>> ALL RIGHT.
GOOD AFTERNOON, EVERYONE, AND
WELCOME TO THE FIRST OF OUR
CONCURRENT SESSIONS.
THANK YOU.
THIS IS SESSION NUMBER 3, THE
SESSION ON THE MYCOG PROGRAM.
SO WHAT WE'LL DO TODAY IS I'LL
INTRODUCE EACH OF OUR SPEAKERS
AS THEY COME UP, THEY WILL GIVE
A BRIEF PRESENTATION AND THEN AT
THE END WE'LL HAVE TIME FOR A
QUESTION AND ANSWER PERIOD
ALTOGETHER.
ALL RIGHT. SO OUR FIRST SPEAKER
TODAY IS LAURA CURTIS FROM
NORTHWESTERN UNIVERSITY, AND
SHE'LL BE TALKING TODAY ABOUT
BARRIERS AND FACILITATORS TO
IMPLEMENTING MYCOG INTO PRIMARY
CARE FOR THE EARLY DETECTION OF
COGNITIVE IMPAIRMENT AND
DEMENTIA, LESSONS FROM THE
TOOLBOX DETECT TRIAL.
THANK YOU.
>> THANK YOU FOR THE
INTRODUCTION.
SO I HAVE NO RELEVANT FINANCIAL
DISCLOSURES, AND FIRST I JUST
WANT TO ACKNOWLEDGE THE TEAM.
MANY OF YOU ARE SITTING HERE IN
THE AUDIENCE.
SO EARLY DETECTION OF COGNITIVE
IMPAIRMENT IS IMPERATIVE.
IT HELPS TO IDENTIFY POTENTIAL
TREATABLE UNDERLYING CONDITIONS
AND PROVIDE SUPPORT SERVICES
WHEN IMPAIRMENT DUE TO -- WHEN
IMPAIRMENT IS DUE TO PROGRESSIVE
CONDITIONS.
HOWEVER, PRIMARY CARE SETTINGS
ARE IDEAL FOR IDENTIFYING CI,
GIVING CLINICIANS FAMILIARITY
WITH THE -- GIVEN CLINICIANS'
FAMILIARITY WITH THE PATIENT AND
REGULAR CONTACT TO MONITOR
CHANGES OVER TIME.
HOWEVER, COGNITIVE IMPAIRMENT
FREQUENTLY GOES UNDETECTED IN
PRIMARY CARE.
IN A 2017 META-ANALYSIS OF 27
STUDIES, OVER 60% THEREOF HAD
671% OF AMBULATORY CARE PATIENTS
IN THE U.S. WITH MCI OR DEMENTIA
SUN DETECTED.
HEALTH RECORD LINKED STRATEGY
FOR THE ROUTINE DETECTION OF
COGNITIVE DECLINE AMONG THE
FIRST PRIMARY CARE SETTINGS.
THIS WAS IN RESPONSE TO THE
LOW-COST DETECTION OF COGNITIVE
DECLINE IN CLINICAL SETTINGS
RFA, AND IN THAT IT INCLUDED A
CALL TO FACILITATE THE
INTEGRATION OF ASSESSMENTS INTO
EXISTING HEALTHCARE SECRETARIES,
PARTICULARLY FOR COGNITIVE
TESTING REQUIREMENT FOR MEDICARE
ANNUAL WELLNESS VISITS.
SO THIS FIT WELL INTO THE
PRIMARY CARE PARADIGM DR. WOLF
SHOWED IN HIS TALK THIS MORNING,
IF HAD THIS LOOKS FAMILIAR.
SO THE TOOLBOX DETECT PARADIGM
FOLLOWS THIS LOWER PATH HERE.
SO THE PATIENTS WHO WERE 65 AND
OLDER BEING SEEN FOR ANNUAL
WELLNESS VISIT, THEY
AUTOMATICALLY GET THE MYCOG
ASSESSMENT.
THEN IF THE ASSESSMENT INDICATES
IMPAIRMENT, A STANDARD PROTOCOL
FOR CLINICAL ACTION, AND I'LL
GET INTO SOME MORE DETAILS ABOUT
THIS AS I GO ON.
SO THE MYCOG ASSESSMENT CONTAINT
IS iPAD BASED, AS YOU KNOW
ALREADY, AND CONTAINS
SELF-ADMINISTERED ADAPTED
VERSIONS OF THE DID HE MEN SHALL
CHANGE CARD SORT AND PICTURE
SEQUENCE MEMORY FROM THE NIH
TOOLBOX VERSION 2.
SO ADAPTATIONS WE MADE WERE BOTH
TO MAKE THEM SELF-ADMINISTERED
TO REDUCE THE PICTURE SEQUENCE
MEMORY FROM TWO TRIALS TO ONE TO
SHORTEN IT, AND THEN WE ALSO
ADDED NEW STIMULI TO MAKE IT
DIFFERENT AND REDUCED THE NUMBER
OF PICTURES FROM FIFTEEN TO
TWELVE.
SO WE WORKED CLOSELY WITH THE
NORTHWESTERN UNIVERSITY TECH
TEAM AND NORTHWESTERN MEDICINE
EPIC TEAM TO BE ABLE TO
INTEGRATE THIS INTO CLINIC
WORKFLOW.
THE MYCOG APP WAS DESIGNED TO
RUN THE ASSESSMENT AND ALSO JUST
TO INTERPRETED IT WERE IN THE
MYCOG APP.
THE ASSESSMENT IS ACTIVATED BY A
DARR CODE THAT'S UNIQUE TO EACH
PATIENT, WHICH AUTOMATICALLY
SHOWS UP WHEN THEY ARE SCHEDULED
FOR AN ANNUAL WELLNESS VISIT.
IT IS TYPICALLY SCANNED BY THE
MEDICAL ASSISTANT WHEN ROOMING
USING THE iPAD AND THEN IT'S
HANDED TO THE PATIENTS TO
SELF-ADMINISTER.
ONCE COMPLETED, THE RESULTS
AUTOMATICALLY POPULATE INTO THE
CHART, AND THEN IF THEY ARE
IMPAIRED, THE PHYSICIANS RECEIVE
A BEST PRACTICE ADVISORY WITH A
SMART SET THAT FACILITATES NEXT
STEPS FOR EVALUATION.
AND THIS INCLUDES THE ABILITY TO
ORDER LABS FOR THEIR TESTING,
REFERRALS, AS WELL AS OTHER
RESOURCES TO SHARE WITH THE
PATIENT.
THE MAIN OBJECTIVES OF THE
TOOLBOX TRIAL WERE TO EVALUATE
THE EFFECTIVENESS OF THE MYCOG
PARADIGM COMPARED TO ENHANCE
EQUAL CARE TO DETECTED TIMELY
DETECTION OF COGNITIVE DECLINE
AND SUBSEQUENT CARE MANAGEMENT
AND ALSO TO INVESTIGATE THE
FIDELITY AND IDENTIFY ANY
PATIENT HEALTHCARE GIVER OR
HEALTHCARE PROVIDER SYSTEM
BARRIERS WITH OPTIMAL
IMPLEMENTATION.
SO IT IS A PRACTICE RANDOMIZED
PROGRESSMATIC TRIAL WHERE
PRIMARY CARE CLINICS ARE
RANDOMIZED TO TOOLBOX DETECT OR
USUAL CARE, WE PLAN TO ENROLL 40
CLINICS THROUGHOUT NORTHWESTERN
MEDICINE HEALTHCARE SYSTEM.
AT THE END OF THE TRIAL, WE WILL
BE COMPARING THE RATES OF
DETECTED AND/OR DIAGNOSED
COGNITIVE IMPAIRMENT AND RATES
OF COGNITIVE TESTING AND THAT
WOULD BE USING DATA FROM
NORTHWESTERN MEDICINE'S
ELECTRONIC MEDICINE DATA
WAREHOUSE.
SINCE THE TRIAL IS STILL ACTIVE,
THIS SYSTEM FOCUSES ON THE
FIDELITY OF TOOLBOX DETECT ANDS
FEEDBACK FROM PRIMARY CARE
CLINICIANS, PRACTICE MANAGERS
AND MEDICAL ASSISTANTS BOTH
REGARDING PARTICIPATION IN THE
TRIAL AND FOR ITS CONTINUED USE.
SO CURRENTLY WE HAVE 30
PRACTICES ENROLLED, 15 IN EACH
ARM.
OVER 17,000 PATIENTS WITH ANNUAL
WELLNESS VISITS OCCURRING IN THE
PARTICIPATING CLINICS.
AFTER A FEW MONTHS OF PILOTING
IN ONE CLINIC, MORE CLINICS WERE
ADDED IN EARLY 2023, AND WE'VE
BEEN ENROLLING AT A CONSISTENT
PACE SINCE.
MYCOG HAS BEEN COMPLETED IN 72%
OF THE ANNUAL WELLNESS VISITS,
AND COMPLETION RATES VARY WIDELY
BY CLINICIANS FROM 38% TO 90%,
AND I'LL GET INTO SOME POTENTIAL
REASONS FOR THIS.
SO IN TERMS OF FACILITATORS, THE
USE OF AN iPAD WAS INTRIGUING
FOR MANY CLINICIANS, AND THEY
THOUGHT OF DIFFERENT WAYS THAT
THEY COULD ALSO USE THE IPADS TO
HELP THEIR WORKFLOW.
THE MA'S LIKED THE SEAMLESS
AUTOMATION OF COGNITIVE TESTING
DATA COLLECTION WITHOUT THE NEED
TO ADMINISTER THE TESTS
THEMSELVES AND THEN ENTER THE
RESULTS INTO THE CHART, AS THEY
WERE CURRENTLY DOING WITH PENCIL
AND PAPER TESTS.
SO BEING ABLE TO SCAN THE
BARCODE AND HANDING IT TO THE
PATIENT TO COMPLETE THEMSELVES
WOULD ALLOW THEM TO COMPLETE
OTHER TASKS DURING THAT TIME,
MAKING THE VISITS MORE
EFFICIENT.
CLINICIANS WERE ALSO INTERESTED
IN A MORE RIGOROUS TEST AND THE
POTENTIAL TO REDUCE
FALSE-POSITIVES.
IT'S IMPORTANT TO NOTE THAT IN
CREATING -- FOR COGNITIVE
IMPAIRMENT WE FAVORED
SPECIFICITY OVER SENSITIVITY
BASED ON EARLY WORK WHERE
CLINICIANS INDICATED THAT
FALSE-POSITIVES WOULD BE MORE
DETRIMENTAL TO PATIENTS THAN
MISSING IMPAIRMENT BEFORE THE
FOLLOWING YEAR.
IN CASES WHERE KIND OF
IMPAIRMENT -- WHERE COGNITIVE
IMPAIRMENT WAS FOUND, THE
INCLUSION OF EXPLICIT CLINICAL
SUPPORT WAS HIGHLY VALUABLE.
SO WHILE TECHNOLOGY USE IS
INCREASING DRAMATICALLY IN OLDER
ADULTS, SOME ARE STILL LESS
COMFORTABLE USING TECHNOLOGY IF
THEY AREN'T AS EXPERIENCED.
THIS CAUSED SOME PATIENTS, A FEW
PATIENTS TO REFUSE AND FOR
OTHERS IT JUST TOOK THE MA JUST
A LITTLE MORE TIME TO HELP
ORIENT THOUGH THE iPAD.
HOWEVER, ONCE THEY BEGAN THE
ASSESSMENT, PEOPLE WERE ABLE TO
COMPLETE IT WITHOUT ANY PROBLEM.
SO THE TIME TO COMPLETE THE
ASSESSMENT CAN ALSO VARY
GREATLY.
WHILE THE AVERAGE OF TEN MINUTES
IS ACCEPTABLE TO MOST
CLINICIANS, THOSE WHO TAKE
LONGER MAY NOT FINISH BY THE
TIME THE PHYSICIAN COMES THE
ROOM, AND THAT WOULD DISRUPT
WORKFLOW.
THE CLINICIANS ALSO USE THE EHR
QUITE DIFFERENTLY.
OUR PARADIGM WAS ADDED TO THE
STANDARD RECOMMENDED ANNUAL
WELLNESS VISIT TEMPLATE, BUT NOT
EVERYONE USES IT.
SO WHILE THE RESULTS ARE STILL
AVAILABLE IF THEY DIDN'T USE
THAT TEMPLATE, WE NEEDED TO
CREATE A WORKAROUND TO TRAIN
THEM ON HOW TO FIND IT, AND
SINCE IT WASN'T AS
STRAIGHTFORWARD, IT COULD
POTENTIALLY AFFECT USE.
SO BASED ON THESE FACILITATORS
AND BARRIERS, ADOPTION AND USE
HAS BEEN VARIABLE.
BOTH PATIENT AND PRACTICE LEVEL
BARRIERS CONTRIBUTE TO THIS
VARIABILITY.
THIS IS NOT A ONE-SIZE-FITS-ALL
APPROACH, EVEN WITHIN CLINICS,
AND IT ALLOWS FOR MORE TAILORED
WORKFLOW TO OPT MIEDZ SCREENING
IN CLINICAL SETTINGS -- TO
OPTIMIZE SCREENING IN CLINICAL
SETTINGS.
ALL RIGHT.
THANK YOU.
OUR NEXT SPEAKER IS MORGAN
BONHAM FROM NORTHWESTERN
UNIVERSITY, AND SHE'LL BE
TALKING WITH US TODAY ABOUT
PRIMARY CARE DETECTION OF
COGNITIVE IMPAIRMENT, LEVERAGING
HEALTH AND CONSUMER TECHNOLOGIES
IN UNDERSERVED U.S. COMMUNITIES,
THE PROTOCOL FOR A PRAGMATIC
RANDOMIZED CONTROLLED TRIAL OF
THE MYCOG PARADIGM.
THANK YOU.
>> ALL RIGHT.
HI, EVERYBODY, MY NAME IS MORGAN
BONHAM.
I'M A CLINICAL RESEARCH
ASSOCIATE AT NORTHWESTERN
UNIVERSITY'S FEINBERG SCHOOL OF
MEDICINE AND I'M SITUATED WITHIN
THE CENTER OF APPLIED RESEARCH
ON AGING, BEEN WORK WITH THIS
GROUP SINCE 2016, PRIMARILY
INVOLVED IN LEADING RESEARCH
PROJECTS FROM OUR COGNITIVE
AGING PROGRAM.
TODAY I'M EXCITED TO HAVE THE
OPPORTUNITY TO INTRODUCE THE
MYCOG TRIAL TO YOU ALL.
FIRST OF ALL, I HAVE NO
FINANCIAL DISCLOSURES TO SHARE.
AND NEXT, I DO WANT TO
ACKNOWLEDGE THE STUDY TEAM.
MANY OF YOU ARE IN THE ROOM
TODAY.
THESE INDIVIDUALS ARE FROM THE
DIVISION OF GENERAL INTERNAL
MEDICINE AND MEDICAL SOCIAL
SCIENCES AT NORTHWESTERN, AND
THEN I ALSO WANT TO ACKNOWLEDGE
OUR COMMUNITY PARTNER O STREET
HEALTH WHO I WILL DEFINITELY
INTRODUCE IN FURTHER DETAIL
LATER ON IN THE PRESENTATION --
OAK STREET HEALTH, JUST FOR
THEIR MANY CONTRIBUTION TO SAY
THE TRIAL THUS FAR.
SO FIRST OF ALL, A FEW OF THESE
SLIDES MAY LOOK FAMILIAR TO YOU,
BUT I WANT TO REMIND YOU ALL
FROM DR. WOLF'S PRESENTATION
FROM EARLIER THIS MORNING THAT
THIS RESEARCH IS SUPPORTED BY
THE NATIONAL INSTITUTE OF
NEUROLOGICAL DISORDERS AND
STROKE AND IS BEING CONDUCTED AS
PART OF THE CONSORTIUM FOR
DETECTING COGNITIVE IMPAIRMENT
INCLUDING DEMENTIA WHICH I'LL
REFER TO AS DETECTCID AND THESE
ARE COLLABORATORS FROM
NORTHWESTERN.
SO PUBLISHED HERE COLLEAGUES
SEEN UP AS KATE'S GROUP HAVE
HIGHLIGHTED DISPARITIES OF
CONCERN OF TIMELY DETECTION AND
FOLLOW-UP ESPECIALLY AMONG
ASIAN, BLACK AND HISPANIC
ADULTS.
WITH THE STARTUP CONSORTIUM IN
2017 UNTIL PRESENT A HIGH
PRIORITY OF DETECT CID HAS BEEN
TO DEVELOP TOOLS THAT ARE
SUITABLE FOR PRIMARY CARE
SETTINGS THAT WILL INCREASE THE
FREQUENCY OF DETECTING COGNITIVE
IMPAIRMENT AND IMPROVED
EVALUATIONS.
SO HERE I WANTED TO HIGHLIGHT
WHAT WAS INCLUDED IN THE RFA AND
WHAT SPECIFICALLY THE TRIAL
SEEKS TO RESPOND TO, WHICH IS TO
ADDRESS THE UNMET NEED TO DETECT
COGNITIVE IMPAIRMENT INCLUDING
DEMENTIA IN LARGE AND DIVERSE
POPULATIONS SEEN IN PRIMARY CARE
ACROSS THE U.S., AND THIS IS NOT
JUST WHEN A PATIENT HAS A
CONCERN, BUT ALSO WHEN A
RELATIVE, CAREGIVER OR MEDICAL
PROVIDER HAS A CONCERN.
SO THIS TRIAL HAS TO MEET THREE
MAJOR REQUIREMENTS, AND THIS IS
THAT IT MUST BE IMPLEMENTED IN
HEALTH DISSPAR AT POPULATIONS,
IT MUST BE INTEGRATED INTO THE
EMR AND MUST PROVIDE TURNKEY
CLINICAL RECOMMENDATIONS.
SO IN REGARDS TO THE CONSORTIUM,
WE ARE NOW IN EFFECT CID TWO.
-- DETECT CID II.
THE GOALS OF THE MYCOG TRIAL ARE
TO INCORPORATE MYCOG INTO A
DIFFERENT EHR.
SO WE'VE DONE THIS WITH EPIC
WITH NORTHWESTERN MEDICINE.
WITH EPIC BEING USED AT MANY
LARGE HEALTH SMEDZ, WE WANTED TO
PIVOT PLATFORMS USED MORE
COMMONLY IN COMMUNITY HEALTH
CENTERS.
OUR STRATEGY IS TO BE
IMPLEMENTED IN LATINO AND BLACK
COMMUNITIES, SO -- WHO BEAR A
DISPROPORTIONATE BURDEN OF
DEMENTIA AND LOWER DETECTION ANY
COGNITIVE DIAGNOSIS.
WE WANT TO STUDY IMPLEMENTATION.
SO THE MYCOG ASSESSMENT IS
AVAILABLE, IT'S DCCS PFM THAT
MISS CURTIS EXPLAINED TO YOU
JUST A MOMENT AGO, IT CAN BE
COMPLETED IN ENGLISH OR IN
SPANISH, AND SPANISH IS A NEW
COMPONENT FOR THE TRIAL.
SO LANGUAGE IS SIMPLY SELECTED
BY THE CLINICIAN PRIOR TO
ADMINISTRATION, AND IT'S BASED
OFF THE PATIENT'S PREFERRED
LANGUAGE.
