Validation study of a Spanish version of the modified Telephone Interview for Cognitive Status (STICS-m)

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Original

article

Validation

study

of

a

Spanish

version

of

the

modified

Telephone

Interview

for

Cognitive

Status

(STICS-m)

Mariana

Mu˜noz-García

a

_,

_Sebastián

_Cervantes

a,b

,

Cristina

Razquin

a,c,d

,

Francisco

Guillén-Grima

a,c,d

,

Juan

B. Toledo

e

_,

_Miguel

_Ángel

_{Martínez-González}

a,c,d,f

,

Estefanía

Toledo

a,c,d,∗

a_Department_of_Preventive_Medicine_and_Public_Health,_School_of_Medicine,_University_of_Navarra_and_University_of_Navarra_Clinic,_Pamplona,_Spain b_Complejo_Hospitalario_de_Navarra,_{Osasunbidea-Servicio}_Navarro_de_Salud,_Pamplona,_Spain

c_CIBER_de_{Fisiopatología}_de_la_Obesidad_y_Nutrición_(CIBERobn),_Spain d_IdiSNA,_Navarra_Institute_for_Health_Research,_Pamplona,_Spain e_Houston_Methodist,_Houston,_TX,_USA

f_Department_of_Nutrition,_Harvard_T.H._Chan_School_of_Public_Health,_Boston,_MA,_USA

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Articlehistory:

Received1March2018 Accepted2May2018 Availableonline24July2018

Keywords:

ModifiedTelephoneInterviewforCognitive Status

Spanish Dementia

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t

Objective: TocomparetheSpanishversionofthemodifiedTelephoneInterviewofCognitiveStatus (STICS-m)withtheMini-MentalStateExamination(MMSE)andpredictitsabilitytodetectthe develop-mentofdementia.

Method: 106participantsinadietaryinterventiontrialunderwentface-to-faceevaluationwiththe MMSE,andphoneinterviewwiththeSTICS-m.ThecorrelationbetweenSTICS-mandMMSEwasassessed withtheintraclasscorrelationcoefficient(ICC)ofconsistency.Secondly,932participantsover55years oldfromthe“SeguimientoUniversidaddeNavarra”cohortwereevaluatedwiththeSTICS-manddataon dementiadiagnosisweregathered(medianfollow-uptimeof6.5years).Alogisticregressionmodel eval-uatedtheassociationbetweenSTICS-mscoreor2-yearchangesinSTICS-mscoreandriskofdeveloping dementia,adjustingforApoE,ageandyearsofuniversityeducation.

Results:TheICCbetweentheMMSEandtheSTICS-mwas0.31(95%confidenceinterval[95%CI]: 0.13-0.48).Theadjustedoddsratio(OR)forthedevelopmentofdementiaforeachadditionalpointinthe baselineSTICS-mscorewas0.85(95%CI:0.72-1.02;p=0.084).Whenconsideringthe2-yearchangein theSTICS-mscoreasexposure,theORforthedevelopmentofdementiawas0.79(95%CI:0.67-0.93; p=0.006).

Conclusions:TheweakcorrelationbetweentheSTICS-mandtheMMSEreflectsmoderate-lowconcurrent validity.Evenso,theSTICS-mcanberegardedasanusefultoolintheepidemiologicalsettingsince increasingscoresappeartobeabletopredictalowerriskofdevelopingdementia.

Validación

de

la

versión

en

espa ˜

nol

de

la

Telephone

Interview

for

Cognitive

Status

modificada

Palabrasclave:

Entrevistatelefónicaparaestatuscognitivo Espa˜nol

Demencia

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e

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u

m

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n

Objetivo: EstudiarlacorrelacióndelaTelephoneInterviewforCognitiveStatusmodificadaenespa˜nol (STICS-m)conelMini-MentalStateExamination(MMSE)ypredecirlacapacidaddelaprimerapara detectareldesarrollodedemencia.

