Screening and Case Finding Tools for the Detection of Dementia. Part I: Evidence- Based Meta-Analysis of Multidomain Tests

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1 SPECIAL ARTICLES Screening and Case Finding Tools for the Detection of Dementia. Part I: Evidence- Based Meta-Analysis of Multidomain Tests Alex J. Mitchell, M.R.C.Psych., Srinivasa Malladi, M.R.C.Psych. Aim: To evaluate the diagnostic accuracy of all brief multidomain alternatives to the Mini-Mental State Examination (MMSE) in the detection of dementia. Methods: A literature search, critical appraisal, and meta-analysis were conducted of robust diagnostic validity studies involving cognitive batteries. Twenty-nine distinct brief batteries were tested in 44 large-scale analyses. Twenty studies took place in specialist settings (11 in memory clinics and 9 in secondary care), ten studies were conducted in primary care, and 14 in the community. Results: In community settings with a low prevalence of dementia, short screening methods of no more than 10 had an overall sensitivity of 72.0% (95% confidence interval CI 60.4% 82.3%) and a specificity of 88.2% (95% CI 83.0% 92.5%). The optimal individual tests were the Telephonic interview based on MSQ, Category fluency/memory impairment screen Telephonic interview and 6itemCognitiveImpairmentTest(6-CIT),butdatawerelimitedbytheabsenceof multiple independent confirmation for any individual test. In primary care where the prevalence of dementia is usually modest, the optimal individual tools were the Abbreviated mental test score/mental status questionnaire (MSQ), and Prueba cognitive de leganes (PCL). Furthermore, the Abbreviated mental test score (AMTS) was superior to the MMSE for case finding, but for screening the MMSE was optimal. If length is not a major consideration, the MMSE may remain the best tool for primary care clinicians who want to rule in and rule out a diagnosis. In specialist settings where the prevalence of dementia is often high, the optimal individual tools were the DEMTECT, Montreal cognitive assessment (MOCA), Memory Alteration test, and MINI-COG. Two tools were potentially superior to the MMSE for rule in and rule out, namely the 6-CIT and MINI-COG. Only four analyses looked specifically at accuracy in early-stage dementia, and each showed at least equivalent diagnostic accuracy, suggesting these methods might be applicable to early identification. Conclusion: A large number of alternatives to the MMSE have now been validated in large samples with favorable rule-in and rule-out accuracy. Evidence to date suggests for those wishing to use brief battery tests then the original MMSE or the AMTS should be considered in primary care and either the 6-CIT or the MINI-COG should be considered in specialist settings. (Am J Geriatr Psychiatry 2010; 18: ) Key Words: Screening, dementia, diagnosis, Alzheimer disease, detection, case finding, MMSE Received November 15, 2007; revised October 13, 2009; accepted October 16, From the Department of Liaison Psychiatry, Brandon Unit, Leicester General Hospital, Leicester (AJM); and Northamptonshire Healthcare NHS Trust, Stuart Road Resource centre, Corby, United Kingdom. Send correspondence and reprint requests to Alex J. Mitchell, M.R.C.Psych., Department of Liaison Psychiatry, Leicestershire Partnership Trust, Brandon Unit, Leicester General Hospital, Gwendolen Road, Leicester LE5 4PW, UK. alex.mitchell@leicspart.nhs.uk 2010 American Association for Geriatric Psychiatry Am J Geriatr Psychiatry 18:9, September

2 Multidomain Screening and Case Finding Tools Considerable evidence suggests that clinicians in primary and secondary care have difficulty identifying dementia, particularly in the early disease stages. 1 6 Underdetection may be linked with the willingness of clinicians to look for possible cases and difficulty separating those with subjective memory complaints and mild cognitive impairment (MCI) from those with dementia. In national surveys, the proportion of primary care physicians (PCPs) who regularly screen for dementia is 56% in Denmark, 7 39% in Australia, 8 and 26% in Canada. 9 One recent study involving 1,107 patients showed documentation of mental status testing in only 15% of subjects who had memory complaints. 10 In response, the American Academy of Neurology strongly recommended identification and active management of demented patients but suggested screening only when cognitive impairment is suspected. 11 The 2006 U.K. guidelines on Dementia Supportive Care from the National Institute for Health and Clinical Excellence recommended formal cognitive testing as part of routine assessment of dementia. 12 The ability of any tool or questionnaire to identify a condition with minimal false negatives is known as case-finding and is often measured by positive predictive value (PPV). Conversely, the ability of a test to rule out a diagnosis with minimal false positives is known as screening and is often reported as the negative predictive value (NPV). There is no consensus about what level of sensitivity (Se) and specificity (Sp) (or indeed PPV and NPV) is acceptable in dementia screening because the consequences of missing cases or misidentifying noncases is open to interpretation. However, in the field of biological testing, the Ronald and Nancy Reagan Research Institute suggested that a Se and Sp of 80% would be acceptable. 13 To date, the Mini-Mental State Examination (MMSE) has been the most extensively studied screening instrument for cognitive impairment. 14,15 O Connor et al. 16 studied the instrument using a cutoff 23 versus 24 in 2,302 primary care patients, of whom 586 received a Cambridge Mental Disorders of the Elderly Examination (CAMDEX) interview. Compared with the CAMDEX, Se was 86% and Sp 92%. A recent meta-analysis of MMSE accuracy suggested a sensitivity and specificity of 77% and 90% for application in high-prevalence specialist settings and 81% and 87% for application in low-prevalence settings, respectively. 15 Therefore, the MMSE seems to be a reasonably accurate method of detecting dementia, but it is not acceptable to many PCPs. 17 It has been described as impractical in primary care because it takes too long to administer. 18 Therefore, there is a need for instruments that are shorter but no less accurate than the MMSE in diagnosing dementia. 8 Short instruments can be divided into two types: single-domain tests that concentrate on one area such as memory or verbal fluency and multidomain tests (battery methods) that assess multiple cognitive domains. The aim of the current study is to examine the accuracy of multidomain methods that take no longer to administer than the MMSE but at the same time retains accuracy in either high-prevalence or low-prevalence settings. In a separate analysis, we also examined the value of single-domain methods (see part II). METHODS Inclusion Criteria We included studies that examined diagnostic validity of brief multidomain screening methods in comparison to a validated diagnostic standard. We defined brief as a method taking no longer to complete than the MMSE. This is about 9 in healthy individuals and 15 in those with dementia (often simplified to 10 ). 19,20 We defined multidomain as those studies that tested at least two distinct aspects of cognitive function. We included studies in all settings but separated those conducted in primary care and specialist centers (includes memory clinics, specialist clinics and hospital wards) from those conducted in the community (includes nursing home studies) to avoid heterogeneity. Excluded Studies We excluded studies that presented inadequate data for inclusion in the analysis. For example, studies in which sensitivity and/or specificity was neither stated nor calculable from the primary data. We excluded studies that looked only at screening for MCI but allowed those that examined only early or mild cases of dementia. Thus, several brief batteries were excluded in this analysis because of data limitations included the AB Cognitive Screen, 21,22 the five-word test, 23 the short cognitive battery, 24 the TE4 Da, 25 the Syndrom-Kurz- 760 Am J Geriatr Psychiatry 18:9, September 2010

