Cochrane Database of Systematic Reviews

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Quinn TJ, Fearon P, Noel-Storr AH, Young C, McShane R, Stott DJ

Quinn TJ, Fearon P, Noel-Storr AH, Young C, McShane R, Stott DJ. Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations. Cochrane Database of Systematic Reviews 2014, Issue 4. Art. No.: CD010079. DOI: 10.1002/14651858.CD010079.pub2.

www.cochranelibrary.com

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

TABLE OF CONTENTS HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 1. . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 2. . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 3. . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 4. . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 5. . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 6. . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 7. . . . . . . . . . . . . . . . . . . . . . . . . . . DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . DATA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Test 3. accuracy of IQCODE at 3.3 threshold or nearest (16 and 26 item included). . Test 4. accuracy of IQCODE at 3.3 threshold (16 and 26 item IQCODE included). Test 5. accuracy of IQCODE at 3.4 threshold (16 and 26 item IQCODE included). Test 6. accuracy of IQCODE at 3.5 threshold (16 and 26 item IQCODE included). Test 7. accuracy of IQCODE at 3.6 threshold (16 and 26 item IQCODE included). Test 8. 16 item IQCODE 3.3 threshold. . . . . . . . . . . . . . . . . Test 9. 16 item IQCODE 3.4 threshold. . . . . . . . . . . . . . . . . Test 10. 16 item IQCODE 3.5 threshold. . . . . . . . . . . . . . . . Test 11. 16 item IQCODE 3.6 threshold. . . . . . . . . . . . . . . . Test 12. 26 item IQCODE 3.3 threshold. . . . . . . . . . . . . . . . Test 13. 26 item IQCODE 3.4 threshold. . . . . . . . . . . . . . . . Test 14. 26 item IQCODE 3.5 threshold. . . . . . . . . . . . . . . . Test 15. 26 item IQCODE 3.6 threshold. . . . . . . . . . . . . . . . Test 16. all IQCODE studies at 3.3 threshold with Srikanth removed. . . . . . Test 17. all IQCODE studies at 3.4 threshold with Senanorong removed. . . . . Test 18. all IQCODE studies at 3.5 threshold with Senanorong removed. . . . . ADDITIONAL TABLES . . . . . . . . . . . . . . . . . . . . . . . APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . DIFFERENCES BETWEEN PROTOCOL AND REVIEW . . . . . . . . . . INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1 1 2 3 5 6 9 10 11 12 14 16 18 20 26 27 28 29 33 58 59 59 60 60 61 61 62 62 63 63 64 64 65 65 66 66 66 67 90 90 90 91 91

i

[Diagnostic Test Accuracy Review]

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations Terry J Quinn1 , Patricia Fearon2 , Anna H Noel-Storr3 , Camilla Young2 , Rupert McShane3 , David J Stott2 1 Cardiovascular

and Medical Sciences, University of Glasgow, Glasgow, UK. 2 Academic Section of Geriatric Medicine, University of Glasgow, Glasgow, UK. 3 Radcliffe Department of Medicine, University of Oxford, Oxford, UK Contact address: Terry J Quinn, Cardiovascular and Medical Sciences, University of Glasgow, Walton Building, Glasgow Royal Infirmary, Glasgow, G4 0SF, UK. [email protected]. Editorial group: Cochrane Dementia and Cognitive Improvement Group. Publication status and date: New, published in Issue 4, 2014. Review content assessed as up-to-date: 1 February 2013. Citation: Quinn TJ, Fearon P, Noel-Storr AH, Young C, McShane R, Stott DJ. Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations. Cochrane Database of Systematic Reviews 2014, Issue 4. Art. No.: CD010079. DOI: 10.1002/14651858.CD010079.pub2. Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

ABSTRACT Background Various tools exist for initial assessment of possible dementia with no consensus on the optimal assessment method. Instruments that use collateral sources to assess change in cognitive function over time may have particular utility. The most commonly used informant dementia assessment is the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). A synthesis of the available data regarding IQCODE accuracy will help inform cognitive assessment strategies for clinical practice, research and policy. Objectives Our primary objective was to determine the diagnostic accuracy of the informant based questionnaire IQCODE, for detection of all cause (undifferentiated) dementia in community-dwelling adults with no previous cognitive assessment. We sought to describe the accuracy of IQCODE (the index test) against a clinical diagnosis of dementia (the reference standard). Our secondary objective was to describe the effect of heterogeneity on the summary estimates. We were particularly interested in the traditional 26-item scale versus the 16-item short form; and language of administration. We explored the effect of varying the threshold IQCODE score used to define ’test positivity’. Search methods We searched the following sources on 28 January 2013: ALOIS (Cochrane Dementia and Cognitive Improvement Group), MEDLINE (OvidSP), EMBASE (OvidSP), PsycINFO (OvidSP), BIOSIS Previews (ISI Web of Knowledge), Web of Science with Conference Proceedings (ISI Web of Knowledge), LILACS (BIREME). We also searched sources relevant or specific to diagnostic test accuracy: MEDION (Universities of Maastrict and Leuven); DARE (York University); ARIF (Birmingham University). We used sensitive search terms based on MeSH terms and other controlled vocabulary. Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

1

Selection criteria We selected those studies performed in community settings that used (not necessarily exclusively) the IQCODE to assess for presence of dementia and, where dementia diagnosis was confirmed, with clinical assessment. Our intention with limiting the search to a ’community’ setting was to include those studies closest to population level assessment. Within our predefined community inclusion criteria, there were relevant papers that fulfilled our definition of community dwelling but represented a selected population, for example stroke survivors. We included these studies but performed sensitivity analyses to assess the effects of these less representative populations on the summary results. Data collection and analysis We screened all titles generated by the electronic database searches and abstracts of all potentially relevant studies were reviewed. Full papers were assessed for eligibility and data extracted by two independent assessors. For quality assessment (risk of bias and applicability) we used the QUADAS 2 tool. We included test accuracy data on the IQCODE used at predefined diagnostic thresholds. Where data allowed, we performed meta-analyses to calculate summary values of sensitivity and specificity with corresponding 95% confidence intervals (CIs). We pre-specified analyses to describe the effect of IQCODE format (traditional or short form) and language of administration for the IQCODE. Main results From 16,144 citations, 71 papers described IQCODE test accuracy. We included 10 papers (11 independent datasets) representing data from 2644 individuals (n = 379 (14%) with dementia). Using IQCODE cut-offs commonly employed in clinical practice (3.3, 3.4, 3.5, 3.6) the sensitivity and specificity of IQCODE for diagnosis of dementia across the studies were generally above 75%. Taking an IQCODE threshold of 3.3 (or closest available) the sensitivity was 0.80 (95% CI 0.75 to 0.85); specificity was 0.84 (95% CI 0.78 to 0.90); positive likelihood ratio was 5.2 (95% CI 3.7 to 7.5) and the negative likelihood ratio was 0.23 (95% CI 0.19 to 0.29). Comparative analysis suggested no significant difference in the test accuracy of the 16 and 26-item IQCODE tests and no significant difference in test accuracy by language of administration. There was little difference in sensitivity across our predefined diagnostic cutpoints. There was substantial heterogeneity in the included studies. Sensitivity analyses removing potentially unrepresentative populations in these studies made little difference to the pooled data estimates. The majority of included papers had potential for bias, particularly around participant selection and sampling. The quality of reporting was suboptimal particularly regarding timing of assessments and descriptors of reproducibility and inter-observer variability. Authors’ conclusions Published data suggest that if using the IQCODE for community dwelling older adults, the 16 item IQCODE may be preferable to the traditional scale due to lesser test burden and no obvious difference in accuracy. Although IQCODE test accuracy is in a range that many would consider ’reasonable’, in the context of community or population settings the use of the IQCODE alone would result in substantial misdiagnosis and false reassurance. Across the included studies there were issues with heterogeneity, several potential biases and suboptimal reporting quality.

PLAIN LANGUAGE SUMMARY A structured collateral interview regarding cognition and function (the IQCODE) for assessment of possible dementia Numbers of people with dementia and other cognitive problems are increasing globally. Early diagnosis of dementia is recommended but there is no agreement on the best approach or how non-memory specialists should assess patients. A potential strategy is to interview friends or family of the subject to assess for change in function or cognition. Various methods of this collateral interview are available and the most commonly used is the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). We searched differing databases of published research for all papers relating to the accuracy of IQCODE for selecting those with dementia. We found eleven studies that tested diagnostic accuracy of IQCODE in community dwelling individuals, we were able to combine their findings to give a summary result. We compared two forms of IQCODE questionnaire and found that a short form with fewer questions was just as accurate as the original longer questionnaire. The overall accuracy of IQCODE was reasonable although not perfect. If IQCODE were Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

2

to be used on its own for assessing large populations of older adults, it would label many people with dementia who do not have the disease and also miss the diagnosis in a substantial proportion.

BACKGROUND Dementia is a substantial and growing public health concern (Ferri 2005). Depending on the case definition employed, contemporary estimates of dementia prevalence in the United States are in the range of 2.5 to 4.5 million individuals (Hebert 2003). Dementia is predominantly a disease of older adults, with a 5% prevalence in adults aged over 60 years, increasing to up to 50% in adults aged over 85 years (Ferri 2005). Changes in population demographics will result in increased absolute and proportional numbers of older adults and will be accompanied by increases in dementia incidence and prevalence, albeit the extent of this increase is debated (Matthews 2013). Dementia is not limited to ’Western’ nations and an increasing prevalence is particularly marked in countries such as China and India (Ferri 2005). Given the projected global increase in dementia prevalence, there is a potential tension between the clinical requirements for robust diagnosis at the individual patient level and the need for equitable, easy access to diagnosis at a population level. The ideal would be expert, multidisciplinary assessment informed by various supplementary investigations. Such an approach may be possible in a secondary or tertiary care setting, however, in a community or primary care setting the population is too large and the prevalence of the disease will be low relative to the more specialist memoryclinic setting. In practice a two-stage process is often employed and initial screening or ’triage’ assessments, suitable for use by non-specialists, are used to select those patients who require further detailed assessment (Boustani 2003). Various tools for initial cognitive screening or case finding have been described (Brodaty 2002; Folstein 1975; Galvin 2005). However, regardless of the methods employed there is scope for improvement with observational studies suggesting that many patients with dementia are not diagnosed (Chodosh 2004; Valcour 2000). Initial assessment often takes the form of brief, direct cognitive testing. Using this method a single test can only provide a ’snapshot’ of cognitive function. However, a defining feature of dementia is cognitive or neuropsychological change over time. Patients themselves may struggle to make an objective assessment of personal change over a period of years and so an attractive approach is to question collateral sources with sufficient knowledge of the patient. Various terms have been used to describe the person(s) providing descriptions of the patient’s cognition including proxy,

collateral, informant, carer etc. We should make no assumptions about the relationship of the person providing the description and for consistency throughout the text we use the term informant. Informant-based interviews have been described that aim to retrospectively assess change in function over a period of time. An instrument prevalent in research and clinical practice is the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), and this is the focus of our review. There is no consensus on the optimal test for dementia and choice of test is currently dictated by experience with a particular instrument, time constraints and training. A better understanding of the diagnostic properties of various strategies would allow for an informed approach to testing. Critical evaluation of the evidence base for short dementia tests or other diagnostic markers is of major importance. Without a robust synthesis of the available information there is the risk that future research, clinical practice and policy will be built on erroneous assumptions about diagnostic validity.

Target condition being diagnosed The target condition for this diagnostic test accuracy review is dementia (clinical diagnosis). Dementia is a syndrome characterised by cognitive or neuropsychological decline sufficient to interfere with usual functioning. The neurodegeneration and clinical manifestations of dementia are progressive and at present there is no ’cure’, although numerous interventions to slow or arrest cognitive decline have been studied.(Birks 2006; Clare 2003; McShane 2006). Dementia remains a clinical diagnosis, based on a history from the patient and suitable informant sources and direct examination including cognitive assessment. Expert committees have described criteria for diagnosis of the dementia syndrome and its various subtypes (Erkinjuntti 2000; McKeith 2005; McKhann 1984; McKhann 2001; Roman 1993). Various clinical diagnostic protocols are available and although there are slight variations in European and American guidance, core features are common to all diagnostic criteria (McKhann 2011) (Appendix 1). We recognise that there is no universally accepted, gold standard dementia diagnostic strategy. We chose expert clinical diagnosis as our gold standard (reference standard) for describing IQCODE accuracy as we believe this is most in keeping with current diag-

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

3

nostic criteria and best practice. Previous studies have used neuropathology as a gold standard. For the purpose of testing diagnostic accuracy in large unselected populations, limiting analysis to those studies with neuropathological confirmed diagnosis is likely to yield limited and highly selected data (Savva 2009). Criteria for diagnosis of dementia are evolving in line with improvements in our understanding of the underlying pathophysiological processes. Various biomarkers based on biological fluid assays or functional and quantitative neuroimaging have shown promise but to date they are not accepted or validated as independent diagnostic tests (McKhann 2011; Noel-Storr 2012). The label of dementia encompasses varying pathologies of which Alzheimer’s disease is the most common. For our reference standard of clinical diagnosis, we accept a dementia diagnosis made according to any of the internationally accepted diagnostic criteria, with exemplars being the various iterations of the World Health Organization International Classification of Diseases (ICD) and the American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders (DSM) for all cause dementia and subtypes (Appendix 1). We also recognise the various diagnostic criteria available for specific dementia subtypes that is the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association (NINCDS-ADRDA) criteria for Alzheimer’s dementia (McKhann 1984); McKeith criteria for Lewy Body dementia (McKeith 2005); Lund criteria for frontotemporal dementias (McKhann 2001); and the National Institute of Neurological Disorders and Stroke - Association Internationale pour la Recherche et l’Enseignement en Neurosciences (NINDS-AIREN) criteria for vascular dementia (Roman 1993). Diagnostic criteria are continually evolving in line with a better clinical and scientific understanding of dementia, for example at the time of review the fifth edition of DSM was in pre-release.

code/). IQCODE has a number of features that make it attractive for clinical and research use. The questions used have an immediacy and relevance that is likely to appeal to users. Assessment and (informant) scoring takes around five to seven minutes and as the scale is not typically interviewer administered it requires minimal training in application and scoring (Holsinger 2007). Proponents of IQCODE suggest several potentially favourable properties of the IQCODE when compared to standard direct assessments. The IQCODE may be less prone to bias from cultural norms and previous levels of education; the scale has good inter-rater reliability; and internal consistency is uniformly high with Cronbach’s alpha in the range 0.93 to 0.97 (Jorm 1989A). Validation work has included validation against measures of cognitive change; neuropathology; neuroimaging and neuropsychological assessment (Cordoliani-Mackowiak 2003; Jorm 2000A; Rockwood 1998). A shortened 16-item version is available; this modified IQCODE is common in clinical practice and has been recommended as the preferred IQCODE format (Jorm 2004). Further modifications to IQCODE are described including fewer items and assessment over shorter time periods. For our analysis we chose to include all versions of IQCODE but present results for the original and modified scales separately in the first instance. In this text, the term IQCODE refers to the original 26-item questionnaire as described by Jorm (Jorm 1988). IQCODE cut-off scores used to define test positivity vary with the demographics of the population and the reason for testing. In the original development and validation work, normative data were described with a total score of > 93 or average score of > 3.31 indicative of cognitive impairment (Jorm 1988). There is no consensus on the optimal threshold and various authors have described improved diagnostic accuracy with other cut-offs. The full 26 and 16-item versions of ICQODE with scoring rules are available as appendices (Appendix 2; Appendix 3).

Index test(s) We chose the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) (Jorm 1988) as our index test of interest. The IQCODE was originally described as a 26-item informant questionnaire designed to retrospectively ascertain change in cognitive and functional performance over a 10-year time period (Jorm 1988). IQCODE is designed as a brief assessment for potential dementia, usually administered as a questionnaire given to the relevant proxy. For each item the chosen proxy scores change on a five-point ordinal hierarchical scale with responses ranging from 1: “has become much better” to 5: “has become much worse”. This gives a sum-score of 26 to 130 that can be averaged by the total number of completed items to give a final score of 1.0 to 5.0, where higher scores indicate greater decline. First described in 1989, use of IQCODE is prevalent in both clinical practice and research (Holsinger 2007) and the questionnaire has been translated into several languages (www.anu.edu.au/iq-

Clinical pathway A key element of effective management in dementia is robust diagnosis. Recent guidelines place emphasis on early diagnosis to facilitate improved management and to allow informed discussions and planning with patients and carers. The utility of screening for an early, unprompted diagnosis of dementia remains a subject of debate. There are major pressures for early diagnosis from third sector organisations, patient representative groups, and the pharmaceutical industry; and in certain countries opportunistic cognitive screening or case-finding is suggested (Brunet 2012; Cordell 2013). We recognise the importance of healthcare setting and populations in describing test properties. We have defined a series of settings and populations for reviews; these are based on the reason for performing the index (IQCODE) test and the likely prevalence of dementia.

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

4

Studies can be based in secondary care, that is where a referral has already been made by a healthcare professional and where there may have been some form of cognitive screening or selection. In the general practice or primary care setting, patients generally self-present to a non-specialist service because of subjective memory complaints, usually with no prior cognitive testing. In this setting the purpose of cognitive testing is to triag’ individuals to inform decisions about onward specialist referral. A study in a community (population) setting will generally be an unselected cohort with no previous cognitive assessment. The purpose of community cognitive testing may be population screening, or to inform epidemiological studies. Our intention with the community setting was to include those studies closest to population level screening. Methodologies for selecting representative community samples differ and for this review we adopted an inclusive approach in the first instance, including studies where the populations were community dwelling and not selected on the basis of cognitive scores or symptoms. We would expect lower prevalence of disease in the community setting compared to other settings. This is an important methodological point as in certain studies researchers ’enrich’ a community population with dementia cases. This process can artificially improve test accuracy and does not allow for description of those metrics that relate to population prevalence, for example positive or negative predictive value. For this review we described the test accuracy of IQCODE when used in a community setting. For consistency through the review we have used the term community. Reviews describing studies in other settings will also be available in due course. Prior test(s) For a review in a community setting, we would expect that the majority of individuals included will have had no previous assessment for cognitive problems. We did not include studies where recruitment was based on results of previous cognitive test(s).

2007). There are fewer informant interviews available. An alternative to IQCODE that is popular in North America is the eightitem Interview to Differentiate Aging and Dementia (AD-8) ( Galvin 2005). For this review we did not consider other cognitive screening or assessment tools and have chosen not to include other tests as comparators. Currently there is no standard practice biomarker or neuropsychological test and so we felt that making decisions on meaningful comparators was premature. Where a paper describes IQCODE with in-study comparison against another tool, we included the IQCODE data only. Where the IQCODE code was used in combination with another tool, we included the IQCODE data only. Our IQCODE diagnostic studies form part of a larger body of work describing the test accuracy of all commonly used scales and Cochrane diagnostic test accuracy (DTA) reviews specific to the AD-8; Abbreviated Mental Test (AMT); Clock Drawing Test (CDT); Mini-Cognitive Assessment Instrument (Mini-Cog); Mini-Mental State Examination (MMSE); Montreal Cognitive Assessment (MoCA) and General Practitioner assessment of Cognition (GPcog) are planned or in production (Appendix 4).

Rationale Clinical properties of a dementia test should not be assumed and formal testing of sensitivity, specificity and other properties of IQCODE should be performed and collated before the tool can be recommended. IQCODE is commonly used in practice and research; it is used internationally and is one of only a few validated informant-based tools. Literature describing test accuracy of IQCODE in different settings is available, although some of these studies have been modest in size. Thus a systematic review and, if possible, metaanalysis of the diagnostic test accuracy of IQCODE is warranted.

