Interactive effects of physical activity and APOE-ε4 on BOLD semantic memory activation in healthy elders

►Recent work, both in animals and humans, has shown that exercise and physical activity benefit cognitive function and offer neuroprotection. There has been great interest and speculation regarding whether or not these benefits extend to older adults at greater risk for Alzheimer's disease. The revised manuscript we submit today is important, and carries broad appeal to the neuroimaging, neuroscience, and geriatrics communities, because it is the first to report increased semantic memory-related brain activation associated with greater levels of physical activity that are specific to older adults at genetic risk for Alzheimer's disease. In other work, we report that increased brain activation among cognitively intact APOE-ε4 allele carriers is protective against future cognitive decline. Here, we extend these findings and report an interaction between the amount of self-reported physical activity and genetic risk. We found that enhanced semantic memory activation was observed specifically in APOE-ε4 allele carriers who reported a higher level of leisure-time physical activity. These findings provide preliminary cross-sectional evidence that physical activity, as a lifestyle behavior, may enhance semantic memory-related neural activation among people at genetic risk for Alzheimer's disease. This work touches upon a broad range of interests among the readership of the NeuroImage, including age-related cognitive decline, the neurobiology of dementia, semantic memory processes, and cortical plasticity, and has important implications for clinicians who treat patients at risk for cognitive decline or dementia.