Journal Article

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

Hantke, Nathan C., Nielson, Kristy A., Seidenberg, Michael, Antuono, Piero, Woodard, John L., Lancaster, Melissa A., Rao, Stephen M., Butts, Alissa M., Smith, J. Carson, Durgerian, Sally

2011

Overview

Evidence suggests that physical activity (PA) is associated with the maintenance of cognitive function across the lifespan. In contrast, the apolipoproteinE-ε4 (APOE-ε4) allele, a genetic risk factor for Alzheimer's disease (AD), is associated with impaired cognitive function. The objective of this study was to examine the interactive effects of PA and APOE-ε4 on brain activation during memory processing in older (ages 65–85) cognitively intact adults. A cross-sectional design was used with four groups (n=17 each): (1) Low Risk/Low PA; (2) Low Risk/High PA; (3) High Risk/Low PA; and (4) High Risk/High PA. PA level was based on self-reported frequency and intensity. AD risk was based on presence or absence of an APOE-ε4 allele. Brain activation was measured using event-related functional magnetic resonance imaging (fMRI) while participants performed a famous name discrimination task. Brain activation subserving semantic memory processing occurred in 15 functional regions of interest. High PA and High Risk were associated with significantly greater semantic memory activation (famous>unfamiliar) in 6 and 3 of the 15 regions, respectively. Significant interactions of PA and Risk were evident in 9 of 15 brain regions, with the High PA/High Risk group demonstrating greater semantic memory activation than the remaining three groups. These findings suggest that PA selectively increases memory-related brain activation in cognitively intact but genetically at-risk elders. Longitudinal studies are required to determine whether increased semantic memory processing in physically active at-risk individuals is protective against future cognitive decline. ►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.

• Publisher: Elsevier Inc
• Subject: Age-related cognitive decline / Aged / Aged, 80 and over / Alzheimer Disease - genetics / Alzheimer's disease / APOE-epsilon4 allele genetic risk / Apolipoprotein E4 - blood / Apolipoprotein E4 - genetics / Auditory Perception / Brain - anatomy & histology / Brain - physiology / Dementia - epidemiology / Educational Status / Exercise / Female / fMRI / Humans / Leisure Activities / Leisure-time physical activity / Magnetic Resonance Imaging - methods / Male / Memory - physiology / Patient Selection / Sensitivity and Specificity / Verbal Learning