Método: Cientoseissujetosdeunestudiodeintervencióndietéticafueronevaluadospersonalmente conelMMSEyporteléfonoconlaSTICS-m.Lacorrelaciónentreambossemidióconelcoeficiente decorrelaciónintraclase(CCI)deconsistencia.Además,932participantesmayoresde55añosdela cohorte“SeguimientoUniversidaddeNavarra”fueronevaluadosconlaSTICS-m.Duranteunamediana deseguimientode6,5años,serecogióinformaciónsobreeldesarrollodedemencia.Medianteregresión logísticaseestudiólaasociaciónentrelapuntuacióndelaSTICS-moelcambioa2añosenla pun-tuaciónyelriesgodedesarrollardemencia,ajustandoporapolipoproteínaE,edadyañosdeeducación universitaria.

Resultados: ElCCIentreelMMSEylaSTICS-mfuede0,31(intervalodeconfianzadel95%[IC95%]: 0,13-0,48).Laoddsratio(OR)ajustadaparaeldesarrollodedemenciaparacadapuntoadicionalen lapuntuaciónbasal delaSTICS-m fuede0,85(IC95%: 0,72-1,02;p=0,084).Alconsiderar el cam-bioenlapuntuaciónalos2a˜noscomovariableindependiente,laORfuede0,79(IC95%:0,67-0,93; p=0,006).

∗ Correspondingauthor.

E-mailaddress:[email protected](E.Toledo). https://doi.org/10.1016/j.gaceta.2018.05.004

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Conclusiones: LacorrelacióndébilentrelaSTICS-myelMMSEreflejasolounamoderada-bajavalidez concurrente.Aunasí,laSTICS-mpuedeconsiderarseútilenelcontextoepidemiológico,yaqueaumentos enlapuntuaciónparecenpredecirunmenorriesgodedesarrollardemencia.

Introduction

Theworldwideprevalenceofdementiain2015was46.8million, withtheexpectancyofthisnumbertoreach131.5millionby2050.1 In2011,forSpain,thelifetimeriskofdementiainpeopleagedover 65was14.1%formenand19.7%forwomen.2_{Alzheimer’s}_disease is theleading causeof dementia, followed byvascular demen-tia.TheincidenceofAlzheimer’sdiseaseintheSouthofEurope (Greece,ItalyandSpain)in2015wasestimatedat8.97per1,000 person-years,withanincreasewithage:from3.43inpeopleaged 65-74yearsoldto35.74per1,000person-yearsinpeopleagedover 85.3_At_the_same_time,_there_is_an_important_expected_rise_in_the populationover65yearsoldinSpain,from18.7%in2016,to34.6% in2066.4 _Nonetheless,_effective_treatments_for_any_type_of cog-nitiveimpairmentstillseemillusive.5_A_strategy_that_could_delay byoneyearthestartandprogressionofdementiawouldreduce theglobalincidenceby9.2millionin2050.6 _Therefore,_there _is asolidinterestinpreventivemeasuresthatwillslowdownthe progressofdecreasingcognitivefunction.Epidemiologicalstudies seekingtodeterminetheimpactofrisk factorsinthe develop-mentofdementianeedareliable,valid,andefficientmethodof evaluatingcognitivefunction.

TheMiniMentalStateExamination(MMSE)7_is_widely_used_as ascreeningtooltoassesscognitivefunctionintheclinicalsetting.8 However,face-to-faceevaluationsaretime-consumingandcostly, andtheirpracticalityforlargeepidemiologicalstudiesislimited. TheTelephoneInterviewforCognitiveStatus(TICS)isabrieftest ofcognitiveevaluationadministeredoverthephone,intendedto beusedinlarge-scalescreeningandepidemiologicalstudies.9 _A modified version ofthe TICS(TICS-m)was developed afterthe inceptionoftheoriginalversion,eliminatingitemsthatwere dif-ficulttoverifyoverthephoneandaddingadelayedrecallitem, improvingsensitivitybutnotaddinglengthtothequestionnaire. TICS-mhasshown anexcellentsensitivity (85%)and specificity (83%) indifferentiatingAlzheimer’s diseasepatientsand cogni-tivelynormalsubjects.10

