Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the detection of dementia within a general practice (primary care) setting

Abstract

Background

The IQCODE (Informant Questionnaire for Cognitive Decline in the Elderly) is a commonly used questionnaire based tool that uses collateral information to assess for cognitive decline and dementia. Brief tools that can be used for dementia "screening" or "triage" may have particular utility in primary care / general practice healthcare settings but only if they have suitable test accuracy.

A synthesis of the available data regarding IQCODE accuracy in a primary care setting should help inform cognitive assessment strategies for clinical practice; research and policy.

Objectives

To determine the accuracy of the informant‐based questionnaire IQCODE, for detection of dementia in a primary care setting.

Search methods

A search was performed in the following sources on the 28th of January 2013: ALOIS (Cochrane Dementia and Cognitive Improvement Group), MEDLINE (Ovid SP), EMBASE (Ovid SP), PsycINFO (Ovid SP), BIOSIS (Ovid SP), ISI Web of Science and Conference Proceedings (ISI Web of Knowledge), CINHAL (EBSCOhost) and LILACs (BIREME). We also searched sources specific to diagnostic test accuracy: MEDION (Universities of Maastricht and Leuven); DARE (York University); HTA Database (Health Technology Assessments Database via The Cochrane Library) and ARIF (Birmingham University). We developed a sensitive search strategy; search terms were designed to cover key concepts using several different approaches run in parallel and included terms relating to cognitive tests, cognitive screening and dementia. We used standardized database subject headings such as MeSH terms (in MEDLINE) and other standardized headings (controlled vocabulary) in other databases, as appropriate.

Selection criteria

We selected those studies performed in primary care settings, which included (not necessarily exclusively) IQCODE to assess for the presence of dementia and where dementia diagnosis was confirmed with clinical assessment. For the "primary care" setting, we included those healthcare settings where unselected patients, present for initial, non‐specialist assessment of memory or non‐memory related symptoms; often with a view to onward referral for more definitive assessment.

Data collection and analysis

We screened all titles generated by 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. Quality assessment (risk of bias and applicability) was determined using the QUADAS‐2 tool. Reporting quality was determined using the STARDdem extension to the STARD tool.

Main results

From 71 papers describing IQCODE test accuracy, we included 1 paper, representing data from 230 individuals (n=16 [7%] with dementia). The paper described those patients consulting a primary care service who self‐identified as Japanese‐American. Dementia diagnosis was made using Benson & Cummings criteria and the IQCODE was recorded as part of a longer interview with the informant.

IQCODE accuracy was assessed at various test thresholds, with a "trade‐off" between sensitivity and specificity across these cutpoints. At an IQCODE threshold of 3.2 sensitivity: 100%, specificity: 76%; for IQCODE 3.7 sensitivity: 75%, specificity: 98%.

Applying the QUADAS‐2 assessments, the study was at high risk of bias in all categories. In particular degree of blinding was unclear and not all participants were included in the final analysis.

Authors' conclusions

It is not possible to give definitive guidance on the test accuracy of IQCODE for the diagnosis of dementia in a primary care setting based on the single study identified. We are surprised by the lack of research using the IQCODE in primary care as this is, arguably, the most appropriate setting for targeted case finding of those with undiagnosed dementia in order to maximise opportunities to intervene and provide support for the individual and their carers.

Plain language summary

A structured interview for assessing change in memory and other thinking skills (the IQCODE) for assessment of possible dementia

Numbers of people with dementia and other memory and thinking 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 memory or other thinking skills. Various methods for this "collateral" interview are available and the most commonly used is called 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 detecting dementia. We found only one study that tested diagnostic accuracy of IQCODE in a primary care/general practice setting. The study was of a select population (Japanese Americans) and the results may not be applicable to patients in other countries. We also noted issues in the study methods used and the reported results. Based on this single study we are unable to give guidance on how well IQCODE may function as a dementia assessment in primary care. More research is needed in this area as many patients with memory or thinking problems will first consult their general practitioner / family doctor.

Background

Dementia is a chronic, progressive, neurodegenerative syndrome that is a substantial and growing public health concern (Ferri 2005; Hebert 2013; Hebert 2003; Prince 2013). Depending on case definition employed, contemporary estimates of dementia prevalence in the United States are in the range 2.5 to 4.5 million individuals. Dementia is predominantly a disease of older adults, with a 10% prevalence in adults aged over 65, increasing to around 30% in adults aged over 85 (Ferri 2005). Changes in population demographics will be accompanied by increases in dementia incidence and prevalence. Consensus opinion based on current epidemiological trends is of a doubling in dementia prevalence every 20 years, with global prevalence of around 81 million cases by 2040. Dementia is not limited to 'Western' nations and an increasing prevalence is particularly marked in countries such as China and India (Ferri 2005).

A key element of effective management in dementia is a firm diagnosis. Recent guidelines place emphasis on early diagnosis to facilitate improved management and to allow informed discussions and planning with patients and carers.(Cordell 2013) 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 (neuropsychology, neuroimaging, or other biomarkers) for all. Such an approach is not feasible in a primary‐care setting where the population requiring assessment will be large and the prevalence of disease will be low relative to 'specialist' settings.

In practice a two‐stage process is often employed, with initial screening or 'triage' assessments, suitable for use by non‐specialists, used to select those people who require further detailed assessment (Boustani 2003). Various tools for initial cognitive screening have been described (Brodaty 2002; Folstein 1975; Galvin 2005). Regardless of the methods employed, there is scope for improvement, with observational work suggesting that many people with dementia are not diagnosed (Chodosh 2004; Valcour 2000). 

Dementia screening assessments often take the form of brief, direct cognitive testing. Such an approach will 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, and so an attractive approach is to question collateral sources with sufficient knowledge of the patient. Informant‐based interviews have been described that aim to retrospectively assess change in function. An instrument prevalent in research and clinical practice is the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) and this was the focus of our review (Jorm 1988). A number of properties can be described for a clinical assessment (reliability, responsiveness, feasibility); for our purposes the test property of greatest interest is diagnostic test accuracy (DTA).

In certain countries screening assessments of older adults have been proposed and informant interviews such as IQCODE have been suggested as a possible screening tool. This opportunistic "case finding" may be better suited to primary care than hospital settings. In this regard an informant based approach may be particularly suited to primary care, where practitioners often have continuity of care over lengthy periods and provide healthcare to families / carers. A synthesis of studies describing the test accuracy of IQCODE when used in unselected older adults is available and suggests that IQCODE may have some utility in this setting.(Quinn 2014) These results should not be extrapolated to primary care. We should not assume that IQCODE will have favourable accuracy in primary care, and so we aimed to give a comprehensive, critical review of the available literature.

Target condition being diagnosed

The target condition for this diagnostic test accuracy review is all‐cause 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 described, for example, pharmacotherapy (acetylcholinesterase inhibitors; memantine) or cognitive rehabilitation therapies (Birks 2006; Bahar‐Fuchs 2013; McShane 2006).

Dementia remains a clinical diagnosis, based on history from the patient and suitable collateral sources and direct examination including cognitive assessment. We have chosen expert clinical diagnosis as our 'gold standard' (reference standard) for describing IQCODE properties, as we believe this is most in keeping with current diagnostic criteria and best practice. We recognise that there is no universally accepted, ante‐mortem, gold standard diagnostic strategy. Although some would argue that the true gold standard would be neuropathological data, for the purpose of testing diagnostic accuracy in primary care, limiting analysis to those studies with neuropathologically confirmed diagnosis is likely to yield limited and highly selected data. We also recognise that clinical‐neuropathological correlations are less apparent in mixed dementia and older people, who form the majority with dementia in the community (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/quantitative neuroimaging have shown promise but to date are not accepted or validated as independent diagnostic tests (McKhann 2011). Here a distinction must be made between dementia diagnosis in clinical practice and dementia diagnosis for clinical research. These novel biomarker and imaging techniques do not currently have a role in primary‐care assessment.