3 Mitchell and Malladi test Test, 26 and the Standardized MMSE. 21 We excluded assessments of function rather than cognition (including combinations). 27,28 We also excluded informant-only interviews (including one brief informant interview) 29 and as these have been reviewed elsewhere. 30 We excluded one study that used the Blessed test as a criterion reference. 31 On the basis of preliminary findings, we performed a sample size calculation regarding the ability of any study to differentiate a sensitivity of 74% and a specificity of 90%. An 80% chance of detecting this difference at p 0.05 requires at least 170 patients. Therefore, we excluded any studies that recruited less than this sample size because this would otherwise encourage studies with unreliable falsenegative or false-positive results. Search Criteria A systematic literature search, critical appraisal of the collected studies, and pooled analysis were conducted. The following abstract databases were searched from inception to July 2009: MEDLINE, PsycINFO, Embase, and CINAHL Four full text collections including Science Direct, Ingenta Select, Ovid Full text, and Wiley-Blackwell were searched. The abstract database web of knowledge (4.0, ISI) was searched, using the above terms as a text word search, and using key papers in a reverse citation search. The following search terms were used: Screen* or test or instrument or measure or tool or diagnos* Abstract and Dementia or Alzheimer* or cognitive Abstract and sensitivity or specificity or accuracy or receiver operator or ROC full text. Critical Appraisal and Meta-Analysis The review guidelines for diagnostic tests recently outlined in Evidence-Based Medicine was followed (see Part II, appendix 1). 32 Critical appraisal for each report included the setting, the data integrity, the choice of reference criterion, the dropout rate, the method of application of the screening questionnaire, prospective or retrospective data collection, and degree of blinding to the gold standard (if applicable). 33 We required that the test under investigation was not used to formulate the diagnostic decision of dementia, that is an independent criterion standard. We undertook a meta-analysis of Se and Sp data and where heterogeneity was moderate to high, a random effects meta-analysis was used. In addition, we used relative risk weighted meta-analysis (based on sensitivity and specificity) where primary studies compared methods head-to-head with the MMSE. Overall accuracy can be calculated using fraction correct (true positives and negatives/all cases); however, scores are dependent on prevalence. To allow for variations in prevalence, a Bayesian plot of conditional probabilities shows all conditional posttest probabilities from all pretest probabilities regardless of prevalence. 34 The area under the Bayesian-positive curve (AUC) allows statistical comparison of rule-in success and 1-AUC (or area above the negative curve) allows statistical comparison of rule-out success without interference from prevalence variations and can be calculated simply using Microsoft Excel. 35 Standards of Accuracy and Level of Recommendation From Bayesian curve analysis, we defined an apriori standard of an AUC of more than 0.80 to be judged as alevel1studyand0.70tobejudgedasalevel2study (Appendix B). Furthermore, we required independent replication for a 1a or 2a recommendation, respectively. This is similar to the recommendation for the accuracy of diagnostic biological tests suggested by the Ronald and Nancy Reagan Research Institute. 36 RESULTS Search Results Our search identified 784 preliminary articles of which 468 were not primary studies, leaving 316 possible hits. Seventy publications were not studies of diagnostic validity but severity ratings and other uses of cognitive tests. Of the remaining studies, we excluded 62 due to low sample size, 30 due to lack of primary data, and 27 that examined single-domain rather than multidomain methods or looked at informant interviews. Furthermore, 49 studies were longer, rather than briefer alternatives to the MMSE, 34 examined the MMSE and one used an insufficient gold standard. Thus, we reviewed 44 analyses of brief alternatives to the MMSE including 19 head-head comparisons with the MMSE itself (table 1, table 2). Am J Geriatr Psychiatry 18:9, September

4 Multidomain Screening and Case Finding Tools TABLE 1. List of Batteries Battery Year of Publication Key References Cognitive Domains 6-Item screener (3 word recall and 3 temporal orientation) Short-term memory 2. Orientation to time 7 minute screen (7MS) 1998 Solomon PR, Hirschoff A, Kelly B, et al: Arch Neurol 1998; 55: Orientation to time 2. Short-term memory recall 3. Visuospatial skills 4. Expressive language Abbreviated Mental Test Score (AMTS) 1972 Hodkinson HM: Age Ageing 1972; 1: Episodic memory 2. Semantic memory 3. Short-term memory 4. Attention Blessed Information Memory Concentration Test Orientation 2. Memory 3. Attention 5. Orientation (Time, Place, and Person) CMT (Chula mental test) Short-term memory 2. Orientation (Time and Person) 3. Attention 4. Calculation 5. Language 6. Abstract thinking 7. Judgment 8. Remote memory Combined CF-T MIS-T Semantic memory 2. Episodic Memory (MIS-T) Combined Isaacs Set Test (IST) or MIS Verbal fluency 2. Memory Combined John Brown Test and Orientation (time) Memory 2. Orientation Combined John Brown Test and Verbal Fluency (animals) Memory 2. verbal fluency DemTect (RDST plus 3 items) Short-term memory 2. Attention 3. Language skills 4. Number processing 5. Calculation East Boston memory test (EBMT) Short-term memory (immediate and delayed memory recall) Epidemiological Dementia Index (EDI) items from the CAMDEX 1. Orientation 2. Fluency 3. Knowledge Eurotest Semantic memory 2. Attention 3. Short-term memory GPCOG (Various scoring methods) (Patients examination covers) 1. Orientation to time 2. Visuospatial skills 3. Short-term memory (Informant interview covers) 1. Short-term memory 2. Language skills 3. Activities of daily living Memory Alteration Test Encoding 2. Temporal orientation 3. Semantic memory 4. Free recall 5. Cued recall Memory impairment screen (MIS) 1999 Buschke H, Kuslansky G, Katz M, et al: Neurology 1999; 52: Delayed free recall 2. Delayed cued recall (Continued) 762 Am J Geriatr Psychiatry 18:9, September 2010

