Formal Literature Search - Cog. Neurorehab

CristinaCurcelliJuly2015

LiteratureSearch:CognitiveNeurorehabilitationinnon-CNSCancerSurvivorsABSTRACTResearchinthefieldofcancersurvivorshiphaslongacknowledgedincreasedcognitivedysfunctioninpatientswithcentralnervoussystem(CNS)cancers.However,inrecentyears,moreresearchhasbeendedicatedtonon-CNScancerpatientsandtohowboththediseasesthemselvesandvarioustreatmentsimpactpatients’cognitivefunction.Withanincreasedunderstandingoftherelationshipbetweencancerandcognitivefunction,someresearchershaveturnedtowardthecognitiveneurorehabilitationofcancersurvivors.Thispaperreviewsexistingstudiesandliteratureoncognitiverehabilitationinanattempttosynthesizeandidentifythemethodsthathaveyieldedthemostsuccessforimprovingcancerpatients’cognition. INTRODUCTIONSurvivorsofcancerhavereporteddifficultywithcognition,andagrowingbodyofresearchsupportstheseself-reportedfindings.Therecontinuestobeincreasingevidenceofactualinjurytothebrainafterchemotherapy,particularlytotheprefrontalcortex,whichisassociatedwithexecutivefunction1.

Manydifferentrehabilitationtacticshavebeenusedtotrytotreatthecognitivedifficultiesassociatedwithcancer.Pharmacologicalagents,notablystimulantssuchasmethylphenidateandmodafinil,havebeenusedinanattempttotreatcognitivedifficulty,thoughnopharmaceuticalhasbeendevelopedspecificallyforcognitivedifficultyrelatedtocancer.2Manyresearchershaveapproachedtheissuewithcognitiverehabilitationinterventions,examiningdifferentpossibilitiestoimprovesurvivorsfunctionastestedbyself-reportsandneuropsychologicalbatteries.

Growingevidencesupportsthatcognitivetherapyholdsthemostpromisefortreatingcognitivedysfunctionassociatedwithcancerpatients–onesystematicreviewfoundcognitivetherapydeliveredafterbreastcancertreatment,withafocusonimprovingverbalmemory,attention,andprocessingspeed,tobemosteffective.2 REVIEWOFCLINICALTRIALSANDFINDINGS Researchexclusivetobreastcancerpatients Studiesoncognitiveneurorehabilitationinnon-CNScancersurvivorshaveoftenfocusedexclusivelyonbreastcancerpatients.Ercoli,Petersen,etalevaluateda5-weekgroupcognitiverehabilitationintervention,withone2-hoursessionaweek.Theinterventionwasfirstpilotedforfeasibility,andthenimplementedinarandomizedstudyof48breastcancersurvivors:32assignedtothecancerrehabilitationgroup,and16assignedtoawaitlistcontrolgroup.Theinterventiontargetedattention,executivefunction,andmemoryfunctioninagroupsetting,withamixofpsychoeducation,techniqueinstruction,andin-classandat-homeexercisesbetweeneachsession.TheprimarymeasureforsubjectivecognitiveimprovementwasthePatients’AssessmentofOwnFunctioning(PAOFI).AdditionalobjectivemeasuresincludedtheReyAuditory-VisualLearningTest(RAVLT),theTrailMakingTest(TMT),theBriefVisualMemoryTestRevised(BVMT-R),amongothermeasures.3


Bothsubjectiveandobjectivemeasuressuggestedimprovementintheinterventiongroup,ascomparedtothewaitlistgroup.RAVLTtotalanddelayedrecallscoresshowedstatisticallysignificantimprovements,alongwiththeself-reportedPAOFIscores.

