Physical activity and brain function in older adults at increased risk for Alzheimer's disease

Abstract

Leisure-time physical activity (PA) and exercise training are known to help maintain cognitive function in healthy older adults. However, relatively little is known about the effects of PA on cognitive function or brain function in those at increased risk for Alzheimer's disease through the presence of the apolipoproteinE epsilon4 (APOE-ε4) allele, diagnosis of mild cognitive impairment (MCI), or the presence of metabolic disease. Here, we examine the question of whether PA and exercise interventions may differentially impact cognitive trajectory, clinical outcomes, and brain structure and function among individuals at the greatest risk for AD. The literature suggests that the protective effects of PA on risk for future dementia appear to be larger in those at increased genetic risk for AD. Exercise training is also effective at helping to promote stable cognitive function in MCI patients, and greater cardiorespiratory fitness is associated with greater brain volume in early-stage AD patients. In APOE-ε4 allele carriers compared to non-carriers, greater levels of PA may be more effective in reducing amyloid burden and are associated with greater activation of semantic memory-related neural circuits. A greater research emphasis should be placed on randomized clinical trials for exercise, with clinical, behavioral, and neuroimaging outcomes in people at increased risk for AD.

Figure 1

Results of voxelwise analysis by Smith et al., 2011 [107] showing brain regions with 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. PA = physical activity. Figure reproduced with permission from [107], Copyright © 2011, Elsevier.

Figure 2

Fifteen functional regions of interest (fROIs) identified by Smith et al., 2011 [107]. In the left panel, region numbers (R#) correspond with activation foci shown on the right. 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 < 0.01). Error bars = S.E.M. Figure reproduced with permission from [107], Copyright © 2011, Elsevier.

Figure 3

Functional Regions of Interest (fROIs) derived from all regions activated in both MCI groups in Smith et al., 2011 [112]. The six regions of interest are shown in the top (left hemisphere) and middle (right hemisphere) panels. The two groups significantly differed only in activation (Famous > Unfamiliar) of the left caudate region (circled in yellow, axial view in the lower left panel, z = +10 mm superior to the AC-PC line). The MR signal intensity difference (%AUC) between the Low-PA and High-PA groups in the left caudate region is shown in the lower right panel. Error bars = SEM. Figure reproduced with permission from [112], Copyright © 2011, Elsevier.