IT WAS VERY IMPORTANT FOR US TO
PRIORITIZE MAKING MYCOG
AVAILABLE IN SPANISH, AS THIS IS
JUST ONE STEP TOWARDS EXPANDING
THE UTILITY OF MYCOG IN PRIMARY
CARE SETTINGS AND OUR COMMUNITY
PARTNER ALSO STRONGLY SUPPORTED
OUR EFFORT IN THIS AREA.
SO NOW I WANT TO INTRODUCE OUR
COMMUNITY PARTNER IN MORE
DETAIL, OAK STREET HEALTH.
SO OAK STREET HEALTH IS A
NETWORK OF PRIMARY CARE CENTERS
FOR ADULTS ON MEDICARE WHO ARE
65 PLUS, AND I WANT TO NOTE IN
FEBRUARY THEY WERE PURCHASED WI
CVS HEALTH WHICH IS ONE OF THE
WORLD'S LARGEST HEALTHCARE
COMPANIES.
JUST SO YOU CAN SEE THE SPREAD
HERE, THIS INCLUDES ABOUT 169
MEDICAL CENTERS ACROSS 21
STATES, AND OAK STREET HEALTH
SUPPORTS A DIVERSE POPULATION
STRATEGICALLY LOCATED IN EASY
ACCESS IN HIGH DENSITY RETAIL
LOCATIONS ACROSS THE NATION.
SO HERE I JUST WANTED TO
SPECIFICALLY HIGHLIGHT OUR
PERFORMANCE SITES.
YOU CAN SEE THEM IN GREEN HERE.
SO THERE ARE FIVE STATES
INCLUDED IN THE TRIAL.
IT'S ILLINOIS, MISH GARNTION
PENNSYLVANIA -- MICHIGAN,
PENNSYLVANIA AND THE CAROLINAS.
24 CLINICS, 12 INTERVENTION, 12
CONTROL, AND WITH THE MYCOG
TRIAL WHERE WE'RE EXPANDING TO
LESS URBAN AREAS AND TO STATES
OUTSIDE -- WHICH IS SUPER
EXCITING.
THEN A FEW MORE DETAILS ABOUT
THEIR EHR SPECIFICALLY.
OAK STREET HEALTH USES GREENWAY,
PRIME SUITE AND CANOPY SOFTWARE,
THIS HAS BEEN A REALLY UNIQUE
CHALLENGE EXPINT GRAITION AS
WE'RE WORKING WITH TWO DIFFERENT
SYSTEM INSTEAD OF JUST ONE.
THE SIMPLEST WAY I CAN EXPLAIN
THIS, OUR TECH TEAMS WERE ABLE
TO WORK TOGETHER TO CUSP EYES
INTEGRATION INTO CANOPY WHICH
THEN REFLECTS INTO GREENWAY.
SO THESE TWO SYSTEMS ARE ABLE TO
COMMUNICATE WITH ONE ANOTHER.
SO AGAIN, BACK TO THE SAME
WORKFLOW, THIRD TIME TODAY, YOU
CAN SEE THIS WORKFLOW AGAIN,
MISS CURTIS SHOWED EARLIER IN
HER PRESENTATION, BUT I WOULD
LIKE TO NOTE THAT WE CAN DELIVER
MYCOG FOR ANNUAL WELLNESS VISITS
AND FOR ROUTINE VISITS MEETING
ANNUAL WELLNESS VISIT
REQUIREMENTS AND ALSO THERAPY
CONCERNS, BUT WHAT I REALLY WANT
TO FOCUS ON IS THE DIFFERENCE
BETWEEN CLINICAL WORKFLOW
ESPECIALLY WHEN THERE ARE
POSITIVE RESULTS.
SO I'M JUST GOING TO FEED THAT
AWAY AND INTRODUCE YOU TO THIS A
LITTLE BIT MORE.
OAK STREAM HEALTH HAS THE
CAPABILITY TO REFER PATIENTS TO
A SPECIALIST OUTSIDE OF THE
CENTER, AND THIS IS CALLED
RUBICON MD.
FOR THOSE WHO DON'T KNOW ABOUT
RUBICON MD, OAK STREET HEALTH
REQUIRED IN OCTOBER 2021 --
ACQUIRED THEM IN OCTOBER 2021,
LEADING TECHNOLOGY PLATFORM
PROVIDING ACCESS TO SPECIALIST
EXPERTISE.
THIS EN AIBLEDZ OAK STREET TO
INTEGRATE VIRTUAL SPECIALTY CARE
INTO THEIR EXISTING CARE MODEL.
THIS IS TO SIGNIFICANTLY
STREAMLINE THE REFERRAL PROCESS,
BETTER MANAGE COSTS, ENHANCE
PATIENT EXPERIENCE AND PROVIDE
MORE COMPREHENSIVE PATIENT CARE.
THERE ARE OVER 230 SPECIAL IS
COVERING ALL MAJOR SPECIALTIES.
SO GETTING CLOSE TO THE END OF
THE CONCLUSION HERE, I JUST
WANTED TO GIVE A LITTLE STATUS
UPDATE ON WHERE WE'RE AT AT THE
MOMENT.
SO WE ARE WORKING TO FINALIZE
THE PILOT, AND WE HAVE ALREADY
GAINED MUCH INSIGHT FROM CLINICS
WHO OFFER IMPLEMENTATION, WHICH
HAS BEEN GREAT.
FOR EXAMPLE, WE'VE BEEN STREEN
LINING THE APP TO BE --
STREAMLINING THE APP TO BE MORE
EFFICIENT, UPDATING SCREEN
VISUALS FOR BETTER WORKFLOW AND
THEN IN TERMS OF IMPLEMENTATION
CHALLENGES, WE MADE CHANGES TO
THE APP PER THE USE OF A QR CODE
INSTEAD OF A BARCODE, AND WHILE
WE COULD USE OUR EPIC
INTEGRATION WITH THE TOOLBOX
DETECT PROJECT AS A GUIDE AND A
FOUNDATION, WE STILL HAD TO
COMPLETELY CUSTOMIZE THE EHR
INTEGRATION INTO CANOPY AND
GREENWAY TO MEET OAK STREET
HEALTH'S SECURITY MEASURES AND
REQUIREMENTS.
AND WITH THAT, I JUST WANT TO
MENTION AT THAT OUR LIMITATIONS
ARE THAT WE ARE COLLECTING DATA
FROM ONLY OAK STREET HEALTH
CLINICS AND THAT WE WILL BE
RELYING ON EHR OUTCOME
PRIMARILY.
AND THAT IS THE END OF MY
PRESENTATION.
THANK YOU SO MUCH.
>> THANK YOU VERY MUCH.
I'M NOT SURE IF WE CAN CONDENSE
THE SLIDE BACK TO OUR
ORIGINAL -- OKAY.
>> ALL RIGHT.
THANK YOU ALL.
SO OUR NEXT GROUP OF TALKS,
WE'LL GO ONE TO THE NEXT, WOULD
YOU LIKE ME TO INTRODUCE YOU ALL
RIGHT NOW, OR ONE BY ONE?
WHATEVER IS EASIEST?
>> YOU CAN DO ALL OF US.
>> OKAY.
ALL RIGHT.
WE'LL DO THEM ALL.
SO THIS IS GOING TO BE A SUITE
OF THREE PRESENTATIONS ON MYCOG
ON THE TABLET AND MOBILE
PROGRAM.
SO WE'LL START OFF WITH
DR. NOWINSKI WHO IS GOING TO BE
SPEAK BEING REMOTE COGNITIVE
SCREENING IN HEALTHY OLDER
ADULTS FOR PRIMARY CARE WITH THE
MYCOG MOBILE APP, ITERATIVE
DESIGN AND USABILITY EVALUATION.
WE'LL THEN CONTINUE ON WITH
DR. STEPHANIE YOUNG WHO WILL BE
PRESENTING ON REMOTE
SELF-ADMINISTRATION OF COGNITIVE
SCREENERS PRIOR TO A PRIMARY
CARE VISIT, A PRELIMINARY
EVALUATION OF THE RELIABILITY
AND USABILITY OF THE MYCOG
MOBILE SCREENING APP, AND THEN
WE'LL FINISH UP WITH CALLIE
JONES, WHO WILL BE TALKING ABOUT
THE CONSTRUCT AND CLINICAL
VALIDATION OF MYCOG MOBILE.
A REMOTE SMARTPHONE BASED
COGNITIVE SCREENER.
ALL RIGHT.
THANK YOU.
>> ALL RIGHT.
GOOD AFTERNOON, EVERYBODY.
I AM VERY EXCITED TO TELL YOU
ABOUT MYCOG MOBILE, WHICH IS THE
SMARTPHONE BASED VERSION OF
MYCOG.
I'M GOING TO PROVIDE AN
INTRODUCTION OVERVIEW TO MYCOG
MOBILE, AND THEN IT WILL BE
FOLLOWED UP BY STEPHANIE AND
CALLIE WHO WILL TELL YOU ABOUT
OUR PROJECTS THAT WE'RE DOING.
YOU HAVE ALREADY BEEN PRESENTED
WITH THE RATIONALE FOR DOING
COGNITIVE SCREENING IN PRIMARY
CARE CLINICS, SO I WON'T GO OVER
THOSE AGAIN, BUT I WILL SAY THAT
MYCOG MOBILE IS ANOTHER ATTEMPT
TO MEET THAT NEED BY A VALID,
RELIABLE ACCURATE AND FEASIBLE
WAY TO ASSESS COGNITIVE FUNCTION
IN PRIMARY CARE CLINICS.
SO IF YOU WERE HERE THIS MORNING
AND HEARD MIKE WOLF'S TALK, THIS
IS AGAIN PART OF IT, WE ARE
TRYING TO PROVIDE A SUITE OF
PRODUCTS THAT CAN MEET DIFFERENT
NEEDS FOR DIFFERENT CLINICS.
MYCOG MOBILE INCLUDES MANY OF
THE SAME FEATURES THAT MYCOG
DOES.
IT CAN BE DONE PRIOR TO A
PRIMARY CARE VISIT, IT IS
SELF-ADMINISTERED, RESULTS ARE
AUTOMATICALLY SENT TO THE EHR
WHEN THE PATIENT IS DONE AND
THERE THE PHYSICIAN CAN VIEW
THEM BEFORE THE PATIENT ACTUALLY
COMES IN, AND AS IT WAS IN
MYCOG, IF THE PATIENT SCORES IN
THE HIGH RISK FOR COGNITIVE
IMPAIRMENT RANGE, THEN
APPROPRIATE BEST PRACTICE ALERTS
ARE AUTOMATICALLY AVAILABLE AND
PUT INTO THE EHR, AND THEN THE
CLINICIAN CAN DISCUSS THOSE
RECOMMENDATIONS WITH THE PATIENT
AND THE FAMILY IF NEEDED AND
THEN DECIDE WHAT ARE THE NEXT
STEPS.
WHAT IS DIFFERENT ABOUT MYCOG
MOBILE AGAIN IS IT'S A
SMARTPHONE, IT DOESN'T USE --
AND IT'S FOR REMOTE ASSESSMENT,
SO IT'S NOT GOING ON USE THE
SAME KINDS OF WAYS OF GETTING
INTO IT.
SO, YOU KNOW, INSTEAD OF HAVING
A BARCODE, IT WILL PROBABLY BE
SOMETHING THROUGH LIKE MY CHART.
THEY WILL DOWNLOAD THE APP AND
THEN THEY WILL TAKE IT ON THEIR
OWN.
IT ALSO LOOKS A LITTLE BIT
DIFFERENT AS YOU CAN SEE, CALLED
COGNITIVE CHECKUP.
THERE'S BEEN SOME DESIGN
ELEMENTS TO MAKE IT MORE
APPROPRIATE FOR SOMEONE DOING ON
THEIR OWN.
MYCOG HAS BEEN ABLE TO TAKE
ADVANTAGE AND LEVERAGE TO OTHER
PROJECTS, SO MYCOG ITSELF, WHICH
IS THE TABLET APP AND WAS
DESIGNED FOR IN PERSON
ADMINISTRATION, AND THEN THE
MOBILE TOOLBOX WHICH YOU HEARD
ABOUT EARLIER TODAY TOO, WHICH
IS A RESEARCH TOOL THAT WAS
DEVELOPED FOR REMOTE ASSESSMENT
OF COGNITION AND OTHER
SUPPLEMENTAL SCALES.
SO WE TOOK WHAT WE LEARNED FROM
THOSE TWO PROJECTS, MEASURES
TECHNOLOGY, AND WE ARE CREATING
THIS REMOTE CLINICAL TOOL.
AND IT USES FOUR MEASURES THAT
ARE EITHER IN MYCOG OR MOBILE
TOOLBOX AND IN EXPROAMENT WE
ADAPTED FOR THIS PARTICULAR USE,
REMOTE SELF-ADMINISTRATION
BEFORE PRIMARY CARE VISIT.
IT CURRENTLY INCLUDES THESE FOUR
MEASURES PLUS WE DECIDED TO ADD
THREE SURVEY QUESTIONS, ONE TO
GET INFORMATION ABOUT SUBJECTIVE
COGNITIVE CONCERNS, BECAUSE AS
YOU HEARD IN SOME OF THE OTHER
PRESENTATIONS THAT IT'S NOT --
THESE MEASURES, THESE PRODUCTS
ARE NOT AIMED ONLY FOR AN ANNUAL
WELLNESS VISIT, BUT ALSO IF
THERE IS A CONCERN IN BETWEEN
VISITS OR A CONCERN RAISED AS
PART OF A VISIT, SO THAT WE CAN
ALSO ADMINISTER FOR THOSE CASES.
AND WE WANTED TO KNOW, IS THERE
A CONCERN.
WE'RE ALSO ASKING ABOUT AGE AND
EDUCATION.
SO FOUR MEASURES IN THESE
ADDITIONAL THREE SURVEY
QUESTIONS, THE MYCOG MOBILE IS
CURRENTLY LONGER THAN WE WANT IT
TO BE FOR A SELF-ADMINISTERED
BATTERY.
SO OUR LONG-TERM GOAL IS TO
REDUCE THE NUMBER OF MEASURES IN
ORDER TO REDUCE TESTING TIME,
AND WE'RE GOING TO DO THIS BY
RUNNING A CLINICAL VALIDATION
STUDY, WHICH YOU WILL HEAR ABOUT
IN LATER PRESENTATIONS, AND
WE'LL USE THE DATA FROM THAT TO
DECIDE WHICH ARE THE BEST
MEASURES OUT OF THOSE FOUR THAT
WILL PREDICT COGNITIVE
IMPAIRMENT.
SO EVEN THOUGH IT'S
SELF-ADMINISTERED REMOTELY, WE
WANT TO MAKE SURE THAT IT'S NOT
TOO LONG SO THAT THE PEOPLE
ACTUALLY DO IT.
NOW WE'RE GOING TO BRIEFLY
EXPLAIN, DESCRIBE THE MEASURES
THAT ARE INCLUDED, AND THESE
HAVE BEEN ADAPTED FROM EXISTING
MEASUREMENT SYSTEMS.
SO THE FIRST ONE THAT IS IN THE
BATTERY SCURNL THE FACE-NAME
ASSOCIATIVE MEMORY EXAM WHICH
THE ORIGINAL VERSION WAS
DEVELOPED BY RENTZ A VERSION IN
THE NIH TOOLBOX AND A VERSION IN
THE MOBILE TOOLBOX, AND IT IS
PRESENTED IN TERMS OF AN INITIAL
LEARNING TRIAL WHERE THE PERSON
IS, YOU KNOW, DOES SOME
PROCESSING SO THEY WILL REMEMBER
THESE FACE-NAME PAIRS, SO IT'S A
FACE-NAME PAIR.
THEN WE HAVE A DELAY, AND THEN
THEY HAVE THESE THREE SUBTESTS
WHERE WE ASSESS THEIR MEMORY FOR
THE FACE-NAME PAIRS IN THREE
DIFFERENT WAYS, DO THEY
RECOGNIZE THE FACE, CAN THEY
MATCH THE NAME WITH THE CORRECT
FACE, AND CAN THEY RECALL THE
FIRST LETTER OF THE PERSON'S
NAME.
AND THE SCORE ON THIS TEST IS
HOW MANY THEY CAN CORRECT ON ALL
THREE OF THESE -- HOW MANY THEY
GET CORRECT ON ALL THREE OF
THESE.
THEY ALSO GET A COGNITIVE
CONTROL EXECUTIVE FUNCTION TEST,
WHICH WE CALL IT MY SORTING IN
MYCOG MOBILE.
IT IS AN ADAPTATION OF A MEASURE
IN THE MOBILE TOOLBOX, AND
THERE'S ALSO A VERSION IN MYCOG.
AND WHAT THE PERSON HAS TO DO IS
THEY HAVE TO CATEGORIZE THE
IMAGE WI COLOR OR SHAPE, THEY
ARE PRESENTED WITH WORD SHAPE OR
THE WORD COLOR, THEY DO THE
CATEGORIZATION, AND THE MEASURE
SWITCHES BACK AND FORTH, BACK
AND FORTH TO ASSESS THEIR
COGNITIVE FLEXIBILITY.
WE ALSO GIVE THEM A WORKING
MEMORY MEASURE.
THIS WAS ADAPTED FROM SEQUENCES
IN MOBILE TOOLBOX, AND IT'S A
WELL-KNOWN EXISTING PARADIGM.
PARTICIPANTS ARE PRESENTED WITH
A SERIES OF NUMBERS AND THE
SERIES GETS LONGER DEPENDING ON
HOW MANY THEY COULD CORRECT.
THEY GET THE SEQUENCE OF LETTERS
AND NUMBERS, AND THEN THEY HAVE
TO REMEMBER THEM AND SORT THEM
IN THEIR MIND AND THEN ORDER
THEM BY THE LETTERS FIRST, THEN
BY NUMBERS.
AND THEN FINALLY WE HAVE MY
PICTURES.
THIS IS AGAIN AN ADAPTATION OF A
TEST THAT'S ALREADY IN THE
MOBILE TOOLBOX, AS WELL AS
MYCOG.
AGAIN, THIS IS A VERSION OF
MYCOG.
AND IT IS AN EPISODIC MEMORY
TEST.
THEY SEE A SEQUENCE OF PICTURES
AND THIS SEQUENCE IS IN A
PARTICULAR ORDER, IT DOESN'T
HAVE TO BE LOGICALLY ARRANGED
THAT WAY, BUT THEY SEE IT IN A
PARTICULAR ORDER.
THERE'S A BRIEF AUDIO
DESCRIPTION.
THE PICTURES SCRAMBLE
THEMSELVES, AND THEY THEN ARE
ASKED TO REARRANGE THE IMAGES IF
THE ORDER BY PUTTING THEM IN THE
SERIES OF, AS YOU CAN SEE HERE,
THESE OPEN BOXES.
SO THEY START OUT WITH A
FOUR-IMAGE PRACTICE TRIAL, AND
THEN IT JUMPS UP TO TWELVE
IMAGES.
YEAH, TWELVE IMAGES.
WE HAD TO DO SOME ADAPTATION IN
TERMS OF CHANGE IT GO FROM MYCOG
BECAUSE OF THE SCREEN SIZE.
YOU KNOW, WE WANT TO BE ABLE TO
MAKE SURE THAT THE PERSON CAN
SEE THESE TWELVE PICTURES
CLEARLY ENOUGH ON A SMALL
SCREEN.
SO THOSE ARE THE FOUR MEASURES,
AND IT'S A BRIEF OVERVIEW OF
WHAT MYCOG MOBILE LOOKS LIKE.
