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Physical activity for older adults at risk for Alzheimer disease.

IN THE LAST 35 YEARS, THERE HAS BEEN INCREASED APPREciation for the health value of habitual exercise and increased attention to the importance of improved physical fitness throughout the lifespan. Exercise appears beneficial for older adults particularly for maintaining function with aging and reducing risk and improving outcomes for common age-related chronic diseases. Past controversies over exercise and heart disease (especially risk of sudden cardiac death) have given way to a general consensus that exercise is an important lifestyle intervention. Physicians and public health experts have been prescribing exercise like a medication, given that its benefits have been amply demonstrated in cohort studies and randomized clinical trials. The effects of exercise on health are perhaps best documented and greatest in primary and secondary prevention of all-cause and cardiovascular disease mortality and diabetes. Effect sizes can be quite dramatic. One review of randomized clinical trials of prevention of diabetes concluded that programs of diet and exercise reduced incidence of diabetes 40% to 60% over 3 to 4 years. A randomized clinical trial involving modest physical activity for at least 150 minutes per week showed a number needed to treat of 7 to prevent 1 case of diabetes in 3 years, compared with 14 for the metformin-treated group. A pertinent question is whether physical activity can influence cognitive changes in late life and delay development of Alzheimer disease and late-life dementias. The article by Lautenschlager and colleagues in this issue of JAMA evaluates the effect of physical activity on cognitive function. In this study, a group at higher risk for cognitive decline and dementia—older patients complaining of memory impairment—was randomly assigned to receive either usual care or a 24-week home-based program of increased physical activity. At the 18-month follow-up, the trial showed a statistically significant difference of 0.69 point between the treatment and control groups in changes on the primary outcome measure, the Alzheimer Disease Assessment Scale–Cognitive Subscale scale (ie, 70-point scale of 11 brief cognitive tests). The mean “improvement” in the exercise group was 0.73 point vs 0.04 point for the control group. Neither patients, family members, nor clinicians could easily detect that level of difference, despite its statistical significance. As in most community-based trials involving walking and modest levels of exercise, adverse events were not an important consequence of the intervention. Comparing physical activity with other possible interventions for cognitive impairment, the authors point out that trials of cholinesterase inhibitors neither provide evidence that donepezil delays onset of Alzheimer disease nor support its use in patients with mild cognitive impairment: “Positive benefits are minor, short lived and associated with significant side effects.” Even though it is difficult to estimate the potency of cholinesterase inhibitors compared with an exercise program, results of the most widely cited prevention trial and Cochrane Reviews on cholinesterase inhibitors in mild cognitive impairment and Alzheimer disease suggest that the effects of cholinesterase inhibitors are at best modest and, in everyday practice, typically difficult to detect. Adverse effects are easier to detect than is effectiveness, and adverse effects are common with cholinesterase inhibitors but not common in exercise trials. Although most patients might find it easier to take a pill a day, patients and their families are likely to be gratified by the benefits of habitual exercise and often may be disappointed with the effects of cholinesterase inhibitors. Neither is very potent, and to date randomized trials have provided no evidence that either exercise or cholinesterase inhibitors prevent conversion to Alzheimer disease. The absence of subjective benefit (of drug or exercise) makes adherence critical. In the United States, pharmaceutical direct-toconsumer advertising has sensitized patients and the public to using cholinesterase inhibitors for Alzheimer disease. This illustrates the appeal of “doing something—anything” that might help prevent a dreaded disease, even if its value is minimal. Promoting habitual exercise for aging patients seems more worthy. An important issue is how well the trial by Lautenschlager et al applies to the population of older adults at greatest risk of cognitive decline who also may have more