5 Mitchell and Malladi TABLE 1. (Continued) Battery Year of Publication Key References Cognitive Domains Memory impairment screen (MIS-T) Telephonic interview MINI-Cog Montreal Cognitive Assessment, (MoCA) Prueba cognitive de leganes (PCL) R-CAMCOG 2000 De Koning et al: Stroke 2000; 31: Rapid dementia screening test (RDST) Saint Louis University Mental Status Examination (SLUMS) Set of items (generic) Short portable mental status questionnaire (SPMSQ) 1975 Pfeiffer E. J Am Geriatr Soc 1975; 23: TELE Telephonic interview for Cognitive Status (TICS) Test Your Memory (TYM) Episodic memory 2. Semantic memory 1. Short-term memory (3 word recall) CDT covers 1. Visuospatial skills 2. Executive function 3. Numerical and Verbal Memory 1. Visual-spatial 2. Language 3. Memory 4. Attention 5. Executive function 6. Orientation 1. Orientation (Time, Place, and Person) 2. Immediate memory recall 3. Delayed recall 1. Orientation (Time and Place) 2. Language (Comprehension and Expression) 3. Memory (learning, recent and remote) 4. Concentration 5. Praxis 6. Calculation 7. Perception 8. Abstraction 1. Language skills 2. Semantic Memory 3. Speed of Processing 4. Attention 5. Cognitive flexibility 6. Problem solving 7. Imagery 8. Executive Functioning 1. Orientation (Time and Place) 2. Short-term memory 4. Attention 5. Expressive language 1. Orientation (Time and Place) 2. Short-term memory 1. Orientation 2. Semantic memory 3. Calculation 1. Short-term memory 2. Similarities 3. Attention 4. Questions on Health 5. Activities of daily living 1. Visual-spatial 2. Language 3. Memory 4. Attention 5. Executive function 6. Orientation 1. Visual-spatial 2. Language 3. Memory 4. Attention 5. Executive function 6. Orientation Types of Batteries. There were 29 distinct brief batteries subjected to validation testing in 44 analyses. These ranged in length from 2 to 29 items and in length from 0.5 to 10. Three possible methods were referred to as the Blessed test namely the Blessed Information Memory Concentration (BIMC) Tests (28 Am J Geriatr Psychiatry 18:9, September

6 Multidomain Screening and Case Finding Tools TABLE 2. Overview and Critical Appraisal of Included Studies and Methods Name/ References Test Tool Number of Items Comparison/ Diagnostic Tool Total Sample (Cases Comparators) Sample Size/Subgroup Severity AD Methodology Results (Description) Test Time Comments Secondary care 47 MINI-COG 2 subtests: 3 item word recall and clock drawing 39 6 Item Screen (3 word recall and 3 temporal orientation) 54 Test Your Memory (TYM) 40 6 Item Screen (3 word recall and 3 temporal orientation) NINCDS-ADRDA for AD 8 Psychiatrists diagnosis (method not stated) 10 Expert clinical diagnosis of AD 6 DSM IV and ICD with probable AD compared with 71 with MCI and 140 healthy controls mild dementia (GDS3 5) and 82 moderate to severe patients and 540 controls aged years 651 Cohort 1 consists of 344 communitydwelling black persons identified from a random sample of 2,212 black persons aged 65 years and older residing in Indianapolis; Cohort 2 consists of 651 subject referrals to the Alzheimer Disease Center Mixed MMSE was compared against MINI-COG. Average ages for normal subjects and those with MCI and dementia were 73, 74, and 78, respectively Mixed 3 Samples recruited 1 seen in local expert centre 2 memory clinic 3 community; administered 6-CIT, MMSE and GDS; 6CIT used with 12 point raw score with multiplier Early Cross sectional study in outpatient clinic using MMSE and ACE-R against TYM Mixed Three-item recall (apple, table, and penny) and three-item temporal orientation (day of the week, month, and year) 6 items; Mean age of the community-based sample was 74.4 years, 59.4% of the sample were women, and the mean years of education was 10.1 The overall accuracy of the MINI-Cog and MMSE was 83% and 81%, respectively. The MINI- Cog had a sensitivity of 58% in MCI versus 51% for MMSE ROC curve presented but AUC not discussed. Some confusion about setting as discussion about primary care TYM was reported to be highly sensitive and specific and may be selfadministered in some cases 26.4% cognitively impaired and 4.3% dementia in community sample 2 4 Results for mild moderate and severe dementia, non-ad dementias presented as well as MCI 2 Several cutoffs presented. 6CIT has been shown to be equivalent to MMSE in a French trial. Davous et al CIT considerably shorter than MMSE and correlates well with it. More useful in identifying mild dementia with sensitivity of 805. Galasko et al 5 TYM was more sensitive than MMSE, specificity comparison not presented 2 It can be administered through telephone or face to face interview. Simple scoring system. brief, easy, reliable. Temporal disorientation occurs before disorientation to place. Within temporal orientation day, month and year are found to have high specificity (Continued) 764 Am J Geriatr Psychiatry 18:9, September 2010