AstudyconductedbyFerguson,McDonaldetalexaminedasimilarly-sizedandcomposedpopulationofbreastcancersurvivors,butwithadifferentinterventionapproach.Theseresearcherslookedattheefficacyofacognitive-behavioraltherapyprogramcalledMemoryandAttentionAdaptationTraining(MAAT).ThisCBTprogramwasevaluatedinatwo-grouprandomizedclinicaltrial,with40stageIandIIbreastcancerpatientswhohadreceivedchemotherapy,dividedintoaninterventionMAATgroupandawaitlistcontrolgroup.ThemaindistinctionbetweentheMAATprogramandothercognitiveskillstraining-orientedneurorehabilitationisMAAT’sfocusoncompensatorystrategyratherthanmentalexercise.Thesestrategieswereaimedto“lessenthenegativeconsequencesofcognitivefailure.”4Eachofthefourin-personofficevisitsconsistedofreviewingcurrentfindings,self-awarenesstraining,andrehearsalofcompensatorystrategies. MAATwaspilotedfiveyearsbeforethisstudyon29breastcancersurvivorswhohadreceivedchemotherapyandreportedcomplaintsregardingmemoryandattention.Thepilotstudyparticipants(all29participatedinMAAT)showedimprovementsinself-reportofcognitivefunction,qualityoflife,andtestperformance.Researchersfoundtheseindicators,alongwithahighrateofsatisfactionamongparticipants,warrantedfurtherstudyandevaluationofsurvivors.5 Inthetwo-armedstudy,self-reporteddailycognitiveproblems,asmeasuredbytheMultipleAbilitySelf-ReportQuestionnaire(MASQ),didnotexperienceastatisticallysignificantlychangeintheMAATgroup.Therewasanimprovementinself-reportedspiritualwell-beingsubscaleofqualityoflife,measuredwiththeQualityofLife-CancerSurvivors(QoL-CS).Participantswereevaluatedforverbalmemory,withCaliforniaVerbalLearningTest-II,andprocessingspeed,usingavarietyofmeasures.Noneofthemeasuresofprocessingspeed,unlikeintheErcolistudy,whichalsousedtheTrailMakingTest,sawstatisticallysignificantimprovement.Verbalmemory,intheCVLT-II,didimproveintheMAATgroup.ResearchersconcludedthatthoughtheMAATCBTshouldstillberefinedfurther,itmeritsadditionalstudiesbedoneusingMAAT’scompensatorystrategy. Incontrasttothisfocusoncompensatorystrategy,adifferentstudyofasimilarcompositionexaminedtheeffectsofanentirelycomputerizedexecutivefunctiontrainingprogramforbreastcancersurvivors.Kessler,Hosseinietaladministeredanonline48-hourtrainingprogramtobecompletedover12weeks,inacontrolled,randomizedstudyof41totalbreastcancerpatients.Theexercises,focusedonthedomainsofcognitiveflexibility,workingmemory,processingspeed,andverbalfluency,adjustedtothe21activeparticipantsperformanceandgaveongoingfeedback.TheprimaryobjectivemeasureforthisstudywastheWisconsinCardSortingTest,ameasureofcognitiveflexibility.ThetraininggroupshowedsignificantimprovementcomparedtothewaitlistgroupontheWCST,aswellastrendingimprovementsinotherobjectivemeasures,andsignificantimprovementinself-ratedexecutivefunction.Researchersinterpretedtheseresultsasindicatorsofimprovedcognitiveflexibility,processingspeed,andverbalfluencyintheactivetraininggroup,andthepotentialforsuchimprovementtooccurasaresultofcognitiveexercise.6 Narrowingthefocusoftraininginterventions:Vohnetal;Poppelreuteretal Onetraining-basedrehabilitationstudyexaminedtwodistinctlydifferentformsofcognitivetraining:onegroupwasassignedtomemorytraining,memoryandprocessingspeed.About30breastcancersurvivorswhohadundergonechemotherapywereassigned


toeachgroup,andanadditionalcontrolgroupof30survivorswasalsocreated.ThememorytraininggroupwasadaptedfromACTIVE,advancedcognitivetrainingforindependentandvitalelderly.During10one-hoursessionsover6to8weeks,participantsweretrainedwithanemphasisonmemorystrategy,suchasmeaningfulness,organization,visualization,andothers.Thespeedofprocessingtraining,entirelyseparatefromthememorygroup,consistedofcomputerizedexercisesfromInsight,whichadjustdifficultybasedonparticipants’performance.7ThoughthecommercialprovidersdifferedbetweenthisspeedofprocessingtrainingandKessleretal’sexecutivefunctiontraining(Insight,andLumos,respectively),structureandcontentoftheprogramsharedmanysimilarities. TheadaptedACTIVEmemorytrainingprogramparticipantsdisplayedimprovedimmediateanddelayedmemoryatatwo-monthpost-interventionvisit(measuredbyReyAuditoryVisualLearningTest,RAVLT),andimprovementinself-reportedcognitivefunctionbasedonFactCog,ameasureofperceivedcognitivefunctiondesignedspecificallyforcancerpatients,atboththe2-monthandpost-interventionassessments.ThespeedofprocessingtraininggroupexperiencedimprovementinprocessingspeedasmeasuredbyUsefulFieldofView(UFOV).7

Besidesthesesomewhatexpecteddomain-specificimprovements,though,participantsintheInSightspeedofprocessingtrainingalsoexperiencedimprovementsontheRAVLTandRivermeadeBehavioralParagraphRecall(measuresofmemory).Theirperceivedcognitivefunction,likethememorygroup,alsoshowedimprovement,andprocessingspeedparticipantsfurthershowedsignificantlylowereddistress.Becauseofthiscross-cognitivedomainimprovement,theresearchersinterpretedthespeedofprocessingtrainingtohavebroadercognitiveeffects.

