Exercise Promotes Healthy Cognitive Aging through the Hippocampus

Physical exercise appears to be a promising strategy to improve or maintain cognitive function, because research suggests it may enhance learning and memory among older adults. It remains unclear exactly how exercise enhances cognition. An improved understanding of the benefits of exercise, and of the biological pathways through which exercise affects the brain, may lead to strategies to prevent or minimize cognitive decline and dementia. A research review in the journal Neurobiology of Disease finds that exercise is likely to offset damage to the hippocampus that is associated with normal aging and accelerated by Alzheimer’s Disease (AD).

The authors reviewed existing research on both humans and animals that addresses the potential relationship between physical activity and cognitive ability. (Animal model studies are often a productive step in understanding biological disease and potential treatments.) The review focused on recent findings that identify the benefits of exercise, and on research on the biological mechanisms through which exercise can improve function in the hippocampus, which is an area of the brain associated with learning, memory, and other functions that are impaired in AD and other dementias.

High levels of physical activity have been consistently associated with better cognitive function among older adults. Physical activity is associated with lower rates of cognitive decline and reduced risk for AD, although the exact nature of this relationship is uncertain and is likely to be bidirectional (i.e., cognitively healthy individuals may be more likely to engage in physical activity). Individuals with existing cognitive impairments can likewise benefit from exercise, with randomized control trials suggesting that individuals with cognitive decline improve their memory and spatial skills following increased physical activity. Older adults who engage in significant physical activity appear to have greater hippocampal volumes, as well as decreased atrophy in other areas of the brain. Randomized control trials among humans have suggested that exercise can directly increase hippocampal volumes in older adults, leading to improvements in spatial and memory skills.

The review also examined the potential biological pathways through which exercise may benefit the brain. Animal models have shown that exercise may increase the body’s ability to produce proteins used to create new neural cells, particularly in the hippocampus. Further, increased physical activity in humans and animals appears to increase blood supply to areas of the hippocampus that may lead to improved memory.

This research suggests that exercise may mitigate several risk factors for AD and other neurological disorders, such as oxidative stress in the brain, brain inflammation, and genetic risk factors. Exercise appears to minimize the damage of oxidative stress because it improves the brain’s ability to convert potential nutrients to usable energy. Studies on humans suggest that regular exercise is associated with reduced chronic inflammation (which is associated with memory problems in older adults) and enhanced immune defenses, with animal models suggesting that anti-inflammatory compounds resulting from exercise may serve to protect the hippocampus.

Animal models also suggest that exercise may reduce the AD risk of individuals with the APOE ε4 genotype, which is a known risk factor for AD: while mice with this genotype perform poorly on spatial tasks known to involve the hippocampus, captive ε4 mice with access to a running wheel show improved hippocampal function relative to sedentary ε4 mice. Recent studies on older humans suggest that individuals with the ε4 genotype are particularly likely to see cognitive benefits from physical activity.

In sum, research suggests that exercise interventions have the potential to reduce cognitive decline and potentially mitigate the cognitive symptoms of AD. Exercise appears to promote hippocampal function and reduce atrophy in the hippocampus that is associated with age and with AD.


Intlekofer KA, Cotman CW. Exercise counteracts declining hippocampal function in aging and Alzheimer’s disease. Neurobiology of Disease (2013); 57: 47–55.

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