>>WELCOME TO THE NIDCD NIA
WEBINAR, I'M SHARING OUR SCIENCE
ALZHEIMER'S DISEASE AND RELATED
DEMENTIAS. WE ARE HAPPY TO HAVE
EVERYONE HERE WITH US THIS
AFTERNOON. AND WITHOUT FURTHER
ADIEU, I WOULD LIKE TO WELCOME
OUR DIRECTOR DR. DEB TUCCI TO
GIVE US A LITTLE BIT OF AN
INTRODUCTION. THANK YOU.
>> THANK YOU, AMY. WELCOME,
EVERYONE TO THE NIDCD NIA
COLLABORATIVE WEBINAR, SHARING
OUR SCIENCE, ALZHEIMER'S DISEASE
AND RELATED DEMENTIAS. I AM
REALLY EXCITED ABOUT THIS
AFTERNOON'S PROGRAM AND THANK
YOU ALL FOR JOINING. SO
COLLABORATIONS BETWEEN OUR TWO
INSTITUTES GO BACK A LONG WAY,
PRE-DATING MY TIME AS DIRECTOR
OF THE NIDCD. OUR SHARED
INTEREST IN AGE RELATED HEARING
LOSS LED US TO ISSUE A JOINT
REQUEST FOR APPLICATIONS OR RFA
IN 2017. THIS RFA RESULTED IN
MULTIPLE GRANT AWARDS TOTALING
MORE THAN $2 MILLION IN
SPENDING, THIS WORK WAS FOCUSED
ON RESEARCH RELATED TO CHANGES
IN THE CENTRAL PATHWAYS AND
NEURAL NETWORKS INVOLVED IN AGE
RELATED HEARING LOSS. THE
SUCCESS OF THAT PROGRAM THEN LED
US TO ANOTHER JOINT RFA THAT WAS
ISSUED IN 2020. THIS TIME ON
BALANCE CONTROL IN OLDER ADULTS.
THESE AWARDS AMOUNTED TO MORE
THAN 5 1/2 MILLION DOLLARS IN
TOTAL COST AND WE EXPECT THAT
THEY WILL PROVIDE IMPORTANT
INSIGHTS THAT CAN LEAD TO
IMPROVED QUALITY OF LIFE IN THIS
POPULATION. A SHARED INTEREST
BETWEEN OUR TWO INSTITUTES ARE
RELATED NOT ONLY TO HEARING LOSS
AND BALANCE DISORDERS BUT TO ALL
OUR MISSION AREAS AS WE WILL
HEAR MORE ABOUT TODAY.
THE FUNDING OF ADMINISTRATIVE
SUPPLEMENTS BY THE NIA HAS
PROVIDED THE OPPORTUNITY FOR OUR
NIDCD INVESTIGATORS TO EXTEND
THEIR RESEARCH INTO NEW
IMPORTANT AREAS OF INTEREST.
THIS WORKSHOP WAS DEVELOPED AS A
WAY FOR THE NIDCD AND OUR
RESEARCH COMMUNITY AND THE NIA
TO LEARN MORE ABOUT THE SCIENCE
AND THE -- AT THE NIA
SUPPLEMENTS FOSTER AND INCREASE
COMMUNICATION AND HOPEFULLY
SPARK FURTHER WORK AND
COLLABORATION. NEXT SLIDE
PLEASE.
I AM MOST GRATEFUL TO THOSE
SHOWN ON THIS SLIDE WHO HAVE
WORKED TOGETHER TO PUT TOGETHER
THIS EXCITING SYMPOSIUM AND NOW
I WILL TURN OVER THE MICROPHONE
TO OUR NIA COLLEAGUES. THANK
YOU.
>> I WOULD LIKE TO WELCOME DR.
RENE ETCHEBERRIGARAY FROM NIA,
WHO IS THE
DIVISIONAL DIRECTOR TO THE
SCIENCE -- SENIOR SCIENTIFIC
ADVISOR TO THE DIRECTOR FOR NIA.
RENE.
>> THANK YOU, AMY. PLEASE COULD
I HAVE MY FIRST SLIDE. GOOD
AFTERNOON, EVERYONE. I AM RENE
ETCHEBERRIGARAY FROM THE
DIVISION OF EXTRAMURAL
ACTIVITIES. OFFICE WHERE WHERE
THIS PROGRAM IS COORDINATED FOR
OUR INSTITUTE BUT ALSO ACROSS
THE NIH. SO TODAY I WILL GIVE
YOU A BRIEF OVERVIEW OF THIS
SUPPLEMENTS PROGRAM FOR GRANTS
THAT ARE NOT INITIALLY FOCUS ON
ALZHEIMER'S DISEASE. I WILL SHOW
YOU SOME OF THE RECENT DATA FROM
THE LAST COUPLE OF YEARS AND
FINALLY SOME OF THE INITIAL
ANALYSIS ABOUT THE PROGRAM. SO
THE MAIN PURPOSE OF THIS PROGRAM
WAS CONCEIVED SEVERAL YEARS AGO
PRIMARILY BY ROBIN BARR AT THE
NIA TO ATTRACT INVESTIGATORS
IDEAS METHODOLOGIES, INNOVATIONS
FROM OTHER FIELDS IN TO THE
ALZHEIMER'S AND ALZHEIMER'S
RELATED DEMENTIA RESEARCH. THE
PROGRAM STARTED BACK IN 2017 AS
PILOT BUT AT THAT TIME ONLY FOR
NIA GRANTEES AND RAPIDLY
EXPANDED AND INCLUDED INSTITUTES
FROM THE BROADER NIH STARTING IN
2018. THE PROGRAM HAS RAN
CONSECUTIVELY THROUGH FISCAL
YEAR 22. WITH A GREAT DEAL OF
INTEREST FROM NOT ONLY OUR
SCIENTIFIC COMMUNITY BUT ALSO
SCIENTIFIC COMMUNITY OF THE NIH
AS A WHOLE. WE HAVE HAD
PARTICIPATION OF AT LEAST 23
DIFFERENT INSTITUTES AND
CENTERS. THE LATEST NOTICE IS
THE ONE RELEASED BACK IN JUNE OF
21, WE ARE IN THE PROCESS OF
FINALIZING REVIEWS. WE RECEIVE
TOTAL AT NIH 288 APPLICATIONS,
THAT'S A LITTLE BIT LESS THAN
LAST YEAR. NIA ITSELF GOT ABOUT
THE SAME NUMBER 45 VERSUS 50
PREVIOUS YEAR. SO THE NUMBERS
AND INTEREST REMAIN ALMOST
(INAUDIBLE). AS YU KNOW AS YOU
ARE RECEIVING THESE AWARDS. SO
JUST TO GIVE YOU A GENERAL SENSE
OF HOW THIS HAS BEEN EVOLVING,
STARTING IN FISCAL YEAR 20, 21,
22, YOU CAN SEE WE HAD A
SIGNIFICANTLY LARGE NUMBER OF
APPLICANTS IN THE INITIAL
PHASES. IN -- BUT THE NUMBER OF
AND PROPORTION OF GRANTS FUNDED
HAS REMAINED STRONG. AS YOU CAN
SEE IN THE THIRD BAR, WE WENT
FROM 283 APPLICATIONS FUNDED
ACROSS THE ENTIRE NIH AND WE
WENT DOWN TO ABOUT 300 IN LAST
YEAR THIS PROCESS WAS COMPLETED.
THE INVESTMENT HAS REMAINED
RELATIVELY CONSTANT, IT HAS
VARIED BETWEEN ABOUT $92 MILLION
TO $105 MILLION. SO THIS HAS A
LOT OF SUPPORT FROM OUR
LEADERSHIP. AND WE HOPE TO
CONTINUE WITH THIS PROGRAM. WE
DO NEED TO COMPLETE A MORE
DETAIL ANALYSIS ON THE SUCCESS
BUT EARLY INDICATION THIS
PROGRAM HAS BEEN SUCCESSFUL.
NEXT SLIDE PLEASE. THIS IS JUST
TO SHOW YOU THE NIH SPECIFIC
NUMBERS. SO WE CAN GO TO MY LAST
SLIDE I BELIEVE. JUST TO GIVE
YOU A SENSE OF THE SUCCESS, WELL
THE FIRST OBJECTIVE ATTRACTING
PEOPLE NEW TO THE FIELD IS VERY
CLEAR. WE HAVE OVER 65% IN SOME
YEARS MORE THAN 70% INDIVIDUALS
THAT ARE NOT -- THAT ARE NEW TO
THE ALZHEIMER'S RESEARCH FIELD.
SO THAT OBJECTIVE IS I THINK A
VERY, VERY CLEARLY ACCOMPLISHED
IN THE OTHER OBJECTIVE TO SEE IF
INDIVIDUALS APPLY FOR
ALZHEIMER'S GRANT TO NIA OR
NINDS OR ANY OTHER INSTITUTE
THAT DIRECTLY FUNDS DEMENTIA
RESEARCH. AS NOT BEEN
OVERWHELMING. BUT THE PEOPLE WHO
DO SUBMIT, MAYBE THIS IS TOO
SOON, THAT IS WHY WE HAVEN'T
SEEN ENOUGH SUBMISSION BUT THE
PEOPLE WHO DO SUBMIT HAVE A HIGH
SUCCESS RATE. AS YOU CAN SEE,
IN THE LAST YEAR WE HAVE FULL
NUMBERS YEAR 2018 TO THIS WAS
THE FIRST YEAR OF THE PROGRAM --
THIRD YEAR OF THE PROGRAM ACROSS
THE NIH. THE PEOPLE GET THE
PRELIMINARY DATA THEY NEED WITH
SUPPLEMENTS AND THE ONE WHOSE
ARE ABLE TO SUBMIT -- ONES WHO
ARE ABLE TO SUBMIT A GRANT VERY
SUCCESSFUL AND WE MOPE HAS BEEN
PROVEN BY LIST OF PRESENTATIONS
HAVE TAKEN GOOD ADVANTAGE OF
THIS PROGRAM AND HAVE BEEN
SUCCESSFUL. I WILL CONCLUDE BY
THANKING YOU ON BEAFTER OF NIA
AND NIH BECAUSE OF YOUR PART OF
THIS SUCCESS OF THIS PROGRAM AND
WE HOPE THAT YOU CONTINUE TO
INTRODUCE YOUR IDEAS FROM OTHER
FIELDS IN TO THE ALZHEIMER'S AND
DEMENTIA RESEARCH. THANK YOU.
>> THANK YOU, RENE. WE ARE
GRATEFUL TO THIS INSTITUTE, WE
HAD 70 GROUPS THAT RECEIVED
SUPPLEMENTS AND WE WILL HAVE A
SUBSET TODAY WHO WILL PRESENT
HAIR WORK AND SHARE THEIR
SCIENCE WITH US. WE HOPE THIS
FURTHERS THE SCIENCE, FURTHERS
POSSIBILITIES FOR COLLABORATION,
GIVES A GOOD IDEA OF THE
CHALLENGES THAT YOU FACED WHILE
WE HAVE THE DISCUSSIONS AND THE
LESSONS LEARNED. SO ADVANCE THE
SLIDE PLEASE. JUST QUICKLY, THE
OVERALL AGENDA IS SPLIT INTO
PRIMARILY ANIMAL STUDIES, THOUGH
WE HAVE SOME HUMAN WORK FIT INTO
THIS AS WELL BY SUBJECT MATTER
AND WE WILL HAVE SHORT FIVE
MINUTE TALKS BY EACH PERSON
LISTED AND THEN DISCUSSION LED
BY SUSAN SULLIVAN FOR 20 MINUTES
AFTERWARDS. THEN SESSION 2 IS ON
HUMAN STUDIES. WE HAVE PEOPLE
DOING BOTH AND THAT WILL LAST A
LITTLE BIT LONGER, WE HAVE A FEW
MORE PRESENTERS, 25 IN ALL
TODAY. AND THEN DISCUSSION FOR
20 MINUTES ON HUMAN
INTERACTIONS, AND AFTER A BREAK
WE WILL END OUR DAY ON
DISCUSSION ON THE FUTURE
DIRECTIONS AND THERE ARE THREE
QUESTIONS SENT TO PARTICIPANTS
TO THINK ABOUT AHEAD OF TIME AND
WE HOPE THAT WE CAN LEARN MORE
ABOUT THOSE SORTS OF THINGS,
CHALLENGE, LESSONS LEARNED,
WHERE WE ARE GOING NEXT. NEXT
SLIDE. SO JUST A FEW OVERALL
THINGS. AS I MENTION WE ARE ARE
VERY QUICK TODAY WITH FIVE
MINUTES TOTAL FOR SPEAKER, WE
ASK ABOUT THREE MINUTES OF
PRESENTATION AND TWO MINUTES FOR
QUESTIONS IF TIME ALLOWS, IF YOU
TAKE YOUR FULL FIVE MINUTES WE
WILL ASK THEN THAT WE MOVE TO
THE NEXT PRESENTER. WHERE MY
VIDEO IS THERE WILL BE A COUNT
DOWN CLOCK, I WILL SAY TWO
MINUTES QUIETLY SO THAT YOU HAVE
SOME IDEA WHEN TWO MINUTES IS
OBSERVED. IF YOU WANT TO THE PIN
SOMEONE'S VIDEO, THE SPEAKER OR
TIME CLOCK OR ASL INTERPRETER
YOU CAN DO SO BY HOVERING OVER
THE THREE DOTS ON YOUR -- ON
THEIR VIDEO SCREEN AND IT WILL
GIVE YOU THE OPTION TO PIN THAT
VIDEO TO THE TOP OF YOUR VIEW IF
YOU WOULD LIKE. WE WILL ADVANCE
YOUR SLIDES AS SOON AS WE SAY
ADVANCE WHEN TIME COMINGS FOR
THAT. WE WANT YOU TO ENTER YOUR
QUESTIONS ON CHAT WE WILL KEEP
AN EYE ON THE CHAT FEATURE AND
AT THE END I MODERATE THE FIRST
SESSION, I WILL BRING UP THE
FIRST QUESTION AFTERWARDS IF WE
HAVE TIME. WE DON'T HAVE TIME WE
CAN DO IT DURING THE DISCUSSION
OR PERHAPS YOU CAN CONTACT THE
SPEAKER AFTER THE WEBINAR. WE
ARE RECORDING OF COURSE TODAY
AND IT WILL BE PUT UP FOR LATER
VIEWING SO YOU CAN ALSO DO THAT
AS WELL. WE INVITE OUR ZOOM
PARTICIPANTS WHO HAD THE ZOOM
LINK TO PRESENT THEIR QUESTIONS
DURING THE CHAT OR DISCUSSIONS.
NEXT SLIDE. SO WE WANT TO AGAIN
THANK ALL OUR SPEAKERS AND
PARTICIPANTS, THIS IS THE FIRST
TIME WE PULLED TOGETHER OUR
SUPPLEMENT RECIPIENTS FROM THE
AD PROGRAM TO DO THIS. AND SO WE
ARE INTEREST IN THERE IS SUCH A
WIDE BREADTH OF INFORMATION BUT
WE ALSO KNOW THERE IS PROBABLY
OVERLAPS IN RESEARCH AS WELL. WE
HOPE WE CAN FOSTER THAT
COLLABORATION AS WE GO ALONG. SO
PLEASE MUTE YOUR MIC, TURN OFF
VIDEO UNLESS YOU ARE PRESENTING
OR DISCUSSING, DURING THE
DISCUSSION PEOPLE TURN ON VIDEOS
FOR THAT, AND IF HAPPEN TO BE
RUNNING -- IT IS HELPFUL TO TURN
THAT OFF AS WELL. SO NOW
WITHOUT FURTHER ADIEU, WE WILL
START SESSION ONE ON ANIMAL
MODELS, KELLY KING WILL BRING
DR. CELLRY KING WILL BRING UP
THE SLIDES FOR US. OUR FIRST
PRESENTER IS DR. RON YU FROM
SOURCE INSTITUTE FOR MEDICAL
RESEARCH. RON.
>> NEXT SLIDE PLEASE. I FEEL
VERY PLEASED TO JOIN THIS
DISCUSSION WITH EVERYONE. SO
BECAUSE I'M FIRST SPEAKER OF THE
OLFACTORY SYSTEM I WILL TALK
ABOUT STRONG CORRELATION BETWEEN
THE OLFACTORY DYSFUNCTION AND
ALZHEIMER'S DISEASE. THIS
MANIFESTATION IN OLFACTORY LOSS
PRECEDES THE FULL MANIFESTATION
OF AD. THE BRAIN AREAS IS
ACTUALLY INVOLVE AND CORTEX HAVE
SHOWN PATHOLOGY. THESE CELLS
THAT WE ARE LOOKING AT STUDYING
IS IN THE OLFACTORY EPITHELIUM,
NEXT SLIDE PLEASE. SO IN
COLLABORATION WE FOUND THAT
EXPRESS MUTANT FORM OF APP EVEN
IN ABOUT 10% OF THE CELL ARE
ABLE TO -- IS ABLE TO DISRUPT
PROJECTION PATTERN OF AXONS AND
THAT ALSO REDUCE THE AUTOIMMUNE
RESPONSE SO WE WANT TO FIND OUT
IS THE NORMAL PATHOLOGY --
NORMAL FUNCTION OF ATP AND ITS
INTERACTING PARTNERS IN
OLFACTORY SENSORY NEURONS. NEXT
SLIDE PLEASE. SO THE IDEA IS
USING THIS APEX 2 PROM
SIMILARITY LABELING TO CONDUCT
PROTEOME ANALYSIS. SO APEX 2 CAN
LABEL IS DIFFUSED TO PROTEIN AND
LABEL PARTNERS TEN NANOMETER
RADIUS. WE WANT TO DIFFUSE WILD
TYPE A TEXTP AND MUTANT AS WELL
AS A BETA AND 42 TO APEX 2 TO
EXPRESS SENSORY NEURONS. NEXT
SLIDE. SO WE CONSTRUCTED THOSE
ADENOVIRUSES CARRYING THOSE FUSE
PROTEINS AND THEN INJECTING TO
THE OLFACTORY INTO THE NOSE, SO
THAT CELLS WILL INFECT. THEN WE
PERFORM IN VIVO LABELING SO THAT
IS A LIVE TISSUE LABELING TO
LABEL OUR CELLS ALL PROTEINS
PROXIMAL TO THE TARGETED
PROTEIN. THEN WE WILL CONDUCT
QUANTITATIVE MASS SPEC
EXPERIMENTS TO IDENTIFY PROTEINS
PEPTIDES, AND PROTEINS THAT ARE
INTERACTING WITH. NEXT SLIDE
PLEASE. WE CAN SKIP THIS
QUANTITATIVE METHOD ON THAT. SO
VERY QUICKLY SHOW SOME DATA WE
HAVE COLLECTED, THIS IS A
ENRICHED A BETA 42 INTERACTING
PROTEIN OVER A BETA 40 THAT WE
HAVE FOUND OLFACTORY EPITHELIUM.
WE FUND THAT IN THIS PART THAT
THERE IS A HEAVY PRESENTATION OF
PROTEOSOME ASSOCIATED WITH IT.
NEXT SLIDE PLEASE. THESE ARE
THE PREDOMINANT PROTEOSOME
SUBUNITS THAT CONSTITUTE IF
PROTEOSOME AND SO THIS RESULT
INDICATE THAT A BETA 42 IS
PREFERENTIALLY DESTINED TO THE
PROTEOSOME. SO WHAT WE ARE
TRYING TO DO NOW IS TO FURTHER
INVESTIGATE OTHER PROTEIN
DIRECTING PARTNERS AS WELL AS
USING STRATEGY TO EXPRESS THESE
FUSION PROTEINS ALSO IN THE
BRAIN AND TO IDENTIFY THOSE
INTERACTING PARTNERS. IN BOTH
NORMAL AN CONDITIONS. SO THIS IS
THE FUNNING SOURCE FROM THE
NIDCD THE PARENT GRANT, AND WE
THANK NIA FOR SUPPORTING THIS.
THIS IS SUPPORTING STAFF AND JAY
IS THE ONE WHO DID ALL THE WORK.
UNFORTUNATELY I CAN'T STAY FOR
PANEL DISCUSSION BUT JAY IS
AVAILABLE TO ANSWER QUESTIONS.
SO I HAVE ONE MINUTE TO ANSWER
ANY QUESTIONS THAT YOU HAVE.
THANK YOU.
>> THANKS, RON. THANK YOU VERY
MUCH. WHAT IS THE NEXT STEP? I
THINK THAT IS WHAT WE MIGHT ASK
AT THE END IF YOU WERE STAYING
DISCUSSION.
>> SO WE WANT -- A LOT OF
ALZHEIMER'S MANIFESTATION IS IN
THE BRAIN SO WE WANT TO PUT THE
SIMILAR CONSTRUCT IN TO MAKING
TRANSGENIC MICE SO WE CAN STUDY
INTERACTING PARTNERS IN THE
BRAIN WHERE THE PATHOLOGY
USUALLY APPEARS. SHORT ANSWER TO
THAT.
>> THANK YOU. AND ANY CHALLENGES
YOU THINK FOR THE FUTURE?
>> YEAH, THERE IS A LOT OF
TECHNICAL CHALLENGES, BECAUSE WE
ARE DOING IN VIVO EXPERIMENTS
AND WE HAVE TO KEEP CELLS ALIVE
SO THAT WE ARE NOT IDENTIFYING
PROTEINS THAT ARE COMING FROM
TISSUE DAMAGE AND GENERATING
TRANSGENIC ANIMALS, WILL BE
CAUSING ADDITIONAL CHALLENGES
NOT TOO MUCH BUT WE CAN DO IT.
>> OKAY. ALL RIGHT. THANKS, RON.
THANKS FOR BEING THE FIRST UP.
APPRECIATE IT. OKAY. NEXT WE
HAVE DR. DEE YEAH GO RESTREPO,
UNIVERSITY OF COLORADO.
>> THANK YOU. I WANT TO THANK
YOU FOR ORGANIZING THE WEBINAR
AND FOR THE FUNDING HAS RESULTED
IN RO1 APPLICATION AND WE ARE
SENDING THE PAPER LATER THIS
MONTHMONTH. AND DOCK TO, YOU
INDICATED THE LOSS OF OLFACTION
IS FAIRLY SYMPTOM OF
ALZHEIMER'S. NEXT SLIDE PLEASE.
WHAT WE ARE DOING IS STUDYING
FAMILIAL ALZHEIMER'S. THIS IS IS
WORLD LARGEST COHORT, THEY HAVE
MUTATION, THEY HAVE DEPOSITS OF
BETA AMYLOID AND THEY GET
ALZHEIMER'S ABOUT 45 TO 50 YEARS
OLD. WHAT WE ARE DOING IS
TRANSCRIPTOME ANALYSIS. WHAT WE
ARE DOING IS A TECHNIQUE TO DO
TRANSCRIPTOME ANALYSIS WITH FFPE
TISSUE SECTIONS. AND WE ARE
INTERESTED IN THE INITIAL PART
OF THE OLFACTORY SYSTEM IN
CENTRAL NERVOUS SYSTEM. WHICH IS
OLFACTORY BULB AND THEN THE
OLFACTORY TRACT THAT TAKES THE
SIGNAL WITH TWO SYNAPSES TO
HIPPOCAMPUS WHICH IS IMPORTANT
IN LEARNING AND MEMORY. YOU SEE
AT THE TOP THERE. WHAT WE FOUND
INITIAL IMMUNOHISTOCHEMISTRY
STUDIES SHOWN HERE IS THAT THERE
IS AREAS OF HIGH AND LOW
MYELINATION IN THE OLFACTORY
TRACT WHICH IS INTERESTING. THAT
WE FIND IN BOTH ALZHEIMER'S FAD
AND CONTROLS. AGE MATCHED. AS
EXPECTED WE FIND THEY HAVE
HIGHER BETA AMYLOID POSITION.
WHICH ALSO FOUND EXPECTED
INCREASE 1, 68 INDICATING
INFLAMMATION IN OLFACTORY TRACT. TRACT.
AND WE DID THE TEMPO SEQ
ANALYSIS WE FOUND YOU SEE ON THE
VOLCANO PLOT SIMILAR CAN'T AND
LARGE NUMBER OF SEQUENCES IN THE
OLFACTORY BULB. BUT WHAT IS
INTERESTING ON THE LEFT SIDE YU
SEE THE OLFACTORY TRACT IN
GENETIC PATHWAY ANALYSIS. AND
THAT ONE YOU FIND AMYLOID
PROCESSING. MAKE SENSE BUT YOU
ALSO FIND INFLAMMATION,
SIGNALING, IL 8 SIGNALING.
THERE'S OTHERS. BUT IN THE
OLFACTORY BULB WHAT WE FOUND IS
SIGNATURE FOR (INAUDIBLE)
BIOINFECTION IS KNOWN TO PRODUCE
-- WHEN WE DID CONVOLUTION OF
THE GLIA WE ALSO FOUND THAT
THERE WERE INCREASE MICROGLIA
NADs. AND OLIGODENDROCYTES
RESPONSIBLE FOR MYELOID
POSITION. NEXT SLIDE. THIS IS
INTERESTING BECAUSE THERE IS A
LOT OF LITERATURE INDICATING
THAT VIRUSES ACTUALLY ARE
IMPORTANT IN ALZHEIMER'S, THEY
MAY ACCELERATE ALZHEIMER'S AND
THIS IS FROM MY COLLABORATOR DR.
NAGLE WHO HAS DONE WORK WITH
ASHIEST VIRUS SHOWS IT PRODUCES
AMYLOID. NEXT SLIDE. WE ALSO
DID A SPATIAL PROTEOMIC ANALYSIS
WITH NANOSTRING, WE CHOSE 88
DIFFERENT PROTEINS EITHER
INFLAMMATORY PROTEINS OR
PROTEINS THAT ARE MARKERS OF
ALZHEIMER'S AND I'M NOT GOING TO
GO INTO DETAIL INTO THESE BUT
WHAT WE FOUND IS THE PROTEINS
MAKE THEY ARE IMMUNE RESPONSES.
WHICH MAKES SENSE WITH
INFLAMMATION BUT THE INTERESTING
THING IS THAT IT IS HETEROGENOUS
IN THAT IT WAS DIFFERENT IN THE
HIGH MYELINATION AND LOW HYLE
NATION AREAS. ON THE RIGHT SIDE
YOU SEE PC ANALYSIS. WHAT THAT
SHOWS IS THERE'S -- BETWEEN TAD
AND CONTROLS AND HIGH
MYELINATION AND LOW MYELINATION
IN FADs ARE TOTALLY DIFFERENT.
THAT YOU CAN SEE ALSO IF YOU
PLUG THE DATA IN THE -- PLUG THE
EXPRESSION OF THE PROTEINS,
THERE'S THAT AREA THAT WE CALL
DEMYELINATION AREA, THERE'S
SUBSET OF PROTEINS THAT ARE HIGH
-- HIGH MYELINATED OLFACTORY
TRACT AND LOW IN ALL THE OTHER
ONES FAD AND CONTROLS SHOWING
THAT HERE AND THE INTERESTING
THING IS THAT ALL THOSE PROTEINS
ARE INVOLVED IN DEMYELINATION.
EITHER RESPONSE TO MYELINATION
OR ACTUAL DEMYELINATION. WE ALSO
FIND ALZHEIMER'S MARKERS IN LOW
MYELINATED. THE INTERESTING
THING IS WHAT THIS SHOWS IS
THERE IS AN INVOLVEMENT LIKELY
INVOLVEMENT OF VIRUSES IN
AXILLARY ALZHEIMER'S DISEASE.
THIS MAKES SENSE BECAUSE VIRUSES
ARE KNOWN TO INVOLVE ENOUGH LOSS
OF SMELL AND THE LAB AT MIT HAS
SHOWN ACTUAL POSTILLINGS IN THE
HIPPOCAMPUS MAKE A DIFFERENCE IN
THE GLIAL INVOLVEMENT. IN
INFLAMMATION. AND IN THE LOSS OF
NEURONAL ACTIVITY. AND IT IS
WELL KNOWN THAT THE OLFACTORY
BULB ENTRAINS THE HIPPOCAMPUS IN
THOSE OSCILLATIONS SO THE
QUESTION IS COULD IT BE THAT THE
OLFACTORY SYSTEM IS PART OF THE
THEOLOGY -- ETIOLOGY OF
ALZHEIMER'S DISEASE. THANKS A
LOT. IF YOU HAVE ANY QUESTIONS I
WILL BE GLAD TO ANSWER.
>> THANK YOU.
>> THE LAST SLIDE THAT'S THE
MOST IMPORTANT ONE. WE ARE
THANKFUL FOR THE PATIENTS AND
EVERYONE INVOLVED.
>> THANK YOU. BECAUSE WE ARE
JUST 30 SECONDS AHEAD OF TIME
THERE WAS A QUESTION ABOUT DR.
LUEBKE, IS THE FAD MOUSE THE
THREE TIMES FAD OR FIVE TIMES OR
ANOTHER MODEL? WHICH MODEL I
GUESS?
>> THIS IS ALL HUMANS. IT IS A
HUMAN COHORT. WE ARE ALSO DOING
WORK IN THE FIVE TIMES FAK MICE
NOT PRESENTING HERE -- FAD MICE,
WE HAVE SIMILAR RESULTS BUT THAT
IS JUST STARTING. WE HAVE
INTERESTING RESULTS THERE. IN
THAT MOUSE WE ARE INFECTING WITH
HSV 1. COLD SOURCE.
>> THANK YOU.
>> THIS IS ALL HUMAN.
>> YES. WE -- PEOPLE ARE
FREQUENTLY DOING WORK IN BOTH
SETS, THANK YOU FOR CLARIFYING
THAT. THANK YOU, DR. LUEBKE FOR
THE QUESTION. NEXT WE HAVE UP
DR. DAN WESSON, UNIVERSITY OF
FLORIDA. AND DON'T FORGET TO
TURN -- GREAT. DAN YOU ALREADY
HAVE YOUR CAMERA ON. FANTASTIC.
>> THANK YOU. THANKS TO THE NIA
AND NIDCD FOR YOUR SUPPORT, THIS
IS GREAT SMELL AND TASTE
COMMUNITY THERE AND ESPECIALLY
SUPPORTING ALL OUR RESEARCH SO
THESE FIVE TALKS FRUSTRATE ME
BECAUSE YOU CAN'T GO DEEP INTO
ONE PARTICULAR QUESTION SO I
HOPE YOU CAN CONCEPTUALIZE THAT
NIDCD AS ABOVE A SAMPLING OF
THINGS WE WORK OR AS IT RELATES
TO OLFACTORY FUNCTION. IF YOU
CAN SKIP TO SLIDE 3. IN OUR WORK
WE APPRECIATE INFORMATION
PROCESS BY VARIETY OF BRAIN
STRUCTURE SPECIFICALLY MY LAB
FOCUSES ON THE TUBECAL WHICH IS
APPARENT RO1 PROJECT THAT
RECEIVED THE SUPPLEMENT, AND IF
YOU CLICK FORWARD ONCE, WE
LARGELY USE RECORDINGS AND MICE
AND INTERESTED HOW ODOR
INFORMATION TAKES ON LEARNED
MEANING AS ANIMALS ARE HUMANS
ASSOCIATE ODORS INTO DIFFERENT
OUTCOMES. A GOOD MEAL ET
CETERA. IF YOU CAN CLICK
FORWARD. SO WE LIKE TO THINK OF
THE OLFACTORY SYSTEM AND
CIRCUITRY I SHOW YOU AS QUINT
ESSENTIAL MODEL TO UNDERSTAND
THE IMPACT OF THE ADRD
PATHOGENESIS ON BRAIN FUNCTION
AND THEREFORE THE ABILITY TO
INTERACT MORAL NORMALLY IN YOUR
WORLD. THIS IS IMPORTANT TO
EMPHASIZE THE NON-OLFACTORY
PEOPLE HERE AS YOU CAN SEE IN
THESE CLASSIC DIAGRAMS RELATED
TO THE STAGING THAT AMYLOIDOSIS
AND TAUOPATHY AND OTHER
ETIOLOGIES START IN THE
OLFACTORY BULB IT IS EMPHASIZE
REVIEW THAT MY COLLABORATIVE
WITH POST DOC WROTE THE
OLFACTORY BULB SERVES AS ENTRY
SITE PATHOGENS CAN TRAVEL
THROUGHOUT THE BRAIN AND
IMPAIRING THE IMPAIRING THE
ABILITY OF OTHER BRAIN SYSTEMS
TO OPERATE NORMALLY. NEXT SLIDE
PLEASE. WHAT WE THINK HAPPENS IS
THAT SYNUCLEIN OR AMYLOID OR
WHAT HAVE YOU INFLUENCES NORMAL
SYNAPTIC TRANSMISSION, WEAKENING
SYNAPTIC FUNCTION. THAT
THEREFORE PERTURBS FUNCTIONING
OF THE CIRCUIT ESPECIALLY AMONG
VULNERABLE NEURON TYPES WITHIN
THAT CIRCUIT THAT DRIVES NETWORK
ACTIVITY DYSFUNCTIONAL THEREFORE
RISING WITH THIS IMPAIRED SENSE
OF SMELL OR OTHER FUNCTIONS BUT
HERE WE ARE USING SMELL AS THE
MAGNIFYING CLASS TO UNDERSTAND
HOW THE ADRD ARE ORIGINATING IN
THE BRAIN. THIS IS CONCEPTUAL
SPIRIT SIMILAR TO WHAT DR.
