Evidence-based Synthesis Program 

A Systematic Evidence Review 

of the Signs and Symptoms

of Dementia and Brief Cognitive

Tests Available in VA

Department of Veterans Affairs

Health Services Research & Development Service

April 2010

Investigators:

Principal Investigator:

Devan Kansagara, MD

Research Associate:

Michele Freeman, MPH

Prepared for:

Department of Veterans Affairs

Veterans Health Administration

Health Services Research & Development Service

Washington, DC 20420

Prepared by:

VA Evidence-based Synthesis Program (ESP) Center

Portland VA Medical Center

Portland, OR

Devan Kansagara, MD, Director
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A Systematic Evidence Review of the Signs and Symptoms 

of Dementia and Brief Cognitive Tests Available in VA Evidence-based Synthesis Program

PREFACE

HSR&D’s Evidence-based Synthesis Program (ESP) was established to provide timely and 

accurate syntheses of targeted healthcare topics of particular importance to VA managers 

and policymakers, as they work to improve the health and healthcare of Veterans. The ESP 

disseminates these reports throughout VA. 

HSR&D provides funding for four ESP Centers and each Center has an active VA affiliation. The 

ESP Centers generate evidence syntheses on important clinical practice topics, and these reports 

help: 

• develop clinical policies informed by evidence, 

• the implementation of effective services to improve patient outcomes and 

to support VA clinical practice guidelines and performance measures, and 

• set the direction for future research to address gaps in clinical knowledge.

In 2009, an ESP Coordinating Center was created to expand the capacity of HSR&D Central 

Office and the four ESP sites by developing and maintaining program processes. In addition, 

the Center established a Steering Committee comprised of HSR&D field-based investigators, 

VA Patient Care Services, Office of Quality and Performance, and VISN Clinical Management 

Officers. The Steering Committee provides program oversight and guides strategic planning, 

coordinates dissemination activities, and develops collaborations with VA leadership to identify 

new ESP topics of importance to Veterans and the VA healthcare system.

Comments on this evidence report are welcome and can be sent to Nicole Floyd, ESP

Coordinating Center Program Manager, at nicole.floyd@va.gov.

Recommended citation: Kansagara D and Freeman M. A Systematic Evidence Review of the 

Signs and Symptoms of Dementia and Brief Cognitive Tests Available in VA. VA-ESP Project 

#05-225; 2010.

This report is based on research conducted by the Evidence-based Synthesis 

Program (ESP) Center located at the Portland VA Medical Center, Portland, OR 

funded by the Department of Veterans Affairs, Veterans Health Administration, 

Office of Research and Development, Health Services Research and Development. 

The findings and conclusions in this document are those of the author(s) who are 

responsible for its contents; the findings and conclusions do not necessarily represent 

the views of the Department of Veterans Affairs or the United States government. 

Therefore, no statement in this article should be construed as an official position of 

the Department of Veterans Affairs. No investigators have any affiliations or financial 

involvement (e.g., employment, consultancies, honoraria, stock ownership or options, 

expert testimony, grants or patents received or pending, or royalties) that conflict with 

material presented in the report.
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A Systematic Evidence Review of the Signs and Symptoms 

of Dementia and Brief Cognitive Tests Available in VA Evidence-based Synthesis Program

TABLE OF CONTENTS

Executive summary

Background.................................................................................................................................................... 1

Methods......................................................................................................................................................... 1

Results

 Key Question #1....................................................................................................................................... 2

 Key Question #2....................................................................................................................................... 3

 Key Question #3....................................................................................................................................... 3

Background............................................................................................................................................................ 4

Methods

Topic development ........................................................................................................................................ 5

Search strategy............................................................................................................................................... 5

Study selection............................................................................................................................................... 6

Data abstraction............................................................................................................................................. 6

Quality assessment ........................................................................................................................................ 6

Data synthesis................................................................................................................................................ 7

Peer review .................................................................................................................................................... 7

Results

Literature search ............................................................................................................................................ 8

Key Question #1: What signs and symptoms should prompt VA providers to assess cognitive function 

as part of an initial diagnostic workup for dementia? ........................................................................... 10

Subjective memory complaints .............................................................................................................. 15

Neuropsychiatric symptoms .................................................................................................................. 16

Sleep disturbance ................................................................................................................................... 17

Gait disturbance ..................................................................................................................................... 18

Neurologic signs .................................................................................................................................... 18

Miscellaneous ........................................................................................................................................ 18

Key Question #2: Which measures of cognitive function provide the optimal sensitivity, 

specificity, and time to completion among the measures available to VA providers? ........................ 19

BOMC..................................................................................................................................................... 26

GPCOG................................................................................................................................................... 26
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A Systematic Evidence Review of the Signs and Symptoms 

of Dementia and Brief Cognitive Tests Available in VA Evidence-based Synthesis Program

Mini-Cog................................................................................................................................................. 27

MoCA ..................................................................................................................................................... 27

SLUMS................................................................................................................................................... 28

STMS...................................................................................................................................................... 28

Key Question #3: What are adverse consequences of using these measures?..................................... 29

Discussion

Signs and symptoms of dementia ................................................................................................................ 31

Brief measures of cognitive function available to VA................................................................................. 31

Limitations................................................................................................................................................... 32

Future research recommendations .............................................................................................................. 32

References............................................................................................................................................................ 34

Tables and Figures

Figure 1. Literature flow............................................................................................................................ 9

Table 1. Study characteristics, sensitivity, and specificity of dementia signs and symptoms................ 10

Table 2. Sensitivity, specificity, and predictive values of subjective memory 

complaints in selected studies.................................................................................................. 16 

Table 3. Pros and cons of the 6 brief mental status measures available for use in VA........................... 20

Table 4. Study characteristics and test performance results for the BOMC, GPCOG, 

Mini-Cog, MoCA, SLUMS, and STMS .................................................................................. 22

Table 5. Cognitive domains, biases, and other characteristics of BOMC, GPCOG, 

Mini-Cog, MoCA, SLUMS, and STMS .................................................................................. 25

Appendix A. Search strategy ......................................................................................................................... 41

Appendix B. Inclusion/exclusion criteria ...................................................................................................... 44

Appendix C. QUADAS criteria for evaluating diagnostic accuracy studies................................................. 45

Appendix D. Peer review comments.............................................................................................................. 46

Appendix E. Glossary.................................................................................................................................... 55
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A Systematic Evidence Review of the Signs and Symptoms 

of Dementia and Brief Cognitive Tests Available in VA Evidence-based Synthesis Program

EXECUTIVE SUMMARY

BACKGROUND

The Veterans Health Administration (VHA) Office of Geriatrics and Extended Care (OGEC) in 

Patient Care Services has primary responsibility for coordination and direction of VHA dementia 

initiatives. OGEC convened an interdisciplinary Dementia Steering Committee (DSC) in 

December 2006, with the goal of making recommendations on comprehensive, coordinated care 

for Veterans with dementia. 

The DSC requested VA HSR&D’s Evidence-based Synthesis Program (ESP) to review evidence 

on selected topics to assist with DSC planning efforts. 

Broad-based dementia screening programs have not been widely advocated given lack of 

evidence that earlier detection will improve health outcomes. Improving the accuracy of 

case-finding techniques depends both on an understanding of signs and symptoms that help 

distinguish patients with dementia from those without, and the reliability of brief assessment 

tests that can be incorporated into primary care practice when appropriate. The purpose of 

this report is to systematically review the evidence on identifying the signs and symptoms of 

dementia in undiagnosed patients, and evaluating several brief mental status measures currently 

being used in VHA. The key questions and scope of this review are the following: 

Key Question #1. What signs and symptoms should prompt VA providers to assess cognitive 

function as part of an initial diagnostic workup for dementia? 

Key Question #2. Which measures of cognitive function provide the optimal sensitivity, 

specificity, and time to completion among the measures available to VA providers? 

Key Question #3. What are adverse consequences of using these measures?

Population: Adults without prior diagnosis of dementia.

Measures to be compared: Blessed Orientation-Memory-Concentration (BOMC) Test, MiniCog, Montreal Cognitive Assessment (MoCA), General Practitioner Assessment of Cognition 

(GPCOG), St. Louis University Mental Status (SLUMS) Exam, and Short Test of Mental Status 

(STMS). 

Outcomes: Likelihood for patients to be appropriately diagnosed and treated for dementia; and 

adverse consequences of assessment, such as depression and anxiety.

Settings: Primary general medicine, mental health, geriatric clinics, specialty clinics, and 

extended-care settings.

The DSC served as the technical expert panel for guiding topic development and reviewing 

drafts of the report.

METHODS

We conducted searches in MEDLINE (PubMed), PsychINFO, CINAHL, HAPI, and AGELINE 

databases for literature published from database inception through July 2009. We obtained 

additional articles from systematic reviews, reference lists of pertinent studies, narrative 

reviews, editorials, and from experts in the field. Two reviewers trained in the critical analysis 
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A Systematic Evidence Review of the Signs and Symptoms 

of Dementia and Brief Cognitive Tests Available in VA Evidence-based Synthesis Program

of literature assessed for relevance the abstracts of citations identified from literatures searches. 

Full-text articles of potentially relevant abstracts were retrieved for further review. We assessed 

the quality of studies of diagnostic test accuracy using the Quality Assessment of Diagnostic 

Accuracy Studies (QUADAS) criteria. We compiled a qualitative synthesis of the evidence.

RESULTS

We reviewed 2,394 titles and abstracts from the electronic search, an additional 88 from 

reference mining, and 57 from an update search of a selected systematic review. We retrieved 

310 full-text articles for further review. Of these, we included 18 studies and 1 systematic review 

in synthesizing evidence for Key Question #1. For Key Question #2, we evaluated the results 

of 15 diagnostic accuracy studies of the 6 VA cognitive measures. To address Key Question #3, 

we included 3 cross-sectional studies on the acceptability of dementia screening and diagnostic 

workup. 

KEY QUESTION #1. What signs and symptoms should prompt VA providers to assess 

cognitive function as part of an initial diagnostic workup for dementia? 

Relatively few studies have rigorously evaluated signs and symptoms that may help distinguish 

people with mild to moderate dementia from non-demented individuals. Subjective memory 

complaints (SMC) and neuropsychiatric symptoms have been the best studied symptoms. 

Epidemiologic studies suggest that SMC – in most cases, elicited with single- or multi-item 

questionnaires rather than spontaneous – are common in community-living elderly adults. The 

ability, however, of SMC to discriminate effectively between healthy elderly adults and those 

with dementia is uncertain. We examined cross-sectional studies comparing rates of SMC 

between persons with dementia and healthy elderly controls. Patient-reported SMC did not 

reliably distinguish demented from non-demented individuals. In populations with low rates 

of dementia, the absence of SMC may have some utility in excluding a diagnosis of dementia. 

Informant-reported memory complaints may better distinguish demented from non-demented 

individuals. 

A limited body of evidence examined neuropsychiatric symptoms in demented and nondemented individuals. In general, the absence of neuropsychiatric symptoms would not 

effectively rule out a dementia diagnosis, but the presence of certain symptoms such as apathy, 

delusions, and/or hallucinations was associated with a dementia diagnosis and may suggest 

the need for further evaluation. Depression and anxiety were common in demented and nondemented individuals, suggesting the presence of either symptom would not be useful in reliably 

ruling in or ruling out a diagnosis of dementia. 

A very limited body of evidence evaluated sleep disturbance, gait disturbance, and physical exam 

findings in demented and non-demented individuals. In general, sleep disturbance is a commonly 

reported symptom in both demented and non-demented individuals, and does not discriminate 

well the two groups. Gait disturbances are probably useful in distinguishing different subtypes of 

dementia, but there is little evidence that gait disturbances can clearly distinguish demented from 

non-demented individuals. Several physical exam findings may be more common in persons with 

Alzheimer’s dementia (AD) than healthy controls. The only finding that was highly specific for 

AD, however, was impaired sense of touch for perceiving the form of an object (stereognosis), or 

the form of a letter or number written on the skin (graphesthesia).
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A Systematic Evidence Review of the Signs and Symptoms 

of Dementia and Brief Cognitive Tests Available in VA Evidence-based Synthesis Program

KEY QUESTION #2. Which measures of cognitive function provide the optimal sensitivity, 

specificity, and time to completion among the measures available to VA providers? 

All 6 measures available in VA test for recall ability, and 5 of the 6 measures assess executive 

function by means of a clock drawing test. The assessment of other cognitive domains, such as 

orientation, abstraction, math, and language skills, varies among the 6 measures. 

The Mini-Cog has the shortest administration time of all 6 tests and has been validated in a large 

sample of the general population. Sensitivity ranged from 76% to 99%, and specificity ranged 

from 83% to 93% in analyses that excluded patients with mild cognitive impairment (MCI). 

The SLUMS test was studied in a VA population and found to have high sensitivity (98-100%) 

and specificity (98-100%) with adjustment for education. The SLUMS takes longer to 

administer than other tests. It was developed more recently than the other tests and has not been 

widely studied.

The STMS has been studied in a primary care setting. The STMS had sensitivity ranging from 

86% to 95%, and specificity was highest (93.5%) when cut-off score was adjusted for age. The 

STMS was evaluated in 2 samples and has not been widely studied. 

The GPCOG has been evaluated in a primary care setting, and includes separate sections for 

patient and informant. The sensitivity of the components ranged from 82% to 98%, but the 

informant section by itself had low specificity (49-66%). The specificity of the combined score 

and 2-stage method ranged from 77% to 86%. 

The BOMC was evaluated in a bi-racial population sample, and found to misclassify more blacks 

than whites as impaired. Specificity ranged from 38% to 94%, and sensitivity ranged from 69% 

to 100%, although the inclusion of patients with previously diagnosed dementia might have 

inflated the sensitivity in 2 studies. 

The MoCA has the longest administration time among the 6 tests, and had low specificity in 2 of 

3 studies (35-50%). The MoCA has been evaluated in a memory clinic population but has not 

been studied in a general practice setting. 

KEY QUESTION #3. What are adverse consequences of using these measures?

