self administered cognitive screening test (tym) for ad detection

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RE SE ARCH

Self administered cognitive screening test (TYM) fordetection of Alzheimers disease: cross sectional study

Jeremy Brown, consultant neurologist George Pengas, clinical research fellow Kate Dawson, research nurse

Lucy A Brown, honorary research assistant Philip Clatworthy, clinical research fellow

ABSTRACT

Objective To evaluate a cognitive test, the TYM (test your

memory), in the detection of Alzheimers disease.

Design Cross sectional study.

SettingOutpatient departments in three hospitals,including a memory clinic.

Participants 540control participantsaged 18-95 and139

patients attending a memory clinic with dementia/

amnestic mild cognitive impairment.

Intervention Cognitive test designed to use minimal

operator time and to be suitable for non-specialist use.

Main outcome measures Performance of normal controls

on the TYM. Performance of patients with Alzheimers

disease on the TYM compared with age matched controls.

Validation of the TYM with two standard tests (the mini-

mental state examination (MMSE) and the Addenbrookes

cognitive examination-revised (ACE-R)). Sensitivity and

specificity of the TYM in the detection of Alzheimersdisease.

Results Control participants completed the TYM with an

average score of 47/50. Patients with Alzheimers disease

scored an average of 33/50. The TYM score shows excellent

correlation with the two standard tests. A score of42/50

had a sensitivity of 93% and specificity of 86% in the

diagnosis of Alzheimers disease. The TYM was more

sensitive in detection of Alzheimers disease than the mini-

mental examination, detecting 93% of patients compared

with 52% for the mini-mental state exxamination. The

negative and positive predictive values of the TYM with the

cut off of42 were 99% and 42% with a prevalence of

Alzheimers disease of 10%. Thirty one patients with non-

Alzheimer dementias scored an average of 39/50.

Conclusions The TYM can be completed quickly and

accurately by normal controls. It is a powerful and valid

screening test for the detection of Alzheimers disease.

INTRODUCTION

Dementia and other cognitive problems are common.An estimated 24 million individuals in the world havedementia and the number affected will double every20 years.1 Milder forms of cognitive dysfunction,including mild cognitive impairment, affect many

more people.2

Alzheimers disease is the commonestform of dementia. Cognitive problems are a feature of

many neurological and medical diseases includingstroke, Parkinsons disease, head injury, and epilepsy.

Assessmentofapatientscognitionisacrucialpartofmany medical consultations. Cognitive tests aid the

diagnosisof dementia andare important in themedicaland social management of patients and in the assess-ment of capacity. Once there are effective treatmentsfor Alzheimers disease there will be an even greaterneed for a quick sensitive test that is suitable for use inprimary care and by non-specialists.

Many cognitive tests are available but none meetsthe three critical requirements for widespread use bya non-specialistthat is, take minimal operator time toadminister, test a reasonable range of cognitive func-tions, and are sensitive to mild Alzheimers disease.We designed the TYM (test your memory) to fulfilthese requirements. The paradox of thorough testing

in minimal time was achieved by allowing patients tofill in the test themselves.The TYM was administered to 540 normal controls

aged 18-95, 108 patients with Alzheimers disease/amnestic mild cognitive impairment, and 31 patientswith non-Alzheimers degenerative dementias. Thetest was validated by comparing scores with thoseobtained with the mini-mental state examination3 andAddenbrookes cognitive examination-revised.4 TheAddenbrookes revised test was developed from theoriginal examination5 and is similar in both contentand scoring.4 We determined the specificity and sensi-tivity of the TYM in the detection of Alzheimers dis-

ease by comparing the scores of 94 patients withAlzheimersdiseasewiththescoresof282agematchedcontrols. Three scorers of differing backgroundsmarked 100 tests to assess inter-rater reliability.

