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Diagnostic Test Accuracy Protocol

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IQCODE for the diagnosis of Alzheimer’s disease dementia and other dementias within a general practice (primary care) setting

  1. Terry J Quinn1,*,
  2. Patricia Fearon2,
  3. Camilla Young2,
  4. Anna H Noel-Storr3,
  5. Rupert McShane3,
  6. David J Stott2

Editorial Group: Cochrane Dementia and Cognitive Improvement Group

Published Online: 14 OCT 2013

Assessed as up-to-date: 16 JAN 2013

DOI: 10.1002/14651858.CD010771


How to Cite

Quinn TJ, Fearon P, Young C, Noel-Storr AH, McShane R, Stott DJ. IQCODE for the diagnosis of Alzheimer’s disease dementia and other dementias within a general practice (primary care) setting (Protocol). Cochrane Database of Systematic Reviews 2013, Issue 10. Art. No.: CD010771. DOI: 10.1002/14651858.CD010771.

Author Information

  1. 1

    University of Glasgow, Cardiovascular and Medical Sciences, Glasgow, UK

  2. 2

    University of Glasgow, Academic Section of Geriatric Medicine, Glasgow, UK

  3. 3

    University of Oxford, Radcliffe Department of Medicine, Oxford, UK

*Terry J Quinn, Cardiovascular and Medical Sciences, University of Glasgow, Walton Building, Glasgow Royal Infirmary, Glasgow, G4 0SF, UK. Terry.Quinn@glasgow.ac.uk.

Publication History

  1. Publication Status: New
  2. Published Online: 14 OCT 2013

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This is not the most recent version of the article. View current version (03 JUL 2014)

 

Background

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Appendices
  6. Declarations of interest

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. 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 community or 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). This approach is particularly pertinent to primary care. 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). 

Screening assessment often takes 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 will be the focus of our review (Jorm 1988). In certain countries opportunistic primary-care screening assessments of older adults have been proposed and informant interviews such as IQCODE have been suggested as a possible screening tool.

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) (Cordell 2013).

 

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 such as acetylcholinesterase inhibitors; the drug 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. Clearly 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 will accept a dementia diagnosis made according to any of the internationally accepted diagnostic criteria, with exemplars being the various iterations of the World Health Organization, International Classification of Diseases (ICD) and 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 Alzheimers 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 will be considered under our rubric of 'all-cause dementia' and will 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 will vary depending on disease stage; for example, true positives are more likely when disease is advanced and diagnosis is clear. For our primary analysis we will include 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 will not be included in this review. 

 

Index test(s)

Our index test will be 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' will refer to the original 26-item questionnaire as described by Jorm 1988. Other versions of IQCODE will be described according to the number of items and administration language (e.g. a 16-item IQCODE for Spanish speakers will be described as 'IQCODE-16 Spanish').

Although we will 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 ICQODE 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 (Jorm 2004). There are fewer published data on the psychometric properties of other 'short' forms of IQOCDE. For our analysis, each form of IQCODE will be described separately.

IQCODE cut-off scores suggestive of a potential dementia or MCI 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. We will restrict our analysis to predefined threshold values of IQCODE as detailed below.

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 will focus on papers that describe IQCODE diagnostic properties, and will not consider other cognitive screening/assessment tools.  Where a paper describes IQCODE with an in-study comparison against another screening tool, we will include the IQCODE data only. Where IQCODE is used in combination with another cognitive screening tool, we will include 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. 

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. 

Although we use the term 'diagnosis' in this review, we recognise that in practice IQCODE alone is not sufficient to make a diagnosis. Rather, IQCODE can be used to 'triage' people presenting with memory problems for further assessment or to inform a diagnosis in conjunction with direct assessment and investigations.

This review will form 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

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Appendices
  6. Declarations of interest

To determine the diagnostic accuracy of the informant-based questionnaire IQCODE, in detection of all-cause (undifferentiated) dementia in adults presenting to primary-care services.

 

Secondary objectives

Where data are available we will 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 will describe 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 will explore include: age of cohort; case mix of cohort; reason for primary-care consultation; technical features of IQCODE; method of dementia diagnosis.