Role of index test(s) Although we use the term diagnosis in this review, we recognise that in practice IQCODE alone is not sufficient to make a diagnosis. Rather IQCODE is used as an initial case finding, triage, or screening test that can inform the need for further assessment or assist with diagnosis in conjunction with direct patient assessment and investigations. For ease of understanding and consistency with other reviews we used the term diagnostic accuracy to infer ’accuracy of IQCODE test for suggesting a possible dementia case’. Alternative test(s) Several other dementia assessment tools have been described, these are usually performance-based measures that rely on comparing single or multi-domain cognitive testing against populationspecific normative data (Brodaty 2002; Burns 2004; Holsinger

OBJECTIVES Our primary objective was to determine the diagnostic accuracy of the informant based questionnaire IQCODE, for detection of all cause (undifferentiated) dementia in community-dwelling adults with no previous cognitive assessment. We sought to describe the accuracy of IQCODE (the index test) against a clinical diagnosis of dementia (the reference standard).

Secondary objectives Where data were available, we planned to describe the following. 1. The diagnostic accuracy of IQCODE at various prespecified thresholds. We recognize that various thresholds or cut-

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

5

off scores have been used to define IQCODE test positive states. We described the test accuracy of IQCODE for the following cut-off scores (rounded where necessary): 3.3, 3.4, 3.5, 3.6. These thresholds have been chosen to represent the range of cutoffs that are commonly used in practice and research; we have been inclusive in our choice of cut-off to maximize available data for review. 2. Accuracy of IQCODE for diagnosis of the commonest specific dementia subtype, Alzheimer’s disease dementia. 3. Effects of heterogeneity (see below) on the reported diagnostic accuracy of IQCODE. Our focused study question, restricting this review to a community setting, was designed to remove potential heterogeneity relating to study design and setting. Other sources of heterogeneity in dementia studies such as treatment, intervention or duration of follow-up are not applicable to this review and were considered within the inclusion and exclusion criteria. The properties of a tool describe the behaviour of the instrument under particular circumstances. Thus for our assessment of potential sources of heterogeneity (where data allowed), we collated data on key features of the study population namely age; features of the index test, namely language of administration and IQCODE format; features of the reference standard, namely diagnostic criteria used; and diagnostic methodology.

METHODS

Criteria for considering studies for this review

Types of studies All studies of community-based cohorts were potentially eligible for the review. As discussed, we used the rubric ’community’ to include studies of community dwelling older adults, unselected on the basis of cognitive scores or symptoms. Many studies that assess test properties use a case control methodology. This approach is prone to a number of potential biases and may give artificially high values for test accuracy. For certain studies, in particular where populations are ’enriched’ with dementia cases, case control methodology may be employed but not explicitly stated. We elected to include potential case control studies in our initial screening review of the search results and then assess studies on a case by case basis. Where case control or study enriching was employed we did not include these in the summary data or pool these data with other studies. Case studies or samples with very small numbers (chosen as 10 participants or less for the purposes of this review) were not included.

Participants All community-dwelling adults (aged over 18 years) were potentially eligible. We suspected that the majority of included participants in the eligible studies would be aged over 65 years. Our definition of a community-based study setting was a study where participants were community dwelling, had not been referred, had not had extensive cognitive testing and had not selfpresented for assessment of subjective memory problems. We anticipated that studies would largely be of unselected communitydwelling adults; this cohort is itself heterogeneous. We did not predefine exclusion criteria relating to the ’case-mix’ of the population studied but assessed applicability for each study. Where a population was community dwelling and unselected on the basis of cognition but was potentially not representative of the population, for example a study with a focus on stroke-survivors, we chose to explore the effect of these studies on the findings using sensitivity analyses.

Index tests Studies had to include (not necessarily exclusively) IQCODE used as an informant questionnaire. IQCODE has been translated into various languages. The properties of a translated IQCODE in a cohort of non-English speakers may differ from the properties of the original English language questionnaire. We collected data on the principle language used for IQCODE assessment in studies to allow for assessment of heterogeneity in relation to language. Since its original description modifications to the administration of IQCODE have been described (Jorm 2004). Shorter forms of informant questionnaires that test fewer domains are available and properties may differ from the original 26-item IQCODE tool. We included all such versions of IQCODE but presented separate analysis limited to the commonest 26 and 16-item versions. A modified IQCODE for self-assessment has been described. As our interest was informant interviews, self-assessment IQCODE was not included in the review (Cullen 2007).

Target conditions Papers reporting any clinical diagnosis of all cause (unspecified) dementia were potentially eligible for inclusion. Defining a particular dementia subtype was not required although where available, these data were recorded.

Reference standards Our reference standard was clinical diagnosis of dementia. We recognise that clinical diagnosis itself has a degree of variability but this is not unique to dementia studies and does not invalidate the basic diagnostic test accuracy approach. Our definition of clinical diagnosis included all cause (unspecified) dementia, using any

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

6

recognised diagnostic criteria (for example ICD-10; DSM-IV). The dementia diagnosis could specify a pathological subtype and all dementia subtypes were included (examples McKeith 2005; McKhann 1984; McKhann 2001; Roman 1993). Clinicians may have used imaging, pathology or other data to aid diagnosis, however, diagnosis based only on these data without corresponding clinical assessment were not included. We recognise that different iterations of diagnostic criteria may not be directly comparable and that diagnosis may vary with the degree or manner in which the criteria have been operationalised (for example individual clinician versus algorithm versus consensus determination) and so data on method and application of dementia diagnosis was collected for each study. We did not set criteria relating to severity or stage of dementia diagnosis, instead any clinical diagnosis of dementia (not mild cognitive impairment or its equivalents) was classified. We planned to explore stage or severity of dementia as a potential source of heterogeneity.

Search methods for identification of studies We used a variety of information sources to ensure all relevant studies were included. Terms for electronic database searching were devised in conjunction with the Trials Search Co-ordinator at the Cochrane Dementia and Cognitive Improvement Group. As part of a body of work looking at cognitive assessment tools, we created a sensitive search strategy designed to capture dementia test accuracy studies. The output of the searches was then assessed to select those papers that could be pertinent to IQCODE, with further selection for directly relevant papers and those papers with a community (population) focus.

We did not apply any language or date restrictions to the electronic searches. Translation services were used as necessary. Initial screening of the search results was performed by a single researcher from the Cochrane Dementia and Cognitive Impairment Group with extensive experience of systematic reviews (ANS). All subsequent assessments of search results, based either on assessment of titles, abstracts or full text, were performed by independent paired assessors (TQ, PF).

Searching other resources Grey literature: ’grey’ literature was identified through searching conference proceedings on EMBASE (OvidSP) and through the ISI Web of Knowledge platform. Handsearching: we did not perform handsearching. The evidence base on handsearching for DTAs is not yet known and there is no clear guidance on whether handsearching is worthwhile. Reference lists: we checked the reference lists of all relevant studies and reviews in the field for further possible titles and repeated the process until no new titles were found (Greenhalgh 2005). Correspondence: we contacted research groups who have published or are conducting work on the IQCODE for dementia diagnosis, informed by results of the initial search. Relevant additional studies were searched for in PubMed using the related article feature. Relevant studies were examined in the citation databases of Science Citation Index and Scopus to ascertain any further relevant studies.

Data collection and analysis

Electronic searches

Selection of studies

We searched ALOIS, the specialised register of the Cochrane Dementia and Cognitive Improvement Group (which includes both intervention and diagnostic accuracy studies), MEDLINE (OvidSP), EMBASE (OvidSP), PsycINFO (OvidSP), BIOSIS (OvidSP), ISI Web of Science and Conference Proceedings (ISI Web of Knowledge), CINAHL (EBSCOhost) and LILACS (BIREME). See Appendix 5 and Appendix 6 for the search strategies. The final search date was 28 January 2013. We also searched sources specific to diagnostic accuracy and healthcare assessment: • MEDION database (Meta-analyses van Diagnostisch Onderzoek: www.mediondatabase.nl); • DARE (Database of Abstracts of Reviews of Effects via The Cochrane Library); • HTA Database (Health Technology Assessments Database via The Cochrane Library); • ARIF database (Aggressive Research Intelligence Facility: www.arif.bham.ac.uk).

One review author (ANS) screened for relevance all titles generated by the initial electronic database searches. The initial search was a sensitive, generic search designed to include many potential dementia screening tools. Titles potentially relevant to IQCODE were selected by two review authors (ANS, TQ). All further reviews of studies and selection were performed by two independent researchers (TQ, PF). The potential IQCODE related titles were reviewed and all eligible studies were assessed as abstracts; potentially relevant studies were assessed against inclusion criteria as full manuscripts. Disagreement was resolved by discussion, with potential to involve a third author (DJS) as arbitrator if necessary. We adopted a hierarchical approach to exclusion, first excluding studies on the basis of index test and reference standard and then on the basis of sample size and study data. Finally, we assessed all IQCODE papers with regard to setting. Where a study may have included useable data but these were not presented in the published manuscript (labelled as data not suitable for analysis on flowchart), we contacted the authors directly to

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

7

request further information. If the same data set was presented in more than one paper we included the primary paper. We detailed the study selection process in a PRISMA flow diagram. Data extraction and management Data were extracted to a study-specific pro forma that included clinical and demographic details of the participants; details of IQCODE administration; and details of the dementia diagnosis process. The pro forma was piloted against two of the included papers before use. Where IQCODE data were given for a number of cut-points, we extracted data for each of our pre-specified cut-points: 3.3, 3.4, 3.5, 3.6. Where thresholds were described to two decimal places, we chose the cut-point closest to the point of interest (that is all scores less than 3.35 would be scored as 3.3; all scores 3.35 or greater would be scored as 3.4. Data were extracted to a standard two by two table. Data extraction was performed independently by review authors (TQ, PF). Authors were based in differing centres and were blinded to each other’s data until extraction was complete. Data pro formas were then compared and discussed with reference to the original papers. Disagreement in data extraction was resolved by discussion, with the potential to involve a third author (DJS) as arbitrator if necessary. For each included paper, the flow of participants (numbers recruited, included, assessed) was detailed in a flow diagram. Assessment of methodological quality As well as describing test accuracy, an important goal of the diagnostic test accuracy (DTA) process is to improve study design and reporting in dementia diagnostic studies. For this reason we assessed both methodological and reporting quality. Quality of study reporting was assessed using the STARD checklist (Bossuyt 2003) (Appendix 7). We recognise that a dementiaspecific extension to complement STARD (STARDdem) (http:// starddem.org/) is proposed, however the content of STARDdem was not finalised at the time of this analysis. STARD data were tabulated and presented as an appendix to the review. We assessed the methodological quality of each study using the QUADAS-2 tool (http://www.bris.ac.uk/quadas/quadas-2) (Appendix 8). This tool incorporates domains specific to patient selection; index test; reference standard; and patient flow. Each domain is assessed for risk of bias and the first three domains are also assessed for applicability. Operational definitions describing the use of QUADAS-2 are detailed in Appendix 8. To create QUADAS-2 anchoring statements specific to studies of dementia test accuracy, we convened a multidisciplinary review of various test accuracy studies with a dementia reference standard (Appendix 9). Both assessments were performed by paired independent raters (TJQ, PF) who were blinded to each other’s scores. Disagreement

was resolved by further review and discussion with the potential to involve a third author (DJS) as arbitrator if necessary. QUADAS-2 data were not used to form a summary quality score, rather we chose to present a narrative summary describing the numbers of studies that found high, low or unclear risk of bias and concerns regarding applicability with corresponding tabular and graphical displays. Statistical analysis and data synthesis We were principally interested in the test accuracy of IQCODE for the dichotomous variable dementia or no dementia. Thus, we applied the current DTA framework for analysis of a single test to fit the extracted data to a standard two by two table showing binary test results cross-classified with the binary reference standard. This process was repeated for each of our pre-specified IQCODE threshold scores. We used RevMan 5.2 (RevMan 2011) to calculate sensitivity, specificity and their 95% confidence intervals (CIs) from the two by two tables abstracted from the included studies. These data were presented graphically in forest plots to allow basic visual inspection of individual studies only. Standard forest plots with graphical representation of summary estimates are not suited to quantitative synthesis of DTA data. Using software additional to RevMan (SAS release 9.1) we used the bivariate method to calculate summary values within each pre-specified cut-off. The bivariate methods (Reitsma 2005) enabled us to calculate summary estimates of sensitivity and specificity while correctly dealing with the different sources of variation: (1) imprecision by which sensitivity and specificity have been measured within each study; (2) variation beyond chance in sensitivity and specificity between studies; (3) any correlation that might exist between sensitivity and specificity. The results for each chosen threshold were described as sensitivity and specificity and all accuracy measures were estimated with their 95% CI. Where data allowed, we chose to present individual study results graphically by plotting estimates of sensitivities and specificities in the receiver operating characteristic (ROC) space. We also described metrics of pooled positive and negative likelihood ratios. To allow an overview of IQCODE test accuracy we performed a further analysis: pooling data at a common threshold (3.3 or closest), chosen to maximise the data available for inclusion. The presence of statistical heterogeneity was assessed by visual inspection of the included study results plotted in the ROC space relative to the putative summary accuracy estimates. Investigations of heterogeneity Heterogeneity is expected in DTA reviews and we did not perform formal analysis to quantify heterogeneity. The properties of a tool describe the behaviour of the instrument under particular circumstances. Thus, for our assessment of potential sources of heterogeneity (where data allowed) we collected

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

8

data to inform two broad pre-specified areas of interest. These were: • clinical criteria used to reach dementia diagnosis (for example ICD-10; DSM-IV) and the methodology used to reach the dementia diagnosis (e.g. individual assessment; group (consensus) assessment); • technical features of the testing strategy (version of IQCODE (language); numbers of items, that is short form of IQCODE or long form). Where data allowed we performed pooled analysis with these factors as covariates and compared results of subgroups. We pre-specified that we would present data from the traditional (26 questions) and short form (16 questions) IQCODE separately. Sensitivity analyses Where appropriate (that is if not already explored in our analyses of heterogeneity) and as data allowed, we planned to explore the sensitivity of any summary accuracy estimates to aspects of study quality guided by the anchoring statements developed in our

QUADAS-2 exercise. We pre-specified sensitivity analysis where we planned to exclude studies of low quality (high likelihood of bias) to determine if the results are influenced by inclusion of the lower quality studies; and sensitivity analysis excluding studies that may have unrepresentative populations.

RESULTS

Results of the search Our search resulted in 16144 citations, of which 71 full text papers were assessed for eligibility. We excluded 61 papers (Figure 1). Reasons for exclusion were: population not from a community (population) setting; no IQCODE data or unsuitable IQCODE data; small numbers of included participants; no clinical diagnosis of dementia; repeat data sets; data not suitable for analysis (Characteristics of excluded studies).

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

9

Figure 1. Study flow diagram.

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

10

Eight studies that were identified required translation, these papers were not suitable for this review but the data have been used for reviews of IQCODE in other healthcare settings. We contacted 14 authors to provide useable data, of whom 10 responded. These data were not suitable for this (community setting) review but have been used for other IQCODE analyses in this family of reviews (see Acknowledgements). This review included 10 studies representing 11 data sets (n = 2644 participants) (Summary of findings 1; Summary of findings 2; Summary of findings 3).

Methodological quality of included studies We described risk of bias using the QUADAS 2 methodology

(Appendix 8). No study was graded low risk of bias for all the categories of QUADAS-2 (Figure 2; Figure 3). Areas of particular concern for bias were around: participant sampling procedures (n = 2 papers graded low risk, with few papers using a true consecutive sampling frame) and application of index test (n = 1 paper graded low risk of bias, with most papers giving insufficient detail on how the IQCODE was actually applied in practice). There were also concerns around applicability, particularly concerning patient selection procedures (n = 1 paper graded no concern, with few studies recruiting a cohort representative of community-dwelling older adults).

Figure 2. Risk of bias and applicability concerns graph: review authors’ judgements about each domain presented as percentages across included studies.

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

11

Figure 3. Risk of bias and applicability concerns summary: review authors’ judgements about each domain for each included study.

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

12

We described reporting quality using the STARD guidance (Appendix 7). One paper (Yamada 2011) was not included in this process as we had an expanded conference abstract or poster and a paper describing the study methodology (Yamada 2008) but a full manuscript with IQCODE data had not yet been published. There were limitations in reporting across all included papers (Appendix 10). No paper included all the details recommended in the STARD statement; particular areas of study reporting that could be improved were: reporting of timing of the index test and reference standard (n = 1 paper reported when the IQCODE was performed in relation to the diagnostic evaluation); handling of indeterminate results (n = 0 papers reported, for example, how incomplete IQCODE questionnaires were handled); and describing variability between assessors (n = 2 papers reported data on interobserver variability for index test or reference standard).

Findings The individual included studies have been described in detail in Characteristics of included studies and Table 1; we have also presented tabulated data for test accuracy by covariate (Summary of findings 2) and form of IQCODE threshold (Summary of findings 3). The total number of participants across the studies was 2644 (range: 37 to 684), of whom 379 (14%) had a clinical dementia diagnosis. The scope of the included studies was international; included data sets were from six countries (Australia, Canada, Japan, Spain, Sri Lanka and Thailand) (Appendix 11). Certain papers contained more than one data set. For one paper the data sets were independent (one urban, one rural) and so we

included these as separate entries (Morales 1997 (urban); Morales 1997 (rural)). One study had a single population assessed by two independent assessors (one with neurology training and one with psychiatry training). We used data from only one assessor for our analysis (Jorm 1996 (psychiatry), favouring the data closest to the expected population dementia prevalence. Ten different versions of IQCODE were used in the included studies (Appendix 11) and eight different diagnostic thresholds (3.0, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 4.0) were used to define a positive IQCODE. We limited our analysis to the validated forms of IQCODE that are in common clinical use, that is the 26 and 16item questionnaires. Within the pre-specified thresholds chosen for analysis there was a spread of sensitivity and specificity (sensitivity range: 44% to 92%; specificity range: 55% to 96%). IQCODE (combined 16 and 26-item questionnaire)

Overview analysis - IQCODE using a 3.3 threshold or closest Across 10 studies there were 11 data sets that contained relevant data (n = 2644). Sensitivity was 0.80 (95% CI 0.75 to 0.85); specificity 0.85 (95% CI 0.78 to 0.90). The overall positive likelihood ratio was 5.27 (95% CI 3.7 to 7.5) and the negative likelihood ratio was 0.23 (95% CI 0.19 to 0.29). The summary ROC curve describing test accuracy across the included studies is presented in Figure 4.

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

13

Figure 4. Summary ROC Plot, IQCODE using a 3.3 threshold score or nearest.The dark point is a summary point, the broken line represents 95% CI

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

14

IQCODE 3.3 threshold or closest - comparing 26 and 16item IQCODE We used the overview data set to examine the effect of heterogeneity relating to IQCODE format (traditional 26-item or short form 16-item). Analysis of the studies using the 26-item IQCODE (n = 7 data sets) gave sensitivity of 0.80 (95% CI 0.73 to 0.85); specificity 0.86 (95% CI 0.74 to 0.95). The overall positive likelihood ratio was 5.6 (95% CI 3.4 to 9.1) and the negative likelihood ratio was

0.24 (95% CI 0.18 to 0.31). Analysis of studies using the 16-item IQCODE (n = 5 data sets) gave sensitivity of 0.80 (95% CI 0.74 to 0.85); specificity 0.82 (95% CI 0.70 to 0.89). The overall positive likelihood ratio was 4.2 (95% CI 2.6 to 6.8) and the negative likelihood ratio was 0.24 (95% CI 0.10 to 0.65). Comparing the two there was no difference in accuracy, with a relative sensitivity of the 26-item versus 16-item IQCODE of 1.00 (95% CI 0.91 to 1.11) and relative specificity 0.94 (95% CI 0.82 to 1.09) (Figure 5).

