Cognitive function and health-related quality of life four years after cardiac arrest

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Resuscitation

jo u r n al hom ep age:w w w . e l s e v i e r . c o m / l o c a t e / r e s u s c i t a t i o n

Clinical paper

Cognitive function and health-related quality of life four years after cardiac arrest ^夽

Eirik Alnes Buanes

, Arne Gramstad

, Karoline Kjellsdotter Søvig

, Karl Ove Hufthammer

, Hans Flaatten

, Thomas Husby

,

Jørund Langørgen

, Jon-Kenneth Heltne

aDepartmentofAnaesthesiaandIntensiveCare,HaukelandUniversityHospital,Bergen,Norway

bDepartmentofClinicalMedicine,UniversityofBergen,Norway

cDepartmentofNeurology,HaukelandUniversityHospital,Bergen,Norway

dDepartmentofBiologicalandMedicalPsychology,UniversityofBergen,Norway

eFacultyofMedicine,UniversityofBergen,Norway

fCentreforClinicalResearch,HaukelandUniversityHospital,Bergen,Norway

gDepartmentofHeartDiseases,HaukelandUniversityHospital,Bergen,Norway

a r t i c l e i n f o

Articlehistory:

Received3October2014 Receivedinrevisedform 27November2014 Accepted13December2014

Keywords:

Cardiacarrest Cognitiondisorders CANTAB

Neuropsychologicaltests Qualityoflife

Treatmentoutcome

a b s t r a c t

Aim:Neuropsychologicaltestinghasuncoveredcognitiveimpairmentincardiacarrestsurvivorswith goodneurologicoutcomeaccordingtothecerebralperformancecategories.Weinvestigatedcognitive functionandhealth-relatedqualityoflifefouryearsaftercardiacarrest.

Methods:Thirtycardiacarrestsurvivorsovertheageof18incerebralperformancecategory1or2on hospitaldischargecompletedtheEQ-5D-5LandHADSquestionnairespriortocognitivetestingusing theCambridgeNeuropsychologicalTestAutomatedBattery.Theresultswerecomparedwithpopulation norms.

Results:Twenty-ninepercentofpatientswerecognitivelyimpaired.Thepatternofcognitiveimpairment reflectsdysfunctioninthemedialtemporallobe,withimpairedshort-timememoryandexecutivefunc- tionslightlybutdistinctlyaffected.TherewasasignificantreductioninqualityoflifeontheEQ-VAS,but notontheEQindex.

Conclusion:Cognitiveimpairmentfouryearsaftercardiacarrestaffectedmorethanonequarterofthe patients.Short-termmemorywaspredominantlyaffected.

©2015TheAuthors.PublishedbyElsevierIrelandLtd.ThisisanopenaccessarticleundertheCC BY-NC-NDlicense(http://creativecommons.org/licenses/by-nc-nd/4.0/).

1. Introduction¹

Cognitivefunctionincardiacarrest(CA)survivorsisreportedto befavourableinthemajorityofpatients.^1–3 Themostfrequently usedcognitiveoutcomehasbeenthecerebralperformancecate- gories(CPC)upondischarge,asspecifiedintheUtsteintemplate.^4,5

夽ASpanishtranslatedversionofthesummaryofthisarticleappearsasAppendix inthefinalonlineversionathttp://dx.doi.org/10.1016/j.resuscitation.2014.12.021.

∗ Correspondingauthorat:HelseBergenHF,HaukelandUniversity Hospital, DepartmentofAnaesthesiaandIntensiveCare,JonasLiesVeg65,NO-5021Bergen, Norway.

E-mailaddress:[email protected](E.A.Buanes).

1Listofuncommonabbreviations:HADS,HospitalAnxietyandDepressionrat- ingScale;CANTAB,CambridgeNeuropsychologicalTestAutomatedBattery;MOT, MotorScreening(testinCANTAB);PAL,PairedAssociatesLearning(testinCANTAB);

DMS,DelayedMatchingtoSample(testinCANTAB);SOC,StockingsofCambridge (testinCANTAB);IED,intra-/extradimensionalsetshift(testinCANTAB).

Afteritsintroductionin1975,theCPCbecameanimportanttoolfor improvingtheassessmentofoutcomesafterseverebraindamage.