7 Mitchell and Malladi TABLE 2. (Continued) Name/ References Test Tool Number of Items Comparison/ Diagnostic Tool Total Sample (Cases Comparators) Sample Size/Subgroup Severity AD Methodology Results (Description) Test Time Comments 49 Eurotest 11 DSM-IV with dementia 380 without dementia; All older than 60 years 51 Isaacs Set Test (IST) or MIS 4 items DSM-IV and NINCDS 43 R-CAMCOG 25 DSM-IIIR. NINDS- AIREN. Original CAMCOG with dementia (mean age 76.2 years) 66.9% presented with AD and 46 (37.1%) with Non- AD dementias consecutive post stroke patients in Rotterdam stroke bank. 1/6th had TIA 10% had intracerebral hemorrhage. 16 excluded. Final total AMTS 10 DSM-IIIR with dementia 84 without 46 AMTS 10 items DSM-IIIR 2,757 Cohort of older people mean age 71 years; 23% had congestive heart failure, 29.2% CHD and 39% hypertension Mixed Eurotest is adaption of the Euro money test suitable for low educational level. Three parts: Part 1 knowledge of currency; Part 2 arithmetic with currency; Part 3 recall of previous. Score is 0 to 35. Sample mean 72 years (6.9); 33.9% illiterate Mixed The weighted sum of MIS and IST scores was calculated, and the logical or rule combination was performed versus MMSE Mixed 55 years included. Screened using Blessed dementia scale, BDAE (Boston diagnostic aphasia examination), between 3 9 months after stroke. Diagnosis made by 2 neurologists, neuropsychologist and trained physician Mixed Retrospective analysis of 299 memory clinic patients mean age 73.4 yrs (SD9.3) 113 male. CAMDEX also performed Mixed Cross-sectional diagnostic validity with principal component analysis AUC 0.93 cf verbal fluency of 0.86 (but no Se and Sp of VF presented) The or rule had overall sensitivities of 0.92 and 0.89 for mild cases, with a specificity of 0.90 CAMCOG and R-CAMCOG equally accurate with ROC area 95% Excluded community sample as size too small At a cutoff of 6 versus 7 Se was 0.81 and Sp 0.84 Dementia 9.2 ; no dementia 8 Low education rate mean performance may be underestimated; performance superior to verbal fluency alone. Based on the individuals knowledge and handling of money % had a CDR of 1, 40 (29%) a CDR of 2, and 31 (22%) a CDR of 3. Data presented for original and crossvalidation sample combined Approximately 10 Possibly the first test to screen poststroke dementia patients. R-CAMCOG tests different types of memory and is better able to detect subcortical features 2 Several cutoffs presented. IQCODE informant QQ also presented alone and in combination. IQCODE validated retrospectively against pathological findings from necropsy. 2 Study based on medical wards. No comparison instruments reported (Continued) Am J Geriatr Psychiatry 18:9, September

8 Multidomain Screening and Case Finding Tools TABLE 2. (Continued) Name/ References Test Tool 42 DemTect (RDST plus 3 items) 45 RDST (Rapid dementia screening test) 53 John Brown Test and Orientation (time) and John Brown Test and Verbal Fluency (animals) Number of Items Comparison/ Diagnostic Tool 5 items NINCDS-ADRDA for AD 2 items DSM-IV, NINCDR- ADRDA 3 items DSM-IIIR NINCDS- ADRDA Total Sample (Cases Comparators) Sample Size/Subgroup Severity AD Methodology Results (Description) Test Time Comments 318 (ADRC sample) controls 121 AD 97 MCI 2 groups 60 and 60 2 groups MMSE 21 MMSE dementia 201 controls 60 years years 106 N 1,058 Mixed with MME 14 Severe dementia excluded. Ninetyseven patients enrolled 67% AD 13% Mixed 8% Parkinson s 12% Dementia unspecified Matched with randomly selected controls ADRC sample 159 dementia 159 controls MMSE 21 Education factor controlled using education correction. Experienced assessors. SPSS Discrimination analysis. Result after transformation Mixed RDST (word generation verbal fluency transcoding #) Retrospective analysis using 2 cohorts MMSE 14, combined matched (age and education) and unmatched data presented Significant age effect on word list, supermarket task and delayed recall (p 0.001) Significant education effect on transcoding task, supermarket task and digit span (p 0.01) No age or education effect on transformed scores 8 10 (including transformation of scores and interpretation) Number transcoding is impaired in early dementia. (Switching from one code to another. Compared to letter fluency tasks, semantic word generation is impaired earlier and more severely in demented patients Reverse digit span requires working memory which RDST well accepted 3 5 Only 12% GPs use Tests that did not show the same sensitivity and specificity as MMSE either by ROC analysis or sensitivity at high specificity included 3 item recall, clock drawing, tests of orientation including date and day. AUC is not available for combined BMT and verbal fluency 1 cognitive tests Semantic verbal fluency task has high specificity because of various cognitive domains that are involved. Compared to letter fluency, semantic fluency is impaired earlier and more severe in dementia. 3 5 Easy (Continued) 766 Am J Geriatr Psychiatry 18:9, September 2010

9 Mitchell and Malladi TABLE 2. (Continued) Name/ References Test Tool Number of Items Comparison/ Diagnostic Tool Total Sample (Cases Comparators) Sample Size/Subgroup Severity AD Methodology Results (Description) Test Time Comments 20 7MS (7 minute screen) 4 subtests MMSE DSM-IV NINCDS- ADRDA 48 MOCA 30 NINCDS-ADRDA for AD 55 Memory Alteration Test 44 MINI Cog-3 item recall OR clock drawing test (algorithm) 424 AD-177 VD-62 LBD- 17 other dementia MCI-87 Depression-31 Controls NINCDS-ADRDA memory clinic (50 amci 66 early AD 25 Moderate and 3 late AD) and 400 community elderly 7 items CERAD, CDR, DSM-IV, NINCDS- ADRDA Mixed Prevalence dementia 341/ 542 (63%) and Alzheimer disease 177/542 (32.6%) of sample. 7MS consisted of- Benton temporal orientation; enhanced cued recall, clock drawing, verbal fluency; Patients with Psychiatric illness also tested 183 Mild Sample included MCI according to Petersen criteria (not analyzed here). AD was mild, MMSE scores of 17 or greater (173 women, 76 men) reflecting 5 major ethnic groups in USA Mild Early AD defined as Global Deterioration Scale stage 4 Mixed DSM-IV diagnosis, CERAD, NINCDS-ADRDA. Probable AD, another dementia or no dementia. Very mild cog. Impairment were excluded (CERAD 0.5) Results for AD alone also presented. AUC AD versus intact: 7MS MMSE but for mild dementia MMSE above 21 7MS and MMSE The MMSE had a sensitivity of 78%, whereas the MoCA detected 100%. Specificity was 100% for MMSE and 87% for MoCA MMSEs AUC for discriminating between Controls and A-MCI 0.651/Controls and early AD In this sample MMSE had a poor sensitivity and specificity for detecting A-MCI. M@T cutscore of 28 discriminated between A-MCI and early AD with a AUC of 0.9 Interrater reliability Blind for diagnosis. Naïve raters 20. Concordance between naïve and expert raters 98% for normal, moderate and severely impaired clocks. Sixty percent for mild impaired 8.5 in intact and 15.6 in impaired Better diagnostic accuracy than MMSE. ROC of 7MS Took longer than in Solomon s study. Scoring system can appear difficult to novice. Specificity with regards to depression and other psychiatric conditions is poor and can limit the use in general 10 Results also presented for MCI. The MOCA is approximately the same length as the MMSE. The sample size was relatively small in this study. 5 Results also presented for amci versus AD.M@T is based on the memory consolidation theory (squire et al., 2004). Controls were older than 60 years and did not complain of significant memory deficits. Patients from memory clinic. Subtest of M@T - encoding, temporal orientation Diagnostic accuracy less CASI but MMSE. Optimal MINI-Cog uses simplest possible CDT scoring system. MINI-Cog algorithms perform well with simple clock scoring techniques. Can be used successfully by relatively untrained raters as a 1st stage dementia (Continued) Am J Geriatr Psychiatry 18:9, September