We found no evidence on adverse effects of the 6 cognitive tests of interest to VA. Three crosssectional studies assessed the acceptability of dementia screening or diagnostic workup among 

older adults. The studies reported that high proportions of older adults were unwilling to be 

routinely tested for memory problems, or to undergo further diagnostic assessment for dementia 

after having positive results on cognitive screening tests. One survey determined that 80% of 

respondents wanted to know if they had dementia, but only 57% would agree to routine testing 

by a physician. Perceived harms included worry about losing insurance, and fear of losing 

drivers license. The high refusal rates of screening and diagnostic workup indicate the need 

for further research to understand the psychological burden associated with cognitive tests and 

assessment for dementia.
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A Systematic Evidence Review of the Signs and Symptoms 

of Dementia and Brief Cognitive Tests Available in VA Evidence-based Synthesis Program

evidence report

BACKGROUND

In 2004, the Office of the Assistant Deputy Under Secretary for Health for Policy and Planning 

estimated that the total number of Veterans with dementia would be as high as 563,758 in FY 

2010.1 A cost analysis of data from the VA determined that the average annual cost of care for a 

patient with dementia was $19,522 in FY 1999.2 

Broad-based dementia screening programs have not been widely advocated given lack of 

evidence that earlier detection will improve health outcomes.3, 4 When implemented, screening 

programs have been associated with high false positive rates, patient hesitation to undergo 

diagnostic confirmation, and high cost per case identified.5 Furthermore, several studies have 

suggested the public is concerned about the implications of dementia screening.6-8 

The alternative to systematic screening is a case-finding approach in which clinicians initiate 

diagnostic assessment of dementia when patients and/or their caregivers describe symptoms or 

present with signs suggestive of dementia. However, with current case-finding approaches, the 

diagnosis of dementia is often missed in primary care practice.9-11

Improving the accuracy of case-finding techniques depends both on an understanding of signs 

and symptoms that help distinguish patients with dementia from those without, and the reliability 

of brief assessment tests that can be incorporated into primary care practice when appropriate. 

Currently, several organizations have issued statements including signs and symptoms that 

should prompt a diagnostic evaluation for dementia.12 However, these recommendations are 

based largely on expert opinion. 

One objective of this review, then, is to determine which signs and symptoms help distinguish 

demented patients from those without dementia. The second objective of this review is to 

compare the relative accuracy and usability of 6 brief dementia assessment methods available for 

use in VA.
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A Systematic Evidence Review of the Signs and Symptoms 

of Dementia and Brief Cognitive Tests Available in VA Evidence-based Synthesis Program

METHODS

Topic development

This review was requested by the VHA Dementia Steering Committee (DSC) and commissioned 

by the Department of Veterans Affairs’ Evidence-based Synthesis Program (ESP). The DSC 

served as the technical expert panel for guiding topic development and reviewing drafts of the 

report.

In 2007, a workgroup of expert VA clinicians identified 6 brief mental status measures as possible 

alternatives to the Mini-Mental State Examination (MMSE): Blessed Orientation-MemoryConcentration (BOMC) Test, Mini-Cog, Montreal Cognitive Assessment (MoCA), General 

Practitioner Assessment of Cognition (GPCOG), St. Louis University Mental Status (SLUMS) 

Exam, and Short Test of Mental Status (STMS). The MMSE, a widely-used clinical instrument 

for detecting cognitive impairment, requires payment or permission before it can be reproduced or 

distributed, under copyright by the Psychological Assessment Resources (PAR). The 6 alternative 

measures were selected by an internal VA panel on the basis of brevity, applicability in a range 

of settings including primary care, accuracy in detecting cognitive disturbance, and availability 

for use in VA clinical and research settings without payment of royalty fees. The instruments are 

available on an internal VA website: http://vaww.mentalhealth.va.gov/mmse.asp. 

The objectives of this review are to address the following questions:

Key Question #1. What signs and symptoms should prompt VA providers to assess cognitive 

function as part of an initial diagnostic workup for dementia? 

Key Question #2. Which measures of cognitive function provide the optimal sensitivity, 

specificity, and time to completion among the measures available to VA providers? 

Key Question #3. What are adverse consequences of using these measures?

These questions were explored within the following contexts:

Population: Adults without prior diagnosis of dementia.

Interventions to be compared: Six specific measures that VA has identified as alternatives to 

MMSE: BOMC, Mini-Cog, GPCOG, STMS, SLUMS, and MoCA. 

Outcomes: Likelihood for patients to be appropriately diagnosed and treated for dementia; and 

adverse consequences of assessment, such as depression and anxiety.

Settings: Primary general medicine, mental health, geriatric clinics, specialty clinics, and 

extended-care settings.

Search strategy

We conducted searches in MEDLINE (PubMed), PsychINFO, CINAHL, HAPI, and AGELINE 

databases for cross-sectional studies comparing demented to non-demented participants, 

published from database inception through July 2009. Appendix A provides the search strategy 

in detail. We obtained additional articles from systematic reviews, reference lists of pertinent 

studies, reviews, editorials, and by consulting experts. All citations were imported into an 

electronic database (EndNote X2).
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A Systematic Evidence Review of the Signs and Symptoms 

of Dementia and Brief Cognitive Tests Available in VA Evidence-based Synthesis Program

Study selection

Two reviewers assessed for relevance the abstracts of citations identified from literature searches. 

Full-text articles of potentially relevant abstracts were retrieved for further review. Each article 

retrieved was reviewed using the eligibility criteria shown in Appendix B. 

Eligible articles had English-language abstracts and provided primary data relevant to the key 

questions. Eligibility criteria varied depending on the question of interest, as described below.

To evaluate the signs and symptoms of dementia, we determined the prevalence of signs/

symptoms potentially associated with dementia in cross-sectional studies that compared patients 

with newly diagnosed, mild to moderate dementia with non-demented participants. We excluded 

studies with only demented individuals or only non-demented individuals, studies that did not 

provide prevalence data regarding signs and symptoms, and studies that did not use a reference 

standard to confirm the diagnosis of dementia. Because we were assessing signs and symptoms of 

prevalent dementia, we excluded studies on signs and symptoms that predicted future dementia. 

To evaluate the 6 cognitive tests selected for use in VA, we included diagnostic accuracy studies 

that compared the performance of the index test against a reference standard for dementia 

diagnosis, such as DSM-IV. We included studies that compared demented patients with 

cognitive normal patients, or that included patients with mild cognitive impairment in either the 

demented or non-demented group. We excluded studies that assessed the performance of the 

index test for detecting mild cognitive impairment only. We included observational studies on 

the adverse effects of cognitive assessment. 

Data abstraction

For each study we abstracted the following: study design, objectives, setting, population 

characteristics, subject eligibility and exclusion criteria, number of subjects, the standard 

diagnostic criteria used, and the severity of and type of dementia. For Key Question #1, we 

additionally abstracted the prevalence of the sign/symptom among demented patients and 

among non-demented patients. For Key Question #2, we additionally abstracted the proportion 

of subjects with dementia; the cognitive measure and cut-off score used; the cognitive groups 

compared; subgroups analyzed (e.g. age, education, race); sensitivity and specificity; the 

administration time of the test; and any additional test characteristics such as inter-rater 

reliability, test-retest reliability, and internal consistency. Positive and negative likelihood ratios 

with 95% confidence intervals were calculated using STATA version 10.1. 

Quality assessment

We assessed the quality of studies using the Quality Assessment of Diagnostic Accuracy Studies 

(QUADAS) criteria for evaluating diagnostic accuracy studies.13 Each sign or symptom was 

considered a diagnostic test, and the QUADAS criteria were used for quality assessment for 

these studies as well. The QUADAS tool includes 14 criteria that assess applicability, validity, 

and potential sources of bias, with each item scored as “yes,” “no,” or “unclear”. Appendix C 

lists the QUADAS criteria in detail. We did not calculate an overall quality score for each study, 

since the importance of individual items varies according to context, and the use of summary 

scores for reviews of diagnostic studies is problematic.14 We noted selected characteristics of 

studies that may affect quality. 
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A Systematic Evidence Review of the Signs and Symptoms 

of Dementia and Brief Cognitive Tests Available in VA Evidence-based Synthesis Program

Data synthesis

We constructed evidence tables showing the study characteristics and results for all included 

studies for Key Questions #1 and #2. We critically analyzed studies to compare their 

characteristics, methods, and findings. We compiled a summary of findings for each key 

question, and drew conclusions based on qualitative synthesis of the findings.

Peer review

A draft version of this report was sent to the technical advisory panel and additional peer 

reviewers. Reviewer comments and our responses are found in Appendix D. 
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A Systematic Evidence Review of the Signs and Symptoms 

of Dementia and Brief Cognitive Tests Available in VA Evidence-based Synthesis Program

RESULTS

Literature search

We reviewed 2,394 titles and abstracts from the electronic search, an additional 88 from 

reference mining, and 57 from conducting an update search of a relevant systematic review. 

After applying inclusion/exclusion criteria at the abstract level, we retrieved 310 full-text articles 

for further review. Of the full-text articles, we rejected 273 that did not meet our inclusion 

criteria (Figure 1). We included 18 studies and 1 systematic review in synthesizing evidence for 

key question #1. For key question #2, we evaluated the results of 15 diagnostic accuracy studies 

of the 6 VA cognitive measures. To address key question #3, we included 3 cross-sectional 

studies on the acceptability of dementia screening and diagnostic workup. 
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A Systematic Evidence Review of the Signs and Symptoms 

of Dementia and Brief Cognitive Tests Available in VA Evidence-based Synthesis Program

Figure 1. Literature Flow 

6

Abstracts imported from MEDLINE

(PubMed), PsychINFO, CINAHL, HAPI,

and AGELINE (1950‐June 2009)

N = 2394

Total citations identified for review:  N = 2539

Articles retrieved:  N = 310

KQ1. Dementia signs  

and symptoms

N = 19

KQ2. Diagnostic accuracy studies of 6 cognitive measures

N=15

BOMC

N = 3

SLUMS

N = 1

MoCA

N = 3

GPCOG

N = 2

Mini‐Cog

N = 4

STMS

N = 2

KQ3. Adverse effects  

of cognitive assessment

N = 3

Reference mining and an updated

search of a systematic review

N = 145

Excluded

N = 273

 Population not in scope: 36

 Did not use standard diagnostic

criteria to confirm dementia: 9

 Index test not in scope: 21

 Did not contain relevant data: 73

 Non‐English language: 7

 Used for contextual purposes

only:  127

Subjective memory

complaints: N = 4

(includes 1 SR of 8

studies)

Neuropsychiatric

symptoms: N = 5

Neurologic signs: N = 2

Gait disturbance: N = 2

Miscellaneous: N = 2

Sleep disturbance: N = 4
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 the Signs and Symptoms 

Tests Available in VA Evidence-based Synthesis Program

t signs and symptoms should prompt VA providers to assess cognitive function as part of an initial 

mentia? 

nd symptoms in demented and non-demented individuals are shown in the table below. The findings for each sign/

wing Table 1. 

cs, sensitivity, and specificity of dementia signs and symptoms

ng, country,

e, type, and 

available)

Sensitivity of sign/symptom 

(unless otherwise specified)

Specificity of sign/symptom 

(unless otherwise specified)

Comments

= 9,148

tudies, U.S.

sed samples

nce: 8.8%

NR

Range: 31 – 96%. Range: 30 – 98% Good quality review, but 

methodologic flaws and study heterogeneity limit confidence in pooled results. Many of the included studies had methodologic flaws. 

 U.S.

nce: 9.7%

R

NR

Self-reported SMC: 15.2% (5/33) Self-reported SMC: 93.5% (285/305) Depended on chart documentation 

of a self-reported symptom – may grossly underestimate the prevalence of the symptom and inflate specificity.

ample, U.S.

 positive 

31.0%

e: NR

.8%

3.5%

4.7%

Self-reported SMC (patients with CDR ≥ 1): 29.5% Self-reported SMC: 82.2% Subjects screened with MMSE so 

prevalence of dementia is higher than would be expected in pure population sample. Prevalence of SMC in patients with CDR = 0.5 (questionable dementia) was 24.8%.

ample, U.S.

nce: NC

e: AD

8%

4.2%

0%

Self-reported SMC (patients with CDR ≥ 1): 75.3%

Informant-reported SMC (patients with CDR ≥ 1): 

98.1% 

Self-reported SMC (including patients with 

questionable dementia in control group): 

35.6%

Self-reported SMC (excluding patients with 

questionable dementia): 56.3%

Informant-reported SMC (excluding patients 

with questionable dementia): 86.1%

The only study using single question assessment of informant-reported SMC. Self-reported SMC correlated with depressive symptoms.
11

 the Signs and Symptoms 

Tests Available in VA Evidence-based Synthesis Program

ng, country,

e, type, and 

available)

Sensitivity of sign/symptom 

(unless otherwise specified)

Specificity of sign/symptom 

(unless otherwise specified)

Comments

elected from 

Brazil

nce: 6.8%

60

 25

althy controls: 

± 4.9

Sensitivities AD v CIND + control:

Delusion 11.7% (7/60)

Hallucination 8.3% (5/60)

Agitation/aggression 20% (12/60)

Depression 38.3% (23/60)

Anxiety 25% (15/60)

Elation 5% (3/60)

Apathy 53.3% (32/60)

Disinhibition 16.7% (10/60)

Irritability 23.3% (14/60)

Aberrant motor behavior 10% (6/60)

Sleep disturbance 38.3% (23/60)

Appetite alteration 23.3% (14/60)

Specificities AD v CIND + control:

Delusion 100% (103/103)

Hallucination 100% (103/103)

Agitation/aggression 94.2% (97/103)

Depression 87.4% (90/103)

Anxiety 89.3% (92/103)

Elation 100% (103/103)

Apathy 96.1% (99/103)

Disinhibition 100% (103/103)

Irritability 96.1% (99/103)

Aberrant motor behavior 100% (103/103)

Sleep disturbance 91.2% (94/103)

Appetite alteration 99.0% (102/103)

Dementia patients were older and less well-educated.

ubstudy of 

h study, U.S.

es) from pool 

or AD and non

tia

33.4% (24% if 

ts excluded)

 27.2%

NR

Dementia (%) vs MCI*

Delusions 18% (65/362) v 3.1 v 2.4

Hallucinations 10.5% (38/362) v 1.3 v 0.6

Agitation/aggression 30.3% (110/362) v 11.3 v 2.9

Depression 32.3% (117/362) v 20.1 v 7.2

Anxiety 21.5% (78/362) v 9.9 v 5.8

Euphoria 3.1% (11/362) v 0.6 v 0.3

Apathy 35.9% (130/362) v 14.7 v 3.2

Disinhibition 12.7% (46/362) v 3.1 v 0.9

Irritability 27.0% (98/362) v 14.7 v 4.6

Aberrant motor behavior 16% (58/362) v 3.8 v 0.4

Sleep disturbance 27.4% (99/362) v 13.8 v NA

Eating disturbance 19.6% (71/362) v 10.4 v NA

Dementia vs MCI:

Delusions 96.9% (310/320)

Hallucinations 98.7% (316/320)

Agitation/aggression 88.7% (284/320)

Depression 79.9% (256/320)

Anxiety 90.1% (290/320)

Euphoria 99.4% (318/320)

Apathy 85.3% (273/320)

Disinhibition 96.9% (310/320)

Irritability 85.3% (273/320)

Aberrant motor behavior 96.2% (308/320)

Sleep disturbance 86.2% (276/320)

Eating disturbance 89.6% (287/320)

Higher dementia prevalence since nearly half the participants had high pre-test probability of cognitive disturbance. Non-demented population data derived from a different cohort.

2

U.S.

