The use of a frailty index to predict adverse health outcomes (falls, fractures, hospitalization, medication use, comorbid conditions) in people with intellectual disabilities

The use of a frailty index to predict adverse health outcomesfalls, fractures, hospitalization, medication use, comorbid conditions in people with intellectual disabilities Josje D.. Inc

The use of a frailty index to predict adverse health outcomes

(falls, fractures, hospitalization, medication use, comorbid

conditions) in people with intellectual disabilities

Josje D Schoufoura,* , Michael A Echtelda, Luc P Bastiaansea,b,

a Intellectual Disability Medicine, Department of General Practice, Erasmus University Center Rotterdam, P.O Box 2040,

3000 CA Rotterdam, The Netherlands

b

Ipse de Bruggen, P.O Box 2027, 2470 AA Zwammerdam, The Netherlands

1 Introduction

Asthelifespanofpeoplewithintellectualdisabilities(ID)increases(Long&Kavarian,2008;Patja,Iivanainen,Vesala,

carefacilities,ashasbeenseeninthegeneralpopulation(Clegg,Young,Iliffe,Rikkert,&Rockwood,2013).Nevertheless, thereisnoinformationonthecauses,developmentandconsequencesoffrailtyinpeoplewithID(Evenhuis,Schoufour,

&Echteld,2013)

Frailtyhasbeendescribedas‘‘adynamicstateaffectinganindividualwhoexperienceslossesinoneormoredomainsof humanfunctioning(physical,psychological, social),whichiscausedbytheinfluenceofarangeofvariablesandwhich

A R T I C L E I N F O

Article history:

Received 15 October 2014

Received in revised form 1 December 2014

Accepted 3 December 2014

Available online 8 January 2015

Keywords:

People with ID

Frailty

Adverse health outcomes

Falls

Comorbid conditions

A B S T R A C T

Frailtyinolderpeoplecanbeseenastheincreasedlikelihoodoffuturenegativehealth outcomes.Lifelongdisabilitiesinpeoplewithintellectualdisabilities(ID)maynotonly influencetheir frailtystatusbut also theconsequences Here,we reporttherelation betweenfrailtyandadversehealthoutcomesinolderpeoplewithID(50yearsandover)

Inaprospectivepopulationbasedstudy,frailtywasmeasuredatbaselinewithafrailty indexin982olderadultswithID(50yr).Informationonnegativehealthoutcomes(falls, fractures, hospitalization, increased medication use, and comorbid conditions) was collectedatbaselineandafterathree-yearfollow-upperiod.Oddsratiosorregression coefficientsfornegativehealthoutcomeswereestimatedwiththefrailtyindex,adjusted forgender,age,levelofID,Downsyndromeandbaselineadversehealthcondition.The frailty indexwas related to anincreased riskof higher medication useand several comorbidconditions,butnottofalls,fracturesandhospitalization.Frailtyatbaselinewas relatedtonegativehealthoutcomesthreeyearslaterinolderpeoplewithID,buttoalesser extentthanfoundinthegeneralpopulation

ß2014ElsevierLtd.Allrightsreserved

* Corresponding author at: Erasmus Medical Center, Department of General Practice, P.O Box 2040, 300 CA, Rotterdam, The Netherlands.

Tel.: +31 107032118; fax: +31107032127.

E-mail addresses: j.schoufour@erasmusmc.nl (J.D Schoufour), m.echteld@erasmusmc.nl (M.A Echteld), l.bastiaanse@erasmusmc.nl (L.P Bastiaanse),

h.evenhuis@erasmusmc.nl (H.M Evenhuis).

ContentslistsavailableatScienceDirect

http://dx.doi.org/10.1016/j.ridd.2014.12.001

0891-4222/ß 2014 Elsevier Ltd All rights reserved.

increasestheriskof adverseoutcomes’’(Gobbens,Luijkx,Wijnen-Sponselee, &Schols,2010)(p.342).Frailtycanbe measuredwithdifferentinstruments,basedondifferentoperationalizations.Previously,wemeasuredfrailtyinpeople withIDusingafrailtyindex(Schoufour,Mitnitski,Rockwood,Evenhuis,&Echteld,2013).Afrailtyindexisamethodthat focusesonthequantity,ratherthanonthenatureofhealthproblems:themoreproblemsarepresentinanindividual,the more frailhe orshe is (Mitnitski,Mogilner, &Rockwood, 2001;Rockwood &Mitnitski, 2011).Itcaptures physical, psychological and social health and has been shown to predict negative health outcomes in several clinical and community-dwellingpopulations(Cleggetal.,2013;Mitnitskietal.,2001;Rockwood&Mitnitski,2007).PeoplewithID showedhighfrailtyindexscorescomparedtothegeneralpopulationofthesameage(Schoufouretal.,2013;Schoufour,

