO THE LOSS OF ESTROGEN
PARTICULARLY IN THE PERIMEN
NOW PAUSE AND MENOPAUSAL
CONDITION LEADS TO ABOUT A
25 PERCENT DECLINE IN THE
FEMALE BRAIN AND THAT
ACTIVATES THE RELEASE OF
ESTROGEN SUPPRESSION OF THE
SCOTT ENDESIGN AND THAT
MITOCHONDRIAL REGULATION
WHICH IS THE FUEL FOR THE
KETONE BODIES IN THE BRAIN.
AND ULTIMATELY WHAT WE FIND
IS THIS DECLINE THAT IS
SIGNIFICANT WITH LOSS OF
ESTROGEN IN THE BRAIN LEADS
TO THIS ADAPTIVE RESPONSE IN
THE METABOLIC SYSTEM SO THAT
THERE IS DECLINE IN GLOWING
-- GLUCOSE METABOLISM IN RED
AND THE FIRST RESPONSE IS
THE AMINO ACIDS THAT CAN BE
CONVERTED TO GLUCOSE OR
KETONE BODIES IN THE BRAIN,
FOLLOWED BY THIS CHANGE IN
PHENOTYPE OF MITOCHONDRIA,
FROM INEFFICIENT TO
EFFICIENT MITOCHONDRIA AND
THAT IS RELATED TO THE PASS
ITY ACID OXIDATION IN THE
BRAIN.
THAT IS THE METABOLIC
RESPONSE OF NOW USING LIPIDS
AS AN AUXILLIARY FUEL TO
GENERATE KETONE BODIES.
ANOTHER COMPONENT OF THIS
WHOLE SYSTEM IS THE IMMUNE
SYSTEM AND ACTIVATION OF THE
INNATE AND ADAPTIVE IMMUNE
SYSTEMS THAT IS COINCIDENT
WITH THESE CHANGES IN THE
REPROGRAMMING OF THE
METABOLIC SYSTEM.
SO WHERE ARE THOSE LIPIDS
COMING FROM THAT CAN NOW BE
AN AUXILLIARY FUEL FOR THE
BRAIN AND CONVERTED INTO
KETONE BODIES?
THE BRAIN IS THE MOST
LIPIDATED ORGAN OF THE BODY
AND WE HAVE DISCOVERED THE
BRAIN CAN METABOLIZE ITS
WHITE MATTER FOR FUEL.
AND THIS IS A SCHEMATIC OF
PROBABLY 20 YEARS OF
RESEARCH THAT SHOWS THAT
THAT DECLINE IN GLUCOSE
DERIVED ATP IN NEURONS SETS
OFF A STARVATION RESPONSE IN
THE BRAIN AND GOD BLESS
THOSE ASTROCYTES, BECAUSE
THOSE ASTROCYTES ARE COMING
TO THE RESCUE.
AND THOSE ARE THE CELLS THAT
ARE ACTIVATED TO CONDUCT
DATA OXIDATION OF FATTY
ACID, WHICH THEN THEY SEND
BACK TO THE NEURONS TO
GENERATE ACETYL-CHOLA FOR
PRODUCTION SO THAT RESPONSE
IS A COORDINATED RESPONSE
FROM NEURONS AND ASTROCYTES.
THE BAD NEWS IS THAT
METABOLISM OF THE WHITE
MATTER FOR FUEL LEADS TO THE
GENERATION OF BASICALLY
MYELIN FRAGMENTS WHICH ARE
RECOGNIZED BY THE MICROGLIA
AS A FOREIGN BODY AND THAT
FOREIGN BODY NOW ACTIVATE AN
ADAPTIVE IMMUNE SYSTEM
RESPONSE TO PRESENT THAT
FRAGMENT ON THE MICROGLIAL
PLASMA WITH THE MTG
RECEPTORS AND ACTIVATING
WHAT LOOKS LIKE TO THE WORLD
AN AUTOIMMUNE RESPONSE IN
THE BRAIN.
SO THIS IS HAPPENING IN THE
MIDLIFE TRANSITION.
THIS IS ALL WORK THAT HAS
BEEN IN THE PRECLINICAL
DISCOVERY SCIENCE SPACE.
WE THEN ASKED THE QUESTION
WITH OUR COLLEAGUE LISA
MUSCONI WHETHER THERE IS
METABOLIC PROGRAMMING IN THE
HUMAN BRAIN.
AND THAT WORK SHOWS US WHEN
SHE PARALLELS THE BASIC
DISCOVERY PROCESS DESIGN AND
LOOKED AT WOMEN WHO WERE
PRE, PERI AND
POSTMENOPAUSAL, WHAT SHE
FOUND IS THAT INDEED THERE
WAS A DECLINE IN GLUCOSE
METABOLISM IN THE MIDLIFE
AGING FEMALE.
AND THAT RELATIVE TO MALES,
THERE IS A GREATER DECLINE
IN AGE MATCHED MALES, A
DECLINE IN GLOWING COWS
METABOLISM RELATIVE TO THE
AGE MATCHED MALES.
AND IS THAT LEADING TO A
CHANGE IN GRAY MATTER?
NONSPECIFIC TO THIS
MENOPAUSAL TRANSITION, IT
LOOKS MORE LIKE A AGING
CHANGE IN GRAY MATTER.
THE REAL CHANGE IS IN THE
WHITE MATTER AND CONSISTENT
WITH OUR FINDINGS IN OUR
DISCOVERY SCIENCE AND THAT
CHANGE IN WHITE MATTER
VOLUME IS COINCIDENT WITH
THE GENERATION OF DATE AM
LLOYD DEPOSITION IN THE
FEMALE BRAIN.
AND THAT THIS CHANGE IN BOTH
WHITE MATTER AND THE
POTENTIAL METABOLISM OF
WHITE MATTER IN HUMAN BRAIN
IS COINCIDENT WITH A PLASMA
METABALOME CHARACTERIZED
WITH SINGLE METABOLOMES.
SO CAN THIS AGING BE
IDENTIFIED AND CAN WE
IDENTIFY WOMEN WHO ARE AT
RISK WHILE THEIR BRAINS ARE
STILL HEALTHY?
AND THIS IS WORK WE HAVE
DONE WITH WENDY MACK AND
OTHERS AT U.S.C. IN AN ELITE
TRIAL AND THE BOTTOM LINE IS
WHEN WE LOOK AT HEALTHY I
THINK AING WOMEN 65 AND
OLDER, WHAT WE FOUND IS IN
THIS HEALTHY POPULATION OF
WOMEN, THERE WERE THREE
GROUPS OF WOMEN.
THERE WERE WOMEN WHO WERE
METABOLICALLY HEALTHY, THERE
WERE WOMEN WHO WERE AT RISK
FOR DEVELOPING METABOLIC
SYNDROME OR DEVELOPING TYPE
2 DIABETES AND A THIRD GROUP
OF WOMEN WHO HAD HIGH
PRESSURE OR AT RISK FOR HIGH
PRESSURE AND CARDIOVASCULAR
DISEASE.
AND WHEN WE LOOK AT THEIR
COGNITIVE DISCUSSION, WHAT
WE FOUND IS THE HEALTHY
WOMEN IN GREEN PERFORM BEST
ON THESE MEASURES IN
COGNITION.
THE WOMEN WITH HIGH BLOOD
PRESSURE WERE NOT
STATISTICALLY DIFFERENT BUT
THEY WERE IN A TRANSITION TO
LOWER COGNITIVE FUNCTION.
BUT IT WAS REALLY THE WOMEN
WHO HAD A POOR METABOLIC
PROFILE, NOT DIAGNOSED WITH
TYPE 2 DIABETES OR METABOLIC
SYNDROME WHO SHOWED
SIGNIFICANT DECLINE IN
COGNITIVE FUNCTION.
AND THEN WE ASKED, WELL, WHO
ARE THOSE WOMEN DRIVING THAT
CHANGE AND IT TURNS OUT THEY
WERE AP4 CARRIERS.
SO THE COMBINATION OF AN
AT-RISK METABOLIC PROFILE
AND THE GENE LED TO DRIVING
THIS SIGNIFICANT CHANGE.
BUT THE INTERESTING
COMPONENT OF THIS IS THAT
APOE4 WAS DISTRIBUTED EVENLY
ACROSS ALL OF THESE
SUGGESTING IF WE TARGET THE
METABOLIC HEALTH OF THESE
WOMEN WE COULD CHANGE OF
BRAIN AGING IN THOSE WOMEN
TO BE CONSISTENT WITH THE
APOE4 CARRIERS IN THE
HEALTHY COGNITIVE FUNCTION
GROUP.
SO IF ESTROGEN LOSS
INITIATES VULNERABILITY FOR
COGNITION AND POTENTIAL FOR
THE DEVELOPMENT OF
ALZHEIMER'S PATHOLOGY, DOES
MENOPAUSAL HORMONE THERAPY
DEVELOP RISK FOR ALZHEIMER'S
LATER IN LIFE.
AND THIS STUDY WAS A MIDLIFE
GROUP MATCHED OVER 1000
WOMEN WHO THE BOTTOM LINE IS
THOSE ON HORMONE THERAPY
SHOWED REDUCED RISK OF
PARKINSON'S, ALZHEIMER'S AND
OTHER NEURODEGENERATIVE
DISEASES AND THE LONGER THEY
WERE ON HORMONE THERAPY, THE
GREAT THE RISK.
GOOD NEWS, BAD NEWS.
THE FACT THERE IS SOME
ASSOCIATION WITH HORMONE
THERAPY, NOT JUST ESTROGEN
ALONE, HAS IMPACTED WOMEN'S
CHOICE TO RECEIVE HORMONE
THERAPY AND 80 PERCENT OF
THEM ELECT NOT TO RECEIVE
HORMONE THERAPY FOR
MENOPAUSAL SYSTEMS VOTING
FOR BREATH HEALTH OVER BRAIN
HEALTH AND THEIR PRINCIPLE
REASON WAS FEAR OF BREAST
CANCER FOR THAT DECISION.
SO TO SUSTAIN BRAIN HEALTH,
WE HAD TO ADDRESS BREAST
HEALTH.
AND TO DO THAT WE DEVELOPED
A STRATEGY THAT TARGETS
ESTROGEN RECEPTIVE BETA AND
FROM CANCER RESEARCHERS, IT
SHOWED ACTIVATING ESTROGEN
BETA IN BREAST TISSUE
REDUCED AND INHIBITS
ESTROGEN BREAST CELL
PROLIFERATION, BREAST CANCER
CELL PROLIFERATION, INHIBITS
BREAST CANCER CELLS
MIGRATION AND SUPPRESSES THE
ONCOGENIC PATHWAY.
SO THAT IS YOU ARE O
OPPORTUNITY TO LOOK AT THE
ESTROGEN RECEPTOR BETA IN
THE BRAIN BASED ON BREAST
HEALTH AND WE DID THIS WITH
THE INSTITUTE OF AGING AND
TARGETED THREE MOLECULES AND
CONDUCTED A PHASE 1B2A TRIAL
BY THE NIA AND THE OUTCOME
INDICATED THERE WERE NO
INDICATORS OF TOXICITY.
SO WE NOW HAVE TWO CLINICAL
TRIALS FOR PLANT BASED
ESTROGEN RECEPTIVE
MODULATORS, THE FIRST IS A
CLINICAL TRIAL TARGETING HOT
FLASHES AND THE SECOND IS
OUR CLINICAL TRIAL TARGETING
BRAIN GLUCOSE METABOLISM AND
COGNITION AND THIS IS BEING
DONE IN COLLABORATION WITH
LISA NASCONI.
SO I THINK THERE IS THE
POTENTIAL FOR ALTERING THE
TRAJECTORY OF AGING DURING
MIDLIFE IN THE FEMALE.
I WANT TO EMPHASIZE THAT
INTERVENTION WITH EITHER
ESTROGEN OR PHYTOSERM IS TO
SUSTAIN BRAIN HEALTH.
IT IS NOT TO REVERSE
DISEASE.
SO AND I THINK THAT HAS
CONTRIBUTED TO SOME OF THE
CONTROVERSY IN THE FIELD BUT
ESTROGEN INSURANCE THE
UTILIZATION OF GLUCOSE AND
THE ACTIVATION OF GLUCOSE
METABOLISM IN THE BRAIN AND
ALL THE DOWNSTREAM
CONSEQUENCES.
ONCE THE BRAIN HAS UNDERGONE
METABOLICALLY PROGRAMMING,
THAT BRAIN IS REPROGRAMMED.
SO THE KEY CONCEPT, THE
NEUROLOGICAL CONDITION THAT
CAN UNMASK VULNERABILITY
INTO AGE ASSOCIATIVE
NEUROGENERATIVE DISEASES AND
THE TRANSITION INVOLVES BOTH
THE IMMUNE AND METABOLIC
SYSTEMS OF THE BRAIN, THAT
ESTROGEN AND HORMONE
THERAPIES SUSTAIN AND
PROMOTE HEALTHY BRAIN AGING
BUT DOES NOT REVERSE
DISEASE.
ONE SIZE WILL NOT FIT ALL.
WE WILL NEED HORMONE THERAPY
AND THAT PROMOTING BRAIN AND
BREAST HEALTH IS FEASIBLE
THROUGH SELECTIVE
FORMULATION AND WITH THAT, I
WILL RECOGNIZE MANY
INDIVIDUALS IN MY CURRENT
GROUP THAT HAVE CONTRIBUTED
TO THE RESEARCH AND FROM THE
GENEROUS SUPPORT FROM THE
NATIONAL INSTITUTE OF AGING
THAT HAS SUPPORTED WOMEN'S
BRAIN HEALTH FOR DECADES.
THANK YOU SO MUCH.
[APPLAUSE]
>> THANK YOU, THAT WAS
WONDERFUL.
PLEASE JOIN ME IN THANKING
ALL FOUR SPEAKERS BEFORE WE
JUMP IN.
[APPLAUSE]
>> PERFECT.
SO I WANT TO TAKE A LITTLE
BIT OF A MINUTE TO GIVE YOU
A LITTLE BIT OF MY
HISTORICAL PERSPECTIVE.
I WAS ACTUALLY HERE IN THE
RELATIVELY JUNIOR ASSISTANCE
PROFESSOR FOR THE 2017
SUMMIT AND JUST SEEING THESE
FOUR TALKS, IT REALLY GIVES
YOU LIKE A LOT OF HOPE AND
ENERGY BECAUSE JUST THE
TECHNIQUES DESCRIBED IN
THESE FOUR TALKS COMPARED TO
WHAT WE WERE TALKING ABOUT
IN 2017, YOU CAN ALREADY SEE
THE ADVANCEMENTS MADE AND
REALLY LOOKING FORWARD TO
SEEING THE ADVANCEMENTS
WE'RE GOING TO MAKE AFTER
THIS PARTICULAR SUMMIT AS
WELL.
BEFORE WE START THE
DISCUSSION, ONE THING THAT I
CAN WE CAN APPRECIATE AND
WHAT THE AUDIENCE BEGINS TO
THINK, A LOT OF TIMES WE
THINK COGNITIVE AGING AND
THINK BRAIN BUT WE HAVE TO
REMEMBER IT IS REALLY AN
AGING PROCESS THAT HAPPENS
THROUGHOUT YOUR ENTIRE BODY.
I THINK WE NEED TO START
THINKING OF BRAIN HEALTH AS
BODY HEALTH AND I THINK THEY
ARE VERY INTIMATELY LINKED.
I DON'T THINK WE WILL BE
ABLE TO DISASSOCIATE THEM
AND ALL THE INFORMATION
SHARED BY THE SPEAKERS IS
LINKED TO THE BODY AND BRAIN
AND UNDERSTANDING THE BRAIN
WITHOUT A FOCUSES ON IT.
SO THAT IS ONE TAKEAWAY ON
THAT.
I CAN OPEN IT A FEW MINUTES
FOR QUESTIONS AND THEN MOVE
ON TO THE DISCUSSION TOPICS.
>> OKAY, PHENOMENAL TALK.
JUST BLOWN AWAY, THANK YOU
SO MUCH.
THIS IS MY FIRST TIME AND I
WILL DEFINITELY BE BACK AT
ROMAN NEW ENGLAND JOURNAL OF
MEDICINE 5 SUMMIT.
SO THE LAST FEW TALKS MADE
ME REALLY THINK ABOUT
UNDERSTANDING WOMEN'S BRAINS
AND THERE'S ABOUT 18 MILLION
PEOPLE IN THE U.S. WHO HAVE
ER POSITIVE BREAST CANCER
AND THEY ARE GIVEN TAMOXIFEN
OR OTHER INHIBITORS.
ARE THERE A LOT OF STUDIES
THAT HAVE LOOKED AT THEM IN
TERMS OF SEEING WHAT HAPPENS
AND THEN ALSO, I MEAN, I
GUESS THEY CAN'T BENEFIT
FROM THIS PHYTO BECAUSE YOU
ARE TRYING TO PURPOSELY
REDUCE IT, AND IT IS NOT A
GRADUAL, IT IS LIKE
IMMEDIATE, BEFORE.
SO HOW CAN WE HELP THOSE
18 MILLION WOMEN?
>> THANK YOU, AND GREAT
QUESTION.
SO ON THE FIRST QUESTION
AROUND WHAT BASICALLY ARE
BREAST CANCER THERAPIES
IMPACTING AND THIS IS WORK
CHRISTINE YAUFIN HAS ALSO
CONTRIBUTED TO THIS WORK.
WE HAVE FOUND THAT WOMEN ON
TAMOXIFEN AND AROMATASE
INHIBITORS WHICH WAS NEWS TO
ME HAVE BEEN EFFICIENT IN
REDUCING THESE DISEASES,
BREAST CANCER IN PARTICULAR.
THE TAMOXIFEN DOES PASS
THROUGH THE BLOOD BRAIN
BARRIER TO DO ITS WORK.
WHAT WE FIND IS THE
SELECTIVE ESTROGEN
MODULATORS AND AROMATASE
INHIBITORS SOLICIT RESPONSES
IN OUR CULTURES AND ANIMAL
MODELS SO THEY HAVE ABOUT --
HORMONE THERAPY REDUCES RISK
ANYWHERE FROM 50 TO
60 PERCENT FOR RISK OF
ALZHEIMER'S AND THE
SELECTIVE ESTROGEN RECEPTIVE
MODULATORS ARE ABOUT HALF
THAT EFFECTIVE.
AND WE HAVE PUBLISHED A
NUMBER OF PAPERS SHOWING
THESE ESTROGEN RECEPTION
MODULATORS ARE ACTIVATING
ESTROGEN RESPONSES IN BRAIN.
NOW, CAN WOMEN WHO ARE --
HAVE A RISK FOR BREAST
CANCER USE PHYTOSERM AS AN
ALTERNATIVE?
I DON'T KNOW, Dr. HODES,
BUT WE COULD DO THAT
CLINICAL TRIAL.
[LAUGHTER]
SO WE DON'T KNOW THAT YET
BUT IT IS A VERY IMPORTANT
QUESTION AND ISSUE.
>> THANK YOU.
>> VERY INFORMATIVE TALK
AND -- [INAUDIBLE].
THE PAGE FROM GLUCOSE
METABOLIC REPROGRAMMING, IS
IT THIS TISSUE THAT SUPPLIES
THE BRAIN AND THE BODY,
THERE IS A LOT OF DATA THERE
ON-- [INAUDIBLE] YOUR
THOUGHTS ON THAT.
>> SO ANOTHER GREAT EXAMPLE
FOR A CLINICAL TRIAL.
THE-- YOU KNOW, MY CONCERN
IS THIS, IS THAT IF THE
BRAIN IS UTILIZING ITS OWN
WHITE MATTER FOR FUEL,
RIGHT, IT HAS AN ABUNDANT
SOURCE OF KETONE BODIES SO
FEEDING IT MORE KETONE
BODIES MAY OR MAY NOT BE
EFFECTIVE FROM THE
PERIPHERY.
SO THE CHALLENGE I THINK
ABOUT, AND COMING BACK TO
THAT TRANSITION, I FIGURE
HOW CAN WE MARCH THE BRAIN
BACKWARDS, RIGHT?
SO WE'RE NOT GOING TO BE
ABLE TO TAKE, A,
INTERVENTION, AND TAKE US
ALL THE WAY BACK TO, YOU
KNOW, BRAIN HEALTH.
I THINK WE'RE GOING TO HAVE
PRECISION THERAPEUTICS THAT
TARGET WHAT TRANSITION STAGE
YOU ARE IN.
NOW, PART OF THE ALZHEIMER'S
PHASE IS YOU KNOW THE
RESTRICTION IS HAZARDOUS IN
THAT GROUP BECAUSE THERE ARE
MANY -- MANY PEOPLE ARE
ALREADY QUITE THIN AND
LOSING WEIGHT.
SO IT IS A VERY GOOD
QUESTION ABOUT HOW WE CAN
CHANGE THE TRAJECTORY
THROUGH NUTRITIONAL
INTERVENTION AND I THINK
THAT IS A KEY QUESTION THAT
REMAINS TO BE ANSWERED.
>> MY THOUGHT IS IF YOU
THINK OF IT FROM THE
OPPOSITE THAT LOOKS AT THE
NORMAL BRAIN AND --
[INAUDIBLE].
>> WELL, AND YOU MAKE A VERY
GOOD POINT BECAUSE I SAW IN
AN EARLIER SLIDE DURING AN
INTRODUCTION, YOU KNOW, WHAT
ABOUT THE 87 PERCENT OF
PEOPLE WHO DON'T DEVELOP
ALZHEIMER'S DISEASE, RIGHT?
AND HOW DO YOU SUSTAIN THAT
BRAIN HEALTH?
I THINK THAT IS A REALLY
IMPORTANT POINT.
AND I KNOW THAT IN THE
PRECISION AGING NETWORK LED
BY CAROL BARNES THAT I HAVE
THE PRIVILEGE TO MAKE A
MINOR CONTRIBUTION TO, IS
REALLY LOOKING INTO THOSE
QUESTIONS.
>> THANK YOU VERY MUCH AND
THEN THE OTHER QUESTION I
HAD IS THAT --
[INDISCERNIBLE]
IS THERE ANY DATA ON HOW TO
PUT IT BACK TO PF4 AND IS
THERE A TARGET --
[INAUDIBLE]
>> YEAH, I AM NOT SURE IF
THERE IS LITERATURE ON THAT
SPECIFICALLY.
BUT THAT IS A GREAT POINT.
THERE IS A LOT OF
ANTIPLATELET REGENERATION
AND WE KNOW THAT PF4 IS THE
MAJOR FACTOR THROUGH WHICH
WOMEN GET NEUROGENERATED BUT
NOT SURE IF PEOPLE LOOKED AT
THE PF4 LEVELS IN THE
POPULATIONS OF PEOPLE BEING
TREATED FOR DISEASE BUT
YEAH, THAT IS A VERY
IMPORTANT POINT.