 

Methods

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Appendices
  6. Declarations of interest
 

Criteria for considering studies for this review

 

Types of studies

We will include those studies concerned with primary-care screening that describe 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 are 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 we will not consider them in this review.

Case-control studies are known to potentially overestimate properties of a test, and we will not include such studies.

We will not include case studies or samples with small numbers (for the purposes of this review, we defined "small" numbers as less than 10 participants).

There may be cases where settings are mixed, for example, a population study 'enriched' with additional cases from primary care. As this design does not fit a particular setting, we will not consider such studies unless separate data are presented for participants from each setting.

 

Participants

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

Our definition of a primary care-based study setting is those where participants have self referred either due to perceived memory problems or to another medical complaint; they will not have had previous extensive cognitive testing. We anticipate that studies will 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. We have not predefined any exclusion criteria relating to the case-mix of the population studied, but will assess this aspect of the study as part of our assessment of heterogeneity. Where we have concerns that the participants are not representative of a primary-care sample we will explore this at study level using the 'Risk of bias' assessment framework outlined below.

 

Index tests

Studies must 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 will collect data on the principal language used for IQCODE assessment. 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 their properties may differ from the original 26-item IQCODE tool. We will include all versions of IQCODE. We will explore the effect of language and version of IQCODE in our assessment of heterogeneity. A modified IQCODE for self assessment has been described. As our interest is in informant interviews, we will not include self-assessment IQCODE in the review (Cullen 2007).

 

Target conditions

We will include any clinical diagnosis of all-cause (unspecified) dementia. Defining a particular dementia subtype is not required, although where these data are available we will record them.

 

Reference standards

Our reference standard will be the 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 will include 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 we will include all dementia subtypes. Clinicians may use imaging, pathology or other data to aid diagnosis; however, we will 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 will collect data on the method and application of dementia diagnosis for each study and will explore potential effects as part of our assessment of heterogeneity.

We recognise that dementia diagnosis often comprises a degree of informant assessment. There is thus potential for incorporation bias. We will explore the potential effects of this bias through our 'Risk of bias' assessment.

Use of other (brief) direct performance tests in isolation will not be an acceptable basis for diagnosis.

 

Search methods for identification of studies

We will use a variety of information sources to ensure all relevant studies are included. We will devise terms for electronic database searching in conjunction with the team at the Cochrane Dementia and Cognitive Improvement Group.

 

Electronic searches

We will search the specialised register of the Cochrane Dementia and Cognitive Improvement Group, ALOIS (which includes both intervention and diagnostic accuracy studies), the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (OvidSP), EMBASE (OvidSP), BIOSIS (Ovid), Science Citation Index (ISI Web of Knowledge), PsycINFO (Ovid), CINAHL (EBSCO) and LILACS (Bireme). See Appendix 5 and Appendix 6 for a proposed draft strategy to be run in MEDLINE (OvidSP) along with a narrative describing how the strategy was developed and validated. We will design similarly structured search strategies using search terms appropriate for each database. We will use MeSH words and other controlled vocabulary where appropriate. Science Citation Index includes conference abstracts in its database and so will allow for assessment of the 'grey literature'.

We will also search sources specific to diagnostic accuracy:

MEDION database (Meta-analyses van Diagnostisch Onderzoek: www.mediondatabase.nl);

DARE (Database of Abstracts of Reviews of Effects: www.york.ac.uk/inst/crd/crddatabases.html);

HTA Database (Health Technology Assessments Database, Cochrane Library);

ARIF database (Aggressive Research Intelligence Facility: www.arif.bham.ac.uk).

We will request a search of the Cochrane Register of Diagnostic Test Accuracy Studies (maintained and managed by the Cochrane Renal Group).
We will not apply any language or date restrictions to the electronic searches. We will use translation services as necessary.
A single researcher with extensive experience of systematic reviewing will perform the initial searches.