Inrecentdecades,ithasbecomeincreasinglyevidentthattheCPC istoocrudetoassessmoresubtlechangesincognitivefunctionthat mayappearafterCA.Neuropsychologicaltestinghasuncovered cognitiveimpairmentinCAsurvivorswithgoodcerebraloutcome accordingtotheCPC.^6–8TheuseofCPCasarobustcerebraloutcome measurehasthereforebeenquestioned.⁹

Withregardtodiagnosticaccuracy,traditionalneuropsycholo- gicaltestingprovidesadetailedassessmentofcerebralfunction.

Thedrawbackisthatthemethodistime-consumingandrequires highlyspecialisedpersonnel.Theidealdiagnostictoolforclinical usemustprovidea sufficientlydetailedassessment ofcognitive functionandbeeasytoadminister.Wehavepreviouslyusedthe CambridgeNeuropsychologicalTestAutomatedBattery(CANTAB) onaCApopulationtreatedwiththerapeutichypothermia.¹⁰The methodissuitedtoclinicalworkandcomparisonacrossdifferent culturesandlanguages.¹¹Inthisstudy,wetestthehypothesisthat

http://dx.doi.org/10.1016/j.resuscitation.2014.12.021

0300-9572/©2015TheAuthors.PublishedbyElsevierIrelandLtd.ThisisanopenaccessarticleundertheCCBY-NC-NDlicense (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Discharged alive n= 61

Unknown ID n=1

Dead before study start n= 14

Alive at study start n= 46

Excluded (n= 16)

Declined to participate: 11

CPC > 2: 4

Could notbe reached: 1

Included in study n= 30

Fig.1. Flowchartshowingincludedandexcludedpatients.

cognitiveimpairmentpersistsinlong-termCAsurvivorswithgood cerebraloutcomeaccordingtotheCPCcomparedwithanageand gender-matchedpopulationnorm.Oursecondaryobjectiveswere toinvestigatehealth-relatedqualityoflifeandwhetherprimary shockablerhythm,thelocationofCA,therapeutichypothermiaor lengthofstayintheintensivecareunit(ICU)couldpredictlong- termcognitivefunctionafterCA.

2. Methods 2.1. Patients

Subjectsfromacohortofpatientsdischargedaliveaftercardiac arrestinBergenbetween1December2008and30November2009, abovetheageof18andaliveinOctober2012,wereconsidered forinclusion.Datafromthispatientcohorthavepreviouslybeen published.¹²PatientswithaCPCabove2onhospitaldischargeand patientswhocouldnot bereachedorhad anunknownidentity wereexcluded(Fig.1).Thepatientsincludedweretestedatasingle timepointamedianof3.6years(ICR:3.4–3.8)afterCA.

2.2. Testsetting

TheHospitalAnxietyandDepressionratingScale(HADS)(Age- ingand health,OsloUniversityHospital,Ullevål,Bygn.37,0407 Oslo,Norway)andtheEQ-5D-5L(EuroQolGroup,MartenMeesweg 107,3068AVRotterdam,theNetherlands)weresentbyposttoall eligiblepatients,alongwithwritteninformationaboutthestudy, aconsentformandapre-paidreturnenvelope.Participantswho returnedtheinitialformswerecontactedbytelephonetoschedule cognitivetesting.Participantswhodidnotreturntheformswere contactedbytelephoneforconsent.Ifconsentwasgiven,theywere remindedtoreturntheformsandcognitivetestingwasscheduled.

CANTAB(CambridgeCognition,TunbridgeCourt,TunbridgeLane, Bottisham,CambridgeCB259TU)testsessionstookplaceatHauke- landUniversityHospitalandlastedapproximatelyonehour.For participantsunabletotraveltothehospital,testingwasarranged atahealthfacilitynearerwheretheylived.

2.3. Testmethods

EQ-5D-5Lwasusedtoevaluatehealth-relatedqualityoflife.