While it is important to certify that the TICS-m correctly evaluatescognitivefunctioncomparedtoalreadyusedand val-idated cognitive function tests, such as the MMSE, its most interestingfeaturewouldbetheapplicablepredictionofdecline incognitivefunctionover theyears. TheTICS-mhasbeen vali-datedinotherstudiesthat confirmitsusefulness inthesetting oflargeepidemiological studies,and ithasalsobeentranslated intoseveralotherlanguages.11–15_There_is_no_other_previous vali-dationstudyfortheSpanishversion(STICS-m),althoughaprevious studyreportedontheusefulnessoftheSTICS-m.16_This_study_aims tovalidatetheSpanishtranslationofthequestionnaire(STICS-m), usingtheMMSEasastandardcriterionofnormalcognitive func-tion.Additionally,ittriestoassesstheSTICS-m’sabilitytopredict dementiacases,evaluatingitsutilityforepidemiologicalstudies.

Method

Subjects

Weapproached volunteersrecruitedat primarycarecenters inNavarre,Spain,withnorelevanthearingimpairment,ableto

understand and speak Spanish, as part of the PREDIMED Plus study. The PREDIMED Plus study is an intervention trial that evaluatestheeffectofanintensivelifestyleprogramwithcaloric restrictionon obesity, weight loss and related conditions such as neurodegenerative diseases. The sample consisted of men between55-75yearsoldand womenbetween60-75yearsold, overweightorobese.Theyunderwentanin-person neurocogni-tiveassessmentbatterybyatrainednurse,includingtheMMSE. Normalcognitivefunction,asassessedbythecomplete neuropsy-chologicalevaluation,wasacriterionforinclusion.TheSTICS-m wasperformed bya neurologist and completed ona subgroup of these subjects within a 2-month period since the baseline MMSE.

Additionally,participantsfromthe“SeguimientoUniversidad deNavarra”(SUN)studywererecruitedthrough detailed ques-tionnaires, which included general information about health, foodhabitsandeducationallevel. TheSUNstudyis anongoing dynamicprospectivecohortofSpainuniversitygraduatesfocused onlifestyleissuesandtheirrelationshiptodisease.17_For_the_SUN study,22,564participantswererecruiteduptoMarch2017.Out ofthese,1,921participantsovertheageof55yearswereinvited tobeevaluatedwiththeSTICS-m.Asubsampleof1,063subjects accepted,outofwhich 933participantscompletedthebaseline questionnaireand892aftertwoyearsoffollowup.The diagno-sisofdementiawasgatheredthroughquestionnairesandmedical reports,whenneeded,duringamedianfollow-uptimeof6.5years. ApoEstatuswasdeterminedthroughgenotypingofDNAextracted fromsalivasamplespreviouslycollectedwiththeOragene-DNA (OG-500)kitfromDNAGenotek.

Cognitiveassessment

1)TheMini-MentalStateExamination

The MMSE is the most widely used tool for initial evalua-tionofcognitivefunctionintheclinicalsetting.Thetestincludes fivedomains:orientation;languageandcomprehension; registra-tionand recall (memory); attention/calculation and praxis.The maximum score is 30, with a score above 24 considered normal and below 21 practically always denoting cognitive deficiency.8 _Each_domain_contributes_almost_equally_to_the_total score14_.

2)TheTelephoneInterviewforcognitivestatus-modified

TheSTICS-misatranslationoftheTICS-minEnglish,whichisa modifiedversionoftheTICS.10_The_TICS-m_includes₁₂_items_that evaluatefourcognitivedomains:orientation;registration,recent memory and delayed recall (memory); attention/calculation; semantic memory, comprehension and repetition (language). The maximum TICS-m score is 51. In contrast to the MMSE, TICS-massignsahigherproportionofthetotalscoretothememory component.14_Some_{investigators}_prefer_to_use_the_original cogni-tivetest,withoutincludingthedelayed-recallcomponent,giving atotalof41points.9_Moreover,_no_optimal_cut-off_score_has_been established,varyingbetween22and28points.18

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TheSTICS-mcontainsthefollowingitems,inparentheseswe state the amount of points given for correctly answering all parts ofeach item: 1)full name(2 points);2)date (5points); 3)address (5 points); 4)counting backward (2points); 5) 10-wordlistlearningexercise(10points);6)serialsevensbackward (5 points); 7) responsive naming (4 points); 8) repetition (2 points);9)semanticmemory(currentSpanishPresidentandKing, 2 points);10) fingertapping (2points);11) word opposites(2 points)and12)delayedrecall ofthe10-wordlistintask5(10 points).