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

15

Figure 5. Summary ROC plot of IQCODE 3.3 threshold or nearest, comparing short form (16 item) and traditional IQCODE.

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

16

As there was no difference we presented further data as the combined (26 and 16-item IQCODE together) test accuracy. IQCODE 3.3 threshold or closest - comparing English and non-English language IQCODE We coded the language of IQCODE administration as a covariate. Study numbers did not allow analysis by individual languages and so we compared the IQCODE in the original wording (English language) with all translated IQCODE forms (non-English language). Analysis of studies using English language IQCODE (n = 5 data sets) gave sensitivity of 0.78 (95% CI 0.69 to 0.85); specificity

0.77 (95% CI 0.63 to 0.86). The overall positive likelihood ratio was 6.7 (95% CI 4.6 to 9.7) and the negative likelihood ratio was 0.28 (95% CI 0.20 to 0.41). Analysis of studies using non-English language IQCODE (n = 7 data sets) gave sensitivity 0.80 (95% CI 0.74 to 0.85); specificity 0.88 (95% CI 0.82 to 0.92). The overall positive likelihood ratio was 6.7 (95% CI 4.6 to 9.7) and the negative likelihood ratio was 0.13 (95% CI 0.08 to 0.24). Comparing the two there was no difference in accuracy, with a relative sensitivity of 1.03 (95% CI 0.91 to 1.16) and relative specificity of 1.15 (95% CI 0.98 to 1.34) (Figure 6).

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

17

Figure 6. Summary ROC Plot of pooled IQCODE data at a 3.3 threshold (or nearest value), with language as covariate.The dark point is a summary point, the broken line represents 95% CI

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

18

As there was no significant difference between groups we presented the data (all languages) for each of our pre-specified thresholds. IQCODE test accuracy at differing diagnostic thresholds We calculated test accuracy at our pre-specified IQCODE thresholds. We chose to present a summary ROC curve for those analyses with greater than three included studies. IQCODE 3.3 threshold: there were six data sets* (n = 1232) that contained relevant data. The sensitivity was 0.83 (95% CI 0.74 to 0.90); specificity 0.80 (95% CI 0.70 to 0.88). The overall positive likelihood ratio was 4.25 (95% CI 2.75 to 6.56) and the negative likelihood ratio was 0.21 (95% CI 0.14 to 0.32) (Figure 7).

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

19

Figure 7. Summary ROC Plot of combined(16 and 26 item) IQCODE data using a 3.3 threshold score.The dark point is a summary point, the broken line represents 95% CI

IQCODE 3.4 threshold: there were three data sets* (n = 988) that contained relevant data. The sensitivity was 0.84 (95% CI 0.70 to 0.93); specificity 0.80 (95% CI 0.65 to 0.90). The overall positive likelihood ratio was 4.42 (95% CI 2.47 to 7.90); the negative likelihood ratio was 0.19 (95% CI 0.10 to 0.35). IQCODE 3.5 threshold: there were three data sets* (n = 1144) that contained relevant data. Sensitivity was 0.82 (95% CI 0.75 to 0.87); specificity 0.84 (95% CI 0.80 to 0.88). The overall positive likelihood ratio was 5.09 (95% CI 4.08 to 6.33); the negative likelihood ratio 0.22 (95% CI 0.16 to 0.29). IQCODE 3.6 threshold: there were three studies (n = 1215) that

contained relevant data. Sensitivity was 0.78 (95% CI 0.68 to 0.86); specificity was 0.87 (95% CI 0.71 to 0.95). The overall positive likelihood ratio was 6.00 (95% CI 2.72 to 13.26); the negative likelihood ratio was 0.25 (95% CI 0.18 to 0.34). * Certain papers included more than one data set Heterogeneity relating to dementia diagnosis A quantitative analysis of the effect of dementia diagnosis criteria (reference standard) was not possible as all but one (Jorm 1996

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

20

(psychiatry) of the studies that specified the approach to dementia diagnosis used the American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders (DSM) to define the dementia state. The remaining study used the World Health Organization (WHO) International Statistical Classification of Diseases and Related Health Problems (ICD) for diagnosis. This study also compared neurologists’ and psychiatrists’ diagnoses against the IQCODE and found that IQCODE was more sensitive compared to a psychiatrist’s diagnosis of dementia (Jorm 1996 (psychiatry). A further original aim was to describe the accuracy of the IQCODE for diagnosis of Alzheimer’s disease dementia. We were unable to assess this based on the available data as only one study defined specific dementia diagnoses (Law 1995); all other studies described the accuracy of IQCODE for diagnosis of all cause dementia only. Other sources of heterogeneity and sensitivity analyses One study was of community-dwelling stroke-survivors (Srikanth 2006); we performed a sensitivity analysis by removing these data from our pooled estimates. We found little difference in test accu-

racy when this study was removed (at a 3.3 threshold, sensitivity 0.81, 95% CI 0.73 to 0.87; specificity 0.81, 95% CI 0.70 to 0.85). We performed a sensitivity analysis removing studies with a ’young’ population. Not all studies provided data on the age of participants and descriptive metrics differed across the papers (Table 2). Two authors (TJQ, PF) reviewed the ages of the included populations and concluded that one study contained a ’younger’ cohort likely to meet our pre-specified arbitrary cut-off of more than 20% aged less than 65 years (Senanorong 2001; see Table 2). This study also had an unusually high prevalence of dementia suggesting that a case-control methodology was employed, although this was not explicitly stated in the paper. We performed a sensitivity analysis excluding this study. Test accuracies at thresholds of 3.4 and 3.5 were similar after exclusion of this study (sensitivity 0.82, 95% CI 0.72 to 0.89; specificity 0.79, 95% CI 0.66 to 0.89 at a 3.4 cut-point; sensitivity 0.82, 95% CI 0.74 to 0.88; specificity 0.83, 95% CI 0.78 to 0.87 at a 3.5 cut-point). Given the modest numbers of papers and the clinical heterogeneity we did not perform any further sensitivity analysis by QUADAS2 metrics or other factors.

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

21

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Summary of findings

Study ID

Country

Subjects (n) IQCODE version Language Dementia diagnosis

Dementia prevalence N (%)

Other assessments

Jorm 1994

Australia

684

26 & 16 item

English

DSM IIIr

n=52

8%

-

Jorm 1996 Australia (psychiatry)

144

26 & 16 item

English

ICD9

n=11

8%

MMSE

Kathriarachi 2001

Sri Lanka

37

26 item

Sinhalese

‘ ‘ clinical ment’’

assess- n=14

38%

MMSE, CDR

Law 1995

Canada

237

26 item

French

DSM IIIr

n=32

14%

MMSE

Mackinnon 2003

Australia

646

16 item

English

DSM IIIr

n=36

6%

MMSE

Morales 1995

Spain

68

26 & 17 item

Spanish

DSM IIIr

n=7

10%

MMSE

Morales (rural)

1997

Spain

160

26 item

Spanish

DSM IIIr

n=23

14%

MMSE

Morales (urban)

1997

Spain

97

26 item

Spanish

DSM IIIr

n=11

11%

MMSE

Senanorong 2001

Thailand

160

16 & 3 item

Thai

DSM IV

n=73

46%

TMSE

Srikanth 2006

Australia

79

16 item

English

DSM IV

n=8

10%

S-MMSE

Yamada 2011

Japan

423

26 item

Japanese

DSM IV

n=112

26%

See Characteristics of included studies for more detailed study descriptors. Abbreviations: DSM - American Psychiatric Associationm Diagnostic and Statistical Manual of Mental Disorders; MMSE - Mini Mental State Examination; AMT - Abbreviated Mental Test; CDR - Clinical Dementia Rating Scale; TMSE - Thai Mental State Exam; S-MMSE standardised Mini Mental State Examination.

22

4 What is the accuracy of the Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE) test for detection of dementia using different versions of IQCODE and using different languages of administration Population

Community-dwelling older adults, with no restrictions placed on case-mix of included cohort

Setting

’Community’ setting; this setting was intended to represent a population screening context. Many of the included studies, although fulfilling our pre-specified inclusion criteria, were of selected population groups (for example stroke-survivors; ex-prisoners of war) the effect of these studies is described in the ’heterogeneity’ section of results

Index test

Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE) administered to a relevant informant. We restricted analyses to the traditional 26-item IQCODE and a commonly used short form IQCODE with 16 items

Reference Standard

Clinical diagnosis of dementia made using any recognised classification system

Studies

Cross-sectional studies were included, we did not include case-control studies

Comparative analyses Test

No. of participants (stud- Dementia prevalence ies) total across studies

Findings

Implications

26 item versus 16 item Total: n=2644 IQCODE (10 studies, 11 data sets) 26 item n=1075 (7 studies, 8 datasets)

Total n=379 (14%) 26 item n=210 (20%) 16 item n=169 (11%)

No difference in accuracy. Relative sensitivity of 26item versus 16-item IQCODE: 1.00 (95% CI 0.91 to 1.11) Relative specificity of 26 item versus 16-item IQCODE: 0.94 (95% CI 0.82 to 1.09)

Short form IQCODE may be preferred as lesser test burden with similar accuracy

English language versus Total: n=2644 non-English (10 studies, 11 data sets) English: n=1553 (4 studies)

Total: n=379 No significant difference (14%) in accuracy. English: n=107 Relative sensitivity of En(6%) glish language versus Non-English: n=272 non-English language: 1. (25%) 03 (95% CI 0.91 to 1.16) Relative specificity of English language versus non-English language: 1. 15 (95% CI 0.98 to 1.34)

IQCODE accuracy is not substantially influenced by language of administration

CAUTION: The results on this table should not be interpreted in isolation from the results of the individual included studies contributing to each summary test accuracy measure. These are reported in the main body of the text of the review

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

23

What is the accuracy of the Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE) test for detection of dementia when differing thresholds are used to define IQCODE positive cases Population

Community-dwelling older adults, with no restrictions placed on case-mix of included cohort

Setting

’Community’ setting; this setting was intended to represent a population screening context. Many of the included studies, although fulfilling our pre-specified inclusion criteria, were of selected population groups (for example stroke-survivors; ex-prisoners of war) the effect of these studies is described in the ’heterogeneity’ section of results

Index test

Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE) administered to a relevant informant. We restricted analyses to the traditional 26-item IQCODE and a commonly used short form IQCODE with 16 items

Reference Standard

Clinical diagnosis of dementia made using any recognised classification system

Studies

Cross-sectional studies were included, we did not include case-control studies

Test

Summary (95%CI)

accuracy No. of participants (stud- Dementia prevalence ies)

IQCODE cut-off 3.3 or sensitivity: 0.80 nearest (95% CI 0.75 to 0.85) specificity: 0.85 (95% CI 0.78 to 0.90) positive LR: 5.27 (95% CI 3.70 to 7.50) negative LR: 0.23 (95% CI 0.19 to 0.29)

n=2644 n=379 (10 studies, 11 datasets) (14%)

Implications Quality and comments There is no obvious preferred cut-off for IQCODE accuracy, within the threshold values commonly used in clinical practice and research So we focus on the summary data across all cut-points. The dementia prevalence across studies is higher than would be expected for this population. Using the accuracy figures re-calculating for a typical population; In the UK 9.9 million people are aged over 65, current estimates are of around 6.6% dementia prevalence. At the IQCODE accuracy calculated, using IQCODE alone to ‘ ‘ screen’’ for dementia would result in:

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

24

87,120 people with dementia not being picked up and 1,314,660 dementia free people being given a possible diagnosis of dementia IQCODE cut-off 3.3

sensitivity: 0.83 (95% CI 0.74 to 0.90) specificity: 0.80 (95% CI 0.70 to 0.88) positive LR: 4.25 (95% CI 2.75 to 6.56) negative LR: 0.21 (95% CI 0.14 to 0.32)

n=1232 (5 studies, 6 datasets)

n=112 (9%)

IQCODE cut-off 3.4

sensitivity: 0.84 (95% CI 0.70 to 0.93) specificity: 0.80 (95% CI 0.65 to 0.90) positive LR: 4.25 (95% CI 2.47 to 7.90) negative LR: 0.19 (95% CI 0.10 to 0.35)

n=988 (3 studies)

n=136 (14%)

IQCODE cut-off 3.5

sensitivity: 0.82 (95% CI 0.75 to 0.87) specificity: 0.84 (95% CI 0.80 to 0.88) positive LR: 5.09 (95% CI 4.08 to 6.33) negative LR: 0.22 (95% CI 0.16 to 0.29)

n=1144 (3 studies)

n=178 (16%)

IQCODE cut-off 3.6

sensitivity: 0.78 (95% CI 0.68 to 0.86) specificity: 0.87 (95% CI 0.71 to 0.95) positive LR: 6.00 (95% CI 2.72 to 13.26) negative LR: 0.25 (95% CI 0.18 to 0.34)

n=1215 (3 studies)

n=180 (15%)

CAUTION: The results on this table should not be interpreted in isolation from the results of the individual included studies contributing to each summary test accuracy measure. These are reported in the main body of the text of the review

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

25

DISCUSSION

Summary of main results We offer a synthesis of the published data describing the accuracy of the IQCODE questionnaire tool for detection of dementia within community-dwelling populations. Our results suggests that although the IQCODE has reasonable test properties, for example the positive likelihood ratio of around 5 and negative likelihood ratio of around 0.2 are classically interpreted as indicative of a ’moderately good test’, the test alone may not be suited for dementia screening within community dwelling older adults. For a clinical assessment the preferred pattern of diagnostic test accuracy (DTA), optimising sensitivity versus optimising specificity, will vary with the purpose of the test. The utility and limitations of screening all community-dwelling older adults for cognitive problems is a topic that is attracting considerable international debate. Our data show that even for a ’good’ initial assessment like IQCODE, at a population level the number of false positives and false negatives is still considerable. Applying our summary data to a population such as the UK, where 9.2 million adults are aged over 65 and 6.6% (435,600) of this group may have dementia, we see that even modest problems in test accuracy can be associated with considerable numbers of false diagnoses or false reassurance at population level (using these population numbers and at sensitivity of 0.80 / specificity of 0.84 we find false positive numbers of around 1314,660; false negative numbers of around 87,120). We appreciate that in practice the use of such tests is more pragmatic, but we give this example to illustrate the potential effects of IQCODE screening at a population level. Accepting that IQCODE is a reasonable initial test, albeit is perhaps not sufficient as a single screening test, our pre-specified analyses around heterogeneity were designed to provide guidance on optimal IQCODE administration with specific reference to form of IQCODE; language of IQCODE and preferred test positive cut-point. There was little difference in sensitivity across the predefined diagnostic cut-points. We had expected a more pronounced ’tradeoff ’ between sensitivity and specificity at differing thresholds. Possible explanations are that the thresholds are too close together to see differences in accuracy between neighbouring cutoffs or that any differences are lost in between study heterogeneity. We can conclude that at the IQCODE values commonly described in research, there is little to choose between the thresholds. There was a suggestion that sensitivity began to fall at cut-points above 3.5 and a trend towards improved specificity with increasing cut-point from 3.3 to 3.6. It would seem intuitive that scores above and below these values would have a more marked difference in sensitivity to specificity ratio. In certain situations, for example in dementia screening where specificity may be preferred to avoid false

positive diagnosis, a cutoffs below 3.3 may be preferred. However, we found few published studies describing thresholds less than 3.3 or greater than 3.6 and so at present this hypothesis is speculative. There were many differing forms of IQCODE application described across the included papers. We pre-specified a comparative analysis of IQCODE when used with the traditional 26 questions and a short form with 16 questions. As the tools had similar accuracy we believe pooling data across these two IQCODE formats was valid. There were insufficient data to describe accuracy of IQCODE assessments that did not use the standard 26 or 16 item questionnaires and we were wary of describing test accuracy of unvalidated IQCODE based assessments. The other area of heterogeneity in IQCODE application was for language of administration. There were insufficient numbers of papers to allow a valid analysis of the effect of individual languages of IQCODE, however summary analysis using dichotomised language (’English’ or ’non-English’) as a covariate suggested no significant difference. Although not reaching significance, there was a trend towards differing accuracy. The effect was not as expected with the non-English language IQCODE seemingly having improved accuracy. However differences were modest and it seems likely that some of these difference will relate to differing study methodologies and populations rather than the scale itself. Nonetheless we should be mindful of potential language effects in interpreting the pooled analysis and future studies should detail the language(s) of administration of tests employed. We restricted our analysis to the healthcare setting of “community based studies”. This setting and terminology was chosen prior to searching and review of the literature. Our intention was to assess those studies where participants had not been included on the basis of cognitive testing or symptoms and we suspected that included studies would have a population level assessment methodology. Across the literature describing IQCODE, the “community” setting proved difficult to operationalize and included a number of differing population sampling methods and study types. Certain included studies could be criticised for not conforming to usual definitions of unselected, community dwelling older adults (for example one study was of ex-servicemen only). We included all community based studies if participants were not selected on the basis of a factor that may relate to dementia or cognitive functioning. One study, although community based, included stroke survivors only. Clearly this group may differ from a non-stroke population and we explored this using sensitivity analyses. In fact, the test accuracy of IQCODE was similar comparing stroke and non-stroke, albeit confidence intervals were necessarily larger. Even where papers seemed to have a population based sampling frame, the prevalence of dementia was unexpectedly high and we must be cautious in our interpretation of these data. For unselected community assessment we would expect a prevalence of dementia in keeping with previous population estimates (5% of adults age over 60 years; 6% to 7% of adults aged over 65 years). Only one of our included papers (Mackinnon 2003) had proportions

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

26

with dementia in this range. One study had a younger population and a high prevalence of dementia suggesting a case-control methodology,albeit this was not explicit in the manuscript, again we explored the effect of removing this potentially unrepresentative study with sensitivity analyses and found little difference to pooled estimates with exclusion of the paper. In many of the included studies there was substantial potential for bias and reporting quality was suboptimal. In general, authors gave sufficient detail and were robust in their clinical dementia assessment (reference standard); however methodology and reporting of patient sampling and use of IQCODE could be improved. Assessment of quality is dependent on adequate reporting and there were many examples where QUADAS scoring was complicated by insufficient detail. One example is the blinding of dementia assessors to IQCODE data, particularly as dementia diagnosis is often partly predicated on information from informants. We hope that the proposed dementia specific reporting guidance of STARDdem may improve quality in future studies that use dementia as reference standard.

a measure of quality of reporting we also assessed the included papers using the STARD approach (Appendix 7). Important clinical and demographic details that could impact on the interpretation of our IQCODE data were not consistently reported and we could not describe the effect of factors such as nature of the informant and severity of dementia. For translating test accuracy studies to clinical practice, an approach that describes numbers who could not be tested with index and reference standard is often useful (i.e. an intention to diagnose approach with a two by three or three by three table; rather than the standard two by two table) (Schuetz 2012). We did not collect data in this format and at present we do not have techniques to allow pooling of such data. We await the results of ongoing systematic reviews and meta-analyses of other dementia assessment strategies (many of which are being completed by the Cochrane Dementia and Cognitive Improvememt Group) before we can begin to compare assessments and suggest the optimal tests for a particular patient group or clinical indication.

