ScienceBackgrounderonCancer–RelatedCognitiveDeclineStudy Introduction.Thisscience“backgrounder”isintendedtofitthefindingsinthenew Cancer–RelatedCognitiveDeclineStudy1intowhatisalreadyknowninabroaderliterature onplasticity-basedbraintraining. Thereisahugeamountofnewbrainsciencebeingpublishedeveryday–morethan18,000 journalarticlesonthesub-specialtyofbrainplasticityhavepublishedinthepastfiveyears. Noonecanbeanexpertandup-to-dateonallofit.An“expert”inoncologyorinpsychiatry orpsychologymayhavelittleknowledgeofrecentfindingsinbrainplasticityorinitssubspecialtyofplasticity-basedbraintraining–whichisthesub-sub-specialtythatisproducing thesenewresults.Afterreadingthis“backgrounder”youwillknowasmuch(oroftenmore) abouttherelevantliteraturethanmanyoftheexpertsyoumightinterview.Ifyouskipto theend,youcanreadaboutcommonmisconceptionsthatmaybeprevalentamongeven expertswhohavenotreadorbeenbriefedontherecentliterature,andyoushouldbebetter positionedtomakesenseofthisfieldforyouraudience. Thisbackgrounder(1)beginswithadescriptionoftheCancer–RelatedCognitiveDecline Study;(2)reviewstheperformanceofthistypeoftraininginpreviouslyreleasedstudieson thiscondition(3)describeshowthistypeoftrainingisdesignedandthoughttoimpactthe brain;(4)reviewstheperformanceofthistypeofbraintraininginpreviouslyreleased studiesinotherconditions;and(5)clarifiessomemisconceptionsandsuggestssometakeawaysregardinghowtheseresultsfittheliteratureandmayadvancethefield. 1.DescriptionofCancer–RelatedCognitiveDeclineStudy.Thestudydescribedinthe article,whichwasjustpublishedintheJournalofClinicalOncologyentitled“Evaluationofa Web-BasedCognitiveRehabilitationPrograminCancerSurvivorsReportingCognitive SymptomsAfterChemotherapy”(“CRCDStudy”)wasdesignedasapragmatic,longitudinal, randomizedcontrolledtrial.Itextendspriorworkdoneusingcognitivetrainingamongthis populationinamorecloselyadministeredsetting(seemorebelowonpriorwork). PragmaticTrial.“Pragmatic”trialsaredesignedtoevaluatetheeffectivenessof interventionsin“real-world”conditions.Here,thetrialwasdesignedtoreachpatientsat home,usingassessmentsandtrainingthatcouldbeperformedwithoutdirectsupervision. StudyParticipants.Theresearchersrecruited242adultcancersurvivors,through18 Australiansites,whohadbeentreatedforaprimary(non-CNS)malignancy,whohad completedatleastthreecyclesofadjuvantchemotherapyintheprior6-60months,and whoreportedpersistentcognitivesymptoms.Participantswererequiredtobefluentin Englishandtohaveaccesstoacomputerandtheinternet.Oftheparticipants,95%were female.Onaverage,ithadbeen27monthssincetheircompletionofchemotherapy,and theiraverageagewas53(withanagerangeof23to74).Some89%hadbreastcancer,5% hadcolorectalcancer,andthebalancewasdistributedacrossothercancers. Randomization.Thestudyparticipantswererandomizedintoacontrolgroupandan interventiongroup.Beforerandomization,allsubjectsparticipatedina30-minute structuredtelephoneconsultationoutliningcognitivecompensatorystrategiesforcognitive decline.Thecontrolgroup(of121participants)receivedstandardcarefromtheir healthcareprofessionals.Theinterventiongroup(of121participants)alsoreceived standardcare,andeachgroupmemberwasaskedtocomplete40hoursofbrainexercises overthecourseof15weeks(at40minutespersession,4timesperweek). 