Statisticalanalysis

Baseline characteristics are reported as mean±standard deviationforquantitativetraitsandaspercentageforqualitative characteristics.

From the data gathered from the PREDIMED Plus study, the distribution of both cognitive screening test scores was plotted with histograms. The consistency between the MMSE (by personal interview) and the STICS-m (by telephone) was evaluated with an intraclass correlation coefficient (ICC) of consistency,without item number 12 ofthe STICS-m.The cor-relationbetweencognitivetestswasevaluatedwithaSpearman correlation coefficient (␳, rho). As sensitivity analysis, an ICC

was calculated using the STICS-m including item number 12. Furthermore, since the memory component is more promi-nent in the STICS-m than in the MMSE, we also calculated an ICC using the total scores of MMSE and STICS-m without the memory items (divided into recent and delayed recall). A comparison of each domain for the MMSE and the STICS-m was also performed, not including the praxis domain of the MMSE.

From the data of the SUN cohort, we described with box-plots baselineand 2-yearchanges in STICS-mscoresseparately among participants who remained free of dementia during follow-upandamongparticipantswhodevelopeddementia dur-ing follow-up. Changes between scores at baseline and at the 2-yearfollow-upwerecomparedbetweenpatientswhodidand whodidnot developdementia witha Student’st-test.In addi-tion,wecalculated baselineand2-year changesintheSTICS-m score among participants who developed and did not develop subsequent dementia during follow-up adjusted for ApoE (do-minantmodel),ageatbaselineSTICS-mascertainmentandyears ofuniversityeducation.Wealsousedmultivariatelogistic regres-sionmodelstoassesstheassociationbetweenbaselineSTICS-m score or 2-year changes in STICS-m score and the subsequent riskofincidentdementia,adjustingforApoE(dominantmodel), age at baseline STICS-m ascertainment and years of university education.

AllanalyseswereperformedusingSTATASE13.0software.

Ethicsapprovalandconsenttoparticipate

Toobtaininformedconsentofpotentialparticipants,weduly informed these potential candidates of their right to refuse to participate in the SUN study or to withdraw their consent to participate at any time without reprisal, according to the principles of theDeclaration of Helsinki.Special attentionwas given to the specific information needs of individual poten-tialcandidatesas wellas tothemethods used todeliver their information and the feedback that they may receive from the research team. After ensuring that the candidate had under-stood the information, we sought their potential freely-given informedconsent,andtheirvoluntarycompletionofthebaseline questionnaire. Participants in the cognitive function subpro-ject of the SUN cohort provided a specific written informed

Figure1.DistributionofscoresofMiniMentalStateExaminationandmodified SpanishTelephoneInterviewforCognitiveStatusamongPREDIMEDPlus partici-pants.

consent. Participants in the PREDIMED-Plus trial provide writ-ten informed consentbefore entering the trial.These methods wereacceptedbytheInstitutionalReviewBoard ofthe Univer-sityofNavarra(ComitédeÉticadelaInvestigación,Universidad de Navarra) as to imply an appropriately-obtained informed consent.

Results

Atotalof106participants(56%men)wereincludedinthe analy-sisofconsistencybetweenMMSEandSTICS-mfromthePREDIMED Plusstudy.Theageoftheparticipantsatrecruitmentwas65±5 years.Thehistogramswiththedistributionofscoresforboththe MMSEandSTICS-mareshowninFigure1.ThemeanMMSEscore was28.4±1.6and themeanSTICS-m scorewas32.4±3.8.The ICCofconsistencybetweentheMMSEandtheSTICS-mwas0.31 (95%confidenceinterval [95%CI]:0.13-0.48)withoutitem 12of theSTICS-mand0.24(95%CI:0.05-0.41)withthisitem.The Spear-mancorrelationcoefficientwas0.27(p=0.0087),aftereliminating nineparticipantswithanimprobableTICSscore,whencompared withtheMMSEscore.Wheneliminatingallmemoryitemsfrom bothcognitivetests(recentmemoryanddelayedrecall),theICC ofconsistencybetweentheMMSEandSTICS-mincreasedslightly toICC=0.33 (95%CI:0.15-0.49).TheICCofconsistencybetween thecognitivetestsforeachdomainwas:0.15(95%CI:−0.04-0.33) fororientation,0.00(95%CI:−0.19-0.19)forrecentmemory,0.36 (95%CI: 0.18-0.52)for attention/calculation,0.14 (95%CI:− 0.05-0.32) for delayed recall, and 0.21 (95%CI: 0.02-0.39) for language.