The label of dementia encompasses varying pathologies, of which Alzheimer’s disease is the most common. For our reference standard of clinical diagnosis, we accepted 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 American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders (DSM) for all‐cause dementia and subtypes (Appendix 1) and the various diagnostic criteria available for specific dementia subtypes, i.e. NINCDS‐ADRDA (National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association) criteria for Alzheimer’s dementia (McKhann 1984); McKeith criteria for Lewy Body dementia (McKeith 2005); Lund criteria for frontotemporal dementias (McKhann 2001); and the NINDS‐AIREN (National Institute of Neurological Disorders and Stroke and the Association Internationale pour la Recherche et l'Enseignement en Neurosciences) criteria for vascular dementia (Roman 1993; Erkinjuntti 2000). We have not defined preferred diagnostic criteria for rarer forms of dementia (e.g. alcohol‐related; HIV‐related; prion disease‐related), which was considered under our rubric of 'all‐cause dementia' and was not be considered separately.

The label 'dementia' can also span a range of disease severities, from mild disease to end‐stage. We recognise that the diagnostic properties of a tool such as IQCODE vary depending on disease stage; for example, a patient is more likely to "screen" positive when disease is advanced and diagnosis is clear. For our primary analysis we included any dementia diagnosis at any stage of disease. Definitions pertinent to various stages of the dementia 'journey' are also described: a preclinical stage occurring years before disease is manifest, which may be characterised by changes in one or more disease biomarkers (Sperling 2011); a stage of mild cognitive impairment (MCI) where problems with cognition are noticed by the patient or others but the disease is not sufficiently advanced to warrant a diagnostic label of dementia (Albert 2011); and finally established dementia as defined above (McKhann 2011). Diagnoses of the preclinical and MCI states were not be included in this review. 

Index test(s)

Our index test was the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) (Jorm 1988).

The IQCODE was originally described as a 26‐item informant questionnaire that seeks to retrospectively ascertain change in cognitive and functional performance over a 10‐year time period (Jorm 1988). IQCODE is designed as a brief screen 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). A literature describing the properties of IQCODE is available including studies of non‐English IQCODE translations; studies in specific patient populations; and modifications to the original 26‐item direct informant interview (Isella 2002: Jorm 1989; Jorm 2004). Versions of the IQCODE have been produced in other languages, including Chinese, Dutch, Finnish, French, Canadian French, German, Italian, Japanese, Korean, Norwegian, Polish, Spanish and Thai (www.anu.edu.au/iqcode/). A shortened 16‐item version is also available; this modified IQCODE is common in clinical practice and has been recommended as the preferred IQCODE format (Jorm 2004). For this review the term 'IQCODE' refers to the original 26‐item questionnaire as described by Jorm 1988. Other versions of IQCODE were described according to the number of items and administration language (e.g. a 16‐item IQCODE for Spanish speakers was described as 'IQCODE‐16 Spanish').

Although we describe the utility of IQCODE for dementia diagnosis, IQCODE used in isolation is not suitable for establishing a clinical diagnosis. The value of IQCODE is in selecting people who require more definitive assessment, and is thus particularly suited as a screening tool for primary care. New diagnostic criteria for dementia make explicit reference to documenting decline and involving collateral informants, emphasising the potential utility of an informant interview tool such as IQCODE. 

The full 26‐ and 16‐item versions of IQCODE with scoring rules are available in Appendix 2 and Appendix 3.

The purpose of this review is to describe the diagnostic test accuracy of IQCODE. Other important psychometric properties for a tool that is to be used in clinical practice include reliability, responsiveness and acceptability. Contemporary reviews of the 26‐ and 16‐item IQCODE suggest good inter‐rater reliability with retest kappa 0.96 at three days and 0.75 at one year (Jorm 1988; Tang 2003). Internal consistency is uniformly high with Cronbach’s alpha in the range 0.93 to 0.97 (Jorm 1989). Validation work has included validation against measures of cognitive change; neuropathology; neuroimaging; and neuropsychological assessment (Cordoliani‐Mackowiak 2003; Jorm 2000; Jorm 2004; Rockwood 1998). Factor analysis suggests that the scale measures a common factor of cognitive decline (http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD010079/full#CD010079‐bbs2‐0025#CD010079‐bbs2‐0025). There are fewer published data on the psychometric properties of other 'short' forms of IQCODE.

IQCODE cut‐off scores suggestive of a potential dementia diagnosis will vary with the demographics of the population tested. In the original development and validation work, normative data were described, with a total score above 93 or an average score above 3.31 indicative of cognitive impairment (Jorm 2004). There is no consensus on the optimal threshold, and various authors have described improved diagnostic accuracy with other cut‐offs. In setting thresholds for any diagnostic test there is a trade‐off between sensitivity and specificity, with the preferred values partly determined by the purpose of the test. For primary care, in a population with ready access to specialist memory services, a more sensitive test may be preferred to ensure all possible cases are appropriately referred. Where diagnostic services are less available, a more specific test may be needed to prevent services from becoming overburdened.

IQCODE has a number of features that make it attractive for clinical and research use, particularly in a primary‐care setting. The questions 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). There are data to suggest that, compared to standard direct assessments, IQCODE may be less prone to bias from cultural norms and previous level of education (Jorm 2004).  

Clinical pathway

Alternative test(s)

Several other dementia screening and assessment tools have been described. Instruments commonly used in primary‐care settings include Folstein’s mini‐mental state examination (MMSE); Montreal cognitive assessment (MoCA); and the MiniCog (Burns 2004; Folstein 1975; Holsinger 2007). Tools specific to primary care have been described, for example, the MiniCog (Brodaty 2002). These performance‐based measures for cognitive screening all rely on comparing single‐ or multi‐domain cognitive testing against population‐specific normative data. Copyright issues may preclude widespread use of certain tools.

Other informant interviews are also available. For example, the AD‐8 is an eight‐question tool, requiring dichotomous responses (yes or no) and testing for perceived change in memory, problem‐solving, orientation and daily activities (Galvin 2005). 

For this review we focussed on papers that describe IQCODE diagnostic properties, and did not consider other cognitive screening/assessment tools.  Where a paper described IQCODE with an in‐study comparison against another screening tool, we included the IQCODE data only. Where IQCODE was used in combination with another cognitive screening tool, we included the IQCODE data only.

Rationale

There is no consensus on the optimal screening test for dementia and the choice 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 screening 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. This is particularly pertinent to primary care, as healthcare systems increasingly favour greater primary care involvement in screening and assessment of cognitive problems (Menon 2011). 

This review is part of a series of three reviews, assessing the diagnostic accuracy of IQCODE in primary care, secondary care and community settings. In a primary care setting, individuals are self‐selecting and present either with subjective memory complaints or for another reason, this is distinct from those studies conducted in a community setting where the population are unselected and provide a closer approximation of a screening programme or epidemiological study. The performance of IQCODE in each setting has potential implications for dementia case‐finding and wider health policy.

IQCODE is commonly used in practice and research; it is used Internationally and is one of only a few validated informant‐based screening/diagnostic tools. A literature describing test accuracy of IQCODE in different settings is available, although some of these studies have been modest in size. Thus systematic review and, if possible, meta‐analysis of the diagnostic properties of IQCODE is warranted. 

This review forms part of a body of work describing the diagnostic properties of commonly‐used dementia tools. The Cochrane Dementia and Cognitive Improvement Group have reviews planned or underway for IQCODE in other settings and for other commonly‐employed dementia assessment scales (Appendix 4). At present we are conducting a single‐test review and meta‐analysis. The intention, however, is then to collate these data, performing an overview allowing comparison of various test strategies.

Objectives

To determine the accuracy of the informant‐based questionnaire IQCODE, for detection of dementia in a primary care setting.