EQ-5D-5L is a self-administered questionnaire assessing five dimensionsof health. It hasfivelevelsfor each dimensionand anoverallself-estimateofhealthonavisualanaloguescale(EQ- VAS).Thefivedimensionsaremobility,self-care,usualactivities, pain/discomfortandanxiety/depression. We reportEQ-VASand healthindex(EQ-index)calculatedonthebasisofvaluesforthe fivedimensions.¹³

HADS was used to screen for anxiety and depression. It is a self-administered questionnaire that yieldsseparatescores for depression and anxiety.¹⁴ A score ≥8 indicates anxiety or depression.¹⁵

Cognitive function wasmeasured usingCANTAB,¹¹ a touch- screen, computer-based cognitive function assessment tool featuringatotalof22testsforseveralcognitivedomains.Language proficiencyisonlyneededfortheverbalinstructionspriortoeach test,sincealltaskstimuliarenon-verbal,consistingofgeometric designsorsimpleshapes.Weassembledabatteryoffiveteststo assessmemoryandexecutivefunctions.Assistantscanadminis- terthetestbatteryin50–70minandtheresultsareimmediately available.Severaloutcomemeasuresareavailableforeach test, reportedeitherasarawscoreorz-score.Thez-scoreisthenum- berofstandarddeviationsthepatient’sscorediffersfromanage andgender-matchedBritishpopulationmean.Fortheclassification ofcognitiveimpairment(CI),wereportz-scoresfromtenparam- etersbasedontest–retestreliability.¹⁶Fiveofthetenparameters representmemoryandfiverepresentexecutivefunction.Cognitive impairmentwasdefinedashavingtwooutoftenz-scoresbelow

−2.0,orthreeoutoftenz-scoresbelow−1.5.¹⁷Thetestbattery consistedofthefollowingtests:

2.3.1. MotorScreening

Asimpleintroductiontothetestapparatusandscreeningfor visualandmotor impairmentthat mayinterferewithcognitive testing.ThesubjecthastotouchX-marksofdifferentcolourson thescreenastheyappear.

2.3.2. PairedAssociatesLearning(PAL)

Atestofvisualepisodicmemoryandlearning.Sixoreightboxes aredisplayed.Allofthemareopenedinrandomorder,andsome containapattern.Thepatternsarethendisplayedoneatatime, andthesubjectmusttouchtheboxwhereeachpatternishidden.

Thetestbecomesprogressivelymoredifficultineightstages.Ifthe subjectmakesanerror,patternsinthatstagearere-presented.The testterminatesaftertentrialsinanygivenstage.

2.3.3. DelayedMatchingtoSample(DMS)

Atestofdelayedmemoryandforceddecision-making.Anon- figurativepatternisdisplayedonthescreen.Subjectsmustrecall itanddistinguishitfromthreesimilarpatternsafteradelayof0,4 or12s.

2.3.4. StockingsofCambridge(SOC)

Atestofexecutivefunction,specificallyspatialplanningand spatialworkingmemory.Thesubjecthastomovecolouredcircles arrangedinstackstomatchagiventemplate.Difficultyincreases withthenumberofmovesrequired.Shouldthesubjectmakemore thandoublethenumberofmovesrequiredforthesimplestsolu- tion,theproblemisterminated.Ifthree problemsin aroware terminated,theentiretestisterminated.

2.3.5. Intra-/extradimensionalsetshift(IED)

Atestofexecutivefunction,attentionandflexibility.Thesub- jecthastoselectthecorrectfigurefromtwoalternativesaccording

toarulethatisacquiredfromfeedback(correct/incorrect).After sixsubsequentcorrectselections,therulechangesasthetestpro- gressestothenextstage.Thesubjectmustdiscovernewrulesand adheretothem inordertoprogressthrough uptonine stages.

Thestagesincludereversal,intradimensionalshiftandextradimen- sionalshift.Thetestterminatesafter50trialsinanygivenstage.

2.4. Datahandling

DatarelatingtoCAandresuscitationwereretrievedfromthe originalcohort.¹²HADSandEQ-5D-5Lquestionnaireswerescored andreviewed byEABand KKS.Dataabout medicalhistory and treatmentfollowingthereturnofspontaneouscirculation(ROSC) wereretrievedretrospectivelyfromtheelectronicpatientjournal byEAB.AlldatawereregisteredinadedicateddatabaseinHelse BergenbyEABandKKS.