>> QUESTION AND ANSWER?
>> KELLY FROM UNIVERSITY OF
MARYLAND SCHOOL OF MEDICINE
DOWN THE ROAD.
I WAS KIND OF PIGGY-BACKING
OFF THE FIRST QUESTION OF
THE LAST INDIVIDUAL BUT
THINKING IT HAVE MORE IN THE
CONTEXT OF THAT INCREASED
RISK IN THE METABOLICALLY
CHALLENGED GROUPS, THOSE
WITH METABOLIC SYNDROME OR
DIABETES AND THAT INTERPLAY
WITH KETONES BECAUSE MANY
ARE PUT ON A KETONE DIET FOR
THE DIABETES AND IT IS SUPER
HELPFUL, YOU KNOW, THE A1C
GOES DOWN, THEY HAVE MORE
ENERGY, SOME COMPLAIN OF
BRAIN FOG BUT SOME SAY THEY
HAVE SUPER SHARP
FUNCTIONING.
SO BEYOND THE OCCASIONAL
FASTING VERSUS THE STRAIGHT
KETONE DIET, HAVE YOU
THOUGHT ABOUT HOW THAT
INTERPLAYS?
>> I HAVE NOT AND AGAIN IT
COMES BACK TO TRANSITION
STATE BIOLOGY.
SO WHAT YOU ARE DESCRIBING
ARE AT LEAST TWO DIFFERENT
GROUPS OF PEOPLE -- ONE WHO
HAVE NOT MADE THAT
TRANSITION AND THE OTHER WHO
MAY IN FACT HAVE MADE A
TRANSITION AND I THINK THIS
COMES BACK AGAIN TO THE
PRECISION AGING STRATEGY OF
HOW DO WE ACTUALLY DESIGN
AND EXECUTE INTERVENTIONS
THAT ARE, YOU KNOW, PRECISE
FOR THIS AGING POPULATION?
WHERE ARE YOU AND HOW CAN WE
PREVENT ADVANCING OR MARCH
BACK TO THIS BRAIN HEALTH
AND METABOLIC HEALTH.
SO I THINK THERE IS A LOT OF
WORK TO BE DONE.
THANK YOU.
>> FROM STANFORD, I AM
DELIGHTED AND INRATED WITH
THIS PANEL AND OF COURSE I
HAVE TO COMPLIMENT ALL OF
YOU ON FANTASTIC
PRESENTATIONS BUT I HAVE A
SPECIFIC QUESTION BUT OF
COURSE I CAN TAKE TIME AND
BE THROWN OUT OF THIS WITH A
NUMBER OF QUESTIONS I HAVE
BUT HOW DO YOU THINK OR
ENVISION THE FUTURE STUDIES
IN BRAIN CONNECTIVITY IN
PREGNANCY, RIGHT, THE 28-DAY
CYCLE AND THROUGH TO
PREGNANCY WHICH YOU CONTROL
AND SUPPORT BUT THE QUESTION
OF THE BMI, WEIGHT GAIN IN
PREGNANCY, METABOLISM
ASSOCIATED WITH PREGNANCY,
WOMEN WHO ARE DEPRIVED OF
PREGNANCY, OBESE, ET CETERA,
ET CETERA.
THERE WAS JUST A PUBLISHED
FANTASTIC STRUCTURAL PAPER
ON THE BRAIN WITH OBESITY.
THE BRAIN STRUCTURE CHANGES
WITH OBESITY AND THERE ARE
SOME COMPOUNDS RESPONSIBLE.
WE FOUND THE LECTINS IN THE
MET A BOLIC FUNCTION, THE
HYPO THALAMUS AS OPPOSED TO
THE HIPPO CAMPUS HAS
PROFOUND IMPACT ON --
[OVERLAPPING SPEAKERS]
>> VERY GOOD.
I THINK THIS FIELD OF
MATERNAL OR PARENTAL BRAIN
ARE JUST GETTING STARTED.
THERE ARE 1001 QUESTIONS
THAT HAVE TO BE ADDRESSED.
I DON'T THINK THIS IS
EXPLAINED BY WEIGHT AND I
SAY THAT BECAUSE THESE
CHANGES DON'T GO AWAY AFTER
PREGNANCY WHEN RATE
REDUCTION COMES BACK DOWN.
THESE ARE MORE OR LESS
PERMANENT ETCHINGS IN THE
GRAIN BOTH WITH THE GRAY
HEART AND WHITE MATTER.
I THINK THIS EXTENDED
NEUROPLASTICITY IS HAPPENING
TO SUPPORT BEHAVIORAL
ADAPTATIONS THAT WE KNOW.
IN PREGNANTCY, WE HAVE
BEAUTIFUL PAPERS BY
COLLEAGUES LOOKING AT THE
STEROID ABILITY TO FINE TUNE
THE RESPONSE PROPERTIES IN
THE MEDIAN AREA OF THE HYPO
THALAMUS AND WITH THAT, THE
BRAIN OF THE MOM GAINED AN
INCREASE IN SENSITIVITY TO
BEING ABLE TO PICK UP
GLOBALZATIONS FROM THE RAT
PUP AND TO SMELL THEM WITH
HIGHER INTENSITY.
I WILL SAY WITH THE HUMAN
IMAGING WORK WE ARE DOING, I
WOULD LOVE TO SEE MORE
SUPPORT WITH THAT SCAN
TELLING US MECHANISTICALLY
WHAT IS GOING ON.
WE KNOW WOMEN RETAIN MORE
WATER, AND THIS PAPER IS
REALLY COMING OUT TO PROVE
THE CONS TO SAY GUYS, WE CAN
DO THIS.
AND IN FACT WE SCAN PREGNANT
WOMEN ALL THE TIME, WE HAVE
BEAUTIFUL MAPS OF THE FETAL
BRAIN GOING BACK TO 20 WEEKS
OF GESTATION, WHY DIDN'T
ANYBODY THINKING TO MOVE THE
BOARD DOWN AND LOOK AT THE
MATERNAL BRAIN?
SO THIS COMES ON THE HEELS
OF A MUCH LARGER MATERNAL
BRAIN PAPER LAUNCHED AT
UC-SANTA BARBARA AND IRVINE
WHERE WE ARE TRACKING LARGE
NUMBERS OF WOMEN OVER TIME
AND THAT INCLUDES LOOKING AT
PERFUSION AND A WHOLE BUNCH
OF OTHER METRICS.
GREAT QUESTIONS, WE'RE JUST
DIGGING INTO THIS.
I THINK THERE WILL BE A
REALLY COOL STORY ABOUT
IMMUNE CHANGES THAT HAPPEN
DURING PREGNANCY AND THAT
THERE IS THIS NEUROIMMUNE
DANCE BECAUSE THE MOTHER HAS
TO TOLERATE THE FETUS AND
THERE ARE ALL SORTS OF
MACHINATIONS THAT MAKE THAT
HAPPEN.
>> OBESITY CHANGES THE BRAIN
CONDITION AND ESTROGEN LEVEL
ITSELF.
THERE IS NO OVULATION IN
OBESE WOMEN PER SE SO THERE
IS A LOT OF GREAT THINGS TO
THINK THROUGH THOSE.
>> HI, THE QUESTION RELATED
TO METABOLIC SHIFT TO
KETONE, USUALLY ARE HUMAN
IMAGING, THE FUNCTION IS
IMMUNE SYSTEM SO SHOULD WE
MODIFY THAT AND LOOK AT
OTHER THINGS LIKE BLOOD
FLOW?
>> YES, THAT IS A GOOD
QUESTION AND WE ARE DOING
MR S IMAGING TO ADDRESS SOME
OF THESE METABOLIC
CONDITIONS BUT YEAH, THE
MORE IMAGING, THE BETTER,
JUST TO LET YOU KNOW.
SO YEAH, I THINK THERE IS A
LOT OF OPPORTUNITIES HERE
AND I THINK ONE OF THESE
THAT HAS ALREADY BEEN
BROUGHT UP IN SEVERAL
INSTANCES, I KNOW FROM
ANDREW'S WORK AND TARA'S
WORK AS WELL AS EMILY'S AND
MINE IS THE DYNAMIC NATURE
OF THE BRAIN AND TO WHAT
EXTENT CAN WE BREAK THIS
DIVIDE FROM KIND OF
MECHANISTIC DISCOVERY
SCIENCE TO THE HUMAN BRAIN
AND ASKING EXACTLY THE KINDS
OF QUESTIONS THAT YOU ARE,
HOW CAN WE PROTECT THIS IN
THE HUMAN BRAIN AND IN WHOM
AND WHEN DO WE PROTECT THIS?
SO I THINK THE BENEFIT, I
THINK THE REAL ADVANTAGE
THAT WE HAD IN OUR BRAIN
IMAGING IS THE FACT WE HAVE
A COLLABORATOR WHO MATCHED
THEIR KIND OF IMAGING
PROTOCOL TO OUR TRANSITION
STATE BIOLOGY.
AND I THINK THAT'S GOING TO
BE REALLY, REALLY CRITICAL.
SO HOPEFULLY YOU WILL JUMP
INTO THE FRAY HERE.
>> SO THANK YOU ALL FOR
REALLY THOUGHT PROVOKING
TALKS.
I HAVE A QUESTION FOR Dr.
JACOBS.
SO LOTS OF SPINNING OF CART
COGRAY MATTER AND DENDRITIC
SPINES ARE ALSO PROMINENT
RECURRENT FINDINGS IN
NEUROPSYCHIATRIC DISORDERS,
LIKE DEPRESSION BUT AT LEAST
AS I AM AWARE NO ONE LOOKS
AT THEM WITH THE HIGH
TEMPORAL VIEW.
SO I THINK WHAT YOU
PRESENTED IS KIND OF AN
ASTONISHINGLY DIFFERENT
PICTURE OF PROCESSES THAT
ARE ACTUALLY FLUCTUATING IN
BOTH DIRECTIONS AT HIGH
TEMPORAL FREQUENCY AND
PROBABLY RESPONSES TO TREUF
AL EVENTS AND IT IS ACTUALLY
A REALLY DIFFERENT PICTURE
OF HOW WE LOOK AT THAT IMAGE
IN A DIFFERENT FIELD AND
WONDERING IF YOU COULD
EXTEND THAT.
WHEN WE TALK ABOUT THESE
THINGS IN TERMS OF
PSYCHIATRIC DISORDERS, IT
PRESENTS THIS --
[INDISCERNIBLE]
-- HIGH FREQUENCY.
>> THANK YOU THAT IS A GREAT
QUESTION AND WHAT THIS CAN
TELL US, THE BRAIN IS A
HIGHLY DYNAMIC ORGAN AND THE
BRAIN ENDOCRINE ORGAN IS
RESPONSIVE TO THE EBBS AND
FLOWS.
AND I HOPE SOME OF THE
PRINCIPLES WE CAN TAKE AWAY
IS HORMONES DRIVE THESE
CHANGES AND IF WE CAN
UNDERSTAND THAT AND BOTTLE
IT UP, IT COULD GIVE US
INTERESTING IDEAS ABOUT
REGENERATIVE MEDICINE AND
HOW TO USE THESE EXTENDED
NEUROPLASTICITY WE SEE IN
THE MATERNAL BRAIN, CAN WE
PROVIDE TO IN OTHER
CONDITIONS WHERE WE NEED
THAT NEUROPLASTICITY.
AND THAT IS WHY I SORT OF
BEGAN IN THE FIRST THREE
MINUTES THAT THERE ARE SO
MANY CONDITIONS THAT HAVE
NOT BEEN ADDRESSED IN LARGE
PART BECAUSE WOMEN'S HEALTH
HAS BEEN IGNORED FOR SO
LONG.
THERE ARE THESE PULSES IN
THE BRAIN THAT ARE ADAPTIVE
AND WE NEED SO MUCH MORE
WORK TO UNDERSTAND THE
CONNECTIVITY OF IT.
>> HI, CAROL BARNES,
UNIVERSITY OF ARIZONA.
I AM WONDERING IF TARA AND
ROBERTA, THE NEUROGENESIS,
YOUR MINDS WERE 20 MONTHS OF
AGE BUT NEUROPRO PLASTOSIS
IS AT 15 MONTHS OF AGE AND
IT STRUCK ME, IS THIS A
TRANSITION AS ROBERTA WAS
TALKING ABOUT AND HOW MANY
THINGS ARE CHANGING
INCLUDING NEUROGENESIS?
>> YES, IN THE 20 MONTH OLD
MICE WHICH ARE RELATIVE TO
THE 25-YEAR-OLD IN HUMANS,
THE NEUROGENESIS IN MICE WAS
QUITE HIGH AND TKR-PD
QUICKLY AT THREE AND FOUR
MONTHS WHERE THE
NEUROGENESIS LEVELS ARE
ALREADY DECLINING.
AND THERE HAS BEEN EVIDENCE
COMING OUT LAST FEW MONTHS
IN HUMANS SO HING SO HE --
SHOWING THE DECREASE IN
NEUROGENERATIVE DISEASE.
SO IT MIGHT BE THE VERY LAST
TRANSITION STAGE BUT MORE
THE ENDPOINT STAGE.
IF YOU WANT TO LOOK AT THE
ENDOCRINE STAGE, I SUGGEST
WE LOOK AT MICE YOUNGER THAN
20 MONTHS.
>> WELL, TO DOVETAIL THAT,
IT MAKES ME THINK OF OUR
EARLIER WORK WHERE WE USE A
MOUSE MODEL OF ALZHEIMER'S
DISEASE WHERE WE ALWAYS HAD
A NORMAL AGE MATCHED CONTROL
MOUSE IN ADDITION TO THE
CONTROL MOUSE.
AND ASTOUNDINGLY FOR
NEUROGENESIS, WE NEVER SAW
FOR THE IMPACT OF THE
THERAPEUTIC FOR ALZHEIMER'S
DISEASE AND IN NORMAL MICE,
WE NEVER SAW NEUROGENESIS
BEING ACTIVATED BY ADOE
ALOE TILL THEY WERE 15
MONTHS OF AGE.
AND WE KNOW IN THOSE MICE,
THERE WAS NO NEUROGENESIS,
HAD ALL THE MARKERS FOR
THAT, SO IT REALLY I THINK
SPEAKS TO THE REGENERATIVE
POTENTIAL OF THE AGING
BRAIN.
NOW, IN THE DATA FROM OUR
PHASE 1B2A CLINICAL TRIAL IN
PERSONS, 60 YEARS AND OLDER,
WE FOUND A SET OF
RESPONDERS.
IT WAS A DOUBLE BLIND
CONTROLLED PHASE 1A2B
CLINICAL TRIAL, SMALL
NUMBERS BUT WE FOUND THERE
WERE INDIVIDUALS WHO HAD
GAINED SMALL, AND JUST OVER
THREE MONTHS FROM TREATMENT,
HAD GAINED HIPPO CAMPAL
VOLUME IN THIS AGING
POPULATION AND THEY WERE PF4
CARRIERS.
SO THOSE WERE THE RESPONDER
SET AND NOW WE'RE IN A STAGE
2B CLINICAL TRIAL WITH THE
CARRIERS ALL OF WHOM ARE 65
AND OLDER.
BUT IN THE NORMAL MOUSE, I
WAS SO THRILLED BECAUSE
THERE WAS THIS LITTLE BLIP
THAT THE OLDER MICE WERE
SHOWING AND WHAT IT SHOWS IS
THAT IT DOESN'T GIVE YOU
MORE IF YOU ARE GOOD, IT THE
ONLY IF YOU HAVE A DEFICIT
IN NEUROGENESIS.
SO THE AGING MICE ARE
BEGINNING TO SHOW THE
DEFICIT BUT THERE IS HOPE.
>> WE SEE THE NEUROGENESIS
IN YOUNGER MICE BUT IT IS
ONLY IN THE OLDER MICE
RECEIVING TREATMENT WHERE
THERE IS AN OBVIOUS DEFICIT,
RIGHT?
IN THE FIRST TEST THAT WAS
USED, THEY WENT TO TESTING
AT EARLY MONTHS OF AGE --
[INAUDIBLE].
>> CAN I JUST SAY SOMETHING?
MY COLLEAGUE JENN BYDAN DID
A STUDY OF NEUROGENUINE
NEUROGENESIS AND FACIAL
COGNITION AND IT WAS DONE
QUITE A LONG TIME AGO BUT
THE OLDER ANIMALS WITH WORSE
NEUROBETWEEN SIS WERE THE
ANIMALS BETTER IN FACIAL
COGNITION SO I AM WONDERING
ABOUT THE LINEARITY BETWEEN
NEUROGENESIS AND FACIAL
RECOGNITION.
>> YES, WE GENERALLY FIND
THE MICE WITH LOWER LEVELS
OF NEUROGENESIS HAVE WORST
FACIAL RECOGNITION.
>> SO I WOULD JUST SAY CAROL
IF THE RATS KNEW THAT CAROL
BARNES WAS WATCHING, THEY
WOULD DO WELL, JUST SAYING.
[LAUGHTER]
>> YES, TIM FROM BROWN
UNIVERSITY AND I LOVE THE
TALKS.
THIS IS A QUESTION FOR
ANDREW YANG SINCE NOBODY
ASKED YOU A QUESTION YET.
I LOVED ALL YOU GUYS' TALKS
AND WE KNOW THE BDP SHIELD
EXTENDS WITH SMALL MONITORS
THAT ARE ALMOST 100 PERCENT
GOING FROM THE BLOOD TO THE
BRAIN AND THESE FANTASTIC
PROTEINS CROSSING THE BBB, I
AM JUST WONDERING IF YOU
HAVE LEARNED THE UNDERLYING
MECHANISM THROUGH WHICH
THOSE PROTEINS ARE INJECTED
IN THE BRAIN SO WE CAN USE
THOSE PROTEINS TO ENABLE THE
BLOOD TO REACH INTO THE
BRAIN?
>> THANK YOU.
IT IS ON, RIGHT?
YEAH, THAT IS A FANTASTIC
QUESTION.
BACK TO THE ANALOGY OF THE
BLOOD BRAIN BARRIER ON
PARTICULAR HOMES OF THE
BRAIN, RIGHT NOW IDENTIFYING
THE BLOOD PROTEINS WITHOUT
THE FUNCTION ITSELF, IT IS
RUNNING INTO A WALL.
BUT IF YOU CAN IDENTIFY THE
PROCESSES, YOU WILL HAVE
BETTER SUCCESS AND AT LEAST
FOR BIOLOGICS.
WE'RE STARTING TO SEE THAT
IN THE INDUSTRY, WHERE THEY
ARE LEVERAGING THIS THIS
TRANSSEPTEMBER TORE
PATHWAY -- TRANSCEPTOR
PATHWAY.
EVERYONE WILL USE THIS IN
DELIVERING MACRO MODELS BUT
THERE ARE EXPAND ABILITIES
WITHIN ONE TARGET.
DIFFERENT TARGET FOR
DIFFERENT DISEASES BECAUSE
WE KNOW FOR EXAMPLE, THE
EXPRESSION OF CREATIVITY
DECREASES WITH NORMAL AGING
AND THIS IS JUST ONE EXAMPLE
SO I HOPE ON TOP OF THAT WE
HAVE THE ABILITY TO NOT JUST
GET MORE CELLS IN THE BRAIN
BUT BECAUSE WE HAVE ALL THIS
BRAIN VASCULATURE AND TUNNEL
SETS, YOU CAN HAVE BRAIN
THERAPY THAT WILL ENTER THE
BRAIN AND THEN HONE THE MIKE
CREEGLIA FOR DIFFERENT
DISEASES.
>> WE HAVE A COUPLE MORE
QUESTIONS AND THEN I WOULD
LIKE TO LEAVE A FEW MINUTES
TO LET ME HAVE A LITTLE FUN
WITH SOME OF THE QUESTIONS.
>> THE DATA YOU SHOW ON
MYELIN METABOLISM AND
MICROGLIAL INTERACTIONS, I
WAS WONDERING DO WE CONSIDER
THAT AS THE MAIN DRIVER OF
INFLAMMATION IN AGING BRAINS
AND THAT MAYBE THERE IS LIKE
SOME SORT OF AUTOIMMUNE
RESPONSE TO MYELIN AGING OR
ARE THERE OTHER DRIVERS WE
THINK ARE IMPORTANT FOR
INFLAMMATION IN BRAIN AND
AGING?
I MEAN, WE KNOW THERE IS
CLEARLY INFLAMMATION AND
MYOCES.
>> YES, GREAT QUESTION AND
THANK YOU.
SO I GOT DRAGGED, KICKING
AND SCREAMING, INTO THE
IMMUNE SYSTEM BUT THAT IS
WHERE THE BRAIN WAS TAKING
ME.
AND TO YOUR POINT, ONE OF
THE THINGS THAT WE ARE ABOUT
TO SUBMIT FOR REVIEW IS
ASKING THE QUESTION, CAN WE
CHANGE THE TRAJECTORY OF
THIS BRAIN AGING BY
TARGETING THE INNATE IMMUNE
SYSTEM BECAUSE THAT IS THE
FIRST SYSTEM THAT IS
ACTUALLY ACTIVATED.
IT IS ACTIVATED BEFORE
METABOLICALLY PROGRAMMING.
SO THE INNATE IMMUNE SYSTEM,
YOU DON'T EVEN KNOW IT IS
HAPPENING AND THEN IT IS
ACTIVATED.
SO WE ASK THE QUESTION CAN
WE ACTUALLY TARGET THE
IMMUNE SYSTEM AND CHANGE
TRAJECTORY OF THAT AGING
PROFILE DURING PERI AND
MENOPAUSAL BRAIN?
AND THE ANSWER IS YES.
IT TAKES COMBINATION
THERAPY, MULTIPLES, BUT IT
IS QUITE EFFECTIVE.
SO I THINK THERE IS THE
POTENTIAL FOR ACTUALLY
CHANGING THE TRAJECTORY OF
AGING WITH EARLY
INTERVENTION IN THIS
TRANSITION STATE AND THEN,
YOU KNOW, THE QUESTION I
THINK ALSO THAT YOU ARE
ASKING HOW CAN WE BRING THAT
BACK AND WHAT WE SEE IS THAT
THERE'S ACTIVATION OF THE
INNATE IMMUNE SYSTEM AND
THEN ACTIVATION OF THE
ADAPTIVE IMMUNE SYSTEM.
SO IT REALLY DEPENDS ON
WHICH END OF THE SPECTRUM
YOU ARE AT.
BECAUSE WHEN WE LOOK AT THAT
LATER STAGE WHERE THERE IS
MYELIN METABOLISM AND THE
GENERATION OF THIS
AUTOIMMUNE, I THINK WE'RE
GOING TO NEED THERAPEUTICS
THAT TARGET OUR IMMUNE
SYSTEM AND IT IS KIND OF NO
ACCIDENT THAT OVER
990 PERCENT OF PEOPLE WHO
DEVELOP MULTIPLE SCLEROSIS
OVER THE AGE OF 50 ARE
WOMEN, RIGHT?