AND NOW MY COLLEAGUES ARE GOING
TO PRESENT THE FINDINGS OR AT
LEAST THE PLAN OF THREE ONGOING
STUDIES THAT WE'RE DOING ON
MYCOG MOBILE.
THE STUDIES WILL GET USABILITY,
THEY LOOK THE AFEASIBILITY AND
THEN CONSTRUCT AND CLINICAL
VALIDATION.
WELL, THANK YOU.
NOW WE'LL TURN IT OVER TO
STEPHANIE.
>> IT LOCKS LIKE OUR
ACKNOWLEDGMENT SLIDE DID MAKE IT
INTO THE DECK.
AGAIN, ACKNOWLEDGING FOLKS ON
THE PROJECT.
THANK YOU SO MUCH.
ALL RIGHT.
SO I'M GOING TO TALK ABOUT TWO
OF THE STUDIES THAT WE'VE
ALREADY COMPLETED USING MYCOG
MOBILE.
THE FIRST SOMEONE A USABILITY
STUDY AND JUST A LITTLE BIT
ABOUT THE DESIGN.
AND THEN A PILOT STUDY THAT WE
COMPLETED WITH THE VERSION ONE
OF THE APP.
I'M JUST GOING ON BRIEFLY GIVE
AN OVERVIEW ON THESE, BUT BOTH
OF THESE STUDIES HAVE BEEN
PUBLISHED IN JMIR AND I'LL GIVE
THE CODE LINK IT IF YOU WANT TO
LOOK AT MORE INFORMATION ABOUT
THEM.
SO WHEN WE SOUGHT OUT TO MAKE
THE MYCOG MOBILE APP, WE KNEW
THAT THE DESIGN WAS GOING TO BE
REALLY IMPORTANT FOR
SELF-ADMINISTERING SMARTPHONE
APP, RIGHT, THIS IS SOMETHING
THAT YOU'RE GOING TO USE ON YOUR
OWN PERSONAL SMARTPHONE AND YOU
DON'T HAVE AS MUCH CONTROL OVER
PARTICIPANTS WHEN THEY'RE TAKING
IT.
SO AS DR. WOLF MENTIONED EARLIER
TODAY, KIND OF THAT ITERATIVE
DESIGN PROCESS WAS VERY
IMPORTANT.
WE USED A HUMAN CENTERED DESIGN
AEXPROACH WE DID HAVE UX
DESIGNERS HELPING US WITH THIS
AND GIVING US SOME INPUT, BUT
WHAT THAT REALLY ENTAILS IS KIND
OF GATHERING DATA FROM THE END
USERS AND THAT COULD BE ADULTS
WHO ARE OVER AGE 65 BUT ALSO OUR
CLINICAL END USERS, SO THEIRS
MULTIPLE PEAM WHO ARE KIND OF
INVOLVED IN THE PROCESS --
MULTIPLE PEOPLE WHO ARE INVOLVED
IN THE PROCESS, INCLUDING
PRACTICE MANAGERS R AND THOSE
GATHERING DATA AT THEIR CLINICS,
GATHER INFO FROM THE
STAKEHOLDERS AND USE THAT TO
INFORM THE DESIGN PIECE BY PIECE
AS WE DEVELOPED THE APP.
SO I'M NOT GOING TO GO INTO TOO
MUCH DETAIL ABOUT THE WHOLE
PROCESS, JUST KIND OF GIVE YOU A
BRIEF OVERVIEW OF WHO WE TALKED
TO.
SO WE STARTED OUT TALKING TO
CLINICIANS.
THESE WERE MOSTLY PRIMARY CARE
PROVIDERS OR PEOPLE WHO WORKED
IN GERONTOLOGY, AND THEY KIND OF
GAVE US THE FORMATIVE
INTERVIEWS, THAT'S WHERE WE
THOUGHT OF KIND OF THE
FOUNDATIONAL DESIGN OF MYCOG
MOBILE, LIKE WHAT DOES IT LOOK
LIKE, HOW DOES IT WORK, HOW IS
IT TAKEN, WHAT ARE THE THINGS
THAT THEY REALLY VALUE OUT OF
IT.
WE ALSO SPOKE WITH CLINIC
ADMINISTRATORS, SO THAT WOULD BE
LIKE MEDICAL ASSISTANTS OR
PRACTICE MANAGERS, TO KIND OF
UNDERSTAND WHAT WOULD BE THE
BEST WORKFLOW FOR ACTUALLY
IMPLEMENTING THIS IN A CLINIC.
AND THEN OF COURSE WE TALKED TO
OLDER ADULTS WHO WOULD ACTUALLY
BE THE PEOPLE WHO USED THIS ON
THEIR OWN SMARTPHONES, SO WE DID
A COMMUNITY STAKEHOLDER PANEL
WHERE WE SPOKE WITH A BUNCH OF
OLDER ADULTS FROM DIVERSE
BACKGROUND AND IS KIND OF ABOUT
THEIR OPINIONS ASK ATTITUDES
ABOUT USING A COGNITIVE SCREENER
LIKE THIS ON A SMARTPHONE, THEN
WE ALSO DID INDIVIDUAL
INTERVIEWS WITH FOLKS AND HAD
THEM ACTUALLY INTERACT WITH
CLICKABLE PROTOTYPES OF THE
DESIGN SO WE COULD GET SOME
FEEDBACK THERE.
SO FINDINGS FROM THE DATA
COLLECTION WITH THESE DIFFERENT
STAKEHOLDERS KIND OF SHOWED US
THAT PEOPLE CARE ABOUT DIFFERENT
THINGS.
SO WHEN WE SPOKE WITH
CLINICIANS, THE THINGS THAT THEY
CARE ABOUT ARE USING WELL
VALIDATED SCREENING TESTS, BEING
ABLE TO VIEW THE SCORES WITHIN
THEIR OWN EHR WAS REALLY
IMPORTANT, SO YOU'RE NOT
ACTUALLY LIKE TAKING SOME SCORES
FROM A PIECE OF PAPER, HAND
SCORING IT AND THEN ENTERING IT,
EHR IS AUTOMATICALLY POPULATING,
THEN ALSO BEING AINL TO KNOW
WHAT TO DO WITH THE SCORES --
ABLE TO KNOW WHAT TO DO WITH THE
SCORES WHEN THEY GET THAT, BEST
PRACTICES, SAYING OKAY, I HAVE A
POSITIVE RESULT, WHAT'S THE NEXT
STEP.
FOR STAFF, IT WAS IMPORTANT TO
KIND OF EFFICIENCY IS THE MOST
REALLY IMPORTANT THING IS KIND
OF MINIMIZING THE STAFF
INVOLVEMENT IN THE SCREENING
PROCESS, MOST OF THESE CLINICS
ARE VERY STRAPPED FOR TIME AND
STAFF RESOURCES AND BEING ABLE
TO KIND OF EASILY COMMUNICATE
WITH A PATIENT WHAT THE
SITUATION IS AND MOVE THROUGH
THE PROCESS SEAMLESSLY.
FOR PATIENTS, THEY CARED ABOUT,
YOU KNOW, A LOT OF THOSE THINGS
AS WELL, BUT REALLY AM I GOING
TO BE GETTING GOOD RESULTS, AM ?
THOSE ARE THE MOTIVATIONS TO
TAKE THESE SCREENING TESTS TO
MONITOR CHANGE OVER TIME AND
KNOW IF THEY HAVE SOME SORT OF
PROBLEM.
AND THEN THERE'S ALSO SHARED
PRIORITIES BY THESE DIFFERENT
STAKEHOLDERS, BUT REALLY THE
MAIN PRIORITY THAT WE FOUND THAT
WAS IN COMMON ACROSS ALL THE
PEOPLE WHO WOULD BE INVOLVED IN
THIS PROCESS IS BEING ABLE TO
SAVE TIME DURING THEIR IN PERSON
VISIT TO FOCUS ON OTHER THINGS
THAT ARE MORE IMPORTANT, RIGHT?
SO TAKING A SCREENING TEST IN AN
IN PERSON VISIT TAKES TIME, AND
IF THERE'S NOTHING WRONG,
THERE'S NO CONCERN, WE DON'T
NEED TO TAKE UP THAT TIME DURING
YOUR VISIT.
SO BASED ON ALL THE INFORMATION
THAT WE GOT FROM THESE DIFFERENT
STAKEHOLDERS, THIS KIND OF SHOWS
THE JOURNEY, USER JOURNEY OF HOW
THEY WOULD USE MYCOG MOBILE.
SO PATIENT SCHEDULES AN ANNUAL
WELLNESS VISIT, IT MIGHT NOT BE
JUST AN ANNUAL WELLNESS VISIT,
IT COULD BE JUST A PRIMARY CARE
VISIT, AS WE'VE SPOKEN ABOUT
BEFORE, OR SOME OTHER TYPE OF
VISIT.
AND PRIOR TO THE VISIT, THEY
WOULD RECEIVE A MESSAGE FROM
THEIR CLINIC THAT SAYS, YOU
KNOW, IT'S TIME TO COMPLETE
MYCOG MOBILE, YOUR DOCTOR HAS
ASKED YOU TO COMPLETE THIS,
PLEASE DOWNLOAD THIS APP.
THEY WILL DOWNLOAD THAT ONTO
THEIR PERSONAL SMARTPHONE,
COMPLETE THE MEASURES, THEY'RE
COMPLETELY SELF-ADMINISTERED SO
THEY'RE DOING THIS ALL ON THEIR
OWN.
AS SOON AS THEY'RE DONE, THOSE
SCORES ARE SENT DIRECTLY TO THE
EHR AND POPULATE WITHIN THE EHR
SO THE CLINICIAN CAN SEE THAT.
IF THERE IS A POSITIVE RESULT
THERE, THEY WILL ALSO GET BEST
PRACTICE ALERTS THAT'S TELLING
THEM OKAY HERE IS THE NEXT STEP,
WHICH ALLOWS THE CLI ANYTHING TO
PREPARE FOR THE VISIT BEFORE THE
PATIENT COMES IN, IF THEY WOULD
LIKE.
THEN DURING THE VISIT.
ARE THAT'S WHEN THE PATIENT WILL
GET THE RESULTS, THEY'LL TALK
ABOUT GET APPROPRIATE REFERRALS
AND NEXT STEPS IN THAT WAY.
SO JUST A FEW KEY TAKE AWAYS IN
DESIGN FEATURES WE'VE LEARNED
FROM THIS ITERATIVE DESIGN
PROCESS.
AGAIN, THE THAT MAIN BENEFIT OF
MYCOG MOBILE IS SAYING THAT IN
OFFICE TIME.
MYCOG MOBILE IS
SELF-ADMINISTERED BY THE PATIENT
REMOTE ON A SECURE APP, SO ONE
OF THE MAIN THINGS WE'VE LEARNED
RIGHT AWAY WAS THAT THIS JUST
COULD NOT BE PROCTORED ANY WAY.
THESE CLINICS ARE TOO STROPPED
FOR TIME -- STRAPPED FOR TIME,
SO IN THIS WAY IT'S COMPLETELY
ON THE PATIENT TO COMPLETE IT.
WE DID LEARN THAT PATIENTS
WANTED TO KNOW KIND OF WHY ARE
THEY TAKING THIS AND WHAT THE
PROCESS IS GOING TO BE.
SO IT WAS IMPORTANT FOR US TO
MAKE REALLY CLEAR INTRODUCTIONS
AND EXIT SCREENS ABOUT THIS IS
WHAT'S GOING ON HAPPEN, THIS IS
WHAT YOU CAN EXPECT, THIS IS
WHEN YOU'LL SEE YOUR RESULTS,
AND THEN ALSO MAKING SURE THAT
WE HAD A USER EXPERIENCE DESIGN
THAT WAS REALLY OPTIMIZED FOR
OLDER ADULTS, FOR EVERYONE, BUT
OLDER ADULTS IN PARTICULAR.
SO SIMPLE INTERACTIVE TASK
INSTRUCTIONS, LARGE TESTS, KIND
OF SIMPLE EASY TO USE GESTURES
ON THE PHONE LIKE TAPPING
INSTEAD OF DRAGGING, THINGS LIKE
THAT.
OKAY.
SO I WILL TALK BRIEFLY ABOUT OUR
PILOT STUDY.
SO THAT WAS THE INFORMATION THAT
WE TOOK TO DESIGN AND ACTUALLY
DEVELOP THE VERSION ONE OF THIS
APP, WHICH WE DID MAKE A
SMARTPHONE APP THAT WAS READY TO
BE USED BY PATIENTS.
SO WE CONDUCTED A SMALL PILOT
JUST TO KIND OF SEE THE
FEASIBILITY OF ACTUALLY
COMPLETING THIS ON THEIR OWN.
SO OUR RESEARCH QUESTIONS FOR
THIS PILOT WERE CAN OLDER ADULTS
COMPLETE THIS BATTERY MYCOG
MOBILE REMOTELY ON THEIR OWN ON
THEIR OWN SMARTPHONES WITH ZERO
SUPPORT?
WHAT ARE THE RELIABILITY OF THE
MEASURES?
WE LOOKED AT INTERNAL
CONSISTENCY AND TEST RETEST
RELIABILITY, WHEN IT'S TAKEN
REMOTELY.
AND THEN WE DID SOME USABILITY
WORK IN THIS AS WELL, HOW DO
THESE PATIENTS RATE THE USER
EXPERIENCE OF USING THE APP.
SO WE HAD A SAMPLE OF 51
PARTICIPANTS HERE.
I DON'T HAVE THE OVERALL END
THERE, BUT 51 OLDER ADULTS
AROUND THE MEAN AGE WAS 74 YEARS
OLD.
THEY WERE E-MAILED INSTRUCTIONS
ABOUT HOW TO DOWNLOAD THE APP ON
TO THEIR OWN SMARTPHONES AND
THEN THEY COMPLETED THE FOUR
ACTIVITIES ON THEIR SMART
DISPOANS A BRIEF SURVEY ABOUT --
SMARTPHONES ASK A BRIEF SURVEY
ABOUT RELIABILITY WITH NO HELP
AND AFTER TWO WEEKS THEY
COMPLETED THEM AGAIN.
WE FOUND THAT 100% OF THE
PATIENTS IN OUR SAMPLE WERE ABLE
TO SUCCESSFULLY DOWNLOAD THE APP
AND COMPLETE ALL FOUR MEASURES
AT THE BASELINE AND WE HAD
PRETTY GOOD FOLLOW-UP THERE, SO
ONLY TWO PEOPLE DID NOT RESPOND
AT FOLLOW-UP, WHICH WAS
PROMISING.
THE MEAN USABILITY RATINGS ON
OUR USABILITY SCALE INDICATED A
POSITIVE USER EXPERIENCE, ABOVE
AVERAGE.
I'M NOT GOING GET TOO MUCH IN
THE WEEDS WITH THIS HERE, BUT WE
DID FIND ACCEPTABLE RELIABILITY,
BOTH INTERNAL CONSISTENCY AND
TEST RETEST RELIABILITY FOR EACH
OF THE MEASURES.
THE NO PRACTICE EFFECTS EXCEPT
FOR I THINK MY FACE IS HERE,
WHICH AS DR. RENTZ EXPECTED
BEFORE, THAT'S WHAT WE WOULD
EXPECT, THIS IS A HEALTHY
POPULATION AND EXPECTED
CORRELATIONS WITH EDUCATION
EXCEPT FOR MY PICTURE WAS NOT
SIGNIFICANT.
OVERALL FINDINGS FROM THIS
STUDY, HEALTHY OLDER ADULTS IN
OUR SAMPLE CAN RELIABLY COMPLETE
MYCOG MOBILE REMOTE ON THEIR OWN
SMARTPHONES.
THE MEASURES HAVE ACCEPTABLE
RELIABILITY METRICS.
THEY CORRELATE POSITIVELY WITH
EDUCATION, AS WE WOULD EXPECT.
MY PICTURES DID NOT CORRELATE
WITH THAT, BUT THAT MIGHT BE DUE
TO THINGS LIKE CHEATING OR
SELF-SELECTION BIAS, AND THAT'S
SOMETHING THAT WE'RE GOING TO
HAVE TO LOOK AT IN OUR NEXT
STUDY.
AND THEN OVERALL PARTICIPANTS IN
THIS SAMPLE RATED USABILITY OF
ABOVE AVERAGE WHICH MEANS THAT
THEY'RE HAVING KIND OF A GOOD
EXPERIENCE, A POSITIVE
EXPERIENCE WITH THE APP.
SO IF YOU ARE INTERESTED IN THE
STUDY, THEY ARE BOTH ON JMIR
JOURNALS, AND I HAVE THE QR
CODES RIGHT THERE IF YOU WOULD
LIKE.
BUT YEAH, THAT'S ALL I HAD.
I'LL HAVE CALLIE TALK ABOUT OUR
UPCOMING STUDY, WHICH IS A
CLINICAL AND CONSTRUCT
VALIDATION.
>> OKAY.
HELLO, EVERYONE.
MY NAME IS CALLIE JONES.
I AM A RESEARCH COORDINATOR IN
THE DEPARTMENT OF MEDICAL SOCIAL
SCIENCES IN THE FEINBERG SCHOOL
OF MEDICINE AT NORTHWESTERN, AND
AS STEPHANIE SAID, I'LL BE
TALKING ABOUT THE JOINT
CONSTRUCT AND CLINICAL
VALIDATION OF BOTH MYCOG AND
MYCOG MOBILE, WHICH IS AN
UPCOMING STUDY THAT WE'RE
RUNNING THIS YEAR.
SO WE WENT INTO THE STUDY WITH
THESE THREE RESEARCH QUESTIONS.
FIRST, IS THERE EVIDENCE OF
CONSTRUCT VALIDITY OF THE MYCOG
MOBILE MEASURES WHEN COMPARED TO
GOLD STANDARD NEUROPSYCHOLOGICAL
ASSESSMENTS AND COGNITIVE
SCREENERS?
TWO, CAN PERFORMANCE ON MYCOG
MOBILE ACCURATELY DIFFERENTIATE
BETWEEN OLDER ADULTS WITH
COGNITIVE IMPAIRMENT AND OLDER
ADULTS WHO ARE COGNITIVELY
NORMAL?
AND THREE, CAN THE MYCOG MOBILE
BATTERY BE SHORTENED BUT STILL
MAINTAIN ADEQUATE PREDICTION
ABILITIES?
SO THIS IS OUR TARGET SAMPLE.
WE ARE ENSURING THAT IT'S
STRATIFIED BY AGE, RACE, GENDER,
AS WELL AS ETHNICITY, AND WE
HAVE A MAXIMUM OF 70% WHITE
NON-HISPANIC PEOPLE AND MAXIMUM
OF 50% OF PEOPLE WITH A
BACHELOR'S DEGREE OR HIGHER TO
ENSURE THAT WE DON'T GET A HOME
OJ NIS I CAN SAMPLE --
HOMOGENOUS SAMPLE.
THESE ARE THE PROCEDURES WE'RE
FOLLOWING, SO WE HAVE TWO
GROUPS, A HEALTHY CONTROL SAMPLE
WITH AN -- OF 200 -- AN N OF
200, CLINICAL SAMPLE 6 R5 BLUS
NO -- FOR HEALTHY CONTROL
SAMPLE, ADULTS 65 BLUS NO
HISTORY OF COGNITIVE IMPAIRMENT
AND MINI COG SCORE OF GREATER
THAN 5.