Poppelreutueretalexploredtwodifferenttrainingprogramsusingaverysimilarmodeltothis.Inastudywithbreastcancerin-patients,34patientswereassignedtoacomputerized(PC)traininggroup,33patientswereassignedtoneuropsychological(NP)training,and25actedascontrols.ThePCgroupcompletedcomputerizedexercisesundersupervision,withtheexercisesadaptingtotheindividual’sresponses.TheNPTgroupparticipatedinsessionsheldbytherapists,coveringabreadthofinformationonmemoryandattention.8However,unlikeVohnetal’smemoryandspeedofprocessingtraininggroups,thePCandNPTgroupsdidnotachieveanymoreimprovementthanthewaitlistcontrolgroup–allparticipantsshowedsignificantimprovement,sonointerventioneffectscouldbeproven.Researcherssuggestedtheoveralltrendinimprovementwasduetothenatureofin-patientrehabandthenaturalrecoverythatfollowstherapy.Anotherpossiblefactorcouldhavebeenpracticeeffects.Theresults,researcherssuggest,likelyspeakmoretothetimingofintervention,andthenon-necessityofcognitivetrainingdirectlyaftertherapy,thantheydototheactualinterventionorpossibilityofpracticeeffects.8 Othertypesofnon-CNScancers

Studiesextendingtosurvivorsacrossdifferenttypesofcanceraresomewhatmorelimited,thoughgenerallynotcontradictory,toresearchinvolvingonlybreastcancerpatients.Furtherresearchneedstobedone,though,todeterminehowtospecializetrainingsandoptimizeefficacybasedoncancertype.

Onecognitiverehabilitationinterventionforsurvivorsofallcancertypesinvolved4weeksofgroupmeetings.Thisstudypilotedaweekly,smallgroupintervention,emphasizingpsychoeducationandskillstraininginvolving.Cognitivefunctionwasmeasuredobjectively(usingRepeatableBatteryforAssessmentofNeuropsychologicalstatus,RBANS,andTMT)andsubjectively(MASQandFactCog).Thisstudyhadavarietyoflimitations,suchassmallsamplesizes,uneventestandcontrolgroups,andperhapsnot


enoughinclusioncriteria(somesurvivorsstartedorfinishedinnormalrangeofcognitivefunctioning).However,researchersfoundimprovementsinobjectivemeasuresofvisuospatial/constructionalperformance,immediatememory,anddelayedmemory,accordingtotheobjectiveRBANSmeasure.TheMASQdidnotshowsignificantself-reportedimprovement.9

Thisintervention,afterbeingpilotedinthisprimarystudy,wasthenintroducedintoagroupof29non-CNScancersurvivors,dividedbetweena“ReCog”interventiongroupandawaitlist,andcomparedagainst16communitycontrolparticipants.Eachofthefour,two-hoursessions,modeledoffthepilotedstudyinterventionhadcomponentsofpsychoeducation,groupdiscussion,skilldevelopment,andapplication.Theprimarymeasuresofcognitivefunctionincluded:theRBANStest,measuringobjectivecognitivefunction;theTMT;theFACT-Cog3,measuringperceptionofcognitivefunction,andtheBriefAssessmentofProspectiveMemory(BAPM)toassesssubjectivemeasures(perceptionofcognitiveimpairment,qualityoflife,andmemory).Avarietyofpsychosocialmethodswerealsousedassecondarymeasures.10However,unlikethepilotstudy,theRBANSmeasuredidnotshowstatisticallysignificantimprovementamonginterventionparticipants.InterventionparticipantsimprovedonTMTA,suggestingtheReCoginterventiontobebeneficialforprocessingspeed,visualscanning,andnumericsequencing.ThisresultalignswiththefindingsofFergusonetalinthestudyconcerningtheMAATprogram.4

SubjectivemeasuresintheReCoginterventiongroupshowedimprovementagainstthewaitlistgroupforperceivedcognitiveabilitytestedinFactCOG,butmeasuresofprospectivememorydidnotshowsignificantchange(contrastingwiththeresultsofthepilotedstudyofthisintervention,whereMASQscoresshowedimprovementinmemoryininterventionparticipants,thoughadifferenttestwasusedtoevaluatethis).Therewasalsoanimprovementincognitiveself-efficacy(CSE)amonginterventionparticipants.Researchersrecognizedthelimitsofasmallsamplesize,amongothers,inthisstudy.10 Cherrieretalexaminedasimilarlytargetedprogramina28-participantstudyofsurvivorsofvariouscancertypes.The12-membertreatmentgroup,beingcomparedtothe16-personcontrolwaitlist,participatedinaone-houraweek,7weeklongintervention,withhomeworkin-betweensessions,focusingonmemoryaids,memoryskills,andmindfulness.Thesmallsamplesizeagainlimitedthestatisticalpoweroftheresults,butimprovementinthetreatmentgroupwasseenasmeasuredbytheFactCogself-reportingmeasure,andcertainsubtestsfromtheWeschlerAdultIntelligenceScalemeasuringattention.11 DIRECTIONFORFUTURERESEARCH