Frailindividualsinthegeneralpopulationaremorelikelytofall,havefractures,getadmittedtoahospital,anddevelop morechronicdiseasesincludingosteoarthritis,depressivesymptoms,coronaryheartdisease,diabetesmellitusandchronic lowerrespiratorytractdisease(Gobbens,vanAssen,Luijkx,Wijnen-Sponselee,&Schols,2010;Hoganetal.,2012;Macklai,

peoplewithIDduetotheirlifelongdisabilities.Forexample,lifelongmobilitylimitationsandlowbonequality(Bastiaanse,

comorbidity(Hermans&Evenhuis,2014)mayleadtoanincreasedriskofhospitaladmission.Contrary,thecareandsupport providedatthecareorganizationsmaylimitthenecessityofhospitalization,specificallyforthosewithseverebehavioral problemsorprofoundlevelsofID.Also,gastrointestinal,neurological,sleep,andmusculoskeletalproblems,epilepsy,and visualandhearingimpairmentscanbelifelong,start ata youngerage,oraremoreprevalentcomparedtothegeneral population,leadingtoearlyinterventionsandpossiblyhabituation(Evenhuis,Henderson,Beange,Lennox,&Chicoine,2001;

foundinthegeneralpublic.Toexplorehowfrailtyisrelatedwithhealthproblems,weusedprospectivedatafromthe HealthyAgingandIntellectualDisabilitystudy(HA-ID)(Hilgenkampetal.,2011).Themainaimofourstudywastoanalyze theabilityofthefrailtyindextopredicttheoccurrenceoffalls,fractures,hospitalization,chronicmedicationuse, and comorbidconditionsoverthreeyears

2 Methods

2.1 Studydesignandparticipants

Thisstudywaspartofthe‘Healthyagingandintellectualdisabilities’study(HA-ID)(Hilgenkampetal.,2011).This observationalstudycollectedinformationonthegeneralhealthstatus ofolderpeoplewithIDusingformalcareinthe Netherlands.Allclientsofthecareorganizationsaged50yearsandoverwereinvitedtoparticipate(N=2322).Thosecapable

ofunderstandingtheavailableinformationsignedtheconsentformthemselves.Legalrepresentativeswereapproachedfor thosewhowerenotabletomakethisdecision.Writteninformedconsentwasprovidedfor1050clients,forminganearly representativestudypopulationfortheDutchpopulationofolderadults(aged50andabove)withIDwhouseformalcare, albeitwithaslightunderrepresentationofmen,peopleaged80andover,andpeoplelivingindependently.Baselinedata collectiontookplacebetweenFebruary2009andJuly2010.TheMedicalEthicsCommitteeoftheErasmusMedicalCenter Rotterdam(MEC-2008-234)andtheethicscommitteesoftheparticipatingcareorganizationsapprovedthisstudy.Details aboutrecruitment,design,inclusioncriteria,andrepresentativenessoftheHA-IDstudyhavebeenpublishedelsewhere

2013.Theparticipants,ortheirlegalrepresentatives,whostillreceivedcareofthecareorganizationswereaskedagainto providewritten informedconsentfor the follow-up study.The follow-up studywas approvedby the Medical Ethics CommitteeoftheErasmusMedicalCenterRotterdam(MEC-2011-309)andtheethicscommitteesoftheparticipatingcare organizations

2.2 Datacollection

Detailsaboutthebaselinedatacollectionhavebeendescribedelsewhere(Hilgenkampetal.,2011).Inshort,baseline characteristicswereretrievedfromtheadministrativesystemsofthecareorganizations.Measurementswereconducted withinthreemainthemes(1)physicalactivityandfitness,(2)nutritionandnutritionalstate,and(3)moodandanxiety.The broadspectrumofdatacollectionincludedanthropometricmeasurements,physicalfitnesstests,psychiatricassessment, andlaboratorytestsinadditiontofilerecords(e.g.medicalfile).LevelofIDwasobtainedfromtherecordsofbehavioral therapistsandpsychologists.ThepresenceofDownsyndromewasobtainedfrommedicalfiles.Mobilitylimitationswere categorizedasnohelp,walking-aidorwheelchairuse.Follow-updatawerecollectedthreeyearsafterbaselinewithout clientinterference

