Exercise, cognition and Alzheimer's disease: more is not necessarily better

Regional hypoperfusion, associated with a reduction in cerebral metabolism, is a hallmark of Alzheimer's disease (AD) and contributes to cognitive decline. Cerebral perfusion and hence cognition can be enhanced by exercise. The present review describes first how the effects of exercise on cerebral perfusion in AD are mediated by nitric oxide (NO) and tissue-type plasminogen activator, the release of which is regulated by NO. A conclusion of clinical relevance is that exercise may not be beneficial for the cognitive functioning of all people with dementia if cardiovascular risk factors are present. The extent to which cardiovascular risk factors play a role in the selection of older people with dementia in clinical studies will be addressed in the second part of the review in which the effects of exercise on cognition are presented. Only eight relevant studies were found in the literature, emphasizing the paucity of studies in this field. Positive effects of exercise on cognition were reported in seven studies, including two that excluded and two that included patients with cardiovascular risk factors. These findings suggest that cardiovascular risk factors do not necessarily undo the beneficial effects of exercise on cognition in cognitively impaired people. Further research is called for, in view of the limitations of the clinical studies reviewed here.