Screening for cognitive impairment in older adults: an evidence update for the U.S. Preventive Services Task Force
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We conducted this systematic review to support the U.S. Preventive Services Task Force (USPSTF) in updating its recommendation on screening for cognitive impairment in older adults. Our review addresses five questions: 1) Does screening for cognitive impairment in community-dwelling older adults improve decisionmaking, patient, family/caregiver, or societal outcomes?; 2) What is the test performance of screening instruments to detect dementia or mild cognitive impairment (MCI) in community-dwelling older adult primary care patients?; 3) What are the harms of screening for cognitive impairment?; 4) Do interventions for early dementia or MCI in older adults improve decisionmaking, patient, family/caregiver, or societal outcomes?; and 5) What are the harms of interventions for cognitive impairment? We reviewed 12 relevant existing systematic reviews; database searches through December 2012 in MEDLINE, PsycINFO, and the Cochrane Central Register of Controlled Trials; and additional searches for ongoing trials through ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform, and Current Controlled Trials (ISRCTN Register). We conducted dual independent review of 16,179 abstracts and 1,190 articles against the specified inclusion criteria, including: screening instruments that could be delivered in primary care in 10 minutes or less by a clinician or self-administered in 20 minutes or less; diagnostic accuracy studies that used a reference standard; screening studies conducted in unselected community-dwelling older adults relevant to primary care in the United States; major pharmacologic and nonpharmacologic interventions in people with MCI or mild to moderate dementia; intervention trials of efficacy; or trials and large observational studies examining adverse effects. We conducted dual independent critical appraisal of all included studies, and extracted all important study details and outcomes from fair- or good-quality studies. For diagnostic accuracy studies, we focused on sensitivity and specificity of instruments that were evaluated in more than one study. For treatment trials, we synthesized results by intervention type. We conducted a qualitative synthesis of results using summary tables and figures to capture key study characteristics, sources of clinical heterogeneity, and overall results of each study. Quantitative synthesis was limited to test performance of the Mini Mental State Examination (MMSE) (due to insufficient number of homogeneous studies for other instruments) and U.S. Food and Drug Administration (FDA)-approved medications to treat AD and other medications and dietary supplements on global cognitive outcomes; caregiver interventions on caregiver burden and depression outcomes; and nonpharmacologic interventions aimed at the patient on global cognitive outcomes. Screening (Key Questions 1-3): No trials examined the direct effect of screening for cognitive impairment on important patient outcomes, including patient, caregiver, and clinician decisionmaking outcomes. We identified 55 studies that addressed the diagnostic accuracy and harms of brief screening instruments to detect cognitive impairment. Most instruments were only studied in a handful of well-designed diagnostic accuracy studies in primary care-relevant populations. The MMSE remains the most thoroughly studied instrument. Pooled estimates across 14 studies (n=10,185) resulted in 88.3 percent sensitivity (95% CI, 81.3 to 92.9) and 86.2 specificity (95% CI, 81.8 to 89.7) for a cut-point of 23/24 or 24/25 to detect dementia. Other instruments with more limited evidence to detect dementia include the Clock Drawing Test (CDT) (k=7; n=2,509), Mini-Cog (k=4; n=1,570), Memory Impairment Screen (MIS) (k=5; n=1,971), Abbreviated Mental Test (AMT) (k=4; n=824), Short Portable Mental Status Questionnaire (SPMSQ) (k=4; n=1,057), Free and Cued Selective Reminding Test (FCSRT) (k=2- n=734), 7-Minute Screen (7MS) (k=2; n=553), Telephone Interview for Cognitive Status (TICS) (k=2; n=677) and Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) (k=5; n=1,108). In general, these tests can have reasonable test performance, but the range of sensitivity and specificity varies across the studies likely due to clinical heterogeneity. The best-quality studies for the MIS and AMT show low sensitivity. The AMT, SPMSQ, FCRST, 7MS, and TICS have very limited evidence in English. Much more limited evidence exists for the following instruments to detect MCI: MMSE (k=15; n=5,758), IQCODE (k=4; n=975), CDT (k=4; n=4,191), Mini-Cog (k=3; n=1,092), TICS (k=3; n=568), and the Montreal Cognitive Assessment (MoCA) (k=2; n=251). The sensitivity and/or specificity of these instruments is generally worse for the detection of MCI compared with dementia. Other instruments (i.e., 6-Item Screener, Visual Association Test, General Practitioner Assessment of Cognition, activities of daily living/instrumental activities of daily living, Benton's Orientation Test, Delayed Recall Test, and the Short Concord Informant Dementia Scale for dementia; AD8, St. Louis University Mental Status Exam, and