2.2.1 Fallsandfractures

Atbaselineandfollow-up,professional caregiversprovided informationonhow often theparticipantsfellinthe pastthreemonths(not fallen,1–2falls, 3–5falls,6–10falls,11fallsormore) Atbaseline, dataonfractureshaving

occurredoverthelast5yearswererequestedfromthephysician.Forthefollow-upmeasurement,dataon fractures having occurredoverthelastthreeyearswererequestedfromboththeprofessionalcaregiverandthephysician 2.2.2 Generalhospitaladmission

Occurrencesofhospitalization(no,once,twice,threetimes,morethanthreetimes)werecollectedviathepersonal caregiveratbaseline(precedingyear)andviaphysiciansatfollow-up(precedingthreeyears).Hospitalizationwasdefinedas

anadmissionofatleastonedayinageneralhospital.Proceduresinoutpatientclinicswerenottakenintoaccount.Clients withseverebehavioralproblems,orclientswhoreceivedahighlevelofcarefromthecareorganization,werethoughtto

be less likely to be admitted for a hospital stay Therefore, an adjustment wasmade for participantswho received intensive support or intensive support and regulation of behavior This classification was based on long term care indicationsundertheDutchActonExceptionalMedicalExpenses(AWBZ)—alawthatfinancesspecializedlong-termcare 2.2.3 Totalnumberofusedmedicines

Currentmedicationusewasrequestedatbaselineandfollow-upfromthephysicianorpharmacy.Totalmedication countincludedthetotalnumberofmedicinestakenatthepointofmeasurement.Vitamins,minerals,basicskincreams (e.g.vaseline),oranti-dandruffshampooprescribedbythephysician,werenotcountedasmedicines,withtheexception

ofvitaminDandcalciumtablets

2.2.4 Comorbidconditions

Information on conditions (cardiovascular,respiratory, gastrointestinaltract,endocrine system, neurological,sleep, psychiatric, musculoskeletal,and hearing and vision), wererequestedfrom theattending physician.Additionally, the anatomicaltherapeuticchemical(ATC)classificationsystem(‘‘WHOCollaboratingCentreforDrugStatisticsMethodology,

BothdiagnosisandATC-codewereusedtoclassifyparticipantsashavingaproblem,diseaseorconditionregardingthat organsystems(Table1 Althoughoriginallyincludedin theATCclassification,‘antiparasitic products,insecticidesand repellents’and‘antineoplaticandimmunomodulatingagents’werenotincludedintheanalysisbecauselessthan1%ofthe participantsusedmedicationinthesegroups.Removingallmorbidityitemsfromtheindexcouldresultinanunbalanced index.Thereforewedidnottestwhetherthefrailtyindexwasabletopredictanincreaseincomorbidity(e.g.allcomorbid conditionstogether)

2.3 Thefrailtyindex

Wepreviouslydevelopedafrailtyindexusing51deficitsfromthebaselinemeasurementsoftheHA-IDstudy.Together, thesedeficitscoveredpsychological,physicalandcognitivehealthaspects.Alldeficitswerecarefullyselectedandfulfilled thecriteriadevelopedbySearleetal.(Searle,Mitnitski,Gahbauer,Gill,&Rockwood,2008).Eachdeficithastobe health-relatedandincreasewithage,andthedeficitshouldnotsaturatetooearly(noceilingeffects).Alldeficitswerere-codedtoa scorebetween0(deficitabsent)and1(deficitpresent).Afrailtyindexscorewascalculatedbythenumberofpresentdeficits dividedbythetotalnumberofmeasurements,resultinginascorerangingfromzero(lowestleveloffrailty)toone(highest level offrailty) Detailedinformation on theselection,diagnosticmethods, deficits, andused cutoff valueshave been reported elsewhere (Schoufour et al., 2013) To examine the associations of frailtywiththe differentadverse health outcomes,theindexwasrescoredtoexcludeitemsthatconcernedthathealthoutcome.Forexample,ifthefrailtyindexwas