METHODS

The TYM test

The TYM is a series of 10 tasks on a double sided sheetof card with spaces for the patient to fill in (see appen-dix 1 on bmj.com). The patients ability to completethe test is an 11th task. The tasks are orientation (10points), ability to copy a sentence (2 points), semanticknowledge (3 points), calculation (4 points), verbal flu-

ency (4 points), similarities (4 points), naming (5points), visuospatial abilities ( 2 tasks, total 7 points),

Department of Neurology,Addenbrookes Hospital,Cambridge CB2 2QQ

Correspondence to: J [email protected]

Cite this as: BMJ2009;338:b2030doi:10.1136/bmj.b2030

BMJ | ONLINE FIRST | bmj.com page 1 of 8


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and recallof a copiedsentence(6 points). Theability todo the test is also scored (5 points), giving a possibletotal of 50 points. The scoresfor thesubsets areprintedon thecard and thetotal score calculated by addingthesubset scores. To ensure consistent scoring a singlesheet of scoring instructions is available.

Participants

Selection of patients with Alzheimers disease

Patientswere seen and diagnosed by a consultant neurol-ogist with an interest in dementia in a dedicated memoryclinic at Addenbrookes Hospital. Patients attended thememory clinic between March and December 2007 andunderwent neurological assessment, the Addenbrookescognitive examination-revised (which includes the mini-mental state examination), structural imaging, and bloodtests. Many also had a psychiatric and neuropsychologi-cal assessment.The diagnosis of Alzheimers disease wasmade with the NINCDS-ARDRA (National Institute of

Neurologicaland CommunicativeDisorders and Stroke-Alzheimers Disease and RelatedDisorders Association)criteria for probable Alzheimers6 without reference totheTYMresult.The diagnosis ofamnestic mild cognitiveimpairment was made according to published criteria.7

We excluded patients whose cognitive problems werethought to be substantially caused by depression.

A total of 108 patients (59 men, 49 women) receiveda clinical diagnosis of Alzheimers disease or amnesticmild cognitive impairment. Alzheimers disease wasdiagnosed in 85 and amnestic mild cognitive impair-ment in 23. Amnestic mild cognitive impairment hasclinical and pathological similarities to Alzheimersdisease89 and patients with amnestic mild cognitiveimpairment who score poorly on the Addenbrookescognitive examination are likely to progress to Alzhei-mers disease.10 These patients were regarded as hav-ing early Alzheimers disease. Nine patients with adiagnosis of amnestic mild cognitive impairment whoscored below the cut off for dementia on the Adden-brookes cognitive examination-revised (834) wereincluded in the Alzheimers cohort. Patients with adiagnosis of amnestic mild cognitive impairment whoscore well on the Addenbrookes cognitive examina-tion are unlikely to progress to Alzheimers disease

over the next two years10

; such patients might neverprogress to Alzheimers disease and might return tonormal.11 The 14 patients with a diagnosis of amnesticmild cognitive impairment who scored >83 on theACE-R were analysed separately.

Selection of controlsControls were recruited from relatives accompanyingpatients to the memory clinic. Additional controlswererecruited fromrelatives of patients attendingneu-rology and medical outpatients departments at twoother hospitals. We also included some dermatologyoutpatients. We excluded people with a history of neu-rological disease, memory problems, or brain injury.All participants gave informed consent.

We tested 540 controls aged 18-95. Over half (54%)were women. We calculated normal values for eachdecade from the age of 30 with standard errors. Threeage matched controls were selected for each patient

with Alzheimers disease. To assess any differences incontrols between different hospitals,we compared100controls from Addenbrookes with 100 age matchedcontrols from the other hospitals. To assess any sexdifferences, we compared 100 male controls with 100age matched female controls.

Testing and validation

The 94 patients in the Alzheimers cohort were giventhe TYM as well as the Addenbrookes cognitiveexamination-revised (that includes the mini-mentalstate examination). The TYM was administered whenthe patient first arrived in the clinic.

We compared the scores of patients and age matchedcontrolson subsetsandtotal scores usingttests withBon-ferroni correction for multiple comparisons (equal var-iances not assumed). We compared the TYM scores ofpatientswiththe Addenbrookes and mini-mentalscoresusing Pearsons correlation coefficients. The internalconsistency of the TYM wasassessedwithCronbachs.