InordertoassesstheassociationbetweenSTICS-mand inci-dentdementia,933participants(71%men)fromtheSUNproject wereevaluated withthe STICS-mquestionnaireat recruitment. Oneparticipant wasexcludedbecauseofan implausible STICS-m score. Nineteen patients reported a diagnosis of dementia

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Figure2. Baselineand2-yearchangesinthemodifiedSpanishTelephoneInterview forCognitiveStatus(STICS-m)SUNProject.Distributionsareshownseparatelyfor participantswhodevelopedanddidnotdevelopdementiaduringamedian follow-upof6.5years.

duringa medianfollow-uptimeof6.5years.Atthetimeofthe first cognitive evaluation mean age was 67±6 years and the mean years of university education 5.3±1.8 years. The mean STICS-m scores at baseline in patients without dementia was 34.0±2.4 and32.7±3.6forpatientswithdementia. For partici-pantswithSTICS-mevaluationafter2-yearsoffollow-up(n=892), meanbaseline age was67±6years. The mean STICS-mscores in patients withoutdementia was 34.3±2.4 and 31.5±4.6 for patientswithdementia. Themean changefor subjectswithout dementiawas0.30±2.6and−1.8±3.5forsubjectswith demen-tia.Figure 2 shows the distributionof the baseline and 2-year changeintheSTICS-mscoreseparatelyforparticipantswho devel-opedanddidnotdevelopdementia.Theunadjustedchangeinthe STICS-mscorebetweenthosewhodidandwhodidnotdevelop dementiawasstatisticallysignificant(p=0.001).Meanchangesin theSTICS-mscoreadjustedforage,yearofuniversityeducation and ApoEgenotype (dominant model)were 0.30 (95%CI: 0.11-0.46)for participantswho didnot develop dementia and−1.66 (95%CI:−2.94to−0.38)forparticipantswhodiddevelopdementia (p=0.011).

Inthelogisticregressionmodel,theadjustedoddsratio(OR)for thedevelopmentofdementiaforeachadditionalpointinthe base-lineSTICS-mscorewas0.85(95%CI:0.72-1.02;p=0.084),adjusted for age at baseline STICS-m ascertainment, years of university educationandApoEgenotype(dominantmodel).TheORforthe developmentofdementiaforeachadditionalpointinthe2-year STICS-mscorewas0.74 (95%CI: 0.63-0.89;p=0.001).Whenwe consideredthe2-yearchangeintheSTICS-mscoreasexposure,the ORforthedevelopmentofdementiawas0.79(95%CI:0.67-0.93; p=0.006).

Discussion

Inthepresentstudy,weobservedaweakconsistencybetween theMMSEandtheSTICS-mscoreamongparticipantswho under-went both tests. Using data from the SUN project, adjusted mean 2-year changes in score demonstrated a maintenance of scores in patients without dementia and a decrease of almost 2pointsinpatientswhosubsequentlydevelopeddementia.The logisticregression modelshowedthatfor each additionalpoint in theSTICS-m score at year 2 of follow-up and in the 2-year changein score, the risk of developing dementia decreased by 26% and 21%,respectively. Therefore, despite thelow ICC with theMMSE,theSTICS-mappearstocorrectlydifferentiatepeople withahigherprobabilityofdevelopingdementiainlongitudinal studies.