Table 1

Classification comorbid conditions according to the anatomical therapeutic chemical classification (ATC) system and diagnosis by the physician Anatomical main group Diagnosis physician First level of the ATC code Alimentary tract and metabolism Gastroesophageal reflux disease, peptic ulcer,

constipation, dysphagia, diabetes mellitus

A

Cardiovascular system Heart failure, valve abnormalities, coronary

heart disease, heart rate disorder, hypertension, hypercholesterolemia, intermittent claudication, stroke

C

Genitourinary system and sex hormones – G

Systemic hormonal preparations,

excl sex hormones and insulins

Hypothyroidism, hyperthyroidism H

Musculoskeletal system Scoliosis, rheumatism, arthrosis, osteoporosis, spasticity M

Nervous system Dementia, epilepsy, Parkinson’s disease, sleep disorders,

depression, anxiety, psychosis

N Respiratory system Asthma, COPD, sleep apnea R

Sensory organs Vision or hearing impairment S

correlatedtofalls,thefalldeficitwasexcludedfromtheoriginalindex,and ifthefrailtyindexwascorrelated tothe cardiovascularsystem,alldeficitsregardingcardiovascularconditionswereexcludedfromtheoriginalindex

2.4 Statisticalanalysis

First,characteristicsofthestudypopulationwereassessedwithanon-responseanalysis.Participantswhoprovided informed consent for the follow-up study, and had medical information available at both baseline and follow-up were included in the study.Differences between participants included and excluded in the follow-up study were assessedusingPearson-chi-square testsfor categoricalvariablesandt-tests for continuousvariables Second,linear regression (number of medication) or logistic regression analysis (falls [one or more], fractures [one or more], hospitalization[oneormore],andcomorbidconditions[asdefinedinTable1])wereused toanalyzetheassociation betweenthebaselinefrailtyindexscoreandnegativehealthoutcomesthreeyearslater.Toaidinterpretation,thefrailty indexscorewasmultipliedby100.Afterunivariateanalysis,multivariateanalyseswereperformed,adjustingforgender (male=0, female=1), age (years), level of ID, and Down syndrome Level of ID was classified in three categories (borderline/mild, moderate, severe/profound) Subsequently, dummy variables were created for level of ID and borderline/mildwasusedasthecomparisoncategory.Dummyvariableswerealsocreatedtocomparetheparticipants withDownsyndrometothosewithoutDownsyndromeandthosewithoutinformationonDownsyndrome.Inorderto assesstheincreasedriskfor anegativehealthoutcome,allmodelswereadjustedforthenegativehealthoutcomeat baseline.Inaddition,themodeltopredictfallswasadjustedformobility(no help,walking-aid,wheelchair) andthe epilepsy,andthe modeltopredict hospitalization wasadjusted for participants who received intensivesupport or intensive support and regulation of behavior The percentage of the explained variance was represented by the Nagelkerke R2 (logistic regression analysis) or the adjusted R2 (linear regression analyses) statistic A Bonferroni correctionwasappliedtothemorbidconditions(0.05/11).AllstatisticalanalyseswereperformedusingSPSSversion 21.0(SPSS,Inc.,Chicago,IL)

3 Results

3.1 Characteristicsofthestudypopulation

Atbaseline,1050participantshadbeenincludedintheHA-IDstudy.After3yearsoffollow-up,19movedand120died Theremaining911participantswereinvitedforparticipation,ofwhom763providedinformedconsent.Atfollow-up,data fromthemedicalrecordswereprovidedfor693participants, ofwhich61didnothavebaselineinformationavailable, leaving632participantsinthefinalanalysis.Thosewhodroppedout,moreoftenhadaborderlineormildintellectual disability,livedmoreofteninthecommunity,hadmoreoftenbeenhospitalizedintheprecedingyear,tookonaveragemore medicines,andshowedonaveragehigherfrailtyindexscoresatbaseline(Table2

3.2 Frailtyandadversehealthoutcomes

For689participantsbaselineandfollow-updataonfallswereknown.Oftheseparticipants,170(25%)reportedfalls

atfollow-up Thefrailty indexat baselinewasnot related withfallsthree yearslater (Table3 Thosewithreported fallsatbaseline(OR=3.5,p<.001),peoplewithepilepsy(OR=1.9,p=.013)andpeoplewithoutDownsyndrome(OR=2.1,

p=.04)weremorelikelytoreportfallsatfollow-up

For651participants,fracturesatbaselineandfollow-upwereknown.Ninety-seven(15%)participantsreportedtohaveat leastonefractureduringthefollow-upperiod.Thefrailtyindexatbaselinewasnotrelatedwithfracturesduringthe

follow-upperiod(Table3 Theonlyvariablessignificantlyassociatedwithanincreasedfractureriskwerebeingfemale(OR=1.84,

p=.013)andpreviousfractures(OR=4.56,p<.001)