RESTREPO MENTIONED, THE NETWORK
TRAIN GAMMA HOW THAT IS
INFLUENTIAL AND ADRD
PATHOGENESIS. THIS SYNAPSE
PRODROME CASCADE ADRD IN A PAPER
COMING OUT IN JOURNAL OF
COMMUNICATIONS. SO WE HAVE DONE
A VARIETY OF THINGS TO LOOK HOW
LEARN ODOR MEANING AND
SPONTANEOUS ODOR MEANING ARE
IMPACTED AND ADRD ANIMALS, THIS
IS SIMPLE WORK FROM THE 5X FAD
MOUSE MODEL, INCREDIBLY
IMPRESSIVE, MODEL OF AM LOY O
SHYSIS AND CYTOKINE
INFROMMATION. IN THIS WORK WE
FOUND AGE DEPENDENCE SO
THEREFORE PROGRESSIVE ALONG
PATHOLOGY. CHANGE AND ODOR
RESPONSES OF MICE TO A PANEL OF
NON-(INAUDIBLE) ODORS. THIS IS
IMPORTANT BECAUSE HUMANS WITH
ALZHEIMER'S AS WELL AS PARKINSON
HAVE ABERRANT EMOTIONAL
RESPONSES TO ODOR INFLAMMATIONS
NOT JUST IMPAIR ABILITY TO
DETECT OR US CRIMINATOR
RECOGNIZE SMELLS BUT ALSO YOU
HAVE A CHANGE IN THE EMOTIONAL
RESPONSE. THAT'S SUPER RELEVANT
BECAUSE ADRD PERSONS HAVE
GENERALIZE ANXIETY DISORDER AND
OTHER EMOTIONAL DYSFUNCTION
WHICH DRAMATICALLY IMPACTS
QUALITY OF LIFE. NEXT SLIDE
PLEASE. WE HAVE ALSO BEEN
WORKING TO GET REGION
SPECIFICITY WHERE THESE THINGS
HAPPEN. SO IN THE WORK ON THE
LEFT WE SEE THAT PRE-FORM
FIBRILS FOR ALPHA SYNUCLEIN
UNIVERSITY OF PENNSYLVANIA IN
OLFACTORY BULB AND WE FIND AWAKE
MICE GIVEN ODORS PRONOUNCED
ELEVATION OF BETA OSCILLATION
ACTIVITY AND THIS IS REALLY
INTERESTING CLINICALLY BECAUSE
THE SAME'SLATORY SIGNATURE
ELEVATED IN THE SUB THALAMIC
NUCLEUS OF PARKINSON PATIENTS
AND HE WILL DOE PA PATIENT ALSO
DRIVE DOWN THIS BETA SEW WITH
INTERESTED HOW BETA OSCILLATION
PLAYS A ROLE IN SHAPING SPIKING
VIRUSES IMPAIRING ODOR
PERCEPTION. WE HAVE ALSO BEEN
SEEING SYNUCLEIN IN AMYGDALA, ON
THE RIGHT SEE CHANGES IN EMOTION
PAL MEMORY RETRIEVAL TO ODORS.
ARE AND CLICK FORWARD ONCE MEAN.
CLICK FORWARD ONCE PLEASE. WE
HAVE ALSO BEEN WORKING AT HOW
SYNUCLEIN IN THE FRONTAL CORTEX
IN THIS CASE THE -- IT WAS
EJECTEEJECTED IN PRELIM BIC CORTEX BUT
PREED SPREAD TO RETRO GRADE,
WHICH WILL GET AT THE RELEVANT
ADRD SYMPTOM OF IMPAIRED
COGNITIVE FUNCTION AND ALL IN
THE THE REALM OF ODOR GUIDED
BEHAVIOR TAKING ADVANTAGE OF
MOUSE MODEL. WITH THAT I WILL
STOP.
>> THANK YOU. I THINK WE ARE
SHORT ON TIME FOR QUESTIONS BUT
VERY INTERESTING, THANK YOU.
HOPEFULLY YOU CAN HANG OUT FOR
THE DISCUSSION.
>> I WILL BE HERE. THANKS.
>> NEXT UP WE HAVE DR. PATRICIA
WHITE, UNIVERSITY OF ROCHESTER.
AND IF YOU CAN TURN ON YOUR
VIDEO THAT WOULD BE GREAT SO
THAT WE CAN SEE YOU AS WELL.
>> I WOULD LIKE TO THANK THE
PROGRAM OFFICERS FOR INVITING ME
TO TALK ABOUT OUR INITIAL FOR
RAYS INTO ALZHEIMER'S RESEARCH.
I WORK ON, COCHLEAR REGENERATION
AND ALZHEIMER'S AND AUDITORY
DEFICIT STRONG CO-MORBIDITY WITH
ALZHEIMER'S PATIENTS HAVING HEAR
LOSS AND ALSO AUDITORY
DIFFICULTIES HEARING AND NOISE.
ADVANCE PLEASE. THIS WORK IS
THE THESIS OF MY TALL LENTED
GRADUATE STUDENT DAXIANG NA. SO
HEARING RESTORATION STUDIES WE
FOCUS ON A CANDIDATE SIGNALING
MOLECULE A MEMBER OF THE EGF
RECEPTOR FAMILY IN COMPLICATED
TRIPLE RAINS GENIC MOUSE MODEL
WE SHOWED THAT CONSTITUTIVE ERB
SIGNALING IS ASSOCIATED WITH
IMPROVED HEARING RECOVERY AFTER
NOISE DAMAGE. THIS WAS THE
MOTIVATION FOR OUR WORK. HOWEVER
ONE PROBLEM WITH OUR WORK IS
THAT WE TERMINATE OUR
EXPERIMENTS WHEN THE ANIMALS ARE
FOUR MONTHS OF AGE WHICH IS
PRIOR TO EVEN THE MOST
AGGRESSIVE MOUSE MODEL 5X FAD
WHICH WHAT WE CHOSE. ANOTHER
PROBLEM IS THAT THIS MOUSE MODEL
MAINTAINED ON C 57 BL 6 WHICH
HAS NUMBER OF BAD HEARING
CHARACTERISTICS SO IN ORDER TO
LOOK AT THE HEARING WE CROSS AND
INVESTIGATE THE F 1, HOWEVER
THESE HAVE NOT BEEN DESCRIBED
BEFORE IN ALZHEIMER'S RESEARCH.
ADVANCE. SO FIRST WE WANTED TO
SHOW PLAQUE DEPOSITION KINETICS
SO WE LOOK AT PLAQUE DEPOSITION
IN HIPPOCAMPUS AND FOUND THAT
AMYLOID BETA IS INDEED DETECTED
THERE AT THREE AND A HALF MONTHS
OF AGE. THE MICE ALSO SHOW
MEMORY DEFICITS SO THEY DO NOT
-- THEY HAVE A REDUCED
ASSOCIATION OF A TONE WITH A
FOOT SHOCK 24 HOURS LATER THIS
IS AT 13 MONTHS OF AGE, ADVANCE.
THEIR NOISE DAMAGE
SUSCEPTIBILITY CHARACTERISTICS
ARE VERY SIMILAR AT THE EARLY
STAGE SO AT THREE AND A HALF
MONTHS OF AGE, YOU CAN SEE THAT
HEARING THRESHOLDS ARE THE SAME
BETWEEN ALZHEIMER'S AND WILD
TYPE MICE, AND THAT ONE IN 14
DAYS AFTER NOISE THE THRESHOLDS
ARE CHANGED. THESE ARE AUDIO
GRAMS AND HIGHER THRESHOLDS ARE
WORSE, JUST ADVANCE. SO WE
WANTED TO LOOK AT THE LONG TERM
DEVELOPMENT OF HEARING LOSS IN
THESE ANIMALS, ADVANCE. WE
DETERMINED HEARING LEARN HOLDS
WERE WORSE AT NINE MONTHS OF
AGE. WHEN WE LOOK AT THE
AUDITORY BRAIN STEM RESPONSE
WHICH IS AN EEG SIGNAL, WHICH
YOU CAN USE TO LOOK AT
CHARACTERISTICS OF THE AUDITORY
BRAIN STEM, ADVANCE. WE FOUND
INCREASE CENTRAL GAIN SHOWING
THERE WAS AN EFFECT ACTUALLY IN
THE AUDITORY BRAIN STEM AND SO
THIS IS CORTEX INDEPENDENT. SO
BECAUSE ALZHEIMER'S PATIENTS
HAVE REDUCED HEARING AND NODES
WE WANT TO LOOK AT THAT IN THESE
MICE AND SO WE USE MICE
ALZHEIMER'S MICE WITH SIMILAR
AUDITORY THRESHOLDS COMPARED TO
CONTROLS. WE SAW THAT THREE
MONTHS OF AGE, WHEN WE LOOK AT
THE ABR MASKING NOISE NOTCH
NOISE THERE WAS NO DIFFERENCE
BETWEEN THE GENOTYPES BUT THAT
ALZHEIMER'S 5X FAD MICE
DEVELOPED WORSE HEARING AND
NOISE IN BOTH CONDITIONS BY 12
MONTHS OF AGE. SO THIS SLIDE
SHOWS HIGH BOTH SIZE AMYLOID
DEPOSITION IN IN CADAVERS OF
ALZHEIMER'S PATIENTS INHIBIT
INHIBITOR SIGNAL AN REDUCE IT.
ADVANCE. THIS COULD LEAD TO THE
HYPERACTIVITY WE MODELS IN OUR
SYSTEM. THAT COULD LEAD TO
EFFERENT CHANGES WHICH DRIVE
HEARING AND NOISE DEFICITS.
SINCE THIS ALSO CONFER SENSE
TVTY TO AGING AND PROVIDE THE AD
LIKE AUDITORY DEFICITS, SO WE
ARE COLLABORATING WITH AT THE
OREGON HEALTH AND SCIENCE
UNIVERSITY TO DIRECTLY TEST THIS
HYPOTHESIS IN THIS MOUSE MODEL.
THANK YOU.
>>
>> THANK YOU, DR. WHITE.
CURIOUS, DO THESE ANIMALS HAVE
ANY OTHER CAN HE HAVE SITS
TENTATIVES OR ANYTHING ELSE
CAUSED BY THE PLAQUES IN THE
BRAIN? CURIOUS.
>> SO MY COLLABORATOR ANNE
LUEBKE WHO WILL TALK LATER IN
THE SESSION WILL TELL YOU MORE
ABOUT MOUSE MODEL AND THE
VESTIBULAR DEFICITS.
>> ANY CHALLENGES OR FUTURE
DIRECTIONS YOU THINK? NEXT
STEPS?
>> WE ARE BREADING TO THE TRIPLE
TRANSGENIC SYSTEM USING A HUGE
AMOUNT OF MICE. IN ORDER TO BE
ABLE TO TEST THAT -- THE
ORIGINAL HYPOTHESIS. SO REALLY
IT IS MOSTLY THE CONSTRAINTS OF
MULTIPLE GENETIC MODELS AND
TRYING TO GET THE CORRECT
ACCOMMODATIONS.
>> ALL RIGHT. THANK YOU. DR.
MARK RUTHERFORD UP NEXT FROM
WASHINGTON UNIVERSITY ST. LOUIS.
YOU CAN TURN ON YOUR VIDEO
CAMERA AS WELL SO WE CAN SEE
YOU.
>> HERE I AM. CAN YOU HEAR ME?
>> YES I CAN HEAR YOU.
>> GREAT. THANKS TO THE
ORGANIZERS FOR THE OPPORTUNITY
TO SPEAK TODAY AND THANK ALSO TO
MY COLLABORATORS AT WASHINGTON
UNIVERSITY ST. LOUIS. NEXT
SLIDE PLEASE. OF THE MANY
POTENTIAL MECHANISMS UNDERLYING
CONNECTION BETWEEN HEARING LOSS
AND COGNITIVE DECLINE, TODAY WE
ARE CONSIDERING THE COMMON CAUSE
HYPOTHESIS. SPECIFICALLY WE WANT
TO KNOW IF MOUSE MODELS OF
AMYLOID GENESIS WILL EXHIBIT
ACCELERATED AGE RELATED HEARING
LOSS OR NEURODEGENERATION IN THE
COCHLEA OR BRAIN STEM. THESE
APPPS 1 DELTA NINE MICE
OVEREXPRESS A BETA, THEY HAVE
PLAQUES IN BRAIN BY SIX MONTHS
AND COGNITIVE IMPAIRMENT BY 12
MONTHS. THE TRANSGENIC CARRIES
ARE HOMOZYGOUS ON HYBRID
BACKGROUND AND WE VERIFIED CAD
HEREIN AGE RELATED HEARING LOSS.
LIKE HUMANS IN COGNITIVE DECLINE
THESE MICE HAVE A REDUCTION IN
THE INHIBITION OF THE ACOUSTIC
REFLEX, THIS IMPAIRMENT OF
SENSORY MOTOR GATING WAS
CORRELATED WITH HIGHER LEVELS OF
A BETA 40 IN HIPPOCAMPUS. WE
HYPOTHESIZE IF THE 80-DECIBEL
PREPULSE WAS LESS SALIENT IN
MICE DUE TO HEARING LOSS THIS
EXPLAINING REDUCTION IN THE
INHIBITION OF STARTLE. SO FIRST
WE ASKED COULD ALZHEIMER'S
DISEASE LIKE PATHOLOGY EXIST IN
THE INNER EAR? ON THE LEFT WE
SHOW THAT AMYLOID PRECURSOR
PROTEIN AND BETA SECRETEST ARE
PRESENT IN THE EAR AND WE CAN
DETECT A BETA AGGREGATES NEAR
SYNAPSES BETWEEN INNER EAR CELLS
AND NEURONS. ON THE RIGHT WE
MEASURE A BETA 40 AND 42 AND
TEMPORAL BONES WE REZA USING APP
KNOCK OUT AS CONTROL. YOU CAN
SEE WE DETECTED LOW LEVELS IN
WILD TYPE AND HIGHER LEVELS IN
THE TEMPORAL BONES TRANSGENIC
MICE, AND THE CORTEX IN
HIPPOCAMPUS SHOWED A SIMILAR
PATTERN OVERALL AND RELATIVELY
MUCH HIGHER LEVELS THAN IN
TEMPORAL BONES. NEXT SLIDE
PLEASE. THE COCHLEAR NUMBERS
APPEAR SYSTEM IN TRANSGENIC MICE
AND THEIR NON-CARRIER SIBLINGS.
HOW IS THE HEARING? THE ABR WAVE
FORMS AND THRESHOLDS ARE NEARLY
IDENTICAL AT SIX MONTHS, 12 TO
14 MONTHS AND 16 TO 17 MONTHS.
NEXT SLIDE PLEASE. AS WELL THE
AMPLITUDES AND LATENCIES IN
WAVES 1 THROUGH 5 WERE NEARLY
IDENTICAL OUT TO 18 MONTHS. WE
VERIFIED WITH REPLICATION COHORT
SO WE ARE CONFIDENT IN THESE
RESULTS BUT THIS IS A LIMITED
MODEL OF ALZHEIMER'S DISEASE. WE
KNOW OUR OTHER GENETIC RISK
FACTORS LIKE APOE AND TAU AND
ENVIRONMENTAL FACTORS AS WELL SO
WE USE AD MORE AGGRESSIVE APP PS
1 MODEL WHICH IS ON A BLACK SIX
BACKGROUND, AND WE ALSO
INTRODUCED APOE KNOCK IN ALLELES
AND SLEEP DEPRIVATION AND WE
INJECTED PATHOGENIC TAU FROM
HUMAN CADAVERS. SO TAU INJECTION
HAPPENED AT FOUR MONTHS AND THAT
WAS FOLLOWED BY SLEEP
DEPRIVATION FO FOR SIX MONTHS
TESTED. SO THIS IS KIND OF LIKE
HAVING 40 HUMANS COME INTO THE
CLINIC, SOME HAVE TAU PATHOLOGY,
SOME DON'T, SOME SLEEP DEPRIVED
SOME NOT, SOME HAVE AMYLOID
PATHOLOGY OTHERS DONE. SOME HAVE
APOE BACKGROUND WHICH INCREASES
RISK IN HUMANS. APOE 3 ISOFORM
AND PROTECTIVE ISOFORM, NO
MATTER HOW WE SEPARATED THESE
OUT, NOTHING JUMPS OUT AS
CAUSING A THRESHOLD INCREASE.
WE LOOK AT WAVE 1 COMPARING THE
MICE THAT DID AND DID NOT HAVE
THE APP AND LUNG MUTATIONS AS
YOU CAN SEE THERE IS VARIABILITY
BUT NO DIFFERENCE ON AVERAGE.
LAST SLIDE PLEASE. I WON'T READ
HE IS BUT MAJOR CONCLUSIONS WE
FOUND NO AFFERENT AUDITORY
DYSFUNCTION IN THESE MICE
SUGGESTING THAT FAMILIAL
ALZHEIMER'S DISEASE AMYLOID
MUTATIONS AND OTHER
MANIPULATIONS THAT WE DID WHERE WERE
NOT SUFFICIENT TO CAUSE HEARING
LOSS. THIS SUGGESTS EXTRA
AUDITORY BRAIN REGIONS IN THE
ALTERED SENSORY MOTOR GATING
PHENOTYPE OF REDUCED PRE-PULSE
INHIBITION OF ACOUSTIC STARTLE
REFLEX. WE DID NOT FIND THESE
MICE HAVE FURTHER ACCELERATED
HEARING LOSS WHEN THEY ARE ON
BLACK 6 BACKGROUND. THANK YOU.
>>PROFESSOR: THANKS, MARK.
THERE WERE TWO QUICK QUESTIONS,
SEE IF YOU CAN GET TO ONE. DO
THE APP PS 1 MICE HAVE NORMAL
PHYSICAL ACTIVITY COMPARED TO
AGE MATCHED CONTROLS.
>> DO THEY HAVE NORMAL PHYSICAL
ACTIVITY? I'M NOT AN EXPERT ON
THE BEHAVIOR OF THESE MICE SO
I'M NOT SURE BUT I THINK IT
DEPENDS UPON WHAT TEST YOU PUT
THEM IN. SO FOR EXAMPLE THE
MORRIS WATER MAZE DON'T PERFORM
WELL ON THAT.
>> WHAT WAS THE RATIONALE FOR
THE SLEEP DEPRIVATION? WAS IT
INDUCE INFLAMMATION?
>> YES. SO SLEEP DEPRIVATION HAS
BEEN SHOWN TO BE CORRELATED WITH
WORSE BEHAVIORAL PHENOTYPES AND
ALZHEIMER'S DISEASE.
>> OKAY. THANK YOU FOR THE QUICK
ANSWERS TOO. WE ARE RIGHT ON
TIME. WE WILL TAKE A VERY SHORT
COUPLE OF MINUTE BREAK AND BE
BACK AT 1:45 WITH DR. KACZMAREK.
JUST A SHORT BREAK HERE.
>> WELCOME BACK, EVERYONE FROM
OUR VERY SHORT BREAK. WE WILL
FINISH WITH THE SECOND HALF.
WITH DR. KACZMAREK'S SLIDES UP
FROM EMORY UNIVERSITY. PLEASE
REMEMBER TO TURN ON YOUR CAMERA.
READY TO GO.
>> THANK YOU TO THE NIDCD AND
THE NIA FOR BOTH GIVING US THE
OPPORTUNITY TO DO THIS WORK AND
TO PRESENT IT TODAY. THE PRIMARY
GOAL OF OUR PRIMARY GRANT IS TO
ROOK AT POTASSIUM CHANNELS AND
HOW THEY MODULATE AUDITORY
PROCESSENING THE AUDITORY BRAIN
STEM. MAINLY WE FOCUS ON CLASS
OF CHANNELS CALLED KB 3 CHANNEL
WHICH IS ABSOLUTELY REQUIRED FOR
FIRING HIGH RATES WITH TEMPORAL
PREPRECISION AND THEY GO DURING
DEVELOPMENT AND STAY HIGH UNTIL
AGING THEN GO DOWN WITH AGING
AND THAT IMPAIRS THE ABILITY TO
LOCALIZE SOUNDS AND NOISE BUT
THERE IS ONE CHANNEL, THAT IS A
OUTLIER, FOUR -- CHANNELS ONE IS
CALLED KD 3.4. THIS IS AN ODD
PATTERN OF DISTRIBUTION, IT IS
PRESENT IN EVERY GROWTH CONE OF
ALL MAJOR FIBER TRACTS DURING
DEVELOPMENT. AND WHILE THOSE
TRACKS ARE NAVIGATING TO THEIR
TARGETS, IT IS THERE IN THE
GROWTH CONES, THEN THEY REACH
THEIR TARGETS, AND KV 3.4
EXPRESSION STOPS AND GOES AWAY.
IT COMES BACK AGAIN IN A FEW
NEURONS THAT USE AS A CLASSICAL
DELAY RECTIFIER TO ACTION
POTENTIAL BUT MOST JUST GOES
AWAY FOREVER. EXCEPT THE ONSET
OF ALZHEIMER'S, THIS IS NOT OUR
WORK, THIS IS WORK BY BUNCH OF
OTHER PEOPLE SHOWING THAT THE
EARLY STAGES OF ON COMES BACK IN
CORTICAL NEURONS THAT NEVER
EXPRESS AND ALSO APPEARS IN
GLIAL CELLS WHERE IT'S NEVER
BEEN BEFORE. SO WHAT WE ARE
ABLE TO FIND IS THAT IT -- THE
KV 3.4 CHANNEL FORMS IN
OBLIGATORY COMPLEX WITH A GWAS
ASSOCIATED GENE ENCODING CELL
ADHESION MOLECULE CAD HEREIN 9.
THEY FORM A COMPLEX WE SHOW IN A
NUMBER OF WAYS AND IF YOU GET
RID OF PCBH 89 THE CHANNEL JUST
GOES AWAY. SO IN THE MIDDLE OF
THE SLIDE ELECTRONIC WIZARD
VOLTAGE CLAMP EXPERIMENTS SHOWN
THE NORMAL KV 3.4 THEN WHEN IT
GOES AWAY, THIS NO CHANNEL ON
WESTERN BLOT YOU CAN SEE THE
CHANNEL GETS DESTROYED IF THERE
IS NO CELL ADHESION MOLECULE.
AND THERE'S NO CHANGE IN RNA,
THIS IS ABSOLUTELY REQUIRED. IF
YOU PUT KB 3.4 INTO A CELL LINE,
YOU FIND THE CELLS START PUTTING
OUT MIGRATING. -- FILIPODIAL AND
MIGRATING, ON THE BOTTOM OF THE
SLIDE. SO THAT IS -- WE HAVE
SHOWN THIS IN NEURONS TOO, THE
NEURONS FAIL TO GIVE YOU
ASCENSION OR BRANCHING IN
NEURONS WHEN YU KNOCK DOWN KV
3.4. SO WE THINK IS GOING ON IS
THIS COLLECTION IS AN ABSOLUTE
ESSENTIALLY ESSENTIAL COMPONENT
OF NEURONAL ELONGATION AND
GROWTH CONES, ALSO INTERACTS
WITH THE MICROTUBULES PROTEINS
THAT REGULATES RETURN OF TAU. SO
WE THINK OF THE ONSET OF
ALZHEIMER'S THESE COMPLEXES
START NEW DEVELOPMENTAL PROGRAM
THAT CAUSES THE NEURORIOTS IN
CORTICAL NEURONS TO START
MIGRATING TO PLACES THEY
SHOULDN'T BE GOING. THAT'S
BASICALLY WHERE I AM. THANK YOU.
>>
>> THANK YOU, DR. KACZMAREK.
WOULD YOU LIKE TO SAY -- WE HAVE
ABOUT A MINUTE WOULD YOU LIKE TO
SAY SOMETHING ABOUT WHERE YU
THINK THE NEXT CHALLENGE LIES OR
WHERE YOU MIGHT GO NEXT, NEXT
STEP?
>> I THINK IT IS CLEAR TO FIGURE
OUT IS THIS GOOD OR BAD, DO WE
WANT THOSE COMING OUT DURING
ALZHEIMER'S, WOULD IT BE BETTER
TO INHIBIT, PROCESSES STAY WHERE
THEY ARE AND DON'T LOOK FOR
OTHER PLACES OR IS THIS PART OF
A REGENERATIVE PROCESS THAT
WOULD BE ACCELERATEDDED AND HELP
CONDITIONS IF THEY CAN FIND NEW
SYNAPTIC CONNECTIONS, KEY
QUESTION THERE.
>> LOVE THE NEXT STEP. THANK
YOU. WE WILL MOVE FORWARD TO DR.
HONG BO ZHAO, UNIVERSITY OF
KENTUCKY.
>> I TURN ON MY CAMERA. DO YO CAMERA. NEXT
SLIDE. IN OUR STUDY WE USE APP
PS 1 AD MIOSES AND WE FOUND --
WE REPORTED ADR CHANGES IN THE
ADD DEVELOPMENT ALSO WE HAVE
DEVELOPED A NEW METHOD TO RECORD
AUDITORY EVOKE CORTICAL
POTENTIAL, AECP, IN MICE TO
ACCESS AECP CHANGES IN AD
DEVELOPMENT AND PROGRESSION IN
APP. AND ESSENTIALLY DATA WE
PUBLISH IN PREVIOUS PAPER. AND
THIS STUDY WE HAVE ALSO
INVESTIGATED EFFECT OF HIDDEN
HEARING LOSS ON THE AD
DEVELOPMENT AND PROGRESS. NEXT
SLIDE. AND THIS IS BETA WE GOT,
WE GAVE MICE FOR NOISE EXPOSURE
94 DB SPL AND PANEL A YOU CAN
SEE THE RED LINE IS THE A PP
MICE WITH NOISE EXPOSURE AND THE
BLACK ONE IS MICE WITH NO
EXPOSURE. YOU CAN SEE AFTER
NOISE EXPOSURE APP MICE CANNOT
COMPLETE RECOVERY. AT THE SAME
EXPOSURE. FOR THE PANEL B YOU
CAN SEE COMPARED TO THE APP MICE
COMPARED TO THE PREVIOUS NOISE
THE (INAUDIBLE) IS INCREASE THE
MICE IS OVER SIX MONTHS OLD.
MOST INTERESTING AFTER NOISE
EXPOSURE WE MAY PANEL A -- YOU
CAN SEE COMPARED TO THE WILD
MICE FOR THE NON-MICE EXPOSURE
APP MICE, AD MICE, THE NOISE
EXPOSURE AD MICE HAVE MORE
SIGNIFICANCE INCREASE FOR A --
RATIO. IN HERE PANEL A WE SHOW
THE CLICK AND ALSO 32-KILOHERTZ.
AFTER WE EXPOSE MICE AT SIX
MONTHS OLD AND WE CAN SEE TEN
MONTHS OLD, AFTER FOUR MONTHS
THERE IS SIGNIFICANCE. PANEL B
WE COMPARED APP MICE WITH THE
NOISE EXPOSURE, APP MICE WITHOUT
THE NOISE EXPOSURE ALSO WILD
TYPE MICE THE SAME AGE TWO
MONTHS OLD CAN SEE RED ONE IS
APP MICE WITH NOISE EXPOSURE B
THE BLUE ONE IS APP MICE WITHOUT
THE NOISE EXPOSURE. AND THE
BLANK ONE IS WILD MICE. NOISE
EXPOSURE CAN BE ACCELERATED OR
MAKE MOUSE WORSE. SO THIS DATA
SUGGEST THAT HIDDEN HEARING LOSS
CAN ACCELERATE AND EXACERBATE AD
DEVELOPMENT AND PROGRESSION. SO
THIS IS PREVIOUS STUDIES THAT
INVOLVE A -- REDUCING APP MICE,
THIS IS ONE -- NEXT SLIDE
PLEASE. THIS IS THE FOR THE
AUDITORY EVOKED CORTICAL
POTENTIAL IN APP AD MICE AND
WILD TYPE MICE. THE RED ONE MICE
IS SIGNIFICANT. SO THIS IS THE
PROGRESS CHANGES IN ACP MICE APP
AND WILD TYPE MICE WITH AGING.
THIS DATA IS SIGNIFICANT CHANGES
FOR INDICATED BY THE RED ARROW,
THE P 3 IS WAVE FORM, IT IS
SIGNIFICANTLY REDUCED IN APP
MICE. IT ALSO PUBLISH -- NEXT
SLIDE PLEASE. THIS IS FOR THE
DIFFERENCE SYNAPSE CHANGES DEP
GENERATION IN APP AND COMPARED
TO THE WILD TYPE MICE IN THE
MOUSE MODEL FOUR MONTHS OLD.
THANK YOU.
>> THANK YOU. CURIOUS ON NOISE
EXPOSURE, WHAT LEVEL OF NOISE?
>> 94 DBS SPL. WILD TYPE NOISE
TWO HOURS
>> TWO HOURS PER DAY.
>> TWO HOURS PER TIME ONE TIME.
>> JUST ONE TIME.
>> YEAH. LIKE TRADITIONAL
(INAUDIBLE) TO MAKE THE HIDDEN
HEARING LOSS,
>> THE NEXT STEP. FOR YOU? IF
YOU CAN CONTINUE THE WORK, THE
NEXT STEP.
>> I THINK I WILL BE CONTINUING
TO DO THE MORE DATA COLLECTION
AND REGARD -- BECAUSE MICE IS SO
EXPENSIVE.
>> AND THERE WAS A QUESTION IN
THE CHAT ABOUT WHAT IS THE MOUSE
STREAM?
>> APP PS 1 AD MICE.
>> THANK YOU, DR. ZHAO, WE WILL
MOVE TO DR. KIBUM LEE,
UNIVERSITY OF RUTGERS. TURN ON
YOUR VIDEO AS WELL.
>> CAN YOU HEAR ME OKAY?
>> I CAN HEAR YOU.
>> THANK YOU. THANK YOU NIDCD
AND NIAA. FOR THIS GREAT
OPPORTUNITY TO PRESENT. THESE SO
I WOULD LIKE TO DISCUSS THE --
RESPONSIBLE TO REMOVE PROTEIN --
ALSO RELATE TO -- PHOSPHOTAU BUT
ALSO RELATED TO ANY DEFECTIVE
RESPONSIBLE PROTEIN LIKE ALPHA
SYNUCLEIN AND AMYLOID BETA WE
MENTIONED THIS MORNING. SO THE
TRANSCRIPTION FACTORS OF TFEB IS
IS MAY PROMOTE PHOSPHOTAU
DEGRADATION. TRANSCRIPTION
FACTORS MAY CAUSE PHOSPHOTAU
DEGRADATION IN ALZHEIMER'S
DISEASE MODEL. THIS IDEA
DEMONSTRATED BY SCIENCE AND
AUTOSOMAL AND OTHER USE WE HAVE
A GOOD TARGET IS CLEAR SEQUENCE
IN THE KPB PROMOTER REGION.