SO I THINK IT IS A GREAT
OPPORTUNITY FOR US TO REALLY
THINK MORE DEEPLY AROUND
THAT IMMUNE SYSTEM.
>> JUST IN THE INTEREST OF
TIME AND BECAUSE I REALLY DO
WANT TO HAVE FUN WITH A FEW
QUESTIONS, I AM GOING TO
START THE DISCUSSION BUT WE
HAVE A 20 MINUTE BREAK AFTER
THIS SO PLEASE COME UP TO
THE STAGE AND GRAB THEM AND
ASK THEM YOUR PRESSING
QUESTIONS.
I HAVE A FEW OF MY OWN AS
WELL.
SO THIS ONE I WILL RANDOMLY
PICK ON YOU ALL AND
PIGGY-BACK ON THE QUESTION
REGARDING THE IMMUNE SYSTEM,
TALKING ABOUT PERIPHERY IN
THE BRAIN AND NO WAY WE CAN
TALK ABOUT THAT WITHOUT
TALKING ABOUT THE IMMUNE
SYSTEM AND THESE FACTORS AND
WE HAVE TRANSITION STATES
WITH DIFFERENT TRAJECTORIES.
SO MANY TIMES WE THINK ABOUT
THIS BEING EXTRA-MENTAL BUT
HOW DO YOU ADAPT THAT IN THE
FIRST PLACE WHERE YOU THINK
IT SORT OF LIES AS A DRIVER
OF AGING VERSUS THE
RESILIENCE AND DELAYED
AGING.
SO I WILL START WITH YOU
TARA.
>> YES, THAT IS A REALLY
GOOD QUESTION.
BASICALLY UNTIL RELATIVELY
RECENTLY, IT HAS BEEN
THOUGHT OF BEING A
DETRIMENTAL PART OF THE
SYSTEM WITH AGING AND
NEUROGENESIS PLATELET
DYSFUNCTION.
SO IT IS VERY RECENTLY
PLATELETS HAVE BEEN SHOWN TO
HAVE ALL THESE OTHER
FUNCTIONS PARTICULARLY
RELATED TO THE BRAIN AND
THIS IS WHY WE ARE SO
INTERESTED IN THEM, IS
BECAUSE THEY DO SEEM TO
CONTAIN MANY, MANY
BENEFICIAL PROTEINS,
EFFECTANTS THAT ARE KNOWN TO
REJUVENATE IN THE BRAIN AND
WE HAVE SEEN A NUMBER OF
STUDIES IN THE LAST FEW
YEARS SHOWING PLATELETS,
GLYSATES AND NEUROGENERATION
THERAPIES, SO I THINK THIS
IS A TOPIC THAT HAS COME UP
RECENTLY IN THE LAST FEW
YEARS AND ONE THAT WE HOPE
TO BRING TO FRUITION --
[INAUDIBLE].
>> I THINK THAT IS A
FANTASTIC QUESTION
PARTICULARLY WITH BRAIN
BARRIERS AND WE'RE BEGINNING
TO UNDERSTAND IT PERMITS OR
CAN EVEN HOUSE THE
AUTOIMMUNE CELLS WITH THE
IMMUNE CELLS, RIGHT?
ONE BEAUTIFUL EMBODIMENT
THAT CAN SHAPE THE BRAIN AT
A DISTANCE, RIGHT?
I THINK WE'RE UNDERSTANDING
THAT THEY DON'T NECESSARILY
BEGIN THAT BUT THE NEURON
EXPRESS ALL THE FLAVORS OF
THE RECEPTORS AND CAN SHAPE
DISEASE BUT MOST
INTERESTINGLY, CAN SHAPE
DIFFERENT TRAJECTORIES IN
THE NORMAL RANGE, I THINK IN
MIDLIFE.
AND WHAT WAS THOUGHT ABOUT
EARLIER ON HOW AUTOIMMUNE
DISEASE AND ITS EFFECTS ON
OUR LIFESTYLE, I THINK WE
WILL REALIZE HAS A PROFOUND
HEALTH ON THE BRAIN BARRIER.
>> I AM GOING TO TOSS TO THE
IMMUNE FOLLOW
IMIMMUNOLOGIST BUT I THINK
THE WAY TO LOOK AT THIS IS
THAT THE SYSTEM IS CHANGING
IN A REALLY VAST WAY.
>> AND I WANT TO COME BACK
TO ANDREW'S POINT AROUND THE
BLOOD BRAIN BARRIER.
IT IS VERY INTERESTING.
WHAT WE FOUND IS THAT WHEN
THE BRAIN IS UNDER METABOLIC
STRESS, THE BLOOD BRAIN
BARRIER IS MUCH MORE
ENGAGABLE.
SO THERE IS THIS CROSS TALK
BETWEEN THE BRAIN SAYING I
AM STARVING AND THE
PERIPHERAL SYSTEM, METABOLIC
SYSTEM AND POTENTIALLY THE
IMMUNE SYSTEM.
AND THEN ONCE THAT SHIFT HAS
HAPPENED, ONCE THINGS HAVE
BEEN REORGANIZED, THERE IS
NOT NO COMMUNICATION BUT IT
WAS REALLY DRIVEN BY THE
METABOLIC STRESS AND THEN IT
WAS LIKE I AM DONE UP HERE,
YOU ARE GOOD, RIGHT?
SO THERE IS THIS, YOU KNOW,
LESS COMMUNICATION BETWEEN
THE BRAIN AND THE PERIPHERY
THROUGH THE BLOOD BRAIN
BARRIER.
THE OTHER THING THAT I WOULD
SAY IS, YOU KNOW, THIS
DYNAMICISM OF THE BRAIN AND
THINKING ABOUT ALZHEIMER'S
DISEASE, WE THINK OF IT AS
THIS, YOU KNOW, YOU START
HERE, END THERE AND IT IS
NOT PRETTY.
BUT WHEN I STEP BACK AND I
LOOK AT THE ALZHEIMER'S
BRAIN, I AM THINKING, MY
GOD, YOU'RE DYNAMIC.
YOU ARE LIVING FOR DECADES
WITH THIS WHAT WE CALL
DISEASE BUT WHEN I STEP BACK
AND LOOK AT THE BRAIN AND
GOING MY GOD, YOU ARE TRYING
SO HARD TO SURVIVE.
YOU ARE TRYING SO HARD TO
SURVIVE AND DOING EVERYTHING
YOU CAN TO SURVIVE FOR
DECADES.
AND SO IT IS REALLY CHANGED
MY PERSPECTIVE, HAVING
STUDIED AGING AND DYNAMICISM
AND LOOKING AT HALZ --
ALZHEIMER'S AND DISEASE
WHERE WE SEE PROGRESSION AND
DECLINE IN BRAIN FUNCTION
BUT BOY, IT IS DOING ITS
BEST TO STAY ALIVE.
>> SO THE LAST COUPLE OF
MINUTES BEFORE THE BREAK, MY
LAST QUESTION IS AROUND
TECHNOLOGY.
IN THE SEVEN YEARS SIN I --
SINCE I HAVE BEEN HERE,
TECHNOLOGY HAS HAD QUITE AN
IMPACT.
WHAT IS THE TYPE OF
TECHNOLOGY OR UNDERSTANDING
WE NEED TO PUSH THESE
QUESTIONS FORWARD AND I WILL
START WITH ANDREW AND GO
TOWN THE LINE.
>> WELL, I THINK IT DOES GO
TO WHAT ROBERTA WAS SAYING
EARLIER ABOUT BRIAN
DYNAMICS.
I THINK THE LAST DECADE, I
HAVE SEEN A REVOLUTION IN
CELL BIOLOGY BECAUSE OF THE
SINGLE CELL CRISPR AND I
THINK TO BE ABLE TO STUDY A
CELL NOT ASSOCIATED WITH
EACH AND THIS SYNAPTIC RANGE
WITH EACH OTHER AS IT
RELATES TO BRAIN HEALTH.
AND IN THE CONTEXT OF OUR
CONVERSATION HERE, IT IS AN
INTERESTING PARALLEL, WHEN
YOU THINK ABOUT THE BRAIN IN
TERMS OF NEURAL ANATOMY, BUT
WE CAN NOW STUDY THINGS THAT
ARE NOT NECESSARILY STABLE
BUT PART OF THE IMMUNE
SYSTEM.
SO THE SPECIFIC NEURONS,
CYTOKINES, I THINK THAT
WOULD BE FASCINATING TO
FIGURE OUT.
>> AND THE LAST ANSWER I
WILL GO TO EMILY.
>> THERE'S SO MANY
TECHNOLOGIES WE COULD BRING
TO BEAR.
YOU KNOW ON THIS QUESTION
ABOUT THE BRAIN IN THE LAB,
OF COURSE.
I THINK SOME OF US ARE SO
TAKEN WITH THE TRANSITIONS
THAT WE FORGET SOMETHING
ELSE ABOUT IT, WHICH IS THAT
IT IS CONNECTED TO THE REST
OF OUR BODY.
IF WE CAN DEVELOP ENDOCRINE
MONITORS, HOW THEY EBB AND
FLOW OVER TIME AND THE
DYNAMICS IN THE BRAIN WOULD
BE REALLY COOL.
WE NEED BETTER LIGANDS TO
DETERMINE WHERE THESE
RECEPTORS ARE IN THE BRAIN.
WE HAVE NOW THESE BEAUTIFUL
GENE EXPRESSION MAPS.
ONE OF THEM FROM A WHOM IS
57 YEARS OLD SO WE JUST NEED
BETTER TECHNOLOGY THAN WE
HAVE TODAY AND TO BE
INCLUSIVE.
ALL OF THESE TECHNOLOGIES WE
HAVE IN THE NEUROSCIENCE
WORLD CAN BE USED TO
LEVERAGE THESE QUESTIONS,
CRISPR BEING ONE OF THEM BUT
THERE ARE MANY OTHERS.
>> AWESOME.
I WANT TO THANK ALL OF THE
SPEAKERS AND ORGANIZERS FOR
THE FIRST SESSION.
AND I THINK WE'RE READY FOR
A BREAK.
>> THIS HAS BEEN WONDERFUL,
ALMOST EXACTLY ON TIME SO WE WILL COME BACK AT 15:55 A.M.
FOR SESSION TWO, SOCIAL AND STRUCTURAL ENVIRONMENT.
SEE YOU THEN.
[APPLAUSE]
>>> OKAY, EVERYONE, WELCOME
BACK FROM THE BREAK, I WANT
TO WELCOME YOU TO SESSION 2.
AND MY NAME IS JENNIFER
MANLY, PROFESSOR IN THE
NEUROLOGY DEPARTMENT AT
COLUMBIA UNIVERSITY.
SO JUST A QUICK INTRODUCTION
TO OUR SESSION, I AM EXCITED
TO HAVE A SESSION DEDICATED
TO TALK ABOUT STRUCTURAL AND
SOCIAL ENVIRONMENT AT THE
COGNITIVE AGING SUMMIT.
OF COURSE CONTEXT IS
CRITICAL FOR ANY APPROACH TO
EXTENDING BRAIN SPAN WHICH
IS WHAT WE'RE FOCUSED ON IN
THIS SUMMIT, THE IMPORTANCE
OF STRUCTURAL AND DESIGN AND
THESE ISSUES ARE IMPORTANT
FOR ALL DIMENSIONS OF THE
ENVIRONMENT THAT WE'RE
TALKING ABOUT TODAY AND
TOMORROW.
AND SHOULD BE INFUSED IN
DISCUSSION OF ALL THE
MECHANISMS WE'RE TALKING
ABOUT AT THIS COGNITIVE
AGING SUMMIT SO WITH THAT I
WILL INTRODUCE THE FIRST
SPEAKER, PARIS AX ADKINS
SHINE JACKSON FROM COLUMBIA
UNIVERSITY.
>> ALL RIGHT, HEY, EVERYONE,
JUST WANTED TO MAKE SURE YOU
WERE READY FOR ME TO SPEAK.
HOW YOU ALL DOING?
OKAY, YOU ALL ARE ASSUMING I
AM WELL VERSED ENOUGH TO
KNOW WHAT TO DO WITH THIS.
IF I CLICK TO THE RIGHT, IS
THAT HOW IT WORKS?
I AM AN UPPER MILLENNIAL SO
YOU CAN'T ASSUME I GREW UP
WITH TECHNOLOGY, DIDN'T SEE
IT IN COLLEGE.
SO AIM -- I AM AJ GOING TO
TALK ABOUT STRUCTURAL
COGNITION TODAY.
WE'RE USED TO SEEING THROUGH
GENERATION WHO ARE
RACE-DISPAIRS IN OUR SO
IS -- DISPARITIES IN OUR
SOCIETY.
IF YOU ARE NOT FAMILIAR, WE
HAVE SOMETHING FROM THE
70s FROM OUR BELOVED
OFFICE OF THE PRESIDENT,
OFFICE OF MANAGEMENT AND
BUDGET THAT CREATED AND
DICTATES THESE RACIALIZED
CATEGORIES WE OFTEN USE IN
THE DISPARITIES RESEARCH
THAT WE HAVE.
NOTICE LARGELY FEW TO AN
EFFORT TO COUNT EQUITY, TO
MAKE SURE THAT THERE IS
ADEQUATE DISTRIBUTION OF
RESOURCES AND SCIENCE FOR
INDIVIDUALS BUT IT IS NOT
MEANT TO IMPLY SOME OF THE
GENETIC FEATURES WE OFTEN
SEE IN SCIENCE.
SO ON THE FIRST PAGE OF THIS
REPORT THAT I FIND
INTERESTING, IT ALWAYS SAYS
THESE GROUPS ARE NOT TO BE
INTERPRETED AS SCIENTIFIC OR
ANTHROPOLOGICAL IN FAVORITE.
HOW MANY OF YOU ACTUALLY
CONSIDER THAT WHEN YOU THINK
OF RACIALIZED DISPARITIES,
THAT WE ARE NOT SUPPOSED TO
INFER THE THINGS WE OFTEN DO
ABOUT THE WORK THAT WE DO,
BUT WE ARE FOR EQUITY
PURPOSES, MAINLY HISTORICAL
PURPOSES, SUPPOSED TO TRACK
THESE DIFFERENCES.
AND SO I LIKE TO ALWAYS
INFORM PEOPLE ON THE HISTORY
OF THESE CATEGORIES BECAUSE
THIS IS THE CONTEXT BY WHICH
THESE CATEGORIES REALLY
MATTER TO US.
THESE CATEGORIES ARE NOT THE
WAY INDIVIDUALS CHARACTERIZE
THEMSELVES BUT THESE ARE
EXTERNAL STHAORSZ SAY ALL OF
YOU GO TOGETHER, AND ALL OF
YOU, YEAH, YOU ALL GO
TOGETHER TOO EVEN THOUGH
THOSE GROUPS FOR HISTORICAL
REASONS WOULD BELIEVE THEY
ARE QUITE DIFFERENT THAN THE
GROUP THEY ARE GROUPED WITH.
SO I WANT TO GIVE YOU
CONTEXT ON A HISTORICAL ERA
THAT GROUP PEOPLE IN THESE
CATEGORIES WE USE.
FOR EXAMPLE, THE
CHARACTERIZATION OF PERSIANS
AND NORTH AFRICANS, NOT
NECESSARILY THEIR OWN
CHARACTERIZATIONS OF
THEMSELVES.
SAME WITH JOHN LOCKE WHOSE
RESEARCH UNDER GIRDERS THE
SITUATION WE HAVE IN THE
U.S. USED COGNITION AS A WAY
TO SEPARATE ALL GROUPS AND
THEN YOU HAVE LINNAEUS AND
BLUMENBACH WHO WERE LARGELY
THE ENGINEERS OF THE
CLASSIFICATION SYSTEM WE
SEE.
SO WHEN YOU THINK OF
RACIALIZED GROUPS, THINK OF
THEM IN THIS HISTORICALINE
CONTEXT THAT WAS CREATED FOR
THEM.
THIS IS WHAT YOU MIGHT REFER
TO AS THE PROCESS OF
RACIALIZATION WHERE YOU LOOK
AT INDIVIDUALS AND YOU GO I
THINK YOU ARE GROUP A, GROUP
B, GROUP C.
WHAT IS NUN SNEAK IN
RACIALIZATION IS IT RANKS
THESE GROUPS.
NOT ONLY DOES IT FORCE YOU
INTO A CATEGORY YOU MAY NOT
THINK BELONGING TO YOUR SELF
BUT WHO GETS ACCESS WHEN IT
COMES TO THESE CATEGORIES
AND THIS IS SOMETHING TO
KEEP IN MIND WITH THE
SCIENCE THAT WE DO.
WE COMPARE GROUPS WITHOUT
HISTORICAL CONTEXT SO WE
HAVE NO WAY OF REALLY
UNDERSTANDING HOW THEY GOT
TO THE OUTCOME THAT WE SEE.
NOW, IF YOU WANT TO SHIFT
THE ENERGY FROM JUST LOOKING
AT THE DIFFERENCES IN THOSE
OUTCOMES, TO LOOKING TO
ACTUAL REASONS WE GOT THERE,
THAT WOULD MEAN TO FOCUS ON
THE EXPOSURES.
THAT MIGHT MEAN TO FOCUS ON
SOCIAL DETERMINANTS OF
HEALTH WHICH ARE SORT OF
ACCESS TO RESOURCES, FOOD,
INCOME, EDUCATION THAT YOU
PREDOMINANTLY SEE IN THE
LITERATURE.
I LIKE TO, WITH MY
COLLEAGUES, REFER TO
STRUCTURAL DETERMINANTS
BECAUSE WE KNOW THERE IS NOT
A POLICY IN OUR RESPECTIVE
PLACES THAT DON'T THEN
DICTATE THAT ACCESS TO
EDUCATION AND INCOME AND
FOOD AND OTHER RESOURCES.
AND BECAUSE OF THAT
RACIALIZATION, IT THEN RANKS
GROUPS IN ACCESS TO FOOD, TO
INCOME, TO EDUCATION, AND I
KNOW MY COLLEAGUE KATRINA
WILL TALK ABOUT THAT IN HER
PRESENTATION.
A LESSER-DISCUSSED PART OF
THIS SORT OF RACIALIZATION
IS THE INTENTION TO DO HARM
TO INDIVIDUALS AND THE
VIOLENCE THAT SOME GROUPS
EXPERIENCE.
I WANT TO HIGHLIGHT THIS
BECAUSE ON THE LEFT WE HAVE
A SITUATION WHERE BECAUSE
THE INDIVIDUAL IS RACIALIZED
THE WAY THEY ARE, THEY ARE
ON THEIR KNEES, YOU CAN SEE
BOTH THEIR HANDS BUT THERE
IS THREE OFFICERS WITH
WEAPONS POINTED AT THEM.
WHEREAS ON THE IMAGE TO THE
RIGHT, THE INDIVIDUALS ARE
ACTIVELY ASSAULTING THE
OFFICERS BUT BECAUSE OF THE
WAY THEY ARE RACIALIZED,
THERE IS NOT A WEAPON
RAISED.
AND SO WITHOUT REALLY
CAPTURING THE DEFICIT THAT
VIOLENCE GIVES TO OUR
BODIES, WE'RE NOT REALLY
GETTING THE FULL PICTURE.
SO ONE OF THESE TYPES OF
VIOLENCES I LIKE TO FOCUS ON
IN MY STUDY OF STRUCTURAL
RACISM IS THE 1994 CRIME
BILL.
THIS WAS A SIGNIFICANT BILL
FOR OUR MOST RECENT TIME AND
I HOPE EVERYBODY IN THE ROOM
HAS BEEN ALIVE SINCE 1994 --
OKAY?
YEAH, WE WERE HERE, GREAT.
BUT WHAT IT DID WAS FUND THE
EXPANSION THROUGHOUT THE
U.S. TO HOUSE, AKA DECREASE
THE CRIME RATE BY INCREASING
THE NUMBER OF INCARCERATED
PEOPLE.
BUT BECAUSE OF THE SCIENCES
LIKE US THAT CREATE THESE
RACE AND DISPARITIES, IT WAS
INFERRED THAT CRIME RATES
WERE HIGHER IN NEIGHBORHOODS
PREDOMINANTLY RACIALIZED
BLACK AND LATIN-X O SO THESE
BECAME THE TARGETS FOR
INCARCERATION.
SO WE WANTED TOY IF THOSE
DISPARITIES OF BLACK IN
PRISON WAS A DISPARITY
ACROSS THE U.S.
SO I HAVE THIS PAPER FROM
GOBAUD AND KIM, I LIKE TO
INCLUDE THE STATICIANS
BECAUSE WITHOUT US, THE
WORLD DON'T TURN.
WE DESERVE AWARDS TOO.
[APPLAUSE]
>> THANK YOU.
[LAUGHTER]
SO STUDYING THE GREATER
INCARCERATION FOR TEN YEARS,
GAVE IT A YEAR FOR
IMPLEMENTATION AND TRACKED
IT FOR TEN YEARS AND
ESTABLISHED THAT NUMBER.
WE THEN LOOKED AT THE
OVERALL COGNITIVE
PERFORMANCE, A BIENNIAL
SURVEY, I AM SURE MANY OF
YOU ARE FAMILIAR WITH IT,
SURE EVERYONE KNOWS ABOUT
THE RETIREMENT STUDY
PARTICULARLY THE COGNITIVE
ASSESSMENT THEY USE BUT FOR
THIS EXAMPLE, PREDOMINANTLY
ADULTS RACIALIZED AS BLACK,
BORN IN THE U.S., BORN IN
THE SOUTH, CIS GENDER WOMEN,
HIGH SCHOOL DIPLOMA,
PARTNERED AND AT AGE 65.
SO THEN WE LINK THAT WITH
OTHER DATA.
SO WE'RE LINKING THIS CODE
WITH THE BASELINE INTERVIEW
WHICH WOULD BE AGE
5 DEPENDING ON WHAT AGE THEY
JOINED THE STUDY BUT WE HAVE
ALSO LINKED THEM AT THEIR
STATE OF BIRTH AND STATE AT
AGE 10.
IS WE SEE A GREATER
INCARCERATION OF PEOPLE
KNOWN AS BLACKS ASSOCIATED
WITH LOWER COGNITIVE
PERFORMANCE AMONG
PARTICIPANTS RACIALIZED AS
BLACK.
WHICH MEANS IF YOU LIVE IN A
COUNTY THAT
DISPROPORTIONATELY INCARS
RATES PEOPLE RACIALIZED AS
BLACKS SHOWING A LOWER
OVERALL COGNITIVE
PERFORMANCE.