For579participants,informationonhospitalizationwasknownatbaselineandfollow-up.Overthreeyears,114(20%)of theparticipantswerehospitalizedat leastonce.Participants witha highfrailtyindexat baseline hadno statistically significantincreaseintheirriskforhospitalization(Table3 Higheragepredictedhospitalizationsignificantly(OR=1.03,

p=.028)

Atfollow-up,participantstookonaverage1.5(SD=2.8)moremedicinesthanatbaseline.Thefrailtyindexwasrelated withthetotalnumberofmedicinesthreeyearslater(p<.001).Also,participantswithhighfrailtyindexscorestendedto increasetheirnumberofmedicinesduringthefollow-upperiod(B=0.07,p<.001;Table3

Overall,therewasanincrease incomorbidconditions withinthe follow-upperiod(Fig.1).Most wererelatedto thealimentarytractandmetabolismgroup(baseline73%,follow-up79%), followedby thenervoussystem(baseline 63%, follow-up 72%) and the sensory organs (baseline 55%, follow-up 60%) After adjusting for the baseline characteristicsandthecomorbidconditionatbaseline,ahighfrailtyindexscorewasrelatedtocomorbidconditions

in thealimentarytract &metabolism, dermatologicals,systemetichormonalpreparations, andnervous system,but afteraBonferronicorrectiononlytherelationwiththealimentarytract&metabolismremainedstaticallysignificant (Table 4)

4 Discussion

Westudiedtherelationbetweenfrailty(definedastheaccumulationofdeficits)andnegativehealthoutcomesin adultswithID,aged50yearsandover,duringafollow-upofthreeyears.Thosewithhighfrailtyindexscoresatbaseline, were morelikely todevelopnewcomorbidconditions andtoget moremedicationprescriptions Theproportionof participantswhoreportedfalls,fracturesorhospitalizationatfollow-up,wasnotrelatedtothefrailtyindex

Table 2

Characteristics at baseline.

Characteristics n (%)

Follow-up Baseline, n = 1050 Included, n = 632 Dropped out, n = 418 X 2

/t p-value Gender

Male 539 (51%) 316 (50%) 223 (53%) 1.13 29 Female 511 (49%) 316 (50%) 195 (47%)

Age (years)

50–59 493 (47%) 310 (49%) 183 (44%) 4.88 30 60–69 370 (35%) 220 (35%) 150 (36%)

70–79 162 (15%) 90 (14%) 72 (17%)

80+ 25 (2.4%) 12 (1.9%) 13 (3.1%)

Level of ID

Borderline 31 (3.0%) 14 (2.2%) 17 (4.1%) 24.1 <.001 Mild 223 (21%) 113 (18%) 110 (26%)

Moderate 506 (48%) 312 (49%) 194 (46%)

Severe 172 (16%) 125 (20%) 47 (11%)

Profound 91 (8.7%) 60 (9.5%) 31 (7.4%)

Unknown 27 (2.6%) 8 (1.3%) 19 (4.5%)

Down syndrome

No Down syndrome 724 (62%) 514 (81%) 210 (50%) 5.7 02 Down syndrome 149 (14%) 91 (14%) 58 (14%)

Unknown 177 (24%) 27 (4.3%) 150 (64%)

Residential status

Central 557 (53%) 385 (61%) 172 (41%) 54.9 <.001 Community 432 (41%) 236 (37%) 196 (47%)

Independent with support 43 (4.1%) 10 (1.6%) 33 (7.9%)

With relatives 7 (0.7%) 1 (0.2%) 6 (1.4%)

Unknown 11 (1.0%) 0 (0%) 11 (2.6%)

Falls 1 preceding 3 months a

233 (24%) 137 (23%) 96 (26%) 1.15 28 Fractures 1 preceding 5 years b

78 (8.8%) 58 (9.5%) 20 (7.4%) 1.08 30 Hospitalization 1 preceding year c 99 (11%) 49 (9.0%) 50 (15%) 7.63 006 Number of medicines (mean [SD]) d

4.1 (3.1) 3.9 (2.8) 4.5 (3.6) 3.7 007 Frailty index (mean [SD]) e

0.27 (0.13) 0.26 (0.12) 0.29 (0.14) 3.5 <.001 Note SD = Standard Deviation.

a

Falls at baseline were missing for 69 participants, 26 were included, 43 dropped out.

b

Fractures at baseline were missing for 168 participants, 22 were included,146 dropped out.

c

Hospitalization was missing for 175 participants, 88 were included, 87 dropped out.

d

Number of medicines was missing for 127, zero were included, 127 dropped out.

e Frailty index unknown for 68 participants from the baseline participants, 22 were included, 46 dropped out.