MMSE screen 

.4%

nd vascular 

a

NR

Sensitivities:

Delusions 18.5% (61/329)

Hallucinations 13.7% (45/329)

Depression 23.7% (78/329)

Anxiety 17.0% (56/329)

Apathy 27.4% (90/329)

Irritability 20.4% (67/329)

Agitation/aggression 23.7% (78/329)

Disinhibition 9.1% (30/329)

Aberrant motor behavior 14.3% (47/329)

Specificities:

Delusions 97.0% (653/673)

Hallucinations 99.3% (668/673)

Depression 92.7% (624/673)

Anxiety 93.3% (628/673)

Apathy 96.6% (650/673)

Irritability 95.1% (640/673)

Agitation/aggression 96.9% (652/673)

Disinhibition 98.8% (665/673)

Aberrant motor behavior 98.4% (662/673)

Population-based design and high participation rates. Subjects screened with MMSE so prevalence of dementia is higher than would be expected in pure population sample.
12

 the Signs and Symptoms 

Tests Available in VA Evidence-based Synthesis Program

ng, country,

e, type, and 

available)

Sensitivity of sign/symptom 

(unless otherwise specified)

Specificity of sign/symptom 

(unless otherwise specified)

Comments

0

udy of general 

udy, Finland

nce: 8.9%

lar dementia

thout dementia 

n chart

 dementia 

n chart

32% (36/112) 81.8% (929/1136) Population-based design and high 

participation rates are strengths. Study mainly looked at rates of documentation in chart.

er, U.S.

ence: NC

e: NR

: NR

Mild, moderate or severe depression according to 

Hamilton Rating Scale for Depression: 40.9%

Mild, moderate or severe depression 

according to Hamilton Rating Scale for 

Depression: 88%

, U.S.

nce: 50%

R

NR

Poor sleep quality (PSQI > 5): 34.2% (53/155) Poor sleep quality (PSQI > 5): 40% 

(62/155)

Subtypes of dementia not reported.

c, U.S.

nce: NC

e AD

± 6.2

Subjective sleep problems: 27.6% (71/258) Subjective sleep problems: 82.7% 

(320/393)

Non-demented patients self-reported information, while caregivers of demented patients often reported information for demented subgroup.

ple of persons 

eden

nce: NR

R

NR

Subjective sleep disturbance (Comprehensive 

Psychopathological Rating Scale): 17.8%

N not reported

Subjective sleep disturbance: 73.1% Unclear duration of dementia 

diagnosis, little information about cohort.
13

 the Signs and Symptoms 

Tests Available in VA Evidence-based Synthesis Program

ng, country,

e, type, and 

available)

Sensitivity of sign/symptom 

(unless otherwise specified)

Specificity of sign/symptom 

(unless otherwise specified)

Comments

 clinic, U.K.

sease

NR

Sensitivity: 77% (10/13) Specificity: 73% (38/52) Applicable to Parkinson’s dementia 

only. Unclear proportion of dementia diagnoses that were made retrospectively. Convenience sample. RBD diagnosed with questionnaire, not polysomnography.

 > 65

s, U.K.

nce: NC

ons, and DLB

on for Mental 

rly Cognitive 

core:

± 4.7

14.5

61.7 ± 18.3

9 ± 16.3

15.0

Gait or balance disorder (Tinetti score < 7 or 

balance score < 22):

AD – 10/40 (25%)

Vascular dementia – 31/39 (79%)

Parkinson’s – 43/46 (93%)

DLB – 24/32 (75%)

Specificity: 93% (39/42) Convenience sample. Not clear if 

reference standard was applied to all controls.

c, U.S.

ence: NC

D

a (CDR 1)

entia (CDR 2)

ntia (CDR 3)

Disequilibrium 58% (32/55)

Wide-based gait 31% (17/55)

Short-stepping gait 35% (19/55)

Resistance to passive movement 18% (10/55)

Disequilibrium 64% (35/55)

Wide-based gait 85% (47/55)

Short-stepping gait 84% (46/55)

Resistance to passive movement 98% 

(1/55)

Convenience sample. Purposive sampling of mild, moderate, and severe dementia. Prevalence of frontal gait disorder correlated with severity of dementia.

 > 75

ustralia

e: NR

NR

Signs associated with dementia in a regression 

model (p < .05): rigidity, spasticity, snout/grasp 

reflex, impaired vibration sense

Major methodologic flaws. Selection criteria, index test, and standard criterion not well described. Large number of variables tested in regression model.
14

 the Signs and Symptoms 

Tests Available in VA Evidence-based Synthesis Program

ng, country,

e, type, and 

available)

Sensitivity of sign/symptom 

(unless otherwise specified)

Specificity of sign/symptom 

(unless otherwise specified)

Comments

, specialty, and 

U.S.

nce: NC

D

± 5.3

Sensitivities:

Release signs – 54.7% (52/95)

Olfaction – 20.2% (19/95)

Stereognosis† and graphesthesia‡ - 22.1% (21/95)

Abnormal gait – 33.7% (32/95)

Specificities:

Release signs – 90.8% (79/87)

Olfaction – 90.7% (79/87)

Stereognosis and graphesthesia – 98.9% 

(1/87)

Abnormal gait – 92.9% (6/87)

Convenience sample. Mean estimated duration of Sx nearly 3 years in dementia group. Not clear if “healthy” defined by self-report or by standard criterion.

and community 

orea

ce: 63.1%

D

± 5.8

Mean pulse pressure, cases: 58.9 ± 16.0 Mean pulse pressure, controls: 54.3 ± 11.3 Convenience samples taken from 

two different populations, with case patients enrolled from a memory clinic.

c, U.S.

 from a larger 

riving and AD

nce: NC

21.5 ± 3.9

4.9 ± 3.6

Self-reported less than “safe” driving ability:

6% (3/50)

Self-reported less than “safe” driving ability:

specificity: 100% (24/24)

Not a population-based sample. Focused mainly on correlation between self-rated and on-road driving performance in demented patients.

therefore figures represent comparison of demented patients to those with MCI

he form of an object by using the sense of touch

ze a number or letter written on the skin by the sensation of touch

se, CIND = Cognitively impaired non-demented, DLB = Dementia with Lewy bodies, MCI = Mild cognitive impairment, NC = cannot be calculated, PSQI = 

subjective memory complaints, Sx = symptoms
15

A Systematic Evidence Review of the Signs and Symptoms 

of Dementia and Brief Cognitive Tests Available in VA Evidence-based Synthesis Program

Subjective memory complaints

Summary of findings (Table 1)

Epidemiologic studies suggest subjective memory complaints (SMC) – in most cases elicited with 

single- or multi-item questionnaires, rather than spontaneous – are common in community-living 

elderly adults.34, 35 The ability, however, of subjective memory complaints to discriminate effectively 

between healthy elderly adults and those with dementia is uncertain. We examined cross-sectional 

studies comparing rates of SMC between persons with dementia and healthy elderly controls.

Conclusions from this body of evidence should be tempered by methodologic flaws in some 

of the studies, as well as variability across studies in populations included and methods used 

for memory complaint elicitation. We found patient-reported SMC did not reliably distinguish 

demented from non-demented individuals. Patient-reported SMC were poorly sensitive for 

detecting dementia and only moderately specific. In populations with low prevalence of 

dementia, the absence of SMC may have some utility in excluding a diagnosis of dementia 

given its relatively high negative predictive value in these settings. Informant-reported memory 

complaints may better distinguish demented from non-demented individuals. 

Detailed description

One recently published systematic review found 8 cross-sectional studies which compared 

elicited patient-reported SMC in demented and non-demented persons.15 All studies were 

community-based and ranged in size from 156 to 3,220 participants. A number of the included 

studies had substantial flaws which reduce the strength of conclusions that can be drawn from 

this body of literature. Three studies established a dementia diagnosis using a widely-accepted 

gold standard.36-38 One of the studies used a less widely-accepted cognitive evaluation,39 and 

another study used an informant interview to establish a diagnosis.40 Three of the studies used 

only brief assessment methods to validate the diagnosis of dementia.41-43 Because of significant 

heterogeneity among studies, the pooled results cannot be used with any degree of confidence. 

Of the 3 studies that used a widely-accepted gold standard to establish a dementia diagnosis,36-38

one was mainly a study of different subtypes of mild cognitive impairment (MCI) and the 

number of patients with dementia was very low.38 Tobiansky, et al.36 and St. John, et al.37 both 

examined large community-based samples, but used different methods for eliciting SMC: 1 

study used a 9-item questionnaire,36 while the other study simply asked whether participants had 

had memory loss during the past year.37 

We found several more recent studies that were not included in the Mitchell review. One 

community-based study found a very low sensitivity of 15.2%, but a relatively high specificity 

of 93.5%.16 However, these rates were likely a reflection of the method of SMC ascertainment, 

which relied on retrospective chart review. A multi-site primary care study of patients with 

largely mild dementia found patient-reported SMC also did not distinguish well between 

demented and non-demented participants.17 Of note, investigators did find greater discrepancies 

between patient interview results and chart notes among patients with more severe dementia. 

In contrast to patient-reported SMC, a small body of evidence suggests informant-reported SMC 

may better distinguish demented from non-demented individuals. One study of patients with 

mild and very mild Alzheimer’s type dementia (AD) found informant complaints of memory 

loss (using a single question assessment) more reliably correlated with dementia than patient 
16

A Systematic Evidence Review of the Signs and Symptoms 

of Dementia and Brief Cognitive Tests Available in VA Evidence-based Synthesis Program

complaints (sensitivity of informant complaints 98.1%, specificity 86.1%).18 Furthermore, 

patient-reported SMC did not predict future onset of dementia, whereas informant-reported SMC 

were associated with an increased risk of future dementia, a finding similar to a prior longitudinal 

study.44 Patient complaints of memory loss in this study were closely associated with depressive 

symptomatology, findings that corroborate those of older studies.44, 45

Table 2 uses data from 2 of the self-reported SMC studies and the informant-reported memory 

complaint study to compare positive and negative predictive values in hypothetical populations 

with differing prevalence rates of dementia. All 3 studies suggest in populations with low rates 

of dementia, the lack of memory complaints may help exclude a dementia diagnosis, and the lack 

of informant memory complaints may most reliably exclude a diagnosis of dementia. 

Table 2. Sensitivity, specificity, and predictive values of memory complaints in selected studies

Population Sensitivity Specificity Prevalence 

assumption

Positive Predictive 

Value

Negative 

Predictive Value

Community sample 37 58.0% 76.0%

10%

50%

75%

21.2%

70.7%

87.9%

94.2%

64.4%

37.6%

Community sample 36 46.0% 97.0%

10%

50%

75%

63.1%

93.9%

97.9%

94.2%

64.2%

37.5%

Community sample

– informant-reported 

memory complaints 18 

98.1% 86.1%

10%

50%

75%

43.8%

87.5%

94.6%

99.7%

97.7%

82.7%

A brief informant questionnaire, which combines 3 questions on informant-reported memory 

complaints with 5 questions covering other domains, including judgment and financial 

management, has been evaluated in demented and non-demented individuals. The questionnaire 

– the AD8 – discriminated well between demented and non-demented individuals (area under 

the curve 0.92; 95% CI 0.88 – 0.95).46 The same authors later compared the utility of informantadministered to patient-administered AD8 and found both distinguished demented from nondemented individuals, but the informant-administered questionnaire performed better.47

Neuropsychiatric symptoms

Summary of findings

We found 3 community-based studies which used the Neuropsychiatric Inventory (NPI)48 to 

compare neuropsychiatric symptoms in demented and non-demented persons. In general, 

neuropsychiatric symptoms were poorly sensitive but moderately to highly specific for dementia. 

Apathy was the most common neuropsychiatric symptom reported in demented persons and was 

present much less frequently in non-demented persons. Depression and anxiety were common in 

both groups, suggesting the presence of either symptom would not be useful in reliably ruling in 

or ruling out a diagnosis of dementia. 
17

A Systematic Evidence Review of the Signs and Symptoms 

of Dementia and Brief Cognitive Tests Available in VA Evidence-based Synthesis Program

Detailed description

One well-conducted study included elderly residents of Cache County, Utah, and used a 

modified, more sensitive version of the Mini-Mental State Exam (MMSE) to identify a 

subpopulation at higher risk for dementia; and also included a randomly selected MMSE screen 

negative population.21 All participants underwent a comprehensive cognitive assessment and 

were categorized as demented or non-demented according to DSM-IV criteria. The prevalence 

of dementia (18.4%) in this study reflects the use of MMSE as an initial screen and is higher than 

would be expected in the general population. Neuropsychiatric symptoms were more common 

in demented than non-demented individuals and 61% of demented individuals had had at least 

one behavorial symptom in the last month. Over 1 in 4 people with dementia were reported 

to display apathy, compared to less than 1 in 20 non-demented people. Depression was least 

helpful in distinguishing healthy elderly controls (specificity 92.7%). 

Another study used a subsample of data from the Cardiovascular Health Study, and nearly half 

the participants had a high pre-test probability of cognitive dysfunction, which was reflected 

in the study’s high prevalence of dementia (33.4%).20 The study cohort included persons with 

dementia and mild cognitive impairment (MCI), but the non-demented comparison group 

was derived from a separate cohort in which sampling methods may have been different. 

Therefore, we only report sensitivity and specificity data comparing persons with dementia to 

persons with MCI. As expected, the specificities were lower, suggesting a higher likelihood of 

neuropsychiatric symptom presence in persons with MCI than healthy controls. 

A community-based Brazilian study with a lower prevalence of dementia also had largely similar 

findings, but findings from this study may be less generalizable to VA populations in the United 

States.19

One population-based study focused on accuracy of dementia documentation in medical records 

of persons with and without dementia, but included the prevalence rates of depression in 

demented and non-demented people.22 Similar to other studies, depression had a low sensitivity 

and specificity for dementia (32.0% and 81.8%, respectively). These results were similar to a 

small, older study of depression in demented and non-demented persons.23 

Sleep disturbance

We found 4 studies comparing the frequency of sleep disturbance in patients with and without 

dementia. One of these studies compared the frequency of REM Sleep Behavior Disorder (RBD) 

in a convenience sample of Parkinson’s disease patients with and without dementia, and is not 

applicable to patients with other types of dementia.27

The remaining 3 studies examined sleep disturbance in persons with and without dementia, 

mainly of Alzheimer’s type.24-26 In general, sleep disturbance is a commonly reported symptom 

in both demented and non-demented individuals, and does not discriminate the groups well. In 

fact, 2 of the studies found a higher prevalence of sleep disturbance complaints in non-demented 

than in demented persons.24, 26 Results from the third study are more difficult to interpret because 

sleep disturbance questionnaires were completed by caregivers of demented participants, whereas 

non-demented participants in the control group completed the questionnaires themselves.25 The 

body of evidence is limited by differences in definition of sleep disturbance, disparate patient 

populations and settings, and limited direct applicability to primary care settings. 
18

A Systematic Evidence Review of the Signs and Symptoms 

of Dementia and Brief Cognitive Tests Available in VA Evidence-based Synthesis Program

Gait disturbance

Summary of findings

Only 2 studies have compared gait disturbance frequency in persons with and without dementia. Gait 

disturbances are probably useful in distinguishing different subtypes of dementia, but there is little 

evidence that gait disturbances can clearly distinguish demented from non-demented individuals.