Secondary objectives

Where data were available we planned to describe the following:

1. The diagnostic accuracy of IQCODE at various prespecified thresholds. We recognise that various thresholds or cut‐off scores have been used to define IQCODE screen‐positive states. We described the properties of IQCODE for the following cut‐off scores (rounded where necessary): 3.6; 3.5; 3.4; 3.3. These thresholds have been chosen to represent the range of cut‐offs that are commonly used in practice and research; we have been inclusive in our choice of cut‐off to maximise available data for review.

2. Accuracy of IQCODE for diagnosis of the commonest specific dementia subtype ‐ Alzheimer’s dementia.

3. Effects of heterogeneity on the reported diagnostic accuracy of IQCODE. Potential sources of heterogeneity that we aimed to explore included: age of cohort; case mix of cohort; reason for primary‐care consultation; technical features of IQCODE; method of dementia diagnosis.

Methods

Criteria for considering studies for this review

Types of studies

This review forms part of a suite of reviews describing IQCODE accuracy in various healthcare settings. We created a generic strategy for searching; selection; data extraction and analysis that would be applicable to all the proposed IQCODE reviews. For consistency with the other reviews we have used the same text description in each, except where the methodology is specific to the setting of interest. In this primary care review we found only one relevant study, however the generic text describing our approach may talk of "papers" and "studies".

We aimed to include all studies concerned with primary‐care screening that described the properties of IQCODE for diagnosis at a single time point in a population robustly and independently assessed for the presence of dementia. This implies that the index and reference were performed contemporaneously.

An alternative approach is to perform the index test and then prospectively follow patients for development of the condition of interest defined using the reference standard. This 'delayed verification' of dementia methodology is best suited to studies describing the progression of mild cognitive impairment (MCI) to dementia, and was not considered in this review.

Case‐control studies are known to potentially overestimate properties of a test, and we did not include such studies. Similarly we excluded case studies and samples with small numbers (for the purposes of this review, we defined "small" numbers as less than 10 participants). Small samples were excluded due to the potential for bias in selection and lack of representativeness.

Where settings were mixed, for example, a population study 'enriched' with additional non‐primary care cases we did not consider such studies unless separate data were presented for participants from each setting. This design suffers from similar biases to a case control design.

Participants

All adults (aged over 18 years) presenting to primary care were eligible.

Our definition of primary care was those setting where participants have self‐referred either due to perceived memory problems or to another medical complaint; they will not often have had previous extensive cognitive testing. We anticipated that studies would largely be of community‐dwelling adults; this cohort is itself heterogeneous and may include a spectrum from functionally independent working adults through to frail care‐home residents. There were no predefined exclusion criteria relating to the case‐mix of the population studied, but this aspect of the study was considered as part of our assessment of heterogeneity. Where there were concerns that the participants were not representative of a primary‐care sample we explored this at study level using the 'Risk of bias' assessment framework outlined below.

Index tests

Studies had to include (not necessarily exclusively) IQCODE used as an informant questionnaire.

IQCODE has been translated into various languages to allow international administration (Isella 2002). 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 principal 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 versions of IQCODE, but present separate analysis limited to the commonest 26‐ and 16‐item versions. A modified IQCODE for self‐assessment has been described (Cullen 2007). As our interest was informant interviews, self‐assessment IQCODE was not included in the review.

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. Clinical diagnosis included all‐cause (unspecified) dementia, using any recognised diagnostic criteria (for example, International Classification of Diseases Edition 10 (ICD‐10); Diagnostic and Statistical Manual of Mental Disorders Edition 4 (DSM‐IV)). Dementia diagnosis may specify a pathological subtype and all dementia subtypes were included, (examples McKeith 2005; McKhann 1984; McKhann 2001; Roman 1993). Clinicians may use imaging, pathology or other data to aid diagnosis; however, we did not include diagnosis based only on these data without corresponding clinical assessment. 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 (e.g. individual clinician versus algorithm versus consensus determination). We set no 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/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 papers. 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 primary care focus.

Electronic searches

We searched ALOIS, the specialised register of the Cochrane Dementia and Cognitive Improvement Group (which includes both intervention and diagnostic accuracy studies), MEDLINE (Ovid SP), EMBASE (Ovid SP), PsycINFO (Ovid SP), BIOSIS (Ovid SP), 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 run. The final search date was 28 January 2013.

We also searched sources specific to diagnostic accuracy and healthcare research 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).

We applied no language or date restrictions to the electronic searches. Translation services were used as necessary.

Initial screening of the search results were performed by a single researcher from the Cochrane Dementia and Cognitive Impairment Group, with extensive experience of systematic reviewing (ANS). All subsequent searches of titles/abstracts/papers were performed by independent paired assessors (TQ,PF).

Searching other resources

Grey literature: "Grey" literature was identified through searching of conference proceedings and theses or PhD abstracts.
Handsearching: We did not perform handsearching. The evidence of the benefits of handsearching are not well defined and we note a study specific to diagnostic accuracy studies suggested little additional benefit of hand searching above a robust initial search strategy (Glanville 2010).
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 IQCODE for dementia diagnosis, informed by results of the initial search.
Relevant studies were searched for in PubMed to search for additional studies using the 'related article' feature. Key studies were examined in the citation databases of Science Citation Index and Scopus to ascertain any further relevant studies.

Data collection and analysis

Selection of studies

One review author (ANS) screened all titles generated by initial electronic database searches for relevance. The initial search was a sensitive, generic search, designed to include all potential dementia screening tools. Titles potentially relevant to IQCODE were selected by two reviewers (ANS, TQ). All further review and selection was performed by two independent researchers (TQ, PF). The potential IQCODE related titles were reviewed and all eligible studies assessed as abstracts, potentially relevant studies were assessed as full manuscripts against inclusion criteria. Disagreement was resolved by discussion, with potential to involve a third author (DJS) as arbitrator as necessary.

We adopted a hierarchical approach to exclusion, first excluding 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 include useable data but these were not described in the published manuscript; or the data as presented could not be extracted to a standard two by two table, we contacted the authors directly to request further information or source data. If authors did not respond or if the required data were not available we did not include the study (labelled as "data not suitable for analysis" on flowchart). 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/demographic details of the participants; details of IQCODE administration and details of the dementia diagnosis process. Data extraction was performed for all IQCODE studies, before dividing them by setting (primary, secondary or community). The pro forma was piloted against two of the included papers before use.

Where IQCODE data were given for a number of cut‐off points, we extracted data for each IQCODE threshold. Where thresholds were described to two decimal places, we chose the cutpoint closest to the point of interest (i.e. 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 others 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 potential to involve a third author (DJS) as arbitrator if necessary.

For each included paper, the flow of patients (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 Standards for the Reporting of Diagnostic accuracy studies (STARD) checklist (Bossuyt 2003) (Appendix 7). We were permitted pre‐publication access to the dementia specific extension to complement STARD (STARDdem; http://starddem.org/) (Appendix 8). This enabled application of STARD and STARDdem items to the identified studies.

We assessed methodological quality of each study using the Quality Assessment tool for Diagnostic Accuracy Studies (QUADAS‐2) tool (http://www.bris.ac.uk/quadas/quadas‐2 Appendix 9). 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 9. 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 (Davis 2013) (Appendix 10).

Both assessments were performed by paired independent raters (TQ, JKH), 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 studies that found high/low/unclear risk of bias/concerns regarding applicability with corresponding graphical display.

Statistical analysis and data synthesis

We were principally interested in the test accuracy of IQCODE for the dichotomous variable "dementia"/"no dementia". Thus, we applied the current DTA framework for analysis of a single test and fit the data extracted to a standard "two by two" data table showing binary test results cross‐classified with binary reference standard. This process was repeated for each IQCODE threshold score described.