10 Multidomain Screening and Case Finding Tools TABLE 2. (Continued) Name/ References Test Tool Number of Items Comparison/ Diagnostic Tool Total Sample (Cases Comparators) Sample Size/Subgroup Severity AD Methodology Results (Description) Test Time Comments 50 Saint Louis University Mental Status Examination Primary care GPCOG 2 Step (if patient score 5 8) then do Informant 2. AMTS 3. GPCOG patient items 62 GPCOG combined 11 DSM-IV normal 180 mild cognitive impairment 82 dementia Mixed 60 years or older mean age 75.3 years; less than high school 30.6%; high school or more 69.4%. SLUMS enhances attention, calculation, recall, fluency, digit span, CDT, figure recognition and paragraph recall 10 DSM-IV diagnosis 246 Mixed 15 item GDS administered. Score of 6 or more indicates depression. SF- 12 health survey CAMDEX Informants interviewed by telephone or person Researchers blinded to GP administered GPCOG 156- cognitive problems 20 cognitively intact (random sample: 176) Patient s cognitive test (max. score 9) and informant questionnaire (max. score 6) Time orientation Clock drawing Reporting a recent event Word recall (4 items) Informant questionnaire Informant asked about patient s memory of recent conversations Ability DSM-IV diagnosis completed study 50 years onwards if cognitive problems pre Sent. Excluded if in nursing homes, diagnosed with depression, delirious or poor English, sight or hearing problems. 11.3% Mixed 15 item GDS administered. Score of 6 or more indicates depression. SF- 12 health survey CAMDEX Informants interviewed by telephone or person Researchers blinded to GP administered GPCOG 156- cognitive problems 20 cognitively intact (random sample: 176) Results shown for high education 7 (SD 3 ) Individual items analyzed by ROC. Delayed 5 item recall best discriminator. Dementia is underdiagnosed 50% of patients with dementia have never received a diagnosis from physician. Refs Annual conversion rate of MCI to AD is 14% AUC Patient interviews took less than 4 to administer and informant interviews less than 2. The instrument was reported by GPs to be practical to administer and was acceptable to patients. Nine cognitive and 6 informant items Significant correlation for GPCOG ( (General practitioner s assessment of cognition)-patient and total scores with patient age, years of education. But not for informant scores. Misclassification rates 14.2 % 4.5 Unclear if dementia was assessed; Age related after regression analysis Independent of education and depression Informant section not affected by any factors tested (Continued) 768 Am J Geriatr Psychiatry 18:9, September 2010

11 Mitchell and Malladi TABLE 2. (Continued) Name/ References Test Tool Number of Items Comparison/ Diagnostic Tool Total Sample (Cases Comparators) Sample Size/Subgroup Severity AD Methodology Results (Description) Test Time Comments 61 PCL- Prueba cognitive de leganes Short portable mental status questionnaire (SPMSQ) 2. MSQ 3. AMTS 4. AMTS and MSQ Short portable mental status questionnaire (SPMSQ) 2. Blessed Information Memory Concentration Test Community 67 Short portable mental status questionnaire (SPMSQ) 10 (SPMSQ) 22 Blessed 32 DSM-IV/IPA-WHO criteria 10 GMS/AGECAT 4 or 5 CAMDEX 9 items Participants randomly selected for clinical assessment. NINCDS- ADRDA final sample Normal 42 AACD-(MCI) 33- Dementia Mixed Calculation for dementia and AD Mixed interview in patients home, 19 lay trained interviewers, only 13 cases DSM-IIIR 795 Culturally mixed sample 355 Latino 299 African American and 136 Non-Latino White 467 Total 3,811 older than 65 years. Four hundred sixty-seven had clinical evaluation 167 unaffected 166 AD 134- Probable AD Mixed Assessments by team of neurologists, physicians and neuropsychologists using DSM-IIIR. Patients aged 65 years Mixed Population survey. By trained trainees. Questionnaires in English or Italian. For 1 hour. The questionnaires included EBMT and SPMSQ. SMPSQ was completed by 3,337. Divided into groups depending on the level of performance. SPMSQ is six orientation QQ 2 generic AUC Not clear about half length of MMSE Combination appeared better than single items Comparison of multiple scales long and short including Blessed; care dementia, Khan- Goldfarb, MMSE, SPMSQ, CARe Homogenous Probably and possible AD, 122 MCI. Probable AD was the main outcome All 2 except AMTS and MSQ 4 5 Designed for people with low education level. 32 items. Orientation to time, place, and person, Memory index, naming objects, immediate recall, and delayed recall, logical memory 2 Acceptability and completion 91%. In general, screening tests that have a high efficiency when applied to a group of individuals selected to be either diseased or nondiseased will perform much more poorly in an unselected population because the false posit (Continued) Am J Geriatr Psychiatry 18:9, September

