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 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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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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A Systematic Evidence Review of the Signs and Symptoms 

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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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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 the Signs and Symptoms 

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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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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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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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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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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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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.
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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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