 

Searching other resources

Grey literature: chosen electronic databases will include assessments of conference proceedings. We will aim to access theses or PhD abstracts from institutions known to be involved in prospective dementia studies.
Handsearching: We will not perform handsearching, as there is little published evidence of the benefits of handsearching for diagnostic studies (Glanville 2010).
Reference lists: We will check the reference lists of all relevant studies and reviews in the field for further possible titles, and will repeat the process until no new titles are found (Greenhalgh 2005).
Correspondence: We will contact research groups who have published or are conducting work on IQCODE for dementia diagnosis, informed by results of the initial search.
We will use relevant studies in PubMed to search for additional studies, using the 'related article' feature. We will examine key studies in citation databases such as Science Citation Index and Scopus to ascertain any further relevant studies.

 

Data collection and analysis

 

Selection of studies

Two review authors will independently screen all titles generated by the electronic database searches for relevance. They will review abstracts of selected titles and will select all potentially eligible studies for full-paper review. Two review authors will independently assess full manuscripts against the inclusion criteria. They will resolve disagreement by discussion, or by involving an arbitrator if necessary.

Where a study may include useable data which are not presented in the published manuscript, we will contact the authors directly to request further information. If the same data set is presented in more than one paper we will include the primary paper only.

We will detail the study selection process in a PRISMA flow diagram.

 

Data extraction and management

We will extract data to a study-specific pro forma that includes clinical/demographic details of the participants (including the reason for primary-care attendance), details of IQCODE administration, and details of the dementia diagnosis process.

Where IQCODE data are given for a number of cut-off points, we will extract data for each of our prespecified cut-off points: 3.6; 3.5; 3.4; 3.3. Where data fall between scores, we will round up the score. For example, we will include a score of 3.46 with 3.5 data. Where two values are given that could be rounded to the same number we will choose the value closest to the threshold of interest. For example, if scores 3.46 and 3.49 are given we will round both up to 3.5 but we will use only the 3.49 data. We will extract data to a standard two-by-two table.

Two blinded review authors will independently perform the data extraction. We will resolve disagreements in data extraction by discussion, using an arbitrator if necessary.

For each included paper, we will detail the flow of participants (numbers recruited, included, and assessed) 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 will assess methodological and reporting quality using two complementary processes.

We will assess the quality of study reporting using the Standards for the Reporting of Diagnostic accuracy studies (STARD) checklist (Bossuyt 2003) (Appendix 7). If it becomes available during the course of the review, we will use the proposed dementia-specific extension to the STARD tool - STARDdem (www.starddem.org/). We will tabulate and present STARD data as an appendix to the review.

We will assess the methodological quality of each study using the Quality Assessment tool for Diagnostic Accuracy Studies (QUADAS-2) (www.bris.ac.uk/quadas/quadas-2). This tool incorporates criteria 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. Certain key areas important for quality assessment are participant selection, blinding, and missing data. Following a group meeting of reviewers we created guidance for the application of QUADAS-2 to dementia screening assessments, specifically developing anchoring statements for QUADAS-based assessment that are suited to dementia test accuracy studies. This QUADAS guidance was created through a multidisciplinary working group and has been extensively piloted. The process and resulting statements for assessment are described in Appendix 8.

We will not use QUADAS-2 data to form a summary quality score, but will create a narrative summary describing the numbers of studies that found high/low/unclear risk of bias/concerns regarding applicability, with corresponding tabular and graphical displays.

Paired, independent raters, blinded to each other’s scores, will perform both assessments. We will resolve disagreement by further review and by discussion, with recourse to a third-party arbitrator where necessary.

 

Statistical analysis and data synthesis

We are interested in the test accuracy of IQCODE for the dichotomous variable 'dementia'/'no dementia'. We will therefore apply the current Cochrane DTA framework for analysis of a single test. We will extract data from included papers to allow the creation of a standard two-by-two data table showing dichotomised IQCODE test results (IQCODE positive or IQCODE negative) cross-classified with binary reference standard (dementia or no dementia). This process will be repeated for each of our prespecified IQCODE threshold scores. 

We will use Review Manager 5 software (RevMan) to calculate sensitivity, specificity and 95% confidence intervals (CIs) from the two-by-two tables abstracted from the included studies. We will present individual study results graphically by plotting estimates of sensitivities and specificities as forest plots and in receiver operating characteristic (ROC) space.