AND LIKEWISE, IF YOU ARE
INCAR RATED AND RACIALIZED
AS WHITE, IT GIVES YOU A
HIGHER OVERALL COGNITIVE
PERFORMANCE.
SO MAYBE IT IS ABOUT
SEPARATING TWO GROUPS AND
LOOKING AT THE EXPOSURE ON
THESE GROUPS SEPARATELY IN
DIFFERENT DATASETS.
NOW, I BASE A LOT OF MY
UNDERSTANDING OF AGING AND
COGNITION FROM THIS PAPER
THAT GOT ME INTO AGING A
COUPLE OF YEARS AGO ABOUT
LIFE COURSE FACTORS,
PARTICULARLY IN INDIVIDUALS
RACIALIZED AS BLACK FROM
Dr. MANLEY AND GLYMOUR AND
THEY TALK ABOUT THESE SOBER
FACTORS THAT WOULD LEAD TO
DOWNSTREAM EFFECTS LIKE WE
SEE IN THE FIRST PANEL, HOW
WE CAN CONNECT SO MANY
DIFFERENT STRUCTURES TO WHAT
IS HAPPENING.
THAT PAPER BEAUTIFULLY TALKS
WITH THE LIFE COURSE AND HOW
THESE EXPOSURES ARE
HAPPENING, NOT ONLY IN
CRITICAL PERIODS LIKE THE
CRIME BILL BUT ALSO THROUGH
TRAJECTORY LIKE POVERTY
PEOPLE ARE SET ON, IMMEDIATE
EXPOSURES LIKE AN ENCOUNTER
WITH A RACE CIVIL DOCTOR OR
EVEN ACCUMULATION EFFECTS
LIKE WHAT WE MIGHT SEE IN
POLLUTION.
SO WHILE THE EXPOSURES FOCUS
ON MID-LIFE, I KNOW THEY ARE
ASSOCIATED WITH LOWER
COGNITIVE PERFORMANCE.
AND THIS LAST PICTURE ARE MY
GRANDPARENTS ALSO
EXPERIENCING COGNITIVE
AGING.
AND THESE ARE PEOPLE THAT
COULD BE LYNCHED FROM THE
TIME PERIOD OF MID-1900S
WHERE PEOPLE WHO WERE
RACIALIZED AS BLACKS,
PHILIPPINE FILIPINO,
CANTONESE, AND THEN THE
PEOPLE WHO DID LYNCH WERE
PROTECTED FROM THE CRIMINAL
CONSEQUENCES OF KILLING
PEOPLE AT RANDOM OR IF THEY
BELIEVED THEM TO HAVE BEEN A
CRIMINAL.
THERE WERE ALSO PUBLICATIONS
THAT PLANNED LYNCHINGS.
THE ONE ON THE LEFT TELLS US
THEY EXPECTED A LYNCHING AT
5:00 P.M. THAT DAY.
THEY PREPPED FOR IT, EVEN
DISCUSSED MAKING JERKY OUT
OF THE BODY OF THE
INDIVIDUALS THEY WOULD KILL.
SO BECAUSE OF THE CRIMINAL
JUSTICE SYSTEM THAT PROTECTS
INDIVIDUALS WHO CREATE THESE
MURDERS HAPPEN AT STATE
LEVEL, WE WANTED TO SEE IF
STATE LEVEL HISTORICAL
LYNCHING PLAYED A ROLE IN
THE CYSTINE PROTEINS IN
THOSE RACIALIZED AS BLACK.
AND SO WHAT WE SAW IS
COMPARING SPACE WITH ONE
LYNCHING TO TWO OR MORE --
BECAUSE WE DIDN'T WANT TO
USE A MEDIAN OR MEAN VALUE
AS IF THERE WERE SOME
PRESCRIBED NUMBER OF PEOPLE
THAT COULD BE KILLED THAT
WOULD BE APPROPRIATE, SO WE
DECIDED TO JUST COMPARE ONE
TO TWO OR MORE AND WE FOUND
JUST BEING IN A STATE WITH
TWO OR MORE WAS ASSOCIATED
WITH 17 PERCENT INCREASE IN
CR & ONE LOWER TEST SCORE ON
THE COGNITIVE ASSESSMENT.
JUST TWO OR MORE.
OKAY NOW I AM DOING WEIRD
STUFF, Y'ALL.
CAN'T TRUST ME.
OKAY, THANK YOU FOR FIXING
THAT BECAUSE YOU JUST CAN'T
TRUST ME.
WE HAVE ALSO LOOKED AT
SOCIOECONOMIC RACISM ACROSS
THE LIFE COURSE SO WHAT WE
DID WAS ENERGY -- EXTRACT
THE COHORT FROM THE HEALTH
AND RETIREMENT STUDY,
MID-BABY BOOMERS BORN
BETWEEN 1954 AND 1959 AFTER
THE BOARD VERSUS BROWN
EDUCATION RULING AND THEN
MAPPED SOCIOECONOMIC RACISM
AND CATEGORIZED THAT BEFORE
THEIR BIRTH, DURING
CHILDHOOD OR ADOLESCENTS,
ADULTHOOD AND MIDLIFE AND
THEN WHAT WE SAW WAS GREATER
SOCIOECONOMIC RACISM WAS IN
CHILDHOOD SO I HAVE TO NOTE
THESE INDIVIDUALS ENTERED
THE STUDY ONLY IN THE LAST
TEN YEARS.
SO LET'S TALK ABOUT
STRUCTURAL ECONOMIC
RESILIENCE?
IS THERE A WAY TO CHANGE
THAT IN MID-LIFE AND WHAT
DOES THIS LOOK LIKE IN
AGGREGATE?
USING THE SAME INDICATORS
FOR SOCIOECONOMIC RACISM WE
DON'T CONFIGURE THE
BLACK-WHITE DISPARITY.
WHAT IS THE PROPORTION OF
PEOPLE RACIALIZED AS BLACK
ABOVE THE POEFRL LEVEL, WHO
OWN HOMES AND THEN LOOK AT
THE COGNITIVE PERFORMANCE
ACROSS THOSE DECADES AND WA
WE SEE IS SOCIOECONOMIC
RESILIENCE BEFORE THEIR
BIRTH WAS ASSOCIATED WITH
SLOWER COGNITIVE DECLINE.
SO THAT FARM OWNERSHIP,
HOMEOWNERSHIP, ALL WAS
PROTECTED.
AND NOW IN THE UNDERSTANDING
OF LIFE COURSE RACISM, IT
MAY NOT JUST BE ABOUT THE
EXPOSURES AN INDIVIDUAL HAS
BUT THE HISTORY OF A PLACE.
SO A PLACE, IRRESPECTIVE OF
WHEN YOU HAVE BEEN THERE,
HOW LONG YOU HAVE BEEN THERE
IN YOUR LIFE COURSE MAY BE
CONTRIBUTING TO THE
COGNITIVE PERFORMANCE YOU
SEE OVER YOUR LIFE COURSE.
AND SO I HAVE BEEN BUILDING
THIS NEW MODEL WITH MY
COLLEAGUE HERE, Dr. MARY
BEL ALTHOUGHBLEDO GONZALEZ
OF THE ANTI--LATINX
STRUCTURAL RACISM, WE START
AT THE MOMENT THE
U .S.-MEXICO BORDER MOVES
AND THEN TRACK RACISM OVER
TIME.
SO NEXT TIME YOU ARE WITH
YOUR COLLEAGUES AND LOOKING
AT DISPARITIES OR TALKING
ABOUT PREFERENCE IMPACT AND
YOU ARE ENCOURAGED TO THINK
ABOUT SOMEONE BEING BORN
WITH SOMETHING, I ENCOURAGE
YOU TO THINK MAYBE IT IS
RACISM.
MAYBE RACISM IS PLAYING A
ROLE IN WHAT HAS HAPPENED TO
INDIVIDUALS AND THE
DISPROPORTIONATE IMPACTS TO
THEIR BODY.
SO I WOULD LIKE TO THANK
THIS HUGE COLLABORATIVE TEAM
THAT WE HAVE, THE MARVIN
GRAY MATTER TEAM -- GET
THAT, MARVIN GRAY MATTER, I
LIKE THAT.
WE COLLABORATE ON MEASURES
OF RACISM, SHARE DATA,
PRACTICALLY A CULT.
AND ARIANA WILL BE GIVING
HER PRESENTATION TOMORROW.
I ALSO WANT TO THANK Dr.
MANLY, Dr. KIM AND OTHERS
WHO HAVE BEEN WRITING THIS
INTO THIS AND ALSO MY BOUGIE
BUT THANK YOU TO MY GRANNY
WHO HAS BEEN TALKING TO ME
MOST ABOUT THIS SCIENCE.
THANK YOU.
[APPLAUSE]
>> THANK YOU SO MUCH, AJ AND
NOW I AM GOING TO INTRODUCE
LAURA ZAHODNE IN THE
PSYCHOLOGY DEPARTMENT AT THE
UNIVERSITY OF MICHIGAN.
>> THANK YOU, THANK YOU SO
MUCH FOR THE OPPORTUNITY TO
BE HERE, THANK YOU FOR THE
OPPORTUNITY TO BE PART OF
THIS PANEL.
THIS IS A HUGE HONOR.
I AM INTERESTED IN MULTIPLE
ASPECTS OF THE SOCIAL AND
STRUCTURAL ENVIRONMENT AND
TO START MY TALK TODAY ON
DISCRIMINATION WHICH MAY
INFLUENCE INEQUALITIES IN
COGNITIVE AGING ALONGSIDE
OTHER SOCIAL DISCRIMINAL
TPHAPBTS OF HEALTH.
OUR WORK IN THIS AREA HAS
BEEN GROUNDED IN THEORETICAL
FRAMEWORK BY BODNEY KIRK --
RODNEY CLARK THAT FOCUSES ON
RACISM AS A STRESSOR FOR
AFRICAN-AMERICANS AND THE
IMPORTANCE OF THIS MODEL AS
IT RELATES TO COGNITIVE
AGING.
SO USING THE STUDY FROM THE
HEALTH AND RETIREMENT AGING,
HERE WE ARE INTERESTED IN
THE VIKE LOGICAL CONSTRUCT
THAT QUALITATIVE DATA HAVE
SHOWN ARE LIKELY INFLUENCED
LIKE CHANGES IN MOOD OR
PERCEPTION OF CONTROL, THAT
YOU ARE NOT IN CONTROL OF
IMPORTANT LIFE OUTCOMES.
AND WHAT WE FOUND IS THOSE
BLACK ADULTS EXPERIENCED
MORE RACIAL SYSTEM NATION
WHICH PREDICTED BOTH MORE
DEPRESSIVE SYMPTOMS AND
EXTERNAL LOCUS OF CONTROL
AND BOTH OF THOSE WERE
RELATED TO COGNITIVE HEALTH.
SO SOME EVIDENCE THAT
DISCRIMINATION MAY INFLUENCE
COGNITIVE AGING IN PART
THROUGH PSYCHOLOGICAL
PATHWAYS.
WE'RE ALSO INTERESTED IN
PHYSIOLOGICAL MECHANISMS BY
WHICH WE NIGHT GET UNDER THE
SKIN TO AFFECT HEALTH.
SO HERE WE SEE THE CRS
PRETTY TO TEEN THAT IS A
MARKER OF INFLAMMATION.
WE KNOW THROUGH HUMAN AND
ANIMAL RESEARCH THAT MARKERS
OF INFLAMMATION ARE ELEVATED
IN CHRONIC STRESS SO WE
WANTED TO TEST WHETHER THIS
MEDIATED LONGITUDINAL
DISTRESS WITH INFLAMMATION
AND COGNITIVE HEALTH.
NOW WE DID NOT SEE ANY
LONGITUDINAL MEDIATION IN
THIS DATA BUT THERE WAS
SOMEWHERE WE LOOKED AT
INDIVIDUAL VARIABILITY,
SPECIFICALLY THOSE
PARTICIPANTS WHO REPORTED
MORE OF A EXPERIENCE OF
DISCRIMINATION HAD HIGHER
CRP WHICH IN TURN WAS
RELATING TO LOWER COGNITIVE
PERFORMANCE.
SO INFLAMMATION MAY BE ONE
THING THAT GETS UNDER THE
SKIN BUT THE PROCESS IS NOT
YET CLEAR.
IN ADDITION TO HOW IT MIGHT
GET UNDER THE SKIN IS HOW IT
MIGHT GET INTO THE SKULL SO
HERE WE ARE SHOWING YOU A
GROUP STUDY WITH 291 BLACK
OLDER ADULTS IN NEW YORK AND
SHOWING YOU THE LONGITUDINAL
DATA ON RACIAL
DISCRIMINATION AND WHITE
MATTER WHICH IS RELATED TO
INFLAMMATION.
AND AS YOU CAN SEE THE OLDER
BLACK ADULTS WHO REPORTED
MORE FREQUENT DISCRIMINATION
SHOWED A FASTER ACCUMULATION
OF THIS PATHOLOGY OVER A
FOUR-YEAR PERIOD.
INDEPENDENT OF WHITE MATTER
HYPER INTENSITY, THIS STUDY
BY A GRADUATE STUDENT IN
MICHIGAN, JORDAN UPONG SHOWS
THE DAY-TO-DAY EXPERIENCE OF
DISCRIMINATION CONTRIBUTES
TO THE WHITE MATTER AGING.
SO WE KNOW THAT THIS IS
CRITICAL IN BRAIN HEALTH
AMONG OLDER PLAQUE ADULTS.
NOW, I WANT TO PAUSE HERE
FOR A MINUTE BECAUSE SO MUCH
THIS FOCUS ON RISK PATHWAYS
BUT WE KNOW THIS
RELATIONSHIP BETWEEN RACE,
THE COMPLEX SOCIOECONOMIC
CONSTRUCT AND COGNITIVE
AGING REALLY REFLECTS THE
SUM OF THOSE RISKS AND
RESILIENT PATHWAYS AND THIS
IS BECAUSE SOCIAL GROUPS
ALSO CULTIVATE NORMS AND
BEHAVIOR THAT COULD BE WORTH
PROMOTING.
SO BY USING RACE AS A SIMPLE
PROXY FOR RACISM OR BY
FOCUSING ONLY ON RISK
PATHWAYS, WE WON'T BE ABLE
TO SEE THE WHOLE PICTURE.
I WILL SHOW YOU ONE EXAMPLE
CONSIDERING BOTH RISK AND
RESILIENCE IN A MODEL OF
COGNITIVE DISPARITIES, THIS
WAS BY EMILY MORRIS AND A
FORMER POST-DOC LAUREN
BROWN.
AND THE WORK WAS TO EXTEND
Dr. BROWN'S RACIAL AND
MENTAL HEALTH TO COGNITIVE
HEALTH.
THE DATA SHOWED OLDER BLACK
AMERICANS REPORTED BEING
EXPOSED TO MORE CHRONIC
STRESSORS THAN WHITE AND
LEADING TO LOWER COGNITIVE
HEALTH BUT THE SAME BLACK
OLDER ADULTS ALSO APPRAISED
STRESSORS AT BEING LESS
UPSETTING, COPING WITH CON
TEMP LIVED EXPERIENCES AND
APPRAISING STRUCTURES LESS
UPSETTING WAS IN AND OF
ITSELF A UNIQUE PREDICTOR OF
BETTER MEMORY INDEPENDENT OF
STRESS EXPOSURE.
SO I THINK THIS PROVIDES
SOME NUANCE EVIDENCE OF BOTH
RISKS AND RESILIENCE FOR
COGNITIVE AGING AMONG BLACK
OLDER ADULTS.
NOW I WANT TO TALK ABOUT
SOME OF THIS WORK ON
DISCRIMINATION.
EVERYDAY DISCRIMINATION
MEASURES MAY NOT BE
MEASURING THE SAME CONSTRUCT
ACROSS GROUPS.
SO WE HAVE SEEN QUANTITATIVE
EVIDENCE FROM LEWIS AND
OTHERS, THIS MORE RECENT
QUALITATIVE STUDY INTERVIEWS
PEOPLE AS THEY COMPLETED THE
EVERYDAY DISCRIMINATION
SCALE, PROBABLY THE MOST
COMMON MEASURE USED IN THIS
WORK AND THEY SHOWED THAT
PEOPLE USE DIFFERENT
COGNITIVE SCHEMAS OR
FRAMEWORKS FOR INTERPRETING
AND RESPONDING TO THE ITEMS
ON THIS SCALE.
SO SOME PEOPLE APPROACHED
THIS SCALE THROUGH A MORE
GENERAL LENS OF NEGATIVE
SOCIAL INTERACTION WHILE
OTHERS APPROACH IT THROUGH A
MORE SPECIFIC LENS OF SOCIAL
INEQUALITY OR RACISM.
AND THESE DIFFERENCES IN USE
OF SCHEMA CORRESPONDED TO
SOCIODEMO GRAPHIC
INTERACTION.
SO THOSE ARE MORE POSITIVE
SCHEMAS WERE BETTER OFF ON
THIS THOSE WITH NEGATIVE
INTERACTIONS.
NOW, THIS BETWEEN-GROUP
STUDIES MAY NOT BE MEASURING
WHAT WE THINK THEY ARE
MEASURING SO THIS IS ONE
REASON WHY A LOT OF OUR WORK
HAS REALLY MOVED TOWARD
SINGLE GROUP STUDIES TO
UNDERSTAND HOW
DISCRIMINATION MAY INFLUENCE
COGNITIVE AGING.
ANOTHER LOOK AT THIS IS
THESE FOCUSES ON OVERT
EXPERIENCES AT THE PERSONAL
LEVEL SO WE DON'T CAPTURE
ALL TYPES OF DISCRIMINATION
INCLUDING INSTITUTIONAL
DISCRIMINATION THAT MAY GET
TRANSMITTED BY POLICY,
EXPERIENCE DISTRIBUTED BY
THE NETWORKS OR SOCIAL MEDIA
OR OTHER INSIDIOUS
DISCRIMINATION THAT COULD
INFLUENCE STRESS AGING
THROUGH PATHWAYS LIKE ACCESS
TO RESOURCES.
SO I WILL TALK ABOUT SOME OF
THE TKR-BGSZ WE HAVE TAKEN
IN CONNECTION WITH THESE
STUDIES.
ONE IS TO SEEK OUT
ALTERNATIVE INDIVIDUAL
LEVELS THAT MIGHT PROVIDE A
BROADER PICTURE OF HOW A
INDIVIDUAL IS IMPACTED BY A
BROADER ARRAY OF
ENVIRONMENTAL EXPOSURE.
SO THIS IS A PSYCHOLOGICAL
CONSTRUCT THAT COMES OUT OF
THE SOCIAL LEARNING THEORY
LITERATURE, WHERE PEOPLE
FEEL THEY HAVE CONTROL OVER
IMPORTANT LIFE OUTCOMES.
IT INCLUDES SUFFERABLE
DIMENSION OF INTERNAL
CONTROL WHICH IS THE MASTERY
OF EFFICACY AND EX PERSONAL
CONTROL WHICH REFLECTS THE
PERCEPTION OF ENVIRONMENTAL
CONSTRAINTS THAT LIMIT ONE'S
INSTRUMENTALITY.
WE HAVE DECADES OF THIS THAT
IS SHAPED BY SOCIAL MEASURE
SO IF YOU WANT TO INFLUENCE
IT, YOU HAVE TO INFLUENCE IT
THROUGH THE ENVIRONMENT.
WE TYPICALLY DON'T SEE RACE
DIFFERENCES IN INTERNAL
CONTROL WHICH IS MITIGATED
BY FAMILY AND FRIENDS BUT WE
DO SEE DIFFERENCES IN
EXTERNAL CONTROL WHICH
APPEARS TO BE SHAPED MORE BY
THE MACRO ENVIRONMENT, THIS
LARGER SOCIAL STRUCTURE.
SO MEASURES OF THE EXTERNAL
CONTROL MAY BE HELPFUL FOR
GAUGING THAT INDIVIDUAL
LEVEL IMPACT OF A BROADER
SET OF ENVIRONMENTAL
EXPOSURES INCLUDING
INTERPERSONAL
DISCRIMINATION.
REMEMBER, EXTERNAL CONTROL
WAS A MEDIATOR OF THE
EFFECTS OF THE FIRST HRS
STUDY I SHOWED YOU BUT ALSO
ACROSS DIFFERENT LEVELS.
MOVING BEYOND THE INDIVIDUAL
LEVEL NOW, WE HAVE THOUGHT
OUT MEASURES THAT DIRECTLY
QUANTIFY EXPOSURE AT OTHER
ECOLOGICAL LEVELS INCLUDING
THE NEIGHBORHOOD LEVEL.
THIS IS EXCITING BECAUSE
NEIGHBORHOOD LEVEL EXPOSURES
MAY BE MORE ACTIONABLE AND
AMENABLE TO POLICY CHANGES
AND INTERVENTION.
SO I WILL SHOW YOU AN
EXAMPLE OF STUDIES USING
DIFFERENT DIRECTIONS FOR
THIS RESEARCH IN HEALTH
INEQUALITY.
SO THOSE INDIVIDUALS LOOKING
AT THIS BLACK-WHITE AND
HISPANIC-WHITE AS FACTORS.
THE MAJORITY UP TO
60 PERCENT WERE
SOCIOECONOMIC FACTORS BUT
PERCEIVED CONTROL EXPLAINED
7-8 PERCENT WHILE THE TWO
COMMONLY USED MEASURES OF
DISCRIMINATION WERE NOT
CONTRIBUTORS AND THAT IS
BECAUSE IN THE EXAMPLE,
NEITHER OF THESE
DISCRIMINATION MEASURES WAS
RELATED TO COGNITIVE HEALTH.
AND IN THE CASE OF
HISPANIC-WHITE DISPARITIES,
THEY DID NOT REPORT HIGHER
LEVELS OF DISCRIMINATION.
SO THEY DID REPORT HIGHER
LEVELS OF EXTERNAL PERCEIVED
CONTROL.
SO SOME EVIDENCE THAT THESE
MEASURES OF EXTERNAL
PERCEIVED CONTROL MIGHT
CAPTURE THOSE PSYCHOSOCIAL
EXPERIENCES OF DIFFERENT
MARGINALIZED GROUPS THAT
MIGHT BE RELEVANT FOR
COGGIZATION.
SO LOOKING AT THE
NEIGHBORHOOD RACIAL INCOME
INEQUALITY, THE BIN LADEN
AND WHITE MEDIAN INCOME AND
IN THIS PARTICULAR STUDY
THAT TAKES PLACE IN AND
AROUND DETROIT, WHITE
FAMILIES WERE REPORTING
INCOMES 73 PERCENT HIGHER
THAN BLACK INCOMES AND THAT
HAS NOT REALLY CHANGED SINCE
THE 1960S.
