Screening for dementia is it a no brainer?

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1 PERSPECTIVE Screening for dementia is it a no brainer? As people are living longer, dementia is becoming a significant issue for society. Dementia is now recognised as a major concern in society, and the numbers of people estimated to have dementia in the UK population appear to have stabilised at around 700,000 (1,2). Globally, 35.6 million people are estimated to meet criteria for dementia, a number predicted to double every 20 years (3). Given the absence of treatments that significantly alter the natural history of the clinical syndrome of dementia, there has been increased emphasis on early diagnosis, with research exploring assessment tools and biomarkers that might predict with certainty a particular clinical outcome. At the same time, there has been pressure to focus on biomedical profiles, which assume a very close link between the pathobiology and the manifest clinical syndrome. Estimates of dementia prevalence have long been used by policy makers to consider what services might be necessary for populations. However, in the last few years, these estimates have come to be used rather differently, as the baseline against which the gap in known cases is measured. The implications for health and social services have become increasingly articulated, most recently in the UK Prime Minister s Challenge and policies that appear to introduce implicit screening into acute and primary care settings. There is, however, a disconnection between the rhetoric on the benefits of an early diagnosis of dementia and the strength of the evidence required to introduce such measures on a national scale. Despite this lack of evidence, public surveys suggest the population thinks that dementia is modifiable, and that screening is self-evidently therefore a good thing. Cognitive impairment has been reported to be unrecognised in significant numbers (up to 80%) of affected patients in primary care (4). There is a significant gap in expected vs. observed prevalence. The reasons are multifactorial. There is a general improvement in general practitioners, attitudes and confidence in diagnosis but there are many factors that lead to under recognition. Reasons highlighted include the complexity of cognitive decline and impairment as part of continua in the ageing population, influenced by many cultural, social and clinical factors; poor awareness of how common it is or, indeed, the opposite, awareness of just how common it is; poor confidence of GPs in their clinical skills; therapeutic nihilism the perception (and possibly knowledge) that current treatments are often ineffective; the belief that the patient would rather not know; perceived lack of time and other resources; and also the belief that diagnosis is not within the realm of general practice. Symptoms may often be seen as part of the normal ageing process by carers, patients and professionals which, from a population perspective, is true. This, from a population perspective, is true as only a proportion of those people with low cognitive performance will meet specific criteria for a diagnosis of dementia. There will be a range of explanations including terminal decline, lifelong poor cognition, comorbidity, effects of medication and impairment associated with specific disorders such as cancer, vascular disorders and ageing itself. The evidence base in dementia Our perspective is that, despite the laudable enthusiasm of political leaders to improve care and quality of life for people with dementia, the active and systematic application of methods to identify people with cognitive impairment that might be dementia (effectively population screening, even if delivered to specific groups) is not the proven way to achieve these ends. We argue that such developments cannot be promoted as known to achieve these aims as the evidence base is insufficient at present. Indeed, there may be several risks to societies that attempt to introduce this type of strategy. For a start, cognitive impairment is not synonymous with dementia, for several reasons: Cognition, however it is measured, has a continuous distribution in the population, which changes in a continuous manner across the life course in older populations as there are no clear delineations between abnormal and normal, most very old people will have some impairment. Sensory and physical impairments may impact upon test performance: for example, arthritis and stroke impair the ability to use devices such as touch pads or tablet computers. Although there is an understandable desire to diagnose dementia as early as possible, there is limited evidence to support this doi: /ijcp