1 Eachparticipantwasmeasuredonaprimaryandanumberofsecondaryoutcomemeasures (seebelow)atthebeginningofthestudy,after15weeks,andsixmonthslater. PrimaryOutcomeMeasure.Theprimaryquestionofthestudywaswhetheruseofthese specificbrainexerciseswouldlessenapatient’sexperienceofnegativecognitivesymptoms. Theexerciseshadthateffect. Morespecifically,theaprioriprimaryoutcomemeasureforthisstudywasself-reported cognitivefunction,asassessedbytheFACT-COGquestionnaire,PerceivedCognitive Impairment(PCI)subscale.TheprimaryoutcomescorewastheFACT-COGPCIscore,as measuredimmediatelyaftertraining. Researchersreportedthattheinterventiongroup,ascomparedtothecontrolgroup, reportedsignificantlybetterperformanceonthePerceivedCognitiveImpairmentmeasure (theprimaryoutcomemeasure:FACT-COGPCI)immediatelyaftertheintervention (p<0.0001),andsixmonthslater(p<0.0002). SecondaryOutcomeMeasures.Thestudyestablishedanumberofsecondaryoutcome measures.Themainsecondaryoutcomemeasurewasneuropsychologicalfunction,as assessedbyCogstate(an18-minutecomputerizedbatterythatcanbedownloadedandselfadministered,athome).Theothersecondaryoutcomemeasureswerewidelyusedand validatedself-assessmentquestionnaires,including:anxiety/depression(12-itemGeneral HealthQuestionnaire),qualityoflife(FACT-General),fatigue(FACT-Fatiguesubscale),and stress(14-itemPerceivedStressScale).Theother(non-PCI)subscalesoftheFACT-COG werealsousedassecondarymeasures. Becauseofthemultiplesecondarymeasuresexplored,thesecondarymeasureswereheldto amoreconservative99%confidenceintervalforsignificance,ratherthanthe95% confidenceintervalnormallyused. Thecomputerizedneuropsychologicalassessment(Cogstate)showednobetweengroup differenceaftertrainingorsixmonthslater.Abouthalfofparticipantsdidnotcompletethe Cogstateassessment. Theinterventiongrouphadsignificantlybetterperformanceonmostofthesecondary measures,includingonthestressmeasureafterinterventionandatsixmonths;onthe fatigueandanxiety/depressionmeasuresaftertrainingandwithatrendtobetter performanceatsixmonths;onthequalityoflifemeasureatsixmonths,butnot immediatelyaftertraining;andonallFACT-COGsubscalesafterintervention,butonlyon someatsixmonths. TheBrainExercises.Theinterventiongroupusedfivevisualspeedofprocessingexercises distributedbyPositScience,andcommerciallyavailableaspartoftheBrainHQonlineand appbrainfitnesssubscriptionservice.TheexercisesthatwereutilizedappearonBrainHQ as: DoubleDecision HawkEye VisualSweeps EyeforDetail 2 TargetTracker TheseexercisesrepresentBrainHQ’scorevisualprocessingsuiteofexercises,targeting visualspeedandaccuracy(previouslymarketedastheInSightsuite,andincludingDouble Decision,whichisoftenreferredtointhescientificliteratureas“UFOV®training”or“speed training”). Morespecifically,theseexercisestargetvisualprocessingspeed,focus,suppression, selectiveattention,dividedattention,workingmemory,accuracy,acuity,search,usefulfield ofview,peripheralandcoreattention,direction,andmultipleobjecttracking. Thepatientsintheinterventiongroupwereaskedtocomplete40hoursoftraining.Usage levelsofthebrainexercisesvariedbypatient,withanaverageusageof25.08hours(anda rangeof0.19to55.82hours)inthe“intenttotreat”group.Some14%ofpatientsassigned totrainingneverstartedit,andtheremaining86%didjustover34hoursoftraining,on average. StudyConclusions:Theauthorsconclude:“Previousresearchhasshowncognitive