2.5. Statistics

Mean scores are reported with the 95% confidence inter- valinbrackets.Categoricaldatawereanalysed usingchi-square tests without continuity correction, and confidence intervals for the difference between proportions were calculated using theAgresti–Caffo method.¹⁸ Correlations werecalculated using Pearson’s product–moment correlation. Simple and multiple regressionswereperformedtoinvestigatewhethercognitivefunc- tion couldbe predicted.Survival data were retrieved fromthe electronicpatientjournalandcomparedtoNorwegianlifetables.¹⁹ Lifetablesfor2009wereusedforsubsequentyears,sincemortal- ity.orgonlycontainedlifetableseriesupto2009.Allstatistical analyseswereconductedinRversion3.1.1.²⁰

2.6. Ethics

The study was conducted in accordance with the protocol approved by the Regional Committee for Medical and Health Research Ethics (2012/1701/REK vest). Written consent was obtainedfromallsubjects.

3. Results

3.1. Demographicandmedicalcharacteristics

Oftheinitial61CAsurvivors,onehadunknownidentity.Forty- sixoftheremaining60werealiveatthestartofthestudy.Four hadCPC>2onhospitaldischarge,onecouldnotbereachedand11 declinedtoparticipate(Fig.1).Noneofthe30patientsincluded hadknownpre-existingbraindamageorbraindisease,demen- tia,psychiatricdiseaseorwereusingorabusingcentralinhibiting orstimulatingmedication.Therewerenostatisticallysignificant differencesinthedistributionofage,gender,medicalhistoryor treatmentbetweenincludedpatientsandpatientswhodeclinedto participateorcouldnotbereached(Table1).

3.2. Treatment

Ofthe30includedpatients,24hadcoronaryangiographyper- formed during their hospital stay, while 16 had percutaneous coronaryinterventionperformed.Only1of30hadsurgerywith coronaryarterybypassgrafting,while7of30weretreatedwith therapeutichypothermia(TH).Thedurationofresuscitationwas longeramongtheincludedpatientsthanamongthepatientswho declinedtoparticipateorcouldnotbereached(Table1).

3.3. Survival

Atthe start ofthestudy, 14 of55 Norwegian patientswith CPC≤2dischargedalivewithknownidentityweredeceased(Fig.

W1).Theexpectednumberofdeathsinanageandgender-matched Norwegianpopulationwas5.0(standardisedmortalityratio:2.8;

95%CI:1.6–4.5;p<0.001).¹⁹

3.4. Depressionandhealth-relatedqualityoflife

ThemeanscoreforEQ-VASwas70.6(95%CI:63.4–77.8),com- paredto80.0(95%CI:79.1–80.9)foranageandgender-matched Danishnormalpopulation.²¹ThemeanscorefortheEQ-indexwas 0.85(95%CI:0.79–0.90),comparedto0.86(95%CI:0.85–0.87)for thesamereferencepopulation.ThemeanscoreforHADS-Awas3.7 (95%CI:2.6–4.9)and3.5forHADS-D(95%CI:2.2–4.7).ForHADS- A,2of30(7%)patientsscored≥8,suggestinganxiety,whereasfor HADS-D,5of30(17%)patientsscored≥8,suggestingdepression.

Correlationsbetweencognitivefunctionanddepressionorhealth- relatedqualityoflifeweremoderateandnotstatisticallysignificant (TableW1).

3.5. Cognition

All participants passed the Motor Screening test and were allowedtoattemptthecognitivetests.Accordingtothecriteria,29%

(8/28;95%CI:15–47%)ofthepatientswerecognitivelyimpaired.¹⁷ OneofthemhadCPC2onhospitaldischarge.Nineofthetenz- scoreshadmeanvalueslowerthanzero,andthreeofthemwere statisticallysignificantfromzero(Table2and Fig.2).Onlyone remainedsoafteradjustingformultipletesting.Allsignificantz- scoresrepresentvisualmemory.Totestsensitivity,weperformed bootstraptestsandconstructedbootstrapconfidenceintervalsfor themeanofthetenz-scores.Theresults(notshown)werevery similartotheresultsofthet-tests,bothforp-valuesandconfidence intervals.

Inthemultipleregressionanalysis,OHCAwasastatisticallysig- nificantpredictor,withOHCAindicatingbettercognitivefunction (Table3).

For reversal stages (stages 5, 7 and 9) of the intra- /extradimensionalsetshift(IED),themeannumberoferrorswas 18.7.Fornon-reversalstages(stages4,6and8),themeannum- beroferrorswas16.1(95%CIfordifference:−1.4to6.5;p=0.20).