TYPICALLY THESE PROTEINS USE
GENE THERAPY, TYPICAL METHOD BUT
THERE ARE MANY PROBLEMS. NEXT
ONE PLEASE. SO FROM THE NIDCD
PARTIAL SUPPORT WE DEVELOPED
(INAUDIBLE) TRANSCRIPT
TRANSLOCATE THE NUCLEUS, IT HAS
MANY DIFFERENT ADVANTAGE WHICH
CAN OVERCOME SOME INDICATION OF
VIRAL VECTOR APPROACH. SO THIS
TECHNOLOGY FULLY DEMONSTRATE
MANY (INAUDIBLE) PROTEIN STEM
CELL DIFFERENTIATION SENSORY
PROGRAMMING IN VITRO IN VIVO.
AND THEN IN THIS PROJECT, WE
WOULD LIKE TO -- THIS NANOSCRIPT
TARGETING TRANSCRIPT VECTORS
PROTEIN MEDIATED GENE REGULATION
SO YOU ARE O APPROACH IS WE --
OUR APPROACH IS WE FIRST
GENERATE NANOSCRIPT HAVING CLEAR
SEQUENCE IN THE DAMAGED NEURON
AND THEN WE WANT TO RECOVER THE
AUTOPHAGE LYSOSOMAL PATHWAY.
THIS CAME OUT WHAT I JUST
DESCRIBED. SO WE HAVE SOME
PRELIMINARY DATA, BASICALLY WE
WOULD LIKE TO COMPLIMENT OR
COMPLETE WITH CONVENTIONAL
APPROACH, ONE OF THE APPROACH
PARTICULAR USE OF VIRUS -- AB
VIRUS SO THAT WE CAREFULLY
COMPARE HOW WE CAN OVERCOME SOME
CONDITIONAL LIMITATION,
SELECTIVE TARGETED ANTIBODY AND
EVEN THE GENE ACTIVATION OR GENE
REPRESSION. SO THE CURRENT DATA
SHOWS COMPARED TO AAB SO WE HAVE
SIGNIFICANT IMPROVEMENT OVER --
JUST MENTIONED. AS ANOTHER
PRIMARY DATA, NEXT ONE PLEASE.
COLLABORATION WITH THE -- MY
COLLEAGUES PARTNERS, SO THE
FIRST PANEL BASICALLY USING THE
PHOSPHOTAU THAT WE WANT TO
DELIVER THE NANOSPACE TO COVER
AUTO PHAGE PATHWAY AND THE
BOTTOM SPACE WE TRY TO USE THE
ANIMAL MOUSE MODEL, CLEARLY
SHOWS THAT HE HAS -- SORRY SHE
HAS TAU MOUSE MODEL SO WE WANT
TO DELIVER NANOSPACE TO RECOVER
THIS AUTOPHAGE LYSOSOMAL PATHWAY
SO THAT WE MOVE THE PHOSPHOTAU
AND SEE SOME BEHAVIOR
IMPROVEMENT. THANK YOU.
>> THANK YOU, DR. LEE. LOOKING
FOR QUESTIONS IN THE CHAT. DO
YOU HAVE ANY PRELIMINARY DATA ON
REMOVING IT AND RESTORING IT?
>> WE HAVE SOME PRELIMINARY DATA
IN VITRO, IT IS CLEARLY
PROMISING DATA, RIGHT NOW SO WE
ARE ALREADY FOCUS ON THE IN VIVO
ANIMAL MODEL BUT IT TAKES TIME.
>> ABOUT HOW LONG? WHAT IS TIME
FRAME?
>> IN VIVO PROTEIN WE MAINLY
FOCUS ON TWO DIFFERENT, ONE IS
ENDOCRINE INJECTION BUT OTHER IS
(INAUDIBLE) SO EVENTUALLY WE
WANT DEMON INVESTIGATE THIS
TECHNOLOGY CAN CROSS THE --
DEGENERATE REGION, AGAIN, THAT'S
CHALLENGING BECAUSE THERE ARE
MANY ISSUE OF EBV BUT WE HAVE
SOME PROMISING DATA BUT IT IS
STILL TOO EARLY. EARLY TO SAY
SOMETHING.
>> THAT IS OKAY. APPRECIATE IT.
GOOD TO KNOW IT IS MOVING
FORWARD. THANK YOU DR. LEE.
MOVE ON TO DR. ANNE LUEBKE FROM
UNIVERSITY OF ROCHESTER.
>> I CAN HEAR YOU. GO AHEAD.
>> NOT SURE WHY IT IS LETTING ME
TURN ON MY CAMERA. THANKS AGAIN
FOR THE OPPORTUNITY TO PRESENT
OUR ANIMAL STUDIES RELATED TO E
GENE AND ALZHEIMER'S DISEASE.
AND THROUGHOUT THE TALK I WILL
CALL IT AD BECAUSE I ONLY HAVE
THREE MINUTES. I WOULD LIKE TO
ACKNOWLEDGE MY GRADUATE STUDENTS
AND HER GRADUATE STUDENT AND
LEFT OUT OF THE SLIDE IS MY
CO-PI FROM UIC WHO WILL BE
PERFORMING THE HISTOLOGY. NEXT
SLIDE PLEASE. NOW I'M ALLOWED
TO DO IT. WE ARE INTERESTED IN
THE EARLY DETECTION OF AD AND
THE AD MOUSE MODEL THAT WE ARE
USING ARE -- I USE THE SAME ONES
THAT PAT WHITE USED, THE 5X FAD
MOUSE WHICH CONTAINS FIVE
FAMILIAR AD GENES CROSSED WITH
BACKGROUND STRAIN MOUSE TO
ENSURE AGE RELATED GENE WAS
ELIMINATED SO THEY ARE NOT
CONFOUND AUDITORY STUDIES AND
NOT VESTIBULAR STUDIES. WE ARE
INTERESTED IN EARLY EVANS BEFORE
THE COGNITIVE DECLINE AS THERE
MAYBE MORE OPTIONS FOR
TREATMENT, IF AD CAN BE DETECTED
EARLIER. AIM'S PREMISE IS BASED
ON AD CLINICAL STUDIES
IMPAIRMENTS AND IMBALANCE THAT
OCCUR DECADES BEFORE COGNITIVE
DECLINE IN PATIENTS AND AIM 2 IS
ON TWO PREMISES, OCCURRING
BEFORE THE AD COGNITIVE DECLINE
AND HEALTHY SUBJECTS ROBUST
THRESHOLDS AND EXTENDED HIGH
FREQUENCY REGION, HAVE BEEN
LINKED TO BETTER AUDITORY
PROCESSING. HOW CAN WE ASSESS
STATIC IMBALANCE OR POSTURAL
SWAY IN MICE? IN PATIENTS SWAY
IS ASSESSED USING A FORCE
PLATFORM WHERE SUBJECTS STAND
STILL WITH EYES OPEN, EYES CLOSE
AND OTHER PERTURBATIONS. IN MICE
THIS IS TRICKIER. INSTEAD PLACE
THE MOUSE IN SIMILAR SENSITIVE
FORCE PLATFORM IN A SENSE WHEN
STILL HAND THAT IS PERIPHERY BIG
YOU GIVE SHORT FIVE MINUTE
ORBITAL ROTATION AND REASSESS
SWAY. THE BALANCE OR GATE IS USE
THE -- WITH LARGER RAT AND AFTER
TRAINING ASSESS THE TIME TO
FOLLOW-UP BEFORE AND AFTER
SIMILAR SHORTER VESTIBULAR
CHALLENGE.
BEFORE WE CAN USE THIS NEW
POSTURAL SWAY ASSAY FOR MICE WE
NEED TO ENSURE SO WE TESTED
POSTURAL SWAY TO FOUR LEGGED TOY
MOIST IN FIGURE D BLOWN UP AND
WE CAN CALCULATE A CENTER OF
PRESSURE, SO IN THE POSTURAL
SWAY FIELD CENTER PRESSURE IS
AREA OF ELLIPSE ENCOMPASSING 95%
SWAY POINTS. FOR EACH MOUSE WE
TEST SWAY BEFORE AN AFTER
VESTIBULAR CHALLENGE AND BNC YOU
CAN SEE EXAMPLES O THREE SWAY
AREAS WHICH IS THREE TESTS, FOR
FEMALE AND MALE MICE AND SINCE
SCAM IS LARGER ON THIS YOU CAN
SEE THERE'S TINY LITTLE DOT AT
BOTTOM RIGHT AND THAT IS OUR TOY
MOUSE SWAY LIST SO OBVIOUSLY
THERE IS NO -- IT IS AVENUESTIVE
MEASURE. WHEN WE TESTED SWAY FOR
THREE MONTHS 5X FAD MICE AN
COMPARED THEIR 5X CONTROL LITTER
MATES, WE FOUND NO DIFFERENCE IN
MALE 5X FAD CONTROLS AND
POSTURAL SWAY, BEFORE OR AFTER
CHALLENGE. THOSE ARE THE BLUE
OPEN OR CLOSE DOTS. WE DID FIND
SIGNIFICANT DIFFERENCE IN SWAY
IN FEMALE 5X FAD MICE WHEN
COMPARED TO CONTROLS. SIMILAR TO
AD PATIENTS. THE BALANCE TESTING
IS ONGOING. OUR -- WE DID A
PIVOT FOR AIM 2 AS YOU RECALL
FROM PAT'S TALK, AUDITORY NOSH
THRESHOLDS WERE SIMILAR BETWEEN
5X FAD AND CONTROL MICE AT THREE
AND SIX MONTHS. SO WE PIVOTED
AND AIM 2 PLANNING TO TEST
HEARING AN NOISE ABILITY USING
ACOUSTIC STARTLE, AND WE ALSO
WILL BE TEST TESTING AVR AND
HIGH FREQUENCY COCHLEAR REGIONS.
SO TODAY WE DETERMINED WE CAN
DETECT POSTURAL SWAY DIFFERENCE
IN THREE MONTHS OLD FEMALE 5X
FAD MICE. FUTURE STUDIES ASSAY
EARLY TREATMENT WITH AD APPROVED
DRUGS BLOCK OR DELAY AD
PROGRESSION IN THIS AND OTHER
MOUSE MODELS ESPECIALLY THE APOE
4 MICE MODEL THAT WAS MENTIONED
EARLIER. INFECTION WITH MOUSE
ADAPTED SARS COV-2 VIRUS CAN
MODEL HIGHER COVID
SUSCEPTIBILITY IN AD PATIENTS.
I'M HAPPY TO TAKE QUESTIONS
RIGHT NOW. IF ANYONE WANTS TO
ASK OTHER COVID RELATED STUFF ON
THE SLIDE I CAN ANSWER THAT.
>> THANKS, ANNE, I DON'T SEE
ANYTHING IN THE CHAT BUT I WAS
CURIOUS WHY THE SEX DIFFERENCES
DO YOU THINK?
>> WE DON'T KNOW. WE SEE SEX
DIFFERENCES IN POSTURAL SWAY, IN
ACTUALLY OUR APPARENT GRANTS ON
VESTIBULAR MIGRAINE AND WE SEE
IT IN VESTIBULAR MIGRAINE 2, BUT
THERE ARE MORE FEMALES GET
ALZHEIMER'S THAN MALES. THERE'S
MORE PREVALENT. IT IS A FOUR TO
ONE MAYBE A THREE TO ONE. SO
COULD BE THAT WE ARE PICKING
THAT UP. WE ARE CONTINUING TO
TEST MICE AT SIX MONTHS OUT. THE
MALE MICE AND ALL THE SAY ASSAY
AND SO FORTH TO SEE IF THEY WILL
SHOW THE DEFICIT JUST A LITTLE
BIT LATER THAN THE FEMALE MICE
DO. THEN JUST A QUICK -- THE
REASON OF DOING POTENTIAL COVID
IS WE HAVE PROOF WE CAN ACTUALLY
INFECT THE MOUSE ADAPTED COVID
MOUSE ADAPTED SARS COV-2 VIRUS
IN TO KNOCK OUT ANIMALS.
THERE'S PAPER RECENT PAPER THAT
SHOWED IN ADDITION TO PERHAPS
HAVING COVID TO SWEEP THROUGH
THE NURSING HOMES AND MEMORY
CARE CENTERS THERE COULD BE A
MECHANISM FOR WHY ALZHEIMER'S
PATIENTS WERE MORE AFFECTED.
THAT IS TO DO WITH INCREASE IL 6
AND SARS COV-2 BINDING TO THE
THETA AMYLOID IMPROVING SARS
COV-2 BINDING TO ACE RECEPTOR.
>> THANKS, ANNE. THANK YOU VERY
MUCH. NEXT WE HAVE DR. SRIRAM
JAYABAL FROM STANFORD. UNMUTE
AND PUT YOUR CAMERA ON.
>> THANK YOU FOR THIS
OPPORTUNITY TO SHARE THIS FORUM.
GOOD AFTERNOON, EVERYONE, TODAY
I WILL TALK TO YOU ABOUT CELL
BELLAIRE MEMORY DEFICITS IN
ALZHEIMER'S DISEASE. THE CENTRAL
FOCUS OF IS ON THE CORTEX. GIVEN
MOUNTING EVIDENCE THAT
CEREBELLUM IS INVOLVED IN HIGHER
COGNITIVE FUNCTION WE WANT --
CONTRIBUTE TO ALZHEIMER'S
DISEASE. ADVANCE. SO THERE'S
BEEN SOME LIMITED EVIDENCE SOME
WHICH IS DOCUMENTED DEFICITS IN
CEREBELLAR ANATOMY PHYSIOLOGY
AND BEHAVIORAL PERFORMANCE
INCLUDING EYE MOVEMENT
PERFORMANCE. WE WANTED TO EXTEND
THIS IN MORE SPECIFICALLY ASK,
IS IT THE LEARNING OR MEMORY
THAT IS AFFECTED? WE DID ADVANCE
A PARTICULAR KIND OF BEHAVIOR
CALLED VESTIBULAR REFLEX WHICH
MAKES COMPANYTORY TO VESTIBULAR
STIMULATION TO STIMULATE RETINA.
ONE CAN QUANTIFY THIS WITH --
WHICH ESSENTIALLY MEASURES HOW
MUCH THE EYE MOVES IN RESPONSE
TO RED REST OF THE HEAD
STIMULUS. THIS TASK HAS BEEN
USED AS A MODEL FOR LEARNING
MEMORY, AS YOU CAN TRAIN THE
MOUSE TO INCREASE ITS GAIN. WE
DO THIS IN LABORATORY BY PAIRING
VISUAL STIMULUS, THAT IS MOVING
OPPOSITE DIRECTION TO VESTIBULAR
STIMULUS. WE TRAIN 5X MICE WHICH
HARBOR -- AND ASSESS HOW THE
PROGRESS BY PRESENTING JUST
VESTIBULAR STIMULUS AT TIME
COURSE. AS YOU CAN SEE THE WILD
TYPE MICE CAN LEARN QUITE WELL
TO INCREASE ITS GAIN OVER THE
COURSE OF LEARNING. SO CAN THE
ALZHEIMER'S MICE. IT CAN JUST
(INAUDIBLE) QUITE AS WELL. SO
THERE SEEMS TO BE -- SEEMS TO BE
THE CASE THAT THE LEARNING IS
RESERVED IN ALZHEIMER'S. HOW
ABOUT THE MEMORY? SO TO LOOK AT
MEMORY, WE ASK HOW MUCH OF THE
LEARN IS RETAINED AT 2 AND 24
HOURS AFTER, ADVANCE. THE WILD
TYPE MICE (INAUDIBLE) AT 24
HOURS. THE ALZHEIMER'S MICE
SHOWS TREND TOWARDS DO OVERS
ADVANCE AND SIGNIFICANTLY
FORGETS AT 24 HOURS. SO WHAT I'M
SHOWING YOU HERE IS A CLEAR SET
OF MEMORY DEFICIT. THIS IS VERY
EXCITING, AND THIS MEANS THAT
THERE COULD BE BIGGER
CONTRIBUTION FROM THE CEREBELLUM
TO OTHER MEMORY DEFICITS IN
ALZHEIMER'S DEISM IT IS VERY
INTERESTING BECAUSE WE FOUND
THAT IT IS NOT THAT ALL
CEREBELLAR MEMORY ARE IMPAIRED.
WE CAN ALSO TRAIN THE MICE TO
DECREASE THE GAIN BY PRESENTING
VISUAL STIMULUS THAT IS MOVING
IN THE SAME DIRECTION AS THE
VESTIBULAR STIMULUS, YOU CAN SEE
WILD TYPE CAN DECREASE ADVANCE.
THE ALZHEIMER'S MICE CAN LEARN
BEHAVIOR AS WELL. IF YOU LOOK AT
MEMORY THE WILD TYPE MICE
ADVANCE THE ALZHEIMER'S MICE
GETS AS MUCH BUT NOT MORE. SO
THERE SEEMS NO SIGNIFICANT
CHANGE IN THE GENOTYPE SO JUST
TO PUT IT ALL TOGETHER THERE
SEEMS TO BE LIKE SELECTIVE
IMPAIRMENT OF CEREBELLAR MEMORY
IN ALZHEIMER'S MICE. THERE IS A
CLEAR MEMORY DEFICIT AND IT IS
SELECTIVE DEPENDING ON THE TASK.
SO I WOULD LIKE TO THANK
MACARENA, JENNIFER FOR EXPLORING
THIS NEW LINE OF INQUIRY AND
(INDISCERNIBLE) FOR FUNDING THE
STUDY. I HOPE I LEFT YOU NOT
ONLY WITH A GOOD MEMORY OF THE
WORK ADVANCE BUT -- AS WELL.
THANK YOU.
>> THANK YOU VERY MUCH. THERE
ARE COUPLE OF QUESTIONS IN THE
CHAT.CHAT. HOW OLD ARE THE MICE IN
THE LEARNING PARADIGM?
>> 5 TO 7 MONTHS.
>> EX THE MICE COMPENSATE FOR
LOSS OF CANAL INPUT IS ANOTHER
QUESTION?
>> WE HAVEN'T ASSESSED THAT
DIRECTLY. BUT THE FACT THAT
THERE IS A DEFICIT INDICATES
MAYBE THEY CANNOT AFTER 7 OR 8
MONTHS OLD. I HAVEN'T -- THEN
THERE IS ONSET OF DISEASE AND
HOW PROGRESSIVE DEFICITS GET SO
ONCE WE DO THAT I WILL BE ABLE
TO ANSWER THAT QUESTION. AND
OTHER MEMORIES WE CAN --
CONDITIONING. THAT IS A GREAT
QUESTION. OUR LAB IS NOT
EQUIPPED TO DO CONDITIONING BUT
WE ARE ASSESSING OTHER FORMS OF
MOTOR MEMORY WHICH ARE DEPENDENT
ON DIFFERENT CELLULAR MECHANISM,
THAT SHED LIGHT ON SELECTIVE
IMPAIRMENT. DO WE KNOW --
>> MEMORY ROTATIONS ARE STORED
IN CEREBELLUM AND ELSEWHERE.
>> THAT IS AN EXCELLENT
QUESTION, WE KNOW THERE IS
SYSTEM CONSOLIDATION HAPPENING
IN THE CEREBELLUM SO WE THINK
THE MEMORIES GET TRANSPORTED
FROM THE -- SO JUST THE BRAIN
REGION THAT -- ONE SYNAPSE DOWN
THE VESTIBULAR -- AND IT IS THE
PHYSIOLOGY OF THIS PARTICULAR
SYNAPSE THAT WOULD LEAD TO
SELECTIVE --.
>> I WILL STOP YOU, THERE ARE
MORE IN THE CHAT, IF YOU ANSWER
THEM IN THE CHAT. THANK YOU. I
HAD MORE MYSELF. SO DOCTOR JUDY
DUBNO, UNIVERSITY OF SOUTH
CAROLINA, IF YOU CAN UNMUTE AND
SHOW YOUR VIDEO FOR US.
>> HI, EVERYONE, THANKS TO NIDCD
AND I FOR BRINGS US TOGETHER
TODAY FOR SCIENCE, I ALSO LIKE
TO THANK -- (INDISCERNIBLE) AS
WELL AS MORAG LOUIS AND ERIC
HAMLETT INVESTIGATOR MS. THE
SUPPLEMENT. OUR GOALS TO DEFINE,
OUR GOAL IN THIS PROJECT WAS TO
FIND AND COMPARE MOLECULAR
CELLULAR ALTERATIONS ASSOCIATED
WITH PRESBYACUSIS AND AD. THIS
WAS A SUPPLEMENT TO THE CLINICAL
RESEARCH CENTER THE APPROACH WAS
MULTI-FACETED INCLUDING HUMAN
GENETICS, HUMAN BRAINS AND
TEMPORAL BONES AND MOUSE MODELS
OF AD. TWO AIMS ON GENETIC
VARIANTS AND ASSOCIATED
PATHOPHYSIOLOGY IN ANIMAL
MODELS. AND PATHOLOGIC
CONSEQUENCES IN HUMAN BRAINS AND
TEMPORAL. . OUR HYPOTHESIS WAS
THAT AD NEUROPATHOLOGY SEVERITY
CORRELATES WITH AUDITORY SYSTEM
PATHOLOGY SEVERITY AND COULD BE
CONCORDANT WITH GENETIC VARIANTS
OF INCREASED SUSCEPTIBILITY TO
AGE RELATED HEARING LOSS. WE
HAVE TWO AIMS THE FIRST AIM
DETERMINES EXTENT OF OVERLAP OF
GENES ASSOCIATED WITH HEARING
IMPAIRMENT AND THOSE ASSOCIATED
WITH DEMENTIA. AND WE USE TWO
MUTANT MOUSE MODELS OF DEMENTIA,
VASCULAR DEMENTIA AND AD TO ASK
IF HEARING LOSS OCCURS BEFORE
REPORTED SCIENCE OF BRAIN OR
COGNITIVE DEFICITS. IN AIM 2 WE
DETERMINE THE EXTENT OF
PERIPHERAL AND CENTRAL AUDITORY
SYSTEM PATHOLOGY AND
NEUROPATHOLOGY SEVERITY IN
BRAINS AND TEMPORAL BONES FROM
HUMAN DONORS WITH AND WITHOUT
CONFIRMED DIAGNOSES OF AD ADRD.
FOR AIM 2 WE ARE CURRENTLY
COMPLETING PROCESSING AND
ANALYSIS OF TISSUE FROM NORMAL
CONTROLS WITH PROMISING
PRELIMINARY FINDINGS, BUT TOO
EARLY TO REPORT. KAREN STEEL
WILL PRESENT RESULTS FROM AIM 1,
PLEASE INCREASE YOUR AUDIO LEVEL
TO BE SURE YOU CAN HEAR KAREN'S
NARRATION.
>> HELLO. THIS IS KAREN STEEL
FROM (INAUDIBLE) I WOULD LIKE TO
HIGHLIGHT TWO APPROACHES THAT WE
HAVE USED TO EXPLORE LINK
BETWEEN HEARING LOSS AND
DEMENTIA. THE FIRST EXAMPLE IS
SHOWN THIS SLIDE, WHERE WE HAVE
COMPARED THE GENES INVOLVED IN
HEARING LOSS AND GENES INVOLVED
IN DEMENTIA. WE HAVE A CURATED
LIST OF 720 GENES INVOLVED IN
HUMAN IMPAIRMENT IN SOME SORT IN
HUMAN AND MOUSE AND TOOK
LITERATURE TOTAL OF 147 GENES
PUBLISHED TO BE ASSOCIATE WITH
DEMENTIA. WE FOUND NO
SIGNIFICANT OVERLAP BETWEEN
THESE TWO GENES, THERE ARE ONLY
7 GENES OCCUR ON DEMENTIA LIST
AND HEARING IMPAIRMENT LIST. SO
WE FOUND LITTLE EVIDENCE FOR
COMMON SHARED GENETIC UNDERLYING
HEARING LOSS AND DEMENTIA. THE
SECOND APPROACH WE HAVE USED IS
TO LOOK AT MOUSE MUTANTS THAT
CARRY MUTATIONS WHICH ARE KNOWN
IN HUMANS AND IN THIS INSTANCE
WE LOOK AT DOUBLE MUTANT MOUSE 3
MUTANTS TO STUDY VASCULAR
DIMENSION. THESE MUTANTS HAVE
BEEN SHOWN TO COGNITIVE DECLINE
EIGHT MONTHS OLD. WE LOOK BEYOND
THRESHOLDS AT DIFFERENT STAGES
SHOWN HERE, FROM TWO MONTHS UP
TO 12 MONTHS, WE FOUND VERY
LITTLE EVIDENCE OF DIFFERENCE
BETWEEN THE THRESHOLDS IN THE
CONTROL GROUP AND MUTANT GROUP.
EVEN AT NINE MONTHS OLD WHICH IS
AFTER THE AGE WHICH COGNITIVE
DECLINE IS REPORTED. SO THESE
VASCULAR DIMENSION MUTANTS,
HEARING ABNORMALITIES DECKED
AFTER COGNITIVE DEFICITS. IT I DEFICITS WE LOOK
TO THE SECOND MUTANT, THE 5X FAD
MUTANT USED AS ALZHEIMER'S
DISEASE, IT HAS A NUMBER OF
DIFFERENT TUMOR MUTATIONS IN THE
APP GENE AND THE PSEN 1 GENE.
THIS HAS EARLY ONSET INDICATIONS
INFUSING AMYLOID PLAQUE DEPOSITS
IN TWO MONTHS OLD FROM SIX TO
NINE MONTHS OLD. BEYOND
THRESHOLD ONE MONTH UP TO NINE
MONTHS OLD. WE FIND LITTLE
EVIDENCE OF ANY DIFFERENCE
BETWEEN THRESHOLDS OF WILD TYPE,
HOMOZYGOTES AND HOMOZYGOTE THESE
MUTATIONS. IN THE 5X FAD
ALZHEIMER'S MUTANTS, ANY HEARING
LOSS THAT MIGHT OCCUR IS LONG
AFTER THE REPORTED BRAIN. SO
SUMMARIZE WE FOUND LITTLE
EVIDENCE FOR COMMON SHARED
GENETIC PATHOLOGY, UNDERLYING
HEARING LOSS DEMENTIA. IN
VASCULAR DEMENTIA OR ALZHEIMER'S
MOUSE MUTANTS ANY HEARING
ABNORMALITIES OCCURRED AFTER THE
REPORTED ONSET OF BRAIN OR
COGNITIVE DEFICITS. SO
THEREFORE, WE FOUND NO
BIOLOGICAL EVIDENCE ABOUT THAT
HEARING LOSS LEADS TO DEMENTIA.
THANK YOU.
>> THANK YOU. THANK YOU FOR
THAT. DOESN'T LOOK LIKE WE HAVE
A MOMENT FROM THE CLOCK. JUST
CURIOUS P THE MALE FEMALE MICE
WERE SEPARATE ARE SEPARATE,
CURIOUS --
>> ANALYZE SEPARATELY.
>> THANK YOU THANK YOU.
>> YES WE HAVE -- WE DON'T SEE
ANY DIFFERENCES IN THE
DIFFERENCE SEXES EITHER. WE HAVE
DONE A LOT MORE -- COLLECTED
MORE DATA BUT HAVEN'T ANALYZED
YET, WE ARE PRESENTING THE
THRESHOLDS TODAY.
>> NOW I INVITE EVERYONE TO TURN
ON CAMERAS WHO WANT TO
PARTICIPATE IN DISCUSSION. DR.
SUSAN SULLIVAN WILL BE
MODERATING AND I WILL TURN IT
OVER TO SUSAN.
>> THANK YOU, EVERYONE, GREAT TO
SEE HOW MUCH PROGRESS IS BEING
MADE AND HOW SUCCESSFUL THIS
PROGRAM IS. I THOUGHT WE START
WITH ARE THERE ANY UNASKED
QUESTIONS OF THE SPEAKERS THAT
YOU WOULD NOW LIKE TO TAKE THE
OPPORTUNITY TO ASK?
>> PLEASE SPEAK UP.
>> I CAN'T SEE EVERYONE ON THE
SCREEN SO PLEASE JUST SPEAK UP.
>> FAN GUANOSINE UNIVERSITY OF -- FAN, GUA NOSINE. GANG, ZENG.
CONCLUSION THAT HEARING LOSS
DOES NOT SEEM RELATED TO
ALZHEIMER'S DISEASE, RIGHT, IF
WE DEFINE HEARING LOSS SIMPLY
BASED ON ABR THRESHOLD, I THINK
PERHAPS YOU ARE RIGHT AND FROM
THE PREVIOUS TALK FROM OTHERS,
THERE IS A HEARING LOSS THAT MAY
NOT BE REFLECTED BY DEGREE OF
ABR THRESHOLD ELEVATION SO MY
QUESTION TO JUDY AND KAREN IS
THAT ANYTHING WE CAN SORT IN
THAT CONCLUSION A LITTLE BIT?
>> THE CONCLUSION IS WE HAVE
FOUND NO EVIDENCE YET. WITHIN
OUR SYSTEM THAT WE HAVE DONE. SO
FAR WE ONLY ANALYZED THE
THRESHOLDS. WE HAVE MORE DATA
TO ANALYZE. WAIT FOR THE DATA
ANALYSIS TO ANALYZE AN MAYBE WE
WILL FIND SOMETHING WHEN WE DO
THIS ANALYSIS BUT WE HAVEN'T
FOUND ANY EVIDENCE YET. SO THAT
WAS OUR CONCLUSION. THAT IS WHAT
WE CAN SAY. THAT IS WHAT THE
DATA --
>> THANK YOU.
>> I GUESS I HAVE A QUICK
QUESTION FOR KAREN, DID YOU -- I
CAN'T REMEMBER FROM THE SLIDES
DID YOU GO UP INTO EXTENDED
HYPERFREQUENCY GENERALS OR DID
YOU STOP AROUND -- REGIONS OR
DID YOU STOP AROUND 32?
>> WE WENT UP TO 42-KILOHERTZ,
THAT IS WHAT WE NORMALLY WOULD
DO.
>> I HAVE A LOUD OF QUESTIONS,
WHAT IS GENETIC BACK GROWN FOR
YOUR WILD TYPE MICE OR AD MICE?
I SEE HIGH RATIO, SPACE BETWEEN
ALL THE MICE. IN YOUR WILD MICE
IS ALL YOU HAVE SO YOU CANNOT
SEE ANY DIFFERENT BETWEEN AD
MICE AND WILD TYPE MICE.
>> WAY CURIOUS -- FOR THIS AD
MOUSE MODEL BECAUSE MOST
TRANSGENIC MOUSE MODEL IS C 57
GENETIC BACK GROWN. THIS IS
WHERE WE ARE KNOWN FOR THE MOUSE
MODEL.
>> SO THE ANSWER TO YOUR
QUESTION IS THAT THESE -- C 57
BLACK BACKGROUND, AND WE WERE
COMPARING THE WILD TYPE MICE ON
C 57 MICE AS WELL. (OVERLAPPING
SPEAKERS)
>> YOU CAN CONCLUSION AND FOR
YOUR DATA. ANALYSIS. THIS IS
DATA IF WE USE ORIGINAL ATPASE
MICE, THIS IS C 57 GENETIC
BACKGROUND YOU CAN SEE HIGH
FREQUENCY RANGE HUGE INCREASE
FOR WILD TYPE MICE OR LIKE ATP
MICE SO THIS GROUP --
>> SORRY, YOU ARE ABSOLUTELY
RIGHT, THE GENETIC BACKGROUND IS
CRITICAL AND WE ARE VERY CAREFUL
ABOUT MATCHING THE BACKGROUND OF
OUR MUTANTS COMPARED TO THE
LITTER MATE CONTROLS, THAT'S
WHAT WE HAVE DONE CERTAINLY WITH
5X CONTROLS THERE. WHAT WE WERE
LOOKING AT APR THRESHOLDS AT
AGES WHEN THERE ARE STILL
REASONABLE SENSITIVITY. WE
DIDN'T SEE ANY DIFFERENCE.