BUT IMPORTANTLY ABOVE AND
BEYOND INDIVIDUAL FDS,
COMPOSITION OF THE
NEIGHBORHOOD, GEOGRAPHIC
CLUSTERING, WE SAW THAT
GREATER NEIGHBORHOOD INCOME
INEQUALITY WAS RELATED TO
POORER COGNITIVE HEALTH.
AND INTERESTINGLY, THIS
ASSOCIATION WAS NOT
MODERATED BY INDIVIDUAL
RACE.
SO THIS COHORT IS RACIALLY
BALANCED, 50 PERCENT BLACK,
50 PERCENT WHITE AND SEESAW
THE SAME ASSOCIATION WITH
BLACK AND WHITE
PARTICIPANTS.
SO THIS MIGHT SUGGEST THAT
INEQUALITY COULD BE BAD FOR
EVERYBODY IN A NEIGHBORHOOD
AND THIS RESEARCH IS
IMPORTANT IN THE UNDERLYING
COGNITIVIZATION.
ANOTHER STUDY ON OVERLYING
CONDITIONS, THIS WORK FROM
Dr. SOL WHO LOOKED AT THE
NEIGHBORHOODS I
INCORPORATING LONGITUDINAL
TRAJECTORY OF NEIGHBORHOOD
'TIS INVESTMENT.
SO USING 17 YEARS OF CENSUS
DATA, Dr. SOL SHOWED
EVIDENCE FOR THREE
CATEGORIES OF NEIGHBORHOODS,
THOSE NEIGHBORHOODS WITH LOW
AND INCREASING DISADVANTAGE.
NEIGHBORHOODS WITH MODERATE
AND INCREASING ECONOMIC
DISADVANTAGE AND THEN IN
RED, THE NEIGHBORHOODS THAT
ARE INCREASINGLY HIGH.
AND SHE LOOKED AT WHETHER
RESIDING IN THESE DIFFERENT
NEIGHBORHOODS HELPS TO
UNDERSTAND RACIAL
DIFFERENCES IN COGNITIVE
HEALTH.
SO HERE SHE FOUND BLACK
PARTICIPANTS IN THIS STUDY
WERE MORE THAN LIKELY TO
LIVE IN NEIGHBORHOODS
DESCRIBED AS MODERATELY HIGH
OR INCREASING SOCIOECONOMIC
DISADVANTAGE BUT ONLY IN THE
NEIGHBORHOOD OF INCREASING
DISADVANTAGE RANKED AS HIGH.
SO THIS MAY NOT TELL US THE
WHOLE STORY.
DYNAMIC CHANGES WITHIN THE
NEIGHBORHOOD ARE OFTEN
IMPORTANT FOR UNDERSTANDING
HOW NEIGHBORHOOD SOCIAL
CONDITIONS AFFECT COGNITIVE
AND BRAIN AGING.
SO JUST SOME SUMMARY POINTS
FROM THE TALK TODAY, I
SHOWED EVIDENCE THAT
DISCRIMINATION MAY BE LINKED
TO COGNITIVE AGING, TO
PSYCHOLOGICAL AND PHYSICAL
MODELS LINK THRAO*ED STRESS
PATHWAYS BUT THEY CAN'T TELL
THE WHOLE STORY WITH HOW IT
GETS UNDER THE SKIN AND
AFFECTS AGING.
WOULD HE ALSO NEED TO
CONSIDER INDIVIDUAL FACTORS,
INDIVIDUAL LEVEL MEASURES
WITH EXTERNAL PERCEIVED
CONTROL THAT MIGHT BE THE
IMPACT OF A BROADER ARRAY OF
ENVIRONMENTAL EXPOSURE
INCLUDING BUT NOT LINKED TO
PERSONAL DISCRIMINATION.
WE SAW MOVING BEYOND THE
NEIGHBORHOOD LEVEL, THAT
EXTERNAL PERCEIVED CONTROL
MIGHT BE IMPORTANT AND WE
NEED CONSIDER LARGER SOCIAL
STRUCTURES.
I WANT TO TAKE THE TIME TO
THANK THE THOUSANDS OF
PARTICIPANTS WHO TOOK TIME
TO PARTICIPATE IN THE STUDY
I PRESENTED TODAY.
THIS WORK COULD BE DONE
WITHOUT ME BUT NOT WITHOUT
THEM.
I ALSO WANT TO FEATURE SOME
FORMER COLLABORATORS ON
THESE STUDIES AS WELL AS OUR
FUNDING INCLUDING THE
NATIONAL AGE INSTITUTES OF
HEALTH ON AGING.
>> THANK YOU, SO NOW WE WILL
WELCOME IN MIGUEL RENTERIA
TO TALK TO US ABOUT
COGNITIVE EFFECTS OF
BILINGUALISM.
>> HELLO, THANK YOU.
I WILL BE TALKING ABOUT HOW
THE COGNITIVE EFFECTS OF
BILINGUALISM AFFECTS SOCIAL
AGING AND THROUGH THE
MECHANISM ITSELF.
WE KNOW THERE IS PLENTY OF
SUPPORT THAT ENGAGING IN
COGNIZANT ACTIVITIES IS
ASSOCIATED WITH LESS
DEMENTIA AND WITH THAT WE
CAN THINK ABOUT WHAT WE KNOW
AS QUALITY OF EDUCATION AND
THE COMPLEXITY BUT SOME
STUDIES HAVE BEEN REPORTING
THIS BILINGUAL CALL
COGNITION MOANING THEY
OUTPERFORM THOSE WITH ONE
LANGUAGE AND FOUND IN
CHILDREN, YOUNG ADULTS,
OLDER ADULTS BUT LIKE WITH
ANY OTHER STUDY, THERE ARE
INCONSISTENT FINDINGS.
SO SWITCHING LANGUAGES CAN
STRENGTHEN NEURONETWORKS AND
REMAIN A POTENTIAL BENEFIT.
HOWEVER, WHAT COULD BE
EXPLAINING SOME OF THESE
DISCREPANCIES IS THERE ARE
PLENTY OF DIFFERENCES.
YOU MIGHT BE AWARE FROM
THOSE IN THE ROOM THAT THERE
ARE DIFFERENCES IN THE
DEFINITION OF BILINGUAL
WALL, RIGHT?
AND WHAT ABOUT BILINGUALISM
IS LIKELY TO AFFECT OR
BENEFIT COGNITION?
HOW YOU ARE USING IT, HOW
PROFICIENT YOU ARE IN THE
LANGUAGE, AND WITHIN THAT,
THERE ARE OTHER FAX TORSION.
IT WILL NOT HAPPEN IN A
VACUUM.
THERE ARE SOME EXPERIENCES
THAT INFLUENCE BILINGUALISM
ASSOCIATIVE WITH BRAIN
HEALTH AND THIS CAN CROSS
STUDIES SO I WANT TO WALK
YOU THROUGH WHY I APPROACHED
THIS FARCE THE FACTORS THAT
COMPLICATE OR ENRICH FACTORS
IN COGNITIVE AGING.
WOULD HE KNOW STUFF HAPPENS
TO THE BRAIN AND THEN THAT
IMPACTS.
AND BILINGUALISM HAPPENS IS
WHERE WILL IN A PERSON'S
LIFE AND THEN CAN PROVIDE
BENEFIT BY LIMITING AGING ON
BRAIN STRUCTURE OR ACTUAL
BRAIN HEALTH ON THE
OUTCOMES.
BUT THEN IN ADDITION, THERE
IS PLENTY OF CHILDHOOD
FACTORS OR ADULT PERCEPTUAL
FACTORS LIKE SOME MY
COLLEAGUES HAVE MENTIONED
TODAY THAT ARE ASSOCIATIVE
WITH BILINGUALISM THAT COULD
HAPPEN IN ANY PERSON'S LIFE
AND ALL OF THESE FACTORS
HAVE BEEN ASSOCIATED WITH
BRAIN AND SOCIAL OUTCOMES
LATE IN LIFE.
SO WE NEED TO KEEP THIS IN
MIND WITH THE POPULATION WE
ARE WORKING WITH.
AND THEN WHAT ABOUT
BILINGUALISM?
WE NEED TO GET MORE DETAILED
CONTEXT TO THAT.
SO A LOT OF THESE STUDIES
COME FROM THE UNITED STATES
OR HIGH INCOME COUNTRIES SO
I WILL BE SHOWING YOU ABOUT
THE STUDY IN NEW YORK, THE
MHAS ANCILLARY STUDY IN
MEXICO AND THEN THE
LONGITUDINAL AGING STUDY IN
INDIA.
SO FIRST TALKING ABOUT THE
OFFSPRING RACE AND ETHNIC
DISPARITIES, THIS CAME FROM
THE NORTHERN PART OF
MANHATTAN.
FOR THIS STUDY, I AM
FOCUSING ON THE SUBCATEGORY
OF THOSE WHO ARE LATINO OR
LATIN-X AND THEN WHAT
LANGUAGE THEY KNOW AND THEN
CONDUCTING THE ASPECTS OF
THE LANGUAGE, HOW PROFICIENT
THEY ARE IN THEIR SECOND
LANGUAGE WHICH IN THIS CASE
WOULD BE ENGLISH IN TERMS OF
SPEAKING, READING, WRITING,
AND UNDERSTANDING AND THEN
WHAT AGE THEY WERE WHEN THEY
HAD TO LEARN IT.
WHAT I WANT TO SHOW HERE
ALREADY LIKE SEEING HOW
IMPORTANT THIS IS, WE'RE
WORKING WITH AROUND 980
PARTICIPANTS AND YOU CAN SEE
I AM GROUPING THEM IN IN OUR
GROUPS, REALLY SEPARATED BY
WHETHER THEY WERE NESTED
SPANISH OR ENGLISH AND
WHETHER THEY WERE IMGRANTS
OR U.S. BORN.
SOME OF THE KEY THINGS TO
POINT OUT IS YOU ONLY HAVE A
MON LOW LINGUAL GROUP,
TESTED IN SPANISH BUT ARE AN
IMMIGRANT, BORN OUTSIDE THE
U.S.
MOST OF THE LATINOS HERE
WERE DOMINICAN AND THOSE
U.S. BORN ARE ALL IMMIGRANTS
AND WANT TO BE TESTED IN
ENGLISH.
SO THE FACTORS GO FROM LEFT
TO RIGHT WITH THE U.S. BORN
BILINGUAL GROUP WHICH LOOK
AT AGE, EDUCATION, PARENT
EDUCATION, AND PROFICIENCY.
THOSE IN ENGLISH HAVE THE
HIGHEST PROFICIENCY WHEN
TESTED VERSUS THOSE TESTED
IN SPANISH.
THE IMMIGRANTS WHO STARTED
LEARNING ENGLISH WERE AROUND
10 YEARS OF AGE AND U.S.
BORN OBVIOUSLY HAPPENED WHEN
THEY WERE KIDS AROUND 3.
SO WHAT I AM SHOWING IS THE
ASSOCIATION BETWEEN BEING
BILINGUAL OR MULTILINGUAL
CALL AND THE LEVELS OF
COGNITION.
NOW AS YOU CAN SEE HERE,
BILINGUAL WALLS ARE
PERFORMING BETTER THAN MON
MONO LINGUALS IN MEMORY,
ATTENTION WORKING MEMORY,
LANGUAGE, EXECUTING
FUNCTIONING AND PROCESSING
SPEED.
SO HERE I WILL SHOW YOU THE
DIFFERENT GROUPS AND HOW
THEY COMPARE TO THE MONO
LINK WALL PERFORMANCE, THE
U.S. BORN GROUP TESTED IN
ENGLISH, YOU CAN SEE THEY
ARE PERFORMING ALL OF THE
GROUPS AND SEVERAL OF THE
ONES WE TALKED ABOUT, THE
IMMIGRANTS TESTED IN
ENGLISH.
THEN THE IMMIGRANT GROUP
TESTED IN SPANISH ONLY
DIFFERED IN THE MONO LINGUAL
GROUP.
AND THEN LOOKING ONLY IN THE
BILINGUAL WALL SAMPLE IS THE
AGE OF ACQUISITION.
HERE WHAT YOU ARE SHOWING IS
THE AGE OF LATER ACCESS IS
SUPPORTED BY WORSE
PERFORMANCE.
FOR EXAMPLE HERE ON THE
RIGHT, YOU SEE MEMORY POP
UP.
THEN HERE WE ARE PRO
EFFICIENCY IN ENGLISH
SUPPORTED ACROSS THE PATH
WHICH MAKES SENSE BECAUSE IT
IS OFTEN ASSOCIATE WITH AGE
OF ACQUISITION AND THE
HIGHER AGE OF ACQUISITION
HAVE HIGHER PROFICIENCY.
THIS IS ALSO THE GROUP BORN
IN THE U.S. WHICH IS NOT
SURPRISING BECAUSE THEY HAD
THE EARLIEST AGE OF
ACQUISITION.
WE HAD SOME IMMIGRANTS WITH
YOUNGER AGE OF ENGLISH BUT
THEY DID NOT PERFORM ANY
BETTER THAN THOSE BORN IN
THE U.S.
SO TO WRAP UP THE RESULTS,
IT WAS ASSOCIATED WITH
BETTER PERFORMANCE ACROSS
SEVERAL DOMAINS, TESTING
ACCURACY, PROFICIENCY,
OBVIOUSLY THESE DIFFERED
BECAUSE OF LANGUAGE AND
GETTING BACK TO THE
BILINGUALISM, IT WAS
ASSOCIATED WITH PERFORMANCE
ACROSS DIFFERENT COGNITIVE
DOMAINS.
AND NOW THIS IS FOR LIKE
LATINOS LIVING IN THE UNITED
STATES, A GOOD CHUNK OF THEM
MIGRANTS AND SO WE COMPARED
THEM WITH THE BILINGUALISM
IN MEXICO.
IN 2015 THEY LAUNCHED A
SUBSAMPLE STUDY OF AGING.
AND WHAT I THINK A LOT OF
PEOPLE DON'T KNOW IS WE HAVE
7MILLION SPEAKERS OF
INDIGENOUS LANGUAGES AND
15 MILLION PEOPLE SPEAKING
ENGLISH.
SO WHAT I AM DOING HERE IS
CATEGORIZING URBAN AND
ENGLISH BECAUSE WE HAVE TWO
GROUPS IN MEXICO, ONE WHO
ARE SPANISH AND ENGLISH OR
THOSE WHO WERE INDIGENOUS.
SO WE STRATIFIED THE
ANALYSIS LOOKING FOR HE
COVARIANTS AND THEN LOOKING
FOR PERFORMANCE ON THE
COGNITIVE BATTERY.
SO IN THE URBAN AREA
COMPARING SPANISH MONO
LINGUALS IN MEXICO, THERE
WAS ALSO NO DIFFERENCE
WHETHER THEY WERE BILINGUAL
WALLS OR MONO LINGUALS IN
THAT AREA.
SO WHEN LOOKING AT THE
COGNITION GROUP YOU SEE THEY
ARE COMPARING LOWER THAN THE
SPANISH MONO LINGUAL GROUP.
SO THERE IS NOT ANYTHING BAD
ABOUT LEARNING A DIFFERENT
LANGUAGE BUT WHAT ARE THE
FACTORS THAT MAYBE WE'RE NOT
ACCOUNTING FOR IN THE STUDY
RIGHT NOW AND THAT LED TO US
TO THINK ABOUT THE VALIDITY
OF THE TESTING AMONG
INDIVIDUALS.
WE DON'T KNOW THE
PROFICIENCY IN SPANISH SO WE
WILL NOW BE COLLECTING THAT
THIS YEAR AND NEXT YEAR AND
EXCITED ABOUT BEING ABLE TO
LOOK AT THESE DIFFERENT
LINGUISTIC PROFILES AMONG
BOTH GROUPS.
SO THEN SOMETHING GOT ME
THINKING FOR THAT STUDY,
SOME OF THE DIFFERENCES
BETWEEN THE LATINOS IN THE
UNITED STATES WHO ARE
PRIMARILY IMMIGRANTS AND THE
MEXICANS LIKE MYSELF, IN
MEXICO, THEY WERE LEARNING A
MINORITY LANGUAGE.
THOSE ACQUIRING ENGLISH,
THAT IS A MINOR LANGUAGE BUT
IN THE U.S., IT IS A
MAJORITY LANGUAGE, RIGHT?
SO IT GOT ME TO THINKING
DOES THAT REALLY HAVE
ANYTHING TO DO WITH THE
FUNCTION.
IN INDIA, IT IS REALLY
LINGUISTICALLY DIVERSE AND
WHAT IS COOL ABOUT THAT IS
MULTILINGUAL WALLISM IS MORE
DISTRIBUTED ACROSS THE
ECONOMIC GRADIENT IN THAT
COUNTRY.
AND SO WITH THAT, I AM
LOOKING AT A SISTER STUDY
WHICH HAS VERY SIMILAR
METHODOLOGICAL DESIGN.
SO WE LOOKED AT THOSE WHO
ARE MULTILINGUAL WALL, THE
MAJORITY VERSUS THE MINORITY
AND SO HIGHLIGHTING THE
DIVERSITY, ALL PARTICIPANTS
WERE SPEAKING THE MAJORITY
LANGUAGE FOR THE REGION.
THEN WE'RE SEEING THE
DIFFERENT LANGUAGES WHO ARE
L1, THEIR MAJORITY LANGUAGE
IS THE FIRST ONE, PRETTY
SIMILAR TO THE MONO LINGUAL.
AND THEN FOR THE MONO
LINGUALS, THEIR FIRST
OFFERING WAS THE LEARNING
LANGUAGE.
SPANISH IS A MINORITY.
AND THEN WE WILL SEE THESE
DIFFERENT LANGUAGES POP UP.
SO WHAT IS ALSO COOL ABOUT
THIS WORK IS WE ARE LOOKING
AT IT ACROSS FTS.
SO WHAT I WILL SHOW YOU HERE
SEEING THE DIFFERENT
COGNITIVE DOMAINS ACROSS THE
THREE GROUPS, THE MINORITY
MULTILINGUALAND MAJORITY
MULTILINGUAL AND HERE THEY
ARE ADJUSTED FOR COVARIANTS.
AND TO START FROM THE
BEGINNING, IT DIDN'T MATTER
WHETHER THEY WERE MAJORITY,
MINORITY, MULTILANGUAGE, IT
DIDN'T REALLY TRANSLATE
ACROSS ALL DOMAINS.
HOWEVER YOU CAN CLEARLY SEE
THIS IS A STRONG ASSOCIATION
WITH AES ACROSS ALL GROUPS.
REALLY IN TERMS OF THE
MULTILINGUAL WALL
DIFFERENCE, WE ONLY SEE THAT
AMONG PEOPLE WHO HAVE THE
HIGHEST SES VERSUS THOSE
THAT HAVE THE LOWEST SES.
IF YOU COMPARE THE TWO, THEY
REALLY HAVE NO DIFFERENCE SO
WE'RE GETTING A STRONG
ASSOCIATION WITH BI
LINGUALISM.
AND REALLY WHAT HIGHLIGHTS
THE ROLES, EVEN THOUGH THE
MULTILINGUALS ARE REPORTING
BETTER THAN THE MONO
LINGUALS, I HIGHEST SES
INDIVIDUALS ARE
OUTPERFORMING THE SES
MINORITY SECTIONS SO THIS
SHOWS THE ROLE THAT SES
PLAYS ON COGNITIVE
FUNCTIONING.
SO TO CONCLUDE, THE
ASSOCIATION BY LANGUAGE AND
COGNITION SEEMS TO DIFFER
NATIONALLY.
THERE IS NO REAL CLEAR STEP
THAT PROVIDES A ADVANTAGE.
IN THE UNITED STATES, IT WAS
ASSOCIATED ACROSS THE
SOCIODOMAINS AND WE SAW
THESE DIFFER ACROSS THE
SOCIAL GROUPS WE
CHARACTERIZE, BEING IN THE
U.S. AND WHETHER THEY WERE
TESTED IN ENGLISH OR SPANISH
BUT ALSO ASKED TO SEE THE
ACCESS, WHETHER THEY WERE
USING TWO LANGUAGES EVERY
DAY COMPARED TO ONE LANGUAGE
AND WE ALSO FOUND AN
ASSOCIATION OF THAT ON
COGNITIVE FUNCTIONING BUT IN
FEWER DOMAINS.
WE HAD ONLY EPISODIC MEMORY
AND PROCESSING SPEED.
IN INDIA, BILINGUALISM WAS
ASSOCIATED WITH BETTER
COGNITION BUT REALLY ONLY
SAW THAT WITH MEDIUM TO HIGH
SES.
AND THEN REALLY INDICATING
HOW THE SOCIAL AND
ENVIRONMENTAL FACTORS
ASSOCIATED WITH MULTILINGUAL
WALLISM IS ASSOCIATED WITH
HIGHER FUNCTIONS.
WE REALLY NEED TO DO MORE
WORK TO SEPARATING THESE IN
THE FUTURE AND HOW THEY
RELATE TO THE COGNITIVE
DECLINE.
SO WITH THAT, I WOULD LIKE
TO ACKNOWLEDGE THE PEOPLE I
AM WORKING WITH, OUR LAB AT
COLUMBIA AND POST-DOC TEAM
IN ALL THE STUDIES, THANK
YOU.
[APPLAUSE]
>> OKAY, THANK YOU MIGUEL
AND THEN THE LAST TALK FROM
OUR SESSION, WE HAVE KATRINA
WALSEMANN WHO IS JOINING US
REMOTELY TO TALK ABOUT
EDUCATIONAL INEQUAL
QUALITIES.
-- INEQUITIES.
>> GOOD MORNING I AM GOING
TO SHARE SOME OF MY WORK ON
THE RELATIONSHIP BETWEEN
SCHOOL INEQUITY IN U.S.
SOUTH PRE- AND POST BROWN.
SO BEFORE I BEGIN I WANT TO
THANK THE NATIONAL INSTITUTE
OF AGING FOR SUPPORTING THIS
WORK AND THE COLLABORATORS
FOR THE VALUABLE EXPERTISE
AND WORK THEY PRESENTED TO
THIS PROJECT.
IN THE UNITED STATES, LARGE
AND PERSISTENT BLACK WHITE
MEMORIES WITH COGNITIVE
FUNCTION ARE WELL
DOCUMENTED.
AND ONE OF THE MOST COMMON
FACTORS IS EDUCATION.
BECAUSE OLDER BLACK ADULTS
COMPLETED FEWER YEARS OF
SCHOOLING THAN THEIR KNIGHT
COUNTERPARTS IT IS OFTEN
USED TO EXPLAIN DISNATURES
COGNITIVE FUNCTION.
HOWEVER, IT ONLY EXPLAINS
ABOUT A QUARTER OF THE BLACK
AND WHITE INEQUITY.