ThetotalnumberoftrialsinIEDintradimensionalshift(ID,stage 6)was6.5(95%CI:5.3–7.7)versus24.8(95%CI:18.0–31.6)forthe extradimensionalshift(ED,stage8)(difference:18.3;95%CIfor difference:11.8–24.8;p<0.001)(Fig.3).

FortheDelayedMatchingtoSample(DMS)percentagecorrect at0sdelay,themeanwas81.4(95%CI:75.4–87.5),whereas,at12s delay,themeanwas68.2(58.8–77.6)(difference:13.2;95%CIfor difference:5.7to20.8;p=0.001.n=28)(Fig.W2).

4. Discussion

Themainfindinginthisstudyisthatcognitiveimpairmentper- sistsin29%(95%CI:15–47%)ofCAsurvivorswithgoodneurological outcomeathospitaldischargefouryearsafterarrest.^10,22Thepat- ternofimpairmentindicatesdysfunctioninmedialtemporallobe structures,asseen,forinstance,inearlyAlzheimer’sdementia.²³ WefoundmemoryimpairmentsinthePairedAssociatesLearning (PAL)andamarkeddecreaseincorrectanswersat12sdelay,com- paredto0sdelay,intheDelayedMatchingtoSample(DMS).Both findingscorrelatewiththehippocampusbeingaffected.²⁴AsDMS andPALbothhavespatialproperties,lowscoresinbothtestsindi- catethatthemedialtemporallobesareaffected.Thesestructures areimportantforprocessingspatialinformation.

Table1

Demographicandmedicalcharacteristics.

Included Declined^a 95%CI^b P-value

Age(mean) 62 61 –16to14 0.90

Malegender 24/30 80% 10/12 83% –26to25 0.80

Medicalhistory

Nopreviousillness 6/30 20% 4/12 33% –43%to15% 0.36

Coronarydisease 12/30 40% 4/12 33% –25%to35% 0.69

Heartfailure 8/30 27% 2/12 17% –20%to33% 0.49

Hypertension 12/30 40% 4/12 33% –25%to35% 0.69

Lungdisease 5/30 17% 1/12 8% –18%to27% 0.49

Diabetes 5/30 17% 3/12 25% –37%to17% 0.53

Stroke 4/30 13% 0/12 0% –10%to27% 0.18

Malignancy 5/30 17% 0/12 0% –7%to31% 0.13

Smoke 9/29 31% 3/11 27% –29%to31% 0.82

Hypercholesterolemia 11/30 37% 4/12 33% –28%to32% 0.84

Primaryrhythm 0.43

Ventricularfibrillation 23/29 79% 6/11 55% – –

Ventriculartachycardia 2/29 7% 1/11 9% – –

Pulselesselectricactivity 2/29 7% 2/11 18% – –

Asystole 2/29 7% 2/11 18% – –

Presumedcauseofarrest 0.32

Cardiac 26/30 87% 8/12 67% – –

Respiratory 2/30 7% 2/12 17% – –

Drowning 0/30 0% 1/12 8% – –

Trauma 1/30 3% 0/12 0% – –

Other 1/30 3% 1/12 8% – –

Resuscitation

Durationofresuscitation(s) 1086 282 –1297to–310 0.002^*

Pre-hospitalcardiacarrest 17/30 57% 6/12 50% –21%to32% 0.69

Witnessedcardiacarrest 28/30 93% 10/12 83% –12%to36% 0.32

BystanderCPR 26/60 87% 6/12 50% –63%to–5% 0.01^*

Treatment

Coronaryangiography 24/30 80% 7/12 58% –9%to51% 0.15

PCI 16/30 53% 5/12 42% –21%to41% 0.49

CABG 1/30 3% 1/12 8% –28%to12% 0.49

Therapeutichypothermia 7/30 23% 3/12 25% –32%to24% 0.91

CI,confidenceinterval;CPR,cardio-pulmonaryresuscitation;PCI,percutaneouscoronaryintervention;CABG,coronaryarterybypassgrafting.

aDeclinedparticipation,unknownIDornocontactestablished.

b 95%CIofmean/percentagedifference.

* P-value<0.05.

