CognitiveAging:WhatEveryOlderAdultShould

KnowDanBlazerMD,MPH,PhD

JPGibbonsProfessorEmeritusPsychiatryandBehavioralSciencesDukeUniversitySchoolofMedicine

Disclosures

•  IchairedtheInstituteofMedicineConsensusCommitteefromwhichlargeportionsofthistalkderive.

•  Ihaveupdatedareaswherenewandrelevantdatahaveemergedinformingourunderstandingofcognitiveaging.

•  Nootherdisclosures

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InstituteofMedicine2015

FreePDFofthereport:www.iom.edu/cognitiveaging

Sponsors:

•  McKnightBrainResearchFoundation

•  NationalInstituteonAging•  NationalInstituteofNeurologicalDisordersandStroke

•  CentersforDiseaseControlandPrevention

•  RetirementResearchFoundation

•  AARP

CognitiveAging:ProgressinUnderstandingand

OpportunitiesforAction

ThanksforSlidesandCollaboration

•  SharonInouye,MD–Harvard

•  BobWallaceMD–UniversityofIowa

•  KristineYaffe,MD–UniversityofCalifornia,SanFrancisco

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WhatisCognitiveAging?

•  Cognitionreferstothementalfunctionsinvolvedinattention,thinking,understanding,learning,remembering,solvingproblems,andmakingdecisions.

•  Cognitiveagingisaprocessofgradual,ongoing,yethighlyvariablechangesincognitivefunctionsthatoccuraspeoplegetolder.

•  Cognitiveagingisalifelongprocess.Itisnotadiseaseoraquantifiableleveloffunction.

•  Inthecontextofaging,cognitivehealthisexemplifiedbyanindividualwhomaintainshisorheroptimalcognitivefunctionwithage.

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KeyFeaturesofCognitiveAging•  Inherentinhumansandanimalsastheyage•  Occursacrossthespectrumofindividualsastheyageregardlessofinitialcognitivefunction

•  Highlydynamicprocesswithvariabilitywithinandbetweenindividuals

•  Includescognitivedomainsthatmaynotchange,maydecline,ormayactuallyimprovewithaging,andthereisthepotentialforolderadultstostrengthensomecognitiveabilities

•  Onlynowbeginningtobeunderstoodbiologicallyyetclearlyinvolvesstructuralandfunctionalbrainchanges

ALifeCourseApproachtoAgingandCognitivePerformance

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Proportionsofpeopleages65andolderwithmoderateorseverememoryimpairmentversusnoormildmemoryimpairment

Health and Retirement Study, United States, 2002. SOURCE: FIFARS (Federal Interagency Forum on Aging-Related Statistics). 2004. Indicator 17: Memory impairment.

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DifferenceinSomeDomainsofCognitiveFunctionbyAge(MIDUSII,N=4,268,UnitedStates,2004-2006)

SOURCE: Lachman, M. E. 2014. Monitoring Cognitive Functioning: National Survey of Midlife in the United States (MIDUS). Presentation given to the IOM Committee at the April 2014 workshop.

DifferencesinCognitiveFunctionbyAgeBasedonDifferentCognitiveTests,MIDUSII,

N=4,268

SOURCES: Lachman, M. E., and P. A. Tun. 2008. Cognitive testing in large-scale surveys: Assessment by telephone. In Handbook of Cognitive Aging: Interdisciplinary Perspectives, edited by S. Hofer and D. Alwin. Thousand Oaks, CA: Sage Publishers. Lachman, M. E. 2014. Monitoring Cognitive Functioning: National Survey of Midlife in the United States (MIDUS). Presentation given to the IOM Committee at the April 2014 workshop.

Intra-individualchangesincognitionscoresovertime(randomsampleof500adults,ages50andolder)

SOURCES: McArdle, J. 2011. Longitudinal dynamic analyses of cognition in the health and retirement study panel. Advances in Statistical Analysis 95(4):453-480. McArdle, J. 2014. Cognitive measurements in the HRS/ADAMS surveys. Presentation given to the IOM Committee at the April 2014 workshop.