RECRUITED THROUGH EXTERNAL
MARKET RESEARCH AGENCY, BE
ADMINISTERED A BATTERY OF
EXTERNAL GOLD STANDARD MEASURES
IN PERSON AND THEY'LL
SELF-ADMINISTER MYCOG AND MYCOG
MOBILE IN THE LAP.
THE CLINICAL SAMPLE, WE'RE
LOOKING FOR ADULTS 65 PLUS WITH
A MINI COG SCORE OF LESS THAN 5
AND A DOCUMENTED DIAGNOSIS
RELATE TO MILD COGNITIVE
IMPAIRMENT, DEMENTIA, COGNITIVE
DEFICITS OR OTHER MEMORY LOSS.
WE'RE RECRUITING THESE PEOPLE
THROUGH SPECIALTY MEMORY CARE
CLINIC IN THE CHICAGO AREA.
WE'RE ALSO ADMINISTERING THE
MINI COG TO THESE ADULTS AND
WILL BE SELF-ADMINISTERING MYCOG
AND MYCOG MOBILE IN THE CLINIC
AS WELL.
SO THESE ARE THE MEASURES OF
CONVERGE ABILITY AND
DISCRIMINATIVE VALIDITY WE'LL BE
USING.
OUR TEST, THESE ARE OUR TEST
LISTS AND PLAN FOR MEASURING
CONVERGE ANT AND DISCRIMINATIVE
VALIDITY.
THESE ARE OUR PROPOSED ANALYSIS.
WE'LL BE LOOKING AT CORRELATIONS
BETWEEN SIMILAR AND DISSIMILAR
MEASURES.
FOR CONVERGEDEANLT VALIDITY,
TESTS -- THESE ARE HIGHER
CORRELATIONS WE EXPECT.
THEN DISSIMILARRING CONSTRUCTS,
FOR EXAMPLE TRAIL MAKING TEST
VERSUS MYCOG MOBILE'S MY
PICTURES, PROCESSING SPEED TIMES
FOR MY SPIBLGHTS A MEMORY TEST
AND WE EXPECT THESE TO HAVE
LOWER CORRELATIONS.
WE'LL ALSO LOOK AT INTERNAL
CONSISTENCY AGAIN IN THE SAMPLE,
AND IN THE CLINICAL SAMPLE WE
LOOK FOR MODELS THAT BEST
PREDICT CLINICAL GROUP STATUS
AND SEE IF WE CAN REDUCE THE
BATTERY OF THE TESTS THAT ARE
THE MOST PREDICTIVE.
FOR OUR NEXT STEPS WE'RE
STARTING DATA COLLECTION NEXT
MONTH.
WE'LL CONDUCT AN SEES OVER THE
SUMMER AND THEN WE WILL DPAISH
ANALYSES OVER THE SUMMER AND
MAKE FINAL VERSION OF APP BASED
ON MODEL PREDICTION AND USER
FEEDBACK AND THEN FIELD TEST
NEXT YEAR IN A PRIMARY CARE
CLINIC, AND ACTUALLY OUR ARTICLE
IN BMJ OPEN PROTOCOLS JUST GOT
PUBLISHED YESTERDAY.
SO YOU CAN GO CHECK THAT OUT.
THANK YOU.
>> ALL RIGHT.
THANK YOU VERY MUCH TO ALL OUR
SPEAKERS.
I'M GOING TO OPEN IT UP NOW FOR
QUESTION AND ANSWER PERIOD.
IF ANYONE HAS ANY QUESTIONS, YOU
CAN EITHER RAISE YOUR HAND AND
SPEAK UP OR COME DOWN THE
MICROPHONE.
YES, SIR?
>> (AWAY FROM MICROPHONE).
>> ACTUALLY, BEFORE YOU ANSWER,
I'M GOING TO JUST REPEAT THE
QUESTION FOR THOSE ONLINE,
BECAUSE I THINK THEY MAY NOT
HAVE BEEN ABLE TO HEAR.
THIS IS A QUESTION FROM A
PRACTICING ENGINEER ON TOLL GIST
WHO IS USING -- GERONTOLOGIST
WHO IS USING MYCOG IN THE HOME
FOR OLDER ADULTS AND HAD A
QUESTION ABOUT MYCOG MOBILE FOR
USE IF HE'S ALREADY SUBSCRIBED
TO THE MYCOG SERVICE.
IS THAT A FAIR RECAPITULATION?
>> IS THIS ON?
>> IT IS ON.
>> ALL RIGHT.
MYCOG MOBILE IS STILL IN
DEVELOPMENT, SO IT'S NOT
AVAILABLE FOR PUBLIC USE RIGHT
NOW.
IF YOU WANTED TO TALK WITH US,
WE WOULD BE HAPPY TO TALK WITH
YOU ABOUT COLLABORATION IN THE
FUTURE BUT RIGHT NOW WE STILL
HAVE TO FINALIZE THE MEASURE.
>> ALL RIGHT.
OTHER QUESTIONS?
YES.
WOULD YOU MIND COMING UP TO THE
MICROPHONE?
THANK YOU.
>> THANK YOU ALL FOR YOUR GREAT
PRESENTATION.
THIS MAY BE MORE ACROSS ALL THE
APPLICABILITY, BUT IS THERE ANY
TALK OR PLANNING STAGES FOR
PEOPLE WITH HEARING OR -- WHAT
WORD AM I LOOKING FOR?
VISION.
VISION-IMPAIRED.
THANK YOU.
IS THERE ANY TALK OF THAT?
THANK YOU.
>> THAT IS A GREAT QUESTION, AND
IT IS SOMETHING WE WOULD LIKE TO
CONSIDER IN THE FUTURE BECAUSE
AS YOU COULD SEE BASED ON THE
EXAMPLES WE SHOWED OF THESE
TESTS, THEY ARE HEAVILY
DEPENDENT ON VISION.
I MEAN, YOU HAVE TO SEE THEM.
SO RIGHT NOW WE DON'T HAVE ANY
ALTERNATIVES TO THAT, BUT WE DO
THINK IT IS IMPORTANT.
NOW, THE MYCOG MOBILE VERSION,
YOU CAN USE SOME OF THE
ACCESSIBILITY FEATURES OF THE
PHONE AS THESE WILL BE THE
PERSON'S OWN SMARTPHONES.
SO THERE WILL BE THAT, AT LEAST
TO SOME EXTENT.
BUT FOR THE MYCOG BATTERY ITSELF
IN CLINIC, IT'S STATIC.
DID THAT ANSWER IT?
>> ALL RIGHT.
THANK YOU.
>> THE ONLY OTHER THING I WOULD
ADD IS THAT AS MIKE WOLF HAD IN
HIS -- I THINK IN ONE
PRESENTATION, THERE IS NO
ONE-SIZE-FITS-ALL SOLUTION.
SO WE KNOW WE CAN'T BE THE
PRODUCT FOR EVERYBODY.
>> TO ME?
OKAY.
QUICK QUESTION.
I NOTICE THAT THE APP, THE MYCOG
MOBILE WAS ON IOS.
ARE THERE ANY PLANS FOR IT TO BE
MADE AVAILABLE FOR ANDROID,
GIVEN THAT YOU'RE DEPLOYING THIS
IN A CLINIC, YOU'RE GOING TO
HAVE A MIX OF PATIENT DEVICES.
>> SO RIGHT NOW IT IS ONLY IOS.
BUT THAT WAS JUST ONE OF OUR
FIRST GROUP OF CONCEPT -- PROOF
OF CONCEPT.
BUT WE DO HAVE PLANS IN THE NEXT
PHASE TO ALSO DEVELOP AN ANDROID
APP, BUT LIKE WAS SAID BEFORE,
WE'RE STILL TRYING TO FIGURE OUT
WHAT'S THE FINAL BATTERY, YOU
KNOW, FINALIZE EVERYTHING.
BUT NEXT.
>> THANKS.
VERY USEFUL PRESENTATION.
MAYBE I MISSED IT, BUT YOU WERE
USING THE HEALTHY ELDERLY TO
COMPARE WITH THE GOLD STANDARD
NEUROPSYCHOLOGICAL MEASURE, NOT
THE CLINICAL BATTERY.
IS THERE A REASON FOR THAT?
>> CAN YOU HEAR ME?
OKAY.
SO WE ARE GOING TO GIVE A MINI
COG TO THE CLINICAL BATTERY AND
THEN ALSO THE MYCOG MOBILE
MEASURES, BUT GIVING LIKE A
LENGTHY NEUROPSYCH BATTERY
WAS -- WE'RE RECRUITING THESE
PATIENTS FROM MANY CLINICS, SO
IT'S REALLY BURDENSOME FOR THEM
TO MOVE ON NEUROPSYCH BATTERY,
USING OUR MEASURE AS CLINICAL
GROUP STATUS.
SO IF YOU HAVE A DIAGNOSIS OF
ONE OF THE ICD-10 CODES RELATED
TO DID HE MEN SHARKS THAT'S SORT
OF THE OUTCOME VARIABLE.
BUT LTS A LIMITATION NOT HAVING
ALL THE GOLD STANDARDS -- BUT IT
IS A LIMITATION NOT HAVING ALL
THE GOLD STANDARDS ON CLINICAL.
>> HI.
I JUST HAVE SOME TECHNICAL
QUESTIONS.
DO YOU THINK WITH -- DO YOU SYNC
WITH ANY -- DO THE RESULTS GO TO
ANY EMR, OR IS IT JUST EPIC, OR
WHAT IS IT?
>> SO RIGHT NOW, IT IS EITHER
EPIC IN CLINIC OR AS YOU HEARD
ABOUT MYCOG TRIAL, IT SENDS THE
RESULTS TO THEIR CANOPY GREENWAY
SYSTEM.
>> OKAY.
>> MYCOG MOBILE BECAUSE WE'RE
GOING TO BE DOING AN INITIAL
EVALUATION AND VALIDATION AT
NORTHWESTERN, IT'S GOING TO BE
EPIC AGAIN, BUT ONE OF THE
THINGS THAT WE'RE VERY AWARE OF
AND THAT WE WANT TO DO AS MUCH
AS WE CAN IS TO HAVE A PRODUCT
THAT IS SCALABLE TO OTHER EHR'S,
BUT WE NEED TO START SOMEWHERE.
>> RIGHT.
WILL.
>> YOU'RE NOT PRESENTING ANY
RESULTS TO THE PARTICIPANTS,
YEAH, TO YOUR PATIENTS, RIGHT?
IT WOULD BE TOO HARD TO
INTERPRET OR MAYBE SCARY OR
SOMETHING, RIGHT?
WOULD YOU THINK ABOUT SOMETHING
LIKE THAT IN THE FUTURE?
>> THAT'S SOMETHING LIKE IN THE
USABILITY STUDIES THAT CAME UP,
I WANT TO KNOW HOW I DID.
BUT THAT'S ALWAYS TRICKY, RIGHT
WHRKS YOU'RE DOING KIND OF A
SELF-ADMINISTERED NEUROPSYCH,
YOU DON'T WANT TO TELL SOMEONE
ON YOUR PHONE THAT YOU HAVE
DEMENTIA OR SOMETHING LIKE THAT,
RIGHT?
SO WE'RE PRETTY CLEAR IN THE
INSTRUCTIONS TO SAY LIKE YOU
WILL TALK ABOUT THIS WITH YOUR
DOCTOR WHEN YOU GO INTO THE
VISIT, BECAUSE IT IS JUST A
SCREENER.
>> FLEATS TI COMMON NOW, WE ALL
TAKE SCREENERS AND FILL THING
OUT BEFORE WE GO.
FLEATS TI COMMON NOW.
THAT MAKES SENSE.
SPEAKING OF YOUR USABILITY, HAVE
YOU PUBLISHED THOSE USABILITY
STUDIES?
ARE YOUR QUESTIONS IN THE PAPER?
WE HAVE AN APP AND --
>> THE QUESTION?
YEAH, YEAH, I MEAN, SORRY, I
ONLY HAD SIX MINUTES AND I HAD
TO GET ALL THOSE IN THERE.
BUT YEAH, IT GOES THROUGH KIND
OF THAT WHOLE PROCESS STARTING
WITH LIKE THOSE FOUNDATIONAL
INTERVIEWS WITH THOSE CLINICIANS
AND THEN, YOU KNOW, TALKING WITH
THE MA'S AND THE PANEL AND ALL
OF THOSE KIND OF DIFFERENT
STAGES UP UNTIL THE LAST STAGE
WHEN WE ACTUALLY HAD THE PROALT
TYPES AND WE'RE USING THEM.
SO YEAH.
>> OKAY, GREAT.
AND THEN I DON'T REMEMBER WHY I
WROTE THIS DOWN, BUT I WROTE DO
YOU HAVE REMINDERS?
LIKE WAS THERE A TASK THAT THEY
HAVE TO TAKE AGAIN?
>> THAT'S A GOOD QUESTION.
OR JUST REMINDERS TO TAKE IT?
>> YEAH, RIGHT.
ARE THERE ANY NOTIFICATIONS?
>> I THINK THAT'S SOMETHING THAT
WE ARE GOING TO LEARN WHEN WE DO
THE FIELD TEST, RIGHT, IS RIGHT
NOW IT'S JUST A PILOT.
RESEARCH STUDY.
BUT WE HAVE TO KIND OF SEE HOW
THIS IS USED IN THE REAL WORLD
OF, YOU KNOW, YOUR CLINIC SENDS
YOU A MESSAGE, WHAT I, DO THIS,
BUT HOW MANY TIMES ARE THEY
ACTUALLY FILLING OUT PAPERWORK
BEFORE THEY COME IN, LET ALONE
THE COGNITIVE TEST, I THINK
THAT'S GOING TO BE ONE OF OUR
CHALLENGES.
>> ALL RIGHT, GREAT JOB.
>> WE'VE GOT ANOTHER QUESTION
COMING.
>> HI.
JUST TO CLARIFY, IF I UNDERSTAND
IT RIGHT, THAT IN THE PROCESS OF
DEVELOPING THIS MYCOG FOR THE
PUBLIC USE, ARE YOU ANTICIPATING
THAT THIS SPACE THAT WE HAVE TO
PAY FOR THOSE COMMUNITY OR BASED
ON INSTITUTIONAL USE OR FOR
THOSE CLINICS?
BECAUSE THIS IS AN NIH FUNDED
STUDY AND IT'S LIKE OPEN TO THE
PUBLIC?
>> THAT IS ALWAYS A GREAT
QUESTION, AND HOW DO YOU GET
THESE PRODUCTS?
RIGHT NOW THEY'RE NOT PUBLICLY
AVAILABLE.
NEITHER OF THEM.
MYCOG IS IN CLINICS, AND WE ARE
USING IT, AND THAT'S WHY I SAID,
YOU KNOW, WE HAVE CONTACT
INFORMATION, YOU CAN TALK TO US
ABOUT COLLABORATING WITH US.
AND I SAY COLLABORATING BECAUSE
IT'S NOT A PUBLICLY AVAILABLE
PRODUCT.
WHEN IT DOES BECOME A PUBLICLY
AVAILABLE PRODUCT, THERE MAY
VERY WELL BE A COST ASSOCIATED
WITH IT, AS THERE IS WITH NIH
TOOLBOX AND BABY TOOLBOX,
BECAUSE YOU HAVE TO KEEP THESE
THINGS UP AND YOU HAVE TO MANAGE
THEVMENT SO IF THERE IS ANY COST
DOWN THE ROAD, THAT WOULD BE FOR
THAT PURPOSE.
IT'S NOT TO MAKE A PROFIT.
IF YOU WANT TO TALK TO ONE OF US
ABOUT USING MYCOG AT YOUR
CLINIC, THE CHALLENGE IS GOING
TO BE EVEN IF YOU'RE AT AN
INSTITUTION THAT HAS EPIC, IT'S
GOING TO BE A PARTICULAR
INSTANCE OF EPIC, SO HAVING OUR
PRODUCTS TALK TO THAT EPIC
INSTANCE IS GOING TO, YOU KNOW,
REQUIRE SOME WORK.
SO THAT'S ONE OF THE THINGS ON
THINK ABOUT, WHICH I SAY, WE
WANT TO MAKE IT SCALABLE, SO WE
WANT TO MAKE IT AS EASY AS
POSSIBLE.
>> THANK YOU, EVERYONE.
ANY MORE QUESTIONS FROM THE
AUDIENCE?
I MAY ASK A QUICK QUESTION
DIRECTED TOWARDS STEPHANIE.
I NOTICED WHEN YOU WERE TALKING
ABOUT THE RESULTS THAT YOU'VE
SEEN YOU CAME IN A PICTURE THAT
WAS UNEXPPPED WE WERE TRYING TO
COME UP WITH POSSIBLE REASONS
FOR THAT, WHICH COULD INCLUDE
CHEATING.
I WAS WONDERING, PERHAPS YOU'LL
BE ABLE TO BETTER IT AS YOU MOVE
FORWARD WITH MORE PEOPLE, BUT
HOW DO YOU GO ASSESSING THAT
WITH A TASK ADMINISTERED
REMOTELY AND WHAT ARE SOME OF
THE THINGS YOU'RE THINKING ABOUT
AS YOU'RE THINKING ABOUT --
>> YOU MEAN LIKE ARE THEY
CHEATING?
>> YES.
>> WE DO THINK ABOUT THAT QUITE
A BIT.
SO WE DON'T HAVE A WAY TO
CONTROL FOR CHEATING RIGHT NOW.
I THINK, YOU KNOW, SOMETHING AS
SIMPLE AS LIKE SAYING THIS IS TO
SCREEN YOUR COGNITIVE HEALTH,
PLEASE DON'T CHEAT, I THINK CAN
GO A REALLY LONG WAY.
THAT TASK IS ADAPTED FROM THE
MOBILE TOOLBOX AND WE DID LOOK
AT THAT.
WE JUST PUBLISHED A PAPER ABOUT
THE VALIDATION OF THE ORIGINAL
MOBILE TOOLBOX VERSION OF THAT
APP AND LOOKED AT ARE WE SEEING
THESE KIND OF LIKE UNIFORMALLY
HIGH SCORES BECAUSE THEY'RE
WRITING IT DOWN?
WE DIDN'T REALLY SEE LIKE
DEFINITIVE EVIDENCE OF THAT, BUT
I HAVE THOUGHT ABOUT WAYS TO
LIKE HOW MIGHT WE EMBED LIKE
PERFORMANCE VALIDITY METRICS
INTO SOME OF THESE TASKS.
BUT YEAH, I MEAN, IT'S A GOOD
QUESTION.
WE DON'T KNOW IF THEY'RE WRITING
DOWN, WE DON'T KNOW IF SOMEONE
ELSE IS HELPING THEM, AND THAT'S
ANOTHER LIMITATION I THINK OF
LIKE REMOTELY SELF-ADMINISTERING
IT.
>> THANK YOU VERY MUCH.
>> RIGHT.
YES.
MANY POTENTIAL BENEFITS AND ALSO
SOME POTENTIAL LIMITATIONS.
ALL RIGHT.
WELL, I THINK WE'RE NEARING THE
END OF OUR TIME, BUT I WANT TO
THANK YOU ALL FOR A REALLY
TERRIFIC SESSION.
THANK YOU.
AND BEFORE WE PART, I ACTUAL
HAVE A MESSAGE, WHICH I CAN PULL
FROM MY PHONE AGAIN, ABOUT OUR
NEXT SESSION.