We used RevMan 5.1 (RevMan 2011) to calculate sensitivity, specificity and their 95% confidence intervals (CIs) from the two by two tables abstracted from the included studies.

Where data allowed we planned summary analyses using forest plots to allow basic visual inspection of individual studies and using bivariate or HSROC methods to calculate summary accuracy values.

Investigations of heterogeneity

Heterogeneity is expected in diagnostic test accuracy reviews and we did not perform formal analysis to quantify heterogeneity.

The properties of a tool describe behaviour of the instrument under particular circumstances. Thus, for our assessment of potential sources of heterogeneity (where data allowed) we collected data to inform two broad pre‐specified areas of interest:

a) Clinical criteria used to reach dementia diagnosis (for example ICD‐10; DSM‐IV) and the methodology used to reach dementia diagnosis (for example, individual assessment; group (consensus) assessment).

b) Format of IQCODE employed (for example traditional IQCODE; 16 item "short" form etc).

Where data allowed we planned to investigate heterogeneity using these factors as co‐variates and comparing results of subgroups.

Sensitivity analyses

Where appropriate (i.e. 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 prespecified sensitivity analysis 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 70 papers (Figure 1). Reasons for exclusions were: population not from a primary care 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 (described in more detail in Selection of studies). (Characteristics of excluded studies).

1.

Study flow diagram.

This review includes 1 study (n=230 participants).

Methodological quality of included studies

We described risk of bias using the QUADAS 2 methodology (Appendix 9). The study was considered at high risk of bias in all four domains of patient selection, index test, reference standard and flow & timing (see below). We found issues with applicability in relation to patient selection and possible issues in relation to the application of clinical dementia diagnosis (Figure 2).

2.

Risk of bias and applicability concerns summary: review authors' judgements about each domain for each included study

Patient selection/sampling

Although the study was based around a sequential inclusion strategy, of 1038 patients attending the primary care centre only 230 were included. Certain exclusions used by the authors, although appropriate for the study, limit the validity of the test accuracy data. For example exclusion on the basis of participation in an observational cognitive study and exclusion on the basis of no telephone access may bias the sample. There were further exclusions on the basis of ethnicity that may impact on external validity, the study population was limited to those self‐identifying as Japanese‐American as this ethnic group was of particular interest to the authors.

IQCODE (index test) application

The IQCODE was performed as one component of a face‐to‐face or telephone interview with the informant. The timing and assessor of IQCODE test was not clear from the published text, we contacted the authors for clarification of methods. They were unable to specify the sequence of events or if any blinding strategies employed. Use of a telephone based IQCODE is not standard practice and it is possible that a telephone administered questionnaire may perform differently to a self‐completed paper questionnaire.

Dementia diagnosis (reference standard) application

The authors described test accuracy of IQCODE against two reference standards, clinical diagnosis of dementia and cognitive impairment. The clinical diagnosis of dementia was made using the Benson and Cummings criteria (Cummings 1986). Although there are published validations of these criteria; this diagnostic classification is not standard practice and was not one of our pre specified list of accepted criteria. The criteria, as originally described, were designed for assessment of Alzheimer’s dementia and the utility for diagnosis of all‐cause dementia is not clear. The description provided by the study authors of the procedure for assessment and application of criteria is limited and it is not clear if this assessment was performed with knowledge of index test results. The reference standard of cognitive impairment was based on low score on the cognitive abilities screening instrument (CASI) but no impairment on the clinical dementia rating scale (CDR). This paradigm is often used to define a state of “cognitive impairment, no dementia”.

Flow and timing

The flow of participants has potential to introduce bias. The time interval between index testing and reference standard application is not clear from the text. Only those completing the cognitive screening and with an informant who could complete the full IQCODE were included in the final analysis and this may bias the test accuracy data reported. No flow diagram of participants is given in the paper to aid interpretation of flow.

Reporting quality

We also found issues with reporting quality. Applying the dementia specific extension to the STARD checklist (Appendix 7); STARDdem (Appendix 8), areas where reporting was suboptimal included choice of cut‐off; training of assessors; description of blinding and handling missing/indeterminate data. (Appendix 11)

Findings

The included study characteristics are described in the Characteristics of included studies and Table 1.

Summary of findings 1. Summary of findings.

Study ID	Country	Subjects (n)	IQCODE version	Language	Dementia diagnosis	Dementia prevalence N (%)	Other assessments
Tokuhara	Hawai'i	230	26 item	English	Benson and Cummings criteria	n=16 (7)	MMSE; CASI; Clock‐Drawing Task; CDR

Abbreviations: MMSE ‐ Mini Mental State Exam; CASI ‐ Cognitive Abilities Screening Instrument; CDR ‐ Clinical Dementia Rating Scale

The total number of participants was 230 of whom 16 (7%) received a clinical diagnosis of dementia and 23 (10%) had cognitive impairment.

The population tested was predominantly an older, female cohort with limited higher education exposure. The authors describe the demographics of informants who were mostly spouses (47%) or sons/daughters (33%). Our pre‐specified assessment of heterogeneity and sensitivity analyses were not possible as only one study was identified for inclusion.

The authors present test accuracy for IQCODE for diagnosing dementia at cut‐off points commonly used in practice (3.2, 3.3, 3.4, 3.5, 3.6 & 3.7). Their results for dementia are presented in Table 2. There is a trade‐off between sensitivity and specificity across the values. The negative predictive value of IQCODE for dementia is consistently high, >90% at all cut‐off points, conferring confidence that a negative result on this initial screen is generally correct. However, the positive predictive value is <50% unless a cut‐off of 3.6 or above is used. This indicates limited clinical utility of a positive result and potential for large numbers of patients with no dementia to be incorrectly referred for specialist assessment.

Summary of findings 2. Summary of findings table.

What is the diagnostic 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	Individuals presenting to primary healthcare providers
Setting	Primary care
Index test	Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE) administered to a relevant informant
Reference Standard	Clinical dementia diagnosis
Studies	Cross‐sectional studies were included, we did not include case‐control studies
Test	Summary accuracy	No. of participants (studies)	Dementia prevalence (%)	Implications, Quality and Comments
IQCODE Cut‐off 3.2	Sensitivity 1.0 Specificity 0.762 PPV 23.9 NPV 100	n=262 (1 study)	n=16 (7)	At the lower cut‐off levels for IQCODE all dementia cases are detected on screening. However if all IQCODE positive patients are referred to memory services, use of the lower cutpoint would necessitate large numbers of individuals without dementia being referred. This has the potential to be harmful as it can cause distress to the individual and their family and is a less judicious use of limited healthcare resources. Using area under ROC curve analyses, the authors suggested an IQCODE cutpoint of 3.35 as giving optimal test properties for diagnosis of cognitive impairment.
IQCODE Cut‐off 3.3	Sensitivity 1.0 Specificity 0.822 PPV 29.6 NPV 100	n=262 (1 study)	n=16 (7)
IQCODE Cut‐off 3.4	Sensitivity 1.0 Specificity 0.874 PPV 37.2 NPV 100	n=262 (1 study)	n=16 (7)
IQCODE Cut‐off 3.5	Sensitivity 0.875 Specificity 0.911 PPV 42.4 NPV 99	n=262 (1 study)	n=16 (7)	At the higher cut‐off value for IQCODE fewer individuals would be referred inappropriately to specialist memory services. However, there are increasing numbers of false negatives, i.e. individuals with dementia not identified as such by the IQCODE and not referred for specialist assessment. Delayed referral to specialist services may miss opportunities for confirming diagnosis and accessing appropriate support, advice and potential treatment.
IQCODE Cut‐off 3.6	Sensitivity 0.813 Specificity 0.963 PPV 61.9 NPV 98.6	n=262 (1 study)	n=16 (7)
IQCODE Cut‐off 3.7	Sensitivity 0.75 Specificity 0.981 PPV 75 NPV 98.1	n=262 (1 study)	n=16 (7)

Abbreviations: PPV ‐ Positive Predictive Value; NPV ‐ Negative Predictive Value

The preferred test properties will vary with the purpose of the test. If sensitivity is low, cases with dementia will be missed on screening. In primary care, it is likely that patients with dementia who are not referred on initial screening will re‐present to healthcare services and diagnosis will eventually be made. If specificity is low, patients with no dementia may be initially misdiagnosed, although the diagnostic label will be reconsidered if they are referred on to specialist services.