rehabilitationstrategiestobefeasible,withpreliminaryevidenceofefficacy.OurlargeRCT [randomizedcontrolledtrial]addsweighttothisevidence,confirmingthattheuseof Insight[thevisualspeedexercises]ledtoanimprovementincognitivesymptoms. Importantly,therewerealsoimprovementsinPRO[patient-reportedoutcomes],including QOL[qualityoflife]andreductioninstress,fatigue,andanxiety/depression.Theprogram hastheadditionaladvantagesofbeingrelativelyinexpensiveandhomebased,allowing individualstodirecttheirowntreatment.Theprogramhasthepotentialtoprovideanew treatmentoptionforpatientswithcancerwithcognitivesymptoms,wherepreviously noneexisted.“[emphasisadded] 2.PriorResultsrelatedtoCancer–RelatedCognitiveDecline.Thisnewstudyextends workreportedin2012inthepaper“Advancedcognitivetrainingforbreastcancer survivors:arandomizedcontrolledtrial”publishedinthejournalBreastCancerResearch Treatment.2TheleadauthorofthatpriorpaperwasDr.DianeVonAh,andwerefertothat priorstudybelowasthe“VonAhstudy.” TheVonAhstudylookedat82breastcancersurvivors,randomizedintothreearms.The firstinterventionarmusedthesamefivevisualspeedofprocessingexercisesfromBrainHQ usedinthenewstudy;thesecondinterventionarmusedamemorytrainingprogramthat taughtstrategiesforremembering;andathirdarmwasawait-listcontrol.Each interventionwasadministeredtogroupsin10one-hoursessions,completedover6-8 weeks. Theprimaryoutcomeassessmentswereprofessionally-administered,objective neuropsychologicaltestsofmemoryandspeedofprocessing.Therewereanumberof secondaryoutcomemeasures,including:perceivedcognitivefunction,symptomdistress (mood,anxiety,fatigue)qualityoflife,andinterventionsatisfaction.Datawerecollectedat baseline,afterinterventionandata2-monthfollow-up. VonAhandcolleaguesfoundthatbothinterventionssignificantlyimprovedthedomainrelatedobjectivecognitiveperformance(i.e.,thememorytraininggroupgotsignificantly betteratmemoryteststhanthecontrol,andthevisualspeedtraininggroupgot significantlybetteratthespeedtestthanthecontrol).However,thespeedtraininggroup 3 showedtransfertomemory,withsignificanteffectsinmemory,aftertrainingandatthe2monthfollow-up,thatwerelargerthanthememorygroup.Bothinterventionshad significanteffectsonmostsecondarymeasuresatbothtimepoints,andwerefound satisfactorybyusers. TheVonAhstudyresultsledtoanewclinicalguidelinefromtheOncologicalNursing Societyrecommendingthiskindofbraintraininginagroupsetting (https://www.ons.org/practice-resources/pep/cognitive-impairment). Thenewstudyextendstheseresults,bymovingtoapragmatictrial,inwhichpatientsare askedtomakeuseoftheBrainHQinterventionontheirown,athome.Thisreflectsamuch lessexpensive,andmuchmorescalable,modeofdistributionandadministration. 3.Plasticity-basedTrainingDesignandMechanisms.Thevisualspeedtrainingusedin theCRCDandVonAhstudiesproducedpositiveresultsincognitiveandrealworld outcomes.Knowingwhatitdoesisnotthesameasknowinghowitdoesit. Tounderstandthemechanismsofaction,weturn,briefly,toratneurologyandanimal studiesabouthowspeedtrainingaffectsthephysiologyofthebrainasacomplexand interrelatedorgan. Brainplasticityresearchershavemeasureddozensofaspectsofthebrainsofhealthyyoung ratsandcomparedthemtothebrainsofolderandimpairedrats,notingthemanyphysical measuresbywhichthebrainsofimpairedratswereslower,lessprecise,haddiminished