Previous validation papers have reported moderate to high correlation between the STICS-m and the MMSE with the use of Pearson (r) or Spearman (␳) correlation coefficients. In our

study, ␳=0.27 (p=0.0087). The original TICS was reported to

have a r=0.94 (p<0.0001), which was evaluated on a pop-ulation of mainly Alzheimer’s disease patients.9 _A _validation of the German TICS-m showed a ␳=0.48 (95%CI: 0.36-0.58)

in a population study of people aged 70 years or older.19 _A thirdstudy,withasampleofrelativelyhighfunctioningadults, found a ␳=0.57 (p>0.001).14 Nonetheless, none of the

afore-mentioned studies reported the ICC. The ICC of consistency is probably a better measure of agreement between diagnostic tests,sincethecorrelationcoefficientsonlymeasureassociation, while theICC isan expression ofthe cognitivetest’s abilityto persistently orientate subjects as either cognitively normal or impaired.20

The low correlationbetween theMMSE and theSTICS-m is probably due to the population of our study, combined with the characteristics of the cognitive tests. The PREDIMED Plus sample,inwhichtheboth MMSEandSTICS-mwereperformed, consistedofcognitivelynormaladults,whichisconfirmedbythe highmeanscoresinboththeMMSEandtheSTICS-m.TheMMSE can be less sensitive to cognitive changes in high functioning individuals, a phenomenon knownas theceiling effect.21 _This, combined with the sparser distribution of the STICS-m scores in comparison tothe MMSE,as representedby thehistograms andstandard deviations,mighthaveaccountedforthelowICC. Furthermore, the memory and registration component of the TICS-m accounted for 20 out of the51 points(vs. 6 out of 28 ontheMMSE),whichmayenhancethesensitivityofthistestto detectearlycognitivedysfunction,22_but_increase_the_differences betweencognitivetests.14_Therefore,_the_low_correlation_can_be partlyjustifiedbythefactthattheMMSEdoesnotidentifywell early memory deficits while the TICS-m has a more thorough memoryevaluation.Forthisreason,weeliminateditem12forour analysis,whichallowsforabettercomparisonbetweenmemory domains(10outof41pointsintheSTICS-mvs.6outof28inthe MMSE).

The data from the SUN study suggests the practical utility of theSTICS-m for epidemiological studies.While these cogni-tivetestsare frequentlyusedtoclassify subjectsascognitively normalorimpairedaccordingtoscore,weusedtheSTICS-mas a quantitative variable to predict the development of demen-tia. While not statistically significant in this sample, a higher baseline STICS-m score appears to predict a lower probabil-ityof developing dementia. Themultivariatelogistic regression model indicates that each additional point in 2-year change in STICS-m score decreased the risk of developing dementia by 21%. Therefore, even as the correlation with the MMSE is weak, the STICS-m score appears to be a suitable tool to

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detect change in cognitive function over the years. A review oftelephone-administeredscreeningtestsfor dementia diagno-sis states that it is more clinically relevant that a screening methodindicatescorrectlywhetheranindividualislikelytohave dementia, rather thancorrelate welltoanother briefscreening measure.23

There are other advantages of using the STICS-m over the MMSEor other in-personcognitive testsin large epidemiolog-ical studies. The TICS-m is a more efficient tool and hasbeen shown to reduce selection bias, as it allows recruiting people over larger areas, and enables follow-up. Even as the use of telephone screening methods are not entirely homogenous,24 the advantages of using telephone interviews may outweigh theirmethodologicallimitations.25_The_STICS-m_can_also_be per-formedinvisually-impairedpopulationsandparticipantsmayfind a cognitive telephoneinterview less threatening than in-clinic assessments,leadingtolowerdropoutsandmorecompletedata collection.14