Sensitivity and specificity of TYM in mild Alzheimers

disease

We used data from the 94 patients with Alzheimer sdisease to plot a receiver operating characteristiccurve. We randomly selected three age matched con-

trols (n=

282) from the 540 controls for each patientwith mild Alzheimers disease. We calculated positive

Age group (years)

Meantotalscore

18-400

40

45

50

41-9 50-9 60-9 70-9

P=0.002

>80

Fig 1 | Mean total TYM scores (out of maximum possible score

of 50) in control participants grouped according to age

(decade). Errors bars are 2SE. Post-hoc testing showed

significant impairment in performance for participants aged

>80 compared with all younger age groups except age 71-80

(mean difference in score between age groups 61-70 and >80

was 2.7, P=0.002)

Table 1 |Average scores on memory test (TYM),

Addenbrooke s cognitive examination-revised (ACE-R), and

mini-mental state examination (MMSE) and variability of

these scores for patients with Alzheimers disease (n=94)

Mean (SD) raw score

TYM (total) 33.2 (8.2)

ACE-R 66.9 (12.0)

MMSE 22.5 (3.8)

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and negative predictive values for different TYMscores for differentprevalences of Alzheimers disease.

Sensitivity of TYM vmini-mental state examination

A direct comparison between the TYM and the mini-mental state examination in identifying the 94 patients

withAlzheimer

s disease was performedby calculatingthe percentage of patients with Alzheimers diseasewho were detected using the cut off of 42 for theTYM and 23 for the mini-mental state examination(the accepted cut off for dementia12).

Performance of TYM v other tests in other forms of

dementia and mild cognitive impairment

In the same period, 31 patients (17 men, 14 women;average age 63.3) with other degenerative dementiasseen in the Addenbrookes memory clinic as newpatients were given the TYMand Addenbrookes cog-nitive examination-revised. Of these patients, 16 haddementia with Lewy bodies, 13 had frontotemporaldementia, and two had progressive supranuclearpalsy. Thediagnoses were made accordingto acceptedcriteria.13-15 Pearson coefficients were used to calculatethe correlation between the TYM scores and the otherexaminations.

TYM in mild cognitive impairment

Fourteen patients in the mild cognitive impairmentcohort (average age 67.9) were given the TYM aswell as the Addenbrookes examination. We com-pared these scores with the TYM scores attained bythe controls used for the Alzheimers cohort.

Inter-rater variabilityThree individuals scored the same 100 TYM sheets(38 patients, 62 controls) using the scoring sheet.One was a consultant experienced in the diagnosisof degenerative dementia (JB), one was a neurologyspecialist registrar working in the memory clinic(GP), and one a registered general nurse (LAB) with

no specialised experience of patients with dementiawho received 10 minutes of tuition. The tests werescored independently.

RESULTS

Reliability and normative data

The TYM was filled in quickly and efficiently by con-trols and patients with minimal supervision from areceptionist or nurse. The average time for a controlto complete the test was five minutes.

The value of Cronbachs for all participants andsubsets was 0.80. Figure 1 shows the results for controlparticipants grouped by age. The average TYM scorewas about 47 for ages18-70. Above the age of 70, therewas a small decline in performance, which became sig-nificant above the age of 80. One way analysis of var-iance confirmed a significant effect of age group on

total TYM score (F5,534=6.4, P


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We found strong and significant correlationsbetween all scores in patients with Alzheimers(TYM v Addenbrookes R2=0.66, P


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the age of 18 to 70 the average score was stable at 47/50, with a small decline after this age. Scores on allsubsets of the TYM deteriorated with age, with theexception of semantic knowledge (these questionswere designed for older patients).

Many of the controls were relatives of patients

attending the memory clinic and came from the samepopulation base. There was a slight male bias in thepatients and slight female bias in the controls, butthere was no significant difference in TYM scoresbetween male and female controls. We recruitedmore controls from two other hospitals in East Angliabecause the age range and number of the memorycliniccontrolswas limited. Thecontrolsfromthe Cam-bridge memory clinic might have been expected toscore slightly higher, but actually scored slightlylower.Thiseffectwasnotlargeenoughtobesignificantor to affect the results. Control participants werescreened fora history of memory problems and neuro-

logical disease but not for other problems such asdepression or vascular disease; such influences wouldbe expected to reduce the TYM scores of controls andreduce differences in cognitive function betweenpatients and control participants.