WE HAVE A FIFTEEN MINUTE BREAK
OR JUST OVER, CR WE MIGHT BE
STOPPING A MINUTE OR SO EARLY,
AND WE'LL BE RECONVENING AT 2
1W5 FOR THE SECOND -- WE'LL BE
RECONVENE BEING AT 2:15 FOR THE
SECOND PORTION OF THE CONCURRENT
SESSIONS, SECTION 4 IS USE OF
NIH TOOLBOX IN DIVERSE
POPULATIONS, IN BALCONY A.
SESSION FIVE, NIH TOOLBOX IN
DEVELOPMENTAL POPULATIONS,
TAKING PLACE IN THE ROOM WE'RE
IN RIGHT NOW AND SESSION 6 IS
THE NIH TOOLBOX ACROSS THE LIFE
SPAN AND IN CRITICAL
POPULATIONS, WHICH WILL TAKE
PLACE IN THE MAIN AUDITORIUM.
ALL RIGHT.
SO THANK YOU VERY MUCH,
EVERYONE.
>> ONE MORE THING.
IT'S IN YOUR SCHEDULES, BUT CAN
I MAKE A PLUG, COME TO SEE THE
DEMONSTRATIONS AND TRY THEM OUT.
WE'RE GOING TO BE AT TABLES, ASK
THE EXPERTS, SO PLEASE COME TALK
TO US.
>> THIS IS THE NIH TOOLBOX USE
IN DEVELOPMENTAL CLINICAL
POPULATIONS AND WE'LL GET
STARTED WITH DR. EMMA KHANDI
FROM NIH THERE, TALKING ABOUT
INDIVIDUALS WITH WILLIAMS
SYNDROME.
>> HI, EVERYBODY.
SO -- DR. EMMA CONDY.
I'M FROM THE INTRAMURAL PROGRAM
OF NIH.
THERE'S THE EXTRAMURAL SIDE THAT
DOES THE GRANT FUNDING AND THING
OF THAT NATURE BUT I DID MY
POSTDOCTORAL TRAINING HERE IN
THE INTRAMURAL PROGRAM WHERE WE
CONDUCT RESEARCH ON CAMPUS.
THIS IS WORK I DID DURING MY
POST-DOC, IF ANYONE WANTS TO
HEAR ABOUT TRAINING
OPPORTUNITIES HERE AT THE NIH
COME AND TALK TO ME DURING THE
POSTER SEETION.
DURING THAT TIME WE DO A LOT OF
MEASURE DEVELOPMENT IN
POPULATIONS WITH INTELLECTUAL
DISABILITY, SO THIS PROJECT WAS
SPECIFICALLY FOCUSED ON A
DISORDER CALLED WILLIAM SYNDROME
THAT WE COLLABORATE WITH ONE OF
OUR COLLEAGUES IN NHLBI WHICH IS
THE HEART LUNG AND BLOOD
INSTITUTE.
SO WILLIAMS SYNDROME THE
BEHAVIORAL PHENOTYPE, IT IS A
NEURO GENETIC CONDITION CAUSED
BY A MICRODELETION ON CHROMOSOME
7 SO THE PARTICIPANTS IN THIS
STUDY WERE ENROLLED AS PART OF
THE NATURAL HISTORY STUDY WHERE
THEY COME IN APPROXIMATELY ONCE
A YEAR TO SEE BEHAVIORAL
COGNITIVELY HOW THEY'RE DOING AS
WELL AS A FULL MEDICAL WORK-UP
BY THE NHLB I TEAM.
AND THEIR NEUROPSYCHIATRIC
PROFILE INCLUDES MILD TO
MODERATE INCIDENT LCT YOU'LL
DISABILITY BUT IT ALSO INCLUDES
ANXIETY AS WELL AS ATTENTIONAL
DEFICITS THAT WE THOUGHT WOULD
BE INTERESTING TO TRY TO INDEX
USING THE NIH TOOLBOX.
SO TO DO THAT, WE DECIDED THAT
THE EARLY CHILDHOOD COGNITIVE
BATTERY WOULD BE THE MOST
APPROPRIATE SET OF TASKS TO USE
WITH THESE PARTICULAR
PARTICIPANTS, SO WE ADMINISTERED
THE INHIBITOR RI CONTROL TAX
TASK -- FLANK ERIN HIB TO HER
CONTROL AND ATTENTION TEST,
PICTURE SEQUENCE MEMORY,
DIMENSIONAL, WE SKIPPED OVER THE
PVT BECAUSE WE WERE DOING THAT
ALREADY.
WE DID THE OTHER THREE WITH ALL
OF THEM AND WANTED TO LOOK
SPECIFICALLY AT THE FEASIBILITY
OF ADMINISTERING THOSE FOUR
TESTS IN THE EARLY CHILDHOOD
COGNITION BATTERY AS WELL AS
WHETHER OR NOT PERFORMANCE ON
THOSE TASKS CORRELATED WITH ANY
OF THE OTHER COGNITIVE VARIABLES
THAT WE WERE GETTING FROM THEM
BECAUSE THEY WERE UNDERGOING
FULL IQ TESTING AS WELL AS A
VARIETY OF OTHER THINGS LIKE THE
CBCL AND OTHER COGNITIVE AND
BEHAVIORAL TESTS OR ASSESSMENTS.
SO WE HAD 47 PARTICIPANTS WITH
WILLIAMS SYNDROME DIAGNOSIS COME
AND UNDERGOING TESTING.
WILLIAMS SYNDROME WAS CONFIRMED
VIA MOLECULAR TESTING BY NHLBI
TEST LG.
THEY WERE BETWEEN FOUR AND 50
YEARS OLD BECAUSE AS I MENTIONED
THIS WAS A NATURAL HISTORY
STUDY, SO THERE REALLY WASN'T AN
AGE LIMIT, IT WAS JUST WHOEVER
WAS AVAILABLE TO COME IN.
MEDIAN AGE WAS AROUND 20 YEARS
OF AGE.
THE MAJORITY HAD A FULL SCALE IQ
OF LESS THAN 70, WOULD MEET THAT
CUTOFF FOR INTELLECTUAL
DISABILITY BUT THE MEDIAN WAS
AROUND 58.
AND NOTABLY INDIVIDUALS WITH
WILLIAMS SYNDROME HAVE
RELATIVELY PRESERVED VERBAL
SKILLS, WHICH FOR THE NIH
TOOLBOX MAKES THEM A
PARTICULARLY GREAT CANDIDATE
NEURO GENETIC CONDITION FOR
ASSESSMENT.
SO THEY UNDERWENT NEURAL
DEVELOPMENTAL PHENOTYPING, WHICH
INCLUDED DEMOGRAPHICS ARE
DEVELOPMENTAL HISTORY AND IQ
TESTING AS WELL AS THIS
CHILDHOOD, EARLY CHILDHOOD
COGNITION BATTERY.
OUR ANALYTIC APPROACH WAS TO
LOOK THE AFEASIBILITY VIA
COMPLETION RATES, WHO WOULD ABLE
TO COMEET TASKS AS WELL AS
VEELINGS SHIPS WITH OTHER
VARIABLE -- RELATIONSHIPS WITH
OTHER VARIABLES, UNPRACTICED
SCORES WITH NONVERBAL IQ AND
CHRONOLOGICAL AGE.
SO FOR THE FLANK ERIN HIB TO HEY
CONTROL TASK, 98 -- LOOKING AT
WHETHER THE TASKS WERE COMING UP
AT FLOOR FOR THE AGE CORRECTED
SCORES -- A 89% COMPLETION RATE.
NIH TOOLBOX IS NORMED SUCH THAT
YOU GET THREE STANDARD
DEVIATIONS BELOW THE MEAN SCORE
AND THEN ONE POINT IS THE LOWEST
SCORE YOU CAN GET IF YOU'RE
LOOKING AT THE AGE CORRECTED
SCORE.
SO THAT'S A 54.
NOW, CONVERSELY, MOST STANDARD
IQ TESTS GO DOWN TO FOUR
STANDARD DEVIATIONS, SO WE WERE
PARTICULARLY CONCERNED ABOUT
FLOOR EFFECTS WITH THE NIH
TOOLBOX TEST, WHAT WE FOUND WAS
THAT FOR THE FLANKER OF THE 89%
THAT WERE ABLE TO SUCCESSFULLY
COMPLETE THE TASK, 27% WERE
SCORING AT THAT 54 OF THE FLOOR
WHEN WE LOOKED AT THE AGE
SCORES.
SO BUT OVERALL A PRETTY HIGH
COMPLETION RATE FOR OUR WILLIAMS
SYNDROME PATIENTS ON THIS TASK
AND THEN THE SCATTERPLOT ON THE
RIGHT-HAND SIDE IS SHOWING THE
AGE CORRECTED SCORES IN BLACK
WHERE YOU SEE THAT SCORE FOR
PARTICIPANTS OVER THE AGE OF 20
AND THEN COMPARED TO THE
UNCORRECTED STANDARD SCORES
WHICH ACT MORE AS A KIND OF
CHANGE SCORE BEING RIGHT, SO
THEY CAN'T NECESSARILY BE
COMPARED BETWEEN SUBJECTS
BECAUSE WE'RE NOT CONTROLLING
FOR AGE WITH THESE SCORES, BUT
WITHIN A SUBJECT COULD BE
HELPFUL TO TELL US IF THEIR
SKILLS ARE INCREASING OVER TIME.
AND THOSE UNCORRECTED STANDARD
SCORES SHOW A SLIGHTLY DIFFERENT
SHAPE IN OUR PARTICIPANTS THAN
THE AGE CORRECTED SCORES DID.
AND THAT'S HIGHLIGHTED.
THEN ON THE DIMENSIONAL CARD
SORT TASK, ADMINISTERED TO 47
SUBJECTS, AGAIN AN 89%
COMPLETION RATE, ABOUT 19%
COMPLETED AT FLOOR, SO AGAIN
IT'S OCCURRING IN THAT SAME
SUBSET OF INDIVIDUALS THAT ARE
AROUND AGE 20 AND SOLDIER THE
ADULTS SEEM PARTICULARLY
AFFECTED BY THIS.
AND AGAIN, ON THE RIGHT-HAND
SIDE, YOU'RE SEEING IN BLACK THE
AGE CORRECTED STANDARD SCORES
VERSUS THEIR UNCORRECTED
STANDARD SCORES, SO A SLIGHTLY
DIFFERENT LOOKING CURVE.
THEN FINALLY, THE PICTURE
SEQUENCE MEMORY TEST DID NOT
APPEAR TO SHOWFLOOR EFFECT.
SO WE GOT AGAIN AN 89%
COMPLETION RATE HERE.
HIGH COMPLETION RATES ACROSS ALL
THREE TASKS, HOWEVER, WE DIDN'T
SEE THIS ISSUE OF OUR
PARTICIPANTS SCORING AT A FLOOR
ON THIS TASK, AND AGAIN, YOU CAN
SEE ON THE SCATTERPLOT IN THE
BLUE IS OUR UNCORRECTED SCORE
VERSUS AGE CORRECTED STANDARD
SCORES IS BLACK.
THEN IF WE LOOK ACROSS ALL THREE
TASKS, AGAIN ABOUT 79% COMPLETED
ALL THREE TASKS.
ONLY ONE PARTICIPANT WAS UNABLE
TO COMPLETE ANY TASK, RIGHT?
SO OUT OF OUR ENTIRE SAMPLE OF
47, ONE PARTICIPANT JUST
COULDN'T ENGAGE WITH THE iPAD
IN A WAY THAT WE FELT WAS
APPROPRIATE TO CONSIDER A VALID
SCORE.
HOWEVER, ANY OTHER MISSING DATA
WAS NOT COMING, THAT # 9%
COMPLETION, IT WASN'T THAT THE
SAME PEOPLE HAD FAILING FOR THE
THREE TESTS.
AND MOST OF THE INVALID
ADMINISTRATIONS IN THIS SAMPLE
SEEMED TO BE TO AN INABILITY TO
PASS THE PRACTICE.
SO IT WAS THAT THEY JUST NEVER
GOT EVEN TO THE SCORED PART OF
THE TEST BECAUSE FOR EXAMPLE ON
THE DIMENSIONAL CHANGE CARD SORT
THEY NEVER GOT PAST THE SIMPLE
TRAINING OF SHAPE VERSUS COLOR.
THEN WHEN WE LOOK AT
RELATIONSHIPS WITH SOME OF THE
OTHER VARIABLES IN OUR SAMPLE,
SPECIFICALLY AGE CORRECT
STANDARD SCORES VERSUS
CHRONOLOGICAL AGE OF NONVERBAL
IQ WE FOUND THAT AGE CORRELATED
HIGHLY WITH THE FLANKER AGE
CORRECTED STANDARD SCORE IN THIS
SAMPLE NEGATIVELY, SO AS YOU HAD
PARTICIPANTS WITH HIGHER AGES
WERE SHOWING LOWER SCORES, WHICH
TRACKS WITH THE FACT THAT WE
WERE SEEING THOSE FOUR EFFECTS
FOR OUR OLDER PARTICIPANTS, AND
THEN YOU SEE SIMILAR TREND BUT
NOT TO THE SAME EXTENT IN THE
DCCS WHERE WE SAW A CORRELATION
OF NEGATIVE .45.
AND THEN THERE WAS ALSO A
RELATIONSHIP BETWEEN DCCS AND
THE FLANKER AGE CORRECTED
STANDARD SCORES IN THE POSITIVE
DIRECTION WHICH IS NOT
SURPRISING SINCE THEY ARE MOST
MEASURING EXECUTIVE FUNCTION.
HOWEVER, THE PART THAT WE WERE A
BET MORE CONCERNED ABOUT WAS
THAT NONVERBAL IQ DID NOT
CORRELATE WITH ANY OF THE NIH
TOOLBOX SCORES WHICH WAS A
LITTLE BIT OF A CONCERN FOR US.
AND THAT'S AGAIN SHOWING THAT IT
DID NOT CORRELATE.
SO OVERALL WE FOUND GOOD
FEASIBILITY OF THE FLANK EEEC
AND DCCS IN WILLIAMS WITH A
POPULATION WITH MILD TO MODERATE
DISABILITY, WE HAD SOME CONCERNS
WITH USING AGE CRECTSDZ STANDARD
SCORES IN THIS GROUP
PARTICULARLY FOR THE FRANKER AND
THE DCCS BECAUSE OF THOSE FLOOR
EFFECTS THAT WE OBSERVED AS WELL
AS THE PRETTY NOTABLE NEGATIVE
CORRELATIONS WITH AGE, AND NO
CORRELATIONS WITH VERBAL IQ,
WHICH AGAIN INDICATES THAT
PERHAPS IT'S NOT SENSITIVE
ENOUGH TO BE ABLE AT THE LOWER
END OF THE SCALE TO BE PICKING
UP ON ACTUAL SKILLS.
THAT'S IT.
THANK YOU.
>> THANK YOU SO MUCH THE OUR
NEXT SPEAKER WILL BE TREY AHRUN
FROM VIRGINIA COMMONWEALTH
UNIVERSITY TALKING ABOUT IN
DEPTH ANALYSIS OF FLUID
COGNITION IN BOYS WITH DUCHENNE
MUSCULAR DYSTROPHY.
SHREYA ARUN.
>> HI, EVERYONE.
MY NAME IS SHREYA ARUN, FROM
VCA, I'LL BE TALKING TO YOU
ABOUT FLUID COGNITION IN BOYS
WITH DUCHENNE MUSCULAR
DYSTROPHY.
TO GIVE AN OVERVIEW ON THE
DISEASE, IT'S NAMED AFTER
DR. DUCHENNE WHO IN 1861
DESCRIBED A COHORT OF YOUNG
CHILDREN, 24 BOYS AND ONE GIRL,
WITH EXTENSIVE MUSCLE WASTING,
SPEECH DELAY AND A DULL
COGNITIVE AFFECT.
THEN IN 1987 LOUIS KUNKEL
DEFINED DMD GENE IN HUMANS X
CHROMOSOME C ABSENCE OF
DYSTROPHIN -- DMD CHARACTERIZED
BY THE ABSENCE OF DYSTROPHIN
ANDLESS SUBSEQUENT RESEARCH
FOCUS ODD SKELETAL MUSCLE
SYMPTOMS, HOWEVER, OUR FOCUS IS
ON COGNITION.
THROUGH STAR NET A SURVEILLANCE
PROGRAM THAT MONITORS PATIENTS
WITH DMD ACROSS THE COUNTRY, WE
KNOW THAT PATIENTS EXPERIENCE
SEVERE DELAYS IN GROSS MOTOR
SKILLS, SPEECH AND LANGUAGE.
WE ALSO KNOW THAT THEY HAVE HIGH
RATES OF SCHOOL GRADE
REPETITION, ESPECIALLY IN THOSE
RECEIVING SPEECH THERAPY.
THEY ALSO UNDERPERFORM
ACADEMICALLY WHEN COMPARED TO
THEIR PEERS AND HAVE -- AND
EXPERIENCE HIGHER LEVEL OF
SCHOOL RELATED STRESS.
IN LATER YEARS, THEY HAVE
TROUBLE FINDING VOCATIONAL
OPPORTUNITIES DUE TO THE
PROGRESSION OF THE DISEASE.
SO THE CDC SUPPORTED CARE
GUIDELINES FOR DMD REGARDING
PSYCHOSOCIAL CARE RECOMMENDS
THAT PATIENTS BE ASSESSED BY A
NEURO PSYCHOLOGIST THROUGHOUT
THEIR LIFE SPAN, WITH A HIGHER
RISK FOR LEARNING AND
INTELLECTUAL DISABILITIES, IT'S
REALLY IMPORTANT TO SCREEN AND
ASSESS THEM FOR THESE CONDITIONS
TO PROVIDE EARLY INTERVENTION.
HOWEVER, DUE TO HIGH
OUT-OF-POCKET COSTS AND LACK OF
ACCESS TO SPECIALISTS, MORE THAN
75% OF DMD PATIENTS HAVE NEVER
BEEN ASSESSED BY A NEURO
PSYCHOLOGIST.
SO ONLY IN MORE RECENT YEARS
HAVE STUDIES BERN FOCUSED ON
COGNITION IN DMD.
BUT THESE STUDIES HAVE ALL BEEN
FOIKSED ON IQ OR IQ BASED
MEASURES.
ONLY ONE PAST STUDY COMPLETED IN
2019 UTILIZED A SUBSET OF THE
NIH COGNITION TOOLBOX AND THEY
FOUND THAT THOSE WITH DISTAL
MUTATIONS IN THE DMD GENE HAD
SIGNIFICANTLY LOWER SCORES IN
EXECUTIVE FUNCTIONING AND
WORKING MEMORY.
THIS IS SUPPORTED BY PATIENT AND
PARENT REPORTS THAT THOSE WITH
DISTAL MUTATIONS TYPICALLY HAVE
A HIGHER NEURO DEVELOPMENT --
SORRY.
THEY TYPICALLY HAVE A HIGHER
BURDEN OF DISEASE.
AND OTHER STUDIES ALSO NOTED
THAT THOSE WITH DMD HAVE POOR
VISUAL-SPATIAL ATTENTION SKILLS.
OUR STUDY WANTED TO FIND OUT
WHETHER DISTAL MUTATIONS ARE
MORE PSYCHOMETRICALLY AFFECTED
IN PROXIMAL MUTATIONS AND WE
ALSO WANTED TO ASSESS WHETHER
THE NIH BATTERY COGNITIVE
TOOLBOX WOULD BE BETTER IN COG
DETECTIVE DEFICITS KNOWN TO BE
AFFECTED BY DMD.