Some strengths and limitations in our study deserve to be mentioned. A potential limitation in this work is the lack of comparison of the STICS-m to a neuropsychological or clinical evaluationoftheparticipantsinthetwosamples.In the PRED-IMEDPlussample,thiswouldhaveallowedtocomparetheSTICS-m toa more suitable gold standard of dementia diagnosis,rather thantheMMSE,andcalculatemeasuresofsensitivityand speci-ficity.Anotherpossibilitycouldhavebeencorrelatingthememory componentoftheneuropsychological teststotheSTICS-m. Fur-thermore,thefirstsample(undergoingbothMMSEandSTICS-m) wasonlyevaluatedwithSTICS-matonepointintimeandnodata onApoEstatuswereavailable.IntheSUNproject,noMMSEwas performed,although a similarcorrelation as seenin this study would have probably been foundsince this populationof uni-versitygraduatescanbedescribedashigh-functioning.Another limitationisthatthenumberofpatientsthatdeveloped demen-tia in this cohort was low. However, despite the low number of dementia cases, the change in STICS-m over 2-year follow-up when comparing patients with and without dementia was statisticallysignificant.Sincethehigh-functioningandhigh-level of education profiles of both samples might explain the low correlation betweencognitive tests,further investigations with the STICS-m in samples withdifferent characteristics are war-ranted.

Within the strengths of our study is the performance of the telephone questionnaire by a single neurologist for the first sample, which demonstrates both quality and consis-tency in the cognitive evaluation. Another positive aspect of our study is the long-term follow up of the SUN project, as few validation papers observe the change or stability in TICS over a long period of time. Furthermore, the informa-tion gathered for the SUN cohort, although self-reported, has been determined to be reliable by a series of studies that establishedthereproducibilityofthequestionnairesandsome self-referreddiagnosis,suchashypertension,depressionandmetabolic syndrome.26–28

Conclusion

Insummary,theSTICS-mcanberegardedasausefultoolin theepidemiologicalsetting.Previousvalidationstudiesin multi-plelanguagesascertainitsvalueasascreeningtoolfordementia diagnosisandthisstudyconfirmsits—albeitlow—correlationto in-personcognitiveassessment,whilealsoprovidingevidenceof itsabilitytopredictcognitivedecline.

Whatisknownaboutthetopic?

The modified Telephone Interview for Cognitive Status (TICS-m)is ascreening toolforcognitive function thathas advantages over face-to-face evaluation, especially in the context of epidemiological studies. The TICS-m has been validatedinseverallanguages,demonstratingithas diagnos-tic validity (goodsensitivity and specificity) and concurrent validity,incomparisonto othercognitivetestswidely used intheclinicalsetting,liketheMini-MentalStateExamination. Inlargeepidemiologicalstudies, itallowstheevaluation of cognitivefunctionatalargerscale,inordertoestablish poten-tial associationsbetween riskfactorsand cognitivedecline, essentialtoimplementprimarypreventionmeasuresagainst dementia.Hitherto,therehasnotbeenavalidationstudyofthe SpanishversionofTICS-m.

Whatdoesthisstudyaddtotheliterature?

Eventhoughwehavefoundalowconsistencybetweenthe resultsoftheMini-MentalStateExaminationandtheSpanish versionofmodifiedTelephoneInterviewforCognitiveStatus (STICS-m),thescoreofthequestionnaireseemsabletopredict agreaterriskofdevelopingdementia.Therefore,the question-naireallowsthestudyoftherelationshipbetweencognitive function and lifestyle factors. The STICS-m has been used inthe “Seguimientode Universidadde Navarra”cohort of Spanishuniversitygraduates,whichhasgatheredinformation onlifestyles.Thestudyoftherelationshipbetweencognitive functionandexercise,dietarypatternsandcardiovascularrisk factorsinthiscohortcanexpandcurrentknowledgeon poten-tialpreventivemeasuresagainstcognitivedecline,inacontext wherethisdiseasewillbemoreandmoreprevalentasthe populationages.

Editorincharge

María-VictoriaZunzunegui.

Transparencydeclaration

The corresponding author on behalf of the other authors guaranteetheaccuracy,transparencyandhonestyofthedataand informationcontainedinthestudy,thatnorelevantinformation hasbeenomittedandthatalldiscrepanciesbetweenauthorshave beenadequatelyresolvedanddescribed.