coordination,anddeterioratedneuralwiring.Instudies3,4theimpairedratsthenengagedin anhourofplasticity-basedspeedtrainingeachdayfor20days.Whenresearcherslookedat thebrainsofthetrainedratstheyfoundvirtuallyeveryphysiologicalmeasurementhad improved.Thetrainedratbrainhadtherestoredphysiologyandfunctionalitysimilartoa healthybrain.Brain-mappingrevealedimprovedspeedandprecision.Tissuesamples revealedincreasednumbersofspecificneuronalcelltypesthatcoordinatebrainactivity, andalsoheightenedlevelsofkeymarkersofneuralwiring. Whenthebraingetsnoisy(e.g.,fromaninjury,adisorderoradvancedaging)virtually everythingdegrades,andwhenitselementalfunctioningimproves,virtuallyeverything improves.Similarly,inhumansweseeplasticity-basedtrainingdrivesimprovementsin speedandprecision,inneuralcoordinationandinneuralwiring. Muchofoldschool,traditionalcognitivetraininghasfocusedontryingtofixaproblem eitherbyadoptingcompensatorystrategiesorbypracticingacognitivebehavior(ifyoujust trytomemorizethings,you’llsomehowrememberhowtohaveagoodmemory). Startingwithexperimentsinvolvingmemorizingpoems,thereisnowabout100yearsof scientificliteratureshowingthatmemorizingonethingdoesnotmakeyoubetterat memorizingthenextthing.Thisiswhy“experts”oftensaycognitivetrainingdoesnot transferorgeneralizebeyondthetasktrained. However,anewtypeofbraintrainingemergedinthe1990sfromtheanimal(andlater human)experimentsthatshowedthatthebrainremainsplastic,ormalleable,throughout life.Thisplasticity-basedbraintrainingfocusedonthemostelementalcognitivefunctions– byfirstimprovingthespeedandaccuracyofsensoryperceptions. 4 Improvedspeedandaccuracyofsensoryperceptionbecomesthefoundationforimproved attention.Improvedattentionisthebuildingblockofworkingmemory,andworking memoryisthebuildingblockofprettymucheverythingelse–immediatememory,delayed memory,executivefunction,reasoning,etc.Allofthestudiesusingthisapproachpointin thesamedirection–thatimprovingthespeedandaccuracyofelementalsensory perceptionhasbroadeffectsonthestructureandhealthofthebrainasaninterrelated organ. Putanotherway:braintrainingneedstobefocusedonimprovingspeedtomeetvarying realworldconditions;itneedstointensivelyandprogressivelyimproveaccuracy;itneeds tobeadaptingcontinuouslyandminutely(e.g.,bythousandthsofasecond)toeachperson’s performanceandability(basedonalgorithmsthatreviewallpriorexercisesresults);it needstobedesignedsothetaskgraduallygeneralizestorealworldexperience;itneedsto beengaginginamannerthatnaturallystimulatesneurotransmitters(chemicalsinthebrain thatenhanceattention,learningandmood)andthatbringsyoubacktodotheexercises againandagain.ThescientistsatPositSciencecallthesefiveprinciplesSAAGE–forSpeed, Accuracy,Adaptivity,GeneralizationandEngagement,andtheyareusedinthe developmentofplasticity-basedtraining(includingthefivevisualexercisesusedinthe studiesofcancersurvivors). 4.PriorResultsrelatedtoBrainInjuriesandOtherConditions. Chemobrainisatypeofbraininjury.BrainHQexerciseshavebeenfoundtohelpimprove variousmeasuresofcognitionandrealworldfunctioninmanypreviouslypublishedstudies ofothertypesofbraininjuries,includinginstudiesoftraumaticbraininjury5,6,stroke7,8,9,10 injuryduetochronicheartfailure(“cardiobrain”)11,12,13,14,15,andinjuryfromHIVinfection 16.,17,18. Inaddition,innumerousstudiesofhealthyolderadultsexperiencingnormal,age-related cognitivedecline,BrainHQexerciseshavebeenshowntoimprovecognitivemeasures(e.g., speed,attention,memory,executivefunction)19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37 andrealworldmeasures(e.g.,depressivesymptoms,locusofcontrol,self-ratedhealth, HRQoL,predictedhealthcarecosts,IADLsTIADLs,driving,balance,gait)38,39,40,41,42,43,44,45, 46,47,48,49,50,51. 