AssessmentofCognitiveAging

– Bestassessedwithinanindividualovertimesothatheorsheservesashisownnorm,thoughthisapproachincorporatespracticeeffects

– Needtoregularlyrevisitthenormsthatweusetostatisticallynormcognition

– CognitiveAgingisnotnormalagingorsuccessfulaging

ImplicationsOfTheDefinition

•  Asconceptsofdiseaseandsyndromeschange,cognitiveagingchanges– MCIwasoncenotMCI,notadiagnosis,sopriorcohortsthatdefinedcognitiveaginglikelyincludedpeoplewhohadMCIwhowouldnotbeincontemporarycohorts

•  Overtime,thenormschange;theyshouldchange•  Yetweoperationalizedefinitionsandreifywhatisadynamicprocess.

Howlongisafoot?Thenatureofoperationaldefinitions

BrainChangeswithCognitiveAging

•  Humanandanimalstudies•  Mechanismsofcognitiveaging:•  -Geneticsundoubtedlyplayarolebutspecificgenetic

associationshavenotasyetbeenidentified.– Decreasesinneuronalfunction,notnumber

•  Declinesinsynapticnumber•  Declinesinsynapticfunction•  Decreasedfunctionofmyelinsheaths

– Neurotransmitterchanges•  DeclineinAMPAreceptorassociatedwithmemoryandsynapticplasticity 16

DeclinesinSynapticIntegrity

•  Studiesonnon-humanprimates

•  Specificclassesofdendriticspineslostindorsolateralprefrontalcortex

•  Thesespinesareveryimportantforsynapticplasticity

•  Losscorrelateswithdeclinesinworkingmemory

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WhataresomeFunctionalMeasuresReflectingCognitiveAging?(IADLs)

•  Fillingoutyourtaxform•  Downloadingandusinganapp•  Renewingyourdrivers’licenseandtagsonline•  Preparingamealfromarecipe•  GoingfromTerminal1toTerminal2atO’Hare•  Servingonacommitteeforavolunteersocialgoal•  Fixingaminorapplianceproblem•  Adaptingtochallengingpersonal,socialsituations•  PreparingPowerPointslides

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PersonalAdaptationstoCognitiveAging(Examples)PsycholAssessment17:168

•  “External”Behaviors–  Shoppinglists–  Bookmarks–  Notebirthdays–  Telephonenumbers

•  “InternalBehaviors– Memorytricks–  Thinkaboutaplan–  Linkoldandnew– Mentalimages

•  “Reliance”–  Askforhelptoremember________

•  “Time”–  Slowdownspeech–  Readmoreslowly

•  “Effort”–  Inconversation–  Concentration–  Tryinghardtoremember

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RiskFactorsforCognitiveAging

•  Factorswhichmayacceleratethedecline•  Factorswhichmaybeopentointervention.

Earlier“LifeCourse”RiskFactorsandConditions

•  Educationaldevelopment(thoughaugmentedbypersonalactivitiessuchastripstothelibrary[inthepast])

•  Adversechildandadolescentexposures

•  Childandearlyadultmental/psychologicalconditions(e.g.,anxiety)

•  Potentialoccupationalandotherenvironmentalexposures(e.g.,workingincognitivelynon-challengingoccupations)

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ImportanceofBehavioralConditionsasaWindowintoSubsequentCognitiveProblems

Behavioralconditions:-AttentionDeficitHyperactivityDisorder-Languagedisorders/Dyslexia-AutismSpectrumDisorder -Conductdisorders-SubstanceAbuse

Otherchildhoodandadultpsychiatricdisorders:-Depression -Eatingdisorders-Gambling-anxiety,negativeaffect,hostility,pessimism,hopelessness,andperceivedconstraints 22

ExternalContributorstoCognitiveAging

•  Inprocessofnormalaging,olderadultsareexposedtomanyfactorswhichmayacceleratecognitiveaging:

•  Thesefactorsareknowntocontributetocognitivedysfunction.