The TYM score of controls remained remarkablyconstant in widely different age ranges in both sexesand all geographical backgrounds. This is likely to bea ceiling effect. The TYM test was designed to be easyfor normal controls to allow quick and accurate com-pletion. Most controls of all ages scored almost fullmarks (for example, 68%of controls aged 60-69 scored48-50). This ceiling effect suggests that education and

social class would have only mild effects on the TYMscore, but we did not formally assess this. The reasonfor the low scoring controls was often apparent fromthescoresheetlackofinterest,readingproblems,orasense of humour. Some lowscoring controls aged over70 show a typical pattern for mild Alzheimers andmight be in the early stages (they were still includedin the control group).

Use in patients with Alzheimers disease

Patients with Alzheimers disease performed muchpoorer than controls on the TYM. They scored anaverage of 33/50; 13.4 points below the control

group. Subtest analysis of scores in patients with Alz-heimers showed that all parts of the test, except copy-ing a sentence,are performed less well by patients thancontrols. There is the expected pattern in patients withAlzheimers performing poorlyon tests of anterogradememory, semantic knowledge, fluency, and

visuospatial tasks. They perform better (although stillsignificantly worse than controls) on naming, orienta-tion, similarities, and calculation subtests. Patients per-formed worse than controls in the copying subtest, butthe difference was not significant; this test was prob-ably too easy to identity patients with mild Alzhei-mers.

We separately analysed patients with mild memoryproblems. These patients had a clinical diagnosis ofamnestic mild cognitive impairment and scored wellon the Addenbrookes examination (>83). Amnesticmild cognitive impairment can be a prodrome of Alz-heimers, but some affected patients have mild pro-blems that do not progress.11 The Addenbrookes testis a good indicator of which patients with amnesticmild cognitive impairment (or questionable dementia)will develop progressive dementia in the two yearsafter testing: patients who score 80 are likely to pro-gress, patients who score >80 are unlikely toprogress.10 In this study as we used the higher cut offof83,theacceptedcutofffordementiafortheAdden-brookes test,5 some non-progressive patients mighthave been included in the Alzheimers cohort. Thepatients with mild cognitive impairment scored anaverage of 45/50 on the TYM, with a trend towardsproblems in anterograde memory; they scored wellin other subtests of the test.

Patients seen in the memory clinic in Cambridgecould be different from those seen in other clinics.Cambridge attracts some younger patients with Alz-heimers from a wide area. The memory clinic servesa dual purpose in Cambridge, and many of the olderpatients in the study were local and referred directly

from primary care. We separately examined the per-formance of the 42 patients with Alzheimers aged 70orover (averageage 76.8).Therewas littledifferenceinthese patients compared with the younger patientseitherin overall TYM score (33.9 v32.6) or in the subt-est pattern. This suggests that it is a useful test to detectolder patients with Alzheimers.

Thesensitivityand specificity of theTYM for detect-ing Alzheimers in this cohort is high. A score of42detects 93% of cases of mild Alzheimers with a speci-ficityof86%;ascoreof44detects96%ofpatientswithmild Alzheimers. The prevalence of dementia andmild cognitive problems (often with reduced insight)

in the population sets a limit on the specificity of a test.The testers and raters were usually aware of whether

individuals were patients or controls at the time of test-ing or rating. As individuals fill in the test sheet them-selves, the tester has minimal influence on the score.All scores were checked by a single rater (JB) usingthe scoring sheet. The use of a strict scoring schememinimises the influence of the rater. Scores calculatedby the single rater correlated closely with the scores ofthe other two raters in the inter-rater analysis.

TYM v mini-mental state examination

The mini-mental state examination has been the stan-

dard short cognitive test for 30 years. It has provedvaluable in the assessment of patients with established

Table 4 | Inter-rater agreement for memory test with three different raters, rating 100

randomly chosen participants (38 patients and 62 controls)

RaterMean(SD)rawscore

(/50)

Pearsons r (r2) correlation

Consultant Trainee Nurse

Consultant 43.8 (6.4) 0.99 (0.98) 0.99 ( 0.98)

Trainee 43.8 (6.5) 0.99 (0.98) 0.99 (0.98)

Nurse 43.8 (6.5) 0.99 (0.98) 0.99 (0.98)

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dementia. It has many strengths but fails three of therequirements for a brief screening test for the non-spe-cialist: minimal operator time, testing a wide range ofcognitive domains, and sensitivity to mild Alzhei-mers.