Table 3

Three-year outcomes associated with the frailty index.

Outcome n (events) Model OR/B (95%CI) p-value R 2

Falls 597 (148) Unadjusted 1.01 (0.99–1.02) 23 0.004

Adjusted *

1.01 (0.98–1.03) 54 0.15 b,c,d

Fractures 617 (97) Unadjusted 1.00 (0.98–1.02) 62 <0.01

Adjusted *

0.99 (0.97–1.02) 32 0.09 a,c

Hospitalization 540 (114) Unadjusted 1.01 (0.99–1.03) 38 <0.01

Adjusted *

1.01 (0.99–1.03) 49 0.03 Medication use 601 (NA) Unadjusted 0.14 (0.12–0.16) <.001 0.21

Adjusted *

0.07 (0.04–0.09) <.001 0.44 c

Note The frailty index was recomposed without the outcome of interest and multiplied by 100 OR = Odds Ratio, B = Beta, events = number of events at follow-up.

* Adjusted for gender, age, level of ID, presence of Down syndrome, outcome at baseline.

Other factors significantly associated with the health outcome in the adjusted model: a

being female, b

absence of Down syndrome, c

outcome at baseline,

d

Falls,especiallyifaccompaniedwithafracture,canbeconsiderednegativehealthoutcomesandareexpectedtobe relatedtofrailty.Nevertheless,inthegeneralpopulation,thereisstillinconsistencyabouttheassociationbetweenfrailty andfalls.Somestudyresultsshowedacorrelation(Ensrudetal.,2008,2009;Fangetal.,2012),whereasothersdidnot(Forti

increasedriskoffallsandfractures.Apossibleexplanationforthisresultisthattheunderlyingriskfactorsrelatedtofalls couldbedifferentinpeoplewithID.Failureinoverallhealthgenerallystartswiththehighestorderfunctions,including walking(Rockwood&Mitnitski,2011).Thislineofthinkingissupportedbythefindingthatphysicalfitnessisrelatedtofalls

0 10 20 30 40 50 60 70 80 90 100

Baseline Follow-up

Fig 1 Percentage of morbidities among participants of the HA-ID study at baseline (black bars) and after 3-year follow-up (gray bars).

Table 4

Logistic regression models to predict comorbidity at follow-up with a frailty index.

Anatomical main group, n = 602 n (events) Model OR (95%CI) p-value R 2

Alimentary tract and metabolism 602 (476) Unadjusted 1.09 (1.07–1.17) <.001 ^ 0.17

Adjusted * 1.06 (1.03–1.09) <.001 ^ 0.41 g

Blood and blood forming organs 602 (84) Unadjusted 1.05 (1.03–1.07) <.001 ^

0.07 Adjusted *

1.02 (0.99–1.05) 25 0.31 e,g

Cardiovascular system 602 (277) Unadjusted 1.01 (0.99–1.02) 34 0.00

Adjusted *

1.01 (0.99–1.03) 47 0.54 f,g

Dermatologicals 602 (127) Unadjusted 1.02 (1.01–1.04) 009 0.02

Adjusted * 1.03 (1.01–1.05) 011 0.08 d,g

Genito urinary system and sex hormones 602 (51) Unadjusted 1.01 (0.99–1.04) 29 0.00

