Frailty syndrome: implications and challenges for health care ...

Second, frailty is conceptualized as a state of decreased physiological reserve and compromised capacity to maintain homeostasis as a ... Journals WhyPublishWithUs? 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GotaroKojima,1AnnEMLiljas,2SteveIliffe11DepartmentofPrimaryCareandPopulationHealth,UniversityCollegeLondon,London,UK;2DepartmentofPublicHealthSciences,KarolinskaInstitutet,Stockholm,SwedenAbstract:Olderadultsareahighlyheterogeneousgroupwithvariablehealthandfunctionallifecourses.Frailtyhasreceivedincreasingscientificattentionasapotentialexplanationofthehealthdiversityofolderadults.ThefrailtyphenotypeandtheFrailtyIndexarethemostfrequentlyusedfrailtydefinitions,butrecentlynewfrailtydefinitionsthataremorepracticalhavebeenadvocated.Prevalenceoffrailtyamongthecommunity-dwellingpopulationaged65yearsandolderis~10%butvariesdependingonwhichfrailtydefinitionsareused.Themeanprevalenceoffrailtygraduallyincreaseswithage,buttheindividual’sfrailtylevelcanbeimproved.Olderadults,especiallyfrailolderadults,formthemainusersofmedicalandsocialcareservices.However,currenthealthcaresystemsarenotwellpreparedtodealwiththechronicandcomplexmedicalneedsoffrailolderpatients.Inthiscontext,frailtyispotentiallyaperfectfitasariskstratificationparadigm.Theevidencefromfrailtystudieshasnotyetbeenfullytranslatedintoclinicalpracticeandhealthcarepolicymaking.Successfulimplementationwouldimprovequalityofcareandpromotehealthyagingaswellasdiminishtheimpactofagingonhealthcaresystemsandstrengthentheirsustainability.Atpresent,however,thereisnoeffectivetreatmentforfrailtyandthemosteffectiveinterventionisnotyetknown.Basedoncurrentlyavailableevidence,multi-domaininterventiontrials,includingexercisecomponent,especiallymulticomponentexercise,whichincludesresistancetraining,seemtobepromising.Thecurrentchallengesinfrailtyresearchincludethelackofaninternationalstandarddefinitionoffrailty,furtherunderstandingofinterventionstoreversefrailty,thebesttimingforintervention,andeducation/trainingofhealthcareprofessionals.Thehazardsofstigmatizationshouldalsobeconsidered.Iftheseconcernsareproperlyaddressed,widespreadapplicationofpublichealthapproacheswillbepossible,includingscreening,identification,andtreatmentoffrailty,resultinginbettercareandhealthieragingforolderpeople.Keywords:frailty,healthcarepolicy,geriatrics IntroductionLifeexpectancyhasmarkedlyincreasedworldwideduringthepast100years,mainlyduetopublichealthimprovements.1Thisdemographictransformationofthepopulationhasresultedingrowingnumbersofolderadultsinbothdevelopinganddevelopedcountries.2Between2000and2050,theproportionofpeopleaged60yearsorolderintheworldisprojectedtodoublefromabout11%to22%,anincreasefrom605millionto2billionadultsaged≥60years.1Thenumberofolderadultsagedover80yearsisexpectedtoquadrupleto395millionduringthesameperiod.1Ingeneral,wetendtodevelopmorehealthproblemsandbecomefrailerasweage.Theincreaseinlifeexpectancyallowschronicdiseasestodevelopwhilephysicalandcognitivefunctionsdecline,whichpredisposesolderpeopletodisabilityordependency.Olderadultsareahighlyheterogeneousgroup.Theirlifecoursesofhealthandfunctionalstatusvarysubstantially,dependingontheirgenetic