PART OF THE REASON WHY IT
MAY NOT DO A GOOD JOB IN
EXPLAINING THE DIFFERENCES
IS THE SCHOOL EXPERIENCE OF
THE BLACK-WHITE DISPARITIES
WERE DIFFERENT.
BEFORE 1954, THE JIM CROW
SCHOOL SEGREGATION LEADING
TO LARGE INEQUITIES IN
EDUCATIONAL RESOURCES
PARTICULARLY AS IT RELATE TO
TERM LENGTH AND THE
INFRASTRUCTURE BETWEEN
SCHOOLS.
ONLY 50 PERCENT OF THE
ADULTS WHO ATTENDED SCHOOL
BEFORE 1954 TO TERM AND
YEARS OF EDUCATION MAY NOT
ACCURATELY MEASURE QUANTITY
OF SCHOOLING.
SO THESE TWO BOXES SUGGEST
1920 TO 1954 IN SEGREGATED
SCHOOLS AND YOU CAN SEE HERE
THERE IS SIGNIFICANT STATE
VARIATION FOR TERM LENGTH
AND BOTH BLACK AND WHITE
SEGREGATED SCHOOLS.
FOR EXAMPLE, THE TERM LENGTH
FOR SOUTH CAROLINA HAD A
LULL OF 0 DAYS IN 1920 AND
NEAR A HIGH OF 180 DAYS IN
THE PERIOD WHEREAS DELAWARE
ALWAYS HAD QUITE LONG SCHOOL
TERMS FOR BOTH THE BLACK AND
WHITE SEGREGATED SCHOOL
SYSTEM.
SO ALL OF THE BOX PLOTS ARE
SCANNED FROM THE TERM LENGTH
OVER THE PERIOD AND HOW IT
CHANGED.
THESE PLOTS PROVIDE THAT
INFORMATION FOR THE SOUTH
ATLANTIC DIVISION TO
ILLUSTRATE THE GENERAL
TRENDS WHERE SCHOOL TERM
LENGTH WAS SHORTER AND THEN
LENGTHENED OVER TIME.
SO BY 1954, SEVEN HAD TERM
LENGTHS THAT WERE ABOUT 160
TO 180 DAYS AND THAT IS ON
PAR WITH THE TERM LENGTH OF
180 DAYS WE HAVE TAUGHT IN
THE UNITED STATES.
SO JUST BECAUSE STATES HAVE
A SET TERM LENGTH DOESN'T
MEAN STUDENTS WILL ATTEND
FOR THE FULL TERM.
SO THIS GRAPH SHOWS THE
PROPORTION OF A SCHOOL TERM
WITH BLACK STUDENTS SHOWN IN
AQUA COLOR AND WHITE
STUDENTS SHOWN IN PURPLE ON
AVERAGE ATTENDED BY STATE.
SO YOU CAN SEE THERE IS
SIGNIFICANT TIME AND STATE
VARIATIONS FOR BOTH BLACK
AND SEGREGATED SCHOOL
SYSTEMS.
BLACKS TYPICALLY ATTENDED
FEWER DAYS OF SCHOOL THAN
WHITES DID.
SO AGAIN WE WILL PICK ON
NORTH CAROLINA, VERY LARGE
IN 1920, NARROWED BY 1954
BUT WERE STILL PRESENT BUT
IF YOU COMPARE THAT TO
DELAWARE AND YOU CAN SEE THE
DIFFERENCE.
SO THE TRAJECTORY OF
COGNITIVE FUNCTION AND
MEASURING YEARS OF SCHOOLING
AND WE DID IN A
REPRESENTATIVE SAMPLE OF
BLACK AND WHITE OLDER ADULTS
WHO ATTENDED SCHOOL IN THE
JIM CROW SOUTH.
OUR FIRST STEP WAS TO
ADDRESS THE SAME WITH
EXTRACTING DATE TO IN THE
SCHOOL SYSTEMS INCLUDING THE
DISTRICT OF COLUMBIA.
THE STATEMENT WAS REPORTED
IN 1919 TO 1954 AND YOU CAN
SEE A PICTURE OF THE
HISTORICAL REPORT ON THE
SIDE.
SO THE MEASURED TERM LENGTH
AND AVERAGE DATES ATTENDED
BY STUDENTS, REPORTED
SEPARATELY BY SEGREGATED
SCHOOL SYSTEMS AND THEY
INCLUDED ALL PRIMARY AND
SECONDARY SCHOOLS IN THE
UNITED STATES.
THEN THE NATIONAL STUDY,
PROSPECTIVE STUDY OF ADULTS
OVER THE AGE OF 15 AND WE
LINKEDIN THIS TO HISTORICAL
DATA FROM THE HEALTH AND
RETIREMENT STUDY THAT ASKED
THE RESPONDENTS WHERE THEY
LIVED WHEN THEY WERE IN
SCHOOL OR AROUND AGE 10.
SO ONCE WE LINKED OUR DATA,
WE COMPARED SAMPLES TO BLACK
AND WHITE RESPONDENTS, THEY
STARTED PRIMARY SCHOOL IN OR
AROUND 1919, COMPLETED A
PRIMARY OR SECONDARY SCHOOL
BY 1954 AND HAD AT LEAST ONE
COGNITIVE FUNCTION.
SO OUR FINAL ANALYSIS
INCLUDED4300 ADULTS WITH
16,000 SEG DATED ADULTS.
SO TO ADDRESS OUR AIM, WE
DID TWO APPLICATIONS TO SEE
WHY WHICH THE COGNITIVE
FUNCTION WAS EXPLAINED FOR
EACH MEASURE.
THE HISTORICAL DATA ONLY
REPORTED SCHOOL LENGTH AND
ATTENDANCE FOR PRIMARY AND
SECONDARY SCHOOLING BUT TO
ACCOUNT FOR ANY DIFFERENCE
IN POST SECONDARY SCHOOL, WE
HAD AN INDICATOR OF
COGNITIVE FUNCTION.
SO THEN TAKEN ACROSS THE
YEARS OUR RESPONDENTS WERE
FINISHING SCHOOL, HOW MANY
YEARS THEY COMPLETED, THE
STATE THEY WERE BORN ON AND
THEIR SELF-REPORTED RACE.
SO WHEN USING THE SCHOOL
MEASURE, BOTH BLACK AND
WHITE OLDER ADULTS SPENT
FEWER YEARS IN SCHOOL THAN
SUGGESTED.
SO THIS WAS TWO AND A HALF
YEARS OF SCHOOL BY BLACK AND
WHITE ADULTS PROSPECTIVELY
ON THE SCHOOL MEASURES.
SO THEN WE ESTIMATE THE
COGNITIVE TRAJECTORIES,
ADJUST FOR A NUMBER OF
COVARIANTS WHICH YOU CAN SEE
AT THE BOTTOM OF THE SLIDE.
THIS AVERAGE ADJUSTED
PREDICTED VALUES ACROSS AGE
FOR BLACK OLDER AND WHITE
OLDER ADULTS SO I WILL USE
THE AGE OF 95 JUST FOR
COMPARISON BUT IT IS
IMPORTANT TO NOTE THE RATE
OF DECLINE DID NOT VARY BY
RATE.
SO HERE YOU SEE THE BLACK
DISPARITY IS 3.5 POINTS ON
THE COGNITIVE FUNCTION SCALE
BUT ONCE WE INCLUDE IN OUR
MODELS, THE SCHOOL MEASURE
AND THE DEGREE ATTAINMENT,
THE DISPARITY REDUCES TO 2.3
POINTS.
SO THE ADDITIONAL EDUCATION
EXPLAINED 34 PERCENT OF THE
RACE DISPARITY.
ALSO THAT THE ADJUSTMENT
ALMOST ENTIRELY OCCURS
BECAUSE THE COGNITIVE
FUNCTION IS OF WHITE VERSUS
BLACK IS BECAUSE OF LOWER
EDUCATIONAL ATTAINMENT.
SO WE VIEWED THAT ON THE
MODEL AND OUR SCHOOL MEASURE
THAT ACCOUNTS FOR THESE
DIFFERENCES IN SCHOOL TERM
LENGTHS ACROSS STATES, TIME
AND SEGREGATED SCHOOL
SYSTEMS.
NOW THESE MODELS OF
DISPARITY SHOWED 1.76
POINTS.
SO DISPARITY IN SCHOOL WITH 39
PERCENT BETWEEN BLACK AND
WHITE STATUS.
SO IN COMPARISON, THE SCHOOL
MEASURE EXPLAINS 57 PERCENT
AND 80 PERCENT IN THE BLACK
WHITE MEASURES EFFECTIVELY.
SO OUR TRADITIONAL RESEARCH
FOUND THE MEASURE OF
EDUCATION ONLY EXPLAINS
ABOUT A THIRD OF THE BLACK
WHITE DISPARITIES AND THIS
IS DUE IN PART BECAUSE
TRADITIONAL EDUCATION DOES
NOT ACCOUNT FOR THE
TRADITIONAL DISPARITIES AS
IT WAS IN THE JIM CROW
SOUTH.
THE DURATION IN SCHOOL MAY
BETTER CAPTURE THE TIME
SPENT DEVELOPING THOSE
SKILLS THAT BUILD COGNITIVE
RESERVE.
SO WHAT HAPPENED TO SCHOOLS
AFTER 1954?
THE YEAR THE SUPREME COURT
DECLARED IN BROWN VERSUS
BOARD OF EDUCATION THAT
SEPARATE AND UNEQUAL SCHOOLS
WERE ILLEGAL.
BECAUSE THEY DID NOT DEFINE
THE DELAY, IT RESULTED IN
THE VARIATION IN THE TIMING
OFY SEGREGATION EFFORTS IN
THE SOUTHERN UNITED STATES.
SO I ADJUSTED THIS FOR ANY
WHITE STUDENTS BETWEEN 1955
AND 1974 AND AS YOU CAN SEE,
ONLY A FEW STATES BEGAN
INTEGRATING DESEGREGATED
SCHOOLS IN THE 1950S.
MOST FROM FEDERAL PROGRAMS
THAT PREVENTED SCHOOLS FROM
DISCRIMINATING ON THE BASIS
OF COLOR.
SO THE DESEGREGATION EFFORTS
IN THE SOUTH AND THAT AFTER
TO DETERMINE WHETHER IT WAS
ASSOCIATED WITH MIDLIFE
COGNITIVE HEALTH DIFFERENCE
BY RACE IN THIS PERIOD.
OUR STUDY WAS FROM A SMALL
NUMBER OF SCHOOLS WITH
MEASURES OF COGNITIVE
FUNCTION AMONG BLACK OLDER
ADULTS.
THIS WORK HAS BEEN CONDUCTED
ON SMALL COMMUNITY SAMPLES
WITH GENERALIZABILITY AND
ALL OF THEM ON REPORTED
COGNITION.
SO LOOKING AT THE FUNCTION,
THERE IS A DIFFERENCE OF 1.
11 WITH BLACK AND FOUND NONE
FOR WHITE ADULTS AND THIS
WAS CONSISTENT WITH SOME OF
THE LITERATURE THAT FOUND NO
DIFFERENCE IN ECONOMIC
FACTORS BETWEEN THESE BLACK
AND WHITE ADULTS.
OTHER STUDY SHOWED THE
TIMING OF THE DESEGREGATED
EXCUSED AN EFFECT ON MEMORY,
AND THIS GRAPH SHOWS THE
BLACK ADULTS WITH
DESEGREGATED SCHOOLS VERSUS
ADULTS WHO NEVER ATTENDED
DESEGREGATED SCHOOLS.
THIS WAS ONLY FOR ELEMENTARY
SO THEY DIDN'T ASSIGN THIS
FOR MIDDLE OR HIGH SCHOOLS.
SO WE EXTRACTED
ADMINISTRATIVE AND
HISTORICAL DATA FROM THIS
OTHER REPORT ON EDUCATION
ABSTRACT TO ADDRESS THE
STATE LEVELS IN 16 STATES
EXCLUDING STRICT OF COLUMBIA
AND MEASURING THE PERCENT OF
BLACK STUDENTS ATTENDING
SCHOOLS WITH WHITE STUDENTS.
SO TO DEFINE THAT BY YEAR OF
SCHOOL ENTRY AND COHORT AND
SELECTED SOUTHERN STATES.
SO THE STATE LEVEL ESTIMATE
CAN REVEAL THE DESEGREGATED
SCHOOLS AND MEMORY.
SO A SCHOOL WHERE THERE WERE
NO DESEGREGATED SCHOOLS TO
WHERE HUNDREDS OF STUDENTS
WERE ATTENDING DESEGREGATED
SCHOOLS.
THE LINE REPRESENTS THE
COHORT ON THE X AXIS AT THE
AGE THE STUDENT WOULD HAVE
ATTENDED THE DESEGREGATED
SCHOOLS AND YOU CAN SEE IN
MARYLAND, THEY WERE EXPECTED
TO SPEND ONE OR TWO YEARS IN
DESEGREGATED SCHOOLS BUT IN
ALABAMA AND NORTH CAROLINA,
STUDENTS IN THAT COHORT
WOULD BE EXPECTED TO SPEND
TEN YEARS OF SCHOOLING IN
DESEGREGATED SCHOOLS BUT
THEY WERE MUCH MORE LIKELY
TO ATTEND DESEGREGATED
SCHOOLS BUT OF COURSE THIS
ALSO VARIED BY STATE.
SO NEXT, LOOKING AT THE
DATA, WITH THE CURRENT
STUDY, LOOKED AT SAMPLES
BETWEEN BLACK AND WHITE
ADULTS ATTENDING PRIMARY
SCHOOL IN THE U.S. SOUTH
BETWEEN 1954 TO 1974, GIVEN
THE EFFECT ON COGNITIVE
FUNCTION AND EPISODIC MEMORY
AND WE FOUND THE EXPOSURE TO
THE DESEGREGATED SCHOOL WAS
ASSOCIATED WITH HIGHER
SCORES AND EPISODIC FUNCTION
BY 2.5 POINTS.
FOR BLACK ADULTS WITH FIVE
YEARS OF EXPECTED COMPOSURE
TO DESEGREGATED SCHOOLS FOR
TEN YEARS, BUT WE DIDN'T
FIND ANY RELATIONSHIP FOR
MENTAL STATUS.
SO PROJECTED RESULTS WITHIN
POPULATIONS AND ANALYSIS IS
CRITICAL FOR UNDERSTANDING
PATHWAYS.
HERE THE DESEGREGATION DATA
AND AND IMPORTANCE OF USING
SUCH INFORMED MEASURES AND
REPRESENTATIVE SAMPLES SHOW
THAT PATHWAYS TO COGNITIVE
HEALTH LIKELY VARY FOR U.S.
POPULATIONS.
NOT ONLY IS THERE AN
IMPORTANCE OF HISTORICALLY
LINKING BLACK ADULTS WITH
EXPERIENCES BUT ALSO HOW
THEY SHAPED THEIR COGNITIVE
HEALTH.
AND THEN JUST TO CLOSE, IF
YOU ARE INTERESTED IN SOME
OF THESE QUESTIONS RELATED
TO DEMENTIA, THE NIH IS NOW
PROVIDING FUNDING ON THE
PATHWAYS AND TKPHAEPBT SHAIN
DIVERSE POPULATIONS AND YOU
WOULD LIKE TO GET INVOLVED,
GO TO THE WEBSITE OR SCAN
THE QR CODE AND YOU CAN SIGN
UP TO BE INVOLVED THERE.
THANK YOU.
>> THANK YOU, KATRINA, I
KNOW YOU ARE JOINING US VIA
ZOOM.
I AM SO EXCITED ABOUT THIS
DISCUSSION SESSION.
I HOPE ALL OF YOU HAVE BEEN
WRITING DOWN YOUR QUESTIONS
AND YOUR COMMENTS.
IT REALLY IS HISTORICAL TO
HAVE A SESSION LIKE THIS AT
THE COGNITIVE AGING SUMMIT
AND I JUST WANT TO THANK --
TAKE A MINUTE TO THANK ALL
THE SPEAKERS FOR ALL OF YOUR
WORK.
WE HAVE BEEN ON ZOOM A FEW
TIMES BEFORE THE MEETING,
PREPARING FOR THIS, SO I
THOUGHT YOUR TALKS WERE
INCREDIBLE AND REALLY JUST
INSPIRING FOR ME PERSONALLY
AS WELL.
SO JON, ARE YOU AT THE MIC?
OKAY, YOU WANT TO --
>> THANK YOU FOR ASKING.
MIC IS EVEN ON, YES.
JUST ONE BRIEF COMMENT.
I HATE TO DISAPPOINT AJ BUT
NOT EVERYBODY KNOWS ABOUT
THE HEALTH AND RETIREMENT
STUDY.
PROBABLY MORE PEOPLE WILL
KNOW ABOUT IT AFTER THIS
SESSION THAN BEFORE BY A LOT
BUT WANT TO POINT OUT IN
ADDITION TO THE RETIREMENT
AND HEALTH STUDY AND THE
BILINGUAL STUDY THAT MIGUEL
MENTIONED, I CAN TELL YOU
THERE IS A LOT MORE THERE
THAN YOU HEARD ABOUT TODAY
AND I WOULD BE HAPPY TO
DISCUSS THAT WITH YOU.
>> AND LET ME TAKE CREDIT
AND BLAME FOR AJ NOT GOING
MORE IN DEPTH WITH THE HR
STUDY.
EVERYONE WILL KNOW A LOT
MORE ABOUT IT NOW SO I WILL
CALL ON PEOPLE AND YOU CAN
ASK YOUR QUESTIONS ON YOUR
MIND.
>> GREAT DISCUSSION AND I
JUST WANTED TO PARTICULARLY
TALK ABOUT AJ.
WHEN I WAS AT THE CLINIC, WE
WROTE HOW TO IMPROVE THE
UNDER REPRESENTED MINORITY
STUDENTS AND WE -- ONE OF
THE HE COULD FACTORS, WE
ASEM WITH BUILD WHAT WAS A
REVIEW OF THE SOCIETY PAPER
BY DUSTA AND IT WAS QUITE
STRIKING.
AT ONE POINT FOR A LONG TIME
IN THE UNITED STATES, IT WAS
ILLEGAL TO EDUCATE THE BASIC
LITERACY TO A BLACK PERSON.
I DON'T REMEMBER FOR HOW
LONG THAT DURATION WAS.
SO LOOKING AT THAT AND SOME
OF THE DIFFERENCES IMPACTING
THE PRESENTATIONS FROM
UNIVERSITY OF MICHIGAN, AND
MINORITY GROUPS THAT COULD
BE LINKED TO THAT TYPE OF
EXPOSURE, CERTAINLY KEY
LATER ON WHEN WE WERE
LOOKING AT THIS SO CAN YOU
COMMENT ON THAT?
>> THANK YOU, SEE, I DIDN'T
KNOW.
SO I HAVE TO DISCLOSE MY
BIAS THAT I TEND TO NOT
THINK OF EDUCATION IN THIS,
IS WHERE I TEND TO DIFFER
FROM A LOT OF COGNITIVE
RESEARCHERS.
I AM OF THE BELIEF THAT WHAT
EDUCATION PROVIDED OVER
HISTORY WAS ACCESS TO GOOD
PAYING JOBS AND ACCESS TO
RESOURCES TO THOSE GOOD
PAYING JOBS LIKE HEALTHCARE,
HEALTH INSURANCE,
RETIREMENT, SO ON AND SO
FORTH SO I ACTUALLY DO NOT
HAVE THE BELIEF THAT HOWEVER
LONG YOU WERE IN SCHOOL OR
WHAT KIND OF TRAINING YOU
PROVIDED IS PROTECTIVE
AGAINST DEMENTIA OR
COGNITIVE DECLINE.
BUT KATRINA WOULD BE SOMEONE
WHO DOES BELIEVE THAT AND
COULD SPEAK TO HOW A HISTORY
OF NOT HAVING ACCESS TO SOME
OF THIS CONTENT COULD THEN
INCREASE RISK FOR COGNITIVE
DECLINE BUT I WOULD ARGUE
THAT IT IS REALLY LACK OF
ACCESS TO COMPLETION OF HIGH
SCHOOL DIPLOMAS, DEGREES
THAT IS REALLY DETRIMENTAL
TO COGNITIVE HEALTH.
>> KATRINA, DO YOU WANT TO
ADD?
>> SURE.
SO I THINK THAT ONE OF THE
THINGS TO CONSIDER ABOUT
EDUCATION AND IS TIMING IN
SOME WAYS, I ALSO AGREE WITH
AJ THAT ACCESS TO RESOURCES
IS PROBABLY ONE OF THE KEY
PATHWAYS WHEN LOOKING AT THE
SOCIAL DETERMINANTS OF
COGNITIVE FUNCTION LATER IN
LIFE.
I THINK EXPOSURE TO HIGH
QUALITY EDUCATION REALLY
MATTERS TO EARLY BRAIN
DEVELOPMENT AND COGNITIVE
DEVELOPMENT THAT CAN SET THE
STAGE FOR ALL THOSE OTHER
THINGS THAT APPLY TO LATER
LIFE.
SO I WOULD SAY THAT SOME OF
THE WORK I HAVE DONE HAS
SHOWN SOME OF THESE
INEQUITIES, INSTITUTIONIZED
INEQUITIES MATTER AND COULD
HELP TO EXPLAIN SOME OF THE
INEQUITIES WE DO DOCUMENT
AMONG THE COHORTS OF OLDER
ADULTS.
>> OKAY, THANKS.
THIS IS A VERY INTERESTING
SESSION.
ONE THING I AM GOING TO
INFER ABOUT THAT, MAYBE
MIGUEL ALLUDED TO IT BUT IT
DIDN'T COME UP MUCH, THE
MEASURES WE USE MADE WITH
CERTAIN DIVERSE POPULATIONS
IN MIND MAY NOT BE VALID TO
THE DIVERSE POPULATIONS
WE'RE LOOKING AT AND WHETHER
THAT IS ALSO THE SOLUTION TO
THE PROBLEM.
>> WONDERFUL QUESTION, THANK
YOU FOR BRINGING THAT UP AND
I DO THINK THE WORK I WAS
SHOWING FROM THE MECKS BOX
STUDY AND THE LOWER
COGNITIVE FUNCTION OF THE
INDIGENOUS, HOW DO WE KNOW
ABOUT THAT?
BOTH OF THOSE STUDIES HAVE
UNDERGONE RIGOROUS
EVALUATION BETWEEN ENGLISH
AND SPANISH OFFSPRING,
EVALUATING IN TERMS OF
MEASUREMENT AND IN INDIA IN
THE LAST STUDY, PARTICIPANTS
COULD BE EVALUATED IN 11 OR
12 DIFFERENT LANGUAGES AND
THE BATTERY WAS CAREFULLY
CONSTRUCTED TO BE USED IN
THOSE LANGUAGES AND IT SHOWS
VARIANCE EVEN ACROSS THAT
CATEGORY SO IT DOESN'T HOLD
THE SAME FOR ALL DOMAINS.