>> BECAUSE YOUR AGING RELATED
HEARING LOSS SO IF YOU ARE
LOOKING FOR YOUR WILD MICE ABOUT
NINE MONTHS OLD OR 12 MONTHS
OLD, HIGH FREQUENCY RANGE, IT IS
-- YOUR WILD TYPE CONTROL MICE
YOU ALREADY HAVE -- SO YOU HAVE
AD HEARING MOUSE ACTUALLY YOU
CANNOT -- CANNOT -- YOU CANNOT
(OVERLAPPING SPEAKERS)
DIFFERENTIATE BETWEEN THEM. I
THINK IT IS FOR THE AGING
RELATED HEARING LOSS UNDER AD IN
HEARING LOSS.
>> OR ALL WE CAN SAY IS REPORTS
SAID A COUPLE OF DEFICITS AND
BRAIN DEFICITS IN THE 5X FAD
MICE MUCH EARLIER THAN --
>> WE BASED ON OUR DATA WE CAN
DEFINE DIFFERENCE BETWEEN THREE
MONTHS OLD IN HIGH FREQUENCY
RANGE. (OVERLAPPING SPEAKERS)
>> I THINK IT IS REALLY
FASCINATING THAT THERE'S
DIFFERENCES THAT EACH OF THE
LABS HAVE FOUND. USING
DIFFERENCE STRAINS AND DIFFERENT
LINES AND I THINK THAT IN TRYING
TO UNDERSTAND WHY WE SEE
DIFFERENCES, IS PROBABLY THE
MOST IMPORTANT THING.
>> YES. I THINK -- WE ARE
(INAUDIBLE)
>> YES. AND I AGREE WITH THAT.
BUT I THINK THAT THAT POINT HAS
BEEN MADE.
>> I AM FROM UC SAN DIEGO. MY
QUESTIONS GOES BACK TO WHAT FAN
GANG RAISED. I'M NEW TO THIS
FIELD BUT WHAT HAVE LEARNED
SINCE I CAME TO THIS DISCIPLINE
IS KNOBBLED I DON'T KNOW TRY ARE
ELEVATED ABR THRESHOLD, DESCRIBE
ONLY FREQUENCY LOSS OF HEARING
AND DOES NOT CAPTURE PHENOMENON
LIKE HIDDEN HEARING LOSS AND IT
MAY BE RELATED TO SOME LANGUAGE
ASPECT NOT JUST PURE FREQUENCY
THRESHOLDS. IF THAT IS A
REASONABLE STARTING POINT, WE
STILL HAVE SOMETHING MORE TO
DISCOVER ON THE HUMAN SIDE LET
ALONE USE ANIMALS FOR
DISCOVERING ARE SUCH KNOWN
UNKNOWNS SO FAR. SO YEAH, IT
MAYBE A VERY NAIVE QUESTION, I
WOULD LIKE RESPONSE FROM JUDY,
OR ANYBODY ELSE.
SPEAKER5: VERY GOOD POINT, I WAS
GOING TO ADD COMMENTS TO FAN
GANG'S SUGGESTION WHICH IS A
VERY GOOD ONE. I THINK THOSE OF
US WHO ALSO WORK WITH HUMANS
UNDERSTAND SELF-REPORTS OF
HEARING DO NOT NECESSARILY
CORRELATE WITH AUDIO METRIC
VALUES ODD I DON'T KNOW TRY OR
ABR, AND WILL IS MORE TO LEARN
IN HUMAN STUDIES WHICH I HOPE TO
LEARN MORE THIS AFTERNOON. SO
BUT THOSE ARE THINGS THAT ARE --
WE ARE NOT ABLE TO EVALUATE IN A
MOUSE. SO I THINK THERE IS A
ROLE FOR BOTH KINDS OF STUDIES,
AND THE COMBINED INFORMATION WE
GET FROM BOTH WILL LEAD TO
CONCLUSIONS. KAREN'S POINT IS
BUY LOGICAL EVIDENCE. THAT IS A
VERY IMPORTANT. HUMAN STUDIES
WE LEARN DIFFERENT ASPECT AND
INFORMATION COMBINED.
>> QUESTION ABOUT VIRUSES. IF
YOU WERE A VIRUS YOU WOULD
PREFER TO GO THROUGH THE NOSE
THAT MAKES SENSE. THE COOL
THING IS WE INFECT NOSE OF THE
MICE WITH HSV 1 THE SITES FOR
IMPLEMENTATION ARE SMALL BUT
VIRUS IMMEDIATELY GOES THROUGH
TRANSGEMNAL NERVE WHERE IT
BECOMES DORMANT. BECAUSE ACTS GO
BOTH WAYS. THE SYSTEM WORKS
STRONGLY IN THE OLFACTORY
EPITHELIUM BUT THERE'S LITTLE
LEAKS THAT GO TO THE TRIGEMINAL
NERVE.
>> THANK YOU.
>> ANNE, DID YOU HAVE A
QUESTION?
>> I WAS GOING TO THE LAST POINT
WITH DIEGO, I WAS CURIOUS IF YOU
-- WHEN -- WITH YOUR VIRUS HAVE
YOU LOOKED AT IF THERE IS VIRUS
IN EPITHELIUM OF EW EUSTACIAN TUBE
OR IN THE NOSE THROUGH THE NASAL
CAVITY
>> WE HAVEN'T DONE IT BUT WE
SHOULD. WE HAVE DONE IT IN
BRAIN, IT GOES TO HYPOTHALAMUS
PLUS TO AREAS OF -- WE SHOULD
LOOK OVER THERE OF COURSE.
>> I'M WONDERING IF THAT COULD
BE A ROOT AT LEAST FROM COVID
STUFF IF THAT IS A ROOT TO INNER
EAR DEFICITS THAT WE SEE.
>> BY ANY MEANS.
>>
>> WE WILL BE LOOKING AT THAT
BUT CURIOUS OF A DIFFERENT VIRUS
IF YOU LOOKED ALREADY.
>> YOUR COLLEAGUES SHOWED BACK
SOME TIME THERE IS A TRIGEMINAL
BRANCH THAT GOES INTO THE BOWL.
>> ONCE WE -- (INDISCERNIBLE)
>> DO WE KNOW IF THAT COULD BE
RELEASING ANYTHING INTO THE BULB
DIRECTLY? THAT WOULD GET INTO
THE NOSE? LIKE VIRUSES?
>> I SUSPECT BUT I DON'T KNOW.
WE GET SOME INFECTION LATER ON
IN THE OLFACTORY BULB. INITIALLY
IT IS VERY SMALL. THE QUESTION
IS, IN THE REACTIVATION DO YOU
GET INFECTION THROUGH THERE.
>> I HAVE A QUESTION, IS ANYONE
WORKING WITH EITHER OTHER
NON-RODENT ANIMAL MODELS OR IN
VITRO SYSTEMS SUCH AS HUMAN
BRAIN ORGANOIDS OR ANYTHING
ALONG THOSE LINES?
>> WE HAVE CULTURES OF HUMAN
OLFACTORY NEURONS. AND WE ARE
INFECTING THEM WITH (INAUDIBLE)
BECAUSE THAT DOES NOT INFECT
MICE. AND ALSO HSV 1 AND SARS
COV-2. THERE IS INTERESTING
RESPONSES OF THE CELLS INCLUDING
CHANGES IN INTERLEUKINS. SO YES.
THAT IS HUMAN ORGANOIDS.
>> HOW WELL DOES DO SOME OF
THESE MODELS MIMIC THE HUMAN
CONDITION?
>> I THINK THAT IS A REALLY
IMPORTANT QUESTION BECAUSE LIKE
IN THE TRANSGENIC MOUSE MODELS
GENES ARE SUPEROVEREXPRESSED IN
THE DEPOSITION PATTERN GENES
DRIVE THROUGHOUT THE CNS IS
ARTIFICIAL. BASED WHERE PROMOTER
IS LOCATED. IN CONTRAST VIRAL
MODELS TO DRIVE PHOSPHORYLATED
TAU, SIMILARLY DEPEND UPON
PROMOTER. MODELS LIKE --
ENCOURAGE WHAT IS ENDOGENOUS,
WHAT IS PHYSIOLOGICAL. LIKE
SYNUCLEIN IN THE SYNAPSE TO
POTENTIALLY BECOME
PHOSPHORYLATED OR PATHOLOGICAL.
SO WILL IS A VARIETY OF
WEAKNESSES THERE.
>> I THINK IT IS A FANTASTIC
QUESTION AND ONE OF THE THINGS
WE ARE INTERESTED IN IS THE IDEA
THAT THERE MIGHT BE DIFFERENT
RATES OF PATHOLOGY IN SYSTEMS
DIFFERENT INDIVIDUALS SO IT
DOESN'T HAVE TO BE THE CASE THAT
ALZHEIMER'S IS GOING TO FOLLOW
THE SAME PROGRESSION OR SAME
PATTERN OF DAMAGE IN EVERY
INDIVIDUAL. MAYBE WE CAN LEARN
ABOUT TREATMENT STRATEGIES BY
LOOKING AT THESE DIFFERENT
SYSTEMS THAT HAVE DIFFERENT
PROGRESSION RATES. WITH AND
WITHOUT HEARING LOSS, MEMORY
LOSS FOR EXAMPLE. THAT IS A
HOPE.
>> I WAS GOING TO SECOND THAT.
IF I HAD MY RATHERS I WOULD LIKE
TO LOOK AT THE 5X FAD WHICH IS
PROBABLY OVEREXPRESSED BUT AND
THE APOE 4 AND THEN OTHER
COMBINATIONS AND IF I'M DOING
AUDITORY AND IT IS POSSIBLE TO
CROSS THEM WITH -- GET OUT THE
CAST AGE RELATED HEARING LOSS
MUTATION, THAT ALSO MAKES IT
CLEANER BUT SOMETIMES WHEN THERE
IS ALL THESE DIFFERENT -- THAT
WAS ONLY REALLY SUPER AVAILABLE
FOR US WITH -- BECAUSE WE ARE
LOOKING AT THE F 1 GENERATION OF
5X FAD. THEN WE CAN HAVE LITTER
MATES THAT DIDN'T HAVE ANY 5X
FAD AND YOU ONLY NEED ONE COPY
TO GET THE EFFECT. OTHER KIND OF
KNOCK OUTS AND SO FORTH, THAT IS
NOT POSSIBLE. BUT THAT IS A
CHALLENGE BECAUSE THE MICE COSTS
ARE EXPENSIVE AND IT WOULD BE
GREAT TO HAVE ALMOST HAVE A
GUIDANCE WHAT MICE AND LINES
WOULD BE USEFUL TO LOOK AT. SO
THAT PEOPLE COULD -- BECAUSE SO
FAR MOST OF THE STUFF IS ALL
BEEN THE AMYLOID BETA MOUSE
MODELS AN ONLY A FEW HAVE TALKED
ABOUT THE TAU. OBVIOUSLY IN
HUMANS IT IS BOTH. SO THAT IS A
COMMENT.
>> DEYEAH GO, DID YOU WANT TO --
DIEGO, DID YOU WANT THE ADD
SOMETHING IN
>> I SEE YOU ARE IN THE CHAT,
MAYBE YOU WANT TO BRING YOUR
POINTS UP?
>> FASCINATED TO SEE FROM
KAREN'S PRESENTATION, RIGHT? OUT
OF 700 GENES THAT CAN CAUSE
HEARING LOSS. AND 70 OR 80 THAT
CAUSE AD, ONLY SEVEN ARE COMMON.
TO BOTH. THAT FROM HUMAN SIDE
WE KNOW VIA LANSETT'S REPORT
THAT IN HUMAN LOSS IS THE
LEADING -- MODIFIABLE RISK
FACTOR. IF MODIFIED THAT CAN
REDUCE ALZHEIMER'S DISEASE. I
DON'T -- I DON'T HAVE ANSWER, I
FINE THERE'S SOMETHING THERE
THAT NEEDS TO BE ASKED. WHY
THERE'S SO FEW GENES COMMON BUT
WHY THEY PLAY SUCH SIGNIFICANT
ROLE. IN TERMS OF HUMAN LOSS,
ALZHEIMER'S DISEASE. IT IS NOT
AN LINEAR INTERACTION WHAT NON-
NON-LINEAR INTERACTION ONE CAN
IMAGINE BIOLOGICALLY.
(OVERLAPPING SPEAKERS)
>> IT TELLS US THAT BIOLOGY
ISN'T THE ONLY THING THAT THERE
MAY ALSO BE SOCIAL FACTORS
INVOLVED, WE WERE ASKING A
COUPLE OF QUESTIONS ABOUT
BIOLOGICAL ASPECT BUT OBVIOUSLY
NOT THE FULL STORY. IT DOESN'T
MEAN TO SAY THAT HEARING LOSS IS
STILL NOT A MODIFIABLE RISK
FACTOR FOR DEMENTIA, IT MAY WELL
BE BUT IT MAYBE A DIFFERENT
MECHANISM LINKED WITH BIOLOGICAL
BASIS.
>> I AGREE. BUT I WAS STRUCK BY
THAT ONE OF THE GENES WAS APOE,
IS THAT CORRECT? BECAUSE FROM
OUR COMORT FA D COHORT THERE WAS
A LADY 70 SOMETHING YEARS OLE, I
THINK 72 THAT DIDN'T GET
ALZHEIMER'S. BECAUSE OF APOE
MUTATION, THAT WAS A PAPER
PUBLISHED TWO YEARS AGO.
>> IF POSSIBLE -- SORRY TO
INTERRUPT, I WANT TO JUMP IN, I
HAD A DIFFERENT REACTION WHICH
IS I PUT IN THE CHAT IN RESPONSE
TO FAN GANG, WHICH WAS WOW,
ISN'T THAT EXCITING? WE SHOULD
LOOK AT THOSE SEVEN GENES.
RIGHT? LET'S TAKE THOSE
SERIOUSLY AND SEE WHAT THEIR
DOWNSTREAM EFFECTORS ARE. AND
ACTUALLY EXPLORE SOME OF THAT
NON-LINEARITY. SO WHAT THIS
LEADS TO GOING FROM A GENE TO A
PROTEIN TO A CIRCUIT FUNCTION TO
SYSTEM FUNCTION, THERE IS ALL
SORTS OF POSSIBILITIES THERE. SO
MY REACTION FAN GANG WAS TOTALLY
OPPOSITE.
>> INTERESTING RESPONSE.
>> 7 GENES IS NOT STATISTICALLY
SIGNIFICANT.
>> MAKE A DIFFERENCE IN THE
PERSON WITH ALZHEIMER'S.
>> IS THERE ONE MORE QUESTION
BEFORE WE WRAP UP THIS
DISCUSSION SECTION?
OKAY SO WE'LL STOP HERE AND
WE'LL TAKE A BREAK THEN WE WILL
COME BACK AND HEAR FROM OUR
COLLEAGUE WHOSE ARE WORKING
HUMAN STUDIES. AND THEN AT THE
END OF THE DAY WE'LL HAVE A
DISCUSSION THAT WE CAN HEAVY SIT
LIKE CHALLENGES AND FUTURE
DIRECTIONS AND THINGS ALONG THAT
LINE. SO EVERYONE ENJOY YOUR
BREAK.
>> PLEASE COME BACK AT 2:45.
>> WELCOME BACK. IT IS 2:45.
WE'LL GET STARTED AGAIN. MUTE
YOUR MIC AND VIDEO DURING THE
PRESENTATIONS, EXCEPT THE
SPEAKER AND WE WILL HAVE DR.
LANA WILL MODERATE THE SECOND
SESSION.
>> HELLO. OKAY. HELLO, EVERYONE,
I'M LANA SHUKUM LIKE AMY SAID.
OUR FIRST SPEAKER COMING UP IS
DR. JAY BUCKEY. PLEASE PROCEED.
>> THANK YOU, HANKS TO THE NIDCD
FOR SUPPORTING THIS AND ALSO MY
CO-INVESTIGATORS NINA KRAUSE
BOTH ROTH PEDRO AND CHRIS. MY
TALK IS I CAN'T UNDERSTAND YOU
WHEN OTHERS ARE YOU CAN TAKING,
WHAT DOES THIS TELL US ABOUT
ALZHEIMER'S IN THE BRAIN? SO WE
CAN UNDERSTAND SPEECH AT LEVELS
BELOW THE BACK GROWN NOISE. THIS
CAPABILITY COMES FROM THE BRAIN.
THERE IS A LOT GOING ON IN T
BRAIN WITH PROCESSING SPEECH AND
BACKGROUND NOISE, IT IS
IMPORTANT TO PROCESS THE SOUND
ACCURATELY. WAS THAT A G OR P,
SIMILAR SOUNDING. CORRECTLY
IDENTIFYING WORDS, DINNER OR
CENTER, MAKING SENSE OUT OF
CONTENT OF THE SENTENCE AND ALL
OF THIS IS HAPPENING REAL TIME.
SO WHILE YOU ARE WORKING ON
SENTENCE A WAS, THE SPEAKER MAY
HAVE MOVED ON TO SENTENCE B SO
PROCESS ISING SPEED IS
IMPORTANT. SO WE GOT INVOLVED IN
THIS THROUGH WORK WITH PEOPLE
WHO ARE LIVING WITH HIV. WE SAW
A RELATIONSHIP BETWEEN
PERFORMANCE ON A SCREEN TEST
COGNITIVE FUNCTION, THE MOCA AND
CENTRAL AUDITORY TEST
PERFORMANCE. WHAT THIS GRAPH
SHOWS ON THE Y AXIS YOU HAVE
MOCA SCORE WITH 30 BEST AND
LOWER SCORES BEING WORSE
COGNITIVE FUNCTION AND ON X AXIS
WE HAVE RESULTS FROM HEARING AND
NOISE TEST. WITH HIGHER NUMBERS
BEING WORSE ABILITY TO
UNDERSTAND SPEECH AND BACKGROUND
NOISE. WHAT WE FOUND WAS A
STRONG CORRELATION BETWEEN
SCREEN TEST, AND ABILITY TO
UNDERSTAND SPEECH OR NOISE,
ADVANCE.
>> PROCESSING COMPARED TO
CONTROLS: AND DETERMINE WHETHER
DIFFERENCES BETWEEN MILD
COGNITIVE IMPAIRMENT AND
COGNITIVE -- RESPONSE WE WON'T
TALK ABOUT THAT TODAY. SO WE
GOT PROJECT GOING, APPROVALS
READY TO GET STARTED AND COVID
INTERVENE, WE ARE BASICALLY
UNABLE TO (INAUDIBLE) BUT DURING
THAT TIME WE DID ESTABLISH A
COLLABORATION WITH DR. PEDRO AND
HIS GROUP AT MCGILL UNIVERSITY
AND DOUGLAS RESEARCH CENTER.
THEY HAVE ESTABLISHED COHORT OF
PATIENTS BOTH WITH ALZHEIMER'S
DISEASE AND MILD COGNITIVE
IMPAIRMENT ALSO WITH NORMAL
CONTROLS. THESE PATIENTS HAVE
EXTENSIVE NEUROIMAGING AND
BIOLOGICAL DATA. SO WE THOUGHT
THIS ALLOWED FOR GREAT
OPPORTUNITY FOR COLLABORATION.
THESE ARE TESTS THAT WE ARE
DOING, A GAP TEST WHICH IS THE
ABILITY TO DETECT SMALL GAP IN
NOISE. HEARING NOISE TEST TO
REPEAT A SENTENCE PRESENTED THE
BACKGROUND NOISE. THE TRIPLE
DIGIT TEST, THE ABILITY TO
DETECT THREE DIGITS PRESENTED IN
BACKGROUND NOISE. AND THE
AWARDS TEST WHICH IS THE ABILITY
TO DETECT WORDS PRESENTED
SIMULTANEOUSLY TO BOTH EARS. SO
THESE ARE JUST SOME OF OUR
PRELIMINARY RESULTS WE HAVE ONLY
JUST GOTTEN STARTED. BUT ON THE
LEFT PANEL, THIS SHOWS A MRI
TEMPLATE A 1 IS PRIMARY AUDITORY
CORTEX, A 2 IS SECONDARY
AUDITORY CORTEX. IN THE MIDDLE,
THE VIOLET AREAS ARE TAUD
DEPOSITION AND ACROSS THE TOP
YOU CAN SEE THE RESULTS IN
CENTRAL AUDITORY TESTS. GAP
DETECTION WAS 5.7 YOU MIGHT
EXPECT SOMETHING LESS THAN 5.
HINT RESULTS WERE YOU MIGHT
EXPECT MINUS 7, MINUS 5. TRIPLE
DIGIT MIGHT BE AROUND MINUS 30,
MINUS 28, 29 AND THEN THERE WERE
32 ERRORS ON THE SSW, NORMAL
USUALLY HAVE NONE. ON THE RIGHT
THIS IS SOMEONE WITH MORE
ADVANCED ALZHEIMER'S DISEASE,
THE AREAS THAT ARE IN BLUE ARE
MORE SEVERE TAU DEPOSITION. IN
THIS CASE YOU CAN SEE THE GAP
DETECTION IS HIGHER 8.4, HINT IS
WORSE, 1.3, TRIPLE DIGIT 23.7,
120 ERRORS IN SSW. SO THESE ARE
PRELIMINARY DATA FOR US BUT
CERTAINLY THINGS SEEM TO BE SO
FAR SUPPORTING OUR IDEAS. OUR
GOAL IS O ESTABLISH CROSS
SECTIONAL RELATIONSHIP BETWEEN
COGNITIVE IMPAIRMENT AND CENTRAL
AUDITORY TEST PERFORMANCE IN
PATIENTS WITH MILD COGNITIVE
IMPAIRMENT ALZHEIMER'SMENT AND
THEN IF WE DO SEE THAT OUR
FUTURE WORK ESTABLISHES CENTRAL
AUDITORY TESTS THAT CAN BE USED
LONGITUDINALLY TO TRACK
COGNITIVE PERFORMANCE. SO WHY
CENTRAL AUDITORY TEST? THE
REASON WE --
>> WE ARE AT FIVE MINUTES.
>> IT IS --
>> IT'S PASSEDED.
>> THEN I WILL STOP.
>> OKAY. THEN GO O THE NEXT
SPEAKER. SORRY TO BE HARD ON
YOU BUT I THOUGHT WE WERE ALL
DOING FIVE MINUTES A PERSON.
>> THAT'S OKAY. I TIMED IT UP
AND THOUGHT IT WAS GOOD.
>> OKAY. OUR NEXT SPEAKER IS DR.
SHANNON SHEPHERD FROM CHAPMAN
UNIVERSITY.
>> THANK YOU, I WANT TO THANK
DR. HILLICSS, PI -- HILLIS, PI
ON THIS, WHO. THE FOCUS OF OUR
PARENT GRANT AND OUR SUPPLEMENT
GRANT IS EMOTIONAL PROSOTY
REFERRING TO CHANGES SPEAKERS
MAKE TO PITCH, RHYTHM, RATE AND
VOLUME OF THEIR SPEECH TO CONVEY
THEIR EMOTION. EMOTIONAL
PROCESSING CAN CHANGE MEANING OF
SENTENCE, SO CONSIDER THE
SENTENCE I DIDN'T KNOW YOU WOULD
BE HERE COMPARED TO THAT SAME
SENTENCE, SPOKEN WITH ANGRY
PROSODY. I DIDN'T KNOW YOU WOULD
BE HERE. THEY HAVE DIFFERENT
INTENDED MEANINGS THOUGH THE
WORDS ARE THE SAME. EMOTIONAL
DEFICITS ARE TERMED APERSODIA.
YOU CAN HAVE EXPRESSSIVE OR
RECEPTIVE APROSODIA. PAST
RESEARCH FOCUSED ON INDIVIDUALS
WITH RIGHT HEMISPHERE STROKE. IT
IS A COMMON CONSEQUENCE OF RIGHT
HEMISPHERE STROKE. HAS THE
FOCUS OF PARENT GRANT. EVIDENCE
SUGGESTS THAT THERE IS EMERGING
EVIDENCE THAT APRISODIA OCCURS
IN INDIVIDUALS WITH
NEURODEGENERATIVE DISEASE,
RECEPTIVE EXPRESSIVE DEFICITS
ARE REPORTED IN INDIVIDUALS WITH
ALZHEIMER'S DISEASE OR AD AND
FRONTOTEMPORAL DEGENERATION OR
FTD. MORE SEVERE ARE INCREASED
DEPRESSION BEHAVIORAL ISSUES
MORAL CONFLICT WITH CAREGIVERS
WHICH IS GOING TO ALL LEAD TO
LOWER QUALITY OF LIFE FOR
PATIENT AS WELL AS FOR THEIR
LOVED ONES. ADVANCE. WE DON'T
UNDERSTAND HOW IT VARIES ACROSS
SUBTYPES OF AD AND FTD AND
STUDYING THESE DEFICITS AND
PATTERNS IN THE DEFICITS IN
NEURODEGENERATION HELP IDENTIFY
EARLY MARKERS OF
NEURODEGENERATIVE DISEASE, HELP
DIFFERENTIATE SUB TYPES OF AD
AND FTD AS WELL ATZ PROVIDERS OF
MORE INFORMATION ABOUT
NEUROCORRELATES OF EMOTIONAL
PROSODY. SO WE HAVE COLLECTED
DATA FROM SEVERAL SUB TYPES OF
AD AND FD BUT TODAY I WILL FOCUS
BRIEFLY ON THE DATA WE COLLECTED
IN PPAER O PRIMARY PROGRESSIVE
AFASCIA, IT IS A CLINICAL
SYNDROME THAT AFFECTS THE
COMPREHENSION AND EXPRESSION OF
LANGUAGE RESULTING FROM
NEURODEGENERATIVE --
NEURODEGENERATION. EACH CARIZED
BY PATTERNS OF LANGUAGE
DEFICITS, THERE IS TO MAN TICK
AND NON-FLUENT VARIANT, BOTH
MOST OFTEN ASSOCIATED WITH FTD
PATHOLOGY. AND THERE IS ALSO A
LOGOPENIC VARIANT, MOST OFTEN
ASSOCIATED WITH ATYPICAL
DISTRIBUTION OF AD. THESE OUR
THREE STAGE MODEL RECEPTIVE
EMOTIONAL PROSODY, WE DEVELOPED
IN OUR WORK IN RIGHT
RECOMMENDATION FEAR STROKE AND
WE ARE CONTINUING TO USE IN THE
CURRENT STUDY. SO JUST BRIEFLY
HERE STAGE 1 INVOLVES ACOUSTIC
ANALYSIS OF THE SPEECH SIGNAL.
STAGE 2 INVOLVES MAPPING
SPECIFIC PROSODIC FEATURES TO
THE APPROPRIATE EMOTION. FOR
EXAMPLE, MAPPING THE FEATURES OF
FAST RATE AND HIGH PITCH, ON TO
EMOTIONAL HAPPY. STAGE 3
INVOLVES SO MAN TICK
REPRESENTATION ACCESS TO THAT
EMOTION. AND THEN STAGE 2 AND 3
INTERACT AND FORM THIS LOOP WITH
DOMAIN GENERAL EMOTIONAL
LANGUAGE PROCESSING WHICH SERVES
EMOTION RECOGNITION IN SPEECH AS
WELL AS OTHER DOMAINS
RECOGNIZING FACIAL EXPRESSES.
SO WE FOUND THAT WITHIN RIGHT
HEMISPHERE STROKE PEOPLE HAVE
DIFFERENT PATTERNS OF DEFICITS
SO THEY HAVE DIFFERENT DEFICITS
THAT ARE CAUSING THE RECEPTIVE
APROSODEUA. WE HAVE INDIVIDUALS
WITH SLINGTIVE DEFICIT OF STAGE
1. -- SELECTIVE DEFICIT OF STAGE
1 AND SELECTIVE DEFICIT OF STAGE
2 AND THOSE WITH DIFFICULT
ADVERTISE WITH GENERAL DOMAIN
KNOWLEDGE PROCESSING. SO THESE
ARE OUR SELECT PRELIMINARY
FINDINGS FROM 18 INDIVIDUALS
WITH PPA. WE HAVE WE FOUND THAT
THERE IS TWO MAIN PATTERNS OF
THE DEFICITS, THE INDIVIDUALS
WITH LOGO PENIC AND SEW MAN TICK
VARIANT HAD DIFFICULTIES WITH
STAGE 1, 3 AND GENERAL
PROCESSING. NON-FLUENT VARIANT
HAD DIFFICULTIES WITH STAGE 1
AND 3, BUT NOT DOMAIN GENERAL.
ADVANCE. TO CONCLUDE THERE ARE
PATTERNS OF DEFICITS VARYING
ACROSS SUBTYPES OF AD AND FTD
AND FUTURE WORK AS COVID OF
COURSE DID EFFECT IT INCLUDES
ANALYZING OUR EXPRESSIVE DATA WE
COLLECTED AS WELL AS IDENTIFY
NEURAL CORRELATES OF EXPRESSIVE
AND RECEPTIVE ACROSS DIFFERENCE
SUB TYPES OF NEURODEGENERATIVE
DISEASE AND FINALLY
INVESTIGATING RELATIONSHIPS
BETWEEN LANGUAGE DEFICITS AN
PPA.
>> THANK YOU, OUR NEXT SPEAKER
IS DR. BRIAN MACWHINNEY. FIVE
MINUTES TOLL, IF YOU WANT
QUESTIONS SPEAK THREE MINUTES
THEN ALLOW TIMES FOR QUESTIONS.
>> I CAN'T START MY VIDEO. OKAY.
THIS IS RECORD ABILITY THE
DEMENTIA BANK. NEXT SLIDE. THE
DEMENTIA BANK IS ONE OF SIX
CLINICAL BANKS AND ALL -- WITH
DIFFERENT COURSES SOME HAVE BEEN
IN PLACE 32 YEARS, OTHERS 15
YEARS, TOTAL PUBLICATION ARE
10,000 FROM ARTICLES PUBLISHED
ON THIS DATAMENT THIS IS A
UNIFIED DATA. WE ARE FOCUSING ON
OPEN DATA SHARING. WHICH HAS
BEEN INTERESTING FOR DEMENTIA.
SAY A LITTLE BIT ABOUT THAT. WE
HAVE A SINGLE TRANSCRIPTION
FORMAT, WE HAVE INTEROPERABILITY
WITH DIFFERENT FORMATS, WE HAVE
A WIDE RANGE OF SOFTWARE, THAT
IS ANALYZE CORPUS ANALYSIS,
CHRONOLOGICAL ANALYSIS.
PROFILING SO ON. A LOT OF
ORIENTATION TOWARDS THE
COMMUNITY IN TERMS OF MEETINGS
AND GOOGLE GROUPS AND ADVISORY
BOARDS. ONE OF THE THINGS WE
ALSO RECEIVE SUPPORT FROM THE
OFFICE OF DATA SCIENCE STRATEGY
AT NIH COUPLE OF SUPPLEMENT
GRANTS FOR THE FAIR TRUST
STANDARDS, ALSO SUBSCRIBED IN
THE CORE TRUST SO WE ARE TRYING
TO BE RESPONSIBLE DATABASE.
NEXT SLIDE. SO FAR THIS WAS
WORK WAS FUNDED THROUGH
SUPPLEMENT TO AFASCIA BANK, WE
HAVE 13 CORPORA. WE HAVE ALSO
SET UP NEW AFASCIA USING BASIS
OF AFASCIA BANK PROTOCOL AND SET
UP PROTOCOL FOR DEMENTIA BANK
WORKING WITH ALISSA IN DELAWARE
TO COLLECT HIGH QUALITY DATA. SO
WE HAVE NOW 265 PUBLICATIONS AND
BASED ON DEMENTIA BANK DATA.
PRIMARILY PARTICULAR CORPUS THAT
WE HAVE GOT FROM ALZHEIMER'S
CENTER AT UNIVERSITY OF
PITTSBURGH. THIS IS REALLY THE
ONLY OPEN SOURCE CORPUS DEMENTIA
THAT IS AVAILABLE, IT IS
ABSOLUTELY REMARKABLE HOW MANY
STUDIES ARE BASED ON THIS.