12 Multidomain Screening and Case Finding Tools TABLE 2. (Continued) Name/ References Test Tool Number of Items Comparison/ Diagnostic Tool 64 MINI-Cog 2 subtests 3 item word recall and clock drawing MMSE and standardized neuropsychological battery DSM- IIIR NINCDR CERAD applied 40 6 item screen (3 word recall and 3 temporal orientation) 6 DSM-IV and ICD10 66 Epidem Dementia Index 10 DSM-IV, NINCDS- ADRDA Total Sample (Cases Comparators) Sample Size/Subgroup Severity AD Methodology Results (Description) Test Time Comments 1,119 1,119 age stratified random sample 344 Cohort 1 consists of 344 communitydwelling black persons identified from a random sample of 2,212 black persons aged 65 years and older residing in Indianapolis; Cohort 2 consists of 651 subject referrals to the Alzheimer Disease Center with dementia 52 without plus 195 assumed intact Mixed Selected sample Applied cognitive tools; Aged 65 years or older; Mean age 73.1 ( -6); Dementia Mean MMSE 21.3) CDR 0.5 excluded Mixed Three-item recall (apple, table, and penny) and three-item temporal orientation (day of the week, month, and year) 6 items; Mean age of the community-based sample was 74.4 years, 59.4% of the sample were women, and the mean years of education was 10.1 Mixed Community rural screening, aged 70 years or older; Epidem Dementia Index CAMCOG items 122, 123, 132,139,142,156,157 scored out of 7; Limitation post-hoc retrospective At cut off 24 MINI-Cog less sensitive and less specific than MMSE. At cut off 25 MINI-Cog was more sensitive but less specific than MMSE 26.4% cognitively impaired and 4.3% dementia in community sample MINI-Cog Much briefer and easy to administer. Less bias for ethnic and language factors. Dementia is unrecognized in 40% to 75% of patients in primary care. Important features of Dementia screening tool should be: Rapid administration Simple scoring Good balance No AUC presented 2 47% had a low education level and this may be linked with poor performance of the MMSE in this study, thus the relative difference with the EPI was greater than expected (Continued) 770 Am J Geriatr Psychiatry 18:9, September 2010

13 Mitchell and Malladi TABLE 2. (Continued) Name/ References Test Tool Number of Items Comparison/ Diagnostic Tool Total Sample (Cases Comparators) Sample Size/Subgroup Severity AD Methodology Results (Description) Test Time Comments TELE 14 DSM-IIIR, NINCDS- ADRDA 2. MSQ with dementia 52 without plus 195 assumed intact Mixed TELE is a telephone adaption of the MSQ supplemented by counting backwards, recalling 3 words and similarities questions about general health. Study used the Swedish Twin Registry with those aged 55 years or older. Weakness was that 195 were not clinical 70 AMTS 10 DSM-IIIR 212 Mixed Conducted in older people homes in Bangkok using Thia MMSE and AMTS. Mean MMSE 9.3. Diagnosis by neurologist 71 Delayed Selective Reminding Test Verbal Fluency 2 NINCDS-ADRDA and CDR subjects, 388 had no dementia diagnosis and 90 had a diagnosis of possible (n 72)/probable (n 18) AD Mixed Part of the Vienna TransDanube Aging (VITA) study No AUC presented 2 Telephone mental status tests, most based on MMSE,dropped items that cannot be administered by telephone. Gatz et al devised TELE based on 10 item MSQ. None of the MSQ questions require face to face contact. In the TELE, MSQ is supplemented by other cognit Attempt to validate Chula mental test versus MMSE and AMTS An area under the ROC curve of was reached 2 items not requiring reading or writing were included and translated into Thai. Has high content, criterion and concurrent validity and internal consistency. It is brief, less education bias can also be applied for visually impaired 2 A combination of the Delayed Selective Reminding Test and Verbal Fluency was best for screening AD (Continued) Am J Geriatr Psychiatry 18:9, September

14 Multidomain Screening and Case Finding Tools TABLE 2. (Continued) Name/ References Test Tool Combined CF-T MIS-T 2. Telephonic interview for Cognitive Status 3. Memory impairment screen (MIS-T) Telephonic interview B-MMSE (age independent) 2. D-MMSE (age independent Number of Items Comparison/ Diagnostic Tool Total Sample (Cases Comparators) Sample Size/Subgroup Severity AD Methodology Results (Description) Test Time Comments DSM-IIIR NINCDS- ADRDA total 300- telephonic battery 27- Dementia 18 AD 273-Non- Dementia 9 DSM-IV /242 with dementia at baseline, mostly mild Mixed 27 dementia and 273 nondementia (of whom 91 CDR 0.5 and 31 MCI) Dem versus Non-Dem and AD versus Non-dem calculated; interview by telephone Mixed MMSE adapted by RASCH; B-MMSE (not correlated with age): orientation to place, registration, recall, reading, and copying; D- MMSE add 3 item recall; The study samples had an age range from 75 to 85 years. Approximately 65% of the population had seven or AUC 0.95 AUC Telephonic interview not useful in hearing impaired and language difficulties. MIS-T is better than CF-T. Many elements of TICS and modified TICS are common with MMSE. CF-T measures semantic memory which is impaired in AD. It is believed by authors that Follow-up data obtained Not-stated High proportion with mild dementia. The mean MMSE score was More than 60% of the subjects with dementia had an MMSE score between 24 and 30. We are aware of only one study that has had levels of cognitive impairments similar to our sample 772 Am J Geriatr Psychiatry 18:9, September 2010