Applicability of findings to the review question Strengths and weaknesses of the review The strength of this review was its focused study question and setting. This review was limited to studies of community dwelling adults. While this approach avoids heterogeneity that may be introduced by test ’setting’ it does limit applicability to other settings and we should not extrapolate the data presented in this review to hospital or primary care populations. Reviews of the test accuracy of IQCODE in other settings and of the test accuracy of other direct and informant tests are planned as separate Cochrane reviews. We performed a comprehensive and sensitive literature search, encompassing cross-disciplinary electronic databases and test accuracy specific resources. Our primary search was complemented by contact with other authors working in the field and we are grateful for all the helpful responses we received. We did not limit by language of paper and this proved to be important as studies of IQCODE were international and several papers required translation. An unexpected finding was the modest numbers of studies describing IQCODE accuracy in community settings from United Kingdom and North America. Due to the modest numbers of papers, we pooled data for our summary analysis across various forms of IQCODE. Our comparative analysis would suggest that 16 and 26 item IQCODE have similar test accuracy, however language of administration may influence properties and as a result our summary data must be interpreted with some caution. We endeavoured to be as robust as possible in our assessment of included studies. Our approach to risk of bias assessment was informed by a short life working group that met to define relevant and workable anchoring statements and definitions of criteria ( Appendix 9). As we felt that assessment of quality should include

We found studies relevant to our focused study question and were able to give summary estimates for certain of our pre-specified co-variates of interest.. Our primary objective was to determine the diagnostic accuracy of the informant based questionnaire IQCODE, for detection of all cause (undifferentiated) dementia in community-dwelling adults and we provide summary data that hopefully will help clinicians and policy makers understand the properties of IQCODE as an initial assessment in this setting. A priori we had defined a number of subgroup and sensitivity analyses, the limited number of included papers precluded many of these analyses and we have not definitively answered our secondary questions of describing the effect of age or dementia diagnosis on test accuracy metrics. Further potential heterogeneity will be introduced by the “stage”/severity of dementia at time of diagnosis, as diagnosis will be easier in advanced disease than in early disease. No included studies gave data on severity of diagnosis that would allow us to describe this effect and so based on available data we can make no specific comment on use of IQCODE in, for example, early stage dementia. When planning the analysis we had conceptualised the “community” setting as being closest to unselected, population screening. Most of the included papers, while fulfilling our criteria for “community”, still described selected populations. It may be that this is of only minor consequence, as test accuracy of IQCODE was similar even when comparing highly selected groups (for example stroke survivors) to the pooled result.

AUTHORS’ CONCLUSIONS

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

27

Implications for practice Accepting the limitations of included studies and the potential for baises, results were fairly consistent across the studies and allow us to give some guidance on the use of IQCODE. Published data suggest that for initial assessment of dementia in older adults the IQCODE with cut-points of 3.3 to 3.6 could be used, however as a single assessment tool IQCODE properties may not be suited to population level screening. We extrapolated the IQCODE summary accuracy data to a United Kingdom context as exemplar and can see that using IQCODE exclusively will lead to substantial false positive diagnosis. Given the public perception of dementia, it is arguable that the distress caused by assigning a dementia label to a person without the disease is greater than the potential harm of initially missing dementia on screening. These are important concepts that need to be considered if large scale cognitive screening is to be introduced. The choice of a screening tool or triage tool for cognitive assessment will not only be driven by test accuracy. Strengths of the IQCODE from a clinician or healthcare perspective are that it is copyright free; available in many languages; and relatively quick and easy to complete. In general, informant-based assessments that do not rely on direct patient testing can capture change over time and are less prone to social-cultural biases (Jorm 2000A; Larner 2013). These are all factors that make IQCODE attractive as an initial assessment tool and explain why it is popular in its clinical and research use. Our analyses of heterogeneity suggest that 26 and 16-item IQCODE have similar test accuracy. It would seem sensible to recommend the short version of IQCODE as administration time or burden is less with comparable accuracy. Other short form versions of IQCODE have been described, at present there are insufficient data available to recommend use of these other modified IQCODE formats. There was a trend, albeit not reaching significance, to suggest that the language of administration may impact on IQCODE accuracy. Our findings do not imply that certain languages of assessment are more or less accurate. The safest interpretation of these data is as a reminder that translating IQCODE items to other languages needs to be sensitive to idioms and cultural nuances. We would encourage assessors using a non-English language IQCODE to ensure that any translation and validation process has been suitably robust. As a single test review, our data do not allow us to comment on how the IQCODE performs in relation to other tests. Given the large number of assessment tools potentially available, this is the question that may be of most interest to clinicians. In many papers and in clinical practice, the information from IQCODE is often used in tandem with a direct patient cognitive assessment tool such as MMSE. While combining instruments is intuitively attractive,

at present we do not have a systematic review of the properties of this approach.

Implications for research Our pooled analysis gives a large test population and the associated estimates of diagnostic accuracy are reasonably robust. However, we still encourage further study of the properties of IQCODE. As an example, despite our focused study question around community setting, the included studies in our review were largely not typical of an unselected, older adult population. The ideal study would involve stratified sampling and testing based, for example, on census data, such approaches have been used in seminal work describing the epidemiology of dementia (Ferri 2005). IQCODE test accuracy was maintained comparing 26 and 16item formats. IQCODE versions with even fewer than 16 items have been described, although numbers were too small for pooled analysis in this review. In practice a brief assessment tool is an attractive option if diagnostic accuracy can be maintained. We would recommend further study of shortened (less than 16-item) IQCODE properties. Our review had a deliberately focused agenda and our data do not allow us to extrapolate the diagnostic properties of IQCODE to other healthcare settings. We recognise that dementia assessment with additional informant interview is common in primary care and hospital settings and reviews of the IQCODE when used in these settings are now required. We have alluded to the need for comparative studies of various tools used alone or in combination. The ongoing body of work by the Cochrane group describing the test accuracy of commonly used direct and indirect tests will offer a substrate for future indirect comparative meta-analysis. Our assessments of reporting quality and risk of bias are concerning but in keeping with results from other areas of dementia research. We urge dementia researchers to work towards improved consistency in both methodology and reporting to assist future reviews of the diagnostic accuracy of tests. The use of dementiaspecific guidance such as the proposed STARDdem initiative may assist future trialists.

ACKNOWLEDGEMENTS We thank the following researchers who assisted with translation: Salvador Fudio, EMM van de Kamp - van de Glind, Anja Hayen. We thank the following researchers who responded to requests for original data: Dr D Salmon, Dr S Sikkes, Dr G Potter, Dr M Razavi, Prof H Henon, Dr JFM de Jonghe, Dr V Isella, Dr AJ Larner, Dr B Rovner, Dr M Krogseth.

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

28

We thank Dr Y Takwoingi for assistance with the statistical analysis.

REFERENCES

References to studies included in this review Jorm 1994 {published data only} Jorm AF. A short form of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE): development and cross validation. Psychological Medicine 1994;24: 145–53. Jorm 1996 (psychiatry) {published data only} Jorm AF, Christensen H, Henderson AS, Jacomb PA, Korten AE, Mackinnon A. Informant ratings of cognitive decline of elderly people relationship to longitudinal change on cognitive tests. Age and Ageing 1996;25:125–9. Kathriarachi 2001 {published and unpublished data} Kathriarachchi ST, Sivayogan S, Jayaratna SD, Dharmasena SR. Comparison of three instruments used in the assessment of dementia in Sri Lanka. Indian Journal of Psychiatry 2005; 47:109–12. Law 1995 {published and unpublished data} Law S, Wolfson C. Validation of a French version of an informant based questionnaire as a screening test for Alzheimer’s disease. British Journal of Psychiatry 1995;167: 541–4. Mackinnon 2003 {published data only} Mackinnon A, Khalilian A, Jorm AF, Korten AE, Christensen H, Mulligan R. Improving screening accuracy for dementia in a community sample by augmenting cognitive testing with informant report. Journal of Clinical Epidemiology 2003;56:358-66. Morales 1995 {published and unpublished data} Morales JM, Gonzalez-Montalvo JI, Bermejo F, Del-Ser T. The screening of mild dementia with a shortened Spanish version of the Informant Questionnaire on Cognitive Decline in the Elderly. Alzheimer’s Disease and Associated Disorders 1995;9:105–11. Morales 1997 (rural) {published and unpublished data} Morales JM, Bermejo F, Romero M, Del-Ser T. Screening of dementia in community dwelling elderly through informant report. International Journal of Geriatric Psychiatry 1997;12: 808–16. [these are data from independent rural cohort] Morales 1997 (urban) {published and unpublished data} Morales JM, Bermejo F, Romero M, Del-Ser T. Screening of dementia in community dwelling elderly through informant report. International Journal of Geriatric Psychiatry 1997;12: 808–16. Senanorong 2001 {published and unpublished data} Senanarong V, Assavisaraporn S, Sivasiriyanonds N, Printarakul T, Jamjumrus S, Udompunthurunk S, Poungvarin N. The IQCODE an alternative screening test for dementia for low educated Thai elderly. Journal of the Medical Association of Thailand 2001;84:648–55.

Srikanth 2006 {published data only} Srikanth V, Thrift AG, Fryer JL, Saling MM. The validity of brief screening cognitive assessments in the diagnosis of cognitive impairments and dementia after first ever stroke. International Psychogeriatrics 2006;18:295–305. Yamada 2011 {published and unpublished data} Mimori Y, Miyachi T, Ohshita T, Nakamura S, Yamada M, Sasaki H, Suzuki G. Cognitive decline and detection of dementia among the Japanese population. Anlaysis with the CASI and IQCODE. conference proceedings (poster). 2011.

References to studies excluded from this review Abreu 2008 {published data only} Abreu ID, Nunes PV, Diniz BS, Forlenza OV. Combining functional scales and cognitive tests in screening for mild cognitive impairment at a university based memory clinic in Brazil. Revista Brasileira de Pisquiatria 2008;30:346–9. Butt 2008 {published data only} Butt Z. Sensitivity of the IQCODE an application of item response theory. Aging, Neuropsychology and Cognition 2008;15:642–55. Cherbuin 2008 {published data only} Cherbuin N, Anstey KJ, Lipnicki DM. Screening for dementia a review of self and informant assessment instruments. International Psychogeriatrics 2008;20:431–58. de Jonge 1997 {published data only} De Jonghe JFM. Differentiating between demented and psychiatric patients with the dutch version of IQCODE. International Journal of Geriatric Psychiatry 1997;12:462–5. Dekkers 2009 {published data only} Dekkers M, Joosten-Weyn Banningh EW, Eling PA. Awareness in patients with mild cognitive impairment. Tijdschrift voor Gerontologie en Geriatrie 2009;40:17–23. Diefeldt 2007b {published data only} Diesfeldt HFA. Informant based measures may over estimate cognitive impairment in elderly patients. International Journal of Geriatric Psychiatry 2007;22:1166–70. Diesfeldt 2007 {published data only} Diesfeldt HFA. Discrepancies between IQCODE and cognitive test performance. Tijdschrift voor Gerontologie en Geriatrie 2007;38:199–209. Ehrensperger 2010 {published data only} Enrensperger MM, Berres M, Taylor KI, Monsch AU. Screening properties of the German IQCODE with a two year time frame in MCI and early Alzheimer’s disease. International Psychogeriatrics 2010;22:91–100.

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

29

Farias 2002 {published data only} Farias ST, Mungas D, Reed B, Haan MN, Jagust WJ. Everyday imaging in relation to cognitive functioning and neuroimaging in community dwelling Hispanic and non Hispanic older adults. Journal of the International Neuropsychological Society 2004;10:342–54. Finneli (abstract) {published data only} Finelli L, Kunze U, Gautier A, Gomez-Mancilla B, Monsch AU. Algorithms to retrospectively diagnose mild cognitive impairment and dementia in a longitudinal study of ageing and dementia. abstract ICAD. 2009. Fuh 1995 {published data only} Fuh JL, Teng EL, Lin KN, Larson EB, Wang SJ, Liu CY, et al. The Informant Questionnaire on Cognitive Dcline in the Elderly as a screening tool for dementia for a predominantly illiterate Chinese population. Neurology 1995;45:92–6.

Jorm 1989 {published data only} Jjorm AF, Scott R, Jacomb PA. Assessment of cognitive decline in dementia by informant questionnaire. International Journal of Geriatric Psychiatry 1989;4:35–9. Jorm 1989b {published data only} Jorm AF, Jacomb PA. The IQCODE; sociodemographic correlates, reliability, validity and some norms. Psychological Medicine 1989;19:1015–22. Jorm 1991 {published data only} Jorm AF, Scott R, Cullen JS, MacKinnon AJ. Performance of the IQCODE as a screening test for dementia. Psychological Medicine 1991;21:785–90. Jorm 1996 (Age and Ageing {published data only} Jorm AF, Christensen H, Henderson AS, Jacomb PA, Korten AE, Mackinnon A. Informant ratings of cognitive decline of elderly people relationships to longitudinal change on cognitive tests. Age and Ageing 1996;25:125–9.

Garcia 2002 {published data only} Forcano Garcia M, Perlado Ortiz de Pinedo F. Cognitive deterioration: use of the short version of the Informant Test (IQCODE) in the geriatrics consultations. Revista Espanola de Geriatria y Gerontolgia 2002;37:81–5.

Jorm 1997 {published data only} Jorm AF. Methods of screening for dementia: a metaanalysis of studies comparing an informant interview with a brief cognitive test. Alzheimers Disease and Associated Disorders 1997;11:158–62.

Goncalves 2011 {published data only} Goncalves DC, Arnold E, Appadurai K, Byrne GJ. Case finding in dementia: comparative utility of three brief instruments in the memory clinic setting. International Psychogeriatrics 2011;23:788–96.

Jorm 2000 {published data only} Jorm AF, Christensen H, Korten AE, Jacomb PA, Henderson AS. Informant ratings of cognitive decline in old age. Psychological Medicine 2000;30:981–5.

Hancock 2009 {published data only} Hancock P, Larner AJ. Diagnostic utility of the IQCODE and its combination with ACE-R in a memory clinic based population. International Psychogeriatrics 2009;21:526–30. Harwood 1997 {published data only} Harwood DMJ, Hope T, Jacoby R. Cognitive impairment in medical inpatients - screening for dementia is history better than mental state. Age and Ageing 1997;26:31–5. Hayden 2003 {published data only} Hayden KM, Khachaturian AS, Tschanz JT, Corcoran C, Nortond M, Breitner JCS. Characteristics of a twostage screen for incident dementia. Journal of Clinical Epidemiology 2003;56:1038–45. Henon 2001 {published data only} Henon H, Durieu I, Guerouaou D, Lebert F, Pasquier F, Leys D. Poststroke dementia incidence and relationship to pre-stroke cognitive decline. Neurology 2001;57:1216–22. Isella 2002 {published data only} Isella V, Villa ML, Frattola L, Appollonio I. Screening cognitive decline in dementia preliminary data on the Italian version of the IQCODE. Neurological Sciences 2002; 23:s79–s80. Isella 2006 {published data only} Isalla V, Villa L, Russo A, Regazzoni R, Ferrarese C, Appollonio IM. Discriminitive and predictive power of an informant report in mild cognitive impairment. Journal of Neurology, Neurosurgery, and Psychiatry 2006;77:166–71.

Jorm 2003 {published data only} Jorm AF. The value of informant reports for assessment and prediction of dementia. Journal of the American Geriatrics Association 2003;51:881–2. Jorm 2004 {published data only} Jorm AF. The IQCODE: a review. International Psychogeriatrics 2004;16:275–93. Khachaturian 2000 {published data only} Khachaturian AS, Gallo JJ, Breitner JC. Performance characteristics of a two stage dementia screen in a population sample. Journal of Clinical Epidemiology 2000;53:531–40. Knaefelc 2003 {published data only} Knafelc R, Giudice DL, Harrigan S, Cook R, Flicker L, Mackinnon A, Ames D. The combination of cognitive testing and an informant questionnaire in screening for dementia. Age and Ageing 2003;32:541–547. Krogseth 2011 {published data only} Krogseth M, Wyller TB, Engedal K, Juliebo V. Delirium is an important predictor of incident dementia among elderly hip fracture patients. Dementia and Geriatric Cognitive Disorders 2011;31:63–70. Larner 2010 {published data only} Larner AJ. Can IQCODE differentiate Alzheimer’s disease from frontotemporal dementia. Age and Ageing 2010;39: 392–4. Larner 2013 {published data only} Cherbuin N, Jorm AF. Chapter 8. The Informant Questionnaire for Cognitive Decline in the Elderly. In:

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

30

Larner AJ editor(s). Cognitive Screening Instruments. London: Springer-Verlag, 2013:166–79. Li 2012 {published data only} Li F, Jia XF, Jia J. The Informant Questionnaire on Cognitive Decline in the Elderly individuals in screening mild cognitive impairment with or without functional impairment. Journal Geriatric Psychiatry and Neurology 2012;25:227–32. Louis 1999 {published data only} Louis B, Harwood D, Hope T, Jacoby R. Can an informant questionnaire be used to predict the development of dementia in medical inpatients. International Journal of Geriatric Psychiatry 1999;14:941–5. Mackinnon 1998 {published data only} Mackinnon A, Mulligan R. Combining cognitive testing and informant report to increase accuracy in screening for dementia. American Journal of Psychiatry 1998;155: 1529–35. Mimori (abstract) {published data only} Mimori Y. Cognitive decline and detection of dementia among the Japanese population analysis with CASI and IQCODE. abstract. 2010:s451. Morales-Gonzalez 1992 {published data only} Morales-Gonzalez JM, Gonzalez-Montalvo JL, De Ser Quijano T, Bermejo Pareja F. Validation of the S-IQCODE [Original paper in Spanish]. Archivos de Neurobiologiá (Madrid) 1992;55:262–6. Mulligan 1996 {published data only} Mulligan R, Mackinnon A, Jorm A, Giannakopoulos P, Michel J. A comparison of alternative methods of screening for dementia in clinical settings. Archives of Neurology 1996; 53:532–6. Narasimhalu 2008 {published data only} Narasimhalu K, Lee J, Auchus AP, Chen CPLH. Improving detection of dementia in Asian patients with low education combining the MMSE and the IQCODE. Dementia and Geriatric Cognitive Disorders 2008;25:17–22. Ozel-kizel 2010 {published data only} Ozel-Kizel ET, Turan ED, Yilmaz E, Cangoz B, Uluc S. Discriminant validity and reliability of the Turkish version of the IQCODE. Archives of Clinical Neuropsychology 2010; 25:139–45. Peroco 2009 {published data only} Perroco TR, Zevallos Bustamente SE, del Pilar Q, Moreno M, Hototian SR, Lopes MA, et al. Performance of Brazilian long and short IQCODE on the screening of dementia in elderly people with low education. International Psychogeriatrics 2009;21:531–8. Potter 2009 {published data only} Potter GG, Plassman BL, Burke JR, Kabeto MU, Langa KM, Llewellyn DJ, et al. Cognitive performance and informant reports in the diagnosis of cognitive impairment and dementia in African Americans and whites. Alzheimer’s & Dementia 2009;5:445–53.