PEOPLE ARE ALMOST ALL COMPUTER
SCIENTISTS USING THESE DATA
LOOKING AT THE LANGUAGE,
ACOUSTICS, IN THESE RECORDINGS,
JUST RECORDING OF NARROW BADLY
RECORDED, 25 YEARS AGO, BUT IT
HAS DRIVEN A HUGE AMOUNT OF
RESEARCH THAT IS ONE OF THE MAIN
CONTRIBUTIONS GETTING UP TO
LEVEL OF 94% ACCURACY IN
DETECTION OF DEMENTIA, EARLY
DETECTION. WE ALSO RUN
INTERSPEECH CHALLENGES,
DIFFERENT METHODS COMPUTATIONAL
LINGUISTIC MACHINE LEARNING,
HERE ARE MACHINE LEARNING MODEL
USED QUEUES USED, ACCURACY UP TO
93%. THESE ARE SOME OF THE
PROGRAMS THAT WE USE TO ANALYZE
DATA. SO WE WANT TO DO NOW IS
DEVELOP MORE DATA BETTER QUALITY
OTHER IS OUR OWN GOAL CORPUS
RIGHT TO APPLY ASR METHODS,
AUTOMATIC TRANSCRIPTION, WE HAVE
COLLABORATIVE COMMENTARY THAT IS
-- WOULD BE USEFUL FOR LEARNING
AND I HI I RAN OUT OF TIME.
RIGHT, LANA? I CAN'T HEAR YOU.
>> I HAVE TIME TO ANSWER
QUESTIONS, YOU HAVE 52 SECONDS.
>> THANK YOU.
>> ANY QUESTIONS? FOR DR.
MACWHINNEY?
>> I SEE A CLOCK THERE. PLEASE
DO LOOK AT THE CLOCK.
>> WE LIKE ALL YOU GUYS TO
CONTRIBUTE DATA. LET ME SAY
THAT.
>> I GUESS I HAVE ONE QUESTION.
IS -- ARE YOU -- IS THERE ANY
PLAN TO DO ANY TWITTER MINING OR
PUTTING IN THIS -- UP ON THE --
ALSO USING ALEXA TO CHECK DATA.
SO THERE ARE -- THEY ARE QUITE A
LOT OF PROJECTS THAT ARE
FILTERING IN TO DEMENTIA BANK
FROM DIFFERENT PLACES BUT THERE
ARE A COUPLE USING ALEXA. VOICE
ACTIVATED RECORDING.
>> ALL RIGHT. TIME IS UP. THANK
YOU.
>> THANK YOU.
>> NEXT SPEAKER IS GOING TO BE
DR. SWATHI KIRAN FROM BOSTON
UNIVERSITY.
>> SO WHAT I WILL TALK ABOUT
TODAY IS COLLABORATION WITH MY
COLLEAGUE AT UT AUSTIN, BOSTON
UNIVERSITY, UNIVERSITY OF
BARCELONA AND MASS GENERAL
HOSPITAL. AS PART OF THE GRANT
WE HAVE DEVELOPED A
COMPUTATIONAL MODEL CALLED --
THIS IS A MODEL OF BILINGUAL
LANGUAGE SYSTEM SEMANTIC SYSTEM,
IN THIS MODEL THERE IS A
SEMANTIC SYSTEM CONNECTED TO TWO
PHONETIC SYSTEMS L 1 AND 2. IN
THIS CASE WE ARE STUDYING
ENGLISH AND SPANISH BUT REALLY
WE CAN APPLY THOSE TO ANY
LANGUAGE COMBINATION. THE KEY
ASPECT OF -- IS TAILORED TO
INDIVIDUALS HISTORY OF EXPOSURE
TO EACH LANGUAGE AND THE PARENT
GRANT USE MODEL TO SIMULATE
AFASCIA BY INTRODUCING NOISE
THAT SO MUCH MATCHES WITH
BEHAVIORAL PERFORMANCE DURING
SEMANTIC PROCESSING AND OR
NAMING THE PARENT GRANT ALSO
SUPPORTS ONGOING RANDOMIZE
CONTROL TRIAL TO DETERMINE
OUTCOMES IN STROKE PATIENTS WITH
AFASCIA. WHILE STROKE CAUSES
DECLINE WITH REHABILITATION
THERE IS IMPROVEMENT IN
PERFORMANCE. WE CAN SIMULATE
INDIVIDUALIZED DECLINE IN
DEMENTIA. TO ORIENT YOU TO THE
SLIDE I WILL SHOW YOU LATER THIS
MODEL WE TEST VALUE WAIT
BEHAVIORAL PERFORMANCE ON TWO
MEASURES. FIRST IS NAMING, IS
LOOKING AT PICTURES AND NAMING
AND THIS IS DONE BOTH
COMPUTATIONAL MODEL AS WELL AS
HUMANS. WE MEASURE THIS USING A
COMMON TEST CALLED (INAUDIBLE)
TEST AND IN HOUSE NAMING SCREEN. SCREEN.
SEMANTIC PERFORMANCE, YOUR
ABILITY TO UNDERSTAND THESE.
DAMAGE IN THE LANGUAGE SYSTEM IS
DIFFERENT FROM DEMENTIA RELATIVE
TO STROKE. SO WE HAVE DEVELOPED
SEVERAL METHODS FOR BY TARGETING
THE FUNCTIONAL LAYERS THAT
CORRESPOND TO BRAIN REGIONS WE
THINK IS BELONGED -- RELATES TO
DEMENTIA PATHOLOGY. SO PICTURED
HERE ARE TWO LESION METHOD THAT
TARGET SEMANTIC MAP, THE FIRST
ONE THE OTHER PARTS OF THE MODEL
ARE LEFT INTACT BY BUT
PROGRESSIVELY MORE NEURONS IN
THE SEMANTIC MAP ARE MOVED OVER
TIME. ON THE TOP REMOVES NEURONS
AT ADJACENT TO THE PREVIOUSLY
REMOVED NEURONS SO FOCAL DAMAGE
VERSUS ONE AT BOTTOM NEURONS
CHOSEN AT RANDOM, WE CALL THIS A
DIFFUSE DECLINE. ANOTHER LESION
TARGETS INPUT TO THE SEMANTIC
MAP SO MOVING MORE SEMANTIC
FEATURES FROM CONSIDERATION WHEN
NEURON CLOSELY ATTACHED MATCHING
SEMANTIC INPUT AS CHOSEN SO
ALMOST LIKE LOSS OF SEMANTIC
FEATURE DEGRADATION UPSTREAM SO
YOU DON'T KNOW WHAT IT LOOKS
LIKE ANY MORE. THE LESION
TARGETS CONNECTIONS BETWEEN
SEMANTIC AND PHONETIC MAP AND
THIS IS PROGRESSIVELY REMOVING
THE CONNECTIONS BETWEEN THE
SEMANTIC AND PHONETIC MAP SO
THIS IS REMOVING CONNECTIONS
BETWEEN BRAIN REGIONS. SO WE
ARE IN THE PROCESS OF COLLECTING
LONGITUDINAL DATA FROM BILINGUAL
DEMENTIA PATIENTS SO PEOPLE WHO
SPEAK SPANISH AND ENGLISH AND
HAVE DEMENTIA. AND IN THE
MEANTIME WE ARE USING EXISTING
DATA FROM MONOLINGUALS WITH
DEMENTIA TO DO PRELIMINARY
ANALYSES OF HOW WELL THESE
LESIONS MATCH WHAT WE SEE IN
HUMAN PATIENTS. SO PICTURED
HERE ARE BEST FITS OF THOSE
LESIONS I JUST EXPLAINED TO YOU
FROM TWO MONOLINGUAL PATIENTS
WHOSE LONGITUDINAL NAMING AND --
SCORES REPORTED IN HOE PAPER FOR
SHARING THE DATA. BLACK LINES
HERE ARE MODEL PAPT SCORES,
SEMANTIC SCORES AND BLACK DOTS
ARE THE ACTUAL PATIENT SCORES
OVER TIME. BLUE LINES ARE MODEL
SCORES AND DOTS ARE ACTUAL
PATIENT SCORES OVER TIME. SO YOU
CAN SEE THAT AFTER -- DIFFERENT
PATTERNS OF DECLINE, FOR BOTH
PATIENTS ON THE RIGHT SIDE BEST
MATCH FIT OF THE DATA. SO YOU
LOOK ON THE TOP RIGHT IT IS A
LESION TARGETING SEMANTIC MAP
WHICH IS MUCH FOR RANDOM AND THE
BOTTOM RIGHT QUADRANT IS LESION
THAT IS MUCH MORE FOCUS. SO THIS
IS DIFFERENT FROM THE STROKE,
THIS IS PROGRESSIVE DECLINE. SO
OUR ONGOING WORK IS TO CONTINUE
TO RECRUIT TEST AND FIT
INDIVIDUALIZED MODELS, SPANISH
ENGLISH BILINGUAL PEOPLE WITH
DEMENTIA AND EXTENDING THESE NEW
LESION TYPES TO OTHER TYPES OF
DEMENTIA SUCH AS DIFFERENCE IN
MILD COGNITIVE IMPAIRMENT AND
PPA. THANKS.
>> THANK YOU DR. KIRAN. WE HAVE
30 SECONDS FOR QUESTION. LET ME
SEE IF THERE IS ANYTHING IN THE
CHAT. NO.
>> I THINK THERE WAS A QUESTION
ABOUT DECLINE IN DEMENTIA. WHAT
WE ARE TRYING TO DO -- CAN YOU
PLEASE RESTATE THE QUESTION FOR
THE VIDEOCAST?
>> WHEN YOU REPORT THE DECLINE
IN DEMENTIA DO YOU MEAN AD MCI
OR OR OTHER PHENOTYPES CAN YOU
BE SPECIFIC. WE ARE TRYING TO
DELINEATE BETWEEN DIFFERENT
TYPES OF DEMENTIA SO WHAT HE
WITH ARE FINDING IN DECLINE IN
MCI INVOLVES DIFFERENCE TYPE OF
LESION SEMANTIC LESION IN THE
MAP THAN PRIMARY AFASCIA, THAT
IS WHAT WE WILL BE ABLE TO FIND
OUT BY THE END OF THIS PROJECT.
>> TIME TO MOVE ON, NEXT SPEAKER
IS DR. NATALIE BUSBY FROM
UNIVERSITY OF SOUTH CAROLINA.
PLEASE TAKE IT AWAY.
>> HI. THANKS FOR HAVING ME.
>> TIMER ON.
>> SORRY. PERFECT. THANK YOU. SO
I WANT TO TELL YOU ABOUT WHAT WE
HAVE BEEN DOING LOOKING AT THE
ROLE OF (INAUDIBLE) COGNITION.
SO NEXT SLIDE PLEASE. SO WE ALL
KNOW OLDER AGE IS RELATED TO
COGNITIVE DECLINE AND THIS IS
LIKELY DUE TO THE ATROPHY THAT
OCCURS AS WE AGE. AS YOU CAN SEE
ON THE IMAGE THERE IS STRUCTURAL
CHANGES THAT OCCUR AS WE AGE,
THINGS LIKE WIDENING OF THE THE
CORTICAL -- AND ENLARGEMENT OF
VENTRICLES AND OVERALL CORTEX.
THIS IS ATTRIBUTE IS LIKELY
RELATED TO COGNITIVE DECLINE WE
SEE IN OLD AGE. NEXT SLIDE
PLEASE. WHEN WE THINK OF THIS
RELATIONSHIP BETWEEN AGE AND
COGNITIVE DECLINE WHAT WE
TYPICALLY THINK OF IS
CHRONOLOGICAL AGE. AND WHAT I
MEAN BY CHRONOLOGICAL AGE IS
SIMPLY HOW MANY YEARS IT WAS
SINCE YOU WERE BORN. WE THINK
CHRONOLOGICAL AGE BECAUSE OF THE
FAIRLY TYPICAL PROGRESSION OF
ATROPHY AS WE AGE WHICH IS
RELATIVELY CONSISTENT ACROSS
INDIVIDUALS. THE RATE WHICH
EXPERIENCES CORTICAL ATROPHY IS
SLIGHTLY DIFFERENT AND NOT
EVERYONE THE SAME CHRONOLOGICAL
AGE MIGHT HAVE THE SAME LEVEL OF
ATROPHY. THIS MIGHT BE AN
IMPORTANT FACTOR MANY THE
RELATIONSHIP BETWEEN AGE AND
COGNITION. SO SOMEONE YOUNG BUT
MORE ATROPHY, WE MIGHT EXPECT
THAT THEY SHOW SYMPTOMS OF MILD
COGNITIVE IMPAIRMENT MORE SO
THAN SOMEONE WITH LESS ATROPHY.
WHEN WE CAN MEASURE CORTICAL
INTEGRITY OF THE BRAIN AND
ESTIMATE SOMEONE'S BRAIN AGE.
WHAT I MEAN BY BRAIN AGE IS WHAT
AGE WE PREDICT SOMEONE IS BASED
ON LEVEL OF ATROPHY IN THE
BRAIN. IN ORDER TO CALCULATE WE
CAN TAKE SOMEONE STRUCTURAL T 1
SCAN SO WE CAN SEGMENT INTO GRAY
MATTER, INTO WHITE MATTER AND
CEREBROSPINAL FLUID TO GET A
SENSE OF OVERALL ATROPHY AND WE
CAN COMPARE TO A HEALTHY
CONTROLS USING THE BRAIN HR
ANALYSIS PROGRAM BY COLE AND
COLLEAGUES. TO USE THIS
ANALYSIS PIPELINE WE GET PREDICT
BRAIN AGE FOR EACH PERSON. ON
THE LEFT HAVE CHRONOLOGICAL AGE
OF 50 BUT ATROPHY THIS BRAIN
SUGGESTS THAT BRAIN AGE IS MORE
SIMILAR TO SOMEONE WHO IS AGE
67. ON THE RIGHT CHRONOLOGICAL
AGE OF 65 ESTIMATED BRAIN AGE IS
SOMEONE WHO IS MORE THAN 52.
USING THIS INFORMATION WE CAN
CALCULATE THE BRAIN AGE GAP. T
SO WE DO THIS BY TRUSTING
SOMEONE'S CHRONOLOGICAL AGE FROM
THE BRAIN AGE. AND IF WE GET A
COGNITIVE MEMBER IT INDICATES
OLDER BRAIN AGE THAN
CHRONOLOGICAL AGE. SO BRAIN AGE
MIGHT SHOW ATROPHY THAN SOMEONE
WE EXPECT FROM THAT AGE. THIS IS
ADVANCED BRAIN AGING. SO HERE IN
-- WE HAVE BEEN LOOKING AT ROLE
OF BRAIN AGE IN COUPLE OF WAYS.
SO ONE OF THESE IS PEOPLE WHO
HAVE CHRONIC AFASCIA FOLLOWING A
STROKE. AND SO FAR WE FOUND THAT
BRAIN AGE IS BETTER PREDICTOR
THAN CHRONOLOGICAL AGE OF
PERFORMANCE ON SEMANTIC TASKS
LIKE PALM TREES TEST. AND WE
FOUND THE BRAIN AGE GAP
DIFFERENCE BETWEEN CHRONOLOGICAL
AGE AN ESTIMATED BRAIN AGE IS A
PREDICTOR OF LANGUAGE APHASIA IN
ACUTE AND CHRONIC STROKE
DELIVERY. ADVANCE. AND THEN WE
HAVE ALSO BEEN INVESTIGATING THE
ROLE OF THE BRAIN AGE GAP IN
HEALTHY AGING WHILE HERE AT THE
UNIVERSITY OF SOUTH CAROLINA.
AND SO FAR WE INVESTIGATE HOW
BRAIN AGE IS ASSOCIATED WITH
RESTING STATE CONNECTIVITY AND
Ph.D. STUDENTS FOUND THAT
ADVANCE BRAIN AGING IS
ASSOCIATED WITH DECREASE
CONNECTIVITY NETWORKS IN THE
BRAIN IN HEALTHY AGING AND
CURRENTLY INTERESTED IN
EXPLORING THIS RELATIONSHIP
BETWEEN THE BRAIN AGE GAP AND
COGNITION. TO TRY TO SEE IF
PEOPLE WHO HAVE ADVANCE BRAIN
AGING MIGHT BE MORE LIKELY TO
DEVELOP MILD COGNITIVE
IMPAIRMENT. WE ARE ALSO
INTERESTED IN WHICH HELP OR
DEMOGRAPHIC FACTORS MIGHT
CONTRIBUTE TO BRAIN AGE GAP, SO
LIFESTYLE CHANGES WE CAN DO
WHICH MIGHT PROMOTE HEALTHY
BRAIN AGING. THIS IS A SHOUT OUT
TO EVERYONE WORKING ON THESE
PROJECTS HERE IN SOUTH CAROLINA
AND OUR COLLABORATORS. THANK
YOU.
>> THANK YOU, DR. BUSBY.
SCANNING FOR THE CHAT, I DON'T
SEE ANYTHING DIRECT. SO LET'S
MOVE ON. DRY JESSICA KLUSEK,
ALSO UNIVERSITY OF SOUTH
CAROLINA. YOU ARE UP NEXT.
>> HI. THANK YOU FOR HOSTING
THIS WEBINAR, VERY EXCITED TO
PRESENT ABOUT MY SUPPLEMENT
WHICH FOCUS ON FMR1 PREMUTATION
GENOTYPE AND ASSOCIATED WITH --
ASSOCIATION WITH AGE RELATED
COGNITIVE LINGUISTIC DECLINE.
BACKGROUND ON -- ON THE FRAGILE
X PERMUTATION, THIS IS A GENETIC
CONDITION CAUSED BY EXPANSION OF
THE TRINUCLEOTIDE SEQUENCE ON
THE FMR GENE ON THE X
CHROMOSOME. YOU MAY HAVE HEARD
OF THIS MUTATION BEING REFERRED
TO AS FRAGILE X CARRIERS BECAUSE
WOMEN WHO CARRY THIS MAY PASS TO
IT CHILDREN WHICH CAUSE FRAGILE
X SYNDROME. BUT EITHER IN THE
PRE-MUTATION OR FRAGILE X WE
KNEW THAT CGG EXPANSION DISRUPTS
THE PRODUCTION OF A REALLY
IMPORTANT PROTEIN FOR BRAIN
HEALTH AND BRAIN FUNCTION FMRP.
AND ACTUALLY THE PRE-MUTATION IS
COMMON, IT AFFECTS ONE IN 150
WOMEN, BUT THOUGH IT IS COMMON
WE DON'T KNOW ABOUT CLINICAL
PHENOTYPE BUT WE KNOW WOMEN WHO
CARRY THIS MUTATION SHOW HIGHER
RATES OF DEPRESSION ANXIETY,
THEY START TO SHOW EXECUTIVE
DYSFUNCTION BEGINNING MID LIFE
AND APPEARS TO WORSEN WITH AGE.
THERE IS ALSO EVIDENCE THAT THE
PREMUTATION IS ASSOCIATED WITH
SPECIFIC AGE RELATED CONDITIONS
SO THERE'S FACTS CHARACTERIZED
BY PREMATURE MENOPAUSE AND FXTAS
WHICH IS NEURODEGENERATIVE
DISEASE SO WE HAVE CONVERGING
LINES OF RESEARCH TO SUGGEST FMR
PERMUTATION MAYBE A CONDITION
ASSOCIATED WITH PREMATURE AGING
OR AGE RELATED DECLINE. Z BUT
THERE'S FEW STUDIES OF OLDER
WOMEN WITH A PREMUTATION, PRIAL
MARELY BECAUSE THE SAMPLE IS
RECRUIT -- PRIMARILY BECAUSE
SAMPLE IS E RECRUITED IN
CHILDREN WITH MOTHERS WITH
FRAGILE X SYNDROME. THAT IS
WHERE MY SUPPLEMENT COMES IN, SO
THE PARENT STUDY WAS A STUDY OF
ORAL AND WRITTEN LANGUAGE SKILLS
TO DEFINE PHENOTYPE AND
PREMUTATION CARRIER WOMEN AND WE
SPECIFICALLY FOCUS ON YOUNGER
WOMEN TO AVOID AGE EFFECTS. SO
FOR THE ADRD SUPPLEMENT WE
RECRUITED AN OLDER COHORT TO
LOOK AT CHANGES ACROSS AGE,
GOING UP TO 75 YEARS. SO OUR
GOALS WERE TO LOOK AT AGE
RELATED CHANGES IN COGNITIVE
LINGUISTIC SKILLS AND LOOK AT
ASSOCIATIONS WITH THAT FMR FMR1 AND
CGG REPEAT SEQUENCE. SO WE ARE
STILL ANALYZING THE DATA, TRY TO
KEEP WITHIN THE TIME LIMIT SO I
POOLED ONE GRAPH, I THINK WE
HAVE A LOT OF EXCITING FINDINGS
BUT THIS IS SHOWING AN EXAMPLE
SO THIS IS A REPETITION SUBTEST.
THAT DIFFERENTIATES IN OTHER
STUDIES PEOPLE WHO ARE AT RISK
FOR MILD COGNITIVE IMPAIRMENT
FROM THOSE WITH HEALTHY AGING
AND YOU CAN SEE HERE WE ARE
STARTING TO SEE PATTERNS OF CGG
REPEAT DEPENDENT VULNERABILITY
FOR AGE RELATED RISK. SO HERE IN
THE RED THOSE ARE WOMEN WITH
PREMUTATION WHO HAVE MID RANGE
CGG REPEAT SIZE. AND THERE IS A
GREATER ASSOCIATION WITH DECLINE
ACROSS AGE COMPARED TO WOMEN
WITH PREMUTATION WHO HAVE LOW OR
HIGH CGG REPIECE AND HEALTHY
CONTROLS. THIS IS CONSISTENT
WITH SOME OTHER RESEARCH SHOWING
THAT THAT MID RANGE CGG REPEAT
SIZE MAYBE ASSOCIATED WITH
INCREASE VULNERABILITY FOR AGE
RELATED DISEASE. CROSS SECTIONAL
DATA, SO WHAT WE WANT TO DO IS
FOLLOW-UP ON THIS WITH SOME
LONGITUDINAL STUDIES OF THE
PREMUTATION AND WE HOPE TO BE
DOING THAT, WE HAVE AN RO1 FROM
NIA PENDING WHERE WE WOULD BE
DOING THAT. SO WE ARE THANKFUL
FOR THIS SUPPLEMENT THAT ALLOWS
US TO GET THIS PRELIMINARY DATA.
>> THANK YOU. YOU HAVE ONE
MINUTE FOR ANSWERING QUESTIONS.
SEE WHERE WE ARE.
>> THERE IS ONE IN THE CHAT THAT
SAYS DO YOU -- EXHIBIT AUDITORY
HYPERSENSITIVITY?
THAT IS A GREAT QUESTION. AS AS
FAR AS I KNOW THERE'S NOT ANY
STUDIES ON THAT. BUT IN FRAGILE
X WE DEFINITELY SEE THAT SO
THERE IS REASON TO BELIEVE WE
SEE ANYTIME PREMUTATION CARRIERS
AS WELL BUT IT IS JUST A
POPULATION THAT HASN'T BEEN
STUDIED EXTENSIVELY SO THERE'S A
LOT OF RESEARCH DIRECTIONS THAT
WOULD BE GOOD TO GO IN.
>> COOL. THANK YOU. I THINK WE
ARE COMING TO OUR BREAK TIME, IT
IS 3:18, WE ARE SUPPOSED TO
BREAK AT 3:15. SO DO LOOK IN THE
CHAT, IF YOU WANT TO ANSWER
DURING THE CHAT OR LEAVE UNTIL
WE COME TO DISCUSSION AS YOU
WISH. LET'S GO ON BREAK FOR NOW.
TEN MINUTES. WE ARE SUPPOSED TO
START AT 3:25 EASTERN TIME.
WELCOME BACK, EVERYONE FOR THE
SECOND HALF ON THE SESSION ON
HUMAN RESEARCH. OUR FIRST
SPEAKER IS DR. BRYAN PFINGST,
UNIVERSITY OF MICHIGAN. PLEASE
PROCEED.
>> THANK YOU, SO THE APPARENT
RO1 THIS WORK IS BASED ON IS
CONCERNED WITH COCHLEAR
IMPLANTS, SPECIFICALLY WE ARE
LOOKING AT WAYS TO IMPROVE
HEARING WITH COCHLEAR IMPLANTS.
NEXT SLIDE PLEASE. SO FOR THE
SUPPLEMENT WHAT WE HAVE DONE IS
TO -- SET OUT TO DO IS LOOK AT
THE RELATIONSHIP BETWEEN THE
HEARING ABILITY, QUALITY OF
HEARING AND COGNITIVE FUNCTION
IN OLDER ADULTS. NEXT SLIDE WILL
SHOW WE HAVE THREE GROUPS WE
STUDIED TO DO THIS. WE HAVE A
GROUP OF EXPERIENCED COCHLEAR
IMPLANT USERS, WE HAVE A GROUP
OF IMPLANT CANDIDATES, WHO ARE
WEARING HEARING AIDS NOT DOING
WELL ENOUGH WITH THEM TO BE
HAPPY. AND WE HAVE A NORMAL
HEARING GROUP THESE ARE ALL AGE
MATCHED AND NORMS ARE BASED ON
AGE. SO WE HAD TWO AUDIO LOGIC
TEST BATTERIES THAT WE USE FOR
THESE SUBJECTS, MAIN ONELY TALK
ABOUT TODAY IS SPEECH IN NOISE
TEST TRACKING TO DETERMINE 50%
CORRECT FOR SIGNAL TO NOISE
RATIO. THEN WE HAVE A
ELECTROPHYSIOLOGICAL TEST WE
JUST USED WITH THE COCHLEAR
IMPLANT SUBJECTS TO ESTIMATE
NERVE SURVIVAL WHICH IS RELATED
TO HEARING ABILITY. WE WILL SAY
MORE ABOUT THAT TODAY.
COGNITIVE TEST BATTERIES INCLUDE
ADAPTED NIH TOOLBOX COGNITION
BATTERY. THAT IS OUR RATHER
INTERESTING BECAUSE (INAUDIBLE)
DEVELOPED THIS, IT TAKES UP A
LOT OF THE AUDITORY AND VERBAL
INSTRUCTIONS AND REPLACE PLACES
WITH WRITTEN INSTRUCTIONS SO IT
IS SUITABLE FOR PEOPLE WITH
HEARING LOSS. THEN WE USE A
REGULAR UDS NEUROLOGICAL TEST
BATTERY THAT WASN'T ADAPTED.
NEXT SLIDE. SO THESE ARE THE
RESULT THE SPEECH AND NOISE
TESTS. YOU CAN SEE WE GOT NICE
DIFFERENCES BETWEEN THE THREE
GROUPS. THE BEST HEARING IS
NORMAL HEARING SUBJECTS AS YOU
MIGHT EXPECT. THOSE ARE SHOWN IN
GREEN. LOWER RIGHT. ON THE LEFT
ARE THE COCHLEAR IMPLANT
SUBJECTS IN DARK BLUE NEXT BEST
AND THEN THE POOREST HEARING ON
AVERAGE WAS IN THE HEARING AID
GROUP. AS YOU CAN SEE, NICE
RANGE OF PERFORMANCE IN BOTH
COCHLEAR IMPLANT AND HEARING
GROUP WHICH IS WHAT WE NEED FOR
OUR STUDY. NEXT PLEASE. WE WILL
SKIP THIS SLIDE AND NEXT SLIDE.
AND GO TO THE SUMMARY FOR THE
COGNITIVE TEST RESULTS.
BASICALLY WHAT WE FOUND IS THAT
THERE ARE DIFFERENCES, BETWEEN
NORMAL HEARING GROUP AND TWO
GROUPS WITH HEARING LOSS ON
SEVERAL COGNITIVE TESTS BUT
TYPICALLY WE DON'T SEE
DIFFERENCE OR HAVEN'T SO FAR.
THIS IS A WORK IN PROGRESS
BETWEEN THAT AND THE HEARING AID
AND THE COCHLEAR IMPLANT GROUP
EXCEPT GERIATRIC DEPRESSION
SCALE, FOR THAT SCALE THE
HEARING AID GROUP SHOWED MORE
DEPRESSION THAN THE COCHLEAR
IMPLANT GROUP. SO THAT WILL BE
INTERESTED TO FOLLOW-UPMEN FOLLOW-UP. LAST
SLIDE I THINK. TALKS ABOUT
FUTURE DIRECTIONS. WE NEED TO
COMPLETE THE STUDY, I EMPHASIZE
WE ARE CHECKING AND ANALYZING
DATA AND PART OF THAT IS TO
COMPLETE THE
ELECTROPHYSIOLOGICAL PART. FOR
FUTURE DIRECTIONS IT WILL BE
INTERESTING TO MONITOR THE
CHANGES IN COGNITION OVER TIME
IF THEY OCCUR IN THAT PRE
IMPLANT GROUP, ALL IMPLANTED
SOON. THEN WE KNOW NOW WE NEED
MORE ADAPTATIONS FOR INDIVIDUALS
WITH HEARING LOSS. I WILL TAKE
30 SECOND WORTH OF QUESTIONS.
>> IS THERE ANY RELATIONSHIP
WEAN THESE FINDINGS AND THE
LENGTH OF TIME BETWEEN HEARING
LOSS ONSET AND TREATMENT? ONE
MIGHT EXPECT DIFFERENCES BETWEEN
PEOPLE TREATED IMMEDIATELY FOR
THEIR HEARING LOSS VERSUS PEOPLE
WHO WENT WITHOUT TREATMENT FOR
SOME TIME.
>> THAT IS AN INTERESTING
QUESTION AND ONE WE ARE TRYING
TO DEAL WITH BUT IT IS VERY
DIFFICULT TO FIGURE OUT EXACTLY
WHEN HEARING LOSS OCCURS. WE ARE
STILL LOOKING AT THAT.
>> ALL RIGHT.
I'M LOOKING FOR THE TIMER. I AM
HAVING TROUBLE FINDING IT.
>> TIME IS UP.
>> OKAY. SO LET'S GET READY FOR
OUR NEXT SPEAKER, THANK YOU, DR.
PFINGST. WHO -- LANA I WILL
INTERRUPT QUICKLY, IF FELICE
LOOK AT THAT QUESTION IN THE
CHAT AND TRY TO ADDRESS THAT,
THAT WOULD BE GREAT. THANKS,
LANA.
>> READY FOR THE NEXT SPEAKER,
DR. POORNA KUSHALNAGAR,
GALLAUDET UNIVERSITY. TAKE IT
AWAY.