,biological,andenvironmentalbackgroundsaswellasotherphysical,psychological,andsocialfactors.Therefore,individualswiththesamechronologicalagecanhavedifferentbiologicalages.3Frailtyhasreceivedincreasingscientificattentionasawayofunderstandinghealthdiversityamongolderadults.4Inthepast,thetermfrailtywasusedalmostinterchangeablywithaging,disability,orcomorbidity,partlybecauseofthesimilarityandhighcoexistencerateofthesedescriptivestates.5However,therearecleardifferencesbetweenfrailty,aging,disability,andcomorbidity.First,advancedageonitsowndoesnotnecessarilymeanvulnerabilitytonegativehealthoutcomessotypicaloffrailty.6Frailtyisatleastpartlyprogrammedinearlylifeandisalsoassociatedwithlowersocio-economicstatusinadulthood.7Second,frailtyisconceptualizedasastateofdecreasedphysiologicalreserveandcompromisedcapacitytomaintainhomeostasisasaconsequenceofage-related,multiple,accumulateddeficits.4Frailolderpeoplearehighlyvulnerabletoadversehealthoutcomeswhenexposedtoaninternalorexternalstressor.4Third,whereasfrailtyreferstoinstabilityandriskoflossoffunction,disabilityindicateslossoffunctionandoftenassessedbasedondifficultyordependencyinperformingactivitiesnecessarytoliveindependently,suchasactivitiesofdailyliving(ADL),eg,bathing,dressing,eating,toileting,continence,andtransferring8andinstrumentalactivitiesofdailyliving(IADL),eg,shopping,telephoneuse,mealpreparation,housekeeping,laundry,transportation,medication,andfinances.9Finally,comorbidityisdefinedashavingtwoormoremedicallydiagnoseddiseases.5Thus,frailtyisclearlydifferentanddistinguishablefromadvancedage,disability,andcomorbidity.DefinitionoffrailtyAnumberofdefinitionshavebeenproposedtoconceptualizeandoperationalizefrailty.10,11Despitethelong-lastingandextensivedebatesonhowbesttodefinefrailty,internationalconsensushasyettobereachedandagoldstandarddefinitionoffrailtyisstilllacking.4Nonetheless,mostconceptualfrailtydefinitionshavesomefactorsincommon,suchasdecreasedreserves/capacitytotolerateminorstressors,increasedvulnerabilitytoadversehealthoutcomes,andimpairmentinmultiplephysiologicalsystems.10Aftertheinclusionofthesefactors,frailtyisconceptuallydefinedas“aclinicallyrecognizablestateinwhichtheabilityofolderpeopletocopewitheverydayoracutestressorsiscompromisedbyanincreasedvulnerabilitybroughtbyage-associateddeclinesinphysiologicalreserveandfunctionacrossmultipleorgansystems”.12ThisdefinitionbytheWHOhasbeenwidelyaccepted4,13andadoptedintheJointActionADVANTAGE,arecentlylaunchedEuropeanUnion(EU)initiative.14Amongvariousfrailtydefinitions,themostcommonlyusedisthefrailtyphenotype,15developedbyFriedetalusingtheCardiovascularHealthStudycohortin2001.16TheFriedfrailtyphenotypeconsistsoffivephysicalcomponentstodefinefrailty:unintentionalweightloss,self-reportedexhaustion,weakness,slowwalkingspeed,andlowphysicalactivity.16Individualsareconsideredtobefrailwhentheymeetthreeormorecriteria,andtheyareconsideredtoberobustwhentheyhavenone.16Individualswhohaveoneortwocriteriaaredefinedasprefrail,astatebetweenrobustandfrail.16TheFrailtyIndexisanotherpopularapproach,15basedonacumulativedeficitmodeladvocatedbyMitnitskietalusingtheCanadianStudyonHealthandAging.17Incontrasttothefrailtyphenotype,thiscumulativedeficitapproachdescribesfrailtyasastatecausedbytheaccumulationofhealthdeficitsduringthelifecourse,andthemoredeficitsindividualshave,themorelikelytheyaretobefrail.15TheFrailtyIndex,acontinuousscorerangingfrom0(nodeficit)to1(alldeficitspresent),iscalculatedastheratioofthenumberofdeficitspresentintheindividualtothenumberoftotaldeficitsconsidered.18FortheFrailtyIndex,atleast30–40deficits,associatedwithageandadversehealthoutcomesthatareprevalentin1%ormoreofthepopulation,shouldbeconsidered,withfewerthan5%ofmissingvalues,anditcanincludesymptoms,signs,diseases,disabilities,abnormalitiesoflaboratory,radiographic,andelectrocardiographicfindings,andsocialcharacteristics.18Therehasbeensomedebateregardingthepracticalapplicationofthesetwomostcommonlyusedfrailtydefinitions.19Thefrailtyphenotyperequiresspecialequipmenttomeasurethehandgripstrengthandspaceformeasuringgaitspeed.Thepopulation-basedlowest20%ofthehandgripstrength,gaitspeed,andphysicalactivityneedtobecalculatedbasedonthepopulationdistributions.CalculationoftheFrailtyIndexrequirestherecordingofvarioustypesofdeficits(typicallymorethan30–40)anddividingthenumberofdeficitspresentbythenumberofdeficitsconsidered,whichmaytake~20–30minutes,19exceptwhendataareextractedandcalculatedautomaticallyfromelectronicmedicalrecords.20FeasiblefrailtyinstrumentsinaclinicalsettingAccordingtotheInternationalAssociationofNutritionandAging(IANA)TaskForce,afrailtytoolshouldbequick,inexpensive,reliable,andeasytouseinclinicalsettingsbecausetheidentificationoffrailolderpeopleatriskisanimportantinitialsteppotentiallyleadingtoappropriatepreventiveand/ortreatmentinterventionsandultimatelytohigherqualitycareforthisvulnerablepopulation.21Fromthisperspective,thefrailtyphenotypeandtheFrailtyIndexmayberatherimpracticalandunfeasibleespeciallyinabusyclinicalsetting.Basedonasystematicreviewoftheliteratureaswellasinputfromapanelofgeriatricexperts,theIANA’sworkinggroupadvocatedanewfrailtytool.21TheFRAILscaleisasimpletoolconsistingoffiveyes/noquestions:Fatigue,Resistance(inabilitytoclimbstairs),Ambulation(inabilitytowalkacertaindistance),Illnesses(morethanfiveofcomorbidities),andLossofweight(morethan5%),21andhasbeenshowntobeabletopredictmortalityandincidentADLandIADLdisabilitiesamongcommunity-dwellingolderpeopleinrecentmeta-analysisstudies.22,23TheFRAILscaleisalsorecommendedasoneofthetoolstodetectfrailtybytheJointActionADVANTAGE,aEUco-fundedinitiativelaunchedin2017involving22memberstatesandover40organizations.14ThemaingoalofADVANTAGEistoestablishacommonEuropeanframeworkforaddressingtheproblemsoffrailty,including:1)improvementsinscreening,diagnosis,prevention,andtreatmentforfrailty,2)healthcaresystemreformsadaptedtopopulationaging,and3)facilitationofresearchandeducationonfrailty.14ADVANTAGEhasproposedthattoolsusedforfrailtyscreeningshouldbequicktoadministrate(nomorethan10minutestocomplete);requirenospecialequipment;validated;andbemeantforscreening.ExistingfrailtyinstrumentsmeetingthesefourcriteriaareClinicalFrailtyScale,EdmontonFrailScale,FRAILscale,INTER-FRAIL,Prisma-7,SherbrookePostalQuestionnaire,ShortPhysicalPerformanceBattery,andStudyofOsteoporoticFracturesIndex.14TheKihonChecklist,aself-reportedcomprehensivequestionnaireconsistingof25simpleyes/noquestionscoveringmultipledomains,isanotherrelativelynewfrailtytool.24,25ThistoolwasoriginallydevelopedbytheJapaneseMinistryofHealth,LabourandWelfarein2005–2006asascreeningtooltoidentifyvulnerableolderadultswhoareathighriskofdependencyandmorerecentlyhasbeenrecognizedasausefulfrailtyassessmenttool.26,27Thisisanotherbrief,simple,quick,andcost-effectiveinstrumentwhichdoesnotneedspecialequipmentandtakes<10minutestocomplete,19andthereforemaybeappropriateforscreening.Thesefrailtyinstrumentscaneasilybeincorporatedintocomprehensivegeriatricassessmentorprimarycareinaclinicalsettingforscreeningfrailolderadults.Someofthemconsistofshortlistsofsimplequestionsandcanbeadministeredbynotonlyphysiciansorotherhealthcareprofessionalsbutalsocaregiversandnon-professionals,inpersonaswellasbyphone,mail,oremail.PrevalenceandnaturalcourseoffrailtyThemeanprevalenceoffrailtyamongthecommunity-dwellingpopulationaged65yearsandolderis~10%butcanrangewidelyfrom4.0%to59.1%dependingonthefrailtycriteriaused.28Advancedageisasignificantriskfactorforfrailtyandaquarterofthoseaged80yearsorolderarefrail.28Ahigherprevalenceoffrailtyisalsoobservedinselectedpopulationswithspecificdiseasesorconditions,suchaspatientswithcancer(42%),29end-stagerenaldisease(37%),30heartfailure(45%),31Alzheimerdisease(32%),32andnursinghomeresidents(52%).33Althoughthemeanprevalenceoffrailtygraduallyincreaseswithage,28,34–37theindividualcourseoffrailtyvariesandtheleveloffrailtycanbereducedeveninoldage.4,38Severallongitudinalpopulation-basedstudieshaveshowedthat8.3%–17.9%ofolderadultsactuallyimprovedtheirfrailtystatus39–44andthatsomeofthemmadefrequentanddynamictransitionsovertime.45ImpactsoffrailtyonhealthcaresystemsFrailolderadultsareatincreasedriskofprematuredeath20,22,27,46andvariousnegativehealthoutcomes,includingfalls,47fractures,48disability,23,49anddementia,50allofwhichcouldresultinpoorqualityoflife51andincreasedcost52anduseofhealthcareresources,53suchasemergencydepartmentvisits,54hospitalization,55andinstitutionalization.56Multiplestudiesusingcohortsofcommunity-dwellingolderadultshaveshowedthatthehealthcarecostsoffrailindividualsaresometimesseveral-foldhigherthanthoseofnon-frailcounterparts.57–61Olderadultsformthemainusersofmedicalandsocialcareservices,62andthemajorityofhealthcarecostsareincurredbythem.Inthecontextofongoingpopulationaging,withanunprecedentedgrowingnumberandproportionofolderadults,thisepidemiologicalanddemographicpopulationshiftisstartingtohaveamajorimpactonhealthcaresystems.Currenthealthcaresystemsaremostlydesignedtoaddressorgan-specificanddisease-specificproblemsoneatatimeandarenotwellpreparedtodealwiththechronicandcomplexmedicalneedsoffrailolderpatientsandtoprovideseamlesscarefortheminthelongterm.63,64Therefore,olderpatientsoftenreceivesuboptimalcareduetothefragmenteddeliveryofappropriatetreatmentsandservices.65InterventionsforfrailtyThereisnostandardtreatmentofchoicespecificallyforfrailty,butthereisaneedforhighqualitycost-effectivehealthcarestrategiestocounterfrailty.66Althoughvarioustypesoffrailtyinterventionmodelshavebeendevelopedandinvestigated,thereisaconsiderabledegreeofheterogeneityintermsofoptimalinterventiontype,samplesize,populationcharacteristic,setting,baselinefrailtystatus,frailtydefinition,andoutcomes,andmostfindingsareinconclusive.67–74Atpresent,itisthereforenotpossibletoconcludewhatinterventionisthemosteffectiveandappropriate.Overall,multi-domaininterventiontrials,whichhavebeenfrequentlyconducted,75,76andmanyofwhichincludedanexercisecomponent,seemedtohavesomefavorableeffects(althoughnotinalltrials)comparedwithmono-domaininterventionsorthecontrol.73,77Amongthevariousoutcomemeasures,functionalability,disability,andfallshavebeencommonlyexaminedwhileonlyalimitednumberoftrialsinvestigatedchangesinfrailtystatusasanoutcome.78Althoughitisstillnotclearwhichfrailtyinterventionisthemosteffective,exerciseprograms,especiallymulticomponentexerciseincludingresistancetraining,havebeenconsistentlysuccessfulandseemlikelytoplayapivotalroleinfrailtyinterventions.79–84ImplicationsandchallengesforhealthcarepolicyOneoftheplausibleimplementationsoffrailtyintoclinicalpracticeistoidentifyfrailpatientsusingelectronichealthrecorddata.85–87InaUKstudy,CleggetaldevelopedtheelectronicFrailtyIndex(eFI)from36deficits,88basedontheFrailtyIndexofcumulativedeficitmodel.17TheeFIwasautomaticallypopulatedfromroutinelycollecteddatastoredintheexistingprimarycareelectronichealthrecordwheregeneralpractitioners(GPs)listallpatientdiagnoses.88TheauthorsshowedeFIwasabletostratifypatientsaccordingtothedegreeoffrailtyandhadrobustpredictivevalidityformortality,hospitalization,andnursinghomeadmission.88In2017,NHSEnglandstartedtorequireGPstoidentifypatientsaged65yearsorolderwithmoderateandseverefrailtyusingvalidatedfrailtyinstrumentsincludingeFI,whichisnowfreelyavailableatmostofGPpractices.89Followingclinicalassessment,patientswithseverefrailtyaremonitoredusinganannualmedicationreviewandotherclinicallyrelevantinterventionsifappropriate.89Thisisprobablythefirstattemptofnation-widepopulation-basedfrailtyriskstratificationandhealthutilizationpredictionsinhealthcaresystems.90Population-basedscreeningforfrailtycouldbeexpensiveandresourceintensive,andcurrentlythereisnoclearevidenceforpotentialbenefit,cost-effectiveness,orimprovedoutcomes.91Nonetheless,attheFrailtyConsensusConferencein2012,itwasconcludedthatscreeningforfrailtyshouldberecommendedforpeoplewithspecificconditionsorincertainsettings.92Oneofthefourconsensuspointswasthatthoseaged70yearsorolderandthosewithsignificantweightloss(≥5%)duetochronicdiseaseshouldbescreenedforfrailty.92ThisrecommendationissupportedbytheADVANTAGEinitiative,whichadvocatesopportunisticfrailtyscreeningofpeopleagedover70yearsreceivinghealthcareatanylevelofthesystem.14TheFrenchSocietyofGeriatricsandGerontologysuggeststhatpeopleagedover75yearswhodonothavedifficultywithsimpleADLbutwithearlyIADLwouldbegoodcandidatesforscreening.93TheUKpracticeguidelinesforfrailtypublishedfromtheBritishGeriatricsSociety,AgeUK,andRoyalCollegeofGeneralPractitionersin2014recommendconductingafrailtyassessmentusingalltheencountersbetweenhealthandsocialcarestaffandolderpeopleincommunityandoutpatientsettings.94Researchanddevelopmenteffortsaimedatestablishinganddisseminatingbestpracticeinfrailtyshouldnotlackpolicyattentiontoolderpeoplewithearly(pre-)frailtythatmissesanopportunitytoaddresssomedemandsonhealthandsocialcareservices.95Amongthecurrentchallengesinthefieldoffrailtyresearch,oneofthemostimportantissuesisthelackofaninternationalstandarddefinitionoffrailty.92,96Despiteaccumulatedresearchevidenceonfrailty,thevariabilityinfrailtydefinitionsusedinexistingstudiesinfluencesinterpretationoftheevidence,comparisonwithotherstudies,generalizationoffindings,anditsimplementationinthehealthcarepolicy.Inordertofurtheradvanceandimprovethehealthcareservicesforfrailolderadults,itisimperativetocometoanagreementintermsoffrailtydefinition.97Ideally,thedefinitionshouldbenotonlyreliablebutalsofeasibleandeasytoapply.98Basedonthecurrentlyavailableevidenceonfrailtyintervention,thereisstrongevidencethatexerciseiscentralandpossiblytheoptimaltreatmentoffrailty.Thisneedstobeexploredfurtherthroughmulti-domaininterventionsthatincludeexercise.Thebesttimingforfrailtyinterventionisnotknownbutcouldrangefrominterveningproactivelytodecreaseriskofdevelopingfrailtyortargetingthosewhoarefoundtobeprefrailorfrailatthetimeofscreening.Iftheseconcernsareproperlyaddressed,widespreadapplicationofpublichealthapproacheswillbepossible,includingscreening,identification,andtreatmentoffrailty,resultinginbettercareandhealthieragingforolderpeople.Involvingfrailolderpeopleinexplorationofresponsestofrailtyislikelytobefruitful;aSwedishstudyshowedthatfinancialsituation,self-ratedhealth,andsocialnetworksweredeterminantsoflifesatisfaction.Actionsthatbenefitlifesatisfaction–socialandfinancialsupport–shouldbepromoted.99Anotherimportantareaoffrailtyresearchiseducationandtraining.Inordertodeliverhighqualitycareandserviceseffectivelyandefficientlytofrailolderadults,healthcareprofessionalsincludingphysicians,nurses,andothermedicalworkersneedtounderstandbasicprinciplesofcareforfrailolderadultsandtobeabletodetectfrailtyandprovidetreatment/interventions.Differentunderstandingsoffrailtymayimpedecommunicationbetweendisciplinesandneedtobeaddressed.However,theevidenceoneducationortrainingforfrailtymanagementislacking.ArecentsystematicreviewthatinvolvedsearchesuntilMay2017foundnorelevantarticleoneducationand/ortraininginterventionsforhealthcareprofessionalsinthefieldoffrailty.100Therearecurrentlyongoingfrailtyprojectsincludingeducationalcomponentstargetinghealthcareprofessionals,patients,andcaregivers,andnewfindingsfromtheseprojectsareexpectedtocontributetothefieldoffrailty.14,100Thereisanincreasinginterestinfrailtyinothermedicalfieldsthanthegeriatrics.101,102Oneexampleisthatfrailtyhasrecentlybeenpursuedasapotentialriskassessmentmeasureforoldersurgicalpatientsandhasshowntobepromisinginpredictingpost-operativecomplications,suchasmortalityorlengthofhospitalstay.103However,thelackofknowledgeaboutfrailtyisamajorbarriertothepreoperativefrailtyassessmentbysurgeons,whichmaybeaddressedbyeducationandtraining.104AUSeducationalinterventionalstudyinvolvingcardiothoracicsurgeryresidentsshowedthatonlineshortcoursesonfrailtysignificantlyimprovedresidents’knowledgeoffrailtyandinfluencedsurgicalriskestimates.105Finally,frailtyresearchmayhaveevolvedwithouttakingintoaccountthepatientperspective.Frailtycanbeconsideredasahighlynegativetermandbeinglabeledasfrailmayaffectnegativelythemostvulnerableindividualsinvariousways.Thosewhowerelabeledas“oldandfrail”byothersweremorelikelytobeassociatedwithalossofinterestinsocialandphysicalactivities,poorphysicalhealth,andincreasedstigmatization.106Thefutureresearchanddevelopmenteffortsneedtoacknowledgetherisksoflabelingolderpeopleinstigmatizingways,andavoidfrailtyfrombecomingthenewcloakofageismandatoolfordiscrimination.107ConclusionThereisanurgentneedtoidentifyandimplementeffectivelong-termcareschemestomeetthecomplexdemandsofolderadults.Frailtyispotentiallyaperfectfitasariskstratificationparadigmandhasthereforebeenrecognizedasanemergingpublichealthpriority.13Althoughagrowingnumberoffrailtystudieshavebeenconductedoverthelasttwodecades,theirfindingshavenotyetbeenfullytranslatedintoclinicalpractice108andtheimplementationofevidenceonfrailtyinhealthcarepolicy-makingisfurtherunderrepresented.95Successfulimplementationhasthepotentialtoimprovequalityofcareforfrailolderadultsandpromotehealthyagingaswellasdiminishtheimpactoffrailtyonhealthcaresystemsandstrengthentheirsustainability.Suchactionsfurtherdemonstratethesubstantialpublichealthimportanceoffrailty.Giventhemultidimensionalandheterogeneousnatureoffrailtyandthecomplexcareneedsoffrailolderadults,amultidisciplinarycollaborativeapproachisneededbetweenresearchers,clinicians,policymakers,andolderpeoplethemselvestoimprovethehealthandwell-beingofthissubgroupofolderadults.109,110Thefieldoffrailtyisstillevolvingandexpandingandwillneedmuchmoretimeandeffortforfurtherprogresstooccur.96Betteroutcomesforolderpeoplearelikelytocomewithatimelag,andaddressingfrailtymayrequireamassivecultural(perhapsgenerational)shiftintheorganizationofhealthandcaresystems.90DisclosureTheauthorsreportnoconflictsofinterestinthiswork.References1.WorldHealthOrganization.WorldHealthDay2012.Areyouready?Whatyouneedtoknowaboutageing;2012.Availablefrom:http://www.who.int/world-health-day/2012/toolkit/background/en/.AccessedMarch2,2016.2.UnitedNations.WorldPopulationAgeing2017.Availablefrom:http://www.un.org/en/development/desa/population/theme/ageing/WPA2017.shtml.AccessedFebruary9,20193.MitnitskiAB,GrahamJE,MogilnerAJ,RockwoodK.Frailty,fitnessandlate-lifemortalityinrelationtochronologicalandbiologicalage.BMCGeriatr.2002;2(1):1.4.CleggA,YoungJ,IliffeS,RikkertMO,RockwoodK.Frailtyinelderlypeople.Lancet.2013;381(9868):752–762.5.FriedLP,FerrucciL,DarerJ,WilliamsonJD,AndersonG.Untanglingtheconceptsofdisability,frailty,andcomorbidity:implicationsforimprovedtargetingandcare.JGerontolABiolSciMedSci.2004;59(3):M255–M263.6.SchuurmansH,SteverinkN,LindenbergS,FrieswijkN,SlaetsJP.Oldorfrail:whattellsusmore?JGerontolABiolSciMedSci.2004;59(9):M962–M965.7.HaapanenMJ,PeräläMM,SalonenMK,etal.Earlylifedeterminantsoffrailtyinoldage:theHelsinkiBirthCohortStudy.AgeAgeing.2018:569–575.8.KatzS,DownsTD,CashHR,GrotzRC.ProgressindevelopmentoftheindexofADL.Gerontologist.1970;10(1):20–30.9.LawtonMP,BrodyEM.Assessmentofolderpeople:self-maintainingandinstrumentalactivitiesofdailyliving.Gerontologist.1969;9(3):179–186.10.GobbensRJ,LuijkxKG,Wijnen-SponseleeMT,ScholsJM.Towardaconceptualdefinitionoffrailcommunitydwellingolderpeople.NursOutlook.2010;58(2):76–86.11.SternbergSA,SchwartzAW,KarunananthanS,BergmanH,MarkClarfieldA.Theidentificationoffrailty:asystematicliteraturereview.JAmGeriatrSoc.2011;59(11):2129–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