Detailed description

Early presence of gait disturbance had been thought an uncommon finding in AD and, in fact, 

is cited as a factor negatively associated with the diagnosis in the NINCDS-ADRDA criteria for 

AD.49 One small study examined the prevalence of various types of gait disturbance in patients 

with various stages of AD and in a poorly defined control population.29 They found that cautious 

gait was a common finding in both early stage AD and in healthy controls. Findings consistent 

with frontal gait disturbance, on the other hand, were more common with increasing severity of 

disease, but very uncommon in healthy participants. 

The second study compared gait and balance disorder frequency between persons with different 

dementia subtypes and also to healthy controls.28 Not surprisingly, gait and balance disorders 

were significantly more common in persons with vascular, Lewy-body, and Parkinson’s dementia 

than in persons with AD. Gait and balance disturbance was slightly more prevalent in persons 

with AD than in controls (odds ratio 4, 95% CI 1.1 – 17). 

Neurologic signs

Several physical exam findings may be more common in persons with AD than healthy controls. 

In one study using a convenience sample of persons with mild AD, release signs, olfactory 

deficit, impaired sense of touch, and an abnormal gait were all more common in persons with 

AD.31 The only finding, however, that was highly specific for AD was stereognosis (the ability 

to perceive the form of an object by using the sense of touch) and graphesthesia (the ability to 

recognize writing on the skin purely by the sensation of touch), with sensitivity of 22.1% and 

specificity of 98.9%. None of the signs were very sensitive for dementia, though release signs 

were present in over half the participants with AD (sensitivity 54.7%). 

Another study using a population-based sample also examined a number of neurologic signs 

and found that rigidity, spasticity, and frontal release signs were associated with dementia in 

a regression model.30 The study findings were somewhat consistent with the aforementioned 

study; however, the study evaluated a large number of signs in a regression model and it is 

possible some of the findings reflect a chance finding given the multiple variables examined. 

Miscellaneous

The final 2 studies provide interesting preliminary data but are not part of a robust enough body of 

evidence to draw firm conclusions. One study examined the relationship between pulse pressure 

and AD, and found higher mean pulse pressure among persons with AD compared with their nondemented counterparts (58.9 vs. 54.3, p < 0.05). The result suggests higher pulse pressure was 

associated with increased white matter changes.32 However, the study has some methodologic flaws, 

the most important being the case and control groups were derived from different populations. 
19

A Systematic Evidence Review of the Signs and Symptoms 

of Dementia and Brief Cognitive Tests Available in VA Evidence-based Synthesis Program

One study focused primarily on the correlation between self-reported and on-road driving 

performance, but did examine self-reported rating of “safe” driving ability in patients with 

and without dementia.33 Most demented persons rated themselves as safe drivers even though 

informants and driving instructors were much less likely to rate their driving as safe. The 

sensitivity of less than safe driving ability for identifying dementia is, not surprisingly, very low. 

Key Question #2. Which measures of cognitive function provide the optimal 

sensitivity, specificity, and time to completion, among the measures available to 

VA providers? 

Summary of findings

All 6 measures available in VA test for recall ability, and 5 of the 6 measures assess executive 

function by means of a clock drawing test. The assessment of other cognitive domains, such as 

orientation, abstraction, and aphasia, varies among the 6 measures. 

The Mini-Cog has the shortest administration time of all 6 tests and has been validated in a large 

sample of the general population. Sensitivity ranged from 76% to 99%, and specificity ranged 

from 83% to 93% in analyses that excluded patients with MCI. 

The SLUMS test was studied in a VA population and found to have high sensitivity (98-100%)

 and specificity (98-100%) with adjustment for education. The SLUMS takes longer to 

administer than other tests. It was developed more recently than the other tests and has not been 

widely studied.

The STMS has been studied in a primary care setting. The STMS had sensitivity ranging from 

86% to 95%, and specificity was highest (93.5%) when cut-off score was adjusted for age. The 

STMS was evaluated in 2 samples and has not been widely studied. 

The GPCOG has been evaluated in a primary care setting, and includes separate sections for 

patient and informant. The sensitivity of the components ranged from 82% to 98%, but the 

informant section by itself had low specificity (49-66%). The specificity of the combined score 

and 2-stage method ranged from 77% to 86%. 

The BOMC was evaluated in a bi-racial population sample, and found to misclassify more blacks 

than whites as impaired. Specificity ranged from 38% to 94%, and sensitivity ranged from 69% 

to 100%, although the inclusion of patients with previously diagnosed dementia might have 

inflated the sensitivity in 2 studies.

The MoCA has the longest administration time among the 6 tests, and had low specificity in 2 of 

3 studies (35-50%). The MoCA has been evaluated in a memory clinic population, but has not 

been studied in a general practice setting. 

Table 3 summarizes the strengths and limitations of each test. Detailed findings are provided in 

the pages that follow. 
20

A Systematic Evidence Review of the Signs and Symptoms 

of Dementia and Brief Cognitive Tests Available in VA Evidence-based Synthesis Program

Table 3. Pros and cons of 6 brief mental status measures available for use in VA

Test Pros Cons

BOMC 	Studied in a general population sample and 2 

specialty clinic settings

	Low specificity (38-77%) in 2 of 

4 studies

	Race and education biases in 1 

study

GPCOG 	Studied in a primary care setting

	Education bias found absent

	The combined score and 2-stage method had 

higher sensitivity and specificity than patient and 

informant sections separately

	Informant section alone has low 

specificity (49-66%)

Mini-Cog 	Shortest administration time (2-4 minutes)

	Studied in a general population sample

	High specificity (83-93%) in studies that excluded 

MCI from comparator group 

	Education and language/race biases found 

absent in U.S. samples 

	May be inappropriate for 

populations with extremely low 

levels of education or literacy

MoCA 	Studied in a memory clinic population

	High sensitivity (94-100%)

	Longest administration time (10-

15 minutes)

	Low specificity (35-50%) in 2 of 

3 studies

SLUMS 	Studied in a VA geriatric clinic population

	High sensitivity and specificity (98-100%)

	Adjusts cut-off score for education

	Longer administration time (7 

minutes)

	Evaluated in only 1 study

STMS 	Studied in a primary care setting

	Shorter administration time (5 minutes)

	High specificity (93.5%) using age-adjusted cutoff 

scores

	Evaluated in 2 studies
21

A Systematic Evidence Review of the Signs and Symptoms 

of Dementia and Brief Cognitive Tests Available in VA Evidence-based Synthesis Program

Detailed description

The literature search identified 16 primary studies that assessed the test performance of one or 

more of the 6 brief cognitive assessments against a standard criterion for diagnosing dementia. 

Table 4 shows the study characteristics and the test performance results for each cognitive 

measure. Positive and negative likelihood ratios were calculated using the reported results for 

sensitivity and specificity, with the exception of 1 study,50 for which sensitivity and specificity 

results were derived from a systematic review compiled in 2003 for the U.S. Preventive Services 

Task Force (USPSTF).51

The BOMC test was assessed in 4 studies reported in 6 publications,50-55 the GPCOG in 2 

studies,56, 57 the Mini-Cog in 3 studies,58-60 the MoCA in 3 studies,61-63 SLUMS in 1 study,64 and 

STMS in 2 studies.65, 66 

The cognitive measures were studied in a variety of populations, including primary care, 

specialty clinics, and residential care/assisted living facilities. The prevalence of dementia varied 

with study setting (Table 4). Prevalence is not shown for studies that used a constructed sample 

(e.g. dementia cases matched 1:1 with controls) or that recruited subjects from heterogeneous 

settings. The prevalence of dementia in Table 4 is defined as the proportion of demented patients 

in the analyzed sample. 

In some studies, subjects with MCI were excluded from the analysis.58, 60, 61, 64 In other studies, 

subjects with MCI were included in the non-demented comparison group,60 or were combined 

with dementia patients for the assessment of test performance.62 The inclusion of subjects 

with MCI in the analysis could negatively affect the operating characteristics of the index test. 

Combining MCI with dementia would decrease sensitivity if MCI patients were more likely than 

dementia patients to be misclassified as unimpaired. Conversely, including MCI in the nondemented group would decrease specificity if MCI patients were more likely than cognitively 

normal subjects to be misclassified as demented. 
22

 the Signs and Symptoms 

Tests Available in VA Evidence-based Synthesis Program

cs and test performance results for the BOMC, GPCOG, Mini-Cog, MoCA, SLUMS, and STMS

Dementia 

(%) Comparison N total Cut-off Score Sens. Spec. +LR (95%CI) -LR (95% CI)

16.9 Black race only: demented v. nondemented 83 11 1.0 0.382 1.56 (1.27-1.91) 0.0881 (0.0057-1.37)

3.7 White race only: demented v. nondemented 81 11 1.0 0.785 3.95 (2.27-6.88) 0.161 (0.012-2.15)

83.3 Combined dementias v. normal 282 7/6 0.91 0.63 2.52

(1.72-3.69)

0.14

(0.0883-0.222)

10/9 0.83 0.77 3.55

(2.11-5.97)

0.222

(0.161-0.307)

33.1 Combined dementias v. normal 133 10/11 0.886 0.944 15.8

(6.69-37.2)

0.12

(0.0527-0.275)

‖ Combined dementias v. normal 321 NR 0.69 0.9 7

(4.06-12.1)

0.346

(0.279-0.428)

+, 

ry 

29.1 Patient section only; demented v. 

non-demented

282 7/8 0.82 0.7 2.72

(2.15-3.45)

0.261

(0.164-0.417)

Informant section only 202 4/5 0.89 0.66 2.62

(2.06-3.34)

0.155

(0.0718-0.333)

Combined score 202 10/11 0.82 0.83 4.85

( 3.3-7.12)

0.224

(0.131-0.384)

Two-stage method 246 --- 0.85 0.86 6.14

(4.18-9.02)

0.177

(0.103-0.306)

‖ Patient section only; definite dementia 

v. normal (excludes MCI)

118 <=7 0.982 0.672 2.95

(2.06-4.22)

0.0259

(0.0037-0.182)

Informant section only 80 <=4 0.942 0.491 1.82

(1.24-2.66)

0.114

(0.0351-0.367)

Combined score; definite dementia v. 

normal (excludes MCI)

80 <=10 0.981 0.774 4.09

(2.03-8.23)

0.0239

(0.0034-0.169)

6.4 Demented v. normal (excludes MCI) 1119 2/3 0.76 0.89 6.95

(5.61-8.62)

0.265

(0.175-0.402)

out 

37.7 Dementia v. (MCI + no cognitive 

impairment)

146 2/3 0.87 0.54 1.89

(1.48-2.41)

0.236

(0.115-0.484)

 

‖ Combined dementias v. normal 

(excludes MCI)

300 2/3 0.969 0.828 5.65

(3.92-8.14)

0.0377

(0.0159-0.0897)

72.7

48††

Dementia v. non-demented (excludes 

MCI)

44 <26 0.94 0.5 1.88

(1.06-3.32)

0.125

(0.0291-0.536)
23

 the Signs and Symptoms 

Tests Available in VA Evidence-based Synthesis Program

Dementia 

(%) Comparison N total Cut-off Score Sens. Spec. +LR (95%CI) -LR (95% CI)

‖ Combined (dementia + MCI) v. 

normal

118 <=26 0.97 0.35 1.51

(1.27-1.79)

0.0647

(0.0091-0.46)

a v. 

‖ Mild AD v. normal (excludes MCI) 183 26 1.0 0.87 7.24

(4.33-12.1)

0.0062

(3.9e-04-0.098)

16.5

12.6††

Education <HS: Dementia v. normal 

(excludes MCI)

164 19.5 1.0 0.98 38.7

(13.7- 109)

0.0183

(0.0012-0.286)

15.4

11.3††

Education >=HS: Dementia v. normal 

(excludes MCI)

358 21.5 0.98 1.0 592

(37.1-9442)

0.0268

(0.0055-0.13)

s in 

‖ Dementia v. normal (excludes MCI) 248 <29 0.864 0.884 7.45

(4.67-11.9)

0.154

(0.096-0.248)

By age:

60-69: 3070-79: 2980-89: 28

>90: 27

0.864 0.935 13.2

(7.01-25)

0.146

(0.091-0.234)

on

y 

‖ Combined dementias v. no dementia 

(excludes MCI)

180 <=29 0.92 0.914 10.7

(5.5-20.8)

0.088

(0.0431-0.18)

AD v. no dementia

(excludes MCI)

160 0.955 0.914 11.1

(5.71-21.6)

0.049

(0.0162-0.148)

Aged 60+ only: Combined dementias 

v. no dementia (excludes MCI)

109 0.947 0.879 7.82

(3.11-19.6)

0.0599

(0.0229-0.157)

dementia; sensitivity may be overestimated. 

 populations.

andomly or consecutively sampled.

ated in the USPSTF 2003 report51 based on an 

d sample. Prevalence could not be calculated.

nce standard were not fully blinded.

udes subjects with mild cognitive impairment.

** Subjects with dementia and MCI are compared with cognitively normal subjects. †† Prevalence of dementia in the total sample that comprised patients with dementia, MCI, and no cognitive impairment. MCI patients were otherwise excluded from the results shown. Abbreviations: +LR = Positive Likelihood Ratio; -LR = Negative Likelihood Ratio; AD = Alzheimer’s Disease; BOMC = Blessed Orientation-Memory-Concentration Test; GPCOG = General Practitioner Assessment of Cognition; MCI = Mild Cognitive Impairment; MoCA = Montreal Cognitive Assessment; Sens. = Sensitivity; SLUMS = St. Louis University Mental Status Exam; Spec. = Specificity; STMS = Short Test of Mental Status
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Table 5 on the following page provides descriptive characteristics of the 6 tests, including the 

time to administer and the cognitive domains assessed.67 All 6 measures test for recall ability, 

and assessment for executive function by means of a clock drawing test is a component in all 

measures except the BOMC. The assessment of other cognitive domains, such as orientation, 

abstraction, math, and language skills, varies among the 6 measures. 

Table 5 also shows characteristics of the tests that were reported in some but not all studies. 

These include inter-rater reliability; test-retest reliability; internal consistency; and the effects 

of education, race, and language on test performance. Among the 6 measures, only the MiniCog and BOMC were examined for differences by race or language in a biracial or multi-ethnic 

sample. 