The mini-mental state examination takes an averageof eight minutes to administer. Many clinicians find

time to complete this but with an average consultationtime in general practice in Europe of 10.7 minutes16

this is too long. Around 58% of physicians in hospitalpractice thought the length of time taken to administerthe mini-mental examination was too long.17

The mini-mental state examination tests several dif-ferent cognitive domains but has a bias towards domi-nant parietal and temporal lobe function. It is a usefultest of orientation, but the language and memory testsare too easy1819 and there is only a single point forvisuospatial tasks. These drawbacks lead to the majorproblem with the testthat it is insensitive in the diag-nosisof mildAlzheimers.5 18-20 In community and hos-

pital studies the sensitivity of the mini-mental stateexamination in detecting Alzheimers using the estab-lished cut off of 23 is low, varying from 49% to69%.5 19-21 In our study it detected 52% of patientswith Alzheimers. This low detection rate probablyreflects the high number of patients with mild Alzhei-mers.

The TYM fulfils the three requirements. If a patientcompletes the test while in the waiting area supervisedbythereceptionist,itcanbescoredandanalysedbythedoctor in two minutes. If there is time during the con-sultation to observe the patients filling in the test, thiscan also be a useful aid to diagnosis.

The11 TYMtasksexaminemorecognitive domainsthan the mini-mental state examination, with less biastowards dominant hemisphere language functions.The language and memory tests are more difficult.The inclusion of two visuospatial tasks, contributing7/50 points, is importantin distinguishingAlzheimersdisease from pure amnestic syndromes. The test has ahigh sensitivity for detecting Alzheimers. In our studyit detected 93% of cases of Alzheimers compared with52% detected by the mini-mental state examination.

There are some additional problems with the mini-mental state examination. The score is influenced byhow the tester asks the questions and also location

spatially disorientated patients might score 4 morepoints at home than in the clinic on the question of

current location. The TYM is less influenced by thetester as it is filled in by the patient and will not varywith location.

The small range of scores in the mini-mental stateexamination limit its suitability for monitoring, but itis widely used for this purpose. It is the main test cho-

sen by the National Institute for Health and ClinicalExcellence (NICE) for deciding which patients in theUnited Kingdomshould havecholinesterase inhibitorsand for monitoring their response to treatment.22 TheTYM has a much wider scoring range than the mini-mental state examination, with over 13 points betweenthe average control and the average patient with mildAlzheimers. In the group of 94 patients with Alzhei-mers in this study the range of mini-mental scores was14-30 while the range of TYM scores was 9-50 (2.5times greater).

TYM v Addenbrookes cognitive examination

TheoriginalandrevisedAddenbrooke

s examinationsare sensitive and specific in the diagnosis of degenera-tive dementia.45 The major drawback of the revisedexamination is that it fails to fulfilthe time requirementfor a test for non-specialists, taking 20 minutes toadminister and score. It tests a similar number of cog-nitive domains to the TYM and is sensitive to mildAlzheimers.

There was a strong correlation between the memoryscore and the Addenbrookes score in both Alzhei-mers and non-Alzheimers dementias. The TYMscore averages 50% of Addenbrookes score, enablingthetwoteststobeeasilycompared.Bothtestsprovidea

permanent record of the patient

s performance, whichcan be assessed later.

TYM v abbreviated mental test and other brief tests

Several brief cognitive tests have been published forscreening for memory problems.2324 Many of theseare simplesuch as clock drawing tests. These can beuseful in distinguishing patients with established Alz-heimers from normal controls but are too limited forroutine screening for mild Alzheimers.25

The abbreviated mental test2627 is the establishedbrief test. It fulfils the time requirement, taking onlytwo minutes to administer. It does not test many cog-

nitive domains and has a strong bias (40% of the score)towards orientation, which is useful to detectdelirium.28 It is less sensitive and specific than themini-mental state examination in detecting mildAlzheimers.29 There are additional problems withthe abbreviated mental test, which is not given andscored consistently by regular users.30

Other strengths and weaknesses of TYM

The TYM has several other advantages over currentbedside cognitive tests. There is a brief but rigorousscoring system. Inter-rater agreement for scoring isexcellent. Ten minutes training and the scoring sheet

alloweda nurse, without experience of memory clinics,to score the TYM sheets as accurately as a specialist.