Razavi 2011 {published and unpublished data} Razavi M, Margrett J, Oakland A, Martin P. Comparison of two informant questionnaire screening tools for dementia. abstract. 2011. Ritchie 1992 {published data only} Ritchie K, Fuhrer R. A comparative study of the performance of screening tests for senile dementia using receiver operating characteristics analysis. Journal of Clinical Epidemiology 1992;45:627–37. Rodriguez-Molinero 2010 {published data only} Rodriguez-Molinero A, Lopez-Dieguez M, Medina IP, Tabuenca AI, de la Cruz JJ, Banegas JR. Cognitive assessment of elderly patients in the emergency department. Revista Espanola de Geriatria y Gerontolgia 2010;45:183–8. Rovner 2012 {published data only} Rovner BW, Casten RJ, Arenson C, Salzman B, Kornsey EB. Racial differences in the recognition of cognitive dysfunction in older persons. Alzheimer’s Disease and Associated Disorders 2012;26:44–9. Sanchez 2009 {published data only} dos Santos Sanchez MA, Lourenco RA. IQCODE cross cultural adaptation for use in Brazil. Cadernos de Saude Publica 2009;25:1455–65. Schofield 2006 {published data only} Schoffield PW. Discrepancies in cognitive history from patient and informant in relation to cognitive function. Research and Practice in Alzheimer’s Disease 2006;11:328–31. Sikkes 2010 {published data only} Sikkes SAM, van den Berg MT, Knol DL, de-Langede Klerk ESM, Scheltens P, Uitdehaag BMJ, et al. How useful is IQCODE for discriminating between Alzheimer’s disease, mild cognitive impairment and subjective memory complaints?. Dementia and Geriatric Cognitive Disorders. 2010;30:411–6. Siri 2006 {published data only} Siri S, Okanurak K, Chansirikanjana S, Kitiyaporn D, Jorm AF. Modified IQCODE as a screening test for dementia for Thai elderly. Southeast Asian Journal Tropical Medicine and Public Health 2006;37:587–94. Starr 2000 {published data only} Starr JM, Nicolson C, Anderson K, Dennis MS, Deary IJ. Correlates of informant rated cognitive decline after stroke. Cerebrovsacular Diseases 2000;10:214–20. Tang 2003 {published data only} Tang WK, Sandra SMC, Chiu HFK, Wong KS, Kwok TCY, Mok V, Ungvari GS. Can IQCODE detect post stroke dementia. International Journal of Geriatric Psychiatry 2003;18:706–10. Thomas 1994 {published data only} Thomas LD, Gonzales MF, Chamberlain A, Beyreuther K, Masters CL, Flicker L. Comparison of clinical state retrospective informant interview and the neuropathological diagnosis of Alzheimer’s disease. International Journal of Geriatric Psychiatry 1994;9:233–6.

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

31

Tokuhara 2006 {published data only} Tokuhara KG, Valcour VG, Masaki KH, Blanchette PL. Utility of the IQCODE for dementia in a Japanese American population. Hawai’i Medical Journal 2006;65: 72–5. Wierderholt 1999 {published data only} Wiederholt WC, Galasko D, Salmon DP. Utility of CASI and IQCODE as screening instruments for dementia in natives of Guam. abstract (World Congress of Neurology). 1997. Wolfe 2009 {published data only} Wolf SA, Kubatschek K, Henry M, Harth S, Edbert AD, Wallesch CW. Informant report of cognitive changes in the elderly. A first evaluation of the German version of the IQCODE. Nervenartz 2009;10:1178–80. Zevallos-Bustamente 2003 {published data only} Zevallos Bustamante SE, Bottino CMC, Lopes MA, Dionísio Azevedo D, Hototatian SR, Litvoc J, Filho JW. Combined instruments on the evaluation of dementia in the elderly preliminary results. Arquivos de Neuro-Psiquiatria 2003;61:601–6. Zhang 2003 {published data only} Zhang XQ, Zhou JS, Wang LD, Meng C, Chen B. Memory complaints in the clinical diagnosis of dementia. Chinese Journal of Clinical Rehabilitation 2003;7:4254–5. Zhou 2002 {published data only} Zhou JS, Zhang XQ, Wang L. Telephone questionnaire a new method for screening dementia. Chinese Journal of Clinical Rehabilitation 2002;6:3166–7. Zhou 2003 {published data only} Zhou J, Xinqing Z, Wang L, Meng C, Chu C, Chen B. Orientation memory concentration test and short IQCODE in the elderly screen dementia by telephone. Chinese Journal of Clinical Rehabilitation 2003;7:1529–31. Zhou 2004 {published data only} Zhou JS, Zhang XQ, Wang L. Telephone IQCODE for dementia. abstract. 2004.

Additional references Birks 2006 Birks J. Cholinesterase inhibitors for Alzheimer’s disease. Cochrane Database of Systematic Reviews 2006;1:CD005593. Bossuyt 2003 Bossuyt PM, Reitsma JB, Bruns DE Gatsonis CA, Glasziou PP, Irwig LM, et al. Towards complete and accurate reporting of studies of diagnostic accuracy: the STARD initiative. BMJ 2003;326:41–4. Boustani 2003 Boustani M, Peterson B, Hanson L, Harris R, Lohr KN. Screening for dementia in primary care: a summary of the evidence for the US Preventative Services Task Force. Annals of Internal Medicine 2003;138:927–37. Brodaty 2002 Brodaty H. The GPCOG a new screening test for dementia designed for general practice. Journal of the American Geriatrics Society 2002;50:530–4.

Brunet 2012 Brunet MD, McCartney M, Heath I, Tomlinson J, Cosgrove J, Deveson P, et al. Open letter to the Prime Minister and Chief Medical Officer for England. There is no evidence base for proposed dementia screening. BMJ 2012;345:e8588. Chodosh 2004 Chodosh J, Petitti DB, Elliott M, Hays RD, Crooks VC, Reuben DB, et al. Physician recognition of cognitive impairment: evaluating the need for improvement. Journal of the American Geriatrics Society 2004;52:1051–9. Clare 2003 Clare L, Woods B. Cognitive rehabilitation and cognitive training for early-stage Alzheimer’s disease and vascular dementia. Cochrane Database of Systematic Reviews 2003;4: CD003260. Cordell 2013 Cordell CB, Borson B, Boustani M, Chodosh J, Reuben D, Verghese J, et al. Medicare Detection of Cognitive Impairment Group. Alzheimer’s Associaton recommendations for operationalizing the detection of cognitive impairment during the Medicare Annual Wellness Visit in a primary care setting. Alzheimer’s & Dementia 2013;9:141–50. Cordoliani-Mackowiak 2003 Cordoliani-Mackowiak MA, Henon H, Pruvo JP, Pasquier F, Leys D. Poststroke dementia influence of hippocampal atrophy. Archives of Neurology 2003;60:585–90. Cullen 2007 Cullen B, O’Neill B, Evans JJ, Coen RF, Lawlor BA. A review of screening tests for cognitive impairment. Journal of Neurology, Neurosurgery, and Psychiatry 2007;78:790-9. Erkinjuntti 2000 Erkinjuntti T, Inzitari D, Pantoni L. Research criteria for subcortical vascular dementia in clinical trials. Journal of Neural Transmission. Supplementa 2000;59:23-30. Ferri 2005 Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M, et al. Alzheimer’s Disease International. Global prevalence of dementia: a Delphi consensus study. Lancet 2005;366:2112–7. Folstein 1975 Folstein MF, Folstein SE, McHugh PR. Minimental state: a practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research 1975;12: 189-98. Galvin 2005 Galvin JE. A brief informant interview to detect dementia. Neurology 2005;65:559–64. Greenhalgh 2005 Greenhalgh T, Peacock R. Effectiveness and efficiency of search methods in systematic reviews of complex evidence: audit of primary sources. BMJ 2005;331:1064–5. Hebert 2003 Hebert LE, Scherr PA, Bienas JL, Bennett DA, Evans DA. Alzheimers disease in the US population: prevalence

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

32

estimates using the 2000 census. Archives of Neurology 2003; 60:1119–22. Holsinger 2007 Holsinger T, Deveau J, Boustani M, Willimas JW. Does this patient have dementia. JAMA 2007;21:2391–404. Jorm 1988 Jorm AF, Korten AE. Assessment of cognitive decline in the elderly by informant interview. British Journal of Psychiatry 1988;152:209-13. Jorm 1989A Jorm AF, Jacomb PA. The informant questionnaire on cognitive decline in the elderly (IQCODE) sociodemographic correlates; reliability; validity and some norms. Psychological Medicine 1989;19:1015–22. Jorm 2000A Jorm AF, Christensen H, Henderson AS, Jacomb PA, Korten AE, Mackinnon A. Informant ratings of cognitive decline in old age: validation against change on cognitive tests over 7-8 years. Psychological Medicine 2000;30:981–5. Matthews 2013 Matthews FE, Arthur A, Barnes LE, Bond J, Jagger C, Robinson L, Brayne C, Medical Research Council Cognitive Function and Ageing Collaboration. A two-decade comparison of prevalence of dementia in individuals aged 65 years and older from three geographical areas of England: results of the Cognitive Function and Ageing Study I and II. Lancet 2013;382(9902):1405–12. McKeith 2005 McKeith IG, Dickson DW, Lowe J, Emre M, O’Brien JT, Feldman H. Diagnosis and management of dementia with Lewy bodies third report of the DLB Consortium. Neurology 2005;65:1863-72. McKhann 1984 McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 1984;34(7): 939-44. McKhann 2001 McKhann GM, Albert MS, Grossman M, Miller B, Dickson D, Trojanowski JQ, Work Group on Frontotemporal Dementia and PIck’s Disease. Clinical and pathological diagnosis of frontotemporal dementia: report of the Work Group on Frontotemporal Dementia and Pick’s Disease. Archives of Neurology 2001;58:1803–9. McKhann 2011 McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, et al. The diagnosis of dementia due to Alzheimer’s disease:recommendations from the National Institute on Aging and the Alzheimer’s Association workgroup. Alzheimer’s & Dementia 2011;7(3):263–9.

McShane 2006 McShane R, Areosa Sastre A, Minakaran N. Memantine for dementia. Cochrane Database of Systematic Reviews 2006;2: CD003154. Noel-Storr 2012 Noel-Storr AH, Flicker L, Ritchie CW, Nquyen GH, Gupta T, Wood P, et al. Systematic review of the body of evidence for the use of biomarkers in diagnosis of dementia. Alzheimer’s & Dementia 2013;9(3):e96-e105. doi:10.1016/ j.jalz.2012.01.014. Reitsma 2005 Reitsma JB, Glas AS, Rutjes AW, Scholten RJ, Bossuyt PM, Zwinderman AH. Bivariate analysis of sensitivity and specificity produces informative summary measures in diagnostic reviews. Journal of Clinical Epidemiology 2005; 58:982–90. RevMan 2011 [Computer program] The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan) 5.1. Copenhagan: The Nordic Cochrane Centre, 2011. Rockwood 1998 Rockwood K. Retrospective diagnosis of dementia using an informant interview based on the Brief Cgnitive Rating Scale. International Psychogeriatrics 1998;10:53–60. Roman 1993 Roman GC, Tatemichi TK, Erkinjutti T, Cummings JL, Masdeu JC, Garcia JH, et al. Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. Neurology 1993;43:250–60. Savva 2009 Savva GM, Wharton SB, Ince PG, Forster G, Matthews FE, Brayne C, et al. Age, neuropathology and dementia. New England Journal of Medicine 2009;360:230–9. Schuetz 2012 Schuetz GM, Schlattmann P, Dewey M. USeo f 3x2 tables with an intention to diagnose approach to assess clinical performance of diagnostic tests: meta-analytical evaluation of coronary CT-angiography studies. BMJ 2013;345: e6717. Valcour 2000 Valcour VG, Masaki KH, Curb JD, Blanchette PL. The detection of dementia in the primary care setting. Archives of Internal Medicine 2000;160:2964–8. Yamada 2008 Yamada M, Mimori Y, Kasagi F, Miyachi T, Ohshita T, Sudoh S, et al. Incidence of dementia, Alzheimers disease and vascular dementia in a Japanese population radiation effects Research Foundation Adult Health Study. Neuroepidemiology 2008;30:152–60. ∗ Indicates the major publication for the study

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

33

CHARACTERISTICS OF STUDIES

Characteristics of included studies [ordered by study ID] Jorm 1994 Study characteristics Patient sampling

Community sampling (unspecified), enriched with care-home residents

Patient characteristics and set- Community (n=945) and care-home dwelling older adults (n=100) approached; n=684 included ting Community setting Index tests

IQCODE 16 and 26 item, English language

Target condition and reference Clinical dementia diagnosis using DSM IIIr, informed by the Canberra Interview for the Elderly standard(s) Flow and timing

Of 1045 potential subjects, 769 had an informant; of this group a clinical diagnosis was possible in 684. Timing not applicable as cross-sectional, contemporaneous IQCODE and dementia assessment

Comparative Notes Methodological quality Item

Authors’ judgement

Risk of bias

Applicability concerns

DOMAIN 1: Patient Selection Was a consecutive or random No sample of patients enrolled? Was a case-control design Yes avoided? Did the study avoid inappropri- Unclear ate exclusions? High DOMAIN 2: Index Test All tests Were the index test results in- Yes terpreted without knowledge of the results of the reference standard?

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

34

Jorm 1994

(Continued)

If a threshold was used, was it No pre-specified? Were sufficient details given on Unclear IQCODE application for the test to be repeated in an independent study Low DOMAIN 3: Reference Standard Is the reference standards likely Yes to correctly classify the target condition? Were the reference standard re- Yes sults interpreted without knowledge of the results of the index tests? Were sufficient details of de- Yes mentia diagnostics given for the assessment to be repeated in an independent sample High DOMAIN 4: Flow and Timing Was there an appropriate inter- Yes val between index test and reference standard? Did all patients receive the same Yes reference standard? Were all patients included in the No analysis? Were missing IQCODE results Yes or un-interpretable IQCODE results reported

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

35

Jorm 1996 (psychiatry) Study characteristics Patient sampling

Subjects were ex-servicemen enrolled in a separate prospective study

Patient characteristics and set- Community-dwelling ex-servicemen (n=144) ting Community setting Index tests

IQCODE 16 and 26 items, English language

Target condition and reference Clinical dementia diagnosis using ICD9 standard(s) Flow and timing

Of 209 potential subjects,144 had an informant and were included. Timing not applicable as crosssectional, contemporaneous IQCODE and dementia assessment

Comparative Notes

These subjects were assessed by a psychiatrist

Methodological quality Item

Authors’ judgement

Risk of bias

Applicability concerns

DOMAIN 1: Patient Selection Was a consecutive or random No sample of patients enrolled? Was a case-control design Yes avoided? Did the study avoid inappropri- No ate exclusions? High DOMAIN 2: Index Test All tests Were the index test results in- Yes terpreted without knowledge of the results of the reference standard? If a threshold was used, was it Yes pre-specified? Were sufficient details given on Unclear IQCODE application for the test to be repeated in an indeInformant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

36

Jorm 1996 (psychiatry)

(Continued)

pendent study Unclear DOMAIN 3: Reference Standard Is the reference standards likely Yes to correctly classify the target condition? Were the reference standard re- Yes sults interpreted without knowledge of the results of the index tests? Were sufficient details of de- No mentia diagnostics given for the assessment to be repeated in an independent sample Unclear DOMAIN 4: Flow and Timing Was there an appropriate inter- Unclear val between index test and reference standard? Did all patients receive the same Yes reference standard? Were all patients included in the No analysis? Were missing IQCODE results Unclear or un-interpretable IQCODE results reported

Kathriarachi 2001 Study characteristics Patient sampling

Stratified community sampling, using census data and door to door assessment in a semi-urban setting

Patient characteristics and set- Community-dwelling older adults (n=37) ting Community setting Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

37

Kathriarachi 2001

(Continued)

Index tests

IQCODE 26 item, Sinhalese language

Target condition and reference Clinical diagnosis of dementia following psychiatrist’s review standard(s) Flow and timing

Of 1400 potential subjects,40 were “randomly” selected for assessment and 37 assessed. Timing not applicable as cross-sectional, contemporaneous IQCODE and dementia assessment

Comparative Notes

Low numbers included and high prevalence of dementia

Methodological quality Item

Authors’ judgement

Risk of bias

Applicability concerns

DOMAIN 1: Patient Selection Was a consecutive or random Unclear sample of patients enrolled? Was a case-control design Yes avoided? Did the study avoid inappropri- Yes ate exclusions? High DOMAIN 2: Index Test All tests Were the index test results in- Unclear terpreted without knowledge of the results of the reference standard? If a threshold was used, was it No pre-specified? Were sufficient details given on No IQCODE application for the test to be repeated in an independent study Unclear DOMAIN 3: Reference Standard

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

38

Kathriarachi 2001

(Continued)

Is the reference standards likely Unclear to correctly classify the target condition? Were the reference standard re- Unclear sults interpreted without knowledge of the results of the index tests? Were sufficient details of de- No mentia diagnostics given for the assessment to be repeated in an independent sample Unclear DOMAIN 4: Flow and Timing Was there an appropriate inter- Unclear val between index test and reference standard? Did all patients receive the same Unclear reference standard? Were all patients included in the No analysis? Were missing IQCODE results No or un-interpretable IQCODE results reported

Law 1995 Study characteristics Patient sampling

Age stratified sample of all community residents

Patient characteristics and set- Randomly selected community-dwelling adults (n=237) ting Community setting Index tests

IQCODE 26 item, French language

Target condition and reference Clinical dementia diagnosis using DSM IIIr standard(s)

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

39

Law 1995

(Continued)

Flow and timing

Of 1800 potential subjects, 454 had psychiatric assessment of this group 364 had suitable informants and 237 were included. Timing not applicable as cross-sectional, contemporaneous IQCODE and dementia assessment

Comparative Notes Methodological quality Item

Authors’ judgement

Risk of bias

Applicability concerns

DOMAIN 1: Patient Selection Was a consecutive or random Unclear sample of patients enrolled? Was a case-control design Yes avoided? Did the study avoid inappropri- Yes ate exclusions? Unclear DOMAIN 2: Index Test All tests Were the index test results in- Unclear terpreted without knowledge of the results of the reference standard? If a threshold was used, was it Yes pre-specified? Were sufficient details given on Yes IQCODE application for the test to be repeated in an independent study Low DOMAIN 3: Reference Standard Is the reference standards likely Yes to correctly classify the target condition?