To illustrate the study findings in context:

Assuming that an average‐sized UK GP Practice has around 6500 patients, of whom around 1000 will be over 65, with a dementia prevalence of 6.6% in this age group. If IQCODE alone were used to opportunistically screen all over patients over 65 in the practice. then applying an IQCODE cut‐off of 3.2 would result in 276 individuals being referred for specialist assessment. Of these, 66 will have dementia, however 210 will be referred inappropriately (false positives). This approach would result in no cases of dementia being missed. If the IQCODE cut‐off was raised to 3.7, only 66 individuals would be referred for specialist assessment. Of these, 50 will have dementia, however 16 would be referred inappropriately (false positives) and 16 individuals with dementia would not be identified and referred for specialist review (false negatives).

Discussion

Summary of main results

We sought to describe the test accuracy of the IQCODE informant based questionnaire for diagnosis of dementia. We found only one relevant study. The study describes IQCODE for assessment of dementia and cognitive impairment in a specific ethnic population. (Table 1)

Strengths and weaknesses of the review

Strengths and weakness of the included study

The single included study gave a comprehensive description of the population tested and the informants who provided IQCODE scores. The authors present a variety of analyses to describe test accuracy.

There were issues with study methodology and reporting that limit the internal and external validity of the data presented. Biases may have been introduced by patient exclusions and through the authors' application of IQCODE and dementia assessment. Generalisability is limited as data are from a single primary care clinic and the data describe only a selected cohort of attendees.

Strengths and weaknesses of review process

The review benefits from a robust search methodology applied to a targeted population. We had not anticipated that we would only identify one study of the use of IQCODE in a primary care setting suitable for inclusion into the review. We would argue this finding reflects a lack of research in this setting, rather than an overly focused search strategy as an equivalent search identified substantial numbers of studies assessing IQCODE’s use in secondary care and community settings (Quinn 2014). We operated no exclusions with regard to study language or year of publication. As part of the suite of reviews describing IQCODE we have contacted research teams with an interest in cognitive screening to check for unpublished or “in press” original data. Where reporting was not clear in the included manuscript we contacted the study authors who supplied additional detail where possible.

The review is strengthened by the application of formal, dementia specific, tools for the assessment of methodological and reporting quality. We used QUADAS‐2 based anchoring statements specifically developed for use with studies that have a cognitive index test/reference standard (Davis 2013). Our complementary assessment of reporting uses the dementia focused extension to standard guidelines STARDdem.

Comparisons with previous research: This review forms part of a series of reviews describing informant based cognitive screening tools. Other reviews describing IQCODE use in a community (Quinn 2014) or hospital context and the AD‐8 tool are available or in production. The limitations in methodology and reporting evident in the primary care paper are common across other papers.

Previous, non‐Cochrane based, reviews of IQCODE and informant screening have been published. These reviews have tended to focus on hospital and memory clinic settings again highlighting the lack of published data on cognitive screening in primary care (Jorm 2004, Cullen 2007).

Applicability of findings to the review question

The study identified is arguably not representative of a typical primary care population. The ideal sampling frame for a primary care population would be sequential unselected attendees. In the included study the authors focused on a particular ethnic group; albeit this group comprised a large proportion of the study clinic’s local population. It could also be argued that the health care facility described in the included study is not representative of primary care as practiced in other countries. In particular we note that the service described is “private” (fee paying) and so the population using the clinic may differ from a service that offers free at point of care services.

The lack of research in primary care is unfortunate, as arguably this is the healthcare setting where cognitive screening or triage is most important. Many older adults with subjective cognitive problems will initially consult the family physician. The available consultation time is limited and the primary care physician must act as gatekeeper referring those who need specialist assessment but not overburdening secondary care memory services. Primary care in this form has the opportunity to access patients and their support networks, including those who may be suitable to act as ‘informant’. Primary care physicians are uniquely placed to develop a relationship with their patients and families, established over many years, that lends itself to testing using an informant based approach such as IQCODE.

Cognitive screening in primary care could operate under two models, screening of those presenting with memory problems or opportunistic screening of older adults presenting for other reasons. As a population level, screening system primary care will not capture an entire population, as individuals must first present and engage with services. However, the model of opportunistic screening for conditions such as hypertension is well established in primary care.

Primary care assessment has advantages over the more commonly studied hospital setting. This system has been advocated by multidisciplinary professionals (Iliffe 2003) and patients (Fowler 2012). Primary care has an integral role in supporting those who are diagnosed, providing continuity in healthcare provision (Iliffe 2009). The focus of much of the available IQCODE research is secondary care. The challenges and validity of dementia assessment in secondary care are well described (Mathews 2013) and case‐finding in the acute hospital setting could arguably be considered too late.(Sampson 2009). We would encourage future test accuracy research to include primary care settings.

A separate but related issue is around the utility or potential harm of unselected cognitive screening. It is widely agreed that a lack of formal dementia diagnosis is not only detrimental to the individual, but also limits health and social service planning (Banerjee 2010). The case for improving rates of diagnosis is predicated on improved access to early diagnostic services in order that individual and societal benefits are realised, such as reducing admissions to long‐term care (Banerjee 2009). However, this clearly relies on making a diagnosis early in the disease process, when the patient has the opportunity to engage in care planning, either formally or informally and may provide an explanation of their symptoms and experiences (Carpenter 2008). There is little robust evidence for routine screening in primary care for dementia (Boustani 2003). Within primary care, increased use of cognitive screening following the National Dementia Strategy increased rates of referral, but this was not followed by increased rates of dementia diagnosis (Menon 2011). Whether this reflects issues with the tools used or the population sampled is not clear. However, this reiterates the need to evaluate the accuracy of the tools being used to ensure that appropriate individuals are identified.

Authors' conclusions

Implications for practice.

The findings of this review are insufficient to recommend any change to current clinical practice given the lack of evidence to support or refute the value of the IQCODE as a tool for detecting dementia in a primary care setting.

Implications for research.

Several studies describing IQCODE accuracy in non‐primary care settings are available and synthesis of these papers will facilitate evidence based approaches to choice of assessment. Intuitively IQCODE could be suited to a primary care setting but we should not assume favourable test properties without original research. Our review would suggest the need for further research into the use of IQCODE as a tool for detecting dementia with a particular focus on primary care settings. Future studies should look to describe test accuracy but also related metrics such as feasibility and patient acceptability.

To allow clinicians and policy makers to make the best use of available data we would encourage the use of tools such as STARDdem reporting guidance to improve consistency and quality in published data.

What's new

Date	Event	Description
15 June 2021	Amended	The title and objectives have been changed to make it clear that screening tests alone cannot give a diagnostic formulation. There have been no other changes. Similar changes have been made to other Cochrane diagnostic test accuracy reviews relating to dementia. These changes were made by Cochrane Dementia and Cognitive Improvement in conjunction with the Cochrane Mental Health and Neuroscience Network and the review authors, following feedback from a group of dementia researchers, expressing concern that the review titles implied that short screening tests could make a diagnosis of a dementia subtype like Alzheimer’s disease. This interpretation was not intended, but the revised titles and objectives clarify the reviews’ scope. Further details are available at add link to page on website
15 June 2021	New citation required but conclusions have not changed	Title and obectives changed for clarification

History

Protocol first published: Issue 10, 2013
Review first published: Issue 7, 2014

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 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.