15 Mitchell and Malladi items), the Blessed Orientation Memory Concentration (six items), and Blessed Dementia Rating Scale. Only the BIMC was suitable for inclusion. One study modified the design of the MMSE post hoc. 37 Only six cognitive tools were examined in multiple studies. These were the 6-CIT (three studies), the AMTS (five studies), Short portable mental status questionnaire (SPMSQ) (three studies), the GPCOG (two studies), the Mental Status Questionnaire (two studies), the MINI-COG (four studies), and the BIMC (two studies). Setting. Twenty studies (in 18 publications) took place in specialist centers including memory clinics and hospital settings. 20,38 55 Ten studies (reported in eight publications) took place in primary care Fourteen studies (reported in 11 publications) were conducted in the community or general population, including one nursing home study. 37,40,63 71 The total number of individuals recruited across all studies was 19,421 (Figure 1). Criterion (Gold) Standard. The most common reference standard in making a diagnosis of dementia was Diagnostic and Statistical Manual of Mental Disorders (III, IIIR, or IV) used in 31 studies (7 primary care; 10 community; and 14 specialist studies). Six used the CAMDEX, five GMS/AGECAT, and two used International Classification of Diseases-10 criteria. Three studies relied on expert diagnosis. Nineteen studies attempted to define patients with probable Alzheimer disease (AD) in addition to dementia using National Institute of Neurological and Communicative Disorders and Stroke-AD and Related Disorders Association criteria. None adequately defined non-ad types of dementia with an adequate sample. Although most studies recruited patients with a full range of dementia (mild, moderate, and severe), five studies looked at diagnostic accuracy in mild cases specifically. 41,42,47,48,54 Seven included individuals with MCI but did not report separate results. Diagnostic Validity Results in Community and Population Studies Prevalence and Group Analysis. Across 14 studies, there were 808 cases of dementia of a sample of 5,022, a prevalence of 16.1%. At a group level across all community studies, battery methods had a detection sensitivity of 72.0% (95% confidence interval CI 60.4% 82.3%) and a detection specificity of 88.2% (95% CI 83.0% 92.5%). Assuming a prevalence of 16%, the PPV would be 53.9% (95% CI 50.9% 56.9%) and NPV of 94.2% (95% CI 93.5% 94.9%). Comparative Accuracy of Individual Methods. Using a Bayesian plot, four methods were satisfactory (AUC 0.80) for case finding in community settings (Fig. 2) namely the CF-T/MIS-T, CAPE, AMTS, TELE. No method achieved satisfactory accuracy for screening in community settings (AUC 0.80) although the optimal methods were 6-CIT and TELE. Looking at performance for both case finding and screening, then the top four tools were TELE, CF-T/ MIS-T, 6-CIT, and AMTS. Evidence-based recommendations are shown in Table 3. Head-to-Head Comparison With the MMSE. Three publications reported head-to-head comparisons with the MMSE in community settings. There was no evidence of publication bias (Using Horbold-Egger statistic), but there was heterogeneity. Therefore, using a random effects model (Mantel-Haenszel and Rothman-Boice), the pooled relative risk comparing sensitivity was 1.12 (95% CI , , df 1, p 0.713). Using a random effects, pooled relative risk comparing specificity was (95% CI , , df 1, p 0.353). Overall accuracy based on the fraction correct was equivalent 1.13 (95% CI ) and is shown in Figure 2. Diagnostic Validity Results in Primary Care Studies Prevalence and Group Analysis. Across 10 studies, there were 1,265 cases of dementia of a sample of 4,440, a prevalence of 28.5%. In primary care, battery methods had a detection sensitivity of 84.0% (95% CI 74.2% 91.8%) and a detection specificity of 89.9% (95% CI 78.3% 97.4%). Assuming a prevalence of 16%, the PPV would be 77.0% (95% CI 74.7% 79.2% and NPV of 93.6% (95% CI 92.7% 94.5%). Comparative Accuracy of Individual Methods. Using a Bayesian plot, five methods achieved a satisfactory rule-in (case finding) performance of 0.80 or above (Fig. 3). These were the AMTS/MSQ, MSQ, WIND- SET, PCL, and AMTS. The latter was pooled from two studies. Three methods had satisfactory screening performance (AUC 0.80) namely, PCL, AMTS/ MSQ, and MSQ alone. Looking at performance for both case finding and screening, then the optimal Am J Geriatr Psychiatry 18:9, September

16 Multidomain Screening and Case Finding Tools FIGURE 1. Quality of Reporting Meta-Analyses (QUOROM) Flow Diagram three tools were AMTS/MSQ, MSQ, and PCL. These all had a mean AUC of 0.80 or above. Two methods, the AMTS and SPMSQ, had evidence from multiple validation attempts. In the case of the AMTS, results appeared inconsistent, but when variations in prevalence were accounted for, the AMTS was successful in a screening capacity. Results for the SPMSQ showed rule-out accuracy. Summary evidencebased recommendations are shown in Table 3. Head-to-Head Comparison With the MMSE. Four studies reported head-to-head comparisons with the MMSE in community settings. Using Horbold-Egger bias calculation, there was no evidence of publication bias, but there was heterogeneity. Using a random 774 Am J Geriatr Psychiatry 18:9, September 2010

17 Mitchell and Malladi FIGURE 2. Bayesian Plot of Performance of Cognitive Tests for Dementia in Community Settings Post-test Probability Pre-test Probability DSRT/VF+ DSRT/VF- Baseline Probability EDI+ EDI- BLESSED+ MSQ+ TELE+ D-MMSE+ BLESSED- MSQ- TELE- D-MMSE- B-MMSE+ B-MMSE- AMTS+ AMTS- 6-CIT+ 6-CIT- TICS+ TICS- CF-T/MIS-T+ CF-T/MIS-T- Mini-Cog+ Mini-Cog- SPMSQ+ SPMSQ- CAPE+ CAPE- effects model, the pooled relative risk comparing sensitivity was (95% CI , , df 1, p 0.626). Using a random effects model, the pooled relative risk comparing specificity was 1.03 (95% CI , , df 1, p 0.316). Overall accuracy based on the fraction correct was not different for battery tools compared directly with the MMSE (pooled relative risk 0.979, 95% CI ) as shown in Figure 3. Diagnostic Validity Results in Specialist Settings Prevalence and Group Analysis. From 20 studies involving 9,959 individuals, 3,784 cases of dementia were diagnosed, an uncorrected prevalence of 38.0% (corrected to 37.4%). The use of battery tools in a secondary care setting gave a detection sensitivity of 88.9% (95% CI 83.9% 93.1%) and a detection specificity of 88.4% (95% CI 85.4% 91.1%). Comparative Accuracy of Individual Methods. From the Bayesian plot, six methods achieved satisfactory case-finding performance (0.80 AUC or above), JBT&VF, 7MS, 6-CIT, DEMTECT, R-CAMCOG, and MINI-COG. Of these, the 6-CIT was pooled from two independent studies and the MINI-COG from three studies. Ten methods achieved a satisfactory screening performance (0.80 AUC or above); the top five being the MOCA, DEMTECT, Memory Alteration Test, MINI-COG, SLUMS, and Eurotest. The MINI- COG deserved a robust recommendation because it was pooled from four independent studies. Looking at both case-finding and screening performance, the optimal tool ( 0.90) was the DEMTECT, although the optimal tool with validation was the MINI-COG. Head-to-Head Comparison With the MMSE. Twelve studies examined the accuracy of brief alternatives to the MMSE in a head-to-head design against the MMSE itself. 20,38 45,50,51,53 These comprised 4,643 individuals administered brief screens and 4,638 administered the MMSE. Using Kendall s tau, there was no evidence of publication bias, but there was heterogeneity. Using a random effects model, the pooled relative risk comparing sensitivity was 1.09 Am J Geriatr Psychiatry 18:9, September

