A – 89 The Impact of Physical Activity on Brain Health in APOE e4 Carriers and Non-Carriers: A Narrative Review

Abstract Objective Dementia is a leading cause of disability and mortality among older adults, and cognitive decline has become a growing public health issue with the aging population. Physical activity (PA) may help delay or prevent cognitive decline, especially in individuals genetically at risk. This review explores whether PA can buffer the effects of APOE e4, a genetic risk factor for dementia, on brain health. Both APOE e4 and PA are linked to cardiometabolic mechanisms, suggesting PA may counteract APOE e4’s negative effects on cognition. Method A PubMed search was conducted using MeSH and keyword terms related to APOE e4, PA, and brain health. Studies involved adults aged 50 years and older, examined PA as a moderator of APOE e4, and reported brain health outcomes. Results Sixteen studies were included, all using PA as the intervention. Brain health outcomes varied, including dementia diagnosis, cognitive performance, brain blood flow, change in white matter integrity, and amyloid levels. Eleven studies found PA moderated the effect of APOE e4. Of these, six showed greater cognitive and neurological benefits for non-carriers, two reported stronger benefits among carriers with higher levels of light or vigorous PA, and three linked low PA in carriers to increased dementia risk or amyloid accumulation. The five remaining studies found no moderation, though PA still showed general brain health benefits. Conclusion Evidence suggests PA may support brain health especially among non-carriers, though carriers may also benefit. Low PA is particularly harmful for carriers, emphasizing the importance of regular PA for all older adults.