Authorshipcontributions

M.Mu˜noz-Garcíawasinvolvedindraftingthemanuscriptand revisingitcriticallyforimportantintellectualcontent.S.Cervantes madesubstantialcontributionstoconceptionanddesign, acquisi-tionofdata,analysisandinterpretationofdata;healsogavefinal approvaloftheversiontobepublished.C.Razquinalsocontributed toconceptionanddesign,acquisitionofdata,analysisand inter-pretationofdata; shealsogave finalapproval oftheversion to bepublished.F.Guillén-GrimaandJ.B.Toledogavefinalapproval oftheversiontobepublished.M.A.Martínez-Gonzálezobtained fundingandmadecontributionstoconceptionanddesign, revis-ingthemanuscriptcriticallyforimportantintellectualcontentand wasinvolvedingivingfinalapprovaloftheversiontobepublished. E.Toledoobtainedfundingandmadesubstantialcontributionsto conceptionanddesign,acquisitionofdata,analysisand interpre-tationofdata,revisingthemanuscriptforintellectualcontent,and givingfinal approvaloftheversiontobepublished.Allauthors

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agreedtobeaccountableforallaspectsoftheworkinensuring thatquestionsrelatedtotheaccuracyorintegrityofanypartofthe work.

Acknowledgments

WethankalltheSUNandPREDIMEDPlusparticipantsfortheir collaboration.WealsothanktheotherSUNProjectinvestigators (A.Alonso,M.T.BarrioLópez,F.J.Basterra-Gortari,S.Benito Cor-chon,M.Bes-Rastrollo,J.J.Beunza,S.Carlos,J.deIrala,P.A.dela Rosa,C. delaFuente,C.L.Donat-Vargas,M.Donazar,A. Fernán-dez Montero, C. Galbete-Ciaurriz, A.Gea, E.Goni-Ochandorena, F. Lahortiga, J. Llorca, C. López del Burgo, A. Mari-Sanchís, A. Martí, R. Mendonça, J.M. Núñez-Córdoba, A.M. Pimenta, R. Ramallal Martínez, A. Rico, A. Ruiz Zambrana, M. Ruiz-Canela López, C. Sayón-Orea, Z. Vázquez Ruiz, I. Zazpe García), the PREDIMED Plus investigators at the University of Navarra and Primary Health Care Centers in Navarra (A. Sánchez- Tainta, P.Buil-Cosiales,J.Díez-Espino,B. Sanjulián,O.Lecea,J.C.Cenoz, R. Bartolomé, S. Eguaras, J.A. Martínez, A. Martí, F.J. Basterra-Gortari,J.Bartolomé,N.Goñi,E.Lozano,J.V.Extremera-Urabayen, L.García-Pérez,C.Arroyo-Azpa,A.Sola-Larraza,F.Bárcena,C. Oreja-Arrayago,M.J. Lasanta-Sáez,P.Cia-Lecumberri, T.Elcarte-López, F. Artal-Moneva, J.M. Esparza-López, E. Figuerido-Garmendia, J.A. Tabar-Sarrias, L. Fernández-Urzainqui, M.J. Ariz-Arnedo, J.A. Cabeza-Beunza, P. Pascual-Pascual, M.D. Martínez-Mazo, E.Arina-Vergara, T. Macua-Martínez,A. Parra-Osés) and tothe otherPREDIMEDPlusinvestigators.WealsothanktheInternational Nut&DriedFruitCouncil-FENADNo.201302,Martínez-González (PI)and theERCAdvancedGrant2013(No340918)“Long-term effects of anenergy-restrictedMediterranean diet onmortality andcardiovasculardisease:thePREDIMED-PlusStudy” Martínez-González(PI).

Funding

The SUN Project has received funding from the Spanish Government-Instituto de Salud Carlos III, and the Euro-pean Regional Development Fund (FEDER) (RD 06/0045, CIBER-OBN, Grants PI10/02658, PI10/02293, PI13/00615, PI14/01668,PI14/01798,PI14/01764,andG03/140),theNavarra RegionalGovernment(45/2011,122/2014),andtheUniversityof Navarra.ThePREDIMEDPlus-NAVARRAtrialhasreceivedfunding fromtheEuropeanResearchCouncil (AdvancedResearchGrant 2013-2018; 340918) granted to MAMG, the Instituto de Salud CarlosIII(PI13/01090,PI16/01522).

Conflictsofinterests

None.

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