5.SomeMisconceptionsandTake-aways. Misconceptions.Mostexpertswillnothavebeenbriefedontheseresultsbeforetheyare published.Becausetheyarebreakthroughresults,youmayhearsomecommentsfrom “experts”thatdonotmakealotofsensetosomeonefamiliarwiththerelevantliterature(as younoware).Suchcommentsmayinclude: “Cognitivetrainingisfilledwithconflictingresults.Thisisjustonestudy.“Thefieldof cognitivetrainingis,infact,litteredwithalotoffailure.Butcognitivetrainingisavery broadfield.Thiscommentisanalogoustosaying“somepillsseemtoworkandothers don’t.“Whenwelookattheefficacyofdrugswelookatindividualdrugsandatclassesof drugs.Weneedtodothesamewithcognitivetraining.Whenlookingattheseresultsthe referencepointisnotallcognitivetraining,itistheexercisesusedinthisstudyandsimilar 5 plasticity-basedbraintraining,whichtargetsimplicit(ratherthandeclarative)learning– thatis,learningtorefinesensoryperceptionandnotfact-basedorstrategy-basedlearning. “Theproblemwithcognitivetrainingisitnevergeneralizestoeverydaylife.”Inmostof traditionalcognitivetraining,users(atbest)getbetteratthetasktrainedandthoseeffects donot“transfer”or“generalize”tostandardcognitivemeasures,nortorealworldactivities. Asyou’vereadabove,theseparticularbrainexercises,andtheclassofplasticity-based training,hasbeenshownoverandoveragaintohavebothneartransfertoproximal cognitivemeasuresandfartransfertomeasuresofbehavioral,functionalandrealworld outcomes.Inthisstudy,theresearchersfoundtheexercisesnotonlyaffectedcognitive symptoms,butalsoshowedtransfertostandardbehavioralmeasuresofeveryday experience,includingonmeasuresof(i)anxiety&depression,(ii)qualityoflife,(iii)fatigue, and(iv)stress. “Theseresultswillneedtobeconfirmedinanotherstudy.”Thatisusuallyareasonable thingtosaywithbreakthroughresults-breakthroughclaimsrequiresubstantialsupport.In thiscase,thenewstudyisactuallythe…“anotherstudy.”TheVonAhstudy,discussed above,wasawell-runrandomizedcontrolledtrialwithtwocompetingcognitive interventionsandawait-listcontrol.Thatstudyreportarguedforalargerfollow-onstudy, whichhasnowbeencompleted,andwhichansweredtheadditionalquestionofwhether theseexercisescouldbeusedbypatientsontheirownathome.Also,asdiscussedabove, theseresults“fit”withsimilarresultsfromstudiesofbraininjuriesfromothersources. “Thisstudyonlyshowspositiveresultsonself-reportmeasures,soitcouldallbe placeboeffect.”Inordertorunthisstudyasapragmatictrial(discussedabove),the researchersreliedonself-reportquestionnairesandoneself-administeredonlinecognitive test.Alloftheself-reportquestionnairesarestandardinstrumentsthathavebeenusedin multipletrialsamongcancersurvivors.Thisstudyuseda“standardofcare”controlrather thananactivecontrol.However,thepriorstudy(theVonAhstudydiscussedabove)found BrainHQout-performedbothapassivecontrolandanotherintervention(memorystrategy training). “Thisstudydidnotshowasignificanteffectintheobjectivecognitivetest,soitdoesnot