In addition, Table 5 displays the sensitivity, specificity, positive likelihood ratio, and negative 

likelihood ratio from a selected study for each cognitive measure. These representative studies 

were selected based on applicability to the settings that the samples were drawn from: the 

general population in the case of the BOMC and Mini-Cog; primary care or a geriatric clinic in 

the case of the GPCOG, SLUMS, and STMS; and a memory clinic population in the case of the 

MoCA.
25

 the Signs and Symptoms 

Tests Available in VA Evidence-based Synthesis Program

BOMC GPCOG Mini-Cog MoCA SLUMS STMS

X X X X XX X X X X X

X

X X X X X

X X

X X X X

X X X

X X X X X

Yes52, 53 No56, 57 No59, 68 Yes*62 No64 Yes66

Yes52 --- No59, 68 --- --- Yes†65

53 56 58 61 64 66

0.83 Patient only: 0.82 Two-stage: 0.85 0.76 0.94 <HS: 1.0 HS+: 0.98 Age-based cutoff: 0.860.77 0.7 0.86 0.89 0.5 0.98 1.0 0.9353.55 

.11-5.97) 2.72 (2.2-3.5) 6.14 (4.2-9.0) 6.95 (5.6-8.6) 1.88 (1.0-3.3) 38.7 (13.7- 109) 592 (37.1-9442) 13.2 (7.0-25)

0.222 

61-0.307) 0.261 (0.16-0.42) 0.177 (0.10-0.31) 0.265 (0.18-0.40) 0.125 (0.03-0.54) 0.0183 (0.001-0.29) 0.0268 (0.006-0.13) 0.146 (0.09-0.23)

4-6 Patient: 2-5 Informant: 1-3 2-4 10-15 7 5

--- Adequate56 Adequate59 --- --- ---

equate53, 54 Adequate56 --- Adequate63 --- ---

--- Adequate56 --- Adequate63 --- ---

correctable by the inclusion of a 1-point education correction for individuals with 12 or fewer years of education.62

e disturbance would preclude use of the STMS. The test could be administered with the help of interpreters to patients who do not speak English. 

measure was selected based on applicability to the setting that the sample was drawn from: the general population in the case of the Mini-Cog; primary care 

 and STMS; and a memory clinic population for the BOMC and the MoCA. 

 education; HS+ = high school or more education. 

, biases, and other characteristics of BOMC, GPCOG, Mini-Cog, MoCA, SLUMS, and STMS
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BOMC

The BOMC is a 6-item measure derived from the Blessed Information-Memory-Concentration 

Test.69 The items are weighted for a total maximum score of 28, and include current date (month, 

year) and time, counting backwards from 20 to 1, reciting the months of the year in reverse order, 

and recalling a previously repeated 5-element address.50 Test-retest reliability of the BOMC was 

assessed and found adequate in 2 studies.53, 54 The administration time is 4 to 6 minutes.

The BOMC was assessed in a population-based sample, a memory clinic, a neurology clinic, and 

in a study with mixed settings (Table 4). Two studies used a cutoff score of 11 (11 or more errors 

on the weighted 28-point scale indicates impairment),52, 54 but the cut-off score of 10/9 (given 

as best score for demented group/worst score for non-demented group) yielded the maximum 

results for both sensitivity (83%) and specificity (77%) in a study of patients in a memory clinic.53 

Although the sensitivity of the BOMC was found to be 100% in the population-based study,52 this 

result may be inflated due to the inclusion of subjects with pre-existing dementia in the sample. 

In a population-based subsample from the Established Populations for Epidemiologic Studies 

of the Elderly (EPESE) cohort, the BOMC was found to misclassify a greater proportion of 

Africans Americans as demented compared with whites.52 Specificity was only 38.2% for 

blacks, compared with 78.5% for whites in this study. Less educated subjects were more 

likely to be classified as impaired, and the effect of education did not vary by race. The lack of 

adjustment for education in this study limits interpretation of the observed racial differences. 

Other studies have reported an association between race and cognitive test scores that persists 

after controlling for education, suggesting that additional factors such as socioeconomic status, 

comorbidity, health habits, and social factors, may contribute to the observed racial differences.70 

GPCOG

The GPCOG contains separate sections for patient and informant. The patient section includes 

items testing time orientation (3 points, including a clock drawing test), awareness of a news 

story within the previous week (1 point), and recall of a name and an address (5 points). The 

informant section includes 6 items that ask an informant to make a comparison between the 

participant’s current function and that from a few years ago. The cognitive and informant 

sections can be scored separately, together, or sequentially. In the sequential or 2-stage method, 

the informant section is not required for participants who score >8 (considered cognitively intact) 

or <5 (considered impaired). For participants who score 5 to 8 (inclusive) on the cognitive 

section, scores of <=3 on the informant section indicate cognitive impairment.56 

The GPCOG was assessed in a primary care setting56 and in subjects recruited through various 

settings including memory clinics, an Alzheimer’s respite program, and other clinics.57 In the 

first study, 67 general practitioners in 4 regional divisions in Australia administered the GPCOG 

to 283 patients aged 75 and older, as well as community-dwelling patients aged 50 to 74 with 

memory complaints. The prevalence of dementia in the sample was 29.1%. The components 

of the GPCOG were assessed separately and in combination: patient section only, informant 

section only, combined score from patient and informant sections, and the 2-stage method. The 

sensitivity of each ranged from 82% to 89%. The specificity was lower for the informant section 

only (66%), and the patient section only (70%), compared with the combined score (83%) 

or 2-stage method (86%). In the study of mixed settings, the sensitivity of the individual or 
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combined sections was higher, ranging from 94.2% to 98.2%; but the specificity was lower: 49% 

for the informant section, 67.2% for the patient section, and 77.4% for the combined score.57 

Mini-Cog

The Mini-Cog combines 2 cognitive tasks (3-item word memory and clock drawing) with a 

sequential scoring method; and was developed in a community sample that overrepresented 

dementia cases, persons of low education and nonwhite ethnicity, and non-English speakers.68 

We identified 3 studies that assessed the operating characteristics of the Mini-Cog.58-60 In each of 

these studies, the results of the Mini-Cog were derived from longer tests that were administered 

to determine whether the minimum data elements that make up the Mini-Cog would perform as 

well as or better than the longer, more complex diagnostic tests. The operating characteristics of 

the Mini-Cog by itself may differ in practice from the research studies included in this review.

Of the 6 VA measures, the Mini-Cog takes the least time to administer (2 to 4 minutes) and has 

been validated in a large (N=1119), age-stratified, random sample of the general population aged 

65 and older (mean age 73.1). The prevalence of dementia in the sample was 6.4%, and the 

sensitivity and specificity of the Mini-Cog were 0.76 and 0.89, respectively.

58

In a sample that had proportionally more demented patients (62%)59 than in the general 

population (6.4%),58 the Mini-Cog had higher sensitivity (97% v. 76%) but similar specificity 

(83% v. 89%). No association was found between education or language on Mini-Cog test 

performance in a study that included ethnic minorities in the U.S., although both education and 

language were significantly associated with MMSE test performance in the same sample.68 In a 

study of adults aged 65+ in residential care and assisted living facilities who did not have a chartdocumented diagnosis of dementia, 37.7% of residents met criteria for probable dementia using 

DSM-IV criteria. The sensitivity of the Mini-Cog in this sample was 87% and the specificity 

was 54%.60 This study included subjects with MCI in the non-demented comparator group, 

potentially causing a decrease in specificity. 

Studies of the Mini-Cog among ethnic minority groups with mixed linguistic and educational 

backgrounds found that the effects of low education and literacy on the accuracy of the Mini-Cog 

were weak or absent.59, 68 In one study, Asian Americans constituted 48% of the sample, African 

Americans 22%, Hispanics 17%, and white non-Hispanic 7%. The mean years of education 

were 11.5 among normal subjects, 10.4 among subjects with MCI, and 8.5 among demented 

subjects in this study.59 The Mini-Cog performed less accurately in a study of elderly with low 

education in Brazil, of whom 76% had less than 5 years of schooling and 25% were illiterate.71 

Given that the Mini-Cog was developed to facilitate cognitive screening in primary care settings 

in first-world countries, the authors of the Mini-Cog suggest that in populations with extremely 

low levels of education or literacy, informant-based screening or individualized function-based 

screening might be preferable to the use of cognitive screening tests.72 

MoCA

The MoCA is a 1-page, 30-point test, and has the longest administration time (10 to 15 minutes) 

among the 6 tests. Short-term memory recall is assessed by 2 learning trials of 5 nouns and 

delayed recall after approximately 5 minutes. Visuospatial tasks include a clock-drawing task 

and a 3-dimensional cube copy. Multiple aspects of executive functions are assessed using an 
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alternation task adapted from the Trail Making B task, a phonemic fluency task, and a 2-item 

verbal abstraction task. Attention, concentration, and working memory are evaluated using a 

sustained attention task, a serial subtraction task, and digits forward and backward. Language 

is assessed using a 3-item confrontation naming task with low-familiarity animals (lion, camel, 

rhinoceros), repetition of 2 syntactically complex sentences, and the aforementioned fluency 

task. Finally, orientation to time and place is evaluated.63 The tests, along with instructions for 

administering and scoring, are available in 30 languages.73

Three studies evaluated the test performance of the MoCA.61-63 One was a prospective study 

of 67 consecutive patients seen in a memory clinic. In this sample, 48% were determined to 

have dementia, 34% had MCI, and 12% had an identifiable psychiatric illness that explained 

subjective memory complaints or had no objective evidence of memory loss.61 The other 2 

studies recruited subjects from mixed settings62 or used a case-control sample,63 and prevalence 

could not be determined. The MoCA has not been validated in a primary care population or a 

sample representative of the general population. 

Although the sensitivity of the MoCA was high (94% to 100%), the specificity of the MoCA was 

low, ranging from 35% to 50% in 2 of the 3 studies. Individuals with <=12 years of education 

performed significantly worse on the MoCA (p<0.05). The effect of education, however, was 

correctable by the inclusion of a 1-point education correction for individuals with 12 years or 

less of education.62

SLUMS

The SLUMS examination is a 30-point, 11-item scale that includes tasks corresponding to 

attention, numeric calculation, immediate and delayed recall, animal naming, digit span, clock 

drawing, figure recognition/size differentiation, and immediate recall of facts from a paragraph.64

The average administration time is 7 minutes.

The SLUMS test was studied in a population of 702 U.S. Veterans aged 60+ in a VA geriatric 

clinic.64 The prevalence of dementia in the total sample, including subjects with MCI, was 

11.6%. The study stratified subjects by level of education, and determined that the optimal cutoff 

score was 19.5 for subjects with less than high school education and 21.5 for subjects with high 

school or more education. Sensitivity and specificity were both high (98% to 100%) with this 

adjustment for education level. 

STMS

The STMS is a 38-point, 8-item scale that tests orientation, attention, immediate recall, 

arithmetic, abstraction, construction, information, and delayed (approximately 3 minutes) 

recall.66 The administration time is approximately 5 minutes. 

The STMS was assessed in 2 studies that used a constructed sample of demented patients and 

non-demented controls. In one study, the demented group included 87 outpatients with mild 

to moderate severity and mean duration of 3.26 years, ranging from newly diagnosed to 10.3 

years.65 Ninety-three non-demented controls were recruited from consecutive patients who came 

to the neurologic practice for consultation during a 10-week period. Using a cutoff score of 

<=29, the sensitivity and specificity of the STMS were high in this study, but generalizability to 

the primary care setting is limited. 
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The second study drew consecutive, newly identified dementia patients (n=110) and controls 

matched on age and sex (n=138) from a primary care clinic.66 This study compared the test 

performance using a cutoff of 29 with an age-adjusted cutoff score that raised the cutoff to 30 

for ages 60-69, and lowered the cutoff by 1 point with each advancing age decade. Adjusting 

the cutoff score for age did not affect the sensitivity (86.4%), but improved the specificity of the 

STMS from 88.4% to 93.5%. To observe the effect of education without the confounding effects 

of dementia, the correlation of STMS total score with age and education was calculated within 

the control group only. The STMS appeared to be modestly influenced by age and education, 

with correlations of -0.34 (P = .0001) for age and 0.41 (P = .0001) for education. The study 

authors additionally noted that a severe language disturbance would preclude the use of the 

STMS. 

KEY QUESTION #3. What are adverse consequences of using these measures?

Summary of findings 

We found no evidence on adverse effects of the 6 cognitive tests of interest to VA. Three crosssectional studies assessed the acceptability of dementia screening or diagnostic workup among 

older adults. The studies reported that high proportions of older adults were unwilling to be 

routinely tested for memory problems, or to undergo further diagnostic assessment for dementia 

after having positive results on cognitive screening tests. One survey determined that 80% of 

respondents wanted to know if they had dementia, but only 57% would agree to routine testing 

by a physician. Perceived harms included worry about losing insurance and fear of losing 

drivers license. The high refusal rates of screening and diagnostic workup indicate the need 

for further research to understand the psychological burden associated with cognitive tests and 

assessment for dementia.

Detailed description

The USPSTF 2003 review determined that most articles on the adverse effects of screening 

for dementia dealt primarily with genetic screening for increased risk of AD and the impact of 

disclosing the diagnosis of dementia.74 Potential harms include psychological morbidity such 

as depressed mood, suicide, suicidal attempts and thoughts, and anxiety; as well as possible 

discrimination due to insurers and employers gaining access to screening results.6, 74

Our review found no literature on the adverse effects of the 6 cognitive tests of interest to VA. 

We found 2 studies that assessed the acceptability of dementia screening among older adults,6,7

and 1 study that assessed refusal of diagnostic workup for dementia after screening.8

 Because 

the studies were cross-sectional surveys, we did not rate them for quality. 

In 1 study, a mailed, self-administered questionnaire sent to residents of continuous care 

retirement communities (CCRCs) determined that the majority of respondents (51%) were not 

willing to be tested regularly for memory problems.6

 The questionnaire was sent to 500 residents 

aged 50 and older in two CCRCs in North Carolina, and excluded residents of assisted living 

and nursing homes, where the prevalence of diagnosed dementia would be greater. The survey 

contained 20 questions that addressed socio-demographic and health status, memory problems, 

depression, and medications; and also asked whether the respondent would like to be tested 
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on a regular basis for memory problems and depression in 2 separate questions. Forty-nine 

percent of respondents were willing to be tested regularly for memory problems, and only 40% 

were interested in being screened regularly for depression. Acceptance of depression screening 

was highly correlated with acceptance of screening for memory problems: 97% of participants 

who were willing to accept routine depression screening would also accept routine screening 

for memory problems, whereas only 17% of those not willing to accept depression screening 

would accept routine memory screening. The study did not explore the reasons why residents 

were unwilling to be screened regularly for dementia, but the study investigators suggested 

that the high refusal rate indicates the need for further research to understand the psychological 

burden due to dementia screening, social stigmatization, health and long-term care insurance, 

employment discrimination, mistrust in the health care system in managing other medical 

conditions, institutionalization, and losing driving privileges. 