SO WE CHOSE THE COGNITION
BATTERY TOOLBOX BECAUSE IT'S A
SHORT ASSESSMENT THAT ASSESSES
SEVEN DOMAINS OF COGNITION AND
PROVIDES THREE SCORES, THE TOTAL
COMPOSITE SCORE, FLUID COGNITION
SCORE AND THE CRYSTALLIZED
COGNITION SCORE.
CRYSTALLIZED COGNITION IS
COMPOSED OF VOCABULARY AND
READING AND FLUID COGNITION
SCORE IS CALCULATED BY
ASSESSMENT ACROSS EXECUTIVE
FUNCTIONING, INHIBITORY CONTROL
AND ATTENTION, EPISODIC MEMORY,
WORKING MEMORY AND PROCESSING
SPEED.
THESE SCORES CAN BE COMPARED TO
POPULATION NORMED DATA AND CAN
BE ASSESSED THROUGHOUT THE
PATIENT'S LIFE SPAN R IT ALSO
TAKES INTO ACCOUNT THE MOTHER'S
EDUCATIONAL BACKGROUND WHEN
ASSESSING CHILDREN AND THE
SUBJECT'S EDUCATIONAL BACKGROUND
WHEN ASSESSING ADULTS.
SO IN A PRELIMINARY STUDY BY
DR. MIRAGE, SHE ASSESSED 30 BOYS
WITH DMD USING NIH COGNITION
BATTERY TOOLBOX.
SHE FOUND THAT WHEN LOOKING AT
THE TOTAL COGNITION SCORE, BOYS
WITH DMD SCORED ONE STANDARD
DEVIATION BELOW THE AGE
CORRECTED NORM, COMPARED TO THE
NORM.
WHEN LOOKING JUST AT FLUID
COGNITION, BOYS WITH DMD SCORED
1.5 STANDARD DEVIATIONS BELOW
THE NORM WITH SIGNIFICANTLY
LOWER SCORES IN ATTENTION,
PROCESSING SPEED AND WORKING
MEMORY H THERE WAS NO DIFFERENCE
IN SCORES WHEN LOOKING AT
CRYSTALLIZED COGNITION.
SO THESE FINDINGS WERE
REPLICATED IN A SECOND DATASET
OF 63 BOYS WITH DMD AGED FOUR
THROUGH 27.
THIS TIME WE NOT ONLY LOOKED AT
THE SCORES ACROSS EACH OF THE
SEVEN DOMAINS, BUT WE ALSO
COMPARED SCORES BASED ON DMD
LOCATION.
SIMILAR TO DR. HEYMARA GE'S
STUDY, FOUND SIGNIFICANTLY LOWER
FOR PROCESSING SPEED, HOWEVER,
WE FOUND NO DIFFERENCE IN SCORES
WHEN COMPARING PROXIMAL
MUTATIONS AND DISTAL MUTATIONS.
SO ALTHOUGH DISTAL MUTATIONS ARE
KNOWN TO HAVE A HIGHER BURDEN OF
DISEASE, THROUGH THE NIH TOOLBOX
WE SHOW THAT THERE IS NO
DIFFERENCE IN COGNITION WHEN
COMPARING PROXIMAL AND DISTAL
MUTATIONS.
IT'S ALSO IMPORTANT TO NOTE THAT
THE NIH COGNITION BATTERY
TOOLBOX CAN SUCCESSFULLY
IDENTIFY THE RELATIVE DEFICITS
AND ATTENTION PROCESSING SPEED
AND WORKING MEMORY AND THESE
DOMAINS OF FLUID COGNITION ARE
KNOWN TO BE AFFECTED BY DMD AS
DEMONSTRATED IN PREVIOUS STUD
STUDIES.
THE TOOLBOX IS A SHORT
ASSESSMENT THAT CAN BE COMPLETED
ACROSS THE PAISH'S LIFE SPAN AND
SCORES CAN BE COMPARED TO
POPULATION NORMED DATA.
THUS, WE PROPOSE THAT THE NIH
TOOLBOX BE USED AS A CLINICAL
TOOL TO SCREEN AND ASSESS DMD
PATIENTS FOR INTELLECTUAL AND
LEARNING DISABILITIES, AS IT WAS
ABLE TO SUCCESSFULLY IDENTIFY
THE DOMAINS AFFECTED BY DMD.
I WOULD LIKE TO TAKE A MOMENT TO
ACKNOWLEDGE DR. HEYMARAGE AND
DR. CAT FOR THEIR CONTRIBUTION
TO THIS PROJECT.
I COULD NOT HAVE DONE THIS
WITHOUT THEM.
THANK YOU ALL FOR LISTENING.
>> GREAT.
NEXT UP IS SALLY WANG FROM
NORTHWESTERN UNIVERSITY TALKING
ABOUT EVALUATING COGNITIVE
PERFORMANCE IN CHILDREN WITH
GALACTO -- WITH GALACTOSEMIA,
RESULTS FROM NIH TOOLBOX
COGNITIVE BATTERY.
CORRECTION.
STELLA ZOONG I NOTICE THE SOLAR
EE CLIPSZ IS HAPPENING SOON, SO
I'LL TALK FASTER AND LEAVE MORE
TIME FOR DATA.
>> THANKS.
>> SO TODAY MY TOPIC IS ON THE
USE OF NIH TOOLBOX TO EVALUATE
THE COGNITIVE PERFORMANCE IN
CHILDREN WITH CLASSIC
GALACTOSEMIA.
HERE IS MY DISCLOSURE.
SO LET'S TALK A LITTLE BIT ABOUT
CLASSIC GALACTOSEMIA.
THERE ARE A LOT OF THINGS ON
THIS SLIDE.
I WANT YOU TO REMEMBER IT'S A
RARE CONDITION BUT IT'S VERY
SERIOUS.
IT IS A RARE MET BOL -- RARE
AUTOSOMAL RECESSIVE METABOLIC
DISEASE EXRRKS IP ABILITY TO
NORMALIZE MET BOL EYES SUGAR
GALACTOSE, ARE NOT ABLE TO
TRANSFORM HAD R IN THESE PEOPLE
LTS TRANSFORMED INTO
GALACCTITOL, HIGHLY TOXIC.
IT BUILDS UP IN BRAIN AND BLOOD
AND ORGANS AND CAUSES MASSIVE
COMPLICATIONS.
RARE CONDITION.
HAPPENS ONLY IN ABOUT 80
CHILDREN PER YEAR IN THE UNITED
STATES AND CURRENTLY ONLY ABOUT
3,000 ADULTS AND CHILDREN HAVE
CLASSIC GALCTOSEMIA, MOST OF
THEM ARE UNDER 40 YEARS OLD.
IT IS A SERIOUS DISEASE BECAUSE
BEFORE THE NEWBORN SCREENING HAD
INCLUDED CLASSIC GALACTOSER MIA
INTO THE PANEL, A MAJORITY OF
THE KIDS WILL NOT SURVIVE
CLASSIC GALACTOS ERB MIA, SO IN
THE TEN DAYS IF THEY'RE NOT
RESTRICTED IN LACTOSE RESTRICTED
DIET THEY WILL DIE BY MASSIVE
INFECTION.
THANKS ON THE NEWBORN SCREENING
AS WELL AS THE GALACTOSE
RESTRICTSDZ DIE THE IT IS THE
ONLY OPTION FOR THIS BE -- THE
DIET.
MORTALITY SIGNIFICANTLY REDUCED.
HOWEVER, GALACTOS ERIC DIET DOES
NOT REALLY PREVENT COMPLICATIONS
BECAUSE THE BODY ALSO PRODUCES
GALACTOSE ENDOGENOUSLY SO
CHILDREN AND ADULTS SURVIVED
CHILDBIRTH OR INFANT STAGE OF
GALACTOSEMIA ALSO DEVELOP A LOT
OF SIGNIFICANT COMPLICATIONS
SUCH AS CATARACTS, SPEECH AND
LANGUAGE ISSUES, COGNITIVE
IMPAIRMENT, MOTOR ISSUES,
FERTILITY ISSUES, BEHAVIOR AND
ADAPTIVE SKILLS IS IMPAIRED AS
WELL AS TREMOR AND SEIZURES.
SO HERE I'M GOING TO PRESENT A
CROSS-SECTIONAL ANALYSIS OF A
LONG TUD NATURAL STUDY THAT
STUDY CHILDREN WITH GALACTOSEEM
YA, PHARMACEUTICAL INTERVENTION
AND PIVOTAL STUDY, AGENT IS
CALLED ATO87 AND -- CURRENTLY IN
REVIEW, I HOPE TO PRESENT FUTURE
DATA R CURRENTLY TALKING ABOUT
COGNITIVE PROFILE OF THESE
CHILDREN.
IN THE STUDY CHILDREN TWO TO
SEVEN WERE ENROLLED WITH
CONFIRMED GENETIC OF CLACK TOE
SEEM YA -- GALACTOSEEM YA.
AS YOU CAN ARE IMAGINE, IT IS
VERY IMPORTANT TO UNDERSTAND COG
IF I HAVE PROFILES OF THE
CHILDREN AND TREATMENT OF THE
PHARMACEUTICAL AGENT AND
PROGRESSION OF THE DISEASE, SO
TBHEED TO HAVE AN IMPORTANT,
GOOD MEASUREMENT TOOL, AND WE
CHOOSE NIH TOOLBOX.
SO WHY NIH TOOLBOX?
I THINK I'M PREACHING TO THE
CHOIR HERE, WE ALL KNOW THAT NIH
TOOLBOX IS NOT ONLY RELIABLE,
VALID AND CAN BE USED IN A WIDE
AGE SPAN FROM THREE TO 85, AND
ALSO I THINK IN OUR CLINICAL
STUDIES, BECAUSE WE HAVE
CHILDREN ALL THE WAY FROM TWO TO
17, IT'S IMPORTANT TO INCLUDE AS
MANY CHILDREN AS POSSIBLE TO USE
THE SAME BATTERY.
SO WHICH IS IMPORTANT.
THE OTHER THING I THINK IN NIH
TOOLBOX IS REALLY A THAIS TOOL
FOR PHARMACEUTICAL INTERVENTIONS
AND STUDIES BECAUSE -- REALLY A
NICE TOOL.
BECAUSE IT TRACKS ASSESSMENT
CHANGE OF THE SCORE, AS WELL AS
THE SCORING AND ADMINISTRATION
DOES NOT HAVE TO BE DONE WITH
EXPERTS. SO WE TRAINED CLINICAL
SITES TO ADMINISTER THE TEST AND
THE SCORE CAN BE INSTANTLY
AVAILABLE AS SOON AS THE
CHILDREN COMPLETE THE TEST.
SO IN THIS STUDY WE USE THE
AGE-APPROPRIATE TASK TO TEST THE
WIDE RANGE, ALL SEVEN COGNITIVE
TESTS, WITH SEVEN DOMAINS.
AND WE ARE USING THE AGE
STANDARD SCORE PRESENTED HERE.
BY THE WAY, ALL THE TESTS WERE
DONE IN ENGLISH.
SO THIS IS A SIMPLE DEMOGRAPHIC
TABLE.
I JUST WANT TO POINT OUT A
COUPLE IMPORTANT THINGS.
THE MEAN AGE IS 9.1 AND IS EQUAL
PERCENTAGE OF MALE AND FEMALE,
AND THESE CHILDREN COME IN WITH
ALSO SOME CNS DISEASE
BACKGROUND.
A MAJORITY OF KIDS ACTUALLY MORE
THAN 50% OF CHILDREN ALREADY
HAVE SPEECH AND LANGUAGE
IMPAIRMENT, LEARNING DISORDER
AND SOME OF THEM HAVE BEHAVIOR
PSYCHIATRIC DISORDER DIAGNOSED,
AD-D ADHD, ANXIETY, DEPRESSION,
AND MANUFACTURE THEM HAVE ALSO
MOTOR IMPAIRMENT SUCH AS TREMOR
AND ATAXIA.
SO HERE WE PRESENT FIRST THE
COGNITIVE IMPAIRMENT SCORE,
COGNITIVE PROFILE, THESE ARE
FOUR COMPOSITE SCORE THAT
GENERATED IF NIH TOOLBOX.
SO AS YOU CAN SEE, THE TOTAL
COMPOSITE SCORE IS RELATIVELY
LOW, CLOSE IT TWO STANDARD
DEVIATIONS BELOW THE MEAN.
HERE THE SOLID LINE IS THE
POPULATION MEAN AND THE TWO
DOTTED LINE IS ONE STANDARD AND
TWO STANDARD DEVIATIONS BELOW
THE MEAN.
CRYSTALIZED COMPOSITE SCORE
COMPARED TO FLUID IS RELATIVELY
CLOSE TO HER THE MEAN SCORE AND
ALSO HAVE A LITTLE BIT LESS
VARIABILITY WITHIN POPULATION.
LOOKING INTO SPECIFIC TESTS
ACROSS OUR DOMAIN HERE, I THINK
WE JUST LOOK AT PREVIOUS STUDY
PRESENTED, NICE THING ABOUT NIH
TOOLBOX IS WE CAN COMPARE SCORE
EVEN WITHIN DIFFERENT DISEASE.
YOU CAN SEE THESE CHILDREN WITH
CLASSIC GALACTOSEMIA ACTUALLY
HAVE ALSO MORE IMPAIRED IN THEIR
FLUID SKILLS AND THEIR CHRIS
SCALLIZED SCALES ARE RELATIVELY
CLOSER TO THE NORMAL SCORE BUT
MILDLY DEFICIT, BUT IN TERMS OF
THEIR FLUID SKILLS FOR EXAMPLE
THE PROCESSING SPEED AND
FLANKERS ARE THE LOWEST AND WITH
ALSO A LOT OF VARIABILITIES
WITHIN THIS POPULATION.
ONE MORE THING WE'RE GOING TO
LOOK AT IS BASED ON ACROSS
DIFFERENT AGE GROUP, WE DID
ANALYSIS LOOKING AT PROPORTION
OF CHILDREN IN THEIR STANDARD
SCORE FALL INTO DIFFERENT
SEVERITY CATEGORIES.
ON THE RIGHT, ON YOUR LEFT YOU
CAN SEE THE RED BAR ARE THE
CHILDREN THAT HAD STANDARD SCORE
LESS THAN 70, AND THE YELLOW BAR
IS BETWEEN SCORES BETWEEN 85,
115, AND PURPLE BAR IS AVERAGE
SCORE.
YOU CAN SEE CHILDREN WITH 13 TO
16 TEENAGERS ACTUALLY HAVE MORE
SEVERE SIGNIFICANT DEFICIT OVER
60% OF THEM HAVE STANDARD SCORE
LESS THAN 60 -- LESS THAN 70,
SORRY.
SO THIS INDICATES THIS
PROGRESSION OF THE DISEASE.
HOWEVER, THESE ARE THE STANDARD
SCORES, SO IT DOES NOT REALLY --
AND IT'S A CROSS-SECTIONAL, SO
WE DON'T HAVE DATA CURRENTLY
PRESENTED IN TERMS OF A LONG TUD
NATURAL RESULTS.
-- LONGITUDINAL RESULTS.
SO IN THE FUTURE IF WE USE
VERSION THREE, WE CAN USE
AGE-SENSITIVE SCORE TO TRACK
INDIVIDUAL CHANGES.
SO LAST BUT NOT LEAST, I WANT TO
HAVE A COUPLE CONCLUSION AND
DISCUSSION POINTS.
SO THE OVERALL, THE
AGE-CORRECTED STANDARD COMPOSITE
SCORE USING NIH TOOLBOX WE CAN
SEE FOR THESE POPULATIONS IS
75.3, AND THERE IS A SIGNIFICANT
COGNITIVE DEFICIT DEFYING AGE
STANDARD SCORE BELOW 70 AND THE
MAJORITY OF THESE AS LESS ENTS
HAD A SIGNIFICANT DEFICIT.
ADOLESCENTS ALSO DEMONSTRATE
MORE IMPAIRMENT IN EXECUTIVE
FUNCTION AS MEASURED BY FLANKER
AND DID HE MENTION SHALL CARD
SORT TEST WITH A MEAN SCORE
AROUND TWO STANDARD DEVIATIONS
BELOW THE MEAN, AND THE YOUNGER
CHILDREN EXHIBITED LOWER SCORES
IN WORKING MEMORY BUT SIMILAR
SCORE IN EPISODIC MEMORY
COMPARED TO OLDER CHILDREN.
AND FOR RECEPTIVE AND EXPRESSIVE
LANGUAGE FOR THE TWO
CRYSTALLIZED TESTS, YOUNGER
CHILDREN ALSO PERFORMED BETTER
THAN THEIR OLDER COUNTERPART.
SO OVERALL, THE OLDER CHILDREN
EXPERIENCED MORE SEVERE
COGNITIVE IMPAIRMENT COMPARED TO
THE YOUNGER CHILDREN,
UNDERSCORING THE PROGRESSIVE
NATURE OF THE DISEASE, AND THESE
FIENDLE DEFINITELY SUPPORT THE
IMPORTANCE OF TARGETING
COGNITIVE DEVELOPMENT IN EARLY
YEARS AND THE NEED FOR
PHARMACEUTICAL INTERVENTION TO
PREVENT FURTHER DECLINE AMONG
CHILDREN WITH CLASSIC
GALACTOSEMIA.
THANK YOU.
>> OUR LAST SPEAKER WILL BE
DR. DAVID HESSL TALKING ABOUT
THE NIH TOOLBOX COGNITION
BATTERY AND ITS UTILITY IN
CLINICAL TRIALS FOR
NEURODEVELOPMENTAL DISORDERS.
>> HI, EVERYONE.
OKAY.
SEE IF I CAN LEARN HOW TO WORK
THIS.
OKAY.
GREAT.
SO I'M DAVID HESSL, FROM UC
DAVIS.
I'VE BEEN THE PI OF A LONG TUD
NATURAL PROJECT THAT HAS BEEN
FOCUSED ON THE NIH TOOLBOX
COGNITION BATTERY IN PEOPLE WITH
INTELLECTUAL DISABILITIES FOR
THE PAST ALMOST TEN YEARS NOW.
WE'VE HAD TWO CYCLES OF FUNDING
FROM NICHD, AND THIS LAST ONE
ACTUALLY IS PARTIALLY SUPPORTED
BY THE INCLUDE DOWN SYNDROME
INITIATIVE, REALLY GRATEFUL FOR
THAT SUPPORT.
IT'S BEEN A REALLY EXCITING PART
OF MY CAREER.
I HAD THIS QUOTE, THIS IS WHERE
THE RUBBER MEETS THE ROAD, AND I
SAY THAT BECAUSE I LEARNED OVER
THE YEARS THAT WHEN IT COMES TO
INTERVENTIONS AND CLINICAL
TRIALS, THE SELECTION AND
SENSITIVITY OF THE OUTCOME
MEASURE THAT WE USE FOR THESE
TRIALS IS REALLY WHERE THE
RUBBER MEETS THE ROAD.
IT'S WHERE WE DECIDE AND WE
DETERMINE WHETHER AN
INTERVENTION IS EFFECTIVE.
SO IT'S A REALLY, REALLY
IMPORTANT THING TO FOCUS ON
OUTCOME MEASURES.
THESE ARE SOME OF MY
DISCLOSURES.
I'VE BEEN INVOLVED IN FRAGILE-X
SYNDROME RESEARCH FOR ALMOST MY
ENTIRE CAREER, AND NOW HAVE BEEN
INVOLVED IN SOME DOWN SYNDROME
STUDIES AS WELL.
