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.
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 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).
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.
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.