WHAT IS ALREADY KNOWN

There is no available short cognitive test that is quick to use, examines various skills, and issensitive to Alzheimers disease

There is confusion over how to score and interpret current short cognitive tests

WHAT THIS PAPER ADDS

Thenew test your memory (TYM) test is quick to use, examines 10 cognitive skills, anddetects 93% of cases of Alzheimers disease

There are normative data and a scoring sheet to allow consistent scoring and interpretation

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The standardisation of the scoring should avoid theconfusion that arises with scoring and interpreting themini-mental state examination and the abbreviatedmental test.

Cognitive testing usually depends on the tester andpatient speaking the same language. The simplicity of

theTYM shouldallow it to be administeredand scoredin a different language with help from a relative. It iscurrently being translated into four different lan-guages. A minor adjustment to the semantic knowl-edge question (president for prime minister) isneeded for American, Irish, and Australian use. Ver-sions are being developed for UK patients who do notspeak English as their first language; in these versionsthere are variations in the semantic knowledge anddrawings to suit the background of the individual.

Normal values, sensitivity, and specificity are on thescoring sheet. As the test is filled in by the patient withlittle help and marked with the help of a scoring sheet,

the tester and rater have little influence on the score.The high negative predictive value of scores 42shows that in unselected groups a good score makesAlzheimers disease unlikely and the TYM is a goodscreening test formemory problems.A score above 42(thatis,43) correctly excludesthe diagnosisof Alzhei-mers disease on 97% of occasions, even when the pre-valence is as high as 30%. In unselected groups thepositive predictive value of a score of42 is relativelylow, showing that the test alone cannot be used to diag-noseAlzheimers disease.In selected groupswhere theprevalence of Alzheimers will be higherfor exam-ple, older patients with memory complaintsthe posi-

tive predictive value of a score

42 is much higher.The TYM was used successfully in patients outsidethis studywith moreseveredementia,visual problems,or other physical disability. The tester needs to fill inthe form with these patients and some tasks might betoodifficult, so thescores of these patients arenot com-parable with scores of the patients or controls in thisstudy. The test is also useful for patients with hearingimpairment who have difficulty with verbal cognitivetests.

The TYM seems more sensitive than the mini-men-tal state examination in screening for non-Alzheimersdementias. In the small group of such patients in our

study the average mini-mental score was 25, close tothe average for the population. The TYM score in thesame group was 39, eight points below the averagecontrol score.

Adisadvantageofthememorytestistheneedforthespecially printed sheets, though the Addenbrookescognitive examination-revised has a similar require-ment. A website is being developed to help to solvethis problem.

This work would not have been possible without the nurses and

receptionists at Queen Elizabeth Hospital, Kings Lynn, North

Cambridgeshire Hospital, Wisbech, and Addenbrookes Hospital,

Cambridge, who administered the tests. We thank colleagues in the

memory clinic, Cambridge, for permission to include their patients and for

helpful discussions. A website is being prepared (www.tymtest.com) thatwill allow downloading of tests, scoring sheets, and instructions.

Contributors:JB devised and helped to design the TYM, he helped toperform and coordinated the clinical research, and wrote the first draft of

the paper. GP helped in the clinical testing and in the writing of the paper

and was an inter-rater tester. KD performed much of the clinical testing

and scoring. PC performed the statistical analysis and prepared the

figures and tables. LAB helped design the test and was an inter-rater

tester. JB is guarantor.

Funding: GP was supported by Alzheimer s Research Trust (UK) and the

Cambridge Commonwealth Trust. PC was supported by the StrokeAssociation. The authors are independent of any funders for this work. All

authors had access to all data in this study.

Competing interests: None declared.Ethical approval: This study was performed under ethical approval fromCambridgeshire 2 research ethics committee. All participants gave

informed consent.

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Accepted: 6 February 2009

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self administered cognitive screening test (tym) for ad detection

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