Adjusted *

1.00 (0.97–1.04) 89 0.44 g

Systemic hormonal preparations 602 (144) Unadjusted 1.03 (1.02–1.05) <.001 ^

0.04 Adjusted *

1.04 (1.01–1.07) 017 0.68 c,g

Anti infectives for systemic use 602 (51) Unadjusted 1.02 (1.00–1.05) 045 0.02

Adjusted *

1.02 (0.99–1.05) 20 0.06 g

Musculo-skeletal system 602 (135) Unadjusted 1.04 (1.02–1.06) <.001 ^ 0.06

Adjusted *

1.01 (0.99–1.04) 33 0.44 b

Nervous system 602 (432) Unadjusted 1.07 (1.05–1.09) <.001 ^

0.13 Adjusted *

1.04 (1.01–1.07) 007 0.47 g

Respiratory system 602 (128) Unadjusted 1.02 (1.00–1.04) 029 0.01

Adjusted *

1.02 (1.00–1.05) 086 0.42 d,g

Sensory organs 602 (360) Unadjusted 1.03 (1.01–1.04) <.001 ^

0.03 Adjusted * 1.00 (0.98–1.02) 86 0.24 a,c,e,g

Note The frailty index was recomposed without the mentioned diseases or conditions, which are included in the original frailty index, events = number of comorbidities at follow-up.

^

Significant after Bonferroni correction (p < 05/11 = 005).

* Adjusted for gender, age, level of ID, Down syndrome, and baseline morbid condition.

Other factors significantly associated with the health outcome in the adjusted model: a

increased age, b

decreased age, c

presence of Down syndrome, d

inthegeneralpopulation(Deandreaetal.,2010;Stenhagen,Ekstrom,Nordell,&Elmstahl,2013).Previousresultsfrom theHA-IDstudyshowedhoweverthatphysicalfitness(i.e.gaitspeed,strength,balance)wasnotrelatedtofallsinpeople

age-relateddeclineinhealth.Sincefalls,inthegeneralpopulation,increasewithage,thiscontributestotheexplanation thatage-relatedfrailtyisassociatedtoincreasedfallrisk.Inthisstudywedidnotobserveanincreaseinfallswithage Also,theexplainedvarianceofthemodelwaslow(explainedvariance=13%)andmainlyrelatedtopreviousfalls,indicating thatotherfactors,suchasepilepsy,visualdeficits,behavioralproblems,andpolypharmacymaybemoreimportantto predict falls in people with ID (Cox, Clemson, Stancliffe, Durvasula, & Sherrington, 2010; Enkelaar, Smulders, van

cautionsincetheusedmeasurementsmayhavelimitedtheaccuracyoftheassociation.Werequestedfallsoverthelast threemonths,whichissubjecttoproblemsinrecallthatcouldhavebeendiminishedwithprospectivedatacollection (forexamplefallsrecords)(Ganz,Higashi,&Rubenstein,2005).Also,fallswereonlyrequestedatfollow-up,sowedonot knowthecompleteoccurrenceoffallsbetweenbaselineandfollow-up.Inaddition,wewereunabletoclassifyrecurrent fallers(>1falls)inaseparategroup,duetothestructureofthequestionnaireusedinourstudy

Frailtywasnotassociatedwithhospitaladmissionduringthefollow-upperiod.Thisresultisdifferentfromseveral studiesinthegeneralpopulationshowingthatfrailtyisassociatedwithhospitalization(Daniels,vanRossum,Beurskens,van denHeuvel,&deWitte,2012;Fangetal.,2012;Hoganetal.,2012;Jungetal.,2014)andwithalongerlengthofhospitalstay

normally requirespecialist servicesmayhave been undiagnosed(Beange, McElduff, &Baker, 1995; Gustavson,

treatmentwasnotinthebestinterestfortheclient(Wallace&Beange,2008;Webber,Bowers,&Bigby,2010).Despitethe attempttoadjustforthis,wedidnotfindanincreasedriskforhospitalizationsinfrailparticipants

Frailtywasassociatedwiththenumberofusedmedicinesandwithanincreasedlikelihoodofincreasingmedicationuse, whichisinlinewithresultsfromthegeneralpopulation(Crentsil,Ricks,Xue,&Fried,2010;Gnjidicetal.,2012).Multiple drugusecancauseseveresideeffects,drug-druginteractionsanddrug-nutrientinteractions(Beijer&deBlaey,2002;Fulton

&Allen,2005).Thehighlevelsofcomorbidity(Hermans&Evenhuis,2014;McCarronetal.,2013)andfrequentprescription errors foundin people withID(Zaal,vanderKaaij, Evenhuis,&vandenBemt,2013), raisesconcernsaboutthehigh medication consumption in frail people Age-relatedphysiological changes related withdrugabsorption, metabolism, distribution and excretionare possibly more extreme in frail individuals(Hubbard, O’Mahony,&Woodhouse, 2013) Potentially,thisincreasestheriskofadversedrugreactions,andcontributestothefrailty-relateddeteriorationinhealth Attempts at diminishing polypharmacy in people with ID applying systematic medication reviews is therefore recommended

