Mens Sana in Corpore Sano

Juvenal's centuries-old dictum to pray for a healthy mind (mens sana) in a healthy body (corpore sano) is taking on a literal meaning: Ongoing research is accumulating evidence that physical activity might delay neurocognitive decline and Alzheimer disease. Alzheimer disease is a major public health problem, affecting an estimated 4.5 million persons in the United States (1). The global aging of the population will translate into many more cases of dementia, further emphasizing the urgency of identifying potentially preventable risk factors. The only established risk factors for Alzheimer disease are advanced age, family history of dementia, low educational attainment, and presence of the apolipoprotein E genotype ε4 allele (2). No amount of behavior modification will alter these risk factors, so it is enticing to think that engaging in regular exercise can delay or prevent the development of Alzheimer disease.

Experimental studies support a role of physical activity in protecting brain structure and function. Compared with inactive adult mice, active adult mice have reduced cerebral accumulation of neurodegenerative byproducts, including β-amyloid plaques (3) and reactive oxygen species (4) that have been implicated in the pathogenesis of dementia. Voluntary exercise upregulates proteins that stimulate neural growth, most prominently brain-derived neurotrophic factor in the hippocampus, an area that is central to learning and memory and is particularly affected in Alzheimer disease and other dementing illnesses (5).

A recent review of observational studies concluded that exercise in late life is inversely associated with risk for all-cause dementia and Alzheimer disease (6). Six of 9 studies reviewed showed a reduced incidence of dementia among persons in the …