Interactions between stress and physical activity on Alzheimer's disease pathology

Physical activity and stress are both environmental modifiers of Alzheimer's disease (AD) risk. Animal studies of physical activity in AD models have largely reported positive results, however benefits are not always observed in either cognitive or pathological outcomes and inconsistencies among findings remain. Studies using forced exercise may increase stress and mitigate some of the benefit of physical activity in AD models, while voluntary exercise regimens may not achieve optimal intensity to provide robust benefit. We evaluated the findings of studies of voluntary and forced exercise regimens in AD mouse models to determine the influence of stress, or the intensity of exercise needed to outweigh the negative effects of stress on AD measures. In addition, we show that chronic physical activity in a mouse model of AD can prevent the effects of acute restraint stress on Aβ levels in the hippocampus. Stress and physical activity have many overlapping and divergent effects on the body and some of the possible mechanisms through which physical activity may protect against stress-induced risk factors for AD are discussed. While the physiological effects of acute stress and acute exercise overlap, chronic effects of physical activity appear to directly oppose the effects of chronic stress on risk factors for AD. Further study is needed to identify optimal parameters for intensity, duration and frequency of physical activity to counterbalance effects of stress on the development and progression of AD.