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 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 hydrocephalus), 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 hydrocephalus), 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 ICD‐10 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

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	Remembering the names of family and friends	Much improved	A bit improved	Not much change	A bit worse	Much worse
2	Remembering the faces of family and friends	Much improved	A bit improved	Not much change	A bit worse	Much worse
3	Remembering things about family and friends, e.g. occupations, birthdays, addresses	Much improved	A bit improved	Not much change	A bit worse	Much worse
4	Remembering things that have happened recently	Much improved	A bit improved	Not much change	A bit worse	Much worse
5	Recalling conversations a few days later	Much improved	A bit improved	Not much change	A bit worse	Much worse
6	Forgetting what he / she wanted to say in the middle of a conversation	Much improved	A bit improved	Not much change	A bit worse	Much worse
7	Remembering her/his address and telephone number	Much improved	A bit improved	Not much change	A bit worse	Much worse
8	Remembering what day and month it is	Much improved	A bit improved	Not much change	A bit worse	Much worse
9	Remembering where things are usually kept	Much improved	A bit improved	Not much change	A bit worse	Much worse
10	Remembering where to find things which have been put in a different place from usual	Much improved	A bit improved	Not much change	A bit worse	Much worse
11	Adjusting to any change in his / her day to day routine	Much improved	A bit improved	Not much change	A bit worse	Much worse
12	Knowing how to work familiar machines around the house	Much improved	A bit improved	Not much change	A bit worse	Much worse
13	Learning to use a new gadget or machine around the house	Much improved	A bit improved	Not much change	A bit worse	Much worse
14	Learning new things in general	Much improved	A bit improved	Not much change	A bit worse	Much worse
15	Remembering things that happened to him/her when he/she was young	Much improved	A bit improved	Not much change	A bit worse	Much worse
16	Remembering things that he/she learned when he/she was young	Much improved	A bit improved	Not much change	A bit worse	Much worse
17	Understanding the meaning of unusual words	Much improved	A bit improved	Not much change	A bit worse	Much worse
18	Understanding magazine or newspaper articles	Much improved	A bit improved	Not much change	A bit worse	Much worse
19	Following a story in a book or on TV	Much improved	A bit improved	Not much change	A bit worse	Much worse
20	Composing a letter to friends or for business purposes	Much improved	A bit improved	Not much change	A bit worse	Much worse
21	knowing about important historical events if the past	Much improved	A bit improved	Not much change	A bit worse	Much worse
22	Making decisions on everyday matters	Much improved	A bit improved	Not much change	A bit worse	Much worse
23	Handling money for shopping	Much improved	A bit improved	Not much change	A bit worse	Much worse
24	Handling financial matters, e.g. the pension, dealing with the bank	Much improved	A bit improved	Not much change	A bit worse	Much worse
25	Handling other everyday arithmetic problems, e.g. knowing how much food to buy, knowing how long between visits from family or friends	Much improved	A bit improved	Not much change	A bit worse	Much worse
26	Using his/her intelligence to understand what’s going on and to reason things through	Much improved	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 things about family and friends, e.g. occupations, birthdays, addresses	Much improved	A bit improved	Not much change	A bit worse	Much worse
2	Remembering things that have happened recently	Much improved	A bit improved	Not much change	A bit worse	Much worse
3	Recalling conversations a few days later	Much improved	A bit improved	Not much change	A bit worse	Much worse
4	Remembering her/his address and telephone number	Much improved	A bit improved	Not much change	A bit worse	Much worse
5	Remembering what day and month it is	Much improved	A bit improved	Not much change	A bit worse	Much worse
6	Remembering where things are usually kept	Much improved	A bit improved	Not much change	A bit worse	Much worse
7	Remembering where to find things which have been put in a different place from usual	Much improved	A bit improved	Not much change	A bit worse	Much worse
8	Knowing how to work familiar machines around the house	Much improved	A bit improved	Not much change	A bit worse	Much worse
9	Learning to use a new gadget or machine around the house	Much improved	A bit improved	Not much change	A bit worse	Much worse
10	Learning new things in general	Much improved	A bit improved	Not much change	A bit worse	Much worse
11	Following a story in a book or on TV	Much improved	A bit improved	Not much change	A bit worse	Much worse
12	Making decisions on everyday matters	Much improved	A bit improved	Not much change	A bit worse	Much worse
13	Handling money for shopping	Much improved	A bit improved	Not much change	A bit worse	Much worse
14	Handling financial matters, e.g. the pension, dealing with the bank	Much improved	A bit improved	Not much change	A bit worse	Much worse
15	Handling other everyday arithmetic problems, e.g. knowing how much food to buy, knowing how long between visits from family or friends	Much improved	A bit improved	Not much change	A bit worse	Much worse
16	Using his/her intelligence to understand what’s going on and to reason things through	Much improved	A bit improved	Not much change	A bit worse	Much worse

Appendix 4. Commonly used cognitive assessments / screening tools

TEST	Cochrane DTA review in process
Mini‐mental state examination (MMSE)	YES
GPcog	Still available
Minicog	YES
Memory Impairment Screen (MIS)	Still available
Abbreviated mental testing	Still available
Clock drawing tests (CDT)	Still available
Montreal Cognitive Assessment (MoCA)	YES
AD‐8 (informant interview)	YES

Appendix 5. Sources searched and search strategies

Source	Search strategy	Hits retrieved
1. Medline In‐process and other non‐indexed citations and MEDLINE 1950‐present (Ovid SP)	1. IQCODE.ti,ab. 2. "informant questionnaire on cognitive decline in the elderly".ti,ab. 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	Apr 2011: 291 Jul 2012: 39 Jan 2013: 19
2. Embase 1980‐2013 January 10 (Ovid SP)	1. IQCODE.ti,ab. 2. "informant questionnaire on cognitive decline in the elderly".ti,ab. 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	Apr 2011: 356 Jul 2012: 49 Jan 2013: 44
3. PsycINFO 1806‐January week 2 2013 (Ovid SP)	1. IQCODE.ti,ab. 2. "informant questionnaire on cognitive decline in the elderly".ti,ab. 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	Apr 2011: 215 Jul 2012: 28 Jan 2013: 17
4. BIOSIS previews 1926 to present (ISI Web of Knowledge)	Topic=(IQCODE OR "informant questionnaire on cognitive decline in the elderly" OR "IQ code") AND Topic=(dement* 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, CPCI‐S, CPCI‐SSH, BKCI‐S, BKCI‐SSH. Lemmatization=On	Apr 2011: 84 Jul 2012: 12 Jan 2013: 2
5. Web of Science and conference proceedings (1945‐present)	Topic=(IQCODE OR "informant questionnaire on cognitive decline in the elderly" OR "IQ code") AND Topic=(dement* 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, CPCI‐S, CPCI‐SSH, BKCI‐S, BKCI‐SSH. Lemmatization=On	Apr 2011: 184 Jul 2012: 24 Jan 2013: 13
6. LILACS (BIREME)	“short‐IQCODE” OR IQCODE OR “IQ code” OR “Informant Questionnaire” OR “Informant Questionnaires”	Apr 2011: 10 Jul 2012: 0 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); 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)	Jan 2013: 3
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‐duplification and first‐assess by the Trials Search Co‐ordinator	71

Appendix 6. Search strategy (Medline Ovid SP) 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 inMedline (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.

MEDLINE In‐process and other non‐indexed citations and MEDLINE 1950‐present (Ovid SP)

1. "word recall".ti,ab. 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. 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. 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 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.
METHODS
Participants	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)?
Test methods	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.
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.
RESULTS
Participants	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).
Test results	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.
Estimates	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.
DISCUSSION	25	Discuss the clinical applicability of the study findings.