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Ref:HHS,ProfileofOlderAmericans,2013

HospitalizationasaRiskforCognitiveDecline

Nearlyeveryolderadultwillexperienceatleastoneacuteillness,surgery,orhospitalizationNearly1/4of65+agegroupwillbehospitalizedeachyear.Thatnumberincreaseddramaticallyforthe85+agegroup.Thefrequencyofdeliriumamongthosehospitalizedis25%(Inouyeetal,1993)

ImpactofHospitalization

WilsonRSetal.Neurology2012;78:950-56 25

ExternalContributorstoCognitiveDecline• Medications(psychoactive)

• Anticholinergics• Polypharmacy

• Vascularriskanddisease(cerebro-andcardio-vascular)

• Hospitalizations• Acutemedicalillness• Majorsurgery• Intensivecareunitstay

• SeriousInfections• Alcoholabuse

• Multimorbidity:• Hypertension• Diabetesmellitus• Chronicrenaldisease• Cancer• Thyroiddisease

Hearingloss • Depression• Visionloss • Headtrauma

• Sleepdisorders,sleepapnea • Geneticfactors26

MedicationsandCognitiveDecline

•  Olderadultsareprescribed14drugsperyearonaverage

•  Highriskmedsincludeanticholinergicdrugs,benzodiazepines,andsedative/hypnotics.

•  20–50%onanticholinergicdrugs(associatedwithcognitiveimpairment)

•  Potentanticholinergicsandover-the-counterantihistaminessuchasdiphenhydramine(Benadryl)especiallyarisk

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Whatarepeopledoingtointerveneincognitiveaging?

-Computerizedbraingames-Drugs(incl.caffeine)-Stimulants:(methylphenidate/amphetamines)-Transcranialelectricstimulation-Nootropics(SeeScience350:379)

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EvidencedBasedMessagesforCliniciansandthePublic

Messaging

RecommendationstoIndividualsandFamilies

RecentStudiesofInterventionforCognitiveAging

•  Sprint-Mind-IntensiveBPcontrolsignificantlyreducedtheriskofmildcognitiveimpairment(14.6vs18.3casesper1000person-years(JAMA,2019)

•  PooledanalysesofMediterraneanDiet-Fifteencohortstudieswith41,492participantsand2RCTswith309and162participantsininterventionandcontrolgroups,respectively,wereincluded.Theprimaryoutcomeofinterestwascognitivefunction,dividedintodomainsofmemoryandexecutivefunction.Meta-analysisofcohortstudiesrevealedasignificantassociationbetweenMeDiandolderadults'episodicmemoryandglobalcognitionbutnotworkingmemoryorsemanticmemoryMeta-analysisofRCTsrevealedthatcomparedwithcontrols,theMeDietimproveddelayedrecallworkingmemory,andglobalcognition.(McEvoyetal,2017)

•  Sleep–nappingtimemaybeassociatedwithincreasedcognitivedecline.(Lengetal,2019

BrainStimulationActivities(BrainGames)•  Noquestionthatifmostpersonspracticeusingbraingames,theywillimproveinfunctiononthegames.

•  Brainstimulationgameshavenotasyetbeendemonstratedto–  Transfertoeverydayactivitiesovertime– MaintaingainsovertimeoncethegamesarenolongerplayedBraingamesdocomewithacost

AsmallbutforsomesignificantfinancialcostAnxietyoverperformanceonthegameandcomparisonwithothers.

TheACTIVEStudy(Reboketal,2014)

•  Nearly3000subjectsfollowedforuptotenyears•  Computerizedbraingamescoupledwithgroupinteractionandinstruction

•  Associatedwithboostersessions

•  CognitivetrainingresultedinlessdeclineinADLs.

•  Reasoningandspeedtrainingimpactfounduptotenyears.