To allow for pooled analysis, we will use software additional to RevMan (SAS release 9.1) with guidance from the DTA UK Support Unit.(Reitsma 2005) Using the Hierarchical SROC approach (a generalised non-linear mixed model), we will describe metrics of pooled sensitivity, specificity, positive and negative predictive values; positive and negative likelihood ratios, all with corresponding 95% confidence intervals.

 

Investigations of heterogeneity

Heterogeneity is expected in diagnostic test accuracy reviews and conventional measures of heterogeneity in meta-analysis are not appropriate to DTA reviews.  

The focused study question, restricting the review to cross-sectional studies in a secondary-care setting is designed to remove potential heterogeneity relating to study design and setting. Other sources of heterogeneity in dementia studies, such as treatment, intervention or duration of follow-up are not applicable to a cross-sectional study and will not be considered separately from the inclusion/exclusion criteria.

The properties of a tool describe behaviour of the instrument under particular circumstances. Thus, for our assessment of potential sources of heterogeneity (where data allow), we will collect data on:

1. Included participants (age and case mix)

In the first instance we will explore age, taking age over 65 years as a reference point. We anticipate that the majority of included participants in eligible studies will be aged over 65 years. IQCODE may have different properties in younger cohorts, and so we will look at age ranges within studies and will grade and analyse separately those that have more than 20% of included participants younger than 65 years as potentially unrepresentative.

We anticipate that most studies will be of unselected adults. However, if the study includes a specific population, for example, stroke survivors, these data will be pooled and analysed separately.

2. Clinical criteria used to reach dementia diagnosis.

We will record the classification used (for example ICD-10; DSM-IV) and the methodology used to reach a dementia diagnosis (for example, individual assessment; group (consensus) assessment).

3. Reason for primary-care consultation.

We will dichotomise this as attending for 'subjective memory problem' or attending for 'other medical problem'.

4. Technical features of the testing strategy.

Our focus will be on the language of assessment. In the first instance, we will classify as English-language IQCODE or non-English-language IQCODE.

If data allow, we will also describe short (16-item) and standard (26-item) IQCODE.

Where data allow we will specifically investigate the effects of heterogeneity on test accuracy parameters by performing sensitivity analyses relating to each of the above variables. We will compare summary estimates for groups of interest; for example, summary diagnostic properties describing effects of language of administration will include all language IQCODE and also subgroups of English-language IQCODE and non-English language IQCODE.

 

Sensitivity analyses

Where appropriate (i.e. if not already explored in our analyses of heterogeneity) and as data allow, we will explore the sensitivity of any summary accuracy estimates to aspects of study quality such as the nature of blinding and loss to follow-up, guided by the anchoring statements developed in our QUADAS-2 exercise. Primary analysis will include all studies, while the sensitivity analysis will exclude studies of low quality (i.e. high likelihood of bias) to determine if the results are influenced by inclusion of the lower-quality studies.

 

Assessment of reporting bias

We will not investigate reporting bias because of current uncertainty about how it operates in test accuracy studies and the interpretation of existing analytical tools such as the funnel plot.

 

Appendices

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Appendices
  6. Declarations of interest
 

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


12345

1Remembering the names of family and friendsMuch improvedA bit improvedNot much changeA bit worseMuch worse

2Remembering the faces of family and friendsMuch improvedA bit improvedNot much changeA bit worseMuch worse

3Remembering things about family and friends, e.g. occupations, birthdays, addressesMuch improvedA bit improvedNot much changeA bit worseMuch worse

4Remembering things that have happened recentlyMuch improvedA bit improvedNot much changeA bit worseMuch worse

5Recalling conversations a few days laterMuch improvedA bit improvedNot much changeA bit worseMuch

worse

6Forgetting what he / she wanted to say in the middle of a conversationMuch improvedA bit improvedNot much changeA bit worseMuch worse

7Remembering her/his address and telephone numberMuch improvedA bit improvedNot much changeA bit worseMuch worse

8Remembering what day and month it isMuch improvedA bit improvedNot much changeA bit worseMuch worse

9Remembering where things are usually keptMuch improvedA bit improvedNot much changeA bit worseMuch worse

10Remembering where to find things which have been put in a different place from usualMuch improvedA bit improvedNot much changeA bit worseMuch worse