SOME OF THE DOMAINS WILL BE
MORE CULTURALLY IMPRACTICED
THAN OTHERS, ALTHOUGH NOT
ALL OF THEM ARE, WHAT
LANGUAGE COULD THEY BE
TESTED IN, WHAT IS THEIR
MOST COMFORTABLE LANGUAGE
AND HOW ARE THE TOOL VALID
FOR MEASURING WHAT WE WANT
TO MEASURE IN THIS
POPULATION.
>> I THINK YOU WERE IN LINE
BEFORE AND THEN I AM JUST
GOING TO GO AROUND SO GO
AHEAD WITH YOUR QUESTION.
>> THANK YOU FOR SUCH AN
AMAZING PANEL.
I AM AN AT APOLOGIST SO VERY
INTERESTING TO HEAR THE
SOCIAL DETERMINANTS AND
INEQUITIES BEING MENTIONED.
AT THE SAME TIME, I CAN'T
BELIEVE HOW MANY DECADES WE
HAVE BEEN TALKING AS SOCIAL
SCIENTISTS ABOUT THE
INEQUITIES IN HEALTH AND IT
IS NOT UNUSUAL TO HEAR ABOUT
THEM IN THIS AREA OF
COGNITIVE AGING.
I THINK WHAT I WOULD
CONSIDER DEEPER IS THE ROLE
OF INTERVENTION AND WHAT I
CONSIDER VALID
INTERVENTIONS, WOULD I WE
DON'T HAVE MORE
INTERVENTIONS AND WHY
CERTAIN MODELS, INTERVENTION
MAPPING AND SO MANY OTHER
PUBLIC HEALTH STUDENTS ARE
LEARNING IN THEIR
INTERVENTION CLASSES SAY AT
THE TIME OF DEVELOPING
INTERVENTIONS, STRUCTURAL
FACTORS ARE USUALLY NOT
CHANGEABLE SO AS PAUL SAID,
CHANGE IS ALSO A SOCIAL
CONSTRUCTION.
SO HOW DO WE GET TO THE
POINT WHERE WE ARE
DISCUSSING NEW INTERVENTION
MODELS AT THE STRUCTURAL
LEVEL, WHAT ROLE DOES NIH
AND OTHER FUNDING AGENCIES
HAVE IN TERMS OF PROVIDING A
WAY TO INTERVENE AT THE
STRUCTURAL LEVEL WITHOUT
SAYING WE ARE PRIMARILY
MODERATING AT THE MICRO
LEVEL OF INTERVENTION WHEN
WE HAVE DECADES AND DECADES
OF SCIENCE SHOWING SOCIAL
FACTORS ARE FUNDAMENTAL
CAUSES OF HEALTH.
SO AGAIN, NOT SURPRISING
THAT WE WOULD SEE IT IN THE
AREA OF COGNITIVE HEALTH.
SO ANY OF YOU -- I WAS
LOOKING TO Dr. JACKSON FOR
HELP ON THIS BUT ANY OF YOU
CAN CERTAINLY ANSWER THE
QUESTION.
THANK YOU.
>> SURE, SO MY MENTOR Dr.
DEREK GRIFFITH TALKS A LOT
ABOUT EXPANDING PRETTY
SIGNATURES MEDICINE BECAUSE
-- PREVENTION AND WHAT IF
YOU CONSIDERED THOSE FACTORS
AS PART OF THE MEDICINE?
WHAT IF YOU KNEW THIS WAS A
COUNTY THAT RACIALIZES BLACK
AND WHAT KIND OF
INTERVENTION WOULD YOU
TARGET FOR A PLACE LIKE
THAT?
HOW WOULD YOU TALK TO PEOPLE
IN CLINICAL SETTINGS ABOUT
THAT INSTEAD OF SAYING THE
RISK FACTOR IS THAT THEY ARE
BLACK, WHAT ABOUT THEIR RISK
FACTOR IS THEY LIVED IN A
CONTEXT WHICH THEY MIGHT
HAVE HAD TO FLEE BECAUSE A
FAMILY MEMBER WAS LUNCHED?
HOW CAN WE RECONFIGURE OUR
YOU A SESMENT TO CAPTURE
THESE VARIABLES AND HOW WE
RECONFIGURE MEDICINE TO
TARGET THE DESTRUCTION SO
THEN WE CAN GET TO THE
INDIVIDUALIZED STUFF BUT WE
HAVE TO TACKLE FIRST THINGS
FIRST.
>> OTHERS WANT TO WEIGH IN?
I WILL SAY THAT, YOU KNOW,
WE HAVE HAD A NUMBER OF
NATURAL EXPERIMENTS THAT,
YOU KNOW, YOU HAVE SEEN SOME
OF THESE DATA PRESENTED JUST
NOW AND THERE IS MORE OUT
THERE THAT, YOU KNOW,
WEREN'T PRESENTED.
THESE ARE WAYS OF, YOU KNOW,
MODELING WHAT AN
INTERVENTION WOULD LOOK
LIKE.
THERE'S A REALLY GREAT
PAPER, FIRST AUTHOR, FOR
GETTING THEIR NAME BUT
PREPARED WHAT WOULD HAPPEN
USING THE DATA AS A
CLINICIAN ON BLACK AND WHITE
MORTALITY DIFFERENCES.
>> WAS THIS HEMMELSTEIN?
>> YES, LOOK IT UP, IT IS A
WONDERFUL PAPER.
SO WE HAVE THE OPPORTUNITY
TO TAKE ADVANTAGE OF SOME OF
THE POLICIES THAT HAVE
CHANGED ACROSS STATES AND
TIME BUT I AGREE AND THANK
YOU FOR THAT SORT OF
RALLYING COMMENT.
>> THANK YOU SO MUCH TO THIS
PANEL, WHICH ABSOLUTELY
BLOWS MY MIND.
THE SCIENCE IS CLEARLY
DEVELOPING BUT THERE ARE SO
MANY THINGS THAT YOU ARE
TALKING ABOUT THAT WE
UNDERSTAND SOME CULTURE
RELATING TO ECONOMIC ISSUES,
RELATING TO CULTURAL
FACTORS, AND SO EVEN THOUGH
YOU CAN'T FIX EVERYTHING
RIGHT NOW, IF I ASK EACH OF
YOU WHAT ARE THE PUBLIC
HEALTH RECOMMEND OCCASIONS,
-- RECOMMENDATIONS, YOU
WOULD PICK ONE THAT WE CAN
START WHAT TO DO?
>> WELL, ANYONE CAN START.
SHOULD I PICK ON KATRINA
SINCE YOU WERE LAST TO
SPEAK?
>> SURE.
I MEAN I AM IN A SCHOOL OF
PUBLIC POLICY AND I ALWAYS
THINK OF POLICY BUT ALL OF
THESE CAN CHANGE.
I AM DOING OTHER WORK OTHER
THAN THE WORK I PRESENTED
HERE IN EDUCATIONAL QUALITY
AND INVESTMENT IN SCHOOLS
AND I WOULD SAY ONE THING
THAT I WOULD ADVOCATE FOR IS
EQUAL ACCESS TO HIGH QUALITY
EDUCATION AS A KEY KIND OF
WAY TO PREVENT SOME OF THESE
LATER LIFE OUTCOMES.
IT IS NOT JUST -- I MEAN
WE'RE TALKING COGNITIVE
HEALTH HERE BUT IT ALSO IS
RELATED TO A LOT OF OTHER
HEALTH OUTCOMES THAT WE'RE
CONCERNED ABOUT TOO,
THINKING ABOUT POPULATION
HEALTH SO THAT WOULD BE MY
RECOMMENDATION.
>> MY RECOMMENDATION FROM MY
WORK IS THE SOCIAL
ECONOMICS.
THE THEME THAT I WAS
PRESENTING ON, THOSE MOST
ECONOMICALLY DISADVANTAGED
ARE DOING WORSE.
AND MAYBE INDIGENOUS
POPULATIONS AND INDIANS WERE
THE ONES THAT WERE WORSE
COMPARED TO EVERYBODY.
SO I THINK IMPROVING
EVERYONE'S ECONOMIC STATUS
AND THE OPPORTUNITY THAT CAN
COME WITH THAT, I THINK THAT
WOULD HELP BRING EVERYBODY'S
BRAIN HEALTH UP.
>> YEAH, I THINK I ANSWERED
THIS QUESTION AND I HAVE TO
THINK BOTH ABOUT WHAT IS THE
BIGGEST CONTRIBUTOR TO THESE
DISPARITIES AND THEN ALSO
WHAT IS MOST TRACTABLE AS AN
INTERVENTION TARGET SO WE
HAVE SEEN EDUCATION AND
ECONOMIC STATUS ARE THE
BIGGEST.
BUT THE FACTORS THAT EXIST
AT THE SCHOOL LEVEL IN TERMS
OF INVESTING IN COMMUNITIES
RATHER THAN INDIVIDUALS
WHICH MAY BE MORE DIFFICULT
TO LEGISLATE.
>> I COMPLETELY DISAGREE
WITH ALL THE SOCIOECONOMIC
STUFF AND HERE IS WHY.
THERE IS ROBUST LITERATURE
FROM WITHIN GROUP STUDIES
THAT SHOW BLACK MIDDLE CLASS
COMMUNITIES EXPERIENCE SOME
OF THE WORST OUTCOMES.
SO YOU WOULD THINK THAT THEY
ARE GOING TO PERFORM WELL IN
A LOT OF OUTCOMES BECAUSE
THEY HAVE "MADE IT".
BUT THE PRESSURE TO EVEN GET
TO THAT LEVEL OR STAY ON
THAT LEVEL IS SO EXTREME
THAT IT IS DELETERIOUS SO
THE BODY SO NOT SURE I WANT
WANT PEOPLE TO DO THAT.
I WOULD ADVOCATE TO
RESTORATIVE INTERVENTIONS.
WE DON'T KNOW IF HISTORICAL
LYNCHINGS ARE PICKING UP ON
FEAR, ANXIETY, TRAUMA,
PICKING UP ON SO MUCH SO
IMAGINE IN A RESTORATIVE
INTERVENTION WHAT IT WOULD
PROVIDE AND ALSO THAT
APOLOGY AND RECOGNITION THAT
YOU WERE NOT CRAZY, THAT YOU
WERE REALLY TAUNTED AND
TRAUMATIZED AND I WOULD
ADVOCATE FOR THAT.
>> I LOVE THAT YOU BROUGHT
UP THAT LITERATURE ABOUT
MIDDLE AND UPPER CLASS BLACK
OLDER ADULTS AND THERE IS
SUCH A RICH LITERATURE ON
THE DISCRIMINATION IN THOSE
GROUPS AND A LOT OF THAT IS
LINKED TO WORK AND
NEIGHBORHOOD ENVIRONMENTS.
SO I THINK ONE OF THE
CHALLENGES OF NEIGHBORHOODS
IS TO IDENTIFY THE COUNTER
FACTUAL, ARE WE TAKING
PEOPLE OUT OF ONE
NEIGHBORHOOD AND PUTTING
THEM IN ANOTHER NEIGHBORHOOD
AND I THINK THAT CAN LEAD TO
MORE STRESS.
I THINK IT IS MORE ABOUT
PUTTING RESOURCES INTO
NEIGHBORHOODS RATHER THAN
MOVING PEOPLE OUT OF THOSE
NEIGHBORHOODS WHICH MIGHT BE
A PROTECTIVE ENCLAVE.
IF THERE WAS NO DIFFERENCE
IN CURRENT NEIGHBORHOOD
ECONOMIC STATUS BETWEEN THE
GROUPS WHO HAD HIGH AND
THOSE WITH MODERATE AND
INCREASING AND THEY WERE THE
ONES DOING ALL THE WORK AND
DEVELOPING RESILIENCE.
SO PLUCKING THEM OUT OF
THOSE NEIGHBORHOODS IS NOT
THE ANSWER BUT MEETING
PEOPLE WHERE THEY ARE IS THE
BEST WAY IF WE WANT TO
INTERVENE ON SOCIOECONOMIC
STATUS.
JUST WANT TO ADD THAT.
>> THANK YOU FOR SUCH A
SPECTACULAR TALK.
THE QUESTION FOR ME IS OUT
OF CURIOSITY, SO I
UNDERSTAND THAT YOU LET THEM
TAKE THE TEST IN WHICHEVER
LANGUAGE THEY PREFER, RIGHT?
SO MY QUESTION IS DO YOU
THINK THERE IS VALUE ON
MAKING A TEST THAT HAS BOTH
LANGUAGES?
I MEAN SO WOULD IT BE
DIFFERENT BECAUSE THE GROUP
OBVIOUSLY THE IMMIGRANTS WHO
ARRIVED IN THE COUNTRY THE
FIRST TEN YEARS OF THEIR
LIFE, THEIR FIRST LANGUAGE
WOULD SWITCH AND I DON'T
KNOW IF THERE WAS ANY
THOUGHT TO THAT SO ANY WAY,
YOUR PERSPECTIVE ON THAT
WHICH COULD BE QUITE
DIFFERENT.
>> YES, THANK YOU SO MUCH
FOR THAT QUESTION.
YOU ARE MAKING THE POINT
THAT THERE COULD BE A CHANGE
IN LANGUAGE, SOMEONE COMING
TO THE U.S. WHERE SPANISH IS
DOMINANT AND THEN BECAUSE OF
CHANGES IN THE ENVIRONMENT,
THEY SPEAK IN ENGLISH AND I
EXPERIENCE THAT MYSELF, GO
BACK AND FORTH.
SO UNDERSTANDING THE TRUE
DOMINANCE AND HOW IT CHANGES
OVER TIME.
IN EVALUATING BOTH ENGLISH
AND SPANISH TOGETHER, I
THINK IT WILL DEPEND ON WHAT
WE'RE TRYING TO GET AT
BECAUSE WE DON'T WANT TO
TEST THEM IN A LANGUAGE THAT
IS HARDER FOR THEM.
THEN WE'RE NOT REALLY
MEASURING MEMORY, PERHAPS
BUT GETTING MORE PROFICIENCY
IN THAT OTHER LANGUAGE.
BUT THERE ARE SOME ASPECTS
HOW THEY RELATE TO BOTH
LANGUAGES.
THOSE AT GREATER RISK OF
DEVELOPING DEMENTIA OR
ALZHEIMER'S DISEASE, WE ARE
SEEING A DECLINE IN THE
SECOND LANGUAGE.
SO MAYBE NOT THE WHOLE
BATTERY IN LANGUAGES BUT
LOOK AT ASPECTS OF ABILITIES
OTHER THAN SELF-REPORT TO BE
DOCUMENTED OVER TIME TO SEE
HOW THEY CHANGE.
>> THANK YOU.
>> HI, DIANE FROM FOCUS
FOUNDATION.
I WOULD LOVE FOR YOU TO
MAYBE PARK SOME SPACE
DIFFERENCES BECAUSE I KNOW
STRUCTURAL AND SOCIETAL
DIFFERENCES BETWEEN MEN AND
WOMEN.
IN THE 1980S, I REMEMBER IN
MY ALGEBRA CLASS TELLING ME
NONE OF THE WOMEN CHOO
UNDERSTAND VECTORS BECAUSE
THEY COULDN'T THINK IN 3D
AND HE DIDN'T BELIEVE ME
WHEN I TOLD HIM I COULD
UNDERSTAND AND THAT WAS IN
THE 19 -- 1980S.
SO CAN YOU GIVE INFORMATION
TO MARS OUT -- TO PARSE
THAT OUT BECAUSE IT IS NOT
ALL ONE COMMUNITY.
>> WELL, SURE, AND MAYBE I
WILL NEED SOME HELP BECAUSE
I DON'T REALLY KNOW.
THERE ARE PEOPLE WHO LOOK AT
INTERSECTIONALITY IN THIS
GROUP AND SHOW RACIAL WOMEN
AS BLACK DO WORSE THAN
RACIALIZED WOMEN IN WHITE
BUT AN ADOLESCENT SURVEY
WHEN STRUCTURE AND RACE
ISN'T PART OF THE EQUATION,
BOYS OR MEN RACIALIZET AS
BLACKS DO WORSE AND I DON'T
KNOW WHAT TO MAKE OF THAT.
I DON'T UNDERSTAND IT FOR
THE LIFE OF ME AND QUITE
FRANKLY, I THINK I AM BIASED
BECAUSE I JUST REFUSE TO
ACCEPT IT AND KEEP LOOKING
AT IT.
BUT WE PUBLISHED BOTH OF
THOSE FINDINGS AND I DON'T
KNOW WHO TO THINK ABOUT IT.
SO THE NEXT STAGE IS TO
SPECIFICALLY LOOK AT THE
RACIALIZED EXPERIENCES OF
BLACK MEN AND BOYS TO FIGURE
OUT WHAT IS GOING ON THERE
BECAUSE IT IS WEIRD.
>> I LOOK FORWARD TO THAT
RESEARCH.
>> YEAH, I WILL TAKE THE
OPPORTUNITY TO HIGHLIGHT
SOME WORK OF A GRADUATE
STUDENT IN MY LAB, KIONA
STANBURG WHO IS INTERESTED
IN THE INTERSECTIONALITY.
SHE HAD LOOKED AT RESILIENCE
TO COGGIZATION AND SOME
INTERESTING THINGS THAT CAME
OUT OF THAT IS IT SEEMED
BLACK WOMEN BENEFITTED LESS
TO PSYCHO RESILIENCE AND
THAT MAKES US THINK ABOUT
THE TYPE OF COPPING PEOPLE
HAVE TO ENGAGE IN TO MANAGE
STRESS.
IT MAY BE EFFECTIVE IN SOME
WAYS BUT DELETERIOUS IN
OTHERS.
AND THOSE DOING WORSE WERE
THE BLACK MEN AND WE THOUGHT
ABOUT WHAT TYPE OF STRESSES,
BOTH RACIALLY AND PATTERNED
BY GENDER AND I THINK AJ'S
FRAMEWORK OF MATH AND
INCARCERATION, WHAT WE SEE
IS LOWER SOCIOECONOMIC
OUTCOMES OF THE MEN IN OUR
SAMPLE ECONOMY PAIRED TO
THAT OF WOMEN AND I THINK
THAT MAY BE RELATED TO
WORKING IN THAT SPACE SO
WHEN WE FIND DISASSOCIATIVE
FINDINGS, THAT HAS US
LOOKING AT WHAT IS GOING ON,
IS IT DIFFERENT STRESSO RS
OR COPING SKILLS.
>> I WANT TO GIVE A SHOUT
OUT TO ONE OF MY COME-UPPERS
AS WELL, HENDERSON WHO HAD A
PAPER AT U.S. F A FEW YEARS
AGO BUT LOOKING AT THE
PAPERS OF INTERSECTIONALITY
AND RELIGIOUS PARTICIPATION
AND IF I RECALL CORRECTLY,
THAT WAS PROTECTIVELY BOUND
FOR BLACK MIDLIFE OLDER
ADULT WOMEN BUT IN TERMS OF
THE COGNITIVE FUNCTION, YOU
CAN'T REALLY FIND THOSE
EFFECTS WITHIN MEN AND FOUND
THE OPPOSITE FOR WHITE MEN
AND WOMEN.
SO MORE PARTICIPATION AND
MORE OFFERING WAS ASSOCIATED
WITH THE CORE FUNCTION OF
WHITE MEN AND WOMEN.
SO I THINK THAT MIGHT TAP
INTO WHAT LAURA WAS SAYING
IN TERMS OF RESILIENCE, WHAT
THE ASPECTS ARE THAT MAKE
PEOPLE MORE RESILIENT AND
NOT RESILIENT.
>> CAN I JUST ADD TO THIS?
I THINK THIS MIGHT BE A
PRIME OPPORTUNITY FOR
LOOKING AT CRITICAL PERIODS
OF EXPOSURE BECAUSE THINKING
ABOUT THE FIRST PANEL AND
THE TOPIC ON MENOPAUSE AND
PREGNANCY, I MEAN, NASA IN
THE 1990S TOOK AWAY THE
INDIGENOUS FARMS IN MEXICO
AND PUT THEM IN THE
SITUATION WHERE THEY HAD TO
MIGRATE AND THESE MAY HAVE
BEEN INDIVIDUALS WHO WERE
PREGNANT, HAD CHILDREN, WHAT
IS THE IMPACT AT THAT
CRITICAL TIME IN WOMEN AND
DID IT RESOLVE LATER SO THIS
MIGHT BE A RIPE OPPORTUNITY.
>> AND I THINK IT IS VERY
INTERESTING THEY HAD THAT
DUTCH WINTER HUNGER FROM
WORLD WAR II SO THAT MAY BE
ANOTHER ONE.
>> THANK YOU FOR THAT FOR
ALL OF US TO CONSIDER
INTERSECTIONALITY IN OUR
WORK, WE SHOULD KNOW WHAT IT
IS AND THE PRINCIPLES OF IT
>> THANK YOU AGAIN FOR THE
DISCUSSION, I FEEL THE
EXCITEMENT.
I HAVE SO MANY QUESTIONS BUT
I WILL GIVE MY TIME TO MAYBE
BRING THE SPOTLIGHT BACK TO
THIS POINT ABOUT
INTERVENTION.
IF YOU HAD TO PICK A SINGLE
BARRIER TO BE ADDRESSED AND
DEVELOPED MORE INTERVENTION,
WHAT WOULD THAT BE, IS IT
MEASURES, FUNDING, GETTING
MORE PEOPLE IN THE PIPELINE
TO DO THIS KIND OF WORK?
>> I WOULD PROBABLY LIKE TO
SEE TAILORED INTERVENTIONS
TO SPOT LIGHTED PLACES THAT
CAN BE REPRESENTATIVE.
SO FOR EXAMPLE, IF THERE IS
A CITY THAT HAS A HISTORIC
RELATIONSHIP TO A STRUCTURAL
RACISM, THEN WE MIGHT WANT
TO SEE A TARGETED
INTERVENTION IN A CITY LIKE
THAT THAT OTHER CITIES COULD
THEN MODEL THEMSELVES AFTER.
SO WE WOULD NEED TO HAVE THE
KIND OF FUNDING THAT WOULD
ALLOW FOR MULTIPLE COMMUNITY
PARTNERSHIPS AND MULTIPLE
SECTORS TO ILLUSTRATE THAT
KIND OF STUFF.
I AM A CYCLE STATISTICIAN
AND I TAKE DISPLEASURE AT
INSTRUMENTS BECAUSE IT TAKES
SO MUCH TIME BUT I KNOW SOME
ON THE PANEL MAY WANT TO
WEIGH IN.
>> I THINK ONE BARRIER TO
REACHING OUT TO COMMUNITIES,
DO MORE COMMUNITY ENGAGED
RESEARCH.
