REVIEW Screening for memory disorders, dementia and Alzheimer’s disease J Wesson Ashford Dementia and its most common cause, Alzheimer’s disease, affect memory and occur Stanford/VA Aging Clinical Research Center, VA Palo Alto predominantly in the elderly. Dementia has become increasingly prevalent in the world as Health Care System, 151-Y, health has improved and life expectancy has increased. However, the fields of clinical care 3801 Miranda Ave, Palo have not responded adequately to develop diagnostic tools and treatments for this rapidly Alto, CA 94304, USA Tel.: +1 650 852 3287; increasing group of conditions. While scientists search for cures for the numerous causes of Fax: +1 650 852 3297; dementia, improvement of diagnostic measures are needed now and should begin with E-mail: [email protected] screening elderly populations for memory difficulties and other cognitive problems. This review examines the history of cognitive screening tests, the numerous excellent tests that are currently available and ready for use, and directions and methods that will lead to progressively better evaluations. There has been a growing question of whether to over the last 100 years and is expected to become screen for dementia [1]. The proposed answer is a much greater proportion of the USA and that screening for memory dysfunction, dementia World population in the future, the time has and Alzheimer’s disease (AD) is important, but come to address the global medical needs to care there are many practical and ethical considerations for individuals with dementia and AD on a that need to be addressed before general screening timely basis. Accordingly, there is a present need practices can be widely implemented [2–5]. to develop appropriate screening programs for As of 2008, there are numerous recommenda- these conditions, so proper care can be initiated. tions for screening for a variety of conditions, The purpose of this discussion is to review the including breast cancer, cervical cancer, colorec- history of testing for the presence of dementia tal cancer, skin cancer, diabetes, hypertension, and the problem of screening for dementia and high cholesterol, obesity, osteoporosis and even AD. There are published guidelines (Box 1) and for depression, provided treatment can be criteria (Box 2) for developing screening pro- offered [6]. However, the evidence for dementia grams, which provide specific information about screening has been complicated by a variety of what to consider in the development of factors, including the complexities of diagnosis screening systems. Finally, an analysis will be pre- and difficulties in assessing treatment benefits [7]. sented for making recommendations for useful For example, screening needs to be directed screening procedures. toward dementia (generic inclusion of a group of The discussion of the secondary steps which related conditions that impair memory and must be taken in response to a positive screen other forms of cognition), AD (a specific disease to establish any diagnosis is beyond the scope Authorprocess), or mild cognitive impairment (MCIProofof this presentation. However, it is critical to [8–13], a loosely defined group of conditions con- recognize that a screening test does not pro- sidered to include states prodromal to dementia, duce any diagnosis, anymore than a nonspe- particularly AD [12,13]). Clinicians should cific blood test result would be considered a become prepared to evaluate and manage the diagnosis. A diagnosis of dementia requires vast numbers of undiagnosed cases currently esti- specific criteria (for example, the Diagnostic mated as well as the huge increase in numbers of and Statistical Manual of Mental Disorders, 4th Keywords: Alzheimer’s demented patients expected between now and Edition [DSM-IV] [15] criteria for Dementia of disease, cognitive, dementia, item response theory, 2050. This preparedness must confront an addi- Alzheimer Type), and the diagnosis of AD has memory, mental, mini-mental tional obstacle, the considerable amount of been accepted to require clinical and neuro- state, modern test theory, ambivalence related to the prejudices about psychological assessment [16,17] to make a possi- neuropsychology, screening aging individuals and their optimal care. How- ble or probable diagnosis, with tissue ever, in general, patients have a positive reaction examination required for a certain diagnosis. part of to dementia diagnostic information [14]. As the There are also considerable differential diag- elderly population has progressively increased nostic issues for memory problems and demen- 10.2217/1745509X.4.4.xxx 2008 Future Medicine Ltd ISSN 1745-509X Aging Health (2008) 4(4), xxx–xxx 1 REVIEW – Ashford Box 1. User’s guides for guidelines and recommendations general, such tests have included the assessment of about screening. a range of functions, but few tests have been developed using specific theory, either about the Are the recommendations valid? mechanisms by which dementing diseases affect • Is there RCT evidence that earlier intervention works? the brain, the continua of dementia severity • Were the data identified, selected and combined in an unbiased fashion? associated with these various diseases, or the methodology of test construction. What are the recommendations and will they help you in caring for Since 1960, many test developers have used your patients? classical test theory concepts, recommending • What are the benefits? unweighted combinations of binary or graded • What are the harms? responses (frequently including Likert scaling) to • How do these compare in different people and with different simple tests or questions. screening strategies? Virtually all cognitive, behavioral and func- • What is the impact of people’s values and preferences? tional tests used in medical research make an • What is the impact of uncertainty? a priori assumption that the items take on val- • What is the cost–effectiveness? ues that are additive. In order for items to be Note: these guidelines are difficult to apply to a large, heterogeneous population such added together to generate a total score, meas- as that at risk for dementia. urement properties of ordinality and concaten- Adapted from [119] for the Evidence-Based Medicine Working Group; authors based in ability must be demonstrated. If ordinality is the British Commonwealth. satisfied, then nonparametric statistical meth- ods can be used to analyze the test results, but tia. There are related conditions for which parametric statistics cannot. If the items can be separate screens might be considered, such as concatenated and ordinality is satisfied, then vascular dementia, alcohol dependence and the items can be added together. Unless appro- depression, which are important for treatment priate measurement properties are satisfied, the determination. Depression, a treatable condi- statistical methods that have been applied to tion, may accompany or confuse the dementia the majority of cognitive, behavioral and func- diagnosis, in some cases even leading to a tional tests in medical research may be invalid. wrong diagnosis. Given the difficulties and This is a general problem in medical research importance of a correct diagnosis [18], careful that has largely been ignored, and is reflected in attention to full clinical assessment following a this review. positive screen is recommended. Several tests have been studied using the A developing issue which has not yet been receiver operator characteristic (ROC) curve addressed in the literature to the point of mak- model (many investigations employing inap- ing a clinical recommendation is screening for propriate subject sampling), though this MCI. The concept of determining the earliest approach requires a binary diagnostic decision signs of cognitive impairment that will precede not easily suited for a syndrome such as demen- dementia has long been a topic of consideration tia that is complex and usually has an insidious [19]. The term MCI was introduced in 1991 [9], onset. Modern test theory (item response the- was defined as a clinically meaningful syn- ory and item characteristic curve analysis [21–26], dromeAuthor in 1999 [8] and has acquired standard- Proofspecifically estimating level of ability/disability ized methods for distinguishing its clinical on a defined continuum based on performance, features [20], so that it is now recognized as a provides a considerably more powerful formal diagnosis (ICD-9 code 331.83), which approach for test development. The implemen- Medicare (USA) recognized as a valid reason for tation of this approach will be discussed. A neuropsychological testing in 2007. Tests are practical example, the brief Alzheimer screen now being developed for screening for MCI, [27], a 3–5 min test (see Appendix), provides and these are discussed below. more information about the presence of dementia than the Folstein Mini-Mental State History & progressive development Exam (MMSE) [28]. Progressively better tests of cognitive assessment for evidence can be developed with this theory. Ideally, of dementia screening tests will become computerized and Since the 1930’s, clinicians have developed a wide provide scores that indicate probability of variety of tests for assessing cognitive function dementia and ‘maximum-likelihood estimates’ and facilitating clinical screening for dementia. In of dementia severity. 2 Aging Health (2008) 4(4) futurefuture sciencescience groupgroup Screening for memory disorders, dementia and Alzheimer’s