Although experimental and epidemiologic studies support the role of exercise in late life as a means to prevent or delay the onset of dementia, several important questions remain unanswered. It is still uncertain whether this association is causal or whether physical activity is just a proxy measure for “life engagement,” for other cognitive activities, or for other lifestyle or sociodemographic characteristics associated with dementia. In all likelihood, the study by Larson and colleagues and other trials have taken us as far as observational data can toward excluding the explanations of reverse causation and confounding by “life engagement.” We need randomized trials to examine the effect of physical activity on cognitive function measures, and we need researchers to include clinical dementia end points in ongoing trials of lifestyle modification. Another unresolved issue is the selectivity of the relationship between exercise and dementia. Does this association apply only to specific subgroups? Previous studies have raised the possibility that the association of exercise with cognitive decline or dementia risk depends on the individual's apoliprotein E ε4 genotype, but the evidence is not consistent (10, 12, 15). Of interest, the study by Larson and colleagues raises the possibility that the potential benefit of exercise may be more pronounced in persons with lower levels of physical function. In this study, the assessment of physical function was based on 4 performance tests: 10-foot timed walk, time to stand from a seated position in a chair to a standing position 5 times, standing balance, and grip strength in the dominant hand. Exercise, particularly weight-bearing activity and strength training, improves physical function and helps maintain independence in older adults (16). Although Larson and colleagues are the first to report an interaction between level of physical function and physical activity and dementia risk, their findings highlight the importance of exercise for persons at all levels of ability but particularly those who already have some limitation in physical function. Finally, no one has defined the type, frequency, intensity, or duration of physical activity that is most beneficial in preventing cognitive deterioration.