I THINK MOST OF THE
PARTICIPANTS IN THE STUDIES
ARE NOT REPRESENTATIVE OF
THE POPULATION.
I THINK IT CAN BE HARD TO DO
COMMUNITY ENGAGED WORK.
IT IS OFTEN MORE EXPENSIVE
AND TIME CONSUMING AND SO WE
DO NEED MORE FUNDING AND IF
YOU CAN LOOK WHERE FUNDING
GOES, THESE STUDIES ARE
UNDERFUNDED COMPARED TO MORE
CLINICALLY BASED TRIALS.
SO WE NEED FUNDING IN ORDER
TO DO THIS SPECIALTY TYPE OF
STUDIES THAT WILL ALLOW US
TO HAVE REPRESENTATIVE
SAMPLES FOR THE STUDIES.
>> WE PLAN ON HIGHLIGHTING
MANY OF THE THINGS YOU
MENTIONED IN THIS
CONFERENCE.
>> SO LUKE FROM MIA, IS THIS
ON?
>> YEAH.
>> GREAT, SO I WROTE MINE
DOWN BECAUSE I DON'T WANT TO
GO OFF SCRIPT HERE.
I ALSO WEAR A HAT AS A
CLINICAL NEUROPSYCHOLOGIST
AS JENN KNOWS AND MY
QUESTION WILL COME FROM THE
TRADITIONAL NEUROPSYCH
CLINIC WHERE PEOPLE ARE
EVALUATED AT WHATEVER POINT
THEY ARE EVALUATED AT RIGHT
NOW.
SO WE OFTEN DON'T KNOW A
PERSON'S BASELINE OR
SO-CALLED PREMORBID
COGNITIVE FUNCTION AND IN
THINGS LIKE EDUCATION, WE
OFTEN USE A LANGUAGE BASED
INDICATION LIKE VOCABULARY
WHICH SOMETIMES WOULD LEAVE
BEHIND NONVERBAL MEASURES
THAT ARE THOUGHT THOUGH HAVE
LESS SENSITIVITY TO
VARIABILITY AND
SOCIOCULTURAL INFLUENCES
WHICH WE KNOW IS NOT TRUE
BUT HISTORICALLY WHAT PEOPLE
HAVE THOUGHT.
SO IN LIGHT OF THESE TALKS
AND BASED ON INFORMATION
EARLIER, HOW SHOULD WE
RETHINK HOW WE ASSESS
PRE-MORBID FUNCTION IN THE
CLINICAL ASSESSMENT.
AND THEN THE FOLLOW UP WOULD
BE HOW DO WE GET INTO A
10-MINUTE ASSESSMENT WHICH
EVERYONE IN A PRIMARY CARE
CENTER IS TRYING TO GET TO
NOW.
>> MIGUEL, YOU WANT TO TRY
THAT?
>> WELL, I CAN TRY.
AS A CLINICAL PSYCHOLOGIST,
I UNDERSTAND THE STRUGGLE
WITH THAT.
I THINK, YOU KNOW, WHAT YOU
WERE MENTIONING, LIKE
WORKING WITH SPANISH
SPEAKING COMMUNITIES, LIKE
THERE IS NO GOOD MEASURE OF
PREMORBID FUNCTION, RIGHT,
AND I THINK IT REALLY
DEPENDS ON WHAT WE'RE TRYING
TO GET AT WITH THAT.
I WOULD SAY FOR ME, TO
CONTINUE TO ADVOCATE FOR THE
STANDARD WITH THE POPULATION
WE'RE WORKING WITH, RIGHT?
BECAUSE NORMALLY WE NEED THE
PREMORBID TEST, THE
PRECLINICAL DATA, ALL OF
THOSE SAMPLES ARE BIASED AND
OFTENTIMES WHAT WE USE IN
THE CLINIC SAMPLE WITH
OUTDATED, REALLY OLD,
PRIMARILY REPRESENTING
ENGLISH SPEAKING OR MONO
LINGUAL INDIVIDUALS AND
REALLY PEOPLE SHOULD VALUE
THE COMMUNITY IN TERMS OF
THE CLINICAL SETTING AND HOW
TO LEVERAGE THE OTHER
STUDIES TO HELP WITH THAT,
CONDUCT OTHER RESEARCH TO
HELP WITH THE PREMORBID
DIAGNOSIS.
WE MAY NOT CARE ABOUT THAT
AS LONG AS WE GET A GOOD
CLINICAL HISTORY AND THAT IS
MY TAKE ON THAT.
>> I AM GOING TO MOVE
FORWARD BECAUSE PEOPLE HAVE
BEEN STANDING FOR QUITE
SOMETIME, ROBERTA, YOU ARE
NEXT.
>> DOCTOR WAL SEMANN, YOU
BROUGHT UP THIS IMPACT OF
HISTORICAL RACE LYNCHING AND
LIKE HOW COULD YOU ASSESS
THAT.
IT TURNS OUT THE EPIGENETIC
POTENTIAL TO TRACK THAT
IMPACT, ANY THOUGHT?
>> YEAH, WHEN WE DID THE
SDS PAPER FOR EXAMPLE, WHAT
WAS INTERESTING ABOUT THAT
IS WE HAD THREE DIFFERENT
PREDOMINANT SORT OF THOUGHTS
ON THIS AND WERE LIKE NO,
THIS IS IN UTERO EXPOSURE
AND THEN OTHERS WERE NO, IT
IS EPIGENETIC AND I HAVE THE
EXPOSURE THAT BOTH EXIST.
I WOULD LIKE TO TEST AT
EXPOSURE BUT I THINK IT IS
MORE COST EFFECTIVE TO
DETERMINE IF THE POLICY IS A
FEATURE IN A GENERATION AND
IF THAT IS NOT THE CASE,
THEN LOOKING IF THIS IS
EPIGENETIC BUT TEASING APART
THAT IS DIFFICULT.
>> WELL, WE DON'T HAVE THE
FUNDS TO DO THAT --
>> HOLLER AT ME AND WE CAN
MAKE THIS HAPPEN.
I AM VERY COLLABORATIVE.
>> THANK YOU SO MUCH FOR
YOUR TALKS AND --
[INAUDIBLE] -- AND I KNOW
HOW DIFFICULT IT IS TO
RECRUIT INDIGENOUS AND SO MY
QUESTION IS HOW WOULD YOU
ADVISE TO APPROACH OR
DEVELOP THE STRUCTURES FOR
INCLUSION OR RECRUITMENT FOR
STUDIES BECAUSE THIS HAS
OCCURRED AND RECRUITMENT IN
THE MINORITY POPULATION IS A
BIG PROBLEM.
>> YOU WANT TO WEIGH IN?
>> YEAH, I WAS JUST GOING TO
SAY DON'T RECRUIT FROM A
CLINIC.
YEAH.
[LAUGHTER]
SO GO INTO A COMMUNITY.
THAT IS THE BEST ADVICE
THERE.
YOU KNOW, FOR THESE
BETWEEN-GROUP STUDIES, IT IS
NOT ALWAYS THE PARTS TO
RECRUIT THE MINOR
POPULATIONS BUT WE'RE KIND
OF LAZY IN RECRUITING THE
WHITE POPULATIONS.
WE GO INTO A COMMUNITY WITH
BLACK RECRUITS AND THEN
COMPARE THEM TO PEOPLE IN
THE CLINIC SO IF WE WANT
BETTER RERECRUITMENT AND
SAMPLES FOR CAUSATIVE
EFFORTS, WE HAVE TO THINKING
ABOUT SAMPLES FROM BOTH
COMPARISON GROUPS.
>> CAN I ADD TO THAT THAT SO
IF YOU THINK ABOUT THE
CLINICAL MODEL WHERE A
PERSON HAS A PROBLEM, THEY
COME IN, GET CLINICAL
INTERVENTION AND YOU ALSO
OFFER THEM THE OPPORTUNITY
TO PARTICIPATE IN A STUDY,
WOULDN'T YOU MAGNIFY THAT TO
THE STRUCTURAL LEVEL?
THAT WOULD MAGNIFY THE
DISTRUST PAUSE PEOPLE HAVE
GREATER DEMANDS GOING ON.
SO IF YOU COME IN AND TACKLE
ECONOMIC DISENFRANCHISEMENT
THROUGH A COMMUNITY THAT
ALSO HAS STRUCTURAL
IMPLICATIONS, YOU ARE
KILLING TWO BIRDS -- SUCH A
HORRIBLE EXPRESSION BUT YOU
CAN DO THIS OTHER THAN GOING
I NEED STUFF FROM YOU BUT
RATHER I CAN FIX THIS FOR
YOU AND MAYBE YOU CAN
PARTICIPATE IN A STUDY
>> WE HAVE TO END, THANK YOU
SO MUCH TO EVERYONE, THANK
YOU MOLLY, THANK YOU, JON,
FOR HAVING THE SESSION AND
WE'RE AROUND DURING LUNCH SO PLEASE IF YOU CAN FIND US,
COME ASK YOUR QUESTIONS.
>> ALL RIGHT.
I THINK WE ARE READY TO START.
I'M NOT CATHERINE KACZOROWSKI,
ALTHOUGH I ASPIRE TO BE.
I'M MOLLIE WAGSTE ARE THE
INTERNATIONAL SESSION ON AGING.
I WILL BE THE SESSION CHAIR.
UNFORTUNATELY CATHERINE
COULDN'T JOIN US THIS AFTERNOON
BUT SHE WILL BE PARTICIPATING
REMOTELY AND WILL BE WITH US
VIRTUALLY.
SO IT'S MY PLEASURE TO START
OFF THE FIRST SESSION OF THE
AFTERNOON.
THIS SESSION IS ENTITLED
GENETIC ENVIRONMENT.
AND OUR FIRST SPEAKER IS DR.
DENA DUBAL FROM THE UNIVERSITY
OF CALIFORNIA, SAN FRANCISCO.
AND THE TITLE HER TALK IS X
CHROMOSOME DERIVED MECHANISMS
IN COGNITIVE AGING.
[ APPLAUSE ]
>> Dena Dubal: THANK YOU TO THE
NIH AND IGNITE FOUNDATION,
MOLLY, JONATHAN, THE
ORGANIZERS, THE SPEAKERS, THE
AUDIENCE.
THIS HAS BEEN AN AMAZING
MEETING SO FAR AND I'M SO HONOR
TODAY BE AMONG YOU AND SHARE
OUR WORK IN X CHROMOSOME IN
COGNITIVE AGING.
WHY IS STUDYING SEX BIOLOGY
IMPORTANT?
BECAUSE EVERY CELL HAS A SEX.
AND SEX INFLUENCES FUNDAMENTAL
BIOLOGY THROUGH HORMONES AS WE
HEARD ABOUT EARLIER TODAY.
THROUGH THE DOSE OF THE X
CHROMOSOME.
FEMALE MAMMALS HAVE TWO X
CHROMOSOMES, MALE MAMMALS HAVE
AN X AND Y.
Y BIOLOGY AND MORE.
TRUE SEX DIFFERENCES EXIST IN
AGING.
FOR EXAMPLE, FEMALES LIVE
LONGER.
WE HEARD THIS MORNING A VERY
COMPELLING RATIONALE ABOUT WHY
IT'S IMPORTANT TO STUDY WOMEN'S
HEALTH.
IT'S ESSENTIAL TO OUR KNOWLEDGE
OF SEX BIOLOGY.
IT'S ESSENTIAL TO PRECISION
MEDICINE.
IT WILL BE THE FIRST FILTER,
MALE, FEMALE, GENDER SPECTRUM,
HOW DOES THIS AFFECT RISK FOR
DISEASE, RESPONSE TO TREATMENT,
AND FUNDAMENTAL BIOLOGY.
IMPORTANTLY, MORE THAN BEING
JUST INTERESTING, SEX
DIFFERENCES WILL MAKE US
UNDERSTAND IF ONE SEX IS MORE
RESILIENT OR VULNERABLE, THIS
UNRAVELS NEW PATHWAYS TO TARGET
WITH NOVEL TREATMENTS THAT
COULD BENEFIT MEN, WOMEN OR
BOTH.
THIS GRAPH IS ASTOUNDING.
FROM THE UNITED NATIONS, A
COUPLE OF YEARS AGO.
THIS RECORDS MORTALITY, ALL
ACROSS THE WORLD.
IN EVERY SOCIETY THAT RECORDS
MORTALITY WITH LIFE EXPECTANCY
OF WOMEN ON THE Y AXIS AND MEN
ON THE X AXIS.
WHAT YOU CAN SEE FROM SOMALIA
TO JAPAN IS WOMEN LIVE LONGER
ALL ACROSS THE WORLD.
REGARDLESS OF SOCIOECONOMIC
STATUS.
EVEN IN TIMES OF FAMINE, GIRLS
WILL LIVE LONGER THAN BOYS.
THERE IS A BIOLOGIC COMPONENT
TO THIS, ALSO BEHAVIORAL,
ENVIRONMENTAL, GENETIC
STRUCTURAL COMPONENT.
BUT ALSO SOMETHING VERY
BIOLOGIC.
IN PREVIOUS STUDIES WE SHOWED
MICE THAT GREW UP WITH XX
CHROMOSOMES REGARDLESS OF
HAVING OVARIES OR TESTES LIVE
LONGER THAN MICE THAT GROW UP
WITH XY CHROMOSOME COMPLEMENT.
WHAT ABOUT THE BRAIN?
WOMEN WILL SHOW LESS COGNITIVE
DECLINE OR INCREASED BASELINE
FUNCTIONS IN MANY POPULATIONS
OF CLINICALLY NORMAL ADULTS.
THE LIMITATIONS OF THESE
STUDIES, THEY ARE PREDOMINANTLY
WHITE.
THESE STUDIES LISTED
APPROXIMATELY 25% OF THE
POPULATIONS COLLECTIVELY WERE
BLACK INDIVIDUALS.
THIS IS AN AREA THAT REALLY
NEEDS TO BE WORKED ON AND
ADVANCED.
SO WOMEN WILL SHOW LESS
COGNITIVE AGING.
NOT TALKING ABOUT DEMENTIA BUT
NORMAL COGNITIVE AGING, WOMEN
WILL SHOW LESS COGNITIVE AGING,
SHOWN BY THE ORANGE LINE THERE,
COMPARED TO MEN.
SO THERE IS SOME RESILIENCE IN
THE BRAIN IN AGING.
IN CONTRAST, YOU WILL HEAR FROM
RACHEL BUCKLEY SOON, WOMEN ARE
ALSO VULNERABLE, WE HEARD THIS
FROM BOBBY BRENTON EARLIER,
GENETICS OF THE APOE E4 ALLELE.
WHAT ABOUT MICE?
DO THEY CAPITULATE SEX
DIFFERENCES IN HUMAN COGNITIVE
AGING.
MY COLLEGE FRIEND FRANCIS CA
DID AN ELEGANT STUDY.
SHE FOUND IN YOUNG MICE XX
COMPARED TO XY THERE WAS
EQUIVALENT COGNITIVE FUNCTIONS.
ABOVE ONE MEANS MEMORY
RETENTION.
IN AGING, AS EXPECTED, MALES
AND FEMALES DECLINED.
BUT SHE SAW SOMETHING VERY
INTERESTING IN THAT THE XX MICE
SHOWED RESILIENCE TO THE
COGNITIVE AGING COMPARED TO XY
MICE.
SIMILAR TO WHAT WE SEE IN SOME
HUMAN POPULATIONS.
SO IN A SUBSEQUENT STUDY I
WON'T SHOW YOU, WE DISSECTED
OUT EFFECTS OF GONADS AND X
CHROMOSOME, AND FOUND IT'S
MEDIATED BY BOTH GONADS AND SEX
CHROMOSOMES. BUT WE WERE SO
STRUCK BY THE EFFECT OF SEX
CHROMOSOMES, WHICH WAS VERY
LARGE, AND SIGNIFICANT THAT WE
DOVE RIGHT IN.
AND ASKED A QUESTION, IF SEX
CHROMOSOMES ARE CONTRIBUTING TO
RESILIENCE, THE XX COMPLEMENT,
IS IT THE SECOND X THAT IS
HELPFUL OR THE Y THAT IS
HARMFUL?
SHE USED AN XY STAR MODEL OF
SEX BIOLOGY, WHICH VARIES DOSES
OF THE X AND Y CHROMOSOME.
WHAT SHE FOUND IS MICE WITH TWO
X'S, SHOWED BETTER COGNITION IN
AGING ON THE LEFT.
COMPARED TO MICE WITH ONE X.
IT DIDN'T MATTER WHETHER THE
MOUSE WAS MALE OR FEMALE.
WHETHER THERE WAS THE PRESENCE
OR ABSENCE OF A Y.
THAT TWO X'S, IMPROVED
COGNITION IN MALE AND FEMALE
MICE GIVING US DATA THAT THE
SECOND X IS IMPORTANT.
ANOTHER GRADUATE STUDENT CAYCE
SHAW SHOWED WHETHER THERE WERE
CHANGES IN THE X CHROMOSOME IN
AGING MICE.
COMPARED TO ALL THE AUTOSOMES
THERE WERE MORE CHANGES IN
AGING ON THE X CHROMOSOME THAN
ANY OTHER CHROMOSOME.
NOW WHAT IS THE BIG DEAL ABOUT
THIS SECOND X?
AS YOU REMEMBER, IN OUR
DEVELOPMENT, IN FEMALE MAMMALS
ONE OF THE XS IS SHUT DOWN.
FEMALES HAVE ONE X AND MALES
HAVE ONE X.
WHY WOULD THAT SECOND X MATTER?
AS A WHOLE, WHEN WE STEP BACK,
THE X CHROMOSOME CONTAINS 5% OF
GENOME.
COGNITION RELATED GENES.
HISTORICALLY THE X CHROMOSOME
HAS BEEN, AS WELL AS THE Y,
BEEN SIPHONED AWAY IN
INFORMATIC STUDIES BECAUSE THEY
POSE TECHNICAL DIFFICULTIES
WITH DIFFERENT DOSAGES BETWEEN
MALES AND FEMALES.
BUT AS WE ENTER THIS ERA IT'S
AN EXCITING TIME TO DIG INTO
THE X.
THAT SECOND X INACTIVATES IN
FEMALE.
WHAT IS THE BIG DEAL?
WHY WOULD A SECOND X MATTER?
THERE ARE MANY REASONS WHY A
SECOND X COULD MATTER.
ONE, FOR EXAMPLE, BASELINE X
ESCAPE THAT WE PUBLISHED ON AND
RACHEL BUCKLEY IS WORKING ON IN
ALZHEIMER'S DISEASE.
THAT IS THAT SILENT X ISN'T SO
SILENT.
SOME GENES ESCAPE THAT
INACTIVATION.
SO FEMALES WILL HAVE MORE OF AN
X DOSE.
BUT TODAY I WILL TALK ABOUT
MIXED PARENT OF X ORIGIN.
IF YOU HAVEN'T DONE YOUR SUDOKU
OR WORDLE TODAY THIS IS A
CHANCE TO REALLY PUT YOUR
PUZZLE HAT ON AND THINK THROUGH
THIS.
SO WHY EXAMINE PARENT OF X
ORIGIN?
MEANING DOES MY X COME FROM MY
MOM OR DAD?
THAT IS PARENT OF X ORIGIN.
THIS IS DONE BY SAMIRA
ABDULAI-SAIKU.
THIS IS HER WORK.
PARENT OF X ORIGIN CONFIRMS
GENETIC AND EPIGENETIC
DIVERSITY AND CAUSE OF
HETEROGENEITY IN WOMEN.
BECAUSE IT'S RANDOM, 1X WILL BE
ACTIVE FOR MOM IN A CELL,
THAT'S ON THE LEFT.
BUT IN A NEIGHBORING CELL,
BECAUSE OF RANDOM X
INACTIVATION, THE X WILL BE
ACTIVE FROM DAD, THE PATERNAL X.
SIDE-BY-SIDE YOU MAY HAVE A
FEMALE CELL WITH MOM'S X ACTIVE
AND NEIGHBORING CELL WILL HAVE
DAD'S X ACTIVE.
THIS IS A PICTURE OF THE CA1
REGION OF MOUSE HIPPOCAMPUS
THERE'S A FLOUR RES ENS
LABELING THAT SHOWS MOM'S X IN
GREEN AND DAD'S X IN PINK.
LOOK AT THE MOSAICKISM,
BEAUTIFUL AND SUCH DIVERSITY.
IT'S NOT GENETIC DIVERSITY.
BUT LET'S SEE IF THERE'S
EPIGENETIC DIVERSITY HERE.
JEREMY NATHANS PUBLISHED A
DECADE AGO IN THE SAME LITTER,
THIS IS TO HIGHLIGHT THE
HETEROGENEITY, SAME LITTER
MATES COULD HAVE SAME RATIO.
ON THE LEFT A GREEN FEMALE,
MOSTLY MOM'S X ACTIVE.
AND ON THE LEFT, I THINK I'VE
BEEN CONFUSING THAT.
ON THE LEFT YOU SEE MOM'S X
ACTIVE MAINLY IN THE RED SISTER.
SO JUST TO SAY THERE'S
INCREDIBLE DIFFERENCES BETWEEN
WOMEN AND EVEN BETWEEN SISTERS
IN WHICH X CAN BE ACTIVE.
SO SAMIRA ASKED DOES THIS
MOSAICISM MATTER?
ARE NEURON THAT'S EXPRESS MOM'S
X DIFFERENT FROM NEURONS THAT
EXPRESS DAD'S X?
TO DO THAT SHE USED A VERY
ELEGANT GENETIC SYSTEM WITH
SYNAPTIC DRIVEN CREE LABELING
NEURONS SPECIFICALLY IN THE
HIPPOCAMPUS SHOWING DAD'S X
RED, MOM'S X GREEN.
SHE SORTED THEM.
HAD A RIGOROUS EXPERIMENTAL
DESIGN AND FOUND SOMETHING THAT
WAS UNBELIEVABLE, IT WAS SO
EXCITING.
I'VE LONG BEEN EXCITED BY EVEN
20% DIFFERENCE IN THE BRAIN.
BUT THIS IS ON/OFF GENE
EXPRESSION CHANGES.
NEURONS THAT EXPRESS MOM'S X IN
THE GRAPH IN GREEN ON THE
RIGHT, HAVE MANY GENES THAT ARE
COMPLETELY SILENCED.
AND SO MOM'S X WILL SILENCE
SPECIFIC GENES IN BOTH THE
YOUNG AND AGING HIPPOCAMPUS.
BUT THE NEURONS THAT SHOW DAD'S
X HAVE VERY ROBUST EXPRESSION
OF THESE GENES.
VERY, VERY CLEAR, VERY ROBUST.
THEN SHE ASKED WELL DOES THIS