In a screening and diagnosis study led by the same investigator, nearly half of patients with 

positive screening results refused diagnostic workup for dementia.8 In this study, 3,340 patients 

aged 65 and older received cognitive screening, regardless of whether cognitive complaints were 

present, in 7 primary care practice centers in Indianapolis. Four hundred and thirty-four patients 

were eligible for diagnostic assessment, having made at least one error on a 6-item screening 

test75 and subsequently scoring <=24 on a modified version of the Community Screening 

Instrument for Dementia.76 Forty-eight percent of the patients with positive screening results 

refused further assessment for dementia. The proportion of refusals did not significantly differ 

between men (46.2%) and women (48.5%), or between African Americans (46.3%) and whites 

(50.4%), although the likelihood of refusal varied among age-race groups. Patients who made 

mistakes on orientation items were more willing to undergo the diagnostic assessment than 

those who did not make such mistakes. The study authors suggest that this finding may reflect 

the individual’s perception as to whether or not s/he is likely to have the illness, in that patients 

who perceive themselves as asymptomatic may be less likely to desire to undergo a clinical 

evaluation.

A third study, published as an abstract,7 sought to capture attitudes and perspectives toward 

dementia screening among 234 non-demented dwelling older adults (mean age 75) in North 

Carolina. This survey determined that 80% of respondents wanted to know if they had 

dementia, but only 57% would agree to routine testing by a physician. Perceived harms included 

worry about losing insurance (40%), and fear of losing drivers license (81%). Regression 

analysis determined that acceptance of routine dementia screening was associated with 

acceptance of routine screening for colon cancer (p<0.001), acceptance of routine depression 

screening (p<0.001), a belief that early detection improves treatment of dementia (p<0.001), and 

a fear that dementia leads to nursing home placement (p<0.038). The study investigators suggest 

that broad-based screening for early dementia may require targeted educational interventions 

regarding its benefits. 
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DISCUSSION

Signs and symptoms of dementia

Efforts to improve dementia case finding in general practice settings may be hampered by the 

protean manifestations of the disease, and the low sensitivity of many of the signs and symptoms 

encountered in practice. The utility of these signs and symptoms in effectively triaging patients 

for further diagnostic assessment would depend on the relative value placed on reducing false 

positive findings as compared to increasing dementia detection rates and reducing false negative 

rates. Determining the long-term benefits and harms of earlier and increased rates of dementia 

detection has been debated in the literature, but is largely beyond the scope of this review.

All of the signs and symptoms we evaluated were poorly sensitive in detecting mild dementia. 

This may reflect inter-individual variation in clinical manifestations of dementia, variations in the 

methods for detecting these signs and symptoms, or simply a reflection of the almost subclinical 

nature of early dementia. 

The best studied of these symptoms are subjective memory complaints (SMC), which are 

theoretically attractive as a very brief initial assessment method in general practice settings. 

However, the presence of self-reported SMC does not correlate well with existing dementia. On 

the other hand, most cognitively intact persons do not have SMC, which may mean that in low 

prevalence settings, lack of SMC may be useful in identifying patients who could forego further 

dementia assessment. One potential consequence of routinely eliciting SMC in general practice 

patients is the likely high rate of false positives. If the finding of SMC would trigger further 

evaluation for dementia, this could lead to significant time pressures in general practice settings 

given that many of the “brief” assessment methods require 2 to 10 minutes to complete.

Of note, several large prospective cohort studies in different populations have found that elicited 

SMC are very common but of questionable significance, as they may not predict future cognitive 

decline.77-79 Rather, studies have suggested self-reported SMC are associated with depression, 

anxiety, physical health and personality traits.18, 45, 77

Informant-reported memory complaints may better differentiate demented from non-demented 

individuals18 and may be a promising area of inquiry for future case-finding approaches. The 

AD8 may be a promising very brief assessment instrument based partly on informant-reported 

memory complaints.46 A number of additional studies have found that caregivers of demented 

patients are reliably able to assess their cognitive deficits.45, 80-82 However, most of these studies 

have evaluated the use of longer questionnaires which may take some time to administer, and 

function almost as a proxy dementia screening tool. 

Some neuropsychiatric symptoms such as apathy, hallucinations, and delusions are relatively 

uncommon in healthy elderly people and may suggest the need for further evaluation when 

present. Depression and anxiety, on the other hand, do not seem to be useful in distinguishing 

demented from non-demented individuals. 

Brief measures of cognitive function available to VA

The 6 measures available in VA all test for memory impairment, while apraxia and executive 

function (including a clock drawing test) are assessed in all measures except the BOMC. The 
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assessment of other cognitive domains such as orientation, abstraction, and aphasia varies among 

the 6 measures (Table 5). A 2007 review by Holsinger, et al. discusses the cognitive domains in 

the DSM-IV criteria for dementia, and describes tasks used to assess each domain.67 

Among the 6 tests, the Mini-Cog has the shortest administration time (2 to 4 minutes), and has 

been studied in a large population sample as well as in multi-ethnic samples. Sensitivity and 

specificity were high in 2 studies, while poor specificity in a third study may have resulted from 

inclusion of subjects with MCI. 

The SLUMS examination had very high sensitivity and specificity in a VA population, and it 

allows for adjustment for education. However, the SLUMS has a longer administration time 

(approximately 7 minutes) compared with other tests, and has only been evaluated in 1 study. 

The other 4 tests had various strengths and limitations. The STMS had high sensitivity and 

specificity in a primary care setting, but has been evaluated in only 2 studies. The GPCOG is 

unique in that it allows for the input of an informant; however, the specificity of the informant 

section by itself was low (49-66%). The BOMC was evaluated in a bi-racial population sample, 

and was found to misclassify more blacks than whites as impaired. Specificity varied widely 

among studies of the BOMC. The MoCA has the longest administration time among the 6 tests, 

and had low specificity (35-50%) in 2 of 3 studies. 

Limitations

Our review does not address the relative value of various signs or symptoms in predicting 

future dementia. Also, because we excluded studies involving only patients with mild cognitive 

impairment (MCI) and because few included studies enrolled patients with very mild or very 

early dementia, these results may not be readily applicable to case-finding approaches designed 

to detect those patients with the earliest manifestations of disease. 

The scope of this review was limited to the 6 brief cognitive measures identified as priorities 

for VA. There are many other cognitive measures available that are not covered in this review. 

Few studies have assessed the 6 instruments in VA populations, and though some of the study 

populations may be similar to VA populations, applicability to VA settings cannot be directly 

assumed. The adverse consequences of the 6 cognitive measures have not been studied. 

Future research recommendations

Consequences of expanded case-finding efforts

The utility and consequences of a targeted case-finding approach in VA primary care settings 

should be assessed. For instance, the utility of routinely asking about memory problems 

followed by a brief dementia assessment method in patients with a positive response should be 

studied. It would be critical in such a study to carefully assess both the rate and consequences of 

false-positive results, as well as the cost and time used to find one additional confirmed case of 

dementia. 

The psychologic, financial, and quality of life consequences of both true- and false-positive 

dementia diagnoses should be more rigorously evaluated. High refusal rates of screening and 

diagnostic workup indicate the need for further research to understand the psychological burden 

associated with cognitive tests and assessment for dementia.
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The role of caregivers in evaluating patients for dementia

The value of routinely asking patient caregivers about memory problems as an alternative to 

patient-reported memory complaints should be studied as well. Given a limited amount of 

literature suggesting informant characteristics may impact the reliability of informant report,82

future studies of informant-administered instruments should also analyze the impact of the 

informant’s relationship to the patient on the diagnostic utility of the instrument. 

The reliability and validity of very brief informant assessment instruments such as the AD8 

should be evaluated in different settings. 

Evaluating combinations of signs and symptoms

Many of the signs and symptoms we examined were reported in isolation. Studies that examine 

the diagnostic utility of groups of signs and symptoms should be conducted. 

Provider response to self-reported subjective memory complaints

Though the value of routine screening for dementia remains an active area of debate, subjective 

memory complaints are common enough that future studies, quality improvement, and education 

improvement efforts should ensure primary care providers are trained to feel comfortable having 

sensitive and holistic discussions with patients and their caregivers about memory loss. Studies 

should also address whether an assessment negative for dementia following a subjective memory 

complaint can be therapeutically useful. 

Dementia and depression

Rates and consequences of the misclassification of dementia as depression (and vice versa) 

should be further studied. 

Operating characteristics of the cognitive measures available in VA

The SLUMS and STMS tests have not been widely studied. Further studies are needed to assess 

the operating characteristics of these tests in various settings. 

Of the 6 measures, only the BOMC and Mini-Cog have been evaluated in multi-ethnic samples. 

Further studies are needed to assess whether race or language biases affect the performance of 

the other cognitive measures. 

Clinical utility of the cognitive measures available in VA

The perceived clinical utility of the GPCOG and Mini-Cog was examined in a narrative review 

and found to be equally high.83 A similar survey among VA providers would be useful for 

determining preferences and utilities of the 6 measures available in VA. Because clinicians 

may need to use these assessment tools in busy primary care practices, studies should assess the 

instruments’ ease of use, time to completion, and adverse effects in real-world VA settings. 
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of Dementia and Brief Cognitive Tests Available in VA Evidence-based Synthesis Program

 APPENDIX A. SEARCH STRATEGY

Symbol Concept Search Strategy (PubMed)

D Dementia “dementia”[MeSH Terms] OR “dementia”[All Fields]

SS Signs + Symptoms (((((“signs + symptoms”[MeSH Terms] OR (“signs”[All 

Fields] + “symptoms”[All Fields]) OR “signs + symptoms”[All 

Fields]) OR (warning sign[All Fields] OR warning signal[All 

Fields] OR warning signal/precue[All Fields] OR warning 

signals[All Fields] OR warning signs[All Fields] OR warning 

signs/symptoms[All Fields])) OR (red flag[All Fields] OR red 

flagging[All Fields] OR red flags[All Fields])) OR presenting[All 

Fields]) OR (suspect[All Fields] OR suspected[All Fields])) OR 

(predict[All Fields] OR predictor[All Fields] OR predictors[All 

Fields])

CS Cross-Sectional Studies “Cross-Sectional Studies”[Mesh]

SR Systematic Review Subset systematic[sb]

G Guidelines, Consensus 

Statement Publication Type

Guideline [pt] OR Consensus Development Conference [pt] 

T Specific Tests ((“montreal cognitive assessment”[tiab]))) OR ((“moca”[tiab]))) 

OR ((“slums”[tiab]))) OR ((“st louis university mental 

status”[tiab]))) OR ((“saint louis university mental 

status”[tiab]))) OR ((“short test of mental status”[tiab]))) OR 

((“STMS”[tiab]))) OR ((“General Practitioner Assessment 

of Cognition”[tiab]))) OR ((“GPCog”[tiab]))) OR ((“minicog”[tiab]))) OR ((“mini cog”[tiab]))) OR ((“orientation memory 

concentration”[tiab]))) OR ((“bomc”[tiab])))) NOT ((poverty 

areas[mesh]))

All searches were performed in July of 2009

Dementia Review #1 Key Question #1 

PubMed

Primary Studies

(D + SS + CS) = 518

Secondary Studies (systematic reviews, guidelines or consensus statements only not general 

reviews)

((D + SS) + (SR OR G)) = 322
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of Dementia and Brief Cognitive Tests Available in VA Evidence-based Synthesis Program

Additional databases

Cochrane central register of controlled trials and database of abstracts of reviews of effects

1 dementia.mp. 

2 (signs and symptoms).mp

3 warning sign.mp. 

4 warning signal.mp. 

5 red flag*.mp. 

6 presenting.mp. 

7 suspect.mp. 

8 suspected.mp. 

9 predict*.mp

10 8 or 6 or 4 or 3 or 7 or 9 or 2 or 5

11 1 and 10

229 results after de-duplication 201

CINAHL

S1 (“dementia”) or (MH “Dementia+”)

S2 (“signs and symptoms”) or (MH “Signs and Symptoms (Non-Cinahl)”)

S3 “warning signs”

S4 “warning signal”

S5 “red flag*”

S6 “presenting”

S7 “suspect”

S8 “suspected”

S9 “predict”

S10 predictor*

S11 S2 or S3 or S4 or S5 or S6 or S7 or S8 or S9 or S10

S12 (“dementia”) or (MM “Dementia+”)

S13 S11 and S12

S14 S11 and S12 Narrow by Subject: Major Heading0: - Dementia 

367 results after de-duplication 309

PsychINFO

1 exp *Dementia/ 30642

2 (signs and symptoms).mp. [mp=title, abstract, heading word, 

table of contents, key concepts] 5567

3 warning sign.mp. or exp Warnings/ 738
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4 red flag.mp. 42

5 red flags.mp. 77

6 exp Symptoms/ or presenting.mp. 131298

7 suspect.mp. 1854

8 suspected.mp. 4720

9 predict.mp. 36261

10 predictor.mp. 27521

11 predictors.mp. 38646

12 6 or 11 or 3 or 7 or 9 or 2 or 8 or 4 or 10 or 5 222250

13 1 and 12 4251

14 limit 13 to (“0800 literature review” or “0830 systematic review” or 1200 meta analysis) 

208 Results after de-duplication 192

AGELINE

Title: dementia

AND

Title: “signs and symptoms” ; “warning sign” ; “warning signal” ; “red flag” ; “red flags” ; 

presenting ; suspect ; suspected ; predict ; predictor

39 items after de-duplication 30 unique

We also re-executed the search described in Mitchell, 2008 in Medline.

 (subjective memory OR memory complaint* OR memory difficult* [abstract]) AND (Dementia 

OR Alzheimer* OR mild cognitive [abstract]) AND (validity OR diagnosis OR sensitivity OR 

specificity OR accuracy OR re receiveOperator OR ROC [full text]) limited to 2008-Sept 2009 

(date of search)

79 Results

Dementia Review #1 Key Question #2 & 3

PubMed

(D + T) = 54

Additional databases (named tests were searched in the following databases)

Cochrane central register of controlled trials and database of abstracts of reviews of effects: 27 

Results, after de-duplication 0

HAPI: 24 Results, after de-duplication 23

PsycINFO: 87 Results, after de-duplication 74

CINAHL: 48 Results, after de-duplication 44
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of Dementia and Brief Cognitive Tests Available in VA Evidence-based Synthesis Program

APPENDIX B. Inclusion/Exclusion Criteria

Author, Year______________________ Title or ID#_______________________________________

1. Do any of the following constitute the study population:

a. A community sample of persons age 60+ that includes non-demented

 individuals as well as patients with mild to moderate dementia ..................

b. Patients with newly diagnosed, mild to moderate dementia ........................

c. Non-demented individuals aged 60+............................................................

d. None of the above..................................................................................STOP

2. Does the study use a standard criterion for diagnosing dementia?

a. No ...........................................................................................................STOP

b. Yes (e.g. DSM-IV)........................................................................................

3. Does the study evaluate any of the following cognitive tests: 

Blessed Orientation-Memory-Concentration Test (BOMC) ...........................

Mini-Cog ..........................................................................................................

General Practitioner Assessment of Cognition (GPCOG)................................

Short Test of Mental Status (STMS) ...............................................................