>> HI, EVERYBODY. I'M POORNA
KUSHALNAGAR, PLEASURE TO BE WITH
YOU ARE, I WORK FOR CENTER FOR
DEATH HEALTH EQUITY AT GALLAUDET
UNIVERSITY. THANK YOU FOR THE
FUNDING IN ORDER TO FOCUS ON
THIS GRANT AWARD FROM NCDIC AND
ALSO THANK YOU TO PEOPLE WHO
HAVE BEEN INFORM MALI CARETAKING
ROLES WITNESS THEIR INDIVIDUAL
FAMILY MEMBER WHOSE ARE DEAF AND
EXPERIENCING ALZHEIMER'S AND
DEMENTIA. I WOULD LIKE THE
MENTION THIS PHENOMENAL TEAM,
ALL THESE INDIVIDUALS ARE DEAF
AND/OR HARD OF HEARING AND SIGN
LANGUAGE USERS. EACH MEMBER ON
THE TEAM HAS A CONNECTION WITH A
LOVED ONE THAT HAS DEMENTIA IN
THEIR FAMILY, A FRIEND AND/OR
WORKING WITH A POPULATION
CURRENTLY OF ADRD FOLKS. THEY
HAVE BEEN WORKING WITH US TO DO
THE DATA COLLECTIONS, THE
RESOURCING, NETWORKING, REACHING
OUT TO INDIVIDUALS WHO ARE THE
-- WHAT WE ARE REFERRING TO AS
INFORMAL CAREGIVERS OF ADRD
FOLKS. NEXT SLIDE PLEASE. WE
HAVE GATHERED DATA QUANTITATIVE
AND QUALITATIVE DATA AND I WOULD
LIKE TO FOCUS ON THE QUALITATIVE
PORTION FOR OUR STUDY TODAY. WE
INTERVIEWED A TOTAL OF 22 DEAF
HARD OF HEARING ADULTS, WHO ARE
CAREGIVERS OF INDIVIDUALS WITH
ADRD AND THEY WERE ALL OVER THE
U.S., PUERTO RICO, HAWAII
ISLANDS AND SO FORTH. SEVERAL
RECURRENT ISSUES ACROSS THE
GROUP INCLUDED MANY OF
EXPERIENCED DIFFICULTIES WITH
ACCESSIBILITY AND INFORMATION
SPECIFIC TO ALZHEIMER'S RELATED
DEMENTIA. THE INFORMATION WAS
AVAILABLE IN ENGLISH AND SPANISH
BUT NOT IN ANY SIGNED LANGUAGE,
THEY HAD DIFFICULTY ACCESSING
THE SUPPORT GROUPS AND OTHER
RESOURCES SPECIFICALLY FOR
CAREGIVERS. BECAUSE THEY WOULD
-- INFORMATION IS NOT
ACCESSIBLE, INTERPRETERS WERE
REQUESTED AN ONCE ENTERLET
PRETTIERS REQUESTED THEY
COULDN'T -- INTERPRET SERS
REQUESTED THEY COULDN'T FIND
SOMEONE QUALIFIED WITH ADRD
GROUPS. THEY ALSO STRUGGLED
FINDING FACILITIES FOR THEIR
LOVED ONES WHO WERE DEAF AND
UTILIZING AMERICAN SIGN
LANGUAGE. THE FACILITIES MAY NOT
HAVE HAD STAFF INDIVIDUALS OR
TRAINED PROFESSIONAL WHOSE
UNDERSTAND WHAT IT IS LIKE TO
WORK WITH A SPECIFIC POPULATION.
SO FAMILY MEMBERS OFTEN ENDED UP
BEING THE CARE TAKER OF THEIR
LOVED ONE IN THEIR RESPECTIVE
HOMES WHEN THEY SHOULD HAVE BEEN
IN MEMORY CARE FACILITIES.
THERE WAS A SIGNIFICANT AMOUNT
OF AGREEMENT THE QUALITY OF LIFE
AT PERCEPTION OF QUALITY OF LIFE
IS MUCH WORSE FOR PEOPLE WHO
CANNOT ACCESS RESOURCES IN THE
UNITED STATES AND TERRITORIES SO
THAT LED TO SEVERAL OF US WHO
YAW SAW IN THE PHOTO BEFOREHAND
THAT FATHERED AND WROTE A PAPER
TOGETHER TO IDENTIFY SEVERAL
CALLS TO ACTION. WE AGREE THERE
NEEDS TO BE INCREASED AWARENESS
OF ADRD IN SIGN LANGUAGE
SPECIFICALLY AND DELIVER
EVIDENCE BASED TRAINING IN SIGN
LANGUAGE TO THOSE CAREGIVERS OF
ADRD FOLKS FORMALLY AND
INFORMALLY. IN ADDITION TO
THAT, TO TRAIN HEALTHCARE
PROFESSIONALS, PRACTICERS AND
FACILITY ADMINISTRATORS AS TO
HOW TO WORK BEST WITH THIS
POPULATION OF INDIVIDUALS WHO
ARE DEAF AND HARD OF HEARING ASL
USERS. NEXT SLIDE PLEASE. THERE
ARE ALSO NEEDS TO BE SIGNIFICANT
AMOUNT OF O ADVOCACY FOR POLICY
INITIATIVES THAT REMEDY
SYSTEMATIC ISSUES AND
REIMBURSEMENT OF BARRIERS. OFTEN
DEAF AND HARD OF HEARING
CAREGIVERS CALL TO DOCTORS
APPOINTMENTS WITH LOVED ONES WHO
MAY BE HEARING BUT THE DEAF AND
HARD OF HEARING CAREGIVER NEEDS
TO HAVE ACCESS TO SIGN LANGUAGE
INTERPRETATION AND ARE OFTEN
ASKED TO PAY OUT OF POCKET
WITHOUT REIMBURSEMENT. -LY,
PROMOTE ONGOING RESEARCH AND
DISSEMINATION OF THAT ROLE OF
PAID DEMENTIA CARE WORKERS AND
FORMALLY AND INFORMALLY IMPACT
ON DEAF FOLKS WITH SHORT AND
LONG TERM ECONOMIC IMPACT TO ALL
THOSE IN THE COMMUNITIES. I'M
OPEN FOR QUESTIONS.
>> THANK YOU. LOOKING AT THE
CHAT. I DON'T -- SEE ANYTHING
RIGHT NOW BUT I WANT TO
ACKNOWLEDGE YOU BECAUSE YOU ARE
A UNIQUE PERSON IN THIS SPACE.
SO KUDOS TO YOU. NOT MANY
PEOPLE IN THIS SPACE. I SEE
SOMETHING IN THE CHAT. THAT WAS
ABOUT THE SCREEN PEOPLE CAN
ENLARGE BY MAXIMIZING THEIR
SCREEN FOR THE ASL. HERE IS A
QUESTION, ANY RELATIONSHIP -- IS
THAT THE OLD ONE? OLD ONE.
SORRY. MAYBE DURING DISCUSSION
WE WILL HEAR MORE ENGAGEMENT ON
THIS TOPIC. MOVING ON. OUR NEXT
-- THE NEXT SPEAKER IS DR.
CARRIE NIEMAN FROM JOHNS HOPKINS
UNIVERSITY.
>> GREAT. THANK YOU VERY MUCH.
SO MY NAME IS CARRIE NIEMAN, O
TOLL GIST AT JOHNS HOPKINS AND
CO-FACULTY AT JOHN HOPKINS
CENTER FOR HEARING AND PUBLIC
HEALTH WHERE I STUDY COMMUNITY
BASED APPROACHES FOR CARE IN
OLDER ADULTS. HEARING CARE OF
PERSONS WITH DEMENTIA TOUGHIE GO GO
IGNORED. WHILE WE LACK
NATIONALLY REPRESENTATIVE DATA
ON AUDIO METRIC HEARING LOSS FOR
PEOPLE WITH DEMENTIA WE CAN LOOK
COMMUNITY BASED COHORT,
COMMUNITY BASED COHORT SUCH AS
ERIC STUDY, THERE ARE A NUMBER
OF OTHERS BUT WE SEE HERE WITHIN
THE ERIC STUDY AND REALLY ACROSS
OTHER STUDIES THAT THE
PREVALENCE OF HEARING LOSS AMONG
PERSONS LIVING WITH DEMENTIA IS
PARTICULARLY HIGH. WHEN WE LOOK
IN ERIC STUDY OVER 80% OF
PERSONS LIVING WITH DEMENTIA IN
THIS COHORT HAVE A CLINICALLY
SIGNIFICANT HEARING LOSS. SO
THAT MAKES HEARING LOSS ONE OF
THE MOST COMMON CO-MORBIDITIES
THAT COMES ALONGSIDE DEMENTIA.
JUST AS WE THINK ABOUT HEARING
LOSS IN THE CONTEXT OF HEALTHY
AGING FOR OLDER ADULTS IN
GENERAL WE NEED TO BE THINKING
ABOUT IN THE CONTEXT OF THOSE
WHO ARE AGING WITH DEMENTIA. AND
ONE THING IN PARTICULAR IS
NEUROPSYCHIATRIC SYMPTOMS. THEY
ARE ALMOST UNIVERSAL FOR THOSE
INDIVIDUALS WITH COGNITIVE
IMPAIRMENT AND THESE REPRESENT
THE NON-COGNITIVE ASPECT OF
DEMENTIA. THESE ARE THINGS LIKE
AGITATION, ANXIETY, DEPRESSION,
AND THEY HAVE A SIGNIFICANT
BURDEN ON THE INDIVIDUAL AS WELL
AS CARE PARTNERS AND SOCIETY. SO
WE FOUND THAT WORSE AUDIO METRIC
HEARING LOSS IS ASSOCIATED
INDEPENDENT WITH INCREASE NUMBER
AND SEVERITY OF NEUROPSYCHIATRIC
SYMPTOMS AND THAT HEARING CARE
SPECIFICALLY USE OF HEARING AIDS
MAY BE PROTECTIVE WHEN IT COMES
TO NEUROPSYCHIATRIC SYMPTOMS.
BUT WE HAVE AN ISSUE IN THAT
SIGNIFICANT DISPARITIES EXIST
WHEN IT COMES TO HEARING AID USE
BY RACE AND ETHNICITY. AND AGAIN
WE DON'T HAVE NATIONALLY
REPRESENTATIVE DATA BUT WE CAN
LOOK AT THE ERIC COHORT. WHAT WE
SEE THERE ARE FOR INDIVIDUALS
WHO IDENTIFY AS AFRICAN
AMERICAN, WHO HAVE DEMENTIA AND
HEARING LOSS, JUST AROUND 7% USE
HEARING AIDS. THIS IS
PARTICULARLY TROUBLING WHEN WE
WITH ARE TALKING ABOUT DISEASE
PROCESS LIKE ALZHEIMER'S DISEASE
DEMENTIAS THAT HAVE
DISPROPORTIONATE AFFECT ON SOME
RACIAL ETHNIC MINORITY
COMMUNITIES, PARTICULARLY
AFRICAN AMERICAN OLDER ADULTS.
SO THIS BRINGS US TO OUR WORK
WITH HEARS. HEARS IS THE PARENT
GRANT. HEARS INTERVENTION IS
HEARING CARE INTERVENTION THAT
IS DESIGNED TO BE DELIVERED BY
COMMUNITY HEALTH WORKERS THAT
USES OVER THE COUNTER HEARING
TECHNOLOGY THAT IS ENTIRELY
DELIVERED BETWEEN IN A COMMUNITY
BASED SETTING. SO THE SUPPLEMENT
IS TO ADAPT THE HEARS
INTERVENTION TO BE SPECIFICALLY
DELIVERED FOR PERSONS LIVING
WITH DEMENTIA. SO THE ADAPTIVE
VERSION HAS KEY DIFFERENCES, THE
KEY DIFFERENCES ARE THAT THE
PROGRAM IS DELIVERED BY SPATHE
LANGUAGE PATHOLOGIST OR SPEECH
LANGUAGE PATHOLOGY ASSISTANT.
AND WE DID THAT REALLY BECAUSE
SPEECH LANGUAGE PATHOLOGISTS
PATHOLOGY ASSISTANCE ARE OFTEN
PRACTICING IN A HOME BASED
SETTING AND THERE ARE
POTENTIALLY REIMBURSABLE CODES
VIA MEDICARE AROUND ORAL
REHABILITATION THAT SPEECH
LANGUAGE PATHOLOGIST CAN BILL
FOR. SO THE INTERVENTION LOOKS
LIKE -- SPEECH LANGUAGE
PATHOLOGIST DELIVERING THE HEARS
INTERVENTION ADAPTED VERSION TO
PERSONS LIVING WITH DEMENTIA AND
HEARING LOSS AND THEIR CARE
PARTNER ENTIRELY IN A HOME BASED
SETTING. INSTEAD OF OUTCOMES
LIKE COMMUNICATION FUNCTION WE
ARE LOOKING AT NEUROPSYCHIATRIC
SYMPTOMS AND CAREGIVER BURDEN.
SO THROUGH A SMALL RANDOMIZE
CONTROL PILOT WE ARE PILOTING
THIS ADAPTED VERSION OF HEARS IN
ORDER TO TEST FEASIBILITY AND
ACCEPTABILITY AND SEE IF THIS
POTENTIALLY REIMBURSABLE MODEL
OF CARE CAN START TO TRULY REACH
THOSE WHO HAVE GONE UNTREATED IN
TERMS OF THEIR HEARING CARE.
THANK YOU VERY MUCH.
>> LOVELY. THANK YOU. CHECKING
THE CHAT.NA DA FOR NOW BUT THANK
YOU VERY MUCH. OKAY. MOVING
AHEAD O THE NEXT SPEAKER, THAT
WILL DR. HELEN COHEN FROM BAYLOR
UNIVERSITY. PLEASE PROCEED.
>> ACTUALLY BAYLOR COLLEGE OF
MEDICINE, BAYLOR UNIVERSITY IS A
DIFFERENT INSTITUTION. THEY HAVE
A FOOTBALL TEAM, WE DON'T BUT WE
HAVE REALLY SMART PEOPLE.
>> MY APOLOGIES. SORRY.
>> COMMON ERROR HERE IN TEXAS.
MY COLLEAGUES AND I ARE GRATEFUL
TO NIDCD AND NIA FOR THE FUNDING
SO THANK YOU VERY MUCH. FOR
SEVERAL YEARS I WAS I HAVE BEEN
DOING WORK ON SCREENING TESTING
PEOPLE FOR VESTIBULAR IMBALANCE
DISORDERS AND THIS IS A GREAT
OPPORTUNITY TO TEST POPULATIONS
TO LOOK AT THE ALZHEIMER'S
DISEASE GROUP. THE MAIN GOALS OF
THE STUDY WERE TO DETERMINE IF
PREVALENCE OF VESTIBULAR
IMPAIRMENTS IN THE ALZHEIMER'S
POPULATION DIFFERED
SIGNIFICANTLY WITH HEALTHY
PEOPLE THE SAME AGE AND 4
DETERMINE IF VOLUME OF
HIPPOCAMPUS IN ALZHEIMER'S
PATIENTS WHO HAVE VESTIBULAR
IMPAIRMENT IS SIGNIFICANTLY
REDUCED.
WE HOPED TO TEST 60 SUBJECTS,
UNFORTUNATELY DUE TO PANDEMIC WE
ONLY TESTED 26, 16 HAD
ALZHEIMER'S DISEASE, 10 HAD
PRECURSOR CONDITION MILD
COGNITIVE IMPAIRMENT. TO BE
DIAGNOSED AT OUR INSTITUTION,
PEOPLE HAVE TO COME IN WITH AN
MRI. SO WE ARE ABLE TO DO MRI
ANALYSES ON 11 OF THOSE PEOPLE,
THE QUALITY OF THE OTHERS WAS
NOT VERY GOOD BECAUSE THEY
WEREN'T ALL DONE AT BAYLOR. SOME
OF THEM WERE DONE IN COMMUNITY
CLINICS OR COMMUNITY TESTING
SITES. SOME WERE TOO OLD. WE
WERE ABLE TO COMPARE 22 SUBJECTS
WHO WERE AGE 70 OR OLDER TO 62
PEOPLE IN HEALTHY DATABASE THAT
WE ALREADY HAD. SUBJECTS WERE
TESTED ON STANDARD BATTERY OF
VESTIBULAR DIAGNOSTIC TEST
INCLUDING CERVICAL MYOGENIC
POTENTIALS WHICH IS TEST OF SACK
LAR FUNCTION, THAT IS ONE OF OUR
RESIDENTS DEMONSTRATING IT LOWER
LEFT. ONE OF THE GOLDEN OLDIES
YOU PROBABLY HER OF BITHERMAL
TESTING, DEX HALL PIKE MANEUVER
IS THE OTHER FOR TESTING
POSTERIOR SEMICIRCULAR CANAL AND
SUPINE ROLL TEST. WE ALSO
ATTEMPTED TO DO BALANCE
SCREENING WHICH I HAVE BEEN
WORKING WITH FOR SEVERAL YEARS,
WE TRIED TO DO TEN STEPS TEN
WALKING WITH EYES CLOSED AND
MODIFY ROMBURG. THE TEST
INSTRUCTIONS WERE TOO DIFFICULT
FOR SOME OF THE ALZHEIMER'S
SUBJECTS. AND THAT IS ME NOT A
PATIENT. NOT TO WORRY. THE
VESTIBULAR TESTING RESULTS SHOW
THAT THE NO DIFFERENCES BETWEEN
STUDY AND HEALTHY CONTROLS IN
VESTIBULAR TESTING BUT WE DID
FIND SIGNIFICANTLY MORE ABOUT
NORMAL RESPONSES, IN THE STUDY
SUBJECTS AND CERVICAL -- OF THE
PEOPLE WHO HAD ABNORMAL CERVICAL
VEM THEY HAVE DECREASED
HIPPOCAMPAL VOLUME, IT SPECIFY
LEFT BECAUSE TURNS OUT EVERYBODY
HAD RIGHT SIDE HIPPOCAM PAL
VOLUME. THIS SUGGESTS DECREASED
VESTIBULAR FUNCTION IN
STRUCTURES INNERVATED BY INFER
YOUR VESTIBULAR NERVE. WE
REPLICATED THE PREVIOUS FINDING
COLLEAGUES REPORT AND WE HAD TWO
NEW FINDINGS ONE ABOUT THE DIX
HALL PIKE TESTING AND TWO THAT
HIPPOCAMPAL VOLUME SO PROBLEMS
WE RAN INTO SMALL SAMPLE SIZE,
AND EVEN SMALLER SAMPLE SIZE FOR
MRI DUE TO POOR QUALITY IMAGING
FROM TESTING THE COMMUNITY. MY
MAIN RECOMMENDATION IS THIS IS A
TERRIFIC PROGRAM SO I HOPE WE
WILL CONTINUE WITH
INVESTIGATORS. IT WOULD BE GOOD
TO DO WITH LARGER SAMPLES BETTER
IMAGING WORK. THANK YOU.
>> THANK YOU, DR. COHEN. I DON'T
SEE ANY QUESTION IN THE CHAT. SO
LET'S MOVE ON. TO OUR NEXT
SPEAKER WHO WILL BE DR. PAMELA
SOUZA AND ANGELA ROBERTS, TWO
SPEAKERS FROM NORTHWESTERN
UNIVERSITY.
>> GOOD AFTERNOON, CAN EVERYONE
HEAR ME?
>> YES. THANK YOU.
>> EXCELLENT. THANK YOU. SO
THANK YOU FOR THE OPPORTUNITY TO
INCLUDE THIS WORK. I WILL
PRESENT ON BEHALF OF MYSELF AND
ANGELA ROBERTS WHO IS SUPPOSED
TO BE HERE TODAY SO THE PARENT
GRANT ON THIS PROJECT IS A WORK
FOCUSING ON OLDER ADULTS WITH
COGNITIVE ABILITY THAT IS NORMAL
FOR THEIR AGE. AND WHAT WE WERE
LOOK AT THERE IS CONTRAST ACROSS
DIFFERENT HEARING AND PROCESSING
TYPES. IN THE SUPPLEMENT WE ARE
EXTENDING THE WORK TO ADULTS
WITH CI AND DEMENTIA. SO JUST TO
GIVE YOU A LITTLE BIT OF
BACKGROUND. MOST OLDER ADULTS
WITH COGNITIVE IMPAIRMENT ALSO
HAVE AGE RELATED HEARING LOSS.
THANK YOU, CARRIE FOR
SUMMARIZING THAT SO WELL. THE
NEED TO DEPLOY COGNITIVE
RESOURCES IN THIS POPULATION IS
A PARTICULAR PROBLEM. BECAUSE
YOU CAN IMAGINE IF YOU HAVE
HEARING LOSS ALREADY, AND YOU
ARE ATTEMPTING TO DO REPAIR
STRATEGIES AND FILL IN MISSED
INFORMATION, THAT THAT IS REALLY
TAXING ON AN ADULT WHO ALSO HAS
COGNITIVE CHANGE, ADVANCE
PLEASEPLEASE. SO HEARING LOSS IS LOW
AMONG ALL OLDER ADULTS BUT
ESPECIALLY LOW AMONG ADULTS WITH
COGNITIVE IMPAIRMENT. AND WHAT
WE KNOW IS THAT THIS HEARING
REHABILITATION MAY NEED TO BE
CUSTOMIZED NOT JUST TO THE
AUDITORY ABILITIES U BUT ALSO
COGNITIVE ABILITIES OF THIS
POPULATION. SO THIS IS A
CLINICAL TRIAL OF HEARING AID
USE IN ALZHEIMER'S DISEASE AND
WHAT WE ARE DOING AGAIN IS
CONTRASTING DIFFERENT SIGNAL
PROCESSING STRATEGIES, BUT ALSO
COLLECTING DATA ON HEARING AID
USE IN GENERAL. THERE ARE VERY
FEW DATA ON THIS AND OLDER
ADULTS WITH COGNITIVE CHANGE ARE
EXCLUDED FROM ALMOST ALL HEARING
AID STUDIES. STUDIES. THEY ARE USUALLY
SCREENED OUT BY INCLUSION
CRITERIA. AND THEN THEY ARE JUST
A HANDFUL OF STUDIES ON THEM,
SOME WITH ADVANCE ALZHEIMER'S
DISEASE. SO WHAT WE DID WAS
RECRUIT A GROUP OF OLDER ADULTS
AND THEIR COMMUNICATION PARTNERS
WHICH TYPICALLY THEIR SPOUSES,
IN TO THIS TRIAL WHERE THEY ARE
TESTED THREE TIMES, FIRST
WITHOUT HEARING AIDS, THEN FIT
WITH HEARING AIDS CONVENTIONAL
HEARING AIDS AND THEY WE ARE
THEM FOR A PERIOD OF ABOUT A
MONTH. THEY COME BACK AND WE
MEASURE OUTCOMES AFTER THEY HAVE
BEEN WEARING THE AIDS IN THEIR
EVERY DAY LIFE OBJECTIVE
OUTCOMES WHICHLY TALK ABOUT
TODAY SUBJECTIVE OUTCOMES. WE
THEN SWITCH THE PROCESSING TYPE
THEY REPEAT THE TRIAL AND WE CAN
HAVE A COMPARISON OF NO HEARING
AID TO HEARING AID AS WELL AS
WITH DIFFERENT HEARING AID
FITTING STRATEGIES. NOW, WE DID
HAVE TO MAKE SOME MODIFICATIONS
WHEN COVID CAME, WE HAD INTENDED
TO RECRUIT OLDER ADULTS WITH
DIAGNOSIS AND EXTENSIVE WORK UP
THROUGH THE NORTHWESTERN
ALZHEIMER'S DISEASE CENTER. BUT
THEY SHUT DOWN TO IN PERSON
TESTING FOR FAIRLY LONG PERIOD
OF TIME, DUE TO COVID. SO THEY
DID A RECRUITING THROUGH THE
COMMUNITY WHICH WORKED WELL. WE
HAD INTENDED TO DO OUR OUTCOME
MEASURES ON A CONVERSATION
ANALYSIS BETWEEN THE
PARTICIPANTS AND PARTNER IN
THEIR HOME AND THAT WAS NO
LONGER FEASIBLE. SO I'M GOING TO
SHOW YOU THE TASK IN A
STRUCTURED WAY. SO THIS IS A
TASK WHERE THEY ARE DESCRIBING
DIFFERENCES IN PICTURES BETWEEN
THE PARTICIPANT AND THEIR
COMMUNICATION PARTNER, THEY
CANNOT SEE EACH OTHER'S PICTURES
AND WE CAN THEN ANALYZE
CONFERENCE DROP OUTS, EFFICIENCY
OF COMMUNICATION AND ACCURACY.
IF YOU PLAY THE SOUND FILE MANY
HERE IS A QUICK EXCERPT OF WHAT
HAPPENS.
>> OKAY. GOOD. IS ONE, DOES ONE
HAVE --
>> A SHEEP.
>> A SHEEP, WHATEVER THEY ARE.
ONE IS SUPPOSED TO BE A SUE AND
A TED, DOES YOURS SAY THAT?
>> WHAT?
>> SUE, SUE. S U E. AND TED. T
E D. A MAN -- A GAL AND A --
>> OH, I GUESS ONE'S A GIRL.
>> DID THEY LOOK DIFFERENT, DOES
ONE HAVE LIKE A BROWN -- DO THEY
LOOK DIFFERENT, THE TWO SHEEP?
>> YES.
>> NEXT SLIDE PLEASE.
>> OKAY. GOOD. IS ONE --
>> GO AHEAD AND ADVANCE. SO HE
HAS A COGNITIVE DIAGNOSIS, HE
HAS HEARING LOSS AND THE WIFE
TRYING TO DESCRIBE TO HIM AND
YOU HEARD THE CONVERSATION DROP
OUT. HE GOES WHAT? SHE TRIES TO
REPAIR. SO IN THIS SLIDE WHAT WE
ARE LOOKING AT IS THE
IMPROVEMENT IN THE LEFT ALL
THESE ARE INDIVIDUAL
PARTICIPANTS BECOME MORE
ACCURATE AT THE TASK. WITH THEIR
HEARING AIDS ON. ON THE RIGHT
SIDE IS EFFICIENCY, THEY BECOME
QUICKER AT THE TASK WITH HEARING
AIDS ON SO WE HAVE A SENSITIVE
MEASURE IN A REALISTIC SITUATION
TO HEARING AID USE. NEXT SLIDE
PLEASE. JUST TO WRAP UP WE ARE
CONTINUING DATA COLLECTION, ALSO
LOOKING AT PATIENT PREDICTORS
COGNITIVE AND AUDITORY
PREDICTORS. AS WELL AS A DEEPER
ANALYSIS ON THE TASK. THANK YOU.
>> THANK YOU, DR. SOUZA. ALL
RIGHT GIVEN THE TIME WE SHOULD
MOVE TO OUR NEXT SPEAKER WHO IS
DR. MELANIE FRIED-OKEN FROM
OREGON. TAKE IT AWAY MELANIE.
>> THANK YOU. I WOULD LIKE TO
SAY BEFORE I BEGIN THAT I HAVE
RESEARCH ENVY FOR ALL OF THOSE
WHO WERE NOT QUITE AS AFFECTED
BY THE PANDEMIC BECAUSE THEY
WEREN'T COLLECTING DATA ON HUMAN
PARTICIPANTS. SO THANK YOU. I'M
IMPRESSED WITH ALL OF THE WAYS
THAT WE WERE ABLE TO COLLECT
DATA ON HUMAN PARTICIPANTS. GOOD
JOB US. I'M GOING TO BE TALKING
ABOUT THE EFFECT OF USING A
BRAIN COMPUTER INTERFACE, THAT
PROVIDES NEUROFEEDBACK ON
COGNITIVE PROCESSES UNDERLYING
READING. IN PERSONS WITH
ALZHEIMER'S DISEASE. NEXT SLIDE
PLEASE. SO THE PARENT GRANT IS
DEVELOPING AND TESTING A BRAIN
COMPUTER INTERFACE FOR
COMMUNICATION WITH INDIVIDUALS
WITH LOCKED IN SYNDROME AN
JUSTIFICATION FOR THE SUPPLEMENT
WAS THAT PRIOR BCI RESEARCH
SUGGESTS THAT NEUROFEEDBACK MAY
IMPROVE COGNITIVE PERFORMANCE.
THAT COGNITIVE ENHANCEMENT WOULD
BE BENEFICIAL FOR INDIVIDUALS
WITH MILD ALZHEIMER'S DISEASE.
THAT AD OFTEN IS ASSOCIATED WITH
FUNCTIONAL IMPAIRMENTS IN
LANGUAGE AND READING. THEREFORE
OUR GOAL WAS TO DEVELOP A BCI
BASED FEEDBACK PARADIGM TO
INVESTIGATE THE EFFECT OF
NEUROFEEDBACK ON COGNITIVE
PROCESSES UNDERLYING READING IN
PEOPLE WITH MILD AD. ADVANCE
PLEASE. WE STARTED WITH SIX
PARTICIPANTS WITH MILD AD FROM
OUR ALZHEIMER'S DISEASE CENTER
HERE IN OREGON. DUE TO THE
PANDEMIC RESTRICTIONS ONLY 2
PARTICIPANTS COMPLETED THE 16
WEEK PROTOCOL. WE USED A
MULTIPLE BASELINE SINGLE CASE
RESEARCH DESIGN. SO WE ADAPTED
OUR BRAIN COMPUTER INTERFACE
SYSTEM WHICH IS A NON-INVASIVE
SYSTEM WHERE SOMEONE WEARS A EEG
CAP AND WE CAN ACQUIRE THEIR P
300 EVENT RELATED POTENTIAL. AND
WE LOOKED AT THREE MEASURES. WE
LOOKED AT WHETHER WE COULD
INCREASE SEQUENCE LENGTH ON
FORWARD AND BACKWARD LETTER SPAN
TASK, WHETHER WE COULD DECREASE
THE TIME TO COMPLETE LETTER
CANCELLATION AND WHETHER WE CAN
INCREASE ACCURACY ON SENTENCE
READING FLUENCY FOR FOLKS WITH
MILD ALZHEIMER'S DISEASE AS A
RESULT OF THIS INTERVENTION. SO
FIRST WE WERE CONFIDENT THAT THE
NEUROFEEDBACK WORKED BECAUSE WE
COULD ACQUIRE THE REQUIRED EEG
POTENTIAL THAT WE NEEDED AND ON
THE RIGHT IS WHAT THE TASK IS.
SO IMAGINE WEARING AN EEG CAP
AND YOU ARE LOOKING AT A SCREEN.
ON THE SCREEN YOU SEE THE LETTER
A. AND THEN YOU WILL BE SHOWN
TEN LETTERS IN SEQUENCE AND WHEN
THE A APPEARS IT PRODUCES A P
300 EVENT RELATED POTENTIAL. IF
THAT OCCURS YOU WILL GET GREEN
NEUROFEEDBACK. IF YOU DON'T
PRODUCE THE P 300 IT WILL
PRODUCE RED FEEDBACK. OUR GOAL
IS TO TRY TO HELP THE INDIVIDUAL
GET TO GREEN FEEDBACK EVERY TIME
THEY SEE THE LETTER. ADVANCE
PLEASE. SO THIS WAS POSSIBLE IN
ALL SIX PARTICIPANTS. EVERYONE
COULD USE THE NEUROFEEDBACK
ADEQUATELY. WHAT I WILL SHOW YOU
NOW ARE SOME OF THE RESULTS FROM
THE TWO PARTICIPANTS WHO
FINISHED. WE DID SEE TRENDS
TOWARD REDUCED TIME FOR LETTER
CANCELLATION WITH BCI
NEUROFEEDBACK. SO THE TOP TWO
GRAPHS ARE LETTER CANCELLATION
WITH CURVED LEERS THE BOTTOM TWO
ARE FOR LETTER CANCELLATION WITH
STRAIGHT LETTERS, YOU CAN SEE A
SLIGHT TREND TOWARD LESS TIME. I
CAN ALSO SHOW YOU TRANSPORT
INCREASING SENTENCE READING
FLUENCY TASK WITH THE BCI
NEUROFEEDBACK. USING THIS TASK,
SLIGHT TRENDS BUT SLIGHTLY
BETTER WITH NEUROFEEDBACK. NEXT
PLEASE. SO SOME OF OUR TAKE
AWAYS FROM THESE TWO CASES FOR
THAT PARTICIPANTS WITH COGNITIVE
IMPAIRMENT SUCH AS MILD
ALZHEIMER'S DISEASE CAN USE P
300 EVENT RELATED POTENTIAL
BASED BCI SPELLER FOR
CALIBRATION SO THE SYSTEM CAN
READ THEIR P 300 WHICH THEY ARE
PRODUCING. THE BCI BASED NEURAL
FEEDBACK INTERVENTION PROTOCOL
IS FEASIBLE TO USE WITH
INDIVIDUALS WITH MILD
ALZHEIMER'S DISEASE. THAT IS
FIRST REPORT OF THAT TYPE WORK.
FOR SPELLING. WE HAVE OPEN
SOURCE SOFTWARE FOR OUR BCI
SYSTEM SO WE SHOW THE USE OF
OPEN SOURCE SOFTWARE AND THE
AVAILABILITY OF CLINICAL
NEUROFEEDBACK DEVICES INCREASE
FEASIBILITY OF FURTHER RESEARCH
AND EVENTUAL CLINICAL
APPLICATION. THAT FINALLY
SINGLE CASE DESIGNS WITH
MULTIPLE ASSESSMENTS BEFORE AND
DURING INTERVENTION ARE
POTENTIAL APPROACH FOR THIS AD
PILOT STUDY.