18 Multidomain Screening and Case Finding Tools TABLE 3. Evidence-Based Recommendations of Battery Methods Community Case-Finding Level of Evidence Evidence Based Grade of Recommendation Community Screening Level of Evidence Evidence Based Grade of Recommendation Primary Care Case- Finding Level of Evidence Evidence Based Grade of Recommendation CF-T/MIS-T, duration 4 CAPE IO Test, duration 2 AMTS, duration 2 TELE, duration 5 6-CIT, duration 2 1b B 6-CIT, duration 2 1b B TELE, duration 5 1b B DSRT/VF, duration 2 1b B B-MMSE, duration 10 2a B CF-T/MIS-T, duration 4 2b C AMTS/MSQ, duration 4 2b C MSQ, duration 2 2b C WIND-SET, duration 1 2b C PCL, duration 11 2b C AMTS, duration 2 1b B 1b B 1b B 1b B 1a A (Continued) TABLE 3. (Continued) Primary Care Screening Level of Evidence Evidence Based Grade of Recommendation Secondary Care Case Finding Level of Evidence Evidence Based Grade of Recommendation Secondary Care Screening Level of Evidence Evidence-Based Grade of Recommendation PCL, duration 11 1b B AMTS/MSQ, duration 4 1b B MSQ, duration 2 1b B SPMSQ, duration 2 2a B GPCOG, duration 5 2b C JBT and VF, duration 1 1b B Memory Alteration Test, duration 5 1b B 7MS, duration 8 1b B 6-CIT, duration 2 1a A MINI-Cog, duration 2 1a A MOCA, duration 10 1b B DEMTECT, duration 9 1b B MINI-Cog, duration 2 1a A SLUMS, duration 7 1b B TYM, duration 5 1b B 776 Am J Geriatr Psychiatry 18:9, September 2010

19 Mitchell and Malladi FIGURE 3. Bayesian Condition Probability Plot of Cognitive Tests for Dementia in Primary Care Post-test Probability 0.60 MSQ PCL WIND-SET BLESSED help clinicians detect dementia. We focused on instruments that took no longer to administer than the MMSE as PCPs report that the MMSE is often too time consuming. 72 We found 29 distinct alternatives to the MMSE that had been subject to robust diagnostic testing in a sample of at least 170 subjects. Although there have been several narrative reviews of such screening methods, no previous group has looked at the quantitative accuracy of these methods using meta-analysis. 30,73 75 One previous meta-analysis has examined the accuracy of informant questionnaires. 76 We acknowledge there is no accepted single gold standard to diagnose dementia and some overlap between competing systems. 72,77 We distinguished between those studies conducted in primary care, community (includes population studies), and specialist settings because each has a distinct prevalence of dementia. A recent meta-analysis of all MMSE studies suggested that the Se and Sp in memory clinic settings, in community settings, and in primary care are 79.8%, 81.3%; 85.1%, 85.5%; and 78.4%, 87.8%, respectively. 15 Here, the over- AMTS+ [2 Studies] AMTS- [2 Studies] Baseline Probability GPCOG+ AMTS/MSQ+ GPCOG- AMTS/MSQ- MSQ- PCL- WIND-SET- BLESSED- SPMSQ+ [2 studies] 0.00 Pre-test Probability SPMSQ- [2 studies] (95% CI ) (df 1) p 0.06, indicating that alternatives to the MMSE had a trend to superior sensitivity. Regarding specificity, the pooled relative risk was (95% CI ). Overall accuracy based on the fraction correct was no different 1.01 (95% CI ) and is shown in Figure 4. Meta-Analytic Comparison of Individual Tools With Multiple Validation Samples. There were five attempts to validate cognitive tools in independent samples. These involved the AMTS and SPMSQ in primary care and AMTS, MINI-Cog, and 6-CIT in secondary care (Fig. 5). From this small sample, the optimal method in primary care was the MMSE and the optimal method in secondary care the 6-CIT. DISCUSSION Our aim was to evaluate the diagnostic validity of all brief multidomain alternatives to the MMSE that may Am J Geriatr Psychiatry 18:9, September

20 Multidomain Screening and Case Finding Tools FIGURE 4. Bayesian Condition Probability Plot of Cognitive Tests for Dementia in Secondary Care Settings Post-test Probability Pre-test Probability Memory Alteration Test Memory Alteration Test Baseline Probability MINI-COG-R+ MINI-COG+ [N=3] IST OR MIS+ BAS+ TYM+ TYM- MINI-COG-R- MINI-COG- [N=3] IST OR MIS- BAS- AMTS+ [N=2] AMTS- [N=2] SLUMS+ SLUMS- 6-CIT+ [N=2] 6-CIT- [N=2] R-CAMCOG R-CAMCOG DEMTECT+ DEMTECT- 7MS+ 7MS- RDST+ RDST- JBT&ORIENT+ JBT&ORIENT- JBT&VF+ JBT&VF- MOCA+ MOCA- Eurotest+ Eurotest- all accuracy of these methods was comparable to that achieved with MMSE, with some methods performing significantly better. The relative risk meta-analysis showed no inferiority against the MMSE head to head and significant improvement in sensitivity in specialist settings. In community and population studies where the prevalence of dementia is often low the optimal individual tests were the TELE, CF-T/MIS-T (combined) and 6-CIT. In primary care where the prevalence of dementia is usually modest, the optimal individual tools were the AMTS/MSQ (combined), MSQ, and PCL. In specialist settings where the prevalence of dementia is often high the optimal individual tools were the DEMTECT, MOCA, and MINI-COG. However, only the MINI-COG had independent corroboration. If data were limited to tests with multiple validation samples and compared against the MMSE then the following recommendations would apply. In primary care, the AMTS was superior to the MMSE for case finding, whereas the SPMSQ was inferior. For screening, the MMSE was optimal, and if length is not a major consideration, the MMSE is the best tool for primary care clinicians who want a rule-in and ruleout tool. In secondary care, two tools were potentially superior to the MMSE for rule in and rule out, namely the 6-CIT and MINI-COG. Regarding detection of mild dementia and MCI, in most cases comparison groups included individuals with MCI. However, this was only formally acknowledged in seven studies and only two presented separate data on accuracy in MCI. 47,48 Conversely, three studies excluded cases of MCI from the analysis. 44,63 Looking at early dementia, four tools were examined in selected cases of mild dementia (all in specialist centers), the BAS, 40 the DEMTECT, 42 the MINI-COG, 47 and the MOCA. 48 All four studies compared results with the MMSE. The DEMTECT was superior to the MMSE in overall accuracy (fraction correct , p 0.01), whereas the BAS, MINI-COG, and MOCA were not statistically different to the MMSE in mild 778 Am J Geriatr Psychiatry 18:9, September 2010