Atfollow-up,frailtywasassociatedwithmostcomorbidconditions,whichhasalsobeenfoundinthegeneralpopulation (Cleggetal.,2013;Tangetal.,2013;Walstonetal.,2006;Weiss,2011).Evenso,afteradjustingfortheconditionatbaseline (i.e.newcomorbidities),therelationwasonly slightornon-significant.A longerfollow-upperiodmayberequiredto monitorthedevelopmentofnewdiseasesandtherebyincreasethepoweroftheanalysis.Becauseinformationwasobtained throughthemedicalfiles,undiagnosedconditionsmayhaveledtoanunderestimationofthisassociation

The comprehensive set of outcome measurements, collected via the physicians and personal caregivers, and the prospective design are themajorstrengths of ourstudy.Our study hasalsoseveral limitations First, theresults are influencedbyspecificdropout.The418participantswhowerenotincludedinthemainanalysiswereonaveragefrailer,took moremedication,andhadmoreoftenbehospitalizedpriortothestudy.Almost30%(n=120)ofthedropoutwascausedby thedeathoftheparticipants.Previouslyweshowedthatsurvivalwasassociatedwithhigherfrailtylevels,moreprofound levelofID,higherageandthepresenceofDownsyndrome(Schoufouretal.,inpress).Also,priortodeath,healthcondition may deteriorate, leading to an underestimation of the association between frailty and health conditions Similarly, deteriorationinhealthcouldhavebeenareasontorefuseparticipationinthefollow-upstudy.Furthermore,participants livinginthecommunity,whoreceivedmedicalcarefromageneralpractitionerinsteadofaspecializedIDphysician,were morelikelytodropout.ThespecificdropoutlimitsgeneralizationoftheresultstothecompleteolderIDpopulation.Second, frailtywasonlymeasuredonce.Ithasbeenshownthatfrailtyisadynamicprocessinwhichpeoplecaneitherbecomeworse

orrecoverfromtheir(pre-)frailstate(Gill,Gahbauer,Allore,&Han,2006;Mitnitski,Song,&Rockwood,2012).Lifeevents

unknownhowtrajectoriesoffrailtymaybeaphenomenoninthispopulationandhowthesetrajectoriesinfluencethe associationbetweenfrailtyandnegativehealthoutcomes

Inconclusion,wedemonstratedthatfrailty,definedasdeficitaccumulation,isrelatedtonegativehealthoutcomesin peoplewithID,buttoalesserextentthanfoundinthegeneralpopulation.Thefrailtyindexisnotsuitableasatooltopredict admission togeneral hospitalsand fallsinthis group.Thelow explainedvariance ofthemodelsimpliesthat specific (individual)problemsmaybemoreimportantriskfactorsthanameasureofgeneralhealth,suchasthefrailtyindex.The frailtyindexdidpredictanincreasein medicationuse.Thisconfirms thatfrailtyisrelatedtodecreasedhealthstatus Previously,wedemonstratedthatfrailtyiscommoninthispopulation,startsatarelativelyyoungageandisrelatedto mortality,increasedcareintensity,anddeteriorationinindependenceandmobility(Schoufour,Evenhuis,&Echteld,2014; Schoufouretal.,2013;Schoufour,etal.,inpress;Schoufour,Mitnitski,etal.,2014).Together,theseresultsshowthatfrailty

hasseriousconsequencesinolderpeoplewithID,andeffectiveinterventionsarerequiredtolimitthisburden.Inaddition, futureresearchshouldfocusonpotentialforclinicalapplicationofthefrailtyindex,i.e.onanindividuallevel.Aclinically applicablefrailtyindexcouldbeusedtorecognizefrailindividualsandtoevaluateinterventions

Funding

Thisstudywassupportedbya grantfromtheNationalCarefor theElderlyProgramme(NPO)which ispartofthe NetherlandsOrganisationforHealthResearchandDevelopment(ZonMW;nr.57000003,314030302).Furthersupportwas providedbythethreeparticipatingcareorganisations(Abrona,IpsedeBruggen,andAmarant)

Ethicscommitteeapproval

ThisstudywasapprovedbytheEthicsCommitteeoftheErasmusMedicalCenterRotterdam(MEC-2008-234)andthe ethicscommitteesoftheparticipatingcareorganizations(Abrona,IpsedeBruggen,andAmarant)

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