11Adjusting to any change in his / her day to day routineMuch improvedA bit improvedNot much changeA bit worseMuch worse

12Knowing how to work familiar machines around the houseMuch improvedA bit improvedNot much changeA bit worseMuch worse

13Learning to use a new gadget or machine around the houseMuch improvedA bit improvedNot much changeA bit worseMuch worse

14Learning new things in generalMuch improvedA bit improvedNot much changeA bit worseMuch worse

15Remembering things that happened to him/her when he/she was youngMuch improvedA bit improvedNot much changeA bit worseMuch worse

16Remembering things that he/she learned when he/she was youngMuch improvedA bit improvedNot much changeA bit worseMuch worse

17Understanding the meaning of unusual wordsMuch improvedA bit improvedNot much changeA bit worseMuch worse

18Understanding magazine or newspaper articlesMuch improvedA bit improvedNot much changeA bit worseMuch worse

19Following a story in a book or on TVMuch improvedA bit improvedNot much changeA bit worseMuch worse

20Composing a letter to friends or for business purposesMuch improvedA bit improvedNot much changeA bit worseMuch worse

21knowing about important historical events if the pastMuch improvedA bit improvedNot much changeA bit worseMuch worse

22Making decisions on everyday mattersMuch improvedA bit improvedNot much changeA bit worseMuch worse

23Handling money for shoppingMuch improvedA bit improvedNot much changeA bit worseMuch worse

24Handling financial matters, e.g. the pension, dealing with the bankMuch improvedA bit improvedNot much changeA bit worseMuch worse

25Handling other everyday arithmetic problems, e.g. knowing how much food to buy, knowing how long between visits from family or friendsMuch improvedA bit improvedNot much changeA bit worseMuch worse

26Using his/her intelligence to understand what’s going on and to reason things throughMuch improvedA bit improvedNot much changeA bit worseMuch 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.


12345

1Remembering things about family and friends, e.g. occupations, birthdays, addressesMuch improvedA bit improvedNot much changeA bit worseMuch worse

2Remembering things that have happened recentlyMuch improvedA bit improvedNot much changeA bit worseMuch worse

3Recalling conversations a few days laterMuch improvedA bit improvedNot much changeA bit worseMuch

worse

4Remembering her/his address and telephone numberMuch improvedA bit improvedNot much changeA bit worseMuch worse

5Remembering what day and month it isMuch improvedA bit improvedNot much changeA bit worseMuch worse

6Remembering where things are usually keptMuch improvedA bit improvedNot much changeA bit worseMuch worse

7Remembering where to find things which have been put in a different place from usualMuch improvedA bit improvedNot much changeA bit worseMuch worse

8Knowing how to work familiar machines around the houseMuch improvedA bit improvedNot much changeA bit worseMuch worse

9Learning to use a new gadget or machine around the houseMuch improvedA bit improvedNot much changeA bit worseMuch worse

10Learning new things in generalMuch improvedA bit improvedNot much changeA bit worseMuch worse

11Following a story in a book or on TVMuch improvedA bit improvedNot much changeA bit worseMuch worse

12Making decisions on everyday mattersMuch improvedA bit improvedNot much changeA bit worseMuch worse

13Handling money for shoppingMuch improvedA bit improvedNot much changeA bit worseMuch worse

14Handling financial matters, e.g. the pension, dealing with the bankMuch improvedA bit improvedNot much changeA bit worseMuch worse

15Handling other everyday arithmetic problems, e.g. knowing how much food to buy, knowing how long between visits from family or friendsMuch improvedA bit improvedNot much changeA bit worseMuch worse

16Using his/her intelligence to understand what’s going on and to reason things throughMuch improvedA bit improvedNot much changeA bit worseMuch worse



 

Appendix 4. Commonly used cognitive assessments / screening tools


TESTCochrane DTA review in process

Mini-mental state examination (MMSE)YES

GPcogStill available

MinicogStill available

Memory Impairment Screen (MIS)Still available

Abbreviated mental testingStill available

Clock drawing tests (CDT)Still available

Montreal Cognitive Assessment (MoCA)Still available

AD-8 (informant interview)YES



 

Appendix 5. Search strategy for use with MEDLINE electronic database


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. "short IQCODE".ti,ab.

