Does physical activity reduce risk for Alzheimer's disease through interaction with the stress neuroendocrine system?

Abstract

Lack of physical activity (PA) is a risk factor for Alzheimer's disease (AD), and PA interventions are believed to provide an effective non-pharmacological approach for attenuating the symptoms of this disease. However, the mechanism of action of these positive effects is currently unknown. It is possible that the benefits may be at least partially mediated by the effects on the neuroendocrine stress system. Chronic stress can lead to dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis, leading to aberrant basal and circadian patterns of cortisol secretion and a cascade of negative downstream events. These factors have been linked not only to reduced cognitive function but also increased levels of amyloid-β plaques and protein tau "tangles" (the neuropathological hallmarks of AD) in the non-demented mouse models of this disease. However, there is evidence that PA can have restorative effects on the stress neuroendocrine system and related risk factors relevant to AD. We explore the possibility that PA can positively impact upon AD by restoring normative HPA axis function, with consequent downstream effects upon underlying neuropathology and associated cognitive function. We conclude with suggestions for future research to test this hypothesis in patients with AD.