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

Abstract

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.

Figure 1

Results of voxelwise analysis showing brain regions demonstrating significant differences between Famous and Unfamiliar name conditions for each of the four groups (Low Risk/Low PA; Low Risk/High PA; High Risk/Low PA; and High Risk/High PA). Areas in red indicate Famous > Unfamiliar; blue areas indicate Unfamiliar > Famous. Location and volume of activation foci delineated in Table 2. PA = physical activity.

Figure 2

Results of 2 (Physical Activity) × 2 (Risk) ANOVA conducted on 15 fROIs (p-values shown in 3 rightmost columns of Table 3). Yellow regions indicate significant effects; blue areas indicate non-significant effects. Main effects of Physical Activity and Risk are shown in left and middle panels; interaction effect (Physical Activity × Risk) in right panel. See Figure 3 for bar graphs illustrating significant main and interaction effects.

Figure 3

The 15 functional regions of interest (fROIs) are identified in the left panel with region numbers (R#) corresponding with activation foci delineated in Table 3. Bar graphs represent mean percent MR signal intensity change for main effects of Physical Activity and Risk (panels A and B, respectively) and interaction effect of Physical Activity × Risk (panel C). Post-hoc group differences are indicated by brackets in panel C (p < .01). Error bars = S.E.M.