reallyhelppatients.”Thisstudyshowedasignificanteffectonitsprimarymeasure(selfreportedcognitivesymptoms).Ultimatelythatiswhatmatters–addressingpatientreportedsymptoms.Thestudyalsoshowedsignificanceonallsecondarymeasures,except theCogstatecomputerizedtest.Thestudyreportindicatesthatparticipantsfaced challengesindownloadingandtakingtheCogstateself-administeredcomputerizedtest.In fact47%ofparticipantsfailedtotakethetestatall,and57%failedtocompletethetestfor the6-monthfollow-up.Whenthestudywaspowered,itwasforapopulationmorethan twiceaslarge,yetatthesix-monthfollow-uptherewasatrend(p=0.09)toward significance.Inaddition,VonAhstudy,usedobjectivecognitiveteststhatwere administeredbyprofessionals(notself-administered).Asareminder,inthatstudy, researchersfoundthatbothinterventions(BrainHQspeedtrainingandthememory strategycourse)significantlyimprovedthedomain-relatedobjectivecognitiveperformance measure(i.e.,thememorytraininggroupgotsignificantlybetteratmemoryteststhanthe control,andthevisualspeedtraininggroupgotsignificantlybetteratthespeedtestthan thecontrol).However,thespeedtraininggroupshowedtransfertomemory,with significanteffectsinmemory,aftertrainingandatthe2-monthfollow-up,thatwerelarger thanthememorygroup. 6 Take-Aways.Whatdoesthisstudy(andtherelatedliterature)tellusaboutaddressing cancer-relatedcognitivedecline.Herearesometake-aways. 1. It’sbeenmorethan30yearssincebreastcancersurvivorgroupsraisedtheissueof cognitivedeclineassociatedwithcanceranditstreatment.Yet,theissueremains largelyunacknowledgedandcompletelyunaddressed.Thereisnowevidencethat somethingcanbedone. 2. Particularvisualspeedofprocessingbraintraininghasnowbeenshowneffectivein addressingthecognitivesymptomsthatareafrequentcomplaintofcancer survivorsintworandomizedcontrolledtrials:(1)anearlier82-personthree-arm randomizedcontrolledtrialin,whichtheseBrainHQexercisesweresuccessfully testedinaclassroomsettingagainsttraditionalmemorystrategytrainingina classroomsettingandagainstawait-listcontrol,and(2)apragmatic242-person trialagainstausualcarecontrol. 3. Thisstudydemonstratesapragmaticinterventionforcancer-relatedcognitive declinethatisreadilyavailable,scalableandinexpensive. Footnotes 1Bray,VJetal(2016)EvaluationofaWeb-BasedCognitiveRehabilitationPrograminCancer SurvivorsReportingCognitiveSymptomsAfterChemotherapy.JClinOncology 2VonAhDetal(2012)Advancedcognitivetrainingforbreastcancersurvivors:arandomized controlledtrial.BreastCancerResTreat.135(3):799-809. 3DeVillars-Sidanietal(2010)Recoveryoffunctionalandstructuralage-relatedchangesintherat primaryauditorycortexwithoperanttraining.Proc.Natl.Acad.Sci.107(31);13900-5 4ZhouXetal(2015)Behavioraltrainingreversesglobalcorticalnetworkdysfunctioninducedby perinatalantidepressantexposure.Proc.Natl.Acad.Sci.112(7);2233-8 5LebowitzMSetal(2012)Feasibilityofcomputerizedbrainplasticity-basedcognitivetrainingafter traumaticbraininjury.JRRD491547-1556 6VoelbelGetal(2014)Computerizedneuroplasticitytrainingincreasesprocessingspeedofverbal information:apilotstudyofadultswithtraumaticbraininjury.doi:10.13140/2.1.3405.3921. 7DeGutisJM,VanVleetTM(2010)Tonicandphasicalertnesstraining:anovelbehavioraltherapyto improvespatialandnon-spatialattentioninpatientswithhemispatialneglect.Front.Hum.Neurosci. 