Appendix 8. Assessment of reporting quality ‐ STARDdem checklist

Section, Topic and Item No.	STARD checklist item	Points of particular relevance to dementia
Title/Abstract/Keywords
1	Identify the article as a study of diagnostic accuracy (recommend MeSH heading 'sensitivity and specificity')	Studies reporting a sensitivity/specificity or 2x2 data derivable, fall within the scope of STARDdem and should be indexed accordingly.
Introduction
2	State the research questions or study aims, such as estimating diagnostic accuracy or comparing accuracy between tests or across participant groups	Some studies describing aims related to 'prognosis' or 'prediction' may also fall within the remit of STARDdem. Report test purpose: 'stand‐alone' test or as an addition to other tests or clinical criteria.
Methods
Participants:
3	The study population: The inclusion and exclusion criteria, setting and locations where data were collected See also Item 4 on recruitment and Item 5 on sampling	Key inclusion criteria: (a) demographic, especially age; (b) cognition‐ or disease‐related criteria. Report referral pathways, precise locations of patient recruitment, where index test and reference standard were performed. For secondary/tertiary settings helpful to report the medical subspecialty or hospital dept (e.g. psychiatry, neurology). Diagnostic accuracy studies in dementia are often nested within larger cohort studies. If this is the case, then the targeted population for the cohort study and the method of cohort selection should be described and/or the parent study cited.
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? See also Item 5 on sampling and Item 16 on participant loss at each stage of the study	For case‐control design, report whether those in intermediate categories (e.g. possible AD or possible DLB) were excluded.
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 See also Item 4 on recruitment and Item 16 on participant loss	Planned analyses showing how characteristics of the subgroup entering the study differ from the eligible population are strongly recommended (i.e. if a convenience sample has been used due to invasive nature of test/s).
6	Data collection: Was data collection planned before the index test and reference standard were performed (prospective study) or after (retrospective study)?	Authors should report the timing of the analysis plan with respect to data collection: was the analysis plan set out in a protocol before index and reference standards were performed? If not, when was the analysis plan created?
Test methods:
7	The reference standard and its rationale	For neuropathological and clinical reference standards the diagnostic criteria used should be specified. Where relevant, reference should be made to studies validating the criteria. Report if standard consensus clinical criteria incorporate the index test (incorporation bias rendering blinding of index test impossible).
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 See also Item 10 concerning the person(s) executing the tests	Use of scales: specify details of administration, which version. Clinical diagnostic criteria: what information was available to inform the diagnoses; how the criteria were applied (e.g. by individual clinicians, by consensus conference, by semi‐automated algorithm). Imaging and laboratory tests : specify materials and instruments, including sample handling and concordance with any harmonisation criteria. In new assays describe all steps in detail. Any particular preparation of participants should be described.
9	Definition of and rationale for the units, cut‐offs and/or categories of the results of the index tests and the reference standard	Explanation of any cut‐off used is warranted; depending on clinical setting a more sensitive or more specific test is required.
10	The number, training and expertise of the persons executing and reading the index tests and the reference standard See also Item 8	Especially where subjective judgments are involved, e.g. the interpretation of neuroimaging results. Report inter‐ and intra‐rater agreement. Reference or describe the content of training materials used. Reference or describe details of lab certification and harmonised biomarker assays.
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 See also Item 7	Also, the index test may form a part of the reference standard. This is often referred to as incorporation bias and renders blinding of the index test impossible.
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	Applies to the reference standard as well as to the index test. Both should be reported/adequately referenced. Recommend reporting inter‐rater and test‐retest reliability of reference standard as applied in the study being reported, rather than simply referring to other studies where reproducibility has been established. The training which image readers receive should be carefully described. Studies in which the accuracy of ‘majority’ judgements are reported should also report data for the minority judgements. Reports of the impact of training should clearly describe the population characteristics of the training group and whether it is representative of the group to which the test will be applied.
Results
Participants:
14	When study was performed, including beginning and end dates of recruitment	Pertinent particularly to longitudinal (delayed verification) studies, authors should report recruitment dates of the study (not to be confused with recruitment dates of the wider cohort study from which it might be drawn), and the beginning (first participant) and end (last participant) dates of the periods during which index test/s and reference standard were performed. Report the period for the index test and period for the reference standard separately if it is not clear.
15	Clinical and demographic characteristics of the study population (at least information on age, gender, spectrum of presenting symptoms) See also Item 18	Report key demographic variables: age, sex and education. Report age distribution of sample in detail. Ethnicity and genetic factors (e.g. APOE genotype) may also be particularly important. The cognitive characteristics are covered in Item 18.
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) See also Item 3, Item 4 and Item 5
Test results:
17	Time‐interval between the index tests and the reference standard, and any treatment administered in between	Specify the follow‐up period for all subjects in relation to their outcomes. It should be specified whether or not participants had received any treatments which might affect disease progression.
18	Distribution of severity of disease (define criteria) in those with the target condition; other diagnoses in participants without the target condition	Include a description of the severity of the target condition at the time the index test is performed. Usually captured by a cognitive score and/or duration of symptoms. For delayed verification studies report distribution of severity of disease and the degree of certainty (such as probable/possible) about the diagnosis at time of case ascertainment. Report other diagnoses (not 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	Report all adverse events, even if unlikely to be related to the diagnostic test performed.
Estimates:
21	Estimates of diagnostic accuracy and measures of statistical uncertainty (e.g. 95% confidence intervals) See also Item 12
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 centers, if done
24	Estimates of test reproducibility, if done See also Item 13
Discussion
25	Discuss the clinical applicability of the study findings	Key to clinical applicability are differences in age and comorbidity between the study population and the patients typically seen in clinical practice. Discuss issue of the 'added’ or ‘incremental’ value of the index test if appropriate. Emphasise: 1. Stage of development of the test (e.g. proof of concept; defining accuracy in a typical spectrum of patients); 2. The further research needed to be done to make test applicable to population in whom likely to be applied in practice; 3. Whether sample was representative of the population in whom the test would be applied in practice.

Appendix 9. Assessment of methodological quality table QUADAS‐2 tool

DOMAIN	PATIENT SELECTION	INDEX TEST	REFERENCE STANDARD	FLOW AND TIMING
Description	Describe methods of patient selection: Describe included patients (prior testing, presentation, intended use of index test and setting):	Describe the index test and how it was conducted and interpreted:	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 random sample of patients enrolled?	Were the index test results interpreted without knowledge of the results of the reference standard?	Is the reference standard likely to correctly classify the target condition?	Was there an appropriate interval between index test(s) and reference standard?
	Was a case‐control design avoided?	If a threshold was used, was it pre‐specified?	Were the reference standard results interpreted without knowledge of the results of the index test?	Did all patients receive a reference standard?
	Did the study avoid inappropriate exclusions?			Did all patients receive the same reference standard?
				Were all patients included in the analysis?
Risk of bias: High/low/ unclear	Could the selection of patients have introduced bias?	Could the conduct or interpretation of the index test have introduced bias?	Could the reference standard, its conduct, or its interpretation have introduced bias?	Could the patient flow have introduced bias?
Concerns regarding applicability: High/low/ unclear	Are there concerns that the included patients do not match the review question?	Are there concerns that the index test, its conduct, or interpretation differ from the review question?	Are there concerns that the target condition as defined by the reference standard does not match the review question?

Appendix 10. 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 system wherein certain items can dominate. For these dominant items, if scored “high risk” then that section of the QUADAS‐2 results table is likely to be scored as high risk of bias regardless of other scores. 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.

We have detailed how QUADAS‐2 has been operationalised for use with dementia reference standard studies below. In these descriptors dominant items are labelled as "high risk of bias for total section regardless of other items".

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.

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 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 bias and this will be assessed as a potential source of heterogeneity.

If case‐control used then grading will be high risk of bias for total section regardless of other items (in fact case‐control studies will not be included in this review)

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.