2 2 Perspective Comorbidity, both physical (e.g. delirium, cerebrovascular events and preterminal cognitive decline associated with specific illnesses such as cancer) and psychological (e.g. depression), can affect cognition and would lead to false positive diagnoses of dementias in screening. The increasing pressure to identify people at risk of dementia means that mild cognitive impairments (MCI) are being increasingly detected. Such impairments are extremely common with increasing age and make will have many underlying causes as noted above. Population-based longitudinal studies suggest that MCI is an unstable state, with reports that more cases return to normal than convert to dementia. MCI is easy to overdiagnose, there is no effective treatment intervention and there are no reliable predictors of who will convert to dementia, so there is a distinct risk of escalating levels of anxiety in otherwise well (or coping) people for no purpose. Until research on relevant populations in relevant clinical settings identifies risk for individuals with a much higher degree of precision, this is a negative consequence of earlier diagnostic testing. Screening and diagnosis In the UK, NICE (Support for commissioning dementia care April uk/support-for-commissioning-dementia-care-cmg48) emphasises that people suspected of having dementia should be asked if they wish to know the diagnosis (which implies that they would agree to go further with testing, although looking for underlying causes of cognitive impairment would presumably still be provided as part of normal clinical care) and with whom this should be shared. It is also recognised that some will not benefit from a diagnosis. However, the new NHS Direct Enhanced Service (DES) for dementia ( resources/resource-primary/) goes further than this. The DES indicates that consideration of dementia should be applied to at-risk patients with income for GPs attached to testing particular groups: (i) people aged 60 and over with cardiovascular disease, stroke, peripheral vascular disease or diabetes; (ii) people aged 40 and over with Down s syndrome; (iii) other people aged 50 and over with learning disabilities; (iv) people with long-term neurological conditions who have a known neurodegenerative element, for example, Parkinson s disease. These assessments will be in addition to other opportunistic investigations carried out by the GP practice (e.g., anyone presenting with a memory concern). This new initiative is effectively a mixture of population screening and case finding despite the clearly articulated lack of recommendation for population screening reflecting the lack of robust evidence for either (United States Preventative Services Task force review policy advice groups; the UK National Screening Committee and UK National Standard Standards Body-NICE 2013). Some of the recent arguments for screening are shown in Table 1 (see also (5)). Early diagnosis There has been an expressed desire from groups of patients and carers, their representatives in voluntary organisations and from some health professionals that it is essential to make a diagnosis as early as possible in every case, and that every person who meets the criteria for dementia should receive a diagnosis as not to do so is withholding known benefit. We argue that these assumptions are not met, that the articulation of these demands does not represent the whole of the population, nor that of the views of many of those working within the services who need to reorganise themselves to screen and deliver some sort of support. It is audacious to assume that the public has a single view on this: indeed, clinical experience suggests that there is a full spectrum of attitudes from enthusiasm for diagnosis to total denial. To push policies through before robust evidence is available is a concern for health and social care systems under strain. The main purpose of diagnosis is timely access to information, advice and support and access to a pathway of effective treatment and care from the time of diagnosis to end of life care and this should be provided in a manner which is sensitive to individuals and their families and the stage of the condition. There is no high quality research evidence for the benefit in diagnosing patients before the usual point of presentation (Table 2) (early diagnosis either through screening or opportunistic testing). If a patient s health and well-being is not enhanced by early diagnosis, then this should not be forced upon them (6). Although new research on biomarkers suggests that the pathological changes of dementia start 25 years before clinical symptoms become evident (7) (a finding already reported for neuropathological and neuropsychological measures decades ago) and that targeting of risk factors in mid and late life could hold promise in reducing incident dementia at particular ages (rather than across an extended life), there is no good quality evidence as yet that screening using such biomarkers will lead to a measurable probability of benefit for individual patients (8). It is true that health promotion messages could have a considerable impact in behavioural change to

3 Perspective 3 Table 1 Arguments for dementia screening (derived in part from Boorson et al., 5) Pro screening (1) Rapidly growing population at risk for dementia something must be done (2) Licensing of pharmaceutical agents for treatment of Alzheimer s dementia, together with a general belief that these drugs slow down the disease process (3) Broad media attention to the human suffering associated with Alzheimer s disease through news coverage of AD (4) Growing potential of both basic science and health services research to improve the outlook for affected people and their families Counter argument The limitations of assessment and parallels with cancer screening identifying cases not requiring treatment These are at best modest in impact and the evidence in asymptomatic and early cases is absent. No evidence of disease modification There is still a lack of understanding of the harms and benefits of screening coupled with assumption that there must be effective treatment if screening is being advocated With no significant breakthrough in basic science, and repeated care system failings in healthcare systems, this is overemphasised and can divert resources from services, e.g. social care, for which there is a better evidence base Table 2 Assumed benefits to early diagnosis Benefit Ability to plan for the future regarding care choices and financial decision-making Early education for families about the disease which can help reduce caregiver stress and reduce burden Package of services to manage early diagnosis can improve quality of life and reduce behavioural symptoms Timely diagnosis has been shown to improve quality of life for patients and carers and can delay transition into care homes Early provision of in-home support has been identified as decreasing risk of institutionalisation by 22% Risk issues such as driving, cooking, medication compliance and inappropriate medication (e.g. anticholinergics) can be managed earlier For health and social care, it can offer the opportunity for better planning and monitoring of patients Comment/limitation This should be a part of planning for older age so applies to all older people Brief programme of support for relatives at diagnosis reduced care home placement by 28% (9). This study was limited by no control group, possible non-specific effects of intervention, and limited follow-up period As above, limitations of design and follow up (9) Evidence from 406 subjects from a single research clinic centre and were self-reported ratings (10). Biased sample and self-report bias likely 4761 patients from eight areas in USA and followed up for 3 years. Not randomly sampled and not representative sample. Those who died or were institutionalised in first 6 months were excluded. Only used duration of care measure and this may have been subject to recall bias (11) No clear evidence that intervention in risk issues is of benefit in this situation this is theoretical and based on opinion No evidence that intervention in risk issues is of benefit in this situation this is theoretical based on opinion improve people s risk profiles (especially smoking, exercise, stroke risk, etc.) but beyond this there is currently no compelling evidence to conduct screening for early biopathological changes. Indeed the benefit to whole populations may be gained years earlier through healthier early life which might be one of the reasons behind the 20 year drop in prevalence observed in England (2). Any potential method for screening and/or early diagnosis needs to have been assessed in the full population for its validity, reliability and cost-benefit-harm profile. The evidence must also show that individuals are at sufficiently high definite risk to warrant known effective intervention of some kind. We are a long way from this state at present. As there are no drug treatments to stop the progression of dementia and existing pharmacological treatments have a weak/modest benefit, there is little to offer on the treatment front. This evidence is at odds with the heavy promotion to the public of dementia treatments which has led to widespread misplaced over-expectation of these therapies. The significant benefits of early diagnosis for patients and carers and local health and social care are often cited as reasons for promoting these policies. The evidence supporting this view is from small numbers of individual studies, limited in size, population representation and generalisability which are continually reported and re-reported until they become accepted as strong evidence, in effect opinion becoming viewed as evidence. These always assume the diagnosis will have been accurate. The diagnostic process for dementia requires preand postdiagnostic counselling to manage potential harms. Patients and families expectations and the push to earlier stage diagnosis require a more tailored approach to minimise these potential harms. Prediagnostic testing should provide people with an honest account about the performance of the tests to