SO I DO HAVE SOME DISCLOSURES
HERE TO SAY THAT I'VE BEEN
SUPPORTING DIFFERENT
TRANSLATIONAL RESEARCH EFFORTS
IN BOTH FRAGILE-X AND DOWN'S
SYNDROME.
SO I LIKE THIS IMAGE BECAUSE IT
DEPICTS JUST HOW MUCH EFFORT AND
TRAINING IT TAKES TO ACHIEVE A
GOAL.
SO I LOVE TALKING -- I LOVE
TRACK AND FIELD AND ONE OF THE
EVENTS I ALWAYS FELT LIKE I
WISHED I COULD HAVE DONE WAS THE
POLE VALUATE.
WHEN YOU THINK ABOUT POLE POLE ,
YOU HAVE TO BE FAST,
COORDINATED, STRONG, YOU HAVE TO
HAVE SOME TECHNICAL EXPERTISE,
AND WHAT I WANT TO TRY TO CONVEY
IS THAT THIS EFFORT TO VALIDATE
MEASURES NOT ONLY FOR USE IN A
POPULATION BUT FOR USE IN
CLINICAL TRIALS, IT'S A VERY
HIGH BAR AND THERE'S A LOT OF
DIFFERENT COMPONENTS TO BEING
SUCCESSFUL.
SO WHAT RAISES THE BAR?
OF COURSE, THE TEST HAS TO BE
DOABLE FOR THE POPULATION YOU'RE
INTERESTED IN.
IT HAS TO HAVE AN ADEQUATE RANGE
TO CAPTURE THE VARIABILITY IN
THE POPULATION.
IT HAS TO BE RELIABLE OVER TIME.
SO WE TALKED ABOUT TEST
RELIABILITY OR STABILITY OF A
MEASURE WHEN THERE'S NO, QUOTE,
REAL CHANGE HAPPENING.
SO THAT'S ESPECIALLY IMPORTANT
TO LOOK AT THE INTERVAL OF TIME
THAT YOU'LL BE STUDYING IN A
CLINICAL TRIAL.
SOME TEST THAT IS WE USE,
ESPECIALLY IN THE COGNITIVE
DEMAIN -- DOMAIN CAN HAVE
COGNITIVE EFFECTS.
SO YOU WOULD LIKE THEM TO HAVE
LESS SUSCEPTIBILITY TO THAT.
YOU WANT THEM TO BE SENSITIVE TO
CHANGE.
SO WHEN THERE'S A TREATMENT AND
SOMEBODY ACTUALLY GETS BETTER,
YOU WANT THE MEASURE TO BE ABLE
TO DETECT THAT CHANGE.
IDEALLY, THE MEASURE WILL HAVE
ESTABLISHED LINKS TO THE KNOWN
COGNITIVE PHENOTYPE OF THE
DISORDER IF YOU'RE FOCUSING ON A
COGNITIVE MEASURE.
SO YOU WANT IT TO KIND OF ALIGN
WITH WHAT YOU WOULD EXPECT TO
SEE.
A BONUS IS IF THE MEASURES HAVE
KNOWN UNDERLYING BRAIN
MECHANISMS THAT ARE UNDERSTOOD
IN PEOPLE WHO ARE TYPICALLY
DEVELOPING AND ARE DEFICIENT OR
ABERRANT IN PEOPLE WHO HAVE THE
CONDITION.
AND THEN THIS LAST ONE, WHICH
WE'VE BEEN WORKING A LOT LATELY,
IS THE CONCEPT OF CLINICAL
MEANINGFULNESS OR IMPORTANCE.
SO WHEN WE HAVE A MEASURE THAT
WE DO IN THE LAB, WE WANT TO BE
ABLE TO DEMONSTRATE THAT IT
ACTUALLY HAS MEANING FOR THE
PEOPLE IN THEIR DAILY LIVES AND
THAT WHEN THE MEASURE GETS
BETTER, WHEN YOU TEST THEM, THAT
IT REFLECTS SOMETHING THAT'S
ACTUALLY HAPPENED IN THEIR LIFE.
SO, MANY YERS AGO, THIS IS THE
KIND OF AHA MOMENT THAT I HAD
WHEN I STARTED READING ABOUT THE
TOOLBOX AND REALIZED THAT THERE
WAS THIS VERY BROAD
DEVELOPMENTAL RANGE THAT WAS
BEING ADDRESSED FROM AGE THREE
TO AGE 89, AND I KNEW THAT MANY
OF OUR INDIVIDUALS THAT WE STUDY
WITH INTELLECTUAL DISABILITIES
ARE OLDER BUT HAVE MENTAL AGES
THAT ARE LOWER.
SO KNOWING THAT IT COULD CAPTURE
THIS BROAD RANGE WAS AN
ADVANTAGE.
I ALSO STARTED READING ABOUT THE
TOOLBOX IN THE MONOGRAPHS PAPERS
THAT CAME OUT MANY YEARS BACK
AND SAW SOME OF THESE GRAPHS
THAT SHOWED THESE VERY NICE
TIGHTER OR BARS AROUND DIFFERENT
AGES CROSS DEVELOPMENT, AND I
SAID AHA, THAT COULD REALLY BE
SOMETHING THAT COULD BE
SENSITIVE NOT ONLY TO
DEVELOPMENTAL CHANGES IN PEOPLE
WHO HAVE DISABILITIES BUT ALSO
WITHIN TREATMENT STUDIES, COULD
THEY ALSO BE EQUALLY SENSITIVE.
I'M GOING TO JUST SKIP BY THIS
BECAUSE YOU'VE HEARD A LOT ABOUT
THE TOOLBOX BATTERY, BUT THIS IS
JUST A DEPICTION THAT WE USE
WHEN WE DO THE TESTING WITH OUR
PARTICIPANTS SO THAT THEY CAN
SEE WHAT TO EXPECT IN THEIR
ASSESSMENT.
ONE OF THE THINGS WE DISCOVERED
IN USING THE TOOLBOX OR MANY OF
THE THINGS THAT WE DISCOVERED
WERE SORT OF GAPS IN THE
CAPACITY OF THE TOOLBOX TO DO A
REALLY GROOD JOB -- GOOD JOB OF
MEASURING COGNITION IN CERTAIN
SUBJECTS, AND WE FOUND THAT IN
SOME PEOPLE WITH INTELLECTUAL
DISABILITY ACTUALLY A
SUBSTANTIAL NOBODY A TEST SUCH
AS PATTERN COMPARISON, WE WERE
GETTING SOME INVALID PATTERN
RESPONDING, WHERE IT SEEMED LIKE
THE INDIVIDUALS WERE DOING THE
TEST PROPERLY BUT WHEN WE
ACTUALLY PAID CLOSE ATTENTION,
THEY WERE ACTUALLY JUST KIND OF
RANDOMLY CHOOSING THE LEFT OR
RIGHT BUTTON, AND WE REALIZED
THAT WE NEEDED TO COME UP WITH
SOMETHING DIFFERENT.
SO AARON, WHO IS HERE IN THE
AUDIENCE, SORRY FOR THE OLD
PICTURE, AARON, YOU'VE GOT TO
GIVE ME A NEW PICTURE, I GUESS,
WE WORKED EXTENSIVELY WITH AARON
TO DEVELOP A NEW TEST THAT WAS
GOING TO BE LESS SUSCEPTIBLE TO
THIS PROBLEM.
SO IN THIS PARTICULAR PROCESSING
SPEED TEST, THE INDIVIDUAL JUST
NEEDS TO MATCH THE IMAGE THEY
SEE IN THE TOP WITH ONE OF THE
FOUR AT THE BOTTOM.
SO INSTEAD OF HAVING TWO
CHOICES, NOW THERE'S FOUR
CHOICES, SO LESS CHANCE
RESPONDING AND LESS
SUSCEPTIBILITY TO PATTERN
RESPONDING.
SO THAT WAS JUST ONE OF THE
ADVANCES THAT WE HAD DURING
WORKING ON THIS PROJECT.
WE ALSO SPENT A LOT OF TIME
COMING UP WITH AN ADMINISTRATORS
MANUAL THAT IS SPECIFICALLY
DESIGNED FOR PEOPLE WHO ARE
TESTING PATIENTS OR INDIVIDUALS
WITH INTELLECTUAL DISABILITIES.
THEY ARE VERY CHALLENGING TO
ASSESS, FOR A VARIETY OF
REASONS, AND THEY ALSO NEED MORE
SUPPORT THAN MOST PEOPLE WHO ARE
TYPICALLY DEVELOPING.
SO WE DEVELOPED SOME
ACCOMMODATIONS AND SOME
GUIDELINES AROUND WHAT KINDS OF
REWARDS CAN BE GIVEN FOR WHICH
TESTS, HOW MANY PROMPTS CAN BE
ALLOWED.
BASICALLY ESSENTIALLY MAKING
SOME JUST TOUGH DECISIONS ABOUT
HOW TO KEEP THINGS CONSISTENT
ACROSS DIFFERENT SITES, AND I
SHOULD MENTION THIS IS A
MULTICENTER PROJECT.
SO WE WANTED TO HAVE A DOCUMENT
BASICALLY TO HELP PEOPLE KNOW
HOW TO GIVE THE TEST
CONSISTENTLY.
WE USE AN ADMINISTRATION FORM
WHERE WE HAVE THE EXAMINERS
RECORD WHETHER THEY DETERMINE
THE TEST TO BE VALID OR NOT, AND
IF IT'S NOT, THE REASONS WHY.
THEY CAN TAKE NOTES.
AND THEN WHEN WE QUERY THE
TOOLBOX DATA, WE ALSO QUERY DATA
FROM THE ADMIN STRAIKS FORM AND
WE CAN THEN KIND OF SCREEN OUT
TESTS OR ADMINISTRATIONS THAT WE
OR THE EXAMINER FELT WAS INVALID
SO THAT WE DON'T MISTAKENLY USE
THAT IN OUR ANALYSIS.
THIS IS JUST KIND OF A QUICK
VIEW OF SOME OF THE
REINFORCEMENT GUIDELINES THAT WE
DEVELOPED THAT ARE DEPENDENT ON
THESE TESTS.
THESE DATA ARE A LITTLE BIT OLD
NOW, BUT I WANTED TO KIND OF
REFLECT ALL THE WORK THAT WE'VE
BEEN DOING OVER THE YEARS.
THIS WAS THE FIRST KIND OF BIG
PAPER THAT CAME OUT OF OUR
PROJECT BY MY GRADUATE STUDENT
REBECCA SHIELDS, AND YOU CAN SEE
THAT WE STUDIED OVER 200
INDIVIDUALS WITH INTELLECTUAL
DISABILITIES.
WE HAD BEEN FOCUSING ON DOWN'S
SYNDROME AND FRAGILE-X SYNDROME
BECAUSE THEY HAVE THE BIGGEST
TRANSLATIONAL RESEARCH PROGRAMS
BASICALLY IN THE UNITED STATES
AND PROBABLY AROUND THE WORLD IN
TERMS OF TAKING TARGETED
TREATMENTS FROM ANIMAL MODELS TO
HUMANS, SO WE FOCUSED ON THAT
AND THEN WE INCLUDED A
COMPARISON GROUP OF PEOPLE WITH
ALL KINDS OF OTHER INTELLECTUAL
DISABILITIES.
THIS IS A REALLY USEFUL SLIDE IF
YOU'RE THINKING ABOUT USING THE
COGNITION BATTERY IN PEOPLE WITH
INTELLECTUAL DISABILITIES.
SO WHAT YOU SEE HERE IS MENTAL
AGE HERE ACROSS THE TOP AS
DETERMINED BY THE STANFORD
BINAY IQ TEST.
THAT DOESN'T REALLY POINT VERY
WELL.
OKAY.
EACH OF THE TOOLBOX TESTS ARE
LISTED ON THE LEFT AND THEN THIS
IS JUST SHOWING YOU WHAT
PRACTICE PORTION OF EACH AGE
GROUP WAS ABLE TO DO THE TEST
AND YIELDED A VALID SCORE.
YOU CAN SEE HOWCH THE BATTERY
REALLY DOES WELL WITH A MENTAL
AGE ANYWHERE FROM ABOUT 5.0
YEARS AND UP AND THEN A LITTLE
BIT SPOTTY AT MENTAL AGE OF FOUR
AND THEN IT DROPS OFF MORE
SIGNIFICANTLY FOR THE FLUID
REASON TEST AND MENTAL AGE OF
THREE AND BELOW, ALTHOUGH IT
DOES QUITE WELL STILL WITH
CRYSTALLIZED COGNITION, AS YOU
CAN SEE WITH PICTURE VOCABULARY
AND ORAL READING AT THE BOTTOM.
WE'VE DONE A LOT OF WORK LOOKING
AT TEST/RETEST RELIABILITY.
FOR EXAMPLE, OVER A FOUR-MONTH
PERIOD -- SORRY, A ONE-MONTH
PERIOD, AND ALSO TRYING TO
DETERMINE WHETHER THERE ARE ANY
PRACTICE EFFECTS.
AND YOU CAN SEE THESE ICC'S ARE
GENERALLY PRETTY GOOD AND IN
LINE WITH WHAT YOU SEE USING
OTHER TEST INSIDE THIS KIND OF
POPULATION MUCH THE ONLY
EXCEPTION REALLY WAS PICTURE
SEQUENCE MEMORY, THAT'S THE
EPISODIC MEMORY TEST.
SO EVEN WHEN WE USED THE SAME --
THIS IS A WEIRD POINTER -- EVEN
THOUGH WE USED THE SAME VERSION
AT BOTH TIME POINTS, WE FOUND
THAT NOT TO BE AS RELIABLE AS
THE OTHER MEASURES.
BUT THE COMPOSITES DID QUITE
WELL.
IN TERMS OF KNOWN GROUPS
VALIDITY, SO I WAS MENTIONING
CAN YOU FIND THE KIND OF
DEFICITS THAT YOU WOULD EXPECT
TO SEE IN A POPULATION, AND WE
NOTED THAT THE DOWN'S SYNDROME
GROUP AND THE FRAGILE-X GROUP
REALLY HAD VERY PROMINENT
EXECUTIVE FUNCTION WEAK NS,
WHICH IS KNOWN IN THE
LITERATURE.
SO WE WERE HAPPY TO SEE THAT IT
WAS PICKING UP ON SOME FEAN
TYPES THAT WE KNOW ABOUT IN
INTELLECTUAL DISABILITIES.
THIS WAS ALSO DONE BY REBECCA.
-- SOME PHENOTYPES.
THIS IS ONE OF MY FAVORITE
GRAPHS FROM ALL OF OUR WORK.
IT SHOWS THE ASSOCIATION BETWEEN
THE COGNITION COMPOSITE SCORE,
THE TOTAL COMPOSITE SCORE ON THE
TOOLBOX AGAINST THE STANFORD
BINAY FULL SCALE IQ, AND ASIDE
FROM THE FACT THAT THERE'S A
STRONG CORRELATION, WHICH YOU
CAN SEE HERE, THE REGRESSION
LINES REALLY FALL KIND OF WHERE
THEY OUGHT TO BE IN TERMS OF NOT
BEING SKEWED TOO HIGH OR TOO
LOW, SO A 25 ON ONE TEST IS
RELATIVELY A GOOD ONE TO A 25 --
IS EQUIVALENT TO 25 ON ANOTHER
TEST AND ON UP TO BELOW THE
AVERAGE RANGE.
SO SOME REASSURING KIND OF
CROSS-VALIDITY WITH ANOTHER
MEASURE.
REBECCA'S -- I HAVE A MINUTE OR
TWO?
OKAY, I'LL TRY TO GO FASTER.
REBECCA HAS DONE SOME
LONGITUDINAL MODELING TO LOOK AT
SENSITIVITY OF CHANGE OVER TIME
AND HAS SHOWN SOME REALLY
INTERESTING KIND OF DEFERENCES
ACROSS SYNDROMES AND ACROSS
COGNITION TESTS, COMPONENTS, AND
I WOULD URGE YOU TO LOOK AT THIS
PAPER IF YOU'RE INTERESTED IN
LOOKING AT DEVELOPMENT OF THE
TOOLBOX.
THIS IS JUST AN EXAMPLE OF KIND
OF AT DIFFERENT AGE POINTS WHICH
TESTS ARE DETECTING SIGNIFICANT
GROWTH IN COGNITION IN
INDIVIDUALS WITH DOWN'S
SYNDROME, SO YOU CAN SEE MORE
GROWTH CENTERED AT AROUND AGE
TEN AND AGE SIXTEEN AND THEN
LESS GROWTH AND MORE PLATEAUING
LATER ON IN DEVELOPMENT.
ANDY DECOPILIS WHO IS WORKING IN
THE ROOM, HAS BEEN WORKING WITH
ME, WELL, HE'S DONE ALL THE
WORK, WE'VE BEEN WORKING AND
TALK SAYING LOT TOGETHER ABOUT
HOW TO LOOK AT CHANGE IN TOOLBOX
COGNITION ALONG WITH DEVELOPMENT
IN DAILY LIFE AS MEASURED BY THE
VINELAND ADAPTIVE BEHAVIOR
SCALES AND ANDY HAS DONE SOME
FANTASTIC WORK SHOWING SOME
COMPONENTS OF THE NIH TOOLBOX
WHEN THEY ARE MOVING ASK THERE
ARE GAINS IN THESE INDIVIDUALS,
WE ALSO SEE GAINS IN SOME
ASPECTS OF ADAPTIVE BEHAVIOR
ESPECIALLY IN DAILY LIVING
SKILLS.
ANDY HAS A POSTER, SO I WOULD
ENCOURAGE HIM TO COME AND LOOK
AT HIS POSTER AND TALK ABOUT HIS
NODLE YOU'RE SO INCLINED TO
LEARN ABOUT THESE SOPHISTICATED
STATISTICS.
DR. BARRY CURBIS ALSO HAS A
POSTER LOOKING AT SENSITIVITY TO
CHANGE IN THE TOOLBOX WITHIN A
CLINICAL TRIAL HEADED BY TETRA
PHARMACEUTICALS LOOKING AT AN
INHIBITOR, I WON'T SPEND TOO
MUCH TIME BECAUSE I THINK I'M
RUNNING OUT, BUT THE BASIC
RESULT OR IMPORTANT THING ON
TELL YOU IS THAT THE TOOLBOX
CRYSTALLIZED COGNITION WAS
SENSITIVE TO THE TREATMENT
BENEFITS OF THIS TARGETED
TREATMENT FOR FRAGILE-X
SYNDROME.
THESE ARE SOME OF THE OTHER
TRIALS THAT ARE EITHER ONGOING
OR PLANNED OR ARE USING THE
TOOLBOX, EITHER AS A PRIMARY ARE
A KEY SECONDARY ENDPOINT.
MOSTLY ON FRAGILE-X SYNDROME,
BUT AT THE BOTTOM THERE I NOTE
THE ONE INITIATIVE BY AELIS
PHARMACEUTICALS THAT'S LOOKING
AT AN ENDOCANNABINOID RECEPTOR
IN DOWNS SIN DROARNLINGS REALLY
EXCITED TO SEE THAT GROUP
PICKING THAT UP AS AN OUTCOME
MEASURE AS WELL.