Table2

Meanz-scorefortenoutcomeparametersfromfourCANTABtests.

n Meanz-score 95%CI P-value

PAL–firsttrialmemoryscore 30 −0.72 −1.03to−0.41 <0.001^*

PAL–stagescompleted 30 −0.21 −0.63to0.22 0.33

PAL–totaltrials(adjusted) 30 −0.47 −0.93to−0.01 0.05^*

DMS–totalcorrect(alldelays) 28 −0.12 −0.62to0.39 0.64

DMS–meanlatencytocorrect(alldelays) 28 −0.73 −1.29to−0.17 0.01^*

SOC–problemssolvedinminimummoves 29 0.12 −1.14to0.17 0.56

SOC–meanthinkingtime(5moves) 29 −0.33 −0.94to0.05 0.17

SOC–meanmoves(5moves) 29 −0.34 −0.30to0.53 0.12

IED–stagescompleted 28 −0.48 −0.80to0.14 0.14

IED–totalerrors 28 −0.45 −0.78to0.09 0.08

CI,confidenceinterval;PAL,pairedassociateslearning;IED,intra-/extradimensionalsetshift;DMS,delayedmatchingtosample;SOC,stockingsofCambridge.

* P-value<0.05.

Fig.2. Dotplotshowingpatientz-scoreson10parametersfrom4CANTABtests(n=28,29or30).

Table3

Regressionofmeanz-scoreonpossiblepredictors.

Multipleregression Simpleregression

Estimate^a P-value 95%CI Estimate^a P-value 95%CI

Intercept −0.56 −0.95to−0.17

Non-shockablerhythm 0.36 0.28 −0.32to1.04 0.35 0.25 −0.26to0.99

OHCA 0.52 0.04 0.04to1.00 0.37 0.08 −0.04to0.79

Therapeutichypothermia −0.20 0.63 −1.03to0.64 −0.08 0.74 −0.59to0.42

LOSICU −0.02 0.67 −0.10to0.07 −0.01 0.81 −0.06to0.05

R²=0.23.AdjustedR²=0.09.

CI,confidenceinterval;OHCA,out-of-hospitalcardiacarrest;LOS,lengthofstay;ICU,intensivecareunit.

aRegressioncoefficient.

Severalmechanisms for ischaemic brain damage have been identified. They include impaired cerebral reperfusion, apopto- sisand alterationsin geneexpression,chemical phenotypeand unfoldedproteinresponse.^25,26Inseverecasesofischaemicbrain damage,thehistopathologicpatternshowsatypicaldistribution affectingthemedialtemporallobes,cerebellumandneocortex.²⁷ Theseareasofthebraincontrolmemoryandexecutivefunctions.

Consideringthephysiologicsubstrate,onewouldexpecttheexec- utivefunctionstobeaffectedinourpatients.Thishaspreviously been documented in CA survivors one and two years after an arrest.^8,10Thefiveselectedz-scoresrepresentingexecutivefunc- tionswerenotaffectedinourpatients.Hence,adetailedanalysis oftheintra-/extradimensionalsetshift(IED)testwasperformedin ordertolookforsimilaritiesbetweenCAsurvivors,ontheonehand, andpatientswithAlzheimer’sdementiaandpatientswithfrontal variant frontotemporal dementia, on the other. These patients havelesionsinregionsofthebrainthatarealsoatriskinglobal

Fig.3.Dotplotshowingnumberoftrialsintheintradimensionalsetshiftstage(ID) andtheextradimensionalsetshiftstage(ED)oftheintra-/extradimensionalsetshift test(IED)(n=28).

hypoxia. Patientswith frontalvariantfrontotemporal dementia showdecreasedperformanceonreversalstagesoftheIED,which correlateswithsocialdisinhibitionandinappropriatebehaviour.²⁸ Suchafindingmightcorrespondtoreportsofpersonalitychanges andalteredbehaviourinCAsurvivors.PatientswithAlzheimer’s dementiashowsignsofexcessivesuppressionofirrelevantinfor- mation,atraitwhichcorrespondstothenumberoftrialsinthe ExtradimensionalShift(ED)stageoftheIED.²³Wefoundnopattern intheIEDsuggestingsimilaritieswithfrontalvariantfrontotempo- raldementia.Therewas,however,apatterncomparabletotheone foundinearlystagesofAlzheimer’sdementia(Fig.3).Thismaybe explainedbythe‘creativehypothesis’,wherebypatientshavemany creativesolutionstoaproblemathandbutfailtotakepreviously irrelevantinformationintoaccount.²³