Computer Assessment of Mild Cognitive Impairment for MCI) appear promising; however, their test performance has not been reproduced in other primary care-relevant populations. No studies directly addressed the adverse psychological effects of screening or adverse effects from false-positive or false-negative testing. One fair-quality study found that approximately half the older adults who screened positive for cognitive impairment refused to complete a formal diagnostic workup. Treatment (Key Questions 4-5): We identified one systematic review and 131 additional studies that addressed the treatment or management of mild to moderate dementia and/or MCI. Pharmacologic Interventions: Overall, based on one systematic review (50 trials) and 14 subsequently published trials evaluating donepezil, galantamine, rivastigmine, and memantine in people with mild to moderate dementia, these medications can improve global cognitive function in people with Alzheimer's Disease (AD) in the short-term. However, the magnitude of these changes is small, at approximately 1- to 3-point change on the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog). The average effect of these changes is likely not clinically meaningful using commonly accepted values to interpret the clinical importance of these changes (4-point change on ADAS-cog over 6 months). Acetylcholinesterase inhibitors (AchEIs), but not memantine, appear to consistently improve measures of global functioning in people with AD in the short-term. Adverse effects from AChEIs are common. While there does not appear to be a difference in total serious adverse events for these medications across randomized trials, estimates of total serious adverse events appear higher in observational studies than in the trials. Trials evaluating other medications or dietary supplements (k=26; n=5,000), including low-dose aspirin, HMG-CoA reductase inhibitors (simvastatin and atorvastatin), nonsteroidal anti-inflammatory drugs (ibuprofen, naproxen, indomethacin, and celecoxib), gonadal steroids (estrogen plus or minus progesterone and testosterone), and dietary supplements (multivitamins, B vitamins, vitamin E plus or minus vitamin C, and omega-3 fatty acids) showed no benefit on global cognitive or physical function in people with mild to moderate dementia or MCI. Nonpharmacologic Interventions: We identified 59 fair- to good-quality trials evaluating the effect of multiple different types of interventions primarily aimed at the caregiver or the patient-caregiver dyad. Complex psychoeducational caregiver interventions (k=48; n=8,216) generally showed a small benefit (standardized effect size, approximately 0.2) on caregiver burden and depression outcomes. Although findings were somewhat inconsistent across cognitive intervention trials (k=15; n=1,128), cognitive stimulation plus or minus cognitive training appears to improve global cognitive function in the short-term for both people with MCI or dementia. Our ability to determine the magnitude and certainty of this benefit, however, is impeded by the limited number of trials and clinical (and statistical) heterogeneity, as well as the very wide confidence intervals (ranging from clinically not meaningful to a large effect). Harms were not reported in the included trials for caregiver or cognitive interventions. Exercise intervention trials (k=10; n=1,033) showed no consistent benefit on global cognitive outcomes or patient depression outcomes in people with MCI or mild to moderate dementia. Limitations include limited reproducibility of the test performance of instruments that are feasible to use in primary care; differences in estimates of test performance, which may be due to differences in populations or administration and scoring (choice of cut-point) of the instrument itself; and lack of clarity and standardization of defining MCI in diagnostic accuracy studies. Research in treatment of dementia other than AD is limited, and the average treatment effects of benefit for FDA-approved medications for AD and intensive interventions are small and generally in people with moderate dementia; thus, it is difficult to interpret its clinical importance and applicability for screen-detected patients. Other important measures of global functioning, such as health-related quality of life, global physical functioning, emergent or unexpected health care utilization, and institutionalization, are generally inconsistently reported. We found no trial evidence that examined the effect of screening for cognitive impairment on patient, caregiver, or clinician decisionmaking or important patient, caregiver, or societal outcomes. Several brief screening instruments can adequately detect dementia, especially in populations with a higher prevalence of underlying dementia. Despite the size of this body of literature, only a handful of instruments have been studied as screening tests in more than one study. AChEIs, memantine, complex caregiver interventions, and cognitive stimulation all have evidence to support their use in mild to moderate dementia, specifically AD. However, the clinical importance of their benefit is unclear because the average effects of benefit observed in trials was small or had a large amount of imprecision.