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