St. Louis University Mental Status Exam (SLUMS) .......................................

Montreal Cognitive Assessment (MoCA) ........................................................

None of the above..........................................................................proceed to Q4

4. Does the study provide prevalence or other descriptive data on signs and/or

symptoms of dementia?*

a. No ...........................................................................................................STOP

b. Yes ................................................................................................................

5. Is the text of the article in English?

a. No ...........................................................................................................STOP

b. Yes ................................................................................................................

6. If this article meets no other criterion, should it be saved for background or

discussion?

a. No ...........................................................................................................STOP

b. Yes: clinical guidelines.................................................................................

c. Yes: narrative review with potentially useful references..............................

d. Yes: qualitative study discussing relevant signs and symptoms...................

e. Yes: other, specify........................................................................................

Key words or categories:

Notes

Circle the Key Question(s) to which this article applies:

1. What signs and symptoms should prompt VA providers to assess cognitive function as part of an initial 

diagnostic workup for dementia? 

2. Which measures of cognitive function provide the optimal sensitivity, specificity, and time to administer, 

and are readily available within the VA? 

3. What are adverse consequences of using these measures?

* Examples of data that do not meet criteria for item 4 include epidemiologic risk factors for dementia; 

diagnostic imaging, laboratory, or physiological tests (e.g. sense of smell; cerebrospinal fluid studies; indicators 

of acute confusion; predictors of DNR orders
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of Dementia and Brief Cognitive Tests Available in VA Evidence-based Synthesis Program

APPENDIX C. QUADAS CRITERIA for evaluating

Diagnostic Accuracy Studies

Table 2: The Quadas tool

Source: Whiting P, Rutjes AW, Reitsma JB, Bossuyt PM, Kleijnen J, Whiting P, et al. The 

development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy 

included in systematic reviews. BMC Medical Research Methodology 2003;3:25. Used with 

permission. 
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R REVIEW COMMENTS

Comment Response

 scope, and methods for this review clearly described?

cope and methods are clearly described. The report is very succinct 

However, I did not see QUADAS criteria fully explained. This 

tly described so a reader can independently evaluate how you did 

Noted. We have clarified in the Methods that the details of the QUADAS criteria are listed in Appendix C.

ery helpful to have a glossary of terms to help non-expert readers 

y-makers) understand the statistical terms (e.g., sensitivity, 

lence, incidence, positive/negative predictive value, screening, 

chnical terms (e.g., stereognosis and graphesthesia). It is important 

 results, and discussion/conclusions/recommendations be clear in 

l as technical terms. 

Will include glossary and we’ve tried to modify the language. 

ent) Noted.

nsider examining warning signs in combination rather than singly 

mplaint in combination with behavioral symptom such as apathy 

on).

e the discriminative properties of the warning signs.

onsidered this – would you consider examining these warning 

tion? That is a likely scenario for clinical use.

e the extent to which you considered studies that discussed 

fication of (sic)

We’ve actually added some studies and narrative re: informant report. We added the suggestion re: consideration of examining these warning signs in combination to our future studies section. 

at this review sheds light on important questions and is very clear 

wers these questions with evidence based response/discussion. 

ery informative in looking at a large body of literature to 

uestions that are very clinically relevant in dementia diagnosis/

Noted.

ation of bias in our synthesis of the evidence? 

nt bias in synthesis of evidence however, limiting to just studies of 

entia severely limits the applicability of this review to the world 

In general there is too much emphasis on diagnosis when this is 

ess at best. There are individuals with severe levels of MCI or 

ple, who suffer in multiple ways due to their disability. We need to 

ients (Veterans) and “treat” them as well and often we do not address 

it is severe enough to be able to classify as “probable dementia.”

The scope of this review was limited to dementia. However, we agree that Veterans with cognitive impairment nondementia (CIND) are an important patient population. The best practices for assessment and management of patients with CIND may warrant a separate evidence review. Noted.
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 the Signs and Symptoms 

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Comment Response

matic bias but an odd ignoring of certain literature with over 

er papers.

Noted. We have responded to the specific points raised in Question 4. 

ome who are strong advocates for screening might complain that 

oked for adverse effects of screening, and have not considered 

f missed diagnosis (e.g, worsened chronic disease control). To my 

 studies have not been done, so I personally do not believe this is a 

Although identifying the consequences of falsely negative results from brief mental status tests was not within the scope of Key Question 2, we agree that the effects of case-finding and missed diagnoses on the improvement or worsening of patient outcomes are important considerations. 

ble in this review. Noted.

ies on dementia signs and symptoms, or on the cognitive measures of interest to the VA, that we have overlooked? 

ncern here is again the filter that was used, as a general concern 

teness of your literature search. Some studies have used tools 

gh probability of dementia based on prior validation studies 

ent. You need to be careful to include studies that also have this 

ven if subjects were not even ostensibly diagnosed. You did this 

Crooks’ study, a study I know well and these patients were not 

had an approximation of diagnosis applied. I conducted a study of 

ent in Veterans and concern about impairment as a strong predictor 

a high probability of dementia that was dictated by conservative 

rior validation research. This should have been considered for 

s it was) especially because it was done within the VA. 

This was designed to be a review case-finding tools rather than tools that are predictive of future dementia. Re: the Crooks paper - we did not include this as a primary study - it was included as part of the Mitchell review and we did, in our revisions, clarify the weaknesses of individual studies from the Mitchell review including Crooks (we agree they did not use a gold standard for dementia assessment). 

ware of specifically. Noted.

gloss over a sizable literature on informant reported memory 

r of focusing on a patient’s own subjective complaints. It has 

epeatedly that subjective memory complaints on the part of the 

ently associated with anxiety and depression while the reports of 

a literature suggesting that spouses are the best informants) are 

ctual cognitive decline yet you avoid discussion of the problems 

al’s complaints and ignore informant complaints almost completely.

many problems and is just about as insensitive as the mini-Cog and 

OMC), but it has the largest body of literature by far and is most 

 providers. 

We’ve added some more discussion points about informant reported memory problems. We had not included some studies (eg - Archer 2007) because they fell outside inclusion criteria (assessing MCI in this case). Many studies investigate association with future cognitive decline. However, we agree it is important to clarify some of the potential weaknesses of patient reported complaints and acknowledge the potential role of informant report. We’ve added the Jorm 1997 review to our dicussion, though it really looks at the value of longer informant questionnaires which is slightly different from “signs/sx” (which a very brief elicitation of SMC might approximate). We added Carr 2000 as well. Re: MMSE - it was simply outside of our review’s scope - the scope of our report reflects the Dementia Steering Committee’s interests - they were interested in literature about six commonly used alternatives to MMSE. 
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Comment Response

ove concerning dementia warning signs considered in combination, 

lation. Also – there are other warning signs type instruments – see 

The AD8, a brief informant interview to detect dementia,Neurology 

.

wing article that may help to illuminate the role of informant 

its usefulness in guiding diagnosis of dementia.

s of cognitive decline in old age: validation against change on 

ver 7 to 8 years. 

nsen H. Korten AE. Jacomb PA. Henderson AS. 

edicine. 30(4):981-5, 2000 Jul. 

is of informant’s ratings of cognitive function in African 

Nigerians. 

nverzagt FW. Ogunniyi A. Baiyewu O. Gureje O. Hendrie HC. 

rnal of Geriatric Psychiatry. 21(7):618-25, 2006 Jul. 

Agree - we’ve added more information re: informant report including the articles you mention and others we found. We mentioned the Shen study in the discussion and future studies section. The warning signs in combination is an interesting point and has not been well-studied - we’ve added it to suggestions for future studies. 

ant document to consider (if not already considered) is the 

ciation 10 warning signs for dementia. I find that these warning 

e recently updated after significant input, are worth sincere 

mentia warning signs.

The suggested document was included in the draft report. 

ional suggestions or comments below. If applicable, please indicate the page and line numbers from the draft report.

bout restrictive (and traditional) intentions of this work: 1) find 

and diagnose dementia patients or those at high risk; 2) do this in a 

ive” way; and 3) find signs and symptoms because screening poses 

rden. Medical providers are drilled on signs and symptoms of CHF, 

 we have Review of System questions to identify potential risk. 

often uncomfortable about screening or ruling in or out dementia. 

gests that warning signs are not helpful – at least there is little 

. Perhaps more attention needs to be put on how to teach providers 

y and comfortably discuss cognitive concerns. Your review 

 suggest that memory complaints might not predict dementia 

 that my study did predict it) and therefore they do not need to 

hink you should include a discussion about addressing patient 

ding memory because of the inherent need to do that as an effective 

ctitioner regardless of the underlying reason for the complaint. A 

n be very reassuring and may address significant anxiety.

, this is a very professional, well organized and thoughtful review. 

ue to VA and its Veterans.

These are well-considered and well-put concerns. Much of this debate is beyond the scope of this review. Because the issue of screening for dementia (as distinguished from case-finding) has been widely debated and there are already excellent publications and reviews outlining both sides of this debate, we have tried to make clear this review does not address the relative value of widespread screening for dementia. The points re: training providers how to sensitively and comprehensively address memory concerns, and the reassurance that a normal screen can offer a patient are welltaken. We have inserted some suggested future areas of study along these lines. 
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 the Signs and Symptoms 

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Comment Response

ed document with comments in Track Changes. This is an 

written report. But we need the methods/results/discussion/

rly presented in non-technical terms so that non-expert policy

rstand the recommendations for further action. Don’t “hide” the 

mmendations within technical terms.

Noted, and we’ve modified the language. 

ody and Exec Summary, Lines 3-7: these data come from VA 

urce Center (ARC) data, which are on the VA Intranet only and are 

ion 1 references the ARC website on the VA Intranet. It has not 

 what parts of the DSC Report can be made public. An alternative 

e the 2004 VA dementia projection from the VHA Office of 

puty Under Secretary for Health for Policy and Planning, also 

ernet at www1.va.gov/vhareorg/reports.htm. There is also a 2003 

A HERC that gives some dementia cost data from 1999 (Yu W, et 

 public data are mentioned on p. 1-2 of the DSC report.

We have replaced this paragraph using data from the suggested references. 

lso page 17 line 12: sterognosis and graphesthesia: use layperson 

 to the technical terms, for non-expert readers

We have defined these terms in the text, and added them to the Glossary.

 line 8: citation 13 is an internal memo, I’m not sure it is 

e it here.

We agree and have deleted reference 13. 

 Can you say more about the decision to exclude studies on signs 

at predict future incident dementia? (e-mail discussion copied 

xplicit would be great. If you could amplify in the report just a 

tence below that I highlighted in yellow, that would be helpful. It 

tter of adding the “layperson” wording, or repeating it in the Study 

 as you did in the Background section.

This was really designed as a review of case-finding tools rather than a review of tools that are predictive of future dementia. Our review does not address the latter issue and I hope this is clear to the reading audience. Given the lack of convincing evidence re: screening for dementia and the lack of clear consensus around this issue, we had thought that a review of methods for predicting dementia would be less applicable. We tried to frame this issue in the introduction, but again please let me know if we should be more explicit.

Word(s) missing? Check sentence: “...questionnaires were 

 by caregivers of demented participants, but by the non-demented 

mselves (22).” 

We have clarified this sentence to read as follows:“Results from the third study are more difficult to interpret because sleep disturbance questionnaires were completed by caregivers of demented participants, whereas non-demented participants in the control group completed the questionnaire themselves (22).” 

 and 16: “cognitive screening instruments” - Define “screening” 

 me, screening means evaluation of asymptomatic individuals; you 

at here. Or reword, e.g. “which brief mental status instruments 

We have reworded the phrase as suggested. 
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 the Signs and Symptoms 

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Comment Response

at the literature is misrepresented. I do not think some of these 

rrectly interpreted in the way you are trying to do here (particularly 

gns and sleep sections). For the performance of the screening 

 strong bias is exerted in the way the studies were done. To ignore 

gical issues is to present data that is much skewed from the actual 

hese instruments in a primary care setting.

Noted - specific responses detailed below. 

 literature. Results from the VA primary care population that 

rectly relevant aren’t available because of the time it has taken 

written up. Still, I think you need to at least factor in the likely 

y the published papers. I have detailed comments below. The 

hese tests is very different than that you present, supporting the 

s introduced in the study design.

Noted - specific responses detailed below. Also, we had completed extensive quality evals of studies and will include these in our appendices. 

o much emphasis on that one meta analysis (ref 15). The 

s included in the cross sectional analyses had some pretty iffy 

tia was called. For instance, the mmse is so insensitive that by the 

s crossed their threshold, the impairment was too far advanced for 

ry complaints to be relevant to a case finding scenario in the clinic. 

milar concerns about the use of a telephone screener to establish a 

entia.

We re-wrote this section and tried to highlight more the deficiencies of some of the included studies. 

 ADAS-Cog for diagnosis of dementia is questionable also. There 

o would support it, but it is hardly a ‘gold standard’ as you call it 

Noted and manuscript updated

d cognitive evaluation but this study examined different definitions 

ne of the criteria for diagnosis is subjective memory complaints, 

valid to then look at how subjective memory complaints do as an 

iagnosis.

Noted in manuscript

nformant interview as their ‘gold standard’. This was done with 

o screened positive and 35 who screened negative on a brief screen. 

hat informant information is more valuable in this area that patient 

ry complaint, I don’t think this is a valid diagnostic method. This 

 the level of correlation between patient complaint and informant 

ng more.

Noted in manuscript
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 the Signs and Symptoms 

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Comment Response

40, again the telephone screener was the primary means of 

pect many, many milder cases were missed. Additionally, the 

ry complaint was based solely on the question “do you have severe 

ment?” as reported on a mailed questionnaire. I don’t know of 

 method, and it isn’t really a straightforward inquiry into subjective 

ms. You go on to say that this method could classify healthy 

mented thus exaggerating reported specificity. The risk is actually 

way, I’d posit.

Noted and this study was de-emphasized

et included? It doesn’t compare prevalence rates of subjective 

ment in those with and without dementia.

True - it compares SMC in patients with various levels of cognitive performance, but does not establish dementia diagnoses -- will exclude

5 of page 14 under the heading “Detailed Description” the use rrect here. The Cache County study used an expanded and 

re sensitive modified mini mental state exam or 3MS. I also 

misrepresenting/misunderstanding this study. While 61% of the 

ts had behavioral disturbances in the past month (hardly low 

nce as you state), this study documented behavioral problems 

was not intended to address the use of behavioral symptoms in 

Thanks for clarifying - we will amend the report accordingly re: the modified MMSE. We hadn’t intended to represent this as a study of use of behavorial sx for screening. Rather, the study was intended to test the hypothesis that in a community-based sample, demented patients would have more neuropsychiatric sx than non-demented patients. This may be useful for case-finding - ie - which sx should prompt a primary care physician to assess for dementia. Many clinicians may not think to assess one for dementia if presenting with sx such as apathy. Re: sx prevalence, we had meant to say neuropsych sx were common, but the prevalence of any one sx was relatively low. We will clarify in the report. 