4. "IQ code".ti,ab.

5. ("informant* questionnair*" adj3 (dement* or screening)).ti,ab.

6. ("screening test*" adj2 (dement* or alzheimer*)).ti,ab.

7. or/1-6



 

Appendix 6. Search strategy (Medline Ovid SP) run for specialised register (ALOIS)


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
1Identify the article as a study of diagnostic accuracy (recommend MeSH heading 'sensitivity and specificity').

INTRODUCTION2State the research questions or study aims, such as estimating diagnostic accuracy or comparing accuracy between tests or across participant groups.

METHODS

Participants3The study population: The inclusion and exclusion criteria, setting and locations where data were collected.

4Participant 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?

5Participant 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.

6Data collection: Was data collection planned before the index test and reference standard were performed (prospective study) or after (retrospective study)?

Test methods7The reference standard and its rationale.

8Technical specifications of material and methods involved including how and when measurements were taken, and/or cite references for index tests and reference standard.

9Definition of and rationale for the units, cut-offs and/or categories of the results of the index tests and the reference standard.

10The number, training and expertise of the persons executing and reading the index tests and the reference standard.

11Whether 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 methods12Methods for calculating or comparing measures of diagnostic accuracy, and the statistical methods used to quantify uncertainty (e.g. 95% confidence intervals).

13Methods for calculating test reproducibility, if done.

RESULTS

Participants14When study was performed, including beginning and end dates of recruitment.

15Clinical and demographic characteristics of the study population (at least information on age, gender, spectrum of presenting symptoms).

16The 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 results17Time-interval between the index tests and the reference standard, and any treatment administered in between.

18Distribution of severity of disease (define criteria) in those with the target condition; other diagnoses in participants without the target condition.

19A 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.

20Any adverse events from performing the index tests or the reference standard.

Estimates21Estimates of diagnostic accuracy and measures of statistical uncertainty (e.g. 95% confidence intervals).

22How indeterminate results, missing data and outliers of the index tests were handled.

23Estimates of variability of diagnostic accuracy between subgroups of participants, readers or centres, if done.

24Estimates of test reproducibility, if done.

DISCUSSION25Discuss the clinical applicability of the study findings.



 

Appendix 8. 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.

Following the creation of this dementia-specific QUADAS guidance, independent assessors 'piloted' our anchoring statements. The guidance is being used for a number of dementia test accuracy studies.

During the focus group and the piloting/validation of this guidance, it was clear that certain issues were key to assessing quality, while other issues were important to record but less important for assessing overall quality. To assist, we describe a 'weighting' system. Where an item is weighted 'high risk' then that section of the QUADAS-2 results table is likely to be scored as high risk of bias. For example, in dementia diagnostic test accuracy studies, ensuring that clinicians performing dementia assessment are blinded to results of index test is fundamental. If this blinding was not present then the item on reference standard should be scored 'high risk of bias', regardless of the other contributory elements.

In assessing individual items, the score of unclear should only be given if there is genuine uncertainty. In these situations review authors will contact the relevant study teams for additional information.

Anchoring statements to assist with assessment for risk of bias

Patient selection

Was a case-control or similar design avoided?

Designs similar to case-control that may introduce bias are those designs where the study team deliberately increase or decrease the proportion of patients with the target condition. For example, a population study may be enriched with extra dementia patients from a secondary care setting. Such studies will be automatically labelled high risk of bias and will be assessed as a potential source of heterogeneity.

Weighting: High risk of bias

Was the sampling method appropriate?

Where sampling is used, the designs least likely to cause bias are consecutive sampling or random sampling. Sampling that is based on volunteers or selecting participants from a clinic or research resource is prone to bias.

Weighting: High risk of bias

Are exclusion criteria described and appropriate?

The study will be automatically graded as unclear if exclusions are not detailed (pending contact with study authors). Where exclusions are detailed, the study will be graded as 'low risk' if exclusions are felt to be appropriate by the review authors. Certain exclusions common to many studies of dementia are: medical instability; terminal disease; alcohol/substance misuse; concomitant psychiatric diagnosis; other neurodegenerative condition. For a community sample we would expect relatively few exclusions.