Smallsamplesizesarerecognizedasoneofthegreateststatisticalweaknessesofstudiesofcancersurvivorsexperiencingcognitivedysfunction.Despitemanyofthesameinterventiontechniques(psychoeducation,computerizedtraining)andsimilarneuropsychologicalmeasures(RAVLT,TMT,FactCog)beingusedacrossstudies,resultsfromoneinterventiontothenextshowlittleconsistency.However,amajorityofcognitiverehabilitationstudieshaveshownsomeobjectiveorself-reportedimprovementsinnon-CNScancersurvivors’cognition.Domain-focusedtrainings,suchasVohnetal’smemory/speedofprocessingtraininggroups,suggeststhatexerciseofsomedomainsmayleadtospecificbenefits,andexerciseofotherdomainstomorewidespreadbenefits.7

Specializedinterventionprogramssuchastheaforementionedmemory/speedofprocessingtrainingsstudy,orPoppelreuteretal’sPC/NPTtrainings,offerinsightthatwouldallowresearcherstodeterminethetypesofinterventionsthatbesttargetimpairedcognition.Computerizedtrainingprogramsinparticular,suchasInSightorLumos6,7,8,warrantfurtherresearchforavarietyofreasons:theconvenienceoftheinterventioncould


potentiallyincreasesamplesizes,inturnallowingformorestatisticallypowerfulresults;thecomputerizationallowsforeasytrackingofparticipants’progressandconsistentparticipationinthestudy—anotherareainwhichalready-smallstudiesstruggletomaintainnumbers;andtheadvantageofhavingimmediatefeedback,sotheexercisescanbeadjustedtoparticipants’performances.


References

1. KeslerSR,KentJS,O’HaraR.PrefrontalCortexandExecutiveFunctionImpairmentsinPrimaryBreastCancer.ArchNeurol.2011;68(11):1447-1453.

2. MoreanDF,O’DwyerL,CherneyLR,TherapiesforCognitiveDeficitsAssociatedwithChemotherapyforBreastCancer:ASystematicReviewofObjectiveOutcomes,ArchivesOfPhysicalMedicineAndRehabilitation(2015),doi:10.1016/j.apmr.2015.05.012.

3. Ercoli,L.M.,Petersen,L.,Hunter,A.M.,Castellon,S.A.,Kwan,L.,Kahn-Mills,B.A.,Embree,L.M.,Cernin,P.A.,Leuchter,A.F.andGanz,P.A.(2015),Cognitiverehabilitationgroupinterventionforbreastcancersurvivors:resultsofarandomizedclinicaltrial.Psycho-Oncology,doi:10.1002/pon.3769.

4. FergusonR,McDonaldB,SaykinA,etal.DevelopmentofCBTforchemotherapy-relatedcognitivechange:resultsofawaitlistcontroltrial.Psycho-Oncology[serialonline].February2012;21(2):176-186.

5. FergusonR,AhlesT,MottL,etal.Cognitive-behavioralmanagementofchemotherapy-relatedcognitivechange.Psycho-Oncology[serialonline].August2007;16(8):772-777.

6. KeslerS,HosseiniSMH,HecklerC,etal.CognitiveTrainingforImprovingExecutiveFunctioninChemotherapy-TreatedBreastCancerSurvivors.Clinicalbreastcancer.2013;13(4):299-306.doi:10.1016/j.clbc.2013.02.004.

7. VonAhD,CarpenterJS,SaykinA,etal.Advancedcognitivetrainingforbreastcancersurvivors:Arandomizedcontrolledtrial.BreastCancerResTreat.2012;135(3):799-809.

8. M.Poppelreuter,J.Weis,H.H.Bartsch.Effectsofspecificneuropsychologicaltrainingprogramsforbreastcancerpatientsafteradjuvantchemotherapy.JPsychosocOncol,27(2009),pp.274–296.

9. SchuursA,GreenH.Afeasibilitystudyofgroupcognitiverehabilitationforcancersurvivors:enhancingcognitivefunctionandqualityoflife.Psycho-Oncology[serialonline].May2013;22(5):1043-1049.

10. KingS,GreenHJ.PsychologicalInterventionforImprovingCognitiveFunctioninCancerSurvivors:ALiteratureReviewandRandomizedControlledTrial.FrontiersinOncology.2015;5:72.

11. CherrierMM,AndersonK,DavidD,etal.ARandomizedTrialofCognitiveRehabilitationinCancerSurvivors:APreliminaryStudy.Lifesciences.2013;93(17):10.1016/j.lfs.2013.08.011.doi:10.1016/j.lfs.2013.08.011.

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Formal Literature Search - Cog. Neurorehab