>> THANK YOU, MELANIE. WE ARE
OUT OF TIME.
>> OKAY.
>> FIVE MINUTES SO WE WILL
DISCUSS LATER OUR LAST SPEAKER
FOR THIS SESSION IS DR. FAN GANG
ZENG, UNIVERSITY OF CALIFORNIA
IRVINE. PLEASE TAKE IT AWAY.
>> THANK YOU, LANA. THANKS TO
NIDCD AND NIH SUPPORT MY POST
DOC YASMEEM HAMZA AND I COMPLETE
TWO STUDIES. THIS IS ONE THAT I
WILL TELL YOU TODAY. YASMEEN
DID MOST OF THE WORK, SHE IS
FINISHING UP POST-DOCTORAL
TRAINING HERE AND WILL JOIN
FLORIDA STATE UNIVERSITY AS A
BRAND NEW FACULTY MEMBER,
CONGRATULATIONS, YASMEEN. SO
REWE LOOK AT THE NATIONAL HEALTH
NUTRITION EXAMINATION SURVEY
DATABASE TO TRY TO FIND OUT WHAT
IS THE INTERACTIONS BETWEEN
HEARING LOSS AND COGNITIVE
DECLINE,TYMYITIS IS SOUNDS ONE
HERES IN THE ERRS OR HEAD WHEN
THERE IS NO EXTERNAL SOUND
PRESENT. AND OVERLAPS WITH
HEARING LOSS BY AS MUCH AS 80%.
80%.TYMYITIS. SO BECAUSE OF THAT
OVERLAP, AND PEOPLE THOUGHT IF
HEARING LOSS CAUSES COGNITIVE
DECLINE SO DOES TINITIS SO
THAT'S WHEY TRYING TO FIGURE O
OUT HERE AND THIS PARTICULAR
SURVEY HAVE PATIENTS WHO HAVE
NOT ONLY THE HEARING LOSS DATA
TINITUS AND COGNITIVE FUNCTION
MEASURES. WE STARTED WITH ABOUT
10,000 PARTICIPANTS IN A
STREAMED DOWN DIVIDED UP TO FOUR
GROUPS AND LOOK THROUGH TO THE
BOTTOM WE FIND ABOUT 400 PEOPLE
WHO HAVE A NORMAL HEARING, NO
TINNITUS AND ABOUT A HUNDRED
PEOPLE WHO HAVE NORMAL HEARING,
AND NO -- AND TINNITUS, BY THAT
DASHED BLUE SQUARE. WE ALSO FIND
TWO ADDITIONAL GROUPS, 79 WITH
HEARING LOSS, NO TINNITUS AND 56
HEARING LOSS WITH TINNITUS SO WE
WILL THEN LOOK AT COGNITIVE
FUNCTION IN THESE FOUR GROUPS.
WE CONTROL FOR AGE, SEX, HEARING
LOSS, EDUCATIONAL LEVEL, SEEK
LOGICAL AND PHYSICAL WELL BEING.
OTHER RISK PARAMETERS. IS WHAT
IS SHOWN HERE IS NORMAL CONTROL
WE SHOW CUMULATIVE HISTOGRAM
THAT X AXIS IS COGNITIVE
FUNCTION NORMALIZED TO ZERO
AVERAGE ANYTHING NEGATIVE ON THE
LEFT IS POOR THAN AVERAGE HIGHER
ON THE RIGHT THAT'S BETTER THAN
AVERAGE. Y AXIS IS PERCENTAGE
GOES FROM 0 TO 100% SO ANYTHING
ON THE LEFT SIDE MEANS POOR
CONTROLND ON THE RIGHT SIDE IS
BETTER THAN NORMAL CONTROL.
SO FOR PEOPLE WHO HAVE NORMAL
HEARING AND TINNITUS NOT MUCH
DIFFERENCE BETWEEN THE TWO
SUGGESTING TINNITUS DOES NOT
IMPAIR COGNITION IN NORMAL
HEARING. OF COURSE YOU HAVE
HEARING LOSS NO TINNITUS THAT'S
BAD, CAUSING COMMISSIONTIVE
DECLINE AND THE KEY FINDING IS
NEXT PLEASE. FOR THOSE WHO HAVE
BOTH HEARING LOSS AND TINNIT,S
IT APPEARS THE TINNITUS SOMEHOW
COMPENSATES FOR THE DEGREE OF
COGNITIVE DECLINE CAUSED BY
HEARING LOSS SO THE CURVE SHIFTS
MORE TOWARDS NORMAL CONTROL. TO
SUMMARIZE, THE GROUP
DATABASEICALLY YOU SEE IF NORMAL
CONTROL ON THE LEFT SIDE BLUE
FILLED SQUARES SINNITUS WITHOUT
-- IN NORMAL HEARING LISTENERS
IS NOT TOO MUCH. HEARING LOSS
DOES COST COGNITIVE DECLINE, BUT
SOMEHOW TINNITUS WITH HEARING
LOSS COMPENSATE FOR THE
COGNITIVE DECLINE DECLINE. SO THIS IS
VERY COUNTER INTUITIVE OF
INTERESTING FINDING SO I WILL
STOP HERE AND TAKE ANY QUESTIONS
YOU MAY HAVE.
>> THANK YOU, LOOKING AT THE
CHAT. WE DO SEE ONE FROM --
VERY INTERESTING PERHAPS THE
COST INTEREST MIGHT ALSO BE
PROTECTIVE BUT HOW WE DON'T
KNOW.
>> I THINK PEOPLE DOING
PHYSIOLOGY MOLECULAR MECHANISM,
AND MAY HELP US UNDERSTAND WHY
IT IS PROTECTIVE. AND THERE IS
ANOTHER ONE FROM JAY, IS MORE
THERE IS ASSOCIATION BETWEEN
COGNITIVE DECLINE AND HEARING
LOSS RATHER THAN COST? I WILL
SAY POSSIBLY. THANK YOU.
>> THANK YOU. SO WE CAN DO
CAMERAS NOW. FOR THE DISCUSSION
PART IF YOU WISH. AND YOU CAN
PUT QUESTIONS IN THE CHAT. THERE
IS A COMMENT ON HEARING. FOR ALL
SPEAKERS IN THIS SESSION A
COMMON REFRAIN THIS PERSON HEARD
FROM PEOPLE WHO HAVE BEEN
SUBMITTED AD MOUSE MODELS
HEARING HEARING LOSS GRANTS IS
REVIEWERS FEEL THE MOUSE MODELS
ARE NOT REPRESENTATIVE OF THE
HUMAN CONDITION. THIS DRIVE
DOWNS THE SCORE. WHAT ASPECT OF
THE HUMAN CONDITION SHOULD WE
MODEL TO MAKE THE MOUSE MODELS
MORE APPLICABLE.
>> ANYBODY WANT TO RAISE THEIR
HAND AND ANSWER THAT QUESTION?
NO?
SCANNING. DID I MISS A HANDD?
YES. DAN WESSON.
>> AND IF I COULD START OFF, I
WOULD SUGGEST, I MEAN, THIS ADRD
THIS ONE YEAR SUPPLEMENT
INITIATIVE WAS OBVIOUS WILL I A
LOT OF PIONEERING WORK. DRIVING
PAPERS GRANTS SUBMISSIONS.
UNFORTUNATELY BECAUSE THERE'S
ONLY ONE YEAR, IT DOESN'T AVAIL
ITSELF TO THE STRONGER
ALZHEIMER'S DISEASE MOUSE MODEL.
WHICH ARE MOUSE MODELS THAT ONLY
HAVE ONE FAD GENE MUTATION
EXPRESSED. NO HOW MANY HAS THREE
FAD GENE MUTATIONS OR FIVE SO
THE 3X AND 5X PEOPLE LOVE TO USE
BECAUSE CHANGES IN TWO MONTHS,
JUST DON'T CLOSELY MIMIC SO MY
SUGGESTION IS IN TERMS OF
GETTING AT THAT COMMENT IS -- ON
THE ONE SIDE FOR THE GRANTS,
PAPERS IS TO CONSIDER MOUSE
MODEL THAT A AT LEAST ALLOWS US
TO TEST HYPOTHESIS THAT ONE
SPECIFIC PATHOLOGICAL VARIABLE
WHETHER AMYLOIDOSIS, TAU,
INFLAMMATION, AND BE CAREFUL
SELECTING THE MODEL BECAUSE SOME
ALSO DRIVE CELL DEATH. AND THAT
WAY YOU CAN BETTER HONE YOUR
HYPOTHESIS, NOT THE TEST THE AD
OR ADRD, BUT YOU CAN HONE YOUR
HYPOTHESIS AROUND ONE PATHOLOGY
WE KNOW IS A COMPONENT OF MANY
ADRDs AND USE THAT TO GO
FORWARD. SO THAT WOULD BE
SUGGESTION BUT THAT REQUIRES
INVESTMENT FROM NIA AND NIDCD
AND GRANT MECHANISMS THAT ALLOW
MORE AGE MOUSE MODELS BECAUSE
THESE MOUSE MODELS WITH ONE FAD
MUTATION TAKE LONGER TO DEVELOP
IMPAIRMENTS.
>> NOTED. THERE IS NO QUESTION
IN THE CHAT BEFORE I SEE -- GO
TO DR. MACWHINNEY, ASSOCIATION
BETWEEN HEARING LOSS AND
COGNITIVE DECLINE SEEMS CLEAR
BUT IT IS NOT CLEAR THAT THERE
IS A CAUSAL RELATIONSHIP. WHAT
IS THE EVIDENCE OF CAUSALITY?
ANYBODY WANT TO TAKE THAT?
ASSUMING IT IS NOT DR.
MACWHINNEY WHO WANTS TO ANSWER
THAT QUESTION, PLEASE LOWER YOUR
HAND.
>> TO ESTABLISH THAT CAUSALITY,
WE NEED TO MAKE SHOE HEARING
LOSS IS NOT ONLY NECESSARY BUT
SUFFICIENT TO CAUSE POTENTIALLY
TREAT COGNITIVE DECLINE. MOST OF
THIS ASSOCIATION STUDIES, HAVE
BEEN BASED ON CROSS SECTIONAL
STUDIES INCLUDING THE ONE I
PRESENTED. SO YOU COMPARE TWO
GROUPS ONE AND WHAT A DIFFERENCE
IS. WE DO NEED LONGITUDINAL
CONDITIONS FROM THE SAME GROUP
OF PATIENTS. I HI THE KIND OF
STUDIES SOME HAVE BEEN PLANNING
AND SOME HAVE BEEN REPORTED
PRELIMINARY RESULTS AND SHOW
THAT FOR EXAMPLE, COCHLEAR
IMPLANTS AFTER IMPLANTATION, NOT
ONLY COCHLEAR IMPLANTS PREVENT
SOMETIMES RECOVER COGNITIVE
FUNCTION, I THINK THAT IS A
PRETTY STRONG EVIDENCE
SUGGESTING THIS PROBABLY MORE
THAN ASSOCIATION, IT IS A CAUSAL
RELATIONSHIP.
>> ALL RIGHT.
>> ALTERNATE, I'M GOING TO
ALERNATE BETWEEN CHAT AND PEOPLE
WHO RAISED THEIR HAND, AKNOW
LEDGE YOU, DR. WHITE. CAN WE
ALLOW DR. MACWHINNEY TO ASK HIS
QUESTION, IF HE STILL WANTS TO?
>> I LIKE WHAT DAN IS SAYING
ABOUT FOCUSING ON SINGLE CAUSE
BUT IN TERMS OF THE MOUSE IT
WOULD BE NICE, I'M IMPRESSED
WHAT THEY -- HAS FOUND FOUND
WITH HIS MICE HE GETS MICE TO
STOTSER I THINK IT IS
INTERESTING TO FIND MICE WHO MAY
HAVE PROBLEMS WITH MEMORY,
HEARING, BALANCE, SO IN GENERAL
TO BE ABLE TO MAP THEIR PROBLEMS
ON TO THE HUMAN ONE, I FIND IT
ANOTHER WAY OF UNDERSTANDING
WHAT'S GOING ON. OBVIOUSLY NOT
AS MECHANISTIC BUT DOES GIVE US
ANOTHER VIEW OF THE THING. THAT
IS ALL.
>> THANK YOU. INDIVIDUALS WHO
DIRECT QUESTIONS FEEL FREE TO
ANSWER THEM IN THE CHAT AND I
WILL GO NOW TO DR. WHITE.
>> I WAS GOING TO CONTINUE THE
CONVERSATION ON HEARING LOTIONS
DEMENTIA PROGRESSION. I THINK
THAT THERE COULD BE FEEDBACK
LOOPS WITHIN THESE TWO
PATHOLOGIES. WHERE YOU MIGHT
HAVE A PERSON WITH HEARING LOSS
WHO IS NOT FACE TO FACE OR
HAVING COMMUNICATIONS AND WE
KNOW THAT SOCIAL CONNECTIONS ARE
VERY IMPORTANT FOR SLOWING THE
DECLINE WITH DEMENTIA. SO THAT
CAN PLAY A ROLE IN IT. YOU MAY
ALSO HAVE SITUATION WHERE PEOPLE
WHO HAVE LOW LEVELS OF DECLINE
-- LOW LEVELS OF DECLINE MAY
HAVE DIFFICULTY ADAPTING TO FOR
INSTANCE USE OF HEARING AIDS.
THAT WAS WHY I FOUND THE STUDY
ON INDIVIDUALS WITH DIFFERENT
HEARING AID IS FASCINATING
BECAUSE MIGHT BE TRYING TO
UNDERSTAND THOSE ASPECTS MIGHT
HELP US TO THEN PROVIDE THE
HEARING TREATMENT THAT PEOPLE
NEED TO HELP THEM GET THE SOCIAL
SUPPORT THEY NEED. THE HEARING
LOSS AND AD COULD BE A VICIOUS
CYCLE IN THAT RESPECT.
>> NOTED. THANK YOU. DR.
SINCLAIR, YOU HAD YOUR HAND UP.
>> SO I WANT TO FOLLOW-UP ON
WHAT DAN AND I BELIEVE BRINE
DISCUSSED ABOUT FINDING THE
RIGHT TYPE OF MODEL. THEY ARE
COMPLETELY ACCURATE IN THE SENSE
THERE ISN'T A SINGLE MODEL THAT
CURRENTLY RECAPITULATES THE FULL
AS PECK OVERSEES DISEASE.
THE GOAL IS TO REPLICATE ASPECTS
BUT THESE MODELS ARE NOT
PERFECT. AND MICE STILL GET AD
SO WE NEED TO KEEP THAT IN MIND
AS WELL. WELL. AND RECENTLY INVESTED
IN MODEL 18 CONSORTIUM, I DON'T
KNOW HOW MANY MIGHT BE FAMILIAR
WITH THIS, IT IS A CONSORTIUM
THAT INCORPORATES INDIANA
UNIVERSITY JACKSON LABS,
UNIVERSITY PITTSBURGH, AND I
BELIEVE UC IRVINE. SO A
SIGNIFICANT GROUP OF
INSTITUTIONS, THAT HAVE COME
TOGETHER TO TRY TO ENGINEER
BETTER CHARACTERIZE MOUSE
MODELS, AND ALSO IMPROVE UPON
THE DEVELOPMENT, THEY ARE ALSO
LOOKING INTO GENERATING
HUMANIZED MOUSE MODELS THAT
WOULD BETTER CAPITULATE THE
DISEASE PATHOLOGY AND THE HUMAN
DISEASE IN GENERAL. I KNOW
THERE IS A PUBLICATION, I THINK
SOMETIME LAST YEAR THERE WAS A
PUBLICATION THAT CAME OUT FROM
THE CONSORTIUM THAT DID A DEEP
PHENOTYPIC ANALYSIS OF THE 5X
MOUSE BECAUSE THAT IS ONE OF THE
MORE POPULAR MOUSE MODELS SO
ENCOURAGE YOU TO TAKE A LOOK AT
THAT, I THINK THERE'S
RECOMMENDATIONS TO WHAT TYPES OF
STUDIES MIGHT BE MORE SUITED TO
THIS PARTICULAR MOUSE MODEL,
WHAT TYPES WOULDN'T.
>> THANK YOU. I'M GOING TO NOT
DO THIS NAME RIGHT. I NEVER
PRACTICED IT. FORGIVE ME. DR.
KUCHIBHOTIA
>> WELL DONE DONE. DONE. DONE. I WANT TO F OLLOW
UP WHEN WE ARE SUBMITTING MOUSE
RELATE AUDITORY AND ALZHEIMER'S
GRANTS. AFTER THE SUPPLEMENT I
DID THAT FOR -- WITH AN RO1 AND
IN BOTH INITIAL SUBMISSION AND
RESUBMISSION, RECEIVED VERY
CLEAR NEGATIVE FEEDBACK THAT IT
WAS NOT CLEAR HOW THE AUDITORY
CORTEX IS RELEVANT IN
ALZHEIMER'S DISEASE. ONE OF THE
REVIEWERS ENDED LIKED A LOT OF
STUFF TECHNOLOGICALLY ADVANCE
SYSTEMS CIRCUIT WORK CORTICAL --
IN THE CORTEX AND MOTIVATED IT,
I THINK WELL WITH THE POTENTIAL
CENTRAL CONTRIBUTION HEARING
IMPAIRMENTS LINKED TO DEMENTIA
BUT THERE STILL TWO OF THE THREE
MADE A STRONG STATEMENT HA IS
NOT CLEAR HOW THE AUDITORY
CORTEX AND AUDITORY SYSTEM IS
RELEVANT IN THE HUMAN CONDITION.
IT IS SOMETHING THAT WE ARE JUST
TRYING TO UNDERSTAND HOW TO KIND
OF PITCH THIS IN A WAY THAT THE
SCIENCE IS GOING TO BE EXTREMELY
VALUABLE TO SAY THAT BUT IT IS
NOT CLEAR HOW IT LINKS TO THE
HUMAN CONDITION. SO JUST A
FOLLOW-UP ON THIS THREAD.
>> RIGHT. SOMETHING TO EXPLORE
WITH THE PROGRAM OFFICER.
>> OKAY.
>> DR. BUCKEY, WOULD YOU LIKE TO
GO NEXT?
>> JUST FOLLOW-UP ON THERE IS A
TENDENCY WHEN YOU ARE TALKING
ABOUT HEARING THAT EVERYONE
ASSUMES THAT YOU ARE TALKING THE
AUDITORY CORTEX. BUT AT LEAST IN
THE WORK THAT WE HAVE BEEN
DOING, THERE IS CERTAINLY A LOT
OF INVOLVEMENT OF THE BRAIN IN
AREAS OUTSIDE THE AUDITORY
CORTEX. WHEN YOU ARE DOING
COMPLEX SPEECH TESTS LIKE
UNDERSTANDING SPEECH AND
BACKGROUND NOISE. SO THE IDEA
THAT IT IS ONLY THE AUDITORY
CORTEX THAT INVOLVED I DON'T
THINK IS TRUE.
>> COMMENT BACK ANYBODY? ALL
RIGHT. NOTED. MOVING ON TO DR.
VERHAGEN.
>> LOOKS LIKE WE HAVE TWO
DISCUSSIONS RUNNING THROUGH EACH
OTHER, ONE IS HEARING AND
ALZHEIMER'S AND OTHER IS MODELS.
PERSONALLY I'M QUITE INTERESTED
MANY THE MODELS PART BECAUSE I
HAVE HAD LONG TERM DOUBTS ABOUT
THE MODELS THAT HAVE BEEN USED
IN TERMS OF THEIR RELEVANCE TO
NON-FAMILIAR ALZHEIMER'S
DISEASE. SO ALZHEIMER'S DISEASE
IS VERY SPECIFIC, VERY CAUSAL,
RELATIONSHIPS TO -- SPECIFIC
GENETIC FACTORS WHEREAS
(INAUDIBLE) MUCH MORE
MULTI-FACTORIAL, LIFESTYLE AGE
SEX MANY, MANY GENETIC FACTORS.
SO I GUESS IF WE ARE TALKING
ALZHEIMER'S DISEASE IT IS REALLY
CRITICAL TO FIGURE OUT WHAT WE
ARE TRYING TO DO AND WHAT WE ARE
TRYING TO MODEL HERE. AND AS DR.
SINCLAIR CLARKE SUGGESTED, THERE
INDEED NO MODELS THERE THAT
WHERE MOUSE MODELS DIRECTLY
REPLICATE GENETIC RISK FACTORS
IN RODENTS AND LIKELY THROUGH
THE SUPPLEMENT THAT MY LAB WAS
GIVEN WE HAVE NOW BEEN SCANNING
APOE FOR TRIM 2 HUMANIZED MICE
WHICH REPRESENTED GENETIC RISK
FACTORS. WE FIND JUST LIKE DR.
HILHILLAIRE CLARKE SAID,
PHENOTYPINGS BUT IMAGINE YOU CAN
CONNECT THAT GENETIC RISK FACTOR
WITH A LIFESTYLE RISK FACTOR AS
WELL AS AGE AND YOU CAN START
LOOKING AT WHAT THE CONGLOMERATE
OF REAL HISTOLOGICALLY RELEVANT
MODEL MIGHT BE THAT ACTUALLY
REPLY CASE AS CLOSE AS POSSIBLE
THE ACTUAL HUMAN CONDITION OF
THESE SPORADIC ALZHEIMER'S
DISEASE SO TOTALLY IN AGREEMENT
WITH DAN, YOU HAVE SUPER -- YOU
HAVE TO BE SUPER CAREFUL WHAT
THE MODELS ARE AND ITS
LIMITATIONS. AND UNFORTUNATELY,
I THINK THE MODEL -- THE AMYLOID
HYPOTHESIS HAS JUST BEEN DAMAGED
AND WE KNOW THAT BASED ON THE
LACK OF PRODUCTS FOR SPORADIC
ALZHEIMER'S DISEASE SO IT IS
TIME I THINK, MAYBE A LITTLE
AHEAD OF THE DISCUSSION BUT IT
IS TIME TO REALLY THINK ABOUT IF
THERE IS ONE MODEL THAT IS SUPER
OR WHETHER MANY APPROACHES ARE
IMPORTANT, I WOULD ARGUE THAT
THE LATTER IS PROBABLY THE CASE.
>> THANK YOU.
>> THANK YOU. DR. FRIED OKEN
HAS HER HAND UP, TWO MORE AFTER
THAT.
>> AS A CLINICAL RESEARCHER I
ALSO WANT TO STRESS THAT JUST
SAYING ALZHEIMER'S DISEASE IS
NOT ADEQUATE. THAT WE REALLY
NEED TO BE MUCH MORE VIGILANT,
LEVEL OF COGNITIVE IMPAIRMENT
AND DOMAINS, THERE'S SO MANY.
AND THAT THIS GROUP AS ASUIT
SCIENTISTS CAN DO THAT, EVEN AT
THE MECHANISTIC LEVEL, SO I JUST
LIKE TO PUT IN MY TWO CENTS FOR
THAT.
>> THANK YOU. NOTED.
>> SORRY FOR THE NAME. BIESCZAD.
>> CHALLENGE OF READING
EVERYBODY'S NAMES. THANK YOU.
>> SAY IT AGAIN.
>> BIESZCZAD. MY STUDENTS CALL
ME C B. WELCOME TO DO THE SAME.
I WANT TO CONTRIBUTE TO THIS
IDEA OF MODELS WHEN WE THINK OF
MODELS WE USUALLY IN THE CONTEXT
OF AD START THINKING ABOUT WHICH
GENES AND HOW MANY GENES AND HOW
MUCH PLAQUE ARE WE MAKING, HOW
MUCH TAU. AND OF CURSE THAT'S
IMPORTANT. I THINK COMPLIMENTARY
IS THIS IDEA OF WHAT TYPE OF
BEHAVIORAL MODELS SHOULD WE
INTRODUCE. WHAT IS RELEVANT ON
THE BEHAVIORAL LEVEL. THERE IS
ALREADY SOME DISCUSSION EARLIER
THIS AFTERNOON, ABOUT ABR
HEARING THRESHOLDS, GIVING US
PART OF THE STORY BUT NOT THE
COMPLETE STORY OF IMPAIRMENT. T
AND THAT IS LIKE THE HEARING
SIDE. I THINK WE WOULD BE REALLY
WISE TO THINK ABOUT WHAT TYPES
OF BEHAVIORS CAN WE MODEL
ANIMALS THAT ARE RELEVANT TO
HUMANS IN THE CLINICAL SETTING
AND WHETHER WE CAN THEN GET AT
THIS QUESTION ALSO OF CAUSALITY
BY USING THE ANIMAL MODEL. SO I
DON'T HAVE AN ANSWER. BUT THIS
GROUP IS CLEVER ENOUGH TO THINK
ABOUT WHAT ARE THE TYPE OF
BEHAVIORS WE HAVE TO ALSO START
TAKING MORE ADVANTAGE OF TO
ADDRESS THESE INTERACTIONS
BETWEEN HEARING AND MEMORY
COGNITION.
>> DEFINITELY A CHALLENGE CHALLENGE. CHALL ENGE. LIKE
WRITING POETRY, DR. WHITE YOU
LOWERED YOUR HAND.
>> BECAUSE DR. B SAID EXACTLY
WHAT I WANTED TO SAY. SO MUCH
BETTER.
>> THANK YOU. NEXT WOULD BE DR.
KUSHALNAGAR. PLEASE UNMUTE. OH.
SORRY.
>> YES, I WOULD ACTUALLY JUST
LIKE TO COMMENT ON THE
METHODOLOGY WHEN YOU ARE
STUDYING PEOPLE WITH A HEARING
LOSS WHAT YOU HAVE TO TRY TO
CONNECT IS HEARING LOSS WITH
DEMENTIA AND/OR ARE YOU WANTING
TO SHOW THAT THERE IS NO
CONNECTION. I THINK IT IS WORTH
INCLUSION OF PEOPLE WHO ARE BORN
DEAF AND/OR LOSE THEIR HEARING
VERY EARLY IN LIFE. IT IS WORTH
IT FOR US NOT TO LIMIT TO PEOPLE
WHO ARE AGING AND LOSING THEIR
HEARING BECAUSE OF THAT. I THINK
IT ALLOWS FOR SIGNIFICANT BIAS
AND IT DOESN'T CONNECT
RELATIONSHIP IN ALL THE WAYS
SHAPES AND FORMS. SO I WOULD
RECOMMEND THAT FOLKS WHO ARE
EITHER CONGENITALLY DEAF AND/OR
LATER -- VERY EARLY IN LIFE LOSE
HEARING. THERE IS DATA 200,000
INDIVIDUALS WHO LOST THEIR
HEARING EITHER PRE-LINGUALLY OR
AT BIRTH. AND THE DIFFERENCE
BETWEEN WHAT YOU ARE USING AS
THE TERM OF HEARING LOSS,
WHETHER IT MEANS DECIBEL OR AGE
ONSET IS SIGNIFICANT AS WELL.
AND I DON'T SEE ANY RELATIONSHIP
BETWEEN THAT AND THE REPORT
COGNITIVE DECLINE. WHAT I DID
SEE HOWEVER IS MORE RELATED TO
LANGUAGE USE. AND NOT THE ONSET
OF THE HEARING LOSS ITSELF SO I
WOULD LOVE FOR ALL OF US HERE
SHARING THIS DIGITAL SPACE TO
CONSIDER THAT IN FUTURE STUDIES
TO HELP CLARIFY YOUR FINDINGS.
>> YEAH. NOTED. THERE IS A NICE
COMMENT IN THE CHAT YOU CAN
READ. WE WILL GO TO DR. STEEL
USING RDOC SORRY.
>> I WOULD LIKE TO SAY WHERE IS
THAT MODEL, I REALLY DISLIKE
THAT TERM AND I AVOID IT
WHEREVER POSSIBLE. I THINK IT IS
VERY MISLEADING TO USE THE WORD
MODEL BECAUSE MY -- THEY ARE
NEVER GOING TO BE ADEQUATE MODEL
FOR HUMAN DISEASE, I DON'T THINK
ANY HUMAN DISEASE, ONLY
COMPLICATED ONE IN INTERVENTION,
-- DISEASES SEEM VERY
HETEROGENOUS, DEAFNESS HEARING
LOSS IS EXTREMELY HETEROGENOUS,
THERE'S HUNDREDS OF GENES
INVOLVED, LOTS OF MOLECULAR
MECHANISMS AND PATHOLOGICAL
MECHANISMS, IT IS NOT A SINGLE
ENTITY. IT IS VERY HETEROGENOUS.
AND FROM WHAT I UNDERSTAND
DEMENTIA IS THE SAME, THERE ARE
MANY DIFFERENT PARTICULAR TYPES
MECHANISMS LIKELY TO BE
MECHANISMS INVOLVED SO THE
CONCEPT OF A MODEL PARTICULARLY
LOOKING FOR A SINGLE MODEL IS
FLAWED. WE NEED TO THINK ABOUT
MICE MUTANTS, DIFFERENT MICE
DIFFERENCE WAYS OF LOOKING AT
MICE AS TOOLS FOR FRYING TO
UNDERSTAND -- TRYING TO
UNDERSTAND ONE FEATURE AT A
TIME. RATHER THAN TRYING TO
MODEL THE WHOLE PHENOTYPE. AND
THAT IS TRUE FOR HEARING LOSS
DEMENTIA AND RELATIONSHIP
BETWEEN TWO. THAT IS MY TWO
CENTS WORTH WHAT I THINK ABOUT
MODELS, I THINK IT IS A FLAWED
CONCEPT MODEL. TOOLS NOT MODELS.
>> DR. BUCKEY.
>> JUST CONTINUE TALKING ABOUT
MODELS. WHAT DR. B WAS SAYING,
WHAT WE SEE WITH OR COMPLEX
AUDITORY TASKS, ASSOCIATION WITH
PROCESSING SPEED, THE ABILITY TO
MAINTAIN ATTENTION, IN THESE
ANIMAL MODELS I DON'T KNOW HOW
YOU CAN SIMULATE THAT, THAT IS
THE -- THERE MUST BE A WAY BUT
SEEMS LIKE THINGS LOOKING AT ABR
OR STUFF LIKE THAT IS NOT
NECESSARILY GOING TO BE TAXING
THE BRAIN SAME WAY THINGS LIKE
UNDERSTANDING SPEECH AND
BACKGROUND NOISE. SO I JUST BE
INTERESTED IN PEOPLE WHO DO
ANIMAL MODELING HOW THEY THINK
WOULD BE THE BEST APPROACH TO
THINGS LIKE THAT.
>> WELL MAYBE PEOPLE CAN PUT THE
ANSWER IN THE CHAT AND WE CAN GO
TO MIKE WEHR IF YOU WOULD LIKE
THE ANSWER OR ASK A NEW
QUESTION.
>> I WANT TO COMMENT ON THE
QUESTION OF MODELS AND
BEHAVIORAL ASSAYS AS WELL.
THERE'S SO MANY DIFFERENT MODEL
MICE, IT IS A CHALLENGE TO TRY
TO FIGURE OUT WHICH TO USE. AND
THEN A CHALLENGE TO FIGURE OUT
WHICH BEHAVIORAL TASK OR SUITE
OF BEHAVIORAL TASKS OR
ELECTROPHYSIOLOGICAL
MEASUREMENTS TO USE. IT IS
EXTREMELY EXPENSIVE TO TRY AND
COMPARE BUNCH OF MICE IN YOUR
OWN LAB. LET ALONE BUNCH OF
BEHAVIORAL TASKS. SO SEEMS TO ME
THE REAL POWER OF THE GROUP WE
HAVE SIMPLE -- ASSEMBLED HERE IS
WE CAN CREATE COLLABORATION
WHERE WE USE CONSISTENT SET OF
BEHAVIORAL TASKS ACROSS VARIETY
OF DIFFERENT MODELS AND TRY TO
BRING THOSE HEAD TO HEAD BECAUSE
IF PEOPLE DON'T COLLABORATE,
THEY USE SLIGHTLY DIFFERENT
VARIATION OF TASKS OR DIFFERENT
GENETIC BACKGROUNDS, HOW
IMPORTANT IT IS TO BE CLEARED BY
EXACTLY WHICH GENETIC BACKGROUND
YOU USE, EVEN WITH SPECIFIC
MODELS, TO GET ALL THOSE THINGS
STRAIGHT REQUIRES COLLABORATION
AND EXPERIMENTAL DESIGN AHEAD OF
TIME AND THIS GROUP CAN SUPPORT
THAT.