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

40

Law 1995

(Continued)

Were the reference standard re- Unclear sults interpreted without knowledge of the results of the index tests? Were sufficient details of de- Yes mentia diagnostics given for the assessment to be repeated in an independent sample Low DOMAIN 4: Flow and Timing Was there an appropriate inter- Yes val between index test and reference standard? Did all patients receive the same Yes reference standard? Were all patients included in the No analysis? Were missing IQCODE results Yes or un-interpretable IQCODE results reported

Mackinnon 2003 Study characteristics Patient sampling

Probability sample of older adults (age > 70 years) drawn from electoral data

Patient characteristics and set- Probability sampling of community cohort (n=646) ting Community setting Index tests

IQCODE 26 and 16 item, English language

Target condition and reference Clinical dementia diagnosis using DSM IIIr standard(s) Flow and timing

Of 945 potential subjects,694 had an informant and 646 were included. Timing not applicable as cross-sectional, contemporaneous IQCODE and dementia assessment

Comparative Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

41

Mackinnon 2003

(Continued)

Notes Methodological quality Item

Authors’ judgement

Risk of bias

Applicability concerns

DOMAIN 1: Patient Selection Was a consecutive or random Yes sample of patients enrolled? Was a case-control design Yes avoided? Did the study avoid inappropri- Yes ate exclusions? Low DOMAIN 2: Index Test All tests Were the index test results in- Unclear terpreted without knowledge of the results of the reference standard? If a threshold was used, was it No pre-specified? Were sufficient details given on Yes IQCODE application for the test to be repeated in an independent study Low DOMAIN 3: Reference Standard Is the reference standards likely Yes to correctly classify the target condition? Were the reference standard re- Unclear sults interpreted without knowledge of the results of the index tests? Were sufficient details of de- Yes mentia diagnostics given for the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

42

Mackinnon 2003

(Continued)

assessment to be repeated in an independent sample High DOMAIN 4: Flow and Timing Was there an appropriate inter- Yes val between index test and reference standard? Did all patients receive the same Yes reference standard? Were all patients included in the No analysis? Were missing IQCODE results Unclear or un-interpretable IQCODE results reported

Morales 1995 Study characteristics Patient sampling

Random selection of community-dwelling older adults (age > 65) from census data with initial door to door assessment

Patient characteristics and set- Community-dwelling adults (n=68) ting Community setting Index tests

IQCODE 26 and 17 item, Spanish language

Target condition and reference Clinical dementia diagnosis using DSM IIIr standard(s) Flow and timing

Of 352 potential subjects, 257 agreed to assessment; 135 completed assessment and data from 68 with suitable informant information were included. Timing not applicable as cross-sectional, contemporaneous IQCODE and dementia assessment

Comparative Notes

Subjects with moderate to severe dementia were not included, so the study assesses IQCODE against “mild” dementia clinical diagnosis

Methodological quality Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

43

Morales 1995

(Continued)

Item

Authors’ judgement

Risk of bias

Applicability concerns

DOMAIN 1: Patient Selection Was a consecutive or random Yes sample of patients enrolled? Was a case-control design Yes avoided? Did the study avoid inappropri- No ate exclusions? High DOMAIN 2: Index Test All tests Were the index test results in- Unclear terpreted without knowledge of the results of the reference standard? If a threshold was used, was it Yes pre-specified? Were sufficient details given on No IQCODE application for the test to be repeated in an independent study Low DOMAIN 3: Reference Standard Is the reference standards likely Yes to correctly classify the target condition? Were the reference standard re- Yes sults interpreted without knowledge of the results of the index tests? Were sufficient details of de- Yes mentia diagnostics given for the assessment to be repeated in an independent sample Unclear Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

44

Morales 1995

(Continued)

DOMAIN 4: Flow and Timing Was there an appropriate inter- Yes val between index test and reference standard? Did all patients receive the same Yes reference standard? Were all patients included in the No analysis? Were missing IQCODE results Unclear or un-interpretable IQCODE results reported

Morales 1997 (rural) Study characteristics Patient sampling

Community sampling stratified by age/sex/place of residence with door to door assessment

Patient characteristics and set- Community (rural) dwelling adults (n=160) ting Index tests

IQCODE 26 item, Spanish language

Target condition and reference Clinical dementia diagnosis using DSM IIIr standard(s) Flow and timing

Data on numbers assessed and not included are not given. Timing not applicable as cross-sectional, contemporaneous IQCODE and dementia assessment

Comparative Notes

This paper presents two separate cohorts; these data refer to those living in a rural setting

Methodological quality Item

Authors’ judgement

Risk of bias

Applicability concerns

DOMAIN 1: Patient Selection Was a consecutive or random No sample of patients enrolled? Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

45

Morales 1997 (rural)

(Continued)

Was a case-control design Yes avoided? Did the study avoid inappropri- Unclear ate exclusions? High DOMAIN 2: Index Test All tests Were the index test results in- Unclear terpreted without knowledge of the results of the reference standard? If a threshold was used, was it Unclear pre-specified? Were sufficient details given on No IQCODE application for the test to be repeated in an independent study Low DOMAIN 3: Reference Standard Is the reference standards likely Yes to correctly classify the target condition? Were the reference standard re- Yes sults interpreted without knowledge of the results of the index tests? Were sufficient details of de- Yes mentia diagnostics given for the assessment to be repeated in an independent sample Low DOMAIN 4: Flow and Timing Was there an appropriate inter- Unclear val between index test and reference standard?

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

46

Morales 1997 (rural)

(Continued)

Did all patients receive the same Yes reference standard? Were all patients included in the No analysis? Were missing IQCODE results Yes or un-interpretable IQCODE results reported

Morales 1997 (urban) Study characteristics Patient sampling

Community sampling stratified by age/sex/place of residence with door to door assessment

Patient characteristics and set- Community (urban) dwelling adults (n=97) ting Community setting Index tests

IQCODE 26 item, Spanish language

Target condition and reference Clinical dementia diagnosis using DSM IIIr standard(s) Flow and timing

Data on numbers assessed and not included are not given. Timing not applicable as cross-sectional, contemporaneous IQCODE and dementia assessment

Comparative Notes

This paper presents two separate cohorts; these data refer to those living in an urban setting

Methodological quality Item

Authors’ judgement

Risk of bias

Applicability concerns

DOMAIN 1: Patient Selection Was a consecutive or random No sample of patients enrolled? Was a case-control design Yes avoided? Did the study avoid inappropri- Unclear ate exclusions? Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

47

Morales 1997 (urban)

(Continued)

High DOMAIN 2: Index Test All tests Were the index test results in- Unclear terpreted without knowledge of the results of the reference standard? If a threshold was used, was it Unclear pre-specified? Were sufficient details given on No IQCODE application for the test to be repeated in an independent study Low DOMAIN 3: Reference Standard Is the reference standards likely Yes to correctly classify the target condition? Were the reference standard re- Yes sults interpreted without knowledge of the results of the index tests? Were sufficient details of de- Yes mentia diagnostics given for the assessment to be repeated in an independent sample Low DOMAIN 4: Flow and Timing Was there an appropriate inter- Unclear val between index test and reference standard? Did all patients receive the same Yes reference standard? Were all patients included in the No analysis?

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

48

Morales 1997 (urban)

(Continued)

Were missing IQCODE results Yes or un-interpretable IQCODE results reported

Senanorong 2001 Study characteristics Patient sampling

“Population” study, no further detail given

Patient characteristics and set- Community-dwelling older adults (n=160) ting Community setting Index tests

IQCODE 16 and 3 item, Thai language

Target condition and reference Clinical dementia diagnosis using DSM IV standard(s) Flow and timing

Data on numbers assessed and not included are not given. Timing not applicable as cross-sectional, contemporaneous IQCODE and dementia assessment

Comparative Notes

This study present two cohorts these data are from “normal eduction” group. Numbers of dementia cases suggest a case-control methodology was used but this is not specified in methodology

Methodological quality Item

Authors’ judgement

Risk of bias

Applicability concerns

DOMAIN 1: Patient Selection Was a consecutive or random Unclear sample of patients enrolled? Was a case-control design Unclear avoided? Did the study avoid inappropri- Unclear ate exclusions? High DOMAIN 2: Index Test All tests

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

49

Senanorong 2001

(Continued)

Were the index test results in- Unclear terpreted without knowledge of the results of the reference standard? If a threshold was used, was it No pre-specified? Were sufficient details given on No IQCODE application for the test to be repeated in an independent study Unclear DOMAIN 3: Reference Standard Is the reference standards likely Yes to correctly classify the target condition? Were the reference standard re- Yes sults interpreted without knowledge of the results of the index tests? Were sufficient details of de- No mentia diagnostics given for the assessment to be repeated in an independent sample Unclear DOMAIN 4: Flow and Timing Was there an appropriate inter- Unclear val between index test and reference standard? Did all patients receive the same Unclear reference standard? Were all patients included in the Unclear analysis? Were missing IQCODE results Unclear or un-interpretable IQCODE results reported

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

50

Senanorong 2001

(Continued)

Srikanth 2006 Study characteristics Patient sampling

Community-based study of all non-aphasic stroke survivors from period 1998-1999 resident in an urban setting

Patient characteristics and set- Community-dwelling stroke-survivors (n=79) ting Community setting Index tests

IQCODE 16 item, English language

Target condition and reference Clinical dementia diagnosis using DSM IV standard(s) Flow and timing

Of 99 subjects, 88 were eligible for assessment and IQCODE data were available for 79

Comparative Notes

These subjects are all stroke-survivors

Methodological quality Item

Authors’ judgement

Risk of bias

Applicability concerns

DOMAIN 1: Patient Selection Was a consecutive or random Yes sample of patients enrolled? Was a case-control design Yes avoided? Did the study avoid inappropri- Yes ate exclusions? High DOMAIN 2: Index Test All tests Were the index test results in- Unclear terpreted without knowledge of the results of the reference standard?

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

51

Srikanth 2006

(Continued)

If a threshold was used, was it Yes pre-specified? Were sufficient details given on Unclear IQCODE application for the test to be repeated in an independent study Unclear DOMAIN 3: Reference Standard Is the reference standards likely Yes to correctly classify the target condition? Were the reference standard re- Yes sults interpreted without knowledge of the results of the index tests? Were sufficient details of de- Yes mentia diagnostics given for the assessment to be repeated in an independent sample Low DOMAIN 4: Flow and Timing Was there an appropriate inter- Yes val between index test and reference standard? Did all patients receive the same Yes reference standard? Were all patients included in the Yes analysis? Were missing IQCODE results Yes or un-interpretable IQCODE results reported

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

52

Yamada 2011 Study characteristics Patient sampling

Community study, sampling method not clear

Patient characteristics and set- Community-dwelling older adults who were participants in another study (n=423) ting Index tests

IQCODE 26 item, Japanese language

Target condition and reference Clinical dementia diagnosis using DSM standard(s) Flow and timing

Unclear

Comparative Notes

Abstract data only

Methodological quality Item

Authors’ judgement

Risk of bias

Applicability concerns

DOMAIN 1: Patient Selection Was a consecutive or random No sample of patients enrolled? Was a case-control design Yes avoided? Did the study avoid inappropri- Unclear ate exclusions? Unclear DOMAIN 2: Index Test All tests Were the index test results in- Unclear terpreted without knowledge of the results of the reference standard? If a threshold was used, was it Unclear pre-specified? Were sufficient details given on No IQCODE application for the test to be repeated in an independent study Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

53

Yamada 2011

(Continued)

High DOMAIN 3: Reference Standard Is the reference standards likely Yes to correctly classify the target condition? Were the reference standard re- Unclear sults interpreted without knowledge of the results of the index tests? Were sufficient details of de- No mentia diagnostics given for the assessment to be repeated in an independent sample Low DOMAIN 4: Flow and Timing Was there an appropriate inter- Unclear val between index test and reference standard? Did all patients receive the same Unclear reference standard? Were all patients included in the Unclear analysis? Were missing IQCODE results No or un-interpretable IQCODE results reported

Characteristics of excluded studies [ordered by study ID]

Study

Reason for exclusion

Abreu 2008

Hospital setting

Butt 2008

Data on less than 10 participants

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

54

(Continued)

Cherbuin 2008

No new data

de Jonge 1997

Data not suitable for analysis

Dekkers 2009

Data not suitable for analysis

Diefeldt 2007b

Repeat data set

Diesfeldt 2007

No dementia diagnosis reference standard

Ehrensperger 2010

Uses unvalidated (two-year) IQCODE

Farias 2002

No dementia diagnosis reference standard

Finneli (abstract)

Data not suitable for analysis

Fuh 1995

Case-control

Garcia 2002

Hospital setting

Goncalves 2011

Hospital setting

Hancock 2009

Hospital setting

Harwood 1997

Hospital setting

Hayden 2003

65yrs only)

Law 1995

80.7

6.5

67 - 97

Mackinnon 2003

76.5

-

70 - 97

Morales 1995

73.1

5.2

65 - 86

Morales 1997 (urban) (urban)

75.2

6.1

66 - 92

Morales 1997 (urban) (rural)

73.5

8.2

61 - 96

Senanorong 2001

65.7

5.0

52 - 85

Srikanth 2006

69.0

14.4

-

Yamada 2011

-

-

-

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

67

APPENDICES Appendix 1. WHO International Classification of Disease - Dementia World Health Organization International Classification of Diseases 10 F00 - F09 ORGANIC, INCLUDING SYMPTOMATIC, MENTAL DISORDERS DEMENTIA G1. Evidence of each of the following: (1) A decline in memory, which is most evident in the learning of new information, although in more severe cases, the recall of previously learned information may be also affected. The impairment applies to both verbal and non-verbal material. The decline should be objectively verified by obtaining a reliable history from an informant, supplemented, if possible, by neuropsychological tests or quantified cognitive assessments. The severity of the decline, with mild impairment as the threshold for diagnosis, should be assessed as follows: Mild: a degree of memory loss sufficient to interfere with everyday activities, though not so severe as to be incompatible with independent living. The main function affected is the learning of new material. For example, the individual has difficulty in registering, storing and recalling elements in daily living, such as where belongings have been put, social arrangements, or information recently imparted by family members. Moderate: A degree of memory loss which represents a serious handicap to independent living. Only highly learned or very familiar material is retained. New information is retained only occasionally and very briefly. The individual is unable to recall basic information about where he lives, what he has recently been doing, or the names of familiar persons. Severe: a degree of memory loss characterized by the complete inability to retain new information. Only fragments of previously learned information remain. The subject fails to recognize even close relatives. (2) A decline in other cognitive abilities characterized by deterioration in judgement and thinking, such as planning and organizing, and in the general processing of information. Evidence for this should be obtained when possible from interviewing an informant, supplemented, if possible, by neuropsychological tests or quantified objective assessments. Deterioration from a previously higher level of performance should be established. The severity of the decline, with mild impairment as the threshold for diagnosis, should be assessed as follows: Mild. The decline in cognitive abilities causes impaired performance in daily living, but not to a degree making the individual dependent on others. More complicated daily tasks or recreational activities cannot be undertaken. Moderate. The decline in cognitive abilities makes the individual unable to function without the assistance of another in daily living, including shopping and handling money. Within the home, only simple chores are preserved. Activities are increasingly restricted and poorly sustained. Severe. The decline is characterized by an absence, or virtual absence, of intelligible ideation. The overall severity of the dementia is best expressed as the level of decline in memory or other cognitive abilities, whichever is the more severe (e.g. mild decline in memory and moderate decline in cognitive abilities indicate a dementia of moderate severity). G2. Preserved awareness of the environment during a period of time long enough to enable the unequivocal demonstration of G1. When there are superimposed episodes of delirium the diagnosis of dementia should be deferred. G3. A decline in emotional control or motivation, or a change in social behaviour, manifest as at least one of the following: (1) emotional lability; (2) irritability; (3) apathy; (4) coarsening of social behaviour. G4. For a confident clinical diagnosis, G1 should have been present for at least six months; if the period since the manifest onset is shorter, the diagnosis can only be tentative. Comments: The diagnosis is further supported by evidence of damage to other higher cortical functions, such as aphasia, agnosia, apraxia. Judgment about independent living or the development of dependence (upon others) need to take account of the cultural expectation and context. Dementia is specified here as having a minimum duration of six months to avoid confusion with reversible states with identical behavioural syndromes, such as traumatic subdural haemorrhage (S06.5), normal pressure hydrocephalus (G91.2) and diffuse or focal brain injury (S06.2 and S06.3). A fifth character may be used to indicate the presence of additional symptoms, in the categories F00-F03 (F00 Dementia in Alzheimer’s disease; F01 Vascular dementia; F02 Dementia in diseases classified elsewhere; and Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

68

F03 Unspecified dementia), as follows: .x0 without additional symptoms .x1 with other symptoms, predominantly delusional .x2 with other symptoms, predominantly hallucinatory .x3 with other symptoms, predominantly depressive .x4 with other mixed symptoms A sixth character may be used to indicate the severity of the dementia: .xx0 mild .xx1 moderate .xx2 severe As mentioned above the overall severity of the dementia depends on the level of memory or intellectual impairment, whichever is the more severe. F00 DEMENTIA IN ALZHEIMER’S DISEASE A. The general criteria for dementia (G1 to G4) must be met. B. There is no evidence from the history, physical examination or special investigations for any other possible cause of dementia (e.g. cerebrovascular disease, Parkinson’s disease, Huntington’s disease, normal pressure hydrocephalus), a systemic disorder (e.g. hypothyroidism, vit. B12 or folic acid deficiency, hypercalcaemia), or alcohol- or drug-abuse. Comments: The diagnosis is confirmed by post mortem evidence of neurofibrillary tangles and neuritic plaques in excess of those found in normal ageing of the brain. The following features support the diagnosis, but are not necessary elements: Involvement of cortical functions as evidenced by aphasia, agnosia or apraxia; decrease of motivation and drive, leading to apathy and lack of spontaneity; irritability and disinhibition of social behaviour; evidence from special investigations that there is cerebral atrophy, particularly if this can be shown to be increasing over time. In severe cases there may be Parkinson-like extrapyramidal changes, logoclonia, and epileptic fits. Specification of features for possible subtypes. Because of the possibility that subtypes exist, it is recommended that the following characteristics be ascertained as a basis for a further classification: age at onset; rate of progression; the configuration of the clinical features, particularly the relative prominence (or lack) of temporal, parietal or frontal lobe signs; any neuropathological or neurochemical abnormalities, and their pattern. The division of AD into subtypes can at present be accomplished in two ways: first by taking only the age of onset and labelling AD as either early or late, with an approximate cut-off point at 65 years; or secondly, by assessing how well the individual conforms to one of the two putative syndromes, early or late onset type. It should be noted that it is unlikely that a sharp distinction exists between early and late onset type. Early onset type may occur in late life, just as late onset type may occasionally have an onset under the age of 65. The following criteria may be used to differentiate F00.0 from F00.1, but it should be remembered that the status of this subdivision is still controversial. F00.0 Dementia in Alzheimer’s disease with early onset 1. The criteria for dementia in Alzheimer’s disease (F00) must be met, and the age at onset being under 65 years. 2. In addition, at least one of the following requirements must be met: (a) evidence of a relatively rapid onset and progression; (b) in addition to memory impairment, there is aphasia (amnesic or sensory), agraphia, alexia, acalculia, or apraxia (indicating the presence of temporal, parietal and/or frontal lobe involvement). F00.1 Dementia in Alzheimer’s disease with late onset 1. The criteria for dementia in Alzheimer’s disease (F00) must be met and the age at onset must be 65 or more. 2. In addition, at least one of the following requirements must be met: (a) evidence of a very slow, gradual onset and progression (the rate of the latter may be known only retrospectively after a course of 3 years or more); (b) predominance of memory impairment G1.1, over intellectual impairment G1.2 (see general criteria for dementia). F00.2 Dementia in Alzheimer’s disease, atypical or mixed type Use this term and code for dementias that have important atypical features or that fulfil criteria for both early and late onset type of Alzheimer’s disease. Mixed Alzheimer’s and vascular dementia is also included here. F00.9 Dementia in Alzheimer’s disease, unspecified F01 VASCULAR DEMENTIA G1. The general criteria for dementia (G1 to G4) must be met. G2. Unequal distribution of deficits in higher cognitive functions, with some affected and others relatively spared. Thus memory may be quite markedly affected while thinking, reasoning and information processing may show only mild decline. Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