24;4.pii:60 8VanVleetTM,DegutisJM(2013)Cross-traininginhemispatialneglect:auditorysustainedattention trainingamelioratesvisualattentiondeficits.Cortex49,679–90. 9MazerBLetal(2001)UseoftheUFOVtoevaluateandretrainvisualattentionskillsinclientswith stroke:apilotstudy.AmJOccupTher.55(5):552-7. 10ChenCXetal(2015)Effectofvisualtrainingoncognitivefunctioninstrokepatients.IntJNursing Sciencesdoi.org/10.1016/j.ijnss.2015.11.002 11PresslerJetal(2011)Nurse-EnhancedMemoryInterventioninHeartFailure:TheMEMOIRStudy. JournalofCardiacFailure.17(10) 12PresslerSJetal(2013)Healthcareresourceuseamongheartfailurepatientsinarandomizedpilot studyofacognitivetrainingintervention.HeartLung.42(5)332-8 13EllisMLetal(2014)EffectsofCognitiveSpeedofProcessingTrainingAmongOlderAdultsWith HeartFailure.JAgingHealth26:4600-615 14AthilingamPetal(2015)Computerizedauditorycognitivetrainingtoimprovecognitionand functionaloutcomesinpatientswithheartfailure:Resultsofapilotstudy.Heart&Lung:JAcute& CritCare44(2):120-28. 15PresslerSJetal(2015)Nurse-enhancedcomputerizedcognitivetrainingincreasesserumbrainderivedneurotropicfactorlevelsandimprovesworkingmemoryinheartfailure.JCardiacFailure 21(8):630-41. 7 16VanceDEetal(2012)SpeedofProcessingTrainingWithMiddle-AgeandOlderAdultsWithHIV:A PilotStudy.JANAC23(6);500-10 17KaurJetal(2014)PredictorsofImprovementFollowingSpeedofProcessingTraininginMiddleAgedandOlderAdultsWithHIV:APilotStudyJNeurosciNurs.46(1):23-33 18CodySLetal(2015)Feasibilityofahome-basedspeedofprocessingtrainingprograminmiddleagedandolderadultswithHIV.JNeurosciNurs47(4):247-54. 19SmithGEetal(2009)Acognitivetrainingprogrambasedonprinciplesofbrainplasticity:results fromtheimprovementinmemorywithplasticity-basedadaptivecognitivetraining(IMPACT)study. JAmGeriatrSoc,57(4),594-603. 20BerryAS,etal(2010)TheInfluenceofPerceptualTrainingonWorkingMemoryinOlderAdults. PLoSOne,5:7,11537. 21MahnckeHWetal(2006)Memoryenhancementinhealthyolderadultsusingabrainplasticitybasedtrainingprogram:arandomized,controlledstudy.ProcNatlAcadSci103(33),12523-28. 22BallKKetal(1988)Ageandvisualsearch:expandingtheusefulfieldofview.JOptSocAmA, 5(12),2210-19. 23BallKetal(2002)Effectsofcognitivetraininginterventionswitholderadults:arandomized controlledtrial.JAMA,288(18),2271-81. 24VanceDetal(2007)TheAccelerateStudy:TheLongitudinalEffectofSpeedofProcessingTraining onCognitivePerformanceofOlderAdults.RehabilPsych;52(1):89-96. 25MahnckeHWetal(2006)Brainplasticityandfunctionallossesintheaged:scientificbasesfora novelintervention.ProgBrainRes,157,81-109. 26AndersonSetal(2013)Reversalofage-relatedneuraltimingdelayswithtraining.ProcNatlAcad Sci,doi:10.1073/pnas.1213555110 27VanceDEetal(2012)Speedofprocessingtrainingwithmiddle-ageandolderadultswithHIV.J AssocNursesAIDSCare,23(6):500-10 28WolinkskyFDetal(2013)ARandomizedControlledTrialofCognitiveTrainingUsingaVisual SpeedofProcessingInterventioninMiddleAgedandOlderAdultsPLoSOne8(5). 29RebokGWetal(2014)Ten-YearEffectsoftheAdvancedCognitiveTrainingforIndependentand VitalElderlyCognitiveTrainingTrialonCognitionandEverydayFunctioninginOlderAdults.JAm GeriatrSoc,62(1):16-24. 30O’BrienJL,EdwardsJDetal(2013)Cognitivetrainingandselectiveattentionintheagingbrain:an electrophysiologicalstudy.ClinNeurophysiol.124(11):2198-208. 