>> AGREE. THAT WAS THE
MOTIVATION TO HAVE Y'ALL COME
TOGETHER AND BEGIN TO CONNECT.
SO YEP. I NODE WE HAVE TWO MORE
MINUTES TO GO. BRIAN HAS A
COMMENT. GOING TO 4:25 THEN
BREAK.
>> VERY QUICKLY, SHARING DATA
MOUSE MODELS, BE ALSO GREAT IF
PEOPLE WOULD DO MORE SHARING OF
LANGUAGE DATA. SO I MEAN, THERE
MUST BE ABOUT FIVE PROJECTS HERE
WHO CONTRIBUTE THEIR DATA. AND
THERE IS ENORMOUS WORK GOING ON
FROM APPLE GOOGLE FACEBOOK, IN
TERMS OF THEIR WORK ON THIS
PROBLEM TOO TOO. SOMETHING TO THINK
ABOUT.
>> OKAY. ONE FINAL -- THE HAND
WENT AWAY. THERE YOU. DR. ZHAO
ONE FINAL COMMENT.
>> YES. I COMPLETELY AGREE
MIKE'S COMMENTS WE SHOULD BE
COME TOGETHER AND ANOTHER ISSUE
IS OUR EMPHASIS DIFFERENT AD
MOUSE MODELS EVERY MOUSE MODEL
CAN BE PROVIDE DIFFERENT
VARIABLE INFORMATION TO US. AND
I ALSO WANT TO EMPHASIZE NOW
(INAUDIBLE) MOUSE MODEL FOR
EXAMPLE, RIGHT MOW WE STILL
DON'T KNOW WHAT IS,D INDUCED
BETWEEN AD HEARING CHANGES AND
AGING HEARING LOSS BUT IN THE
HUMAN SUBJECT HARD TO
DISTINGUISH THESE TWO ISSUES.
BECAUSE OLDER PEOPLE IS ALWAYS
HAVE SOME AGE RELATED -- MOUSE
OR MAYBE THEY ALSO HAVE AD
RELATED IN MOUSE. SO YOU LOOK AT
LITERATURE AND SO SOME SAID OH,
THEY HAVE A LIKE AD INDUCED
HEARING LOSS AND SOME PEOPLE
SAID OH NOTHING AND MAYBE THE
(INAUDIBLE) MOUSE SO FOR HUMAN
SUBJECTS I THINK IS SO DIFFICULT
TO DISTINGUISH THESE ISSUES BUT
FOR THE MOUSE MODEL ACTUALLY
RELATIVELY SIMPLE SO AGREE FOR
THE MOUSE MODEL HAVING
(INAUDIBLE) FOR EVERY STUDY
INITIAL STEP WE CAN BE USE MOUSE
MODEL. THE NEXT STEP WE CAN GO
AHEAD O TO HUMAN SUBJECTS IF WE
CAN DEFINE WHAT IS DIFFERENCE
BETWEEN THE AD INDUCED CHANGES
ALSO AGING RELATED PANELS.
>> THANK YOU. IT IS 4:25 AND WE
ARE SUPPOSED TO BREAK. I SEE
YOU, DR. WHITE BUT LET'S TAKE A
FIVE MINUTE BREAK SO THAT WE CAN
RESUME AS INDICATED FOR THE LAST
PIECE. ON THE AGENDA.
THANK YOU VERY MUCH.
>>ON BEHALF OF MY NIA
COLLEAGUE, DR. CORYSE ST.
HILLAIRE CLARKE AND I, THANK YOU
FOR THE PRESENTATIONS AND YOUR
PARTICIPATION. YOUR THOUGHTS
YOUR IDEAS TODAY AND FOR STAYING
ON TIME SO WE CAN REACH THIS
POINT. WE DO HAVE ONE MORE
REQUEST ENTERING THE HOME
STRETCH, THAT'S DISCUSSION ABOUT
FUTURE POSSIBLE DIRECTIONS
RELATED TO AD ADRD RESEARCH AND
COMMUNICATION DISORDERS. CORYSE
AND I WANT TO HEAR YOUR COMMENTS
AND YOUR THOUGHTS ABOUT THE
QUESTIONS THAT WE SENT YOU
EARLIER THIS WEEK AND WE ARE
GOING TO SEE THOSE ON THE SLIDE
MAYBE NOW. WHAT WERE THE BIGGEST
CHALLENGES AS YOU EXABOUTED YOUR
WORK INTO AD ADRD RELATED
SCIENCE AND WHAT WERE THE
LESSONS THAT YOU LEARNED THAT
MAYBE WILL BE OF BENEFIT TO
OTHERS WHO ARE EXPLORING THIS
AREA? SO THE NEXT ISSUE IS WHAT
IS THE MOST EXCITING FUTURE
DIRECTION YOU CONSIDER OR
CERTAINLY IN YOUR OPINION THAT
HAS POTENTIAL TO ADVANCE AND
MAYBE BE FEASIBLE WITHIN THE
NEXT FIVE TO TEN YEARS? AND THEN
THE FINAL ISSUE WE WANT TO TALK
ABOUT IS WHAT ARE THE BEST WAYS
AND NOTE THERE IS A LITTLE
ASTERISK INDICATING THAT THIS IS
NOT JUST ADDITIONAL DOLLARS BUT
WHAT ARE THE BEST NON-MONETARY
WAYS THAT WE AT THE NIH BUT NOT
ONLY NIH, CAN HELP PROMOTE
COLLABORATIONS WE HAVE TALKED
ABOUT IN SOME OF YOU HAVE BEEN
VERY SUCCESSFUL IN OBTAINING.
WHO WORKING NOT ONLY CD BUT AK
ADRD TO ACCELERATE SCIENCE AND
SLIDE TO IMPROVEMENTS IN HUMAN
HEALTH. I WANT TO START WITH THE
BIGGEST CHALLENGES THAT YOU FEEL
LIKE YOU FACE AND ANY LESSONS
LEARNED, AND I ASK THAT YOU USE
YOUR VIRTUAL HAND TO RAISE AND
TRY TO TURN ON VIDEO WHEN READY
TO SPEAK. SWATHI FOR YOU FIRST.
>> THANK YOU.
>> I THINK JAMIE ANSWERED MY
QUESTION ABOUT CHALLENGES
ESPECIALLY DURING COVID BECAME
ALMOST IMPOSSIBLE TO DO ANY
HUMAN STUDY AND I THINK THAT WE
HAVE TO FIGURE OUT OTHER WAYS TO
DO THIS WORK THAT IS IMPORTANT.
T BUT WHAT I THINK IS A
EXCITEMENT OR POTENTIAL
OPPORTUNITY P BRIAN MENTIONED
THIS, I WANT TO QUOTE THIS IS AT
LEAST IN HUMAN COMMUNICATION IN
LANGUAGE AND COGNITION, THE
TECHNOLOGY THAT IS MOVING REALLY
FAST IN TERMS OF ALEXA AND
NATURAL LANGUAGE PROCESSING
ALGORITHMS IS MAKING A LOT
EASIER FOR US TO COLLECT DATA AS
PEOPLE ARE TALKING AND
INTERACTING AND USING THAT TO
DETECT DEMENTIA SO THIS IS
SPECIFIC TO OUR SUBGROUP TALKING
LANGUAGE COGNITION AND
COMMUNICATION. IT IS A HUGE
OPPORTUNITY FOR US AND LOOKING
FORWARD FOR US TO NOT BE TRYING
TO COLLECT DATA IN THE LAB BUT
ONE PATIENT AT A TIME AND
COLLECTING A LOT MORE DATA IN
REAL WORLD SETTINGS AND USING
THAT TO DIAGNOSE AND HELP THESE
PATIENTS.
>> THANK YOU. BRIAN.
>> SURE. I THINK OF COURSE THAT
IS RIGHT, I THINK THERE IS ALSO
THE INTEREST IN FINDING OTHER
THINGS BESIDES LANGUAGE THAT WE
CAN GATHER TYPES OF DATA WE CAN
GATHER WITH LANGUAGE, THAT WOULD
INDICATE PROGRESSION AND WE NEED
EVENTUALLY IF THERE IS GOING TO
BE TREATMENT WE NEED TO KNOW THE
PRE AND THE POST. WE HAVE TO
HAVE PRETTY GOOD PSYCHO METRICS
TO KNOW WHETHER THE TREATMENT IS
DOING ANYTHING. BUT I THINK THAT
THERE IS A LOT OF INTEREST IN
PUTTING TOGETHER WEARABLES AND
OTHER DEVICES THAT ARE GOING TO
BE EASY ENTRY, SOME OF THESE
OTHER THINGS OTHER MEASURES
PEOPLE HAVE USED ARE GOING TO BE
MUCH MORE DIFFICULT. SO THE
THINGS THAT ARE EASY FOR PEOPLE
TO WEAR, TO REPORT, AND THEN AT
THE SAME TIME BUT THEY HAVE TO
BE INDICATIVE SO YOU HAVE A
TRADE OFF. THERE MAYBE SOME
INDICATIVE THINGS THAT HARD TO
FIND, SOME BRAIN RESPONSES AND
SO ON. SO I JUST THINK PUTTING
THIS ALL TOGETHER NOT JUST
LANGUAGE STUFF BUT ADD ON
LANGUAGE STUFF MANY OTHER
MEASURES, WHAT A LOT OF PEOPLE
ARE TRYING TO DO ACTUALLY, MORE
COMMERCIAL SIDE. WE SHOULD BE
DOING THAT TOO.
>> THANK YOU, BRIAN. JUDY.
>> THANK YOU. I THINK ONE
CHALLENGE IS IN AN AREA THAT I
DIDN'T GET TO TALK ABOUT AND
THAT WAS THE OTHER PART OF OUR
SUPPLEMENT WHICH INVOLVED
LOOKING FOR CENTRAL AUDITORY
SYMPTOM PATHOLOGY AN NEURAL
PATHOLOGY IN BRAINS AND BONES
FROM HUMAN DONORS WITH AN
WITHOUT CONFIRMED DIAGNOSES OF
AD. AND THAT WORK WE FOUND VERY
CHALLENGING TO FIND NORMAL
CONTROLS AND ALSO FIND RACIALLY
DIVERSE SAMPLES. THAT I THINK
IS A LIMITATION OF OUR WORK AND
MAYBE OTHERS, WE FIND THAT A
CHALLENGE IN YOUR WORK FINDING
THE WITH AND WITHOUT DIAGNOSIS
OF AD WHO DO AND DON'T HAVE
HEARING LOSS WAS VERY
CHALLENGING TO GET ALL THOSE
COMPARISONS. BECAUSE THAT'S
REALLY WHAT WE ARE LOOKING FOR.
IN ORDER I THINK SOMEONE EARLIER
MAY HAVE SAID THAT IT WAS IN A
CONVERSATION ABOUT THE CORTEX,
WE DON'T KNOW MUCH ABOUT WHAT IS
GOING ON IN THE AUDITORY SYSTEM
CENTERS IN PEOPLE WITH AD. THAT
IS WHAT WE ARE LOOKING FOR BUT
IN CHALLENGING TO FIND THE
SAMPLES IN ORDER TO DO THIS
WORK. ESPECIALLY SAMPLES FROM
RACIALLY DIVERSE DONORS. AND
NORMAL CONTROLS. SO THAT I FEEL
WAS OUR BIGGEST CHALLENGE.
>> THANK YOU. DR. SHEPHERD.
>> I WANTED TO ADD TO THIS
DISCUSSION, INITIALLY WE DID OF
COURSE EXPERIENCE CHALLENGES
OBVIOUSLY AS HUMAN RESEARCH SHUT
DOWN WITH COVID BUT ULTIMATELY
IT HAS CHANGED THE WAY THAT WE
DO RESEARCH AND I THINK WILL
PROBABLY CHANGE THE WAY I WILL
ALWAYS DO RESEARCH IN MY LAB. WE
TRANSITIONED EVERYTHING TO BE
ABLE TO COLLECT DATA AS MUCH
DATA AS POSSIBLE OBVIOUSLY NOT
NEUROIMAGING DATA, OVER ZOOM.
AND I THINK BECAUSE OF THAT WE
ENDED UP REACHING A LOT OF
PARTICIPANTS WHO INITIALLY
ORIGINALLY WOULDN'T HAVE
PARTICIPATED IN THIS STUDY.
PEOPLE WHO HAVE A LOT MORE
SEVERE MEDICAL CONDITIONS,
PHYSICAL DIFFICULTIES THAT WOULD
HAVE KEPT THEM HOME AND
PREVENTED THEM FROM ENROLLING IN
A STUDY THAT REQUIRED THEM TO
VISIT THE LAB MULTIPLE TIMES.
ONE CHALLENGE WE DID FIND WITH
PARTICIPANTS OF DEMENTIA, THEY
DID HAVE DIFFICULTY NAVIGATING
THE TECHNOLOGY BUT WE ARE ALWAYS
ABLE FOR ALL PARTICIPANTS TO
WORK WITH CAREGIVERS AND FAMILY
MEMBERS TO HELP THEM NAVIGATE
THOSE CHALLENGES SO ULTIMATELY
HOPING IT WILL BE A POSITIVE IN
FUTURE AND WE ARE REACHING MORE
PEOPLE THAT WE WOULDN'T HAVE
REACHED BEFORE.
>> DR. GARUDADRI. I'M HARI FROM
UK SAN DIEGO. I HAVE A COMMENT
FROM WHAT DR. KIRAN AND WHAT DR.
BRIAN MACWHINNEY SAID AND
FOLLOWING THAT I HAVE A COMMENT
TO JUDY'S QUESTIONS,
SPECIFICALLY (INAUDIBLE). THE
FIRST ONE IS IN USING TOOLS THAT
HAVE BECOME AVAILABLE FROM
GOOGLE, FACEBOOK, AMAZON, ALEXA
STUFF, THERE'S MISALIGNED
INCENTIVES ON WHAT THESE
COMPANIES REALLY WANT TO DO.
WITH A LOT OF PRIVACY AND OTHER
CONSIDERATIONS. SO I WOULD LIKE
TO UNDERSTAND WHY YOU ARE SO
EXCITED ABOUT THAT APPROACH.
GIVEN ALL THE PITFALLS WITH THE
BIG FIVE COMPANIES. THE COMMENT
FOR DR. MACWHINNEY IS --
>> WE HAVE LOTS OF PEOPLE WHO
WANT TO HAVE A COMMENT AND I
DON'T KNOW THAT I CAN GIVE YOU
THREE CHIPS. SO LET'S GET THE
ANSWER TO THAT ONE AND THEN IF
WE HAVE TIME AT THE END IF THAT
IS O DA I.
>> THAT'S PERFECT.
>> WHO WAS THAT QUESTION TO IN
GENERAL?
>> WE ARE NOT SAYING WE WORK
WITH BIG TECH COMPANIES TO
DETECT DEMENTIA. WHAT WE ARE
SAYING IS THAT THAT THERE IS A
LOT OF TECHNOLOGY IN USING AND
TRANSCRIBING SO BIG PART -- THE
WAY THINGS GET DONE IS PEOPLE
ARE IN LABS TESTING PATIENTS AND
THEN TRANSCRIBING AND THEN
TRYING TO UNDERSTAND WHAT HOW TO
TAKE THAT DATA AND DIAGNOSE
DEMENTIA OR TREAT DEMENTIA AND
WE ARE SAYING THERE IS A LOT OF
TECHNOLOGICAL ADVANCEMENTS IN
NATURAL LANGUAGE PROCESSING OF
JUST USING MACHINE LEARNING TO
DETECT ABNORMALITIES IN THAT
SPEECH. THAT IS ADVANCEMENTS
THAT I WAS TALKING ABOUT. I WILL
LET BRIAN CHIME IN AND SEE IF HE
WANTS TO SAY SOMETHING
DIFFERENT.
>> I THINK I ALWAYS DOUBT
COMPANIES, I AGREE WITH YOU, I
WORRY ABOUT THEIR PRIVACY. BUT
THEY TRYING TO DO GOOD THINGS,
TRYING TO IMPROVE COMMUNICATION
WITH PEOPLE, ADAPT SYSTEMS TO
WORK WITH PEOPLE WITH DEMENTIA
BETTER TO RESPOND TO THEIR
NEEDS. SO I THINK SOME GOALS
ARE NOT BAD AND WE HAVE TO BE
CAREFUL WITH INTERACTIONS WITH
THEM TOTALLY AGREE.
>> LET'S GO ON TO DR. BUCKEY.
>> THANKS, YES. SO I THINK FOR
THE CHALLENGES THAT WE HAVE SEEN
FOR CROSS SECTIONAL STUDIES WITH
PEOPLE, SO MANY CONFOUNDERS,
EDUCATION, SOCIOECONOMIC STATUS,
GENDER RACE ALL THOSE ARE BIG
FACTORS SO HAVING A LARGE COHORT
IS VERY IMPORTANT FOR PARAMETERS
MEASURED SO IF THERE IS A WAY TO
MAKE STANDARDIZED MEASUREMENTS
RECOMMENDED, AND HAVE
MULTI-CENTER ENROLLMENT TO
COHORT, THAT WOULD BE GOOD. THE
SECOND PART IS TO GET AT THESE
QUESTIONS ABOUT CAUSALITY. WILL
REQUIRE THE LONGITUDINAL
STUDIES. THOSE ARE HARD TO PUT
TOGETHER. BUT IF THERE IS WAY TO
ENCOURAGE ENROLLMENT TO
LONGITUDINAL COHORT FOLLOWED FOR
KEY EPIDEMIOLOGICAL FACTOR, THAT
WOULD BE GREAT.
>> THANK YOU. DR. KUSHALNAGAR.
>> GREAT, THANK YOU SO MUCH. TWO
COMMENTS ABOUT CHALLENGES. FOR
ME WORKING WITH EARLY DEAF
ADULTS OR SIGN LANGUAGE USERS IF
YOU WILL, THERE IS NO CHALLENGE
IN FINDING PEOPLE -- WE CAN FIND
A VERY DIVERSE GROUP OF PEOPLE
THE CHALLENGE IS THEIR
WILLINGNESS TO PARTICIPATE IN
THIS COMMUNITY BECAUSE A DEAF
COMMUNITIES ARE SO SMALL AND THE
LACK OF INFORMATION ACCESS IS SO
REAL, IT REALLY IS SUCH WHAT
ENDS UP HAPPENING IS PEOPLE
EXPRESS SHAME AN ANXIETY AND
BECAUSE OF ISSUES OF ADVANTAGE
TAKING, IN THE PAST FROM
RESEARCHERS AS SUBJECT THEIR
WILLINGNESS TO SHARE THEIR DATA
WITH US, IS VERY SMALL. WHEN IT
COMES TO CLINICAL TRIALS RIGHT
NOW I THINK IT IS BETTER BUT
MORE WORK TO BE DONE BECAUSE
THERE IS HISTORY OF EXCLUSIVE
PARTICIPANTS WHO ARE LITED RATE
IN READING AND WRITING. --
LITERATE IN READING AND WRITING WRITE AN
PARTICIPATING IN TRIALS, THAT'S
A TRIAL TO CONSIDER TO ALLOW
INCLUSIVITY OF ALL LANGUAGES,
NOT JUST INDIVIDUAL WHOSE
UTILIZE ONE LANGUAGE OR JUST USE
SPANISH BUT HAVE VISUAL AND
AUDITORY LANGUAGES. AND THE
DIFFICULTY IS TO FIND THOSE
INDIVIDUALS WITH DEMENTIA OR
HEARING LOSS AND BOTH.
>> DR. COHEN.
>> THANK YOU, TWO COMMENTS. ONE
IS I DISAGREE WITH P PERSON WHO
SAID THERE'S NO MORE LONGER A
ROLE FOR LABORATORY RESEARCH I
CAN TELL YOU THERE'S NO WAY THE
TEST VESTIBULAR SYSTEM NOT USING
THE LABORATORY. I TRIED TO DO IT
CLINICALLY, TO DO TELEHEALTH AND
IT CAN'T BE DONE SO I THINK
THERE IS A ROLE. BUT I LIKE
SOMEBODY SAID ABOUT USING
CLINICAL -- RESOURCES IN THE
COMMUNITY. SO I WILL THINK ABOUT
THAT. IN THE FUTURE. I ALSO
THINK SOMETHING ELSE THAT NIDCD
AND NIA CAN DO IS USE THIS
WEBINAR FORMAT AGAIN. I'M THE
ONLY ONE WHO DISCUSSED HUMAN
WORK VESTIBULAR SYSTEM, I WASN'T
TUNED IN TO THE WORK DONE ON
LANGUAGE AND HEARING SO I
THOUGHT THIS WAS REALLY
INTERESTING AND GOOD WAY TO
BRING TOGETHER DIVERSE GROUPS OF
PEOPLE, I HOPE YOU CONTINUE THIS
KIND OF THING.
>> THANK YOU.
>> DR. CHANDRASEKAREN.
>> I WAS GOING TO HEAVY SIT THE
QUESTION I HAD ON CHAT AND POSE
IT TO NIDCD OR NIA PROGRAM
STAFF. THESE ARE QUESTIONS THAT
NIMH IS ALREADY DEALING WITH
LIKE TEN YEARS AGO IN TERMS OF
HETEROGENEITY, CO-MORBIDITY,
CURIOUS ABOUT LESSONS LEARNED
FROM THE SEARCH DOMAIN CRITERIA
APPROACH USED BY NIH TEN YEARS
AGO AND WHETHER IT IS APPLIED
SPECIFICALLY EXPLORING
DIMENSIONS OF FUNCTIONING ACROSS
THE RANGE OF HUMAN BEHAVIOR,
UNITS OF ANALYSIS AND HOW THAT
CAN FRAMEWORK CONNECT THE DOTS
THIS ISN'T THE CONTEXT OF FUTURE
-- THIS IS IN THE CONTEXT OF
FUTURE DIRECTIONS.
>> ANY COMMENT OR REACTION TO
THIS?
>> CAN A COMMENT, PROGRAM
OFFICER AT NIDCD ABOUT ARTA. SO
I LOVE RDOC AND POINTED OUT
REPEATEDLY TO MANY PEOPLE IN THE
VOICE AND SPEECH IMMUNITIES.
RDO -- COMMUNITIES. RDOC IS A
GOOD THING TO LOOK AT.
>> MAYBE FOR THOSE IN THE
AUDIENCE NOT FAMILIAR YOU MIGHT
SAY A WORD OR TWO ABOUT IT.
>> IT IS A SYSTEM THAT NIMH
STARTED MANY YEARS AGO TO LOOK
AT DEVIL LEVELS OF ANALYSIS.
GENETIC BEHAVIORAL IMAGING AND
IT HAS A BUNCH OF INFORMATION SO
RATHER THAN LOOK AT THE DSMB
THEY WANTED TO REALLY CLEAN THE
DESCRIPTION OF THE INCOMING
SCIENCE SO I CAN'T SPEAK TO NIMH
BUT IT IS OUT THERE. RDOC. I
CAN PUT THE LINK IN THE CHAT.
>> ANY OTHER COMMENT, ANY OTHER
-- BACK TO OUR THREE QUESTIONS
ISSUE OF FUTURE DIRECTIONS WE
TALKED ON THAT A BIT AND WE ALSO
TALKED ABOUT WAYS TO ENCOURAGE
COLLABORATIONS. MAKE SOME
LESSONS LEARNED ON HOW YOU
ESTABLISHED COLLABORATIONS WITH
AS YOU WENT TO A NEW DIRECTION.
>> JEW DATE, MAY I PLEASE
COMMENT ON -- JUDITH, MAY I
COMMENT ON THAT?
>> SURE.
>> I WAS LISTENING TO TODAY'S
TALK FROM A VERY DIVERSE GROUP
OF RESEARCHERS, ESPECIALLY THOSE
FROM OLFACTORY SUB FIELD WITHIN
NIDCD SOMEHOW I FELT A GAP
BETWEEN OLFACTORY RESEARCHERS
AND HEARING RESEARCHERS IN THAT
SOME OF THE MEASURES WE USE A
LOT IN OUR STUDIES FOR EXAMPLE
AUDITORY BRAIN STEM RESPONSES
ABR YU HEARD OF THE TERM QUITE A
FEW TIMES, I WONDER,CAN THOSE
WHO STUDY SMELL TASTE IS SIMILAR
TECHNOLOGY IF NOT ABR MAYBE A
STITCH OR TWO HIGHER UP CORTICAL
RESPONSES. SO THAT WE CAN
UNDERSTAND SYSTEM LEVEL CHANGE
FROM A DIFFERENT ANGLE, TO
ADDRESS VERY COME PRIA KATEED
DISEASE LIKE ALZHEIMER'S.
COMPLICATED DISEASE LIKE
ALZHEIMER'S.
>> REALLY INTERESTING POINT IF I
CAN ADDRESS THAT ACTUALLY THE
OLFACTORY PEOPLE WHO SPOKE TODAY
ALL OF THEM ARE WELL VERSED AT
DOING CENTRAL AND PERIPHERAL
ELECTROPHYSIOLOGY AN OPTIMAL
METHODS AND -- WHO DIDN'T SPEAK
IS A LEADER IN THAT AS WELL. THE
FIRST CENTRAL SENSORY BOTH
ACTION POTENTIALS WERE IN
OLFACTORY BULB TO AT LEAST THE
ODOODORS, GET A NOBEL PRIZE FOR
THAT LONG TIME AGO BUT THAT IS
SOMETHING WE DO IN OLFACTION, IT
IS A TERRIFIC MODEL SYSTEM
BECAUSE THE INFORMATION GOES TO
BRAIN IN ONE SYNAPSE SO YOU HAVE
A DIRECT WAY LOOKING AT
INFORMATION, THE BULB IS
ACCESSIBLE. GREAT SYSTEM. I
APPRECIATE YOU POINT THAT OUT,
WE DIDN'T TALK AIN'T TODAY. THAT
IS SOMETHING THE OLFACTORY
COMMUNITY THINKS HAS BEEN ABLE
TO MAKE INCREDIBLE DISCOVERIES
IN.
>> THANK YOU FOR THAT. WE HAVE
TIME FOR ONE COMMENT FROM
MELANIE FRIED OKEN AND ONE FROM
NINA AND THEN WE NEED TO WRAP
UP. MELANIE.
>> I WANT TO STRESS THAT EVERY
LAB SHOULD INCLUDE INDIVIDUALS
WHO ARE EXPERIENCING WHATEVER
CONDITION YOU ARE LOOKING AT
WHETHER YOU ARE LOOKING AT MOUSE
MODELS OR DOING IMAGING IF YOU
ARE DOING IT -- IF YOU ARE
STUDYING INDIVIDUALS WITH
ALZHEIMER'S DISEASE PLEASE
INCLUDE INDIVIDUALS WITH
ALZHEIMER'S DISEASE AND THEIR
FAMILIES IN YOUR RESEARCH. THEY
WILL DRIVE THOSE QUESTIONS. OUR
ENGINEERS WHO DESIGN GREAT
COMPUTER INTERFACES GOING TO THE
HOMES OF INDIVIDUALS WITH LOCKED
IN SYNDROME, TO SEE WHY THEY ARE
DESIGNING THE SYSTEMS, AND I
THINK EVERY ONE ON THIS CALL
WOULD BENEFIT FROM WORKING AT A
COMMUNITY BASED PARTICIPATORY
RESEARCH LEVEL WITH INDIVIDUALS
WHO HAVE THOSE CONDITIONS WE ARE
EXAMINING.
>> THANK YOU, MELANIE. AND NINA,
YOU HAVE THE LAST WORD BEFORE WE
FINISH UP.
>> YOU ARE ON MUTE STILL.
>> NO.
>> THERE YOU GO. OKAY. THANKS
FOR THIS SESSION. IN TERMS OF
COLLABORATION, SOME OF THE
PITFALLS OR THE DIFFICULTIES
THAT WE HAVE HAD IS PEOPLE ARE
VERY, VERY BUSY. BUT HAVING
FORMS LIKE THIS WITH DEDICATED
TIME TO REALLY DISCUSS THESE
ISSUES AND THE POTENTIAL
COLLABORATION MY EXPERIENCE HAVE
BEEN INCREDIBLY SUCCESSFUL IN
REALLY GETTING PEOPLE TO THINK
ABOUT THESE ISSUES, AND THINK
ABOUT HOW THEY COLLABORATE. BUT
IF THERE IS NOT A SET TIME FOR
IT IN A SET FORUM IT IS
DIFFICULT TO GET PEOPLE OUT OF
THEIR BUSY SCHEDULES TO TALK
ABOUT THESE COLLABORATIONS.
>> THANK YOU, DR. DRONKERSS. WE
ALL AGREE WITH THAT. CORYSE, ANY
FINAL COMMENTS BEFORE I TURN IT
BACK OVER TO DR. POREMBA.
>> I WAS GETTING A FOA FOR THE
CHAT. I HAVE HEARD SO MUCH
RESEARCH, I'M SAL INVESTIGATING
OTHER THE STUDIES THAT CAN COME
TO NIA IN THE FUTURE. AND I WAS
CURIOUS HOW MANY OF YOU ARE
AFTER USING THE SUPPLEMENT TO
GENERATE PRELIMINARY DATA HOW
MANY OF YOU ARE ACTUALLY READY
TO PUT INTO RO1 OR DO YOU NEED
ANOTHER STEPPINGSTONE TO GET
THERE, SUCH AS RO 3. I WAS GOING
TO PUT THAT IN THE CHAT, WE HAVE
A RO 3 THAT IS ACTIVE NOW, I
KNOW IT EXPIRES LATER THIS YEAR
SO THAT BRINGS TWO MORE
OPPORTUNITIES LEFT WHEREBY IF
YOU NEED THE GENERATE ADDITIONAL
PRELIMINARY DATA YOU CAN USE
THIS AS POTENTIAL MECHANISM. IT
IS A MUCH LARGER BUDGET,
$100,000 PER YEAR FOR TWO YEARS.
SO MUCH LARGER THAN THE STANDARD
RO 3. SO I WILL INVITE YOU THE
CHECK THAT OUT IN THE CHAT.
>> THANK YOU, CORYSE. OKAY. I
THINK SO WE CAN STAY -- SINCE
Y'ALL WERE SO DILIGENT ABOUT
STAYING ON TIME WE WANT TO STAY
ON TIME TOO, WE SAID WE WERE
GOING TO END AT 5 SO AMY, I HAND
IT BACK TO YOU.
>> THANK YOU, JUDITH. THANK YOU
ALL FOR YOUR PARTICIPATION.
AGAIN, THANK YOU TO ALL OUR
STAFF AS WELL FOR HANGING IN
THERE THROUGHOUT THE DAY. IF YOU
HAVE FURTHER QUESTIONS, OR
COMMENTS, YOU CAN EMAIL DR.
COOPER, DR. CORYSE ST. HILLAIRE
CLARKE, MYSELF OR KELLY OR ANY
OF OTHER PROGRAM OFFICERS YOU
SAW ON TODAY, LAUREN OR SUSAN IF
MORE RELATED TO YOUR RESEARCH
AREA. I SAW LOTS OF WONDERFUL
DISCUSSION TODAY. THIS IS
EXACTLY THE KIND OF THING WE
WANTED WAS TO GET THE COMMUNITY
TOGETHER KIND OF FOR THE FIRST
TIME, DOING AD RESEARCH AND
COMMUNICATION, AND FIGURE OUT
WHERE WE ARE AT SO I THINK WE
HAVE GOT A LOT OF FOOD FOR
THOUGHT AND HOPING MANY OF YOU
WILL REACH OUT TO EACH OTHER AND
CONTINUE TO START TO THINK ABOUT
COLLABORATIONS AND COMMONALITIES
AMONG YOUR WORK. THANK YOU ALL.