69

G3. There is clinical evidence of focal brain damage, manifest as at least one of the following: (1) unilateral spastic weakness of the limbs; (2) unilaterally increased tendon reflexes; (3) an extensor plantar response; (4) pseudobulbar palsy. G4. There is evidence from the history, examination, or tests, of a significant cerebrovascular disease, which may reasonably be judged to be etiologically related to the dementia (e.g. a history of stroke; evidence of cerebral infarction). The following criteria may be used to differentiate subtypes of vascular dementia, but it should be remembered that the usefulness of this subdivision may not be generally accepted. F01.0 Vascular dementia of acute onset A. The general criteria for vascular dementia (F01) must be met. B. The dementia develops rapidly (i.e. usually within one month, but within no longer than three months) after a succession of strokes, or (rarely) after a single large infarction. F01.1 Multi-infarct dementia A. The general criteria for vascular dementia (F01) must be met. B. The onset of the dementia is gradual (i.e. within three to six months), following a number of minor ischaemic episodes. Comments: It is presumed that there is an accumulation of infarcts in the cerebral parenchyma. Between the ischaemic episodes there may be periods of actual clinical improvement. F01.2 Subcortical vascular dementia A. The general criteria for vascular dementia (F01) must be met. B. A history of hypertension. C. Evidence from clinical examination and special investigations of vascular disease located in the deep white matter of the cerebral hemispheres, with preservation of the cerebral cortex. F01.3 Mixed cortical and subcortical vascular dementia Mixed cortical and subcortical components of the vascular dementia may be suspected from the clinical features, the results of investigations (including autopsy), or both. F01.8 Other vascular dementia F01.9 Vascular dementia, unspecified F02 DEMENTIA IN OTHER DISEASES CLASSIFIED ELSEWHERE F02.0 Dementia in Pick’s disease A. The general criteria for dementia (G1 to G4) must be met. B. Slow onset with steady deterioration. C. Predominance of frontal lobe involvement evidenced by two or more of the following: (1) emotional blunting; (2) coarsening of social behaviour; (3) disinhibition; (4) apathy or restlessness; (5) aphasia. D. Relative preservation, in the early stages, of memory and parietal lobe functions. F02.1 Dementia in Creutzfeldt-Jakob disease A. The general criteria for dementia (G1 to G4) must be met. B. Very rapid progression of the dementia, with disintegration of virtually all higher cerebral functions. C. The emergence, usually after or simultaneously with the dementia, of one or more of the following types of neurological symptoms and signs: (1) pyramidal symptoms; (2) extrapyramidal symptoms; (3) cerebellar symptoms; (4) aphasia; (5) visual impairment. Comments: An akinetic and mute state is the typical terminal stage. An amyotrophic variant may be seen, where the neurological signs precede the onset of the dementia. A characteristic electroencephalogram (periodic spikes against a slow and low voltage background), if present in association with the above clinical signs, will increase the probability of the diagnosis. However, the diagnosis can be Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

70

confirmed only by neuropathological examination (neuronal loss, astrocytosis, and spongiform changes). Because of the risk of infection, this should be carried out only under special protective conditions. F02.2 Dementia in Huntington’s disease A. The general criteria for dementia (G1 to G4) must be met. B. Subcortical functions are affected first and dominate the picture of dementia throughout; manifest as slowness of thinking or movement and personality alteration with apathy or depression. C. Presence of involuntary choreiform movements, typically of the face, hands or shoulders, or in the gait. The patient may attempt to conceal them by converting them into a voluntary action. D. A history of Huntington’s disease in one parent or a sibling; or a family history which suggests the disorder. E. The absence of clinical features otherwise accounting for the abnormal movements. Comments: In addition to involuntary choreiform movements there may be development of extrapyramidal rigidity or spasticity with pyramidal signs. F02.3 Dementia in Parkinson’s disease A. The general criteria for dementia (G1 to G4) must be met. B. Diagnosis of Parkinson’s disease. C. Absence of cognitive impairment attributable to anti-parkinsonian medication. D. There is no evidence from the history, physical examination or special investigations for any other possible cause of dementia, including other forms of brain disease, damage or dysfunction (e.g. cerebrovascular disease, HIV disease, Huntington’s disease, normal pressure hydrocephalis), a systemic disorder (e.g. hypothyroidism, vit. B12 or folic acid deficiency, hypercalcaemia), or alcohol or drug abuse. If criteria are also fulfilled for dementia in Alzheimer’s disease with late onset (F00.1), this category F00.1 should be used in combination with Parkinson’s disease G20. F02.4 Dementia in human immunodeficiency (HIV) disease A. The general criteria for dementia (G1 to G4) must be met. B. Diagnosis of HIV infection. C. There is no evidence from the history, physical examination or special investigations for any other possible cause of dementia, including other forms of brain disease, damage or dysfunction (e.g. Alzheimer’s disease, cerebrovascular disease, Parkinson’s disease, Huntington’s disease, normal pressure hydrocephalis), a systemic disorder (e.g. hypothyroidism, vit. B12 or folic acid deficiency, hypercalcaemia), or alcohol or drug abuse. F02.8 Dementia in other specified diseases classified elsewhere Dementia can occur as a manifestation or consequence of a variety of cerebral and somatic conditions. To specify the etiology, the ICD10 code for the underlying condition should be added. F03 UNSPECIFIED DEMENTIA This category should be used when the general criteria for dementia are met, but when it is not possible to identify one of the specific types (F00.0-F02.9).

Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision

Dementia Codes Dementia of the Alzheimer’s Type, with early onset 294.10 Without behavioural disturbance 294.11 With behavioural disturbance Dementia of the Alzheimer’s Type, with late onset 294.10 Without behavioural disturbance 294.11 With behavioural disturbance Vascular dementia 290.40 Uncomplicated 290.41 With delirium 290.42 With delusions 290.43 With depressed mood Dementia due to HIV disease Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

71

294.10 Without behavioural disturbance 294.11 With behavioural disturbance Dementia due to head trauma 294.10 Without behavioural disturbance 294.11 With behavioural disturbance Dementia due to Parkinson’s disease 294.10 Without behavioural disturbance 294.11 With behavioural disturbance Dementia due to Huntington’s disease 294.10 Without behavioural disturbance 294.11 With behavioural disturbance Dementia due to Pick’s disease 294.10 Without behavioural disturbance 294.11 With behavioural disturbance Dementia due to Creutzfeldt-Jakob Disease 294.10 Without behavioural disturbance 294.11 With behavioural disturbance Dementia due to... [indicate other general medical condition] 294.10 Without behavioural disturbance 294.11 With behavioural disturbance 294.8 Dementia NOS

Appendix 2. Twenty-six item IQCODE Instructions: Now we want you to remember what your friend or relative was like 10 years ago and to compare it with what he/she is like now. 10 years ago was 19˙˙. On the next page are situations where this person has to use his/her memory or intelligence and we want you to indicate whether this has improved, stayed the same or got worse than in that situation over the past 10 years. Note the importance of comparing his/her present performance with 10 years ago. So if 10 years ago this person always forgot where he/she had left things and he/she still does this, then this would be considered ‘Not much change’. Please indicate the changes you have observed by circling the appropriate answer.

1

2

3

4

5

1. Recognizing the Much improved faces of family and friends

A bit improved

Not much change

A bit worse

Much worse

2. Remembering the Much improved names of family and friends

A bit improved

Not much change

A bit worse

Much worse

3. Remembering Much improved things about family and friends e.g. occupations, birthdays, addresses

A bit improved

Not much change

A bit worse

Much worse

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

72

(Continued)

4. Remember- Much improved ing things that have happened recently

A bit improved

Not much change

A bit worse

Much worse

5. Recalling conver- Much improved sations a few days later

A bit improved

Not much change

A bit worse

Much worse

6. Forgetting what Much improved he/she wanted to say in the middle of a conversation

A bit improved

Not much change

A bit worse

Much worse

7. Remembering Much improved his/her address and telephone number

A bit improved

Not much change

A bit worse

Much worse

8. Much improved Remembering what day and month it is

A bit improved

Not much change

A bit worse

Much worse

9. Remember- Much improved ing where things are usually kept

A bit improved

Not much change

A bit worse

Much worse

10. Remembering Much improved where to find things which have been put in a different place from usual

A bit improved

Not much change

A bit worse

Much worse

11. Adjusting to any Much improved change in his/her day-to-day routine

A bit improved

Not much change

A bit worse

Much worse

12. Knowing how Much improved to work familiar machines around the house

A bit improved

Not much change

A bit worse

Much worse

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

73

(Continued)

13. Learning to use Much improved a new gadget or machine around the house

A bit improved

Not much change

A bit worse

Much worse

14. Learning new Much improved things in general

A bit improved

Not much change

A bit worse

Much worse

15. Remem- Much improved bering things that happened to him/ her when he/she was young

A bit improved

Not much change

A bit worse

Much worse

16. Remem- Much improved bering things he/she learned when he/she was young

A bit improved

Not much change

A bit worse

Much worse

17. Understanding Much improved the meaning of unusual words

A bit improved

Not much change

A bit worse

Much worse

18. Understanding Much improved magazine or newspaper articles

A bit improved

Not much change

A bit worse

Much worse

19. Following a Much improved story in a book or on TV

A bit improved

Not much change

A bit worse

Much worse

20. Composing a Much improved letter to friends or for business purposes

A bit improved

Not much change

A bit worse

Much worse

21. Knowing about Much improved important historical events of the past

A bit improved

Not much change

A bit worse

Much worse

22. Making deci- Much improved sions on everyday matters

A bit improved

Not much change

A bit worse

Much worse

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

74

(Continued)

23. Handling Much improved money for shopping

A bit improved

Not much change

A bit worse

Much worse

24. Handling finan- Much improved cial matters, e.g. the pension, dealing with the bank

A bit improved

Not much change

A bit worse

Much worse

25. Handling other Much improved everyday arithmetic problems, e.g. knowing how much food to buy, knowing how long between visits from family or friends

A bit improved

Not much change

A bit worse

Much worse

26. Using his/her in- Much improved telligence to understand what’s going on and to reason things through

A bit improved

Not much change

A bit worse

Much worse

Appendix 3. Sixteen-item IQCODE Instructions: Now we want you to remember what your friend or relative was like 10 years ago and to compare it with what he/she is like now. 10 years ago was 19˙˙. On the next page are situations where this person has to use his/her memory or intelligence and we want you to indicate whether this has improved, stayed the same or got worse than in that situation over the past 10 years. Note the importance of comparing his/her present performance with 10 years ago. So if 10 years ago this person always forgot where he/she had left things and he/she still does this, then this would be considered ‘Not much change’. Please indicate the changes you have observed by circling the appropriate answer.

1

2

3

4

5

1

Remembering Much improved things about family and friends, e.g. occupations, birthdays, addresses

A bit improved

Not much change

A bit worse

Much worse

2

RememberMuch improved ing things that have happened recently

A bit improved

Not much change

A bit worse

Much worse

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

75

(Continued)

3

Recalling conversa- Much improved tions a few days later

A bit improved

Not much change

A bit worse

Much worse

4

Remembering Much improved her/his address and telephone number

A bit improved

Not much change

A bit worse

Much worse

5

RememberMuch improved ing what day and month it is

A bit improved

Not much change

A bit worse

Much worse

6

ReMuch improved membering where things are usually kept

A bit improved

Not much change

A bit worse

Much worse

7

RememberMuch improved ing where to find things which have been put in a different place from usual

A bit improved

Not much change

A bit worse

Much worse

8

Knowing how to Much improved work familiar machines around the house

A bit improved

Not much change

A bit worse

Much worse

9

Learning to use a Much improved new gadget or machine around the house

A bit improved

Not much change

A bit worse

Much worse

10

Learning new Much improved things in general

A bit improved

Not much change

A bit worse

Much worse

11

Following a story Much improved in a book or on TV

A bit improved

Not much change

A bit worse

Much worse

12

Making decisions Much improved on everyday matters

A bit improved

Not much change

A bit worse

Much worse

13

Handling money Much improved for shopping

A bit improved

Not much change

A bit worse

Much worse

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

76

(Continued)

14

Handling financial Much improved matters, e.g. the pension, dealing with the bank

A bit improved

Not much change

A bit worse

Much worse

15

Handling other ev- Much improved eryday arithmetic problems, e. g. knowing how much food to buy, knowing how long between visits from family or friends

A bit improved

Not much change

A bit worse

Much worse

16

Using his/her intel- Much improved ligence to understand what’s going on and to reason things through

A bit improved

Not much change

A bit worse

Much worse

Appendix 4. Commonly used cognitive assessments or screening tools

TEST

Cochrane DTA review in process

Mini-Mental State Examination (MMSE)

YES

GPcog

Still available

Minicog

Still available

Memory Impairment Screen (MIS)

Still available

Abbreviated mental testing

Still available

Clock drawing tests (CDT)

Still available

Montreal Cognitive Assessment (MoCA)

Still available

AD-8 (informant interview)

YES

For each test, the planned review will encompass diagnostic test accuracy in community; primary and secondary care settings. As well as standard diagnosis, where applicable reviews will also describe delayed verification design trials.

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

77

Appendix 5. Sources searched and search strategies

Source

Search strategy

Hits retrieved

1. MEDLINE In-Orocess and other non- 1. IQCODE.ti,ab. Apr 2011: 291 indexed citations and MEDLINE 1950- 2. “informant questionnaire on cognitive Jul 2012: 39 present (OvidSP) decline in the elderly”.ti,ab Jan 2013: 19 3. “IQ code”.ti,ab. 4. (“informant* questionnair*” adj3 (dement* or screening)).ti,ab 5. (“screening test*” adj2 (dement* or alzheimer*)).ti,ab. 6. or/1-5 2. EMBASE 1980-2013 January 10 (OvidSP)

1. IQCODE.ti,ab. Apr 2011: 356 2. “informant questionnaire on cognitive Jul 2012: 49 decline in the elderly”.ti,ab Jan 2013: 44 3. “IQ code”.ti,ab. 4. (“informant* questionnair*” adj3 (dement* or screening)).ti,ab 5. (“screening test*” adj2 (dement* or alzheimer*)).ti,ab. 6. or/1-5

3. PsycINFO 1806-January week 2 2013 (OvidSP)

1. IQCODE.ti,ab. Apr 2011: 215 2. “informant questionnaire on cognitive Jul 2012: 28 decline in the elderly”.ti,ab Jan 2013: 17 3. “IQ code”.ti,ab. 4. (“informant* questionnair*” adj3 (dement* or screening)).ti,ab 5. (“screening test*” adj2 (dement* or alzheimer*)).ti,ab. 6. or/1-5

4. BIOSIS Previews 1926 to present (ISI Topic=(IQCODE OR “informant ques- Apr 2011: 84 Web of Knowledge) tionnaire on cognitive decline in the el- Jul 2012: 12 derly” OR “IQ code”) AND Topic=(de- Jan 2013: 2 ment* OR alzheimer* OR FTLD OR FTD OR “primary progressive aphasia” OR “progressive non-fluent aphasia” OR “frontotemporal lobar degeneration” OR “frontolobar degeneration” OR “frontal lobar degeneration” OR “pick* disease” OR “lewy bod*”) Timespan=All Years. Databases= SCI-EXPANDED, SSCI, A&HCI, CPCIS, CPCI-SSH, BKCI-S, BKCI-SSH Lemmatization=On

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

78

(Continued)

5. Web of Science and conference proceed- Topic=(IQCODE OR “informant ques- Apr 2011: 184 ings (1945-present) tionnaire on cognitive decline in the el- Jul 2012: 24 derly” OR “IQ code”) AND Topic=(de- Jan 2013: 13 ment* OR alzheimer* OR FTLD OR FTD OR “primary progressive aphasia” OR “progressive non-fluent aphasia” OR “frontotemporal lobar degeneration” OR “frontolobar degeneration” OR “frontal lobar degeneration” OR “pick* disease” OR “lewy bod*”) Timespan=All Years. Databases= SCI-EXPANDED, SSCI, A&HCI, CPCIS, CPCI-SSH, BKCI-S, BKCI-SSH Lemmatization=On 6. LILACS (BIREME)

“short-IQCODE” OR IQCODE OR “IQ Apr 2011: 10 code” OR “Informant Questionnaire” OR Jul 2012: 0 “Informant Questionnaires” Jan 2013: 0

7. CINAHL (EBSCOhost)

S1 TX IQCODE S2 TX “informant questionnaire” S3 TX “IQ code” S4 TX screening instrument S5 S1 or S2 or S3 or S4 S6 (MM “Dementia+”) S7 TX dement* S8 TX alzheimer* S9 S6 or S7 or S8 S10 S5 and S9

Apr 2011: 231 Jul 2012: 53 Jan 2013: 12

8. Additional other review sources: MEDION database (searched 31 Jan for all dates); Jan 2013: 3 Database of Abstracts of Reviews of Effects (searched Issue 1 of the Cochrane Library 2013); Health Technology Assessments Database (searched Issue 1 of the Cochrane Library 2013); ARIF: Aggressive Research Intelligence Facility www.arif.bham.ac.uk (searched 31 Jan for all dates). Terms used: IQCODE, “IQ code”, “Informant Questionnaire”, “Informant Questionnaires” 9 ALOIS (see Appendix 6 for the Medline strategy used to populate ALOIS)

Jan 2013: 22

TOTAL before de-duplication of search results

Apr 2011: 1361 Jul 2012: 215 Jan 2013: 107 (+3 from additional review sources) TOTAL: 1708

TOTAL after de-duplication and first-assess by the Trials Search Co-ordinator

69

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

79

Appendix 6. Search strategy (MEDLINE OvidSP) run for specialised register (ALOIS) Search strategy (MEDLINE OvidSP) run for specialised register (ALOIS) Search narrative: The searches detailed above are very simple, single concept strategies based on the index test (IQCODE). This is a sensitive approach to take. More complex and developed searches are run each month for the dementia group. Every month the following strategy is run in Medline (via Ovid SP), with similar strategies run in Embase (via Ovid SP) and PsycINFO (via Ovid SP). The results are screened based on a reading of title and abstract. The full texts (where there is one) are then obtained and a few key details about each study are extracted including Index test/s and details of population and setting. For this review it was expected that most studies would be identified through a search of multiple sources based on one concept (the index test in question). However, we felt it was worth also searching ALOIS for any studies which had evaluated the accuracy of IQCODE but had not referred to it in the title or abstract of the reference.