31BelchiorPetal(2013)Videogametrainingtoimproveselectivevisualattentioninolderadults. ComputHumanBehav29(4):1318-24 32WolinskyFDetal.(2011)Interimanalysesfromarandomizedcontrolledtrialtoimprovevisual processingspeedinolderadults:theIowaHealthyandActiveMindsStudy.BMJOpen 2011;1:e000225doi:10.1136/bmjopen-2011-000225 33ZelinskiEMetal(2011)ImprovementinMemorywithPlasticity-BasedAdaptiveCognitive Training:Resultsofthe3-monthfollow-up.JAmGeriatrSoc.59(2):258-65 34StrenziokMetal(2014)Neurocognitiveenhancementinolderadults:Comparisonofthree cognitivetrainingtaskstotestahypothesisoftrainingtransferinbrainconnectivity.NeuroImage 85:31027–1039. 35MishraJetal.(2015)Neuralplasticityunderlyingvisualperceptuallearninginaging.JGerontolB PsychSciSocSci.2016;71(1):87-97. 36ClarkDOetal.(2015)Doestargetedcognitivetrainingreduceeducationaldisparitiesincognitive functionamongcognitivelynormalolderadults?IntJGeriatrPsychiatry.doi10.1002/gps.4395 37BamidisPDetal(2015)Gainsincognitionthroughcombinedcognitiveandphysicaltraining:the roleoftrainingdosageandseverityofneurocognitivedisorder.FrontAgingNeurosci. doi.org/10.3389/fnagi.2015.00152 38EdwardsJDetal(2002)Transferofaspeedofprocessinginterventiontonearandfarcognitive functions.Gerontology,48(5),329-40. 39EdwardsJDetal(2005).Theimpactofspeedofprocessingtrainingoncognitiveandeveryday performance.AgingMentHealth,9(3),262-71. 8 40WillisSLetal(2006)Long-termeffectsofcognitivetrainingoneverydayfunctionaloutcomesin olderadults.JAMA,296(23),2805-14. 41WolinskyFDetal(2006)TheeffectsoftheACTIVEcognitivetrainingtrialonclinicallyrelevant declinesinhealth-relatedqualityoflife.JGerontolBPsychSciSocSci,61(5)S281 42WolinskyFDetal(2006)TheACTIVEcognitivetrainingtrialandhealth-relatedqualityoflife: protectionthatlastsfor5years.JGerontolABiolSciMedSci,61(12),1324-29. 43WolinskyFDetal(2009)Theeffectofspeed-of-processingtrainingondepressivesymptomsin ACTIVE.JGerontolABiolSciMedSci,64A(4):468-72. 44WolinskyFDetal(2009)TheACTIVEcognitivetraininginterventionsandtheonsetofand recoveryfromsuspectedclinicaldepression.JGerontolBPsychSciSocSci,64B(5)577-85. 45WolinskyFDetal(2010)DoesCognitiveTrainingImproveInternalLocusofControlAmongOlder Adults?J.GerontolBPsychSciSocSci,Sep;65(5):591-8. 46WolinskyFDetal(2010)Speedofprocessingtrainingprotectsself-ratedhealthinolderadults: enduringeffectsobservedinthemulti-siteACTIVErandomizedcontrolledtrial.Int Psychogeriatr;22(3):470-8. 47RebokGWetal(2014)Ten-YearEffectsoftheAdvancedCognitiveTrainingforIndependentand VitalElderlyCognitiveTrainingTrialonCognitionandEverydayFunctioninginOlderAdults.JAm GeriatrSoc,62(1):16-24. 48Smith-RayRLetal(2014)ImpactofCognitiveTrainingonBalanceandgaitinOlderAdults.J GerontolPsychSciSocSci,doi:10.1093/geronb/gbt097. 49Smith-RayRLetal(2014)ARandomizedTrialtoMeasuretheImpactofaCommunity-Based CognitiveTrainingInterventiononBalanceandGaitinCognitivelyIntactBlackOlderAdults,Health EducBehav41:162S-69S. 50MorimotoSetal(2012)Neuroplasticity-basedcomputerizedcognitiveremediationfortreatmentresistantgeriatricdepression.IntJGeriatrPsychiatry.27(12):1239–47 51MRossLAetal(2016)Thetransferofcognitivespeedofprocessingtrainingtoolderadults’ drivingmobilityacross5years.JGerontolBPsychSciSocSci.;71(1):87. 9
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