Abstract
Leisure-time physical activity (PA) and exercise training are known to help maintain cognitive function in healthy older adults. However, relatively little is known about the effects of PA on cognitive function or brain function in those at increased risk for Alzheimer’s disease through the presence of the apolipoproteinE epsilon4 (APOE-ε4) allele, diagnosis of mild cognitive impairment (MCI), or the presence of metabolic disease. Here, we examine the question of whether PA and exercise interventions may differentially impact cognitive trajectory, clinical outcomes, and brain structure and function among individuals at the greatest risk for AD. The literature suggests that the protective effects of PA on risk for future dementia appear to be larger in those at increased genetic risk for AD. Exercise training is also effective at helping to promote stable cognitive function in MCI patients, and greater cardiorespiratory fitness is associated with greater brain volume in early-stage AD patients. In APOE-ε4 allele carriers compared to non-carriers, greater levels of PA may be more effective in reducing amyloid burden and are associated with greater activation of semantic memory-related neural circuits. A greater research emphasis should be placed on randomized clinical trials for exercise, with clinical, behavioral, and neuroimaging outcomes in people at increased risk for AD.
Highlights
Cognitive decline in late life is associated with loss of independence, functional decline in activities of daily living, nursing home placement, and mortality [1,2,3]
A greater research emphasis should be placed on randomized clinical trials for exercise, with clinical, behavioral, and neuroimaging outcomes in people at increased risk for Alzheimer’s disease (AD)
Some have shown that the protective effects of physical activity (PA) on risk for future dementia appear to be larger in those at increased genetic risk for AD, but others have not observed this association
Summary
Cognitive decline in late life is associated with loss of independence, functional decline in activities of daily living, nursing home placement, and mortality [1,2,3]. A physically active lifestyle and greater cardiorespiratory fitness have long been associated with reduced all-cause mortality [11,12,13], and more recently with reduced mortality attributable to dementia [14,15] In both healthy human subjects [16] and in animal models [17,18], exercise and PA have been shown to benefit cognitive function and may offer neuroprotection. The neuroprotective effects of exercise have been shown to be robust in the hippocampal complex and dentate gyrus [16,22,23] These brain areas are important to learning and memory and are attacked early in the course of AD, the most common cause of dementia in older adults [24]. We propose that the question of whether PA and exercise interventions may impact future cognitive decline and brain function, and possibly slow AD progression, may best be addressed by focusing on those individuals at greatest risk for AD
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