4 4 Perspective be used and the exact benefit/harms known from what would follow from a diagnosis. Such integration of evidence-based benefit is not available at present. This type of information is that which has led to the major debate about the breast screening programme in the UK with a complete re-evaluation of the way that information is provided to women before they decide to take part in the national screening programme. An alternative approach is to educate the whole public about the risks and likelihood of dementia at given ages and before death, with encouragement to consider and discuss these with appropriate others in later life. The way forward Evaluation of screening for dementia in population studies may lead to evidence of more benefit than harm and then the detailed plans for translational research to support roll out for a whole service including implementation science should be undertaken. Rigorous research of different types is needed: formal trials, experimental roll out with evaluation, implementation research and qualitative research. There is, as yet, no unequivocal evidence that earlier diagnosis is associated with better outcomes for people with dementia and their carers and there is a significant deficit in observational research data from population studies and clinical cohorts from which to draw conclusions. New diagnostic tools need to be sufficiently evaluated including consideration of their impact; for example, if they result in overdiagnosis or excessive investigations and diversion of resources (12). The misdiagnosis of dementia at present remains an important issue (13). Although biomarkers may assist, we are not there yet. We do not have the ideal dementia biomarker which, for the population to which they are to be applied, should: (i) have a sensitivity of well over 90% in dementia detection; (ii) have a specificity near 100%; (iii) be reliable; (iv) detect one or more fundamental feature of relevant neuropathology; (v) be non-invasive; (vi) be easy to perform; (vii) inexpensive. Given the fact that no single neuropathology accounts for the mixed dementias (which are most common in the oldest age groups), it is hard to be confident that this ideal will be reached. Rather, the current biomarkers being investigated are likely to identify large proportions of the older population without certainty of progression to dementia during their lifetimes. The National Institute on Aging in the USA has funded a randomised controlled dementia screening study in primary care that will address these issues in the US context (due to report 2016). In addition, the US Preventive Services Task Force is updating its 2003 recommendation regarding dementia screening imminently. The economic arguments in favour of early diagnosis have been promoted as promising, but tentative and the assumptions underpinning them must be tested (14). We argue that policy development within the area of early and presymptomatic detection of dementia should be driven by high-quality evidence not opinion and that timely diagnosis with sensitive identification of dementia at the right time for the particular person within their context, with clear capacity to benefit should be the emphasis until such research evidence is in place. In the UK, we await the outcome of a recent national consensus meeting to be published on the NHS England website in 2013 (5th June 2013 Timely diagnosis of dementia) with interest. Disclosure All authors have no conflicts of interest to report. All the authors except MB were in receipt of a grant from the Alzheimer s Society for a systematic review of screening in dementia. C. Fox, 1 L. Lafortune, 2 M. Boustani, 3,4 T. Dening, 5 G. Rait, 6 C. Brayne 2 1 Department of Psychological Sciences, Faculty of Medicine and Health Sciences, Norwich Medical School, University of East Anglia, Norwich, UK 2 Department of Public Health and Primary Care, Cambridge Institute of Public Health, University of Cambridge, Cambridge, UK 3 Indiana University School of Medicine, Indianapolis, IN, USA 4 Indiana University Center for Aging Research, Regenstrief Institute, Inc, Indianapolis, IN, USA 5 Institute of Mental Health, University of Nottingham, Nottingham, UK 6 PRIMENT Clinical Trials Unit, Research Department of Primary Care and Population Health, UCL Medical School, London, UK Correspondence to: Chris Fox, Department of Psychological Sciences, Faculty of Medicine and Health Sciences, Norwich Medical School, University of East Anglia, Norwich, UK Tel.: Fax: Chris.Fox@uea.ac.uk References 1 Alzheimer s Society Dementia 2012 Report. php?fileid=1390 (accessed 19 July 2013). 2 Matthews FE, Arthur A, Barnes LE et al. A two-decade comparison of prevalence of dementia in individuals aged 65 years and older from three geographical areas of England: results of the Cognitive Function and Ageing Study I and II. The Lancet doi: /S (13)

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