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

80

MEDLINE In-Process and other non-indexed citations and 1. “word recall”.ti,ab. MEDLINE 1950-present (OvidSP) 2. “7-minute screen”.ti,ab. 3. “6 item cognitive impairment test”.ti,ab. 4. “6 CIT”.ti,ab. 5. “AB cognitive screen”.ti,ab. 6. “abbreviated mental test”.ti,ab. 7. “ADAS-cog”.ti,ab. 8. AD8.ti,ab. 9. “inform* interview”.ti,ab. 10. “animal fluency test”.ti,ab. 11. “brief alzheimer* screen”.ti,ab. 12. “brief cognitive scale”.ti,ab. 13. “clinical dementia rating scale”.ti,ab. 14. “clinical dementia test”.ti,ab. 15. “community screening interview for dementia”.ti,ab. 16. “cognitive abilities screening instrument”.ti,ab. 17. “cognitive assessment screening test”.ti,ab. 18. “cognitive capacity screening examination”.ti,ab. 19. “clock drawing test”.ti,ab. 20. “deterioration cognitive observee”.ti,ab. 21. “Dem Tect”.ti,ab. 22. “fuld object memory evaluation”.ti,ab. 23. “IQCODE”.ti,ab. 24. “mattis dementia rating scale”.ti,ab. 25. “memory impairment screen”.ti,ab. 26. “minnesota cognitive acuity screen”.ti,ab. 27. “mini-cog”.ti,ab. 28. “mini-mental state exam*”.ti,ab. 29. “mmse”.ti,ab. 30. “modified mini-mental state exam”.ti,ab. 31. “3MS”.ti,ab. 32. “neurobehavioural cognitive status exam*”.ti,ab. 33. “cognistat”.ti,ab. 34. “quick cognitive screening test”.ti,ab. 35. “QCST”.ti,ab. 36. “rapid dementia screening test”.ti,ab. 37. “RDST”.ti,ab. 38. “repeatable battery for the assessment of neuropsychological status”.ti,ab 39. “RBANS”.ti,ab. 40. “rowland universal dementia assessment scale”.ti,ab. 41. “rudas”.ti,ab. 42. “self-administered gerocognitive exam*”.ti,ab. 43. (“self-administered” and “SAGE”).ti,ab. 44. “self-administered computerized screening test for dementia”. ti,ab 45. “short and sweet screening instrument”.ti,ab. 46. “sassi”.ti,ab. 47. “short cognitive performance test”.ti,ab. Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

81

48. “syndrome kurztest”.ti,ab. 49. “six item screener”.ti,ab. 50. “short memory questionnaire”.ti,ab. 51. (“short memory questionnaire” and “SMQ”).ti,ab. 52. “short orientation memory concentration test”.ti,ab. 53. “s-omc”.ti,ab. 54. “short blessed test”.ti,ab. 55. “short portable mental status questionnaire”.ti,ab. 56. “spmsq”.ti,ab. 57. “short test of mental status”.ti,ab. 58. “telephone interview of cognitive status modified”.ti,ab 59. “tics-m”.ti,ab. 60. “trail making test”.ti,ab. 61. “verbal fluency categories”.ti,ab. 62. “WORLD test”.ti,ab. 63. “general practitioner assessment of cognition”.ti,ab. 64. “GPCOG”.ti,ab. 65. “Hopkins verbal learning test”.ti,ab. 66. “HVLT”.ti,ab. 67. “time and change test”.ti,ab. 68. “modified world test”.ti,ab. 69. “symptoms of dementia screener”.ti,ab. 70. “dementia questionnaire”.ti,ab. 71. “7MS”.ti,ab. 72. (“concord informant dementia scale” or CIDS).ti,ab. 73. (SAPH or “dementia screening and perceived harm*”).ti,ab 74. or/1-73 75. exp Dementia/ 76. Delirium, Dementia, Amnestic, Cognitive Disorders/ 77. dement*.ti,ab. 78. alzheimer*.ti,ab. 79. AD.ti,ab. 80. (“lewy bod*” or DLB or LBD).ti,ab. 81. “cognit* impair*”.ti,ab. 82. (cognit* adj4 (disorder* or declin* or fail* or function*)).ti,ab 83. (memory adj3 (complain* or declin* or function*)).ti,ab. 84. or/75-83 85. exp “sensitivity and specificity”/ 86. “reproducibility of results”/ 87. (predict* adj3 (dement* or AD or alzheimer*)).ti,ab. 88. (identif* adj3 (dement* or AD or alzheimer*)).ti,ab. 89. (discriminat* adj3 (dement* or AD or alzheimer*)).ti,ab. 90. (distinguish* adj3 (dement* or AD or alzheimer*)).ti,ab. 91. (differenti* adj3 (dement* or AD or alzheimer*)).ti,ab. 92. diagnos*.ti. 93. di.fs. 94. sensitivit*.ab. 95. specificit*.ab.

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

82

96. (ROC or “receiver operat*”).ab. 97. Area under curve/ 98. (“Area under curve” or AUC).ab. 99. (detect* adj3 (dement* or AD or alzheimer*)).ti,ab. 100. sROC.ab. 101. accura*.ti,ab. 102. (likelihood adj3 (ratio* or function*)).ab. 103. (conver* adj3 (dement* or AD or alzheimer*)).ti,ab. 104. ((true or false) adj3 (positive* or negative*)).ab. 105. ((positive* or negative* or false or true) adj3 rate*).ti,ab 106. or/85-105 107. exp dementia/di 108. Cognition Disorders/di [Diagnosis] 109. Memory Disorders/di 110. or/107-109 111. *Neuropsychological Tests/ 112. *Questionnaires/ 113. Geriatric Assessment/mt 114. *Geriatric Assessment/ 115. Neuropsychological Tests/mt, st 116. “neuropsychological test*”.ti,ab. 117. (neuropsychological adj (assess* or evaluat* or test*)).ti,ab 118. (neuropsychological adj (assess* or evaluat* or test* or exam* or battery)).ti,ab 119. Self report/ 120. self-assessment/ or diagnostic self evaluation/ 121. Mass Screening/ 122. early diagnosis/ 123. or/111-122 124. 74 or 123 125. 110 and 124 126. 74 or 123 127. 84 and 106 and 126 128. 74 and 106 129. 125 or 127 or 128 130. (animals not (humans and animals)).sh. 131. 129 not 130 The concepts for this are: A Specific neuropsychological tests B General terms (both free text and MeSH) for tests/testing/ screening C Outcome: dementia diagnosis (unfocused MeSH with diagnostic sub-headings) D Condition of interest: Dementia (general dementia terms both free text and MeSH - exploded and unfocused) E Methodological filter: not used to limit all search The concept combinations are: 1. (A OR B) AND C

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

83

2. (A OR B) AND D AND E 3. A AND E

Appendix 7. Assessment of reporting quality - STARD checklist

Section and Topic TITLE/ABSTRACT KEYWORDS

1

Identify the article as a study of diagnostic accuracy (recommend MeSH heading ’sensitivity and specificity’)

INTRODUCTION

2

State the research questions or study aims, such as estimating diagnostic accuracy or comparing accuracy between tests or across participant groups

3

The study population: The inclusion and exclusion criteria, setting and locations where data were collected

4

Participant recruitment: Was recruitment based on presenting symptoms, results from previous tests, or the fact that the participants had received the index tests or the reference standard?

5

Participant sampling: Was the study population a consecutive series of participants defined by the selection criteria in item 3 and 4? If not, specify how participants were further selected

6

Data collection: Was data collection planned before the index test and reference standard were performed (prospective study) or after (retrospective study)?

7

The reference standard and its rationale.

8

Technical specifications of material and methods involved including how and when measurements were taken, and/or cite references for index tests and reference standard

9

Definition of and rationale for the units, cut-offs and/or categories of the results of the index tests and the reference standard

10

The number, training and expertise of the persons executing and reading the index tests and the reference standard

11

Whether or not the readers of the index tests and reference standard were blind (masked) to the results of the other test and describe any other clinical information available to the readers

METHODS Participants

Test methods

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

84

(Continued)

Statistical methods

12

Methods for calculating or comparing measures of diagnostic accuracy, and the statistical methods used to quantify uncertainty (e.g. 95% confidence intervals)

13

Methods for calculating test reproducibility, if done.

14

When study was performed, including beginning and end dates of recruitment

15

Clinical and demographic characteristics of the study population (at least information on age, gender, spectrum of presenting symptoms)

16

The number of participants satisfying the criteria for inclusion who did or did not undergo the index tests and/or the reference standard; describe why participants failed to undergo either test (a flow diagram is strongly recommended)

17

Time-interval between the index tests and the reference standard, and any treatment administered in between

18

Distribution of severity of disease (define criteria) in those with the target condition; other diagnoses in participants without the target condition

19

A cross tabulation of the results of the index tests (including indeterminate and missing results) by the results of the reference standard; for continuous results, the distribution of the test results by the results of the reference standard

20

Any adverse events from performing the index tests or the reference standard

21

Estimates of diagnostic accuracy and measures of statistical uncertainty (e.g. 95% confidence intervals)

22

How indeterminate results, missing data and outliers of the index tests were handled

23

Estimates of variability of diagnostic accuracy between subgroups of participants, readers or centres, if done

24

Estimates of test reproducibility, if done.

25

Discuss the clinical applicability of the study findings.

RESULTS Participants

Test results

Estimates

DISCUSSION

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

85

Appendix 8. Assessment of methodological quality table QUADAS-2 tool

DOMAIN

PATIENT SELECTION

INDEX TEST

REFERENCE STANDARD

FLOW AND TIMING

Description

Describe methods of pa- Describe the index test tient selection: Describe and how it was conincluded patients (prior ducted and interpreted: testing, presentation, intended use of index test and setting):

Describe the reference standard and how it was conducted and interpreted:

Describe any patients who did not receive the index test(s) and/or reference standard or who were excluded from the 2x2 table (refer to flow diagram): Describe the time interval and any interventions between index test(s) and reference standard:

Signalling questions (yes/no/unclear)

Was a consecutive or ran- Were the index test re- Is the reference standard dom sample of patients sults interpreted without likely to correctly classify enrolled? knowledge of the results the target condition? of the reference standard?

Was there an appropriate interval between index test(s) and reference standard?

Was a case-control de- If a threshold was used, Were the reference stansign avoided? was it pre-specified? dard results interpreted without knowledge of the results of the index Did the study avoid intest? appropriate exclusions?

Did all patients receive a reference standard? Did all patients receive the same reference standard? Were all patients included in the analysis?

Risk of bias: High/low/ Could the selection of Could the conduct or inunclear patients have introduced terpretation of the inbias? dex test have introduced bias?

Could the reference stan- Could the patient flow dard, its conduct, or its have introduced bias? interpretation have introduced bias?

Concerns regarding Are there concerns that applicability: High/low/ the included patients do unclear not match the review question?

Are there concerns that the target condition as defined by the reference standard does not match the review question?

Are there concerns that the index test, its conduct, or interpretation differ from the review question?

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

86

Appendix 9. Anchoring statements for quality assessment of IQCODE diagnostic studies We provide some core anchoring statements for quality assessment of diagnostic test accuracy reviews of IQCODE in dementia. These statements are designed for use with the QUADAS-2 tool and were derived during a two-day, multidisciplinary focus group. During the focus group and the piloting/validation of this guidance, it was clear that certain issues were key to assessing quality, while other issues were important to record but less important for assessing overall quality. To assist, we describe a ’weighting’ system. Where an item is weighted ’high risk’ then that section of the QUADAS-2 results table is likely to be scored as high risk of bias. For example, in dementia diagnostic test accuracy studies, ensuring that clinicians performing dementia assessment are blinded to results of index test is fundamental. If this blinding was not present then the item on reference standard should be scored ’high risk of bias’, regardless of the other contributory elements. In assessing individual items, the score of unclear should only be given if there is genuine uncertainty. In these situations review authors will contact the relevant study teams for additional information. Anchoring statements to assist with assessment for risk of bias Patient selection Was a case-control or similar design avoided? Designs similar to case control that may introduce bias are those designs where the study team deliberately increase or decrease the proportion of patients with the target condition. For example, a population study may be enriched with extra dementia patients from a secondary care setting. Such studies will be automatically labelled high risk of balance and will be assessed as a potential source of heterogeneity. Weighting: High risk of bias We did not include papers with case-control or “enriched” populations. Was the sampling method appropriate? Where sampling is used, the designs least likely to cause bias are consecutive sampling or random sampling. Sampling that is based on volunteers or selecting participants from a clinic or research resource is prone to bias. Weighting: High risk of bias Are exclusion criteria described and appropriate? The study will be automatically graded as unclear if exclusions are not detailed (pending contact with study authors). Where exclusions are detailed, the study will be graded as “low risk” if exclusions are felt to be appropriate by the review authors. Certain exclusions common to many studies of dementia are: medical instability; terminal disease; alcohol/substance misuse; concomitant psychiatric diagnosis; other neurodegenerative condition. For a community sample we would expect relatively few exclusions. Post hoc exclusions will be labelled “high risk” of bias. Weighting: Low risk Index Test Was IQCODE assessment performed without knowledge of clinical dementia diagnosis? Terms such as “blinded” or “independently and without knowledge of ” are sufficient and full details of the blinding procedure are not required. This item may be scored as “low risk” if explicitly described or if there is a clear temporal pattern to order of testing that precludes the need for formal blinding i.e. all IQCODE assessments performed before dementia assessment. Weighting: High risk Were IQCODE thresholds pre-specified? For scales there is often a reference point (in units or categories) above which participants are classified as “test positive”; this may be referred to as threshold; clinical cut-off or dichotomisation point. A study is classified high risk of bias if the authors define the optimal cut-off post-hoc based on their own study data. Certain papers may use an alternative methodology for analysis that does not use thresholds and these papers should be classified as not applicable. Weighting: Low risk Were sufficient data on IQCODE application given for the test to be repeated in an independent study? Particular points of interest for IQCODE include method of administration (for example, self-completed questionnaire versus direct questioning interview); nature of informant; language of assessment. If a novel form of IQCODE is used, details of the scale should be included or a reference given to an appropriate descriptive text. Where IQCODE is used in a novel manner, for example, a translated questionnaire, there should be evidence of validation. Weighting: Low risk Reference Standard Is the assessment used for clinical diagnosis of dementia acceptable? Commonly used international criteria to assist with clinical diagnosis of dementia include those detailed in DSM-IV and ICD-10. Criteria specific to dementia subtypes include but are not limited to NINCDS-ADRDA criteria for Alzheimer’s dementia; McKeith criteria for Lewy Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

87

Body dementia; Lund criteria for frontotemporal dementias; and the NINDS-AIREN criteria for vascular dementia. Where the criteria used for assessment is not familiar to the review authors and the Cochrane Dementia and Cognitive Improvement group this item should be classified as “high risk of bias”. Weighting: High risk Was clinical assessment for dementia performed without knowledge of IQCODE? Terms such as “blinded” or “independent” are sufficient and full details of the blinding procedure are not required. This may be scored as “low risk” if explicitly described or if there is a clear temporal pattern to order of testing i.e. all dementia assessments performed before IQCODE testing. Informant rating scales and direct cognitive tests present certain problems. It is accepted that informant interview and cognitive testing is a usual component of clinical assessment for dementia, however, specific use of the scale under review in the clinical dementia assessment should be scored as high risk of bias. We have pre-specified that dementia diagnosis that explicitly uses IQCODEwill be classified as high risk of bias. Weighting: High risk Were sufficient data on dementia assessment method given for the assessment to be repeated in an independent study? The criteria used for clinical assessment are discussed in another item. Particular points of interest for dementia assessment include the background of the assessor, training/expertise of the assessor; additional information available to inform diagnosis (neuroimaging; neuropsychological testing). Weighting: Low risk Patient flow Was there an appropriate interval between IQCODE and clinical dementia assessment. For a cross-sectional study design, there is potential for the patient to change between assessments. The ideal would be same day assessment. We have set an arbitrary maximum interval of one month between tests, although this may be revised depending on the test and the stability of the condition of interest. Weighting: High Did all patients get the same assessment for dementia regardless of IQCODE result? There may be scenarios where only those patients who score “test positive” on IQCODE have a more detailed assessment. Where dementia assessment (or other reference standard) differs between patients this should be classified as high risk of bias. Weighting: High risk Were all patients who received IQCODE assessment included in the final analysis? If dropouts these should be accounted for; a maximum proportion of drop outs to remain low risk of bias has been specified as 20%. Weighting: Low risk Were missing IQCODE results or un-interpretable IQCODE results reported? Where missing results are reported if there is substantial attrition (we have set an arbitrary value of 50% missing data) this should be scored as high risk of bias. Weighting: Low risk Applicability Were included patients representative of the general population of interest? The included patients should match the intended population as described in the review question. If not already specified in the review inclusion criteria, setting will be particularly important - the review authors should consider population in terms of symptoms; pre-testing; potential disease prevalence. Studies that use very selected patients or subgroups will be classified as poor applicability. Was IQCODE performed consistently and in a manner similar to its use in clinical practice? IQCODE studies will be judged against the original description of its use. Was clinical diagnosis of dementia (or other reference standard) made in a manner similar to current clinical practice? For many reviews, inclusion criteria and assessment for risk of bias will already have assessed the dementia diagnosis. For certain reviews an applicability statement relating to reference standard may not be applicable. There is the possibility that a form of dementia assessment, although valid, may diagnose a far larger proportion of patients with disease than usual clinical practice. In this instance the item should be rated poor applicability.

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

88

Appendix 10. STARD (reporting quality) results

Methods Au- Tithor tle

Intro

Results

Participants

Test methods

Statistics

Participants

Estimates Discussion

Item Item Item Item Item Item Item Item Item Item Item Item Item Item Item Item Item Item Item Item Item 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 21 22 23 24 25 no

yes

yes

yes

yes

Fuh 1995 no

no

yes

yes

yes

un- yes clear

yes

yes

yes

yes

yes

no

no

yes

no

yes

yes

no

no

partially no

yes

yes

yes

Jorm 1994

yes

yes

yes

yes

partially

yes

yes

yes

no

no

no

yes

no partially

yes

no

partially

no

no

no

yes

no

no

no

yes

no

no

yes

yes

no

no

no

yes

par- partially tially

partially

yes Kathriarachchi

yes par- partially tially

yes

Jorm 1996

yes

yes

yes

no

yes

no

no

par- partially tially no

partially

par- partially tially

yes

yes

un- yes par- par- par- clear tially tially tially

yes

yes

yes

no

no

no

unyes par- par- clear par- partially tially tially tially

no

yes

no Mackinnon 2003

yes

yes

un- yes clear

yes

yes

yes

no

yes

no

no

yes Morales 1995

yes

yes

yes

no Morales 1997

no

Law 1995

yes yes Senanorong 2001

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

no

no

no

yes

no

no

no

yes

no

no

no

yes

no

yes

par- partially tially

yes

un- yes clear

yes

yes

yes

yes

yes

no

no

yes

yes partially

yes

no

no

no

no partially

un- no clear

yes

un- yes clear

yes par- partially tially

yes

yes

no

no

yes

no

no partially

partially

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

89

(Continued)

yes Srikanth 2006

yes

yes

yes

yes

yes

yes

yes

yes

yes

no

yes

no

yes

yes

yes

yes

no

yes

no

yes

Appendix 11. Heterogeneity in use of IQCODE

26 item English

2 studies

French

1 study

Japanese

1 study

Sinhalese

1 study

Spanish

2 studies

Thai

17 item

16 item

10 item

3 item

1 study

1 study

2 item

4 studies

1 study 1 study

Only 26-item and 16-item IQCODE data were included in the pooled analyses Some studies used more than one IQCODE

CONTRIBUTIONS OF AUTHORS ANS assisted with search terms and translation; TJQ and PF drafted the protocol, performed data extraction and quality assessment; CY assisted with data handling; RMcS and DJS provided support and contributed to manuscript content.

DECLARATIONS OF INTEREST The review authors have no declarations specific to the review.

SOURCES OF SUPPORT

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

90

Internal sources • No sources of support supplied

External sources • RCPSG Travelling Fellowship, UK. Dr Quinn spent a period working directly with the Cochrane Group; this was supported by a RCPSG travelling fellowship. • Graham Wilson Travelling Scholarship, UK. Dr Quinn’s travel and accomodation to allow training in review methodology and analysis was supported by a Graham Wilson Travelling Scholarship.

DIFFERENCES BETWEEN PROTOCOL AND REVIEW All differences between the protocol and review are described in the main body of the text. A priori we had planned a number of covariate and sensitivity analyses, however the data set was limited in numbers of studies and studies were too heterogenous to allow all of our planned analyses. We had originally planned to review the test accuracy of the 16 and 26-item IQCODE separately, however given the modest number of studies and a comparative analysis suggesting no systematic difference between the two IQCODE formats we used pooled data for our primary analysis.

INDEX TERMS Medical Subject Headings (MeSH) ∗

Independent Living; ∗ Proxy; Dementia [∗ diagnosis]; Surveys and Questionnaires [∗ standards]

MeSH check words Aged; Aged, 80 and over; Humans

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

91

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations.

Various tools exist for initial assessment of possible dementia with no consensus on the optimal assessment method. Instruments that use collateral so...
932KB Sizes 2 Downloads 3 Views