Post hoc exclusions will be labelled 'high risk of bias'.

Weighting: Low risk

Index Test

Was IQCODE assessment performed without knowledge of clinical dementia diagnosis?

Terms such as 'blinded' or 'independently and without knowledge of' are sufficient and full details of the blinding procedure are not required. This item may be scored as 'low risk' if explicitly described or if there is a clear temporal pattern to order of testing that precludes the need for formal blinding i.e. all IQCODE assessments performed before dementia assessment.

Weighting: High risk

Were IQCODE thresholds 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 not applicable.

Weighting: Low risk

Reference Standard

Is the assessment used for clinical diagnosis of dementia acceptable?

Commonly used international criteria to assist with clinical diagnosis of dementia include those detailed in DSM-IV and ICD-10. Criteria specific to dementia subtypes include but are not limited to NINCDS-ADRDA criteria for Alzheimer’s dementia; McKeith criteria for Lewy 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 and the Cochrane Dementia and Cognitive Improvement Group this item should be classified as 'high risk of bias'.

Weighting: High risk

Was clinical assessment for dementia performed without knowledge of IQCODE?

Terms such as 'blinded' or 'independent' are sufficient and full details of the blinding procedure are not required. This may be scored as 'low risk' if explicitly described or if there is a clear temporal pattern to order of testing i.e. all dementia assessments performed before IQCODE testing.

Informant rating scales and direct cognitive tests present certain problems. It is accepted that informant interview and cognitive testing is a usual component of clinical assessment for dementia; however, specific use of the scale under review in the clinical dementia assessment should be scored as high risk of bias. We have prespecified that a dementia diagnosis that explicitly uses IQCODE will be classified as high risk of bias.

Weighting: High risk

Patient flow

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

For a cross-sectional study design, there is potential for the patient to change between assessments. The ideal would be same-day assessment. We have set an arbitrary maximum interval of one month between tests, although this may be revised depending on the test and the stability of the condition of interest.

Weighting: High

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

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

Weighting: High risk

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

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

Weighting: Low risk

Were missing IQCODE results or uninterpretable IQCODE results reported?

Where missing results are reported, if there is substantial attrition (we have set an arbitrary value of 50% missing data) this should be scored as high risk of bias.

Weighting: Low risk

Applicability

Were included patients representative of the general population of interest?

The included patients should match the intended population as described in the review question. If not already specified in the review inclusion criteria, setting will be particularly important – the review authors should consider population in terms of symptoms; pre-testing; potential disease prevalence. Studies that use very selected patients or subgroups will be classified as poor applicability.

Was IQCODE performed consistently and in a manner similar to its use in clinical practice?

IQCODE studies will be judged against the original description of its use.

Was clinical diagnosis of dementia (or other reference standard) made in a manner similar to current clinical practice?

For many reviews, inclusion criteria and assessment for risk of bias will already have assessed the dementia diagnosis. For certain reviews an applicability statement relating to reference standard may not be applicable. There is the possibility that a form of dementia assessment, although valid, may diagnose a far larger proportion of patients with disease than usual clinical practice. In this instance the item should be rated poor applicability.

Were sufficient data on IQCODE application given for the test to be repeated in an independent study?

Particular points of interest for IQCODE include method of administration (for example, self-completed questionnaire versus direct questioning interview); nature of informant; language of assessment. If a novel form of IQCODE is used, details of the scale should be included or a reference given to an appropriate descriptive text. Where IQCODE is used in a novel manner, for example, a translated questionnaire, there should be evidence of validation.

Weighting: Low risk

Were sufficient data on dementia assessment method given for the assessment to be repeated in an independent study?

The criteria used for clinical assessment are discussed in another item. Particular points of interest for dementia assessment include the background of the assessor, training/expertise of the assessor; additional information available to inform diagnosis (neuroimaging; neuropsychological testing).

Weighting: Low risk

 

Declarations of interest

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Appendices
  6. Declarations of interest

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

References

Additional references

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Appendices
  7. Declarations of interest
  8. Additional references
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