Case Study

RG, a 75-year-old, college-educated man, presents for an annual physical examination. His friend recently was diagnosed with Alzheimer’s disease. RG is concerned about his occasional memory lapses and is worried that he also has the disease. He has heard about a medication that can treat Alzheimer’s disease and wants to use it. He has begun taking ginkgo biloba and vitamin E supplements. You consider whether he should be screened for dementia and how to advise him on his interest in medications.

Case Study Questions

1. Which one of the following statements describes the current U.S. Preventive Services Task Force’s (USPSTF) recommendations on screening for dementia?

   A. The USPSTF recommends screening for dementia in all adults older than 65 years.

   B. The USPSTF recommends screening for dementia in all adults older than 50 years.

   C. The USPSTF recommends asking the caregivers or relatives of adults older than 65 years about symptoms indicative of dementia.

   D. The USPSTF found insufficient evidence to recommend for or against routine screening for dementia in older adults.

   E. The USPSTF recommends against routine screening for dementia in asymptomatic adults.

2. Which of the following statements regarding dementia screening tests are accurate?

   A. The Mini-Mental State Examination (MMSE) has a high positive predictive value in diagnosing cognitive impairment in primary care settings.

   B. The accuracy of the MMSE depends on the age, education level, and ethnicity of the patient.

   C. The Clock Drawing Test has not yet been evaluated adequately in primary care settings.

   D. The Functional Activities Questionnaire (FAQ) can be used only in patients with caregivers and measures only functional impairment.

3. Which one of the following statements about the treatments available for mild to moderate dementia is correct?

   A. Cholinesterase inhibitors markedly improve the daily functioning of persons with moderate Alzheimer’s disease.

   B. Ginkgo biloba markedly improves cognitive function in persons with moderate Alzheimer’s disease.

   C. Cholinesterase inhibitors improve cognitive function and can slow the progression of disease in persons with mild to moderate Alzheimer’s disease.

   D. Vitamin E supplementation improves cognition in persons with moderate Alzheimer’s disease.

   E. Estrogen supplementation improves cognition in women with mild to moderate Alzheimer’s disease.

Answers

1. The correct answer is D. The USPSTF concludes that the evidence is insufficient to recommend for or against routine screening for dementia in older adults. The USPSTF found good evidence that some screening tests have good sensitivity but only fair specificity in detecting cognitive impairment and dementia. Although there are several medications that can improve cognitive function in the short term, their effect on daily functioning is not clearly beneficial, and there is insufficient evidence to determine whether the benefits observed in drug trials are generalizable to patients whose disease would be detected by primary care screening. The accuracy of diagnosis, the feasibility of screening and treatment in routine clinical practice, and the potential harms of screening (e.g., labeling effects) also are unknown. The task force therefore could not determine whether the benefits of screening for dementia outweigh the harms.

2. The correct answers are B, C, and D. The accuracy of the MMSE depends on the age, education level, and ethnicity of the patient; using an arbitrary cut-point can lead to more false-positive results in older, less educated persons and more false-negative results in younger, more educated persons. The MMSE is most accurate in white patients with at least a high school education. The positive predictive value of the MMSE in a population with a 10 percent prevalence of dementia may range from 15 to 72 percent. The best evidence is available from studies in primary care settings that used standardized diagnostic instruments (e.g., the Diagnostic and Statistical Manual of Mental Disorders, 4th ed.) as a gold standard. Depending on the cut-point used for an abnormal result, the sensitivity of the MMSE for dementia ranges from 71 to 92 percent, and the specificity ranges from 56 to 96 percent.

The Clock Drawing Test, Short Portable Mental Status Questionnaire, Modified MMSE, Mini-Cog, Hopkins Verbal Learning Test, and seven-minute screen are promising tests that can detect cognitive impairment, but they have yet to be adequately evaluated in primary care settings. The FAQ has sensitivity and specificity of 90 percent, but it can be used only in patients with care-givers. Furthermore, it measures functional impairment but not cognitive impairment. Other informant-based functional tests, such as the Informant Questionnaire on Cognitive Decline in the Elderly and the Instrumental Activities of Daily Living Questionnaire, also have been tested. The functional test instruments offer the advantage of “everyday relevance,” acceptability by patients, adaptability to various types of patients, administrative ease, longitudinal perspective, and cross-cultural portability. Few methodologically sound studies on the accuracy of these questionnaires in primary care settings have been completed.

3. The correct answer is C. There is fair to good evidence that several drug therapies have a beneficial effect on cognitive function in the short term, but the evidence of their beneficial effects on instrumental activities of daily living is mixed, with the benefit being small, at best. For example, cholinesterase inhibitors benefit cognitive function and can slow the progression of disease in persons with mild to moderate Alzheimer’s disease. Most studies comparing the effect of cholinesterase inhibitors with placebo among patients with mild to moderate Alzheimer’s disease found a statistically significant difference favoring cholinesterase inhibitors. A slowing of decline is approximately equivalent to a delay in disease progression of up to seven months in a person with mild dementia, or a delay of two to five months in a person with moderate dementia. However, the evidence of the effects of cholinesterase inhibitors on functional measures, such as instrumental activities of daily living, is mixed. In general, the studies have shown little or no effect of cholinesterase inhibitors on functional decline after six months of treatment and a small but statistically significant difference from placebo after 12 months of treatment.

Evidence that other drugs have important benefits in Alzheimer’s disease is weak. High-quality studies comparing ginkgo biloba with placebo found a small (i.e., approximately 3 percent) difference in cognitive scales. Randomized controlled trials of vitamin E and estrogen found no evidence of cognitive improvement.