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 of bias 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.

Post hoc exclusions will be labelled high risk of bias for total section regardless of other items.

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 of bias 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.

If there is no attempt at blinding grading will be high risk of bias for total section regardless of other items.

Were IQCODE thresholds prespecified?

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 low risk of bias.

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 work.

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 Body dementia; Lund criteria for frontotemporal dementias; and the NINDS‐AIREN criteria for vascular dementia. Where the criteria used for assessment are not familiar to the review authors or the Cochrane Dementia and Cognitive Improvement Group this item should be classified as high risk of bias.

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 of bias 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 prespecified that dementia diagnosis that explicitly uses IQCODE will be classified as high risk of bias for total section regardless of other items.

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).

Flow

Was there an appropriate interval between IQCODE and clinical dementia assessment?

For a cross‐sectional study design, there is potential for change between assessments. The ideal would be same day assessment but this is not always feasible. 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.

Did all get the same assessment for dementia regardless of IQCODE result?

There may be scenarios where only those who score “test positive” on IQCODE have a more detailed assessment. Where dementia assessment (or other reference standard) differs depending on the IQCODE result this should be classified as high risk of bias.

Were all who received IQCODE assessment included in the final analysis?

If the study has drop outs these should be accounted for; a maximum proportion of drop outs to remain low risk of bias has been specified as 20%.

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 for total section regardless of other items.

Applicability

Were those included representative of the general population of interest?

Those included 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 groups 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 with disease than would be seen in usual clinical practice. In this instance the item should be rated poor applicability.

Appendix 11. STARDdem (reporting quality) Results

Section and Topic and Item No.	Rating
Title/Abstract/Keywords
1	No
Introduction
2	Yes
Methods
Participants:
3	Yes
4	No
5	Yes
6	Yes
Test methods:
7	Partially
8	Partially
9	No
10	No
11	No
Statistical methods:
12	No
13	No
Results
Participants:
14	Partially
15	Partially
16	No
Test results:
17	No
18	No
19	No
20	No
Estimates:
21	No
22	No
23	No
24	No
Discussion
25	Yes

Data

Presented below are all the data for all of the tests entered into the review.

Tests. Data tables by test.

Test	No. of studies	No. of participants
1 IQCODE for diagnosis of dementia at threshold 3.2	1	230
2 IQCODE for diagnosis of dementia at threshold 3.3	1	230
3 IQCODE for diagnosis of dementia at threshold 3.4	1	230
4 IQCODE for diagnosis of dementia at threshold 3.5	1	230
5 IQCODE for diagnosis of dementia at threshold 3.6	1	230
6 IQCODE for diagnosis of dementia at threshold 3.7	1	230

1. Test.

IQCODE for diagnosis of dementia at threshold 3.2

2. Test.

IQCODE for diagnosis of dementia at threshold 3.3

3. Test.

IQCODE for diagnosis of dementia at threshold 3.4

4. Test.

IQCODE for diagnosis of dementia at threshold 3.5

5. Test.

IQCODE for diagnosis of dementia at threshold 3.6

6. Test.

IQCODE for diagnosis of dementia at threshold 3.7

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Tokuhara 2006.

Study characteristics
Patient Sampling	Sequential attenders at primary care centre in Hawai'i (analysis limited to those who self‐identified as Japanese Americans)
Patient characteristics and setting	Sequential attenders (n=1038 eligible; n=230 included), attendance not necessarily related to cognitive symptoms. Primary care Hawai'i
Index tests	IQCODE 26 item, English language
Target condition and reference standard(s)	Clinical dementia diagnosis using Benson and Cummings criteria, informed by cognitive testing (CASI, MMSE and Clock‐Drawing Task), interview data and an assessment of function
Flow and timing	Cross sectional study, no follow up. Unclear sequencing of index test and reference standard and degree of blinding. Substantial number of patients not included in test accuracy analyses.
Comparative
Notes
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Yes
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	No
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Unclear
Could the reference standard, its conduct, or its interpretation have introduced bias?		High risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Unclear
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Unclear
Were all patients included in the analysis?	No
Could the patient flow have introduced bias?		High risk

Characteristics of excluded studies [ordered by study ID]

Study	Reason for exclusion
Abreu 2008	Hospital setting
Butt 2008	Data on less than 10 participants
Cherbuin 2008	No new data
de Jonge 1997	Data not suitable for analysis
Dekkers 2009	Data not suitable for analysis
Diefeldt 2007b	Repeat dataset
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 study
Garcia 2002	Hospital setting
Goncalves 2011	Hospital setting
Hancock 2009	Hospital setting
Harwood 1997	Hospital setting
Hayden 2003	<10 IQCODE
Henon 2001	Uses a delayed verification analysis
Isella 2002	Uses a delayed verification analysis
Isella 2006	Data not suitable for analysis
Jorm 1988a
Jorm 1989	Data not suitable for analysis
Jorm 1991	Hospital setting
Jorm 1994	Community setting
Jorm 1996A	No dementia diagnosis reference standard
Jorm 1997	No new data
Jorm 2000	No dementia diagnosis reference standard
Jorm 2000a
Jorm 2003	No new data
Jorm 2004	No new data
Kathriarachi 2001	Community setting
Khachaturian 2000	No IQCODE index test data
Knaefelc 2003	Hospital setting
Krogseth 2011	Uses a delayed verification analysis
Larner 2010	Looks at diagnosis accuracy comparing two dementia types rather than dementia/no dementia dichotomy
Larner 2013	Review article
Law 1995	Community setting
Li 2012	No dementia diagnosis reference standard
Louis 1999	Uses a delayed verification analysis
Mackinnon 1998	Hospital setting
Mackinnon 2003	Community setting
Mimori (abstract)	No new data
Morales 1995	Community setting
Morales 1997 (rural)	Community setting
Morales 1997 (urban)	Community setting
Morales‐Gonzalez 1992	Hospital setting
Mulligan 1996	Hospital setting
Narasimhalu 2008	Hospital setting
Ozel‐kizel 2010	Hospital setting
Peroco 2009	Hospital setting
Potter 2009	Data not suitable for analysis
Razavi 2011	Hospital setting
Ritchie 1992	No IQCODE data
Rodriguez‐Molinero 2010	No dementia diagnosis reference standard
Rovner 2012	Data not suitable for analysis
Sanchez 2009	No dementia diagnosis reference standard
Schofield 2006	Data not suitable for analysis
Senanorong 2001	Community setting
Sikkes 2010	Hospital setting
Siri 2006	Hospital setting
Srikanth 2006	Community setting
Starr 2000	No dementia diagnosis reference standard
Tang 2003	Hospital setting
Thomas 1994	Hospital setting
Wierderholt 1999	Data not suitable for analysis
Wolfe 2009	No dementia diagnosis reference standard
Yamada 2011	Community setting
Zevallos‐Bustamente 2003	Hospital setting
Zhang 2003	Data not suitable for analysis
Zhou 2002	Hospital setting
Zhou 2003	Repeat dataset
Zhou 2004	Repeat dataset

Contributions of authors

JK Harrison assisted with drafting review; study assessment and analyses. TJ Quinn assisted with study selection; data extraction and analyses. P Fearon assisted with study selection and assessment. A Noel‐Storr assisted with development of search strategy and review content. R McShane and DJ Stott provided critical review and supervision.

Sources of support

Internal sources

• No sources of support provided

External sources

• Royal College of Physicians and Surgeons Glasgow Travel Scholarship, UK

  To develop the suite of dementia test accuracy reviews, Dr Quinn worked with the Cochrane Dementia and Cognitive Improvement Group in Oxford, UK. Travel and accomodation were supported by the RCPSG.

• Graham Wilson Research Fund, UK

Declarations of interest

No relevant disclosures or conflicts of interest for the content of this review.

Edited (no change to conclusions)