THESE ARE ALL MY COLLABORATORS,
IT'S A MULTICENTER STUDY, SO
WE'VE HAD TEN YEARS OF WORK AND
SO WE'VE HAD DIFFERENT STAFF
MEMBERS COMING AND GOING BUT
LOTS AND LOTS OF CONTRIBUTIONS
ACROSS MOSTLY UC DAVIS, RUSH,
LED BY LIZ BERRY-CRAVIS, YEULT
OF DENVER OR REGIS WITH KAREN
RILEY AND JEANINE COLEMAN AND
CRAIG ERICSON AT SIN SENATE TI
AND ALL THE HELP AND SUPPORT
FROM THE TOOLBOX TEAM AT
NORTHWESTERN.
SO I WILL STOP THERE.
THANK YOU.
>> AND I WILL HAVE OUR SPEAKERS
COME UP.
THIS TABLE OR THE Q & A SESSION.
DO YOU HAVE ANY QUESTIONS FOR
THEM?
THE MICROPHONE IS UP FRONT.
>> IT'S BETTER FOR PEOPLE
ONLINE, POTENTIALLY.
I CAN TRY TO REPEAT THINGS THEY
DON'T PICK UP.
>> THANK YOU FOR ALL THE TALKS.
I HAVE A QUESTION, I GUESS I'LL
ASK ONE OF YOU IF YOU CAN
SYNTHESIZE ACROSS THE TALKS,
THERE WERE A COUPLE DIFFERENT
LABORS OF RESULTS IN TERMS OF
IQ.
I WONDER IF YOU WANT TO TALK
ABOUT THAT.
YOU TWO ARE PITTED AGAINST EACH
OTHER.
>> WHICH TESTS?
>> SO WE USED A COMBINATION OF
(?) AND I KNOW -- OF IQ SCALES.
I KNOW YOU ALL USED STANFORD
BINET SCORING, I THINK THAT
MIGHT BE PART OF IT, IS THAT
THESE ARE JUST SLIGHTLY
DIFFERENT GOING ON THE STANFORD,
THAT YOU COULD PRESENT.
I THINK THAT MAY BE SOME OF IT.
I THINK ALSO HE WILL THE --
(AWAY FROM MICROPHONE).
>> WELL, YEAH, FOUR EFFECTS ARE
A PROBLEM IN LOCALITIES OF
STUDIES, IN INTELLECTUAL
DISABILITIES, SO I'M SURE WE REC
TI FADE THAT WITH THE SCORING WE
USED.
EVEN WHEN WE USED THE STANDARD
SCORE THAT'S NOT THE DEVIATION,
I THINK WE STILL GET FAIRLY
DECENT CORRELATIONS WITH THE
TOOLBOX.
YEAH, I REALLY HOW TO EXPLAIN
IT.
I THINK, YOU KNOW, IT'S REALLY
OFTENTIMES YOU JUST HAVE TO GO
DOWN AND LOOK AT THE ITEMS THAT
PEOPLE ARE ADMINISTERED AND SEE
HOW MUCH OVERLAP THERE IS IN THE
SCRUBLGHTS THAT ARE BEING TESTET
ARE BEING TESTED.
I DON'T KNOW HOW ELSE TO...
>> I KNOW ANOTHER ISSUE WE RAN
INTO WITH OUR POPULATION WAS THE
NUMBER ONE DROPOUT REASON WAS
ATTENTION.
SO IN ADDITION TO EITHER NOT
PASSING -- LIKE THE REASON THEY
WEREN'T PASSING THE PRACTICE WAS
BECAUSE THEY COULD NOT ATTEND TO
THE TASK.
SO SOME LIKE THE FLANKER AND THE
DCCS DEFINITELY HAVE FAIRLY
SPECIFIC MEASURING PART SO IT
MAYBE RELATED TO THAT, WHERE
THEY'RE NOT EVEN THROUGHOUT
TESTING WE HAD TO REDIRECT THEM
A NUMBER OF TIMES BECAUSE THEY
WOULD BE TRYING TO TALK TO THE
EXAMINER AND THINGS LIKE THAT,
SO IT MAYBE RELATED TO THAT.
>> I'M SORRY, JUST IF I COULD.
WOULD THERE BE ANYTHING UNIQUE
ABOUT WILLIAMS SYNDROME IN TERMS
OF THEIR VISUAL-SPATIAL
CRAZINESS -- NOT CRAZINESS, JUST
THEY HAVE SO MUCH TROUBLE WITH
IT.
IS THERE SOMETHING UNIQUE ABOUT
THAT THAT WOULD MAKE THE
CORRELATION MORE DIFFICULT TO
DETECT?
>> I DON'T THINK SO BECAUSE THE
TASK WE USED -- (AWAY FROM
MICROPHONE), THE DCCS AND THE
FLANKER.
>> RIGHT.
>> WELL, RIGHT.
SO THEIR MAIN THING, VERBAL AND
NONVERBAL.
LIKE THEIR VERBAL SCALES --
(AWAY FROM MICROPHONE).
>> TOOLBOX DOESN'T REALLY HAVE
VISUAL-SPATIAL PROCESSING.
>> NO.
>> WHEREAS THE -- (AWAY FROM
MICROPHONE).
THAT COULD BE 6789.
COULD BE.>> RIGHT.
>> I WONDERED A BIT, DO YOU
THINK THERE'S -- SO IS THERE
ENOUGH VARIABILITY IN THE RAW
SCORES WHEN YOU'RE LOOKING AT
THESE KIND OF FLOOR EFFECTS THAT
POTENTIALLY RENORMING IT FOR
THESE TYPES OF CLINICAL
POPULATIONS WOULD HAVE UTILITY?
>> SO WE DIDN'T RENORM, BUT WE
LEVERAGED THE NORMATIVE DATA
THAT THE PUBLISHERS GAVE US
ACCESS TO.
FOR EXAMPLE, FROM THE STANDFORD
BINET AND WE ESSENTIALLY
DISREGARDED THEIR THIS
WINDSORRIZING, THEIR CUTTING OFF
AT A CERTAIN POINT, AND WE JUST
CALCULATE THE NUMBER OF STANDARD
DEVIATIONS ESSENTIAL OF
DEVIATION FROM AVERAGE USING THE
RAW SCORES.
SO THAT WAS REALLY EFFECTIVE.
IT WASN'T RENORMING, BUT IT WAS
A WAY TO GET SOMETHING THAT
GIVES US MORE SENSITIVITY TO
DIFFERENCES.
>> STILL RELATED TO THE TOOLBOX,
I THINK POTENTIALLY MY
UNDERSTANDING IS THAT THERE'S NO
REASON IT NEEDS TO BE
WINDSORRIZED AT 64.
>> YES, YES.
THANKS FOR REMINDING ME.
[LAUGHTER]
>> SO ON THAT POINT, BECAUSE OUR
POPULATION, AS YOU CAN SEE,
THEIR SCORE IS NEARLY TWO
STANDARD DEVIATIONS BELOW, SO WE
ACTUALLY CALCULATED, FOR
EXAMPLE, IF THEY DON'T PASS THE
PRACTICE TEST OR THEY GOT ZERO,
SO WE HAVE TO CALCULATE THE
SCORE RATHER THAN, YOU KNOW, USE
THE SAME SCORE.
YEAH.
NOT WINDSORIZE.
>> SO FROM THOSE WHO HAVE USED
IT LONGITUDINALLY, I KNOW THAT
SOME OF THE SCORES ARE CHANGING
WITH THE VERSION THREE TO MAKE
IT, I THINK, MORE AMENABLE TO
CHANGE OVER TIME, BUT WHAT DO WE
THINK NEEDS TO HAPPEN NOW TO
MAKE THE MEASURE READY FOR IT
BEING USED AS AN ENDPOINT OR
SENSITIVE TO CHANGE IN THESE
KIND OF TRIALS?
>> SINCE I THINK ABOUT THIS ALL
THE TIME, I GUESS I'LL TRY TO
ANSWER IT.
SO WE'VE DONE A LOT OF THE WORK,
I WOULD SAY, ALREADY THAT THE
FDA IS INTERESTED IN.
THERE ARE SOME GAPS, THOUGH
THAT, ARE SUPER-IMPORTANT TO
FILL, AND DR. CAT IS ADDRESSING
ONE OF THEM, WHICH IS CLINICALLY
MEANINGFUL CHANGE.
SO WHEN A SINGLE PATIENT, YOU
KNOW, HAS AN IMPROVEMENT, WE
DON'T KNOW WHETHER TO INTERPRET
THAT AS A CLINICALLY MEANINGFUL
IMPROVEMENT OR NOT.
SO WE NEED TO DO SOME ANALYSES
THAT WILL HELP US GIVE AT LEAST
AN ESTIMATE WITH A CONFIDENCE
INTERVAL AROUND IT OF HOW MANY
POINTS OF GAIN ON EACH COMPONENT
IS CONSIDERED CLINICALLY
MEANINGFUL.
SO I THINK THAT'S REALLY
IMPORTANT.
I THINK THE WORK THAT ANDY IS
DOING LOOKING AT ASSOCIATIONS
WITH WHAT'S HAPPENING IN THEIR
DAILY LIFE IS IMPORTANT.
AND I THINK JUST MORE WORK TO
EDUCATE THE DECISION MAKERS
ABOUT, YOU KNOW, WHAT THE
STREJTS AND LIMITATIONS --
STREJTS AND LIMITATION --
STRENGTHS AND LIMITATIONS ARE OF
THE TOOLBOX AND SEEING IT DONE
IN MORE TRIALS AND HOW IT
PERFORMS.
LIDS, DOCUMENT TO ADD TO THAT?
DO YOU WANT TO GET UP TO THE
MICROPHONE?
>> FROM BEING AT FDA MEETINGS.
SO IT SEEMS LIKE THE THING THEY
WANT IS TO REALLY BE ABLE TO SEE
THIS VALIDATION DATA BECAUSE WE
HAD A LONG DISCUSSION ABOUT IT
WHEN WE FIRST WENT IN WITH TETRA
AND THEY SEEM TO P THE DATA IN
ADDITION TO BEING PUBLISHED IN
THE LITERATURE, TO BE SOMETHING
THEY CAN SEE IN AN FDA COMPLIANT
DATABASES, LIKE THROUGH A
SPONSOR.
I THINK TETRAIS GOING TO HELP
WITH THAT, BECAUSE WE'RE
RERUNNING ALL OF DAVID'S
VALIDATION ANALYSES IN THE
TETRA TRIAL.
GRANTED, IT'S NOT THE IDEAL
POPULATION BECAUSE IT'S THE
PLACEBO GROUP OR IT'S A GROUP
BEFORE THEY ACTUALLY START
TREATMENT, BUT IT'S KIND OF WHAT
THEY'RE GOING TO HAVE TO WORK
WITH.
SO I THINK IT'S JUST GOING ON
TAKE TIME FOR FDA TO ACCEPT IT.
BUT I DON'T KNOW IF ANYONE IS
FROM FDA-H BUT I WAS REALLY
HOPING FDA WOULD ATTEND THIS
MEETING BECAUSE THERE'S SO MUCH
WORK THAT'S BEEN DONE ON THIS,
AND WHEN WE FIRST WENT IN, YOU
KNOW, IT WAS ALMOST LIKE THEY
HADN'T HEARD OF IT, AND IT WAS
LIKE DAVID WAS AT THE MEETING
TOO, IT WAS LIKE A WHOLE NEW
CONCEPT.
AND I THINK IT'S REALLY
IMPORTANT FOR THEM TO START
LOOKING AT THIS.
>> ALL RIGHT TOVMENT REPEAT THAT
QUESTION FOR THE ONLINE PEOPLE,
ARE THERE ANY OTHER SORT OF
SYNDROMES THAT YOU WOULD LIKE TO
REPEAT THESE STUDIES ON IN THE
FUTURE?
>> I THINK FOR ME AND A LOT OF
US, IT DEPENDS A LOT ON THE
SUCCESS OF BABY TOOLBOX.
WHAT YOU CAN SEE FROM THE DATA
THAT I SHOWED, THAT THERE'S A
DROPOFF IN THE UTILITY OF THE
REGULAR TOOLBOX AT A CERTAIN
DEVELOPMENTAL LEVEL, AND WE NEED
THAT GAP TO BE FILLED WITH THE
BABY TOOLBOX TO ENABLE US TO
INCLUDE THESE OTHER SYNDROMES
THAT ARE MORE SEVERELY AFFECTED
THAN PEOPLE WITH DOWN'S
SYNDROME, NOT THAT PEOPLE WITH
FRAGILE-X AND DOWN'S SYNDROME
ARE NOT SOMETIMES SEVERELY
EFFECTED, BUT THERE ARE
SYNDROMES WHERE THE DELAY IS
EVEN MORE SIGNIFICANT, OR PEOPLE
WHO HAVE A REALLY COMMON
SYNDROME LIKE DOWN'S SYNDROME OR
EVEN JUST IDIOPATHIC
INTELLECTUAL DISABILITY WHO JUST
HAPPEN TO BE KIND OF BELOW THE
LEVEL OF THE REGULAR TOOLBOX.
SO WE REALLY, REALLY NEED THAT
BABY TOOLBOX.
THEN I THINK WE'LL BE ABLE TO
STUDY MORE BROADLY THESE OTHER
CONDITIONS.
>> (AWAY FROM MICROPHONE) WHAT
YOU SAID BECAUSE ESPECIALLY IN
RARE DISEASE, CHILDREN ARE BORN
WITH THOSE CONDITIONS, SO YOU
WON'T REALLY HAVE
INTERVENTIONS -- SO YOU WANT TO
HAVE INTERVENTIONS AS EARLY AS
POSSIBLE.
BUT WHEN YOU DON'T REALLY HAVE A
VALID TOOL TO UNDERSTAND THE
DEVELOPMENTAL DLAIF COGNITIVE
IMPAIRMENT, YOU CAN'T REALLY,
YOU KNOW, DO MUCH ABOUT IT.
SO ADVANCEMENT IN BABY TOOLBAR
AND KEEP ADVANCING THE NIH
TOOLBOX IS SUPER IMPORTANT.
I THINK FROM THE STUDY WE
CONDUCTED FROM THE
PHARMACEUTICAL INDUSTRY I THINK
THERE IS A LOT OF UTILITY IN
USING SORT OF A COMMON -- SUCH
AS NIH TOOLBOX USING IN
DIFFERENT DISEASE AND COMPARE
THE SCORE TO UNDERSTAND IN THIS
RARE DISEASE POPULATION OR IS IT
IN GENERAL, IMPAIRMENT.
>> I WILL BE THE THIRD TO ECHO
WHAT THEY ALREADY SAID.
>> (AWAY FROM MICROPHONE).
>> YEAH, AND RELATEDLY, A LOT OF
THE WORK THAT WE DO IN THE
NEURODEVELOPMENTAL AND
PHENOTYPING ON CAMPUS, I SAY WE,
IT'S NOT REALLY ME ANYMORE, BUT
IS WITH NONVERBAL OR PREVERBAL
POPULATIONS, SO AGAIN, THE BABY
TOOLBOX AND THOSE EYE TRACKING
MEASURES THEY REALLY CAN WORK IN
THESE POPULATIONS COULD BE
POTENTIALLY VERY VALUABLE.
>> CAN I ANSWER THIS QUESTION
TOO?
[LAUGHTER]
>> I WANT TO ANSWER THIS
QUESTION TOO.
I THINK ONE OF THE PLACES WHERE
I WANT TO SEE MORE POPULATIONS
THAT WE'RE WILLING TO TEST IS
SOME OF THE EXAMPLES WHERE WE
HAVE PRIMARILY MOTOR DISORDERS
AND WE'VE NEGLECTED COGNITION
FOR MAYBE TOO LONG WHERE IT'S
MORE OF A SUBTLE DEFICIT, SO WE
HEARD A LITTLE OF THAT, AND I
APPRECIATE THAT.
BUT I THINK THERE'S A LOT OF
DISORDERS WHERE WE MIGHT NOT
THINK OF THEM AS AFFECTING
COGNITION.
AND IT'S TIME HA WE SAY THIS IS
AN IMPORTANT THING FOR SAFETY
PURPOSES, IT'S AN IMPORTANT
THING BECAUSE WE'RE NOT
RECOGNIZING SUBTLE DEFICITS, AND
IF WE CAN DO A BETTER JOB WITH
THAT F WE STOP THINKING ABOUT
NEURO DEVELOPMENT AND BEING ONLY
ABOUT THOSE THAT ARE PRIMARILY
IN COGNITION, WE MITT REALIZE
SOME THINGS THAT WE'VE NEGLECTED
FOR TOO LONG.
>> OR THOSE DISORDERS THAT HAVE
BOTH MOTOR AND COGNITIVE
IMPAIRMENTS AND THE COGNITIVE
ASSESSMENT IS NOT ACCURATE
BECAUSE OF SOME OF THE MOTOR
SKILLS.
I THINK THERE'S A PLACE FOR
TOOLBOX HERE AS WELL.
SO WE HAVE A BUNCH OF THOSE
DISORDERS.
BUT I WANTED TO ASK YOU, SO IT'S
INTERESTING THIS PERCENTAGE OF
PATIENTS THAT FALLS IN THE,
QUOTE, SEVERE RANGE, WHICH IS
BASICALLY BELOW NORMAL AS TIME
GOES ON.
WE'VE NOTICED THIS ACTUALLY IN
OUR LONG-TERM FOLLOW-UP OF OUR
NIEMANN PIC PATIENTS AS WELL,
AND THEY HAVE DISEASE AND GET
THEM ON TREATMENT AT A CERTAIN
POINT, THEN WE KIND OF FREEZE
THE DISEASE.
BUT THEY'RE YOUNG, SO WE'RE NOT
REALLY TESTING EXECUTIVE
FUNCTION.
SO WHEN THEY HAVE AN EMERGING
PROBLEM WITH EXECUTIVE FUNCTION
OR SOMETHING, WE DON'T REALLY
KNOW WHETHER THAT IS THE
EMERGENCE OF THE DAMAGE THAT WAS
DONE BEFORE OR WHETHER THAT IS A
NEW DEFICIT.
DO YOU HAVE ANY THOUGHTS ON THAT
IN GALACTOSEMIA?
>> I THINK I DON'T HAVE A
DEFINITE ANSWER, BUT I'M
THINKING BECAUSE GALACTOSEMIA,
GALACTOTOL IS PRODUCED IN THOSE
CHILDREN, NORMAL CHILDREN DON'T
PRODUCE GALACTOTOL.
SO EVEN THOUGH THESE GALACTOSOAS
RESTRICT DIET THE GALACTOSOS
ACCUMULATE IN THE BODY, PRESUME
THAT ALREADY HAPPENED IN THE
PRENATAL PERIOD OF TIME,
POTENTIALLY WILL NOT RECOVER
FROM T BUT BECAUSE THE BODY
STILL PRODUCE GALACTOSSSO, CR
DAMAGE IS STILL GOING ON,
SOMETHING WE CAN FURTHER DECLINE
LACK OF FUNCTION COULD BE
BENEFICIAL BUT HOW MUCH WE CAN
DO THAT IS ALSO DEPENTDING ON
HOW MUCH MEASUREMENT WE CAN SEE
IS THERE A DECLINE S THE PLACEBO
POPULATION, HOW DOES THAT
COMPARE TO THE ACTIVE TREATMENT.
SO LINK THERE IS A LOT OF
UNKNOWN FOR RARE DISEASE BECAUSE
THERE IS JUST NOT BEING WELL
STUDIED.
>> ALREADY.
THAT.>> ALL RIGHT.
THAT WRAPS UP THIS.
THANK YOU VERY MUCH TO OUR 3317 01:59:22,922 SPEAKERS.