18, do you mean the accuracy of dementia documentation 

ds of persons with and without dementia or with and without 

 is the former there is a whole literature that you ignore that 

umentation of a dementia diagnosis in the primary care setting. 

We meant the latter - we do reference the former issue in the background section.

 given that the average mmse of those they consider undiagnosed 

, I suspect they missed the mild cases. A MMSE of 17 isn’t on 

 diagnosis. I’m also not convinced of their depression diagnoses, 

the inadequacies of the diagnoses, I wouldn’t jump to the 

some persons with mild dementia may have been misclassified as 

 (page 15, line 22/23). I don’t think they caught those with mild 

 relationship between depression and dementia is nuanced and 

n experienced geriatricians and geriatric psychiatrists.

Agreed - last statement was cut.
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 the Signs and Symptoms 

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Comment Response

at a sample of Parkinson’s disease patients and say anything about 

tia except in the specific case of sleep and dementia in Parkinson’s 

 16).

We agree - our statement is meant to refer only to this study, but we will make clearer in the text that the results don’t apply to patients with other types of dementia. 

ncomplete. It had originally been published online - we fixed the refoo old for me to access it electronically, but if frontal release signs 

ver half the participants, this is a severely demented group of 

relevant to your topic.

Mean MMSE scores in the demented group were about 21 and suggested this was not a group with severe dementia. I agree this was not representative of a screen-diagnosed group of patients, but the findings may be relevant to case-finding discussions. Also interesting is that 9% of controls had release signs. 

also available to me only in abstract, but the abstract says ‘with 

f impaired vibration sense, loss of upward gaze, and bradykinesia, 

sociated with the neurodegenerative syndromes and stroke’ which 

han what you report.

The abstract is slightly misleading - many of the signs were associated with stroke and/or Parkinsons, not dementia. The signs we mentioned were the ones associated with dementia. The study has numerous flaws in any case. 

relates an individual’s assessment of their driving ability with that 

d neurologist and a driving instructor. It doesn’t address use of 

a screen for cognitive ability. Again, I think you misrepresent the 

It technically fit our inclusion criteria - I agree it’s not a very useful study and we amended the paragraph to clarify the focus of the paper (was in the table, but I agree could have been clearer). 

 can you really report sensitivities of the Short Blessed (BOMC) 

field diagnoses’ of dementia are suspect. Those felt to be demented 

Duke for a real evaluation. There were seven of these. The Short 

nd easily memorized by clinicians and requires no props. It is not, 

with a sensitivity of 100%.

We agree that sensitivity may be overestimated because 13 subjects had a documented history of dementia, among the 26 identified as probably demented by field diagnosis. We have noted this limitation in Table 4 and in the text of the Results, in the BOMC section. Because the field methods used DSM criteria as a guide, the study meets our criteria for inclusion. However, we have replaced the results from this study in Table 5 with the results from Stuss 1996, a memory clinic sample that did not include patients who had been previously diagnosed with dementia.

 old to pull up, seems to focus on severe dementia. Do your 

c come from a severely demented subgroup?

The sample in this study (Stuss 1996) consisted of patients who had been referred to a memory clinic for possible dementia, including some who on successive evaluations turned out not to have dementia. The final diagnosis was determined subsequent to the BOMC test. Although the results of the referral sample may not be applicable to primary care populations, the patients did not have a history of dementia. It does not appear that the sens/spec results were weighted by a more severely demented subgroup. 
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 the Signs and Symptoms 

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Comment Response

aragraph on informant reports of memory loss on pg 28? Again, 

ole literature on this topic to focus on this paper? 

We agree that this paragraph was not relevant to this section, and have removed it accordingly.

t you ought to stress more that the six measures you look at are 

pert panel’ for various clinical reasons, not for rigorous scientific 

as a series of phone conferences with people who were tasked with 

es to the MMSE. 

We agree, and have added text to the Methods section to indicate that the six measures reviewed were based on several clinical criteria.

as not actually administered in MoVIES (ref 56) or in the 

shington ADC (ref 64). Items incorporated in testing actually 

 to create a miniCog score. In actual practice, the sensitivities 

re considerably lower. Again, a brief test, easily remembered by 

quiring no props except a paper and pencil, but not that sensitive.

We have added text to the Results to clarify that the MiniCog results from these studies were derived from components of longer tests, and that these results may not be directly comparable to the use of the Mini-Cog by itself in practice. 

 dementia in ref 54 was based purely on informant interview, no 

 Not sufficient. Also, half of this ADC population was made up of 

kers. How many of the informants spoke sufficient English to give 

The study notes that non-English speakers were administered cognitive tests by foreign-born native speakers who were also fluent in English, although it is not explicitly specified that non-English speaking informants were interviewed likewise by an interpreter. However, we agree that this study does not meet criteria for the use of a full reference standard such as DSM-IV, because diagnostic workup for dementia was based on positive informant history, regardless of other patient evaluations that were conducted. We thank you for bringing this to our attention. We have excluded this study from our review.

 that investigators actually did any cognitive testing to arrive at a 

sis for the SLUMS study (ref 61). You comment on the inclusion 

opulation. They did not diagnose MCI (and could not without 

 rather a “mild neurocognitive disorder.” There isn’t such a 

M IV that I know of. 

In Tariq 2006, the Methods state that each participant was evaluated during a routine clinic visit, a history was obtained from corroborating sources, a complete physical and mental status exam was performed, and lab findings were reviewed. Based on these data (which included a mental status exam) the investigators appear to have used, and state that they used, DSM-IV criteria to diagnose dementia. We concur that MCI is not a DSM-IV diagnosis; individuals with MCI fit neither criteria for normal or demented. Because different studies dealt differently with this subgroup, and some excluded them from analyses altogether, we noted how their inclusion could affect results.
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 the Signs and Symptoms 

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Comment Response

e heading of “Qualitative studies of the GPCOG and the Mini

purely volunteer sample of clinicians. For a questionnaire with a 

e (less actually since that 25% seems to be those who completed 

urvey and there were the most responses familiar with the MMSE), 

of respondents unfamiliar with the GPCOG and 75% unfamiliar 

og. This suggests giving weight to the 35 practitioners who said 

f the GPCOG and the 73 who said they’d heard of the miniCog. 

We agree, and have removed the qualitative studies. We contacted the author of the IPA survey, who clarified that respondents rated the perceived quality on those tests with which they had some familiarity. Consequently the results for the GPCOG and Mini-Cog are based on a small, potentially biased sample. The 2nd qualitative study examined 2 of the 6 VA measures and ranked them equally high. Therefore we have noted in Future Research Recommendations that similar surveys be conducted among VA providers for input on the use of the 6 measures in practice. 

ability of screening, please note that you are basing your section 

 investigator using samples very different from the VA where we 

etter response from the Veterans concerning cognitive screening.

We have made note in the Results for KQ3 that 2 of the 3 studies were led by the same investigator. We have also removed some of the details about the studies and kept the more general findings, because these studies do not provide direct evidence about the 6 cognitive measures used in VA.

rt very informative overall and it does justice to this large body of 

ng to this important topic.

Noted.

RN, GCNS, BC
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APPENDIX E. GLOSSARY

Agnosia: Failure to recognize or identify objects despite intact sensory function.

Alzheimer’s disease (AD): A disease usually characterized by loss of memory, especially for 

learning new information, reflecting deterioration in the functioning of the medial temporal lobe 

and hippocampus areas of the brain. Later in the illness, other higher functions of the cerebral 

cortex become affected: these include language, praxis (putting theoretical knowledge into 

practice) and executive function (involved in processes such as planning, abstract thinking, rule 

acquisition, initiating appropriate actions and inhibiting inappropriate actions, and selecting 

relevant sensory information). Behavioral and psychiatric disturbances are also seen, which 

include depression, apathy, agitation, disinhibition, psychosis (delusions and hallucinations), 

wandering, aggression, incontinence and altered eating habits. 

Aphasia: Deterioration in language skills, such as word-finding difficulties, reduction in output, 

loss of fluency, and poor comprehension. 

Apraxia: Total or partial loss of the ability to perform coordinated movements or manipulate 

objects in the absence of motor or sensory impairment.

Case-finding: The strategy of identifying a new occurrence of disease among patients selected on 

the presence of risk factors, signs, or symptoms. 

Cohort: A group of persons with a common characteristic or set of characteristics. Typically, 

the group is followed for a specified period of time to determine the incidence of a disorder or 

complication of an established disorder (prognosis).

Cohort Study: (Cohort Analytic Study): Prospective investigation of the factors that might cause 

a disorder in which a cohort of individuals who do not have evidence of an outcome of interest 

but who are exposed to the putative cause are compared with a concurrent cohort who are also 

free of the outcome but not exposed to the putative cause. Both cohorts are then followed to 

compare the incidence of the outcome of interest. Used for Prospective Study.

Dementia: The development of multiple cognitive deficits that include memory impairment and 

at least 1 of the following cognitive disturbances: agnosia, aphasia, apraxia, or a disturbance in 

executive functioning. Deficitsmust be severe enough to cause significant decline in social or 

occupational functioning and must represent a decline fromprevious baseline functioning.

Dementia with Lewy bodies (DLB): One of the most common types of progressive dementia 

and shares characteristics with both Alzheimer’s and Parkinson’s diseases. Its central feature 

is progressive cognitive decline, combined with three additional defining features: pronounced 

fluctuations in alertness and attention, such as frequent drowsiness, lethargy, lengthy periods 

of time spent staring into space or disorganised speech; recurrent visual hallucinations; and 

parkinsonian motor symptoms, such as rigidity and the loss of spontaneous movement. The 

symptoms of DLB are caused by the build-up of Lewy bodies (protein deposits found in nerve 

cells) in areas of the brain that control particular aspects of memory and motor control.

Executive Functioning: The ability to think abstractly and to plan, initiate, sequence, monitor,

and stop complex behavior.
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Graphesthesia: The ability to recognize a number or letter written on the skin by the sensation of 

touch.

Heterogeneity: A term used to illustrate the variability or differences between studies in the 

estimates of effects.

Incidence: The number of new cases of a disease per population over a given time period. 

Incidence measures how frequently a new case of disease occurs, as opposed to prevalence, 

which conveys how widespread a disease is in a population. 

Inter-rater reliability: A measure of the extent to which multiple raters or judges agree when 

providing a rating, scoring, or assessment.

Key questions: Questions posed by the advisory panel that are used to guide the identification 

and interrogation of the evidence base relevant to the topic of the guideline.

Likelihood Ratio: For a screening or diagnostic test (including clinical signs or symptoms), 

expresses the relative likelihood that a given test result would be expected in a participant with 

(as opposed to one without) a disorder of interest.

Mild Cognitive Impairment (MCI): Presence of a memory complaint, preferably corroborated by 

an informant, objective memory impairment, and normal general cognitive function. Activities of 

daily living are intact and the patient does not meet clinical criteria for dementia. 

Neuropsychiatric symptoms: Symptoms which generally fall within one of three symptom 

clusters: agitation, psychosis and mood disorders. Symptoms of agitation often include 

aggressiveness or irritability. Symptoms of psychosis are hallucinations – auditory or visual, and 

delusions. Mood disorders would include depression and anxiety. 

Odds ratio: A ratio of the odds of having the disease of interest in a group with a particular 

exposure, symptom, or characteristic of interest, to the odds of disease in a group that does 

not have the exposure /symptom / characteristic. An odds ratio of 1 indicates that the disease 

is equally likely to occur in both groups. On odds ratio of 4 indicates that the disease is 4 

times more likely to be present in the group that has the symptom or characteristic of interest, 

compared with the group that does not have this symptom. 

Predictive Value (PPV): Positive Predictive Value – the proportion of people with a positive test 

who have the disease; Negative Predictive Value – proportion of people with a negative test who 

are free of disease.

Prevalence: The total number of cases of the disease in the population at a given time, expressed 

as a proportion in which the number of cases is the numerator and the population at risk is the 

denominator.

Release signs: Primitive reflexes that are normally present in infants, including the suck, snout, 

palmomental, and grasp reflexes. They are seen in disorders that affect the frontal lobes, such as 

dementias, metabolic encephalopathies, closed head trauma, and hydrocephalus.

Remote/over-learned memory: The ability to remember people or events from the distant past, 

or over-learned information such as the days in the week or one’s birthday.

Registration/recall: The processing of received information, and the retrieval of the information 

in response to a cue for use in a process or activity.
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Screening: A strategy used in a population to detect a disease in individuals without signs or 

symptoms of that disease. Universal screening involves screening of all individuals in a certain 

category, for example, all persons age 65 and older. 

Screening test: A brief instrument used to determine the likelihood of whether a disease may 

be present, and whether more comprehensive diagnostic testing may be needed. The predictive 

value of a screening test is influenced by the prevalence of the disease in the population. In 

universal screening, a screening test would be administered to all persons in a certain category 

(e.g. age 65+). In a case-finding approach, the screening test would be selectively administered 

when a patient has risk factors or presents with signs or symptoms of the disease. 

Sensitivity: The proportion of people who truly have a designated disorder who are so identified 

by the test. The test may consist of, or include, clinical observations. The proportion of truly 

diseased persons in the screened population who are identified as diseased by the screening 

test—that is, the true-positive rate.

Specificity: The proportion of people who are truly free of a designated disorder who are so 

identified by the test. The test may consist of, or include, clinical observations. The proportion 

of truly nondiseased persons who are identified as such by the screening test—that is, the truenegative rate.

Stereognosis: The ability to perceive the form of an object by using the sense of touch.

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American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 

Fourth Edition, Text Revision. Washington, DC: American Psychiatric Association, 2000. 

Guyatt G, Rennie D. User’s Guides to the Medical Literature: A manual for evidence-based 

clinical practice. Chicago: AMA Press, 2002.

Holsinger T, Deveau J, Boustani M, Williams JW, Jr. Does this patient have dementia? JAMA 

2007;297(21):2391-404.

National Institute for Health and Clinical Excellence (NICE). Dementia: A NICE–SCIE 

Guideline on supporting people with dementia and their carers in health and social care. In: 

National Clinical Practice Guideline Number 42: The British Psychological Society and Gaskell; 

2007.

Petersen RC, Stevens JC, Ganguli M, Tangalos EG, Cummings JL, DeKosky ST. Practice 

parameter: early detection of dementia: mild cognitive impairment (an evidence-based review). 

Report of the Quality Standards Subcommittee of the American Academy of Neurology. 

Neurology 2001;56(9):1133-42.

Walker, HK. The suck, snout, palmomental, and grasp reflexes. Clinical Methods – the History, 

Physical, and Laboratory Examinations. Third Edition. Butterworth Publishers, 1990.

West S, King V, Carey TS, et al. Systems to rate the strength of scientific evidence: Evidence 

Report/Technology Assessment, Number 47. Rockville, MD: Agency for Healthcare Research 

and Quality. AHRQ Publication No. 02-E016, April 2002.