IncreasedmortalityamongCAsurvivorswhowerecognitively impaired mightexplain thelow frequency of cognitiveimpair- ment in our material.²⁹ Our CA survivors have a standardised mortalityrateof2.8(95%CI:1.6–4.5), comparedtoanageand gender-matched Norwegianpopulation. Themortalityis higher thanexpected upuntilthreeyears afterCA(Fig.W1).Ifexcess mortalityweretoexplaintheperformanceincognitivetests,one wouldexpectbothmemoryandexecutivefunctionstobecloseto thenorm.Memoryimpairmentwasclearinourpatients,butexec- utivefunctionswereonlyslightlyaffectedintheextradimensional shiftstageoftheIED.Analternativeexplanationisthatpatients havedevelopedstrategiestodealwithexecutivedysfunctionover theyearsfollowingCA.Thisisnotunlikely,sinceexecutivedysfunc- tionmayimprovethroughamindfulapproachtoreal-lifetasksthat poseproblems.³⁰Incontrast,thetreatmentofamnesiaislimited.

ThequalityoflifereportissimilartoaDanishageandgender- matchedreferencepopulationwhenmeasuredontheEQ-index derivedfromthefivedimensionsofhealth,butsignificantlylower thanthereferencewhenmeasuredontheEQ-VAS.We haveno clearexplanationforthisdifference.Onecouldspeculatethatcere- bralischaemiareducesspatialawarenessandthusaffectspatient responsestovisualanaloguescales.However,thiswouldquestion theuseofvisualanaloguescalesinlargepatientgroups,andthere isnoscientificbasisinourstudytosupportthis.

Intheregressionanalysis,OHCAappearstobeapredictorof improvedlong-termCF.Duetothesmallsamplesize,multiplevari- ablesinthemodelandap-valueclosetothelimitofsignificance, wequestionthereproducibilityofsuchafinding.Repeatedstudies withlargersamplesizesareneededtoestablishcausality.

The main strength of our study is standardised, detailed cognitive testing using computer-based test delivery. The two investigatorsfollowedastrictprotocolandcognitivetestingwas conductedinpublichealthfacilitiestoensuresimilarconditions forallpatients.Limitationsincludethesmallsamplesizeandlack ofinformationaboutphysicalhealthatthetimeofinvestigation.

AlackofNorwegianpopulationnormshasledustouseDanish normsforEQ5DandBritishnormsforCANTAB,bothofthemclose approximationsoftheparentpopulation,inouropinion.

GivenaEuropeanpopulationof740millionand3.7millionhos- pitalbeds,anestimated186,000personsaredischargedfollowing CAinEuropeeachyear.^31–34Atleast90,000ofthesepatientsare stillaliveoneyearafterCA,andbetween25,000and40,000ofthem willhavemildcognitiveimpairment.^10,29,35Thehealthimpactis largein aEuropeanperspective and,inouropinion,it mustbe systematicallyaddressed.Patientsandtheirfamiliesneedtobe informedaboutthepossibilityofcognitiveimpairmentfollowing CA.Ifthereisanysuspicionofcognitiveimpairmentthataffects qualityoflifeoneyearafterCA,itshouldbedocumented.Thor- oughneuropsychologicalevaluationonsuchascaleisnotfeasible, sinceitistime-consuminganddependentonhighlytrainedper- sonnel.Inouropinion,CANTABcanserveasascreeningtoolto identifypatientsforneuropsychologicalevaluationwherecogni- tiveimpairmentissuspected.

5. Conclusions

Cognitiveimpairmentfouryearsaftercardiacarrestseemscom- parable to early Alzheimer’s dementia. Memory appears to be predominantly affected,withexecutive functionsbeing slightly affected.

Conflictsofinterest

Theauthorsdeclarenoconflictsofinterest.

Acknowledgments

Inadditiontodepartmentalfunding,agrantwasreceivedfrom theLaerdalFoundationforAcuteMedicine(2012/2869).Funding foropenaccesspublicationwasreceivedfromtheUniversityof Bergen.Sponsorshadnoroleinthestudy.

AppendixA. Supplementarydata

Supplementarydataassociatedwiththisarticlecanbefound, intheonlineversion,athttp://dx.doi.org/10.1016/j.resuscitation.

2014.12.021.

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