Physical activity (PA) is a well-studiedprotective factor for Alzheimer’s disease (AD), with a recent evidence review identifyingit as the modifiable factor with the highest impact on reducing the nationalprevalence of AD.
1 Several studies have investigated the relationship betweenPA, cognition, brain structure, and neuropathological markers of AD amongcognitively normal adults. Available evidence indicates that higher levels ofPA associates with better cognitive performance2 particularlyon measures of visuospatial functioning,3,4 verbal episodic memory,3 and speed and flexibility.4,5 ln a randomizedcontrol trial (RCT) of 58 cognitively middle-aged adults, aerobic exercise trainingover a period of six months improved overall cognition, encompassing severalcognitive domains ranging from executive function to processing speed.5 Cross-sectionaland RCT evidence suggests that engagement in PA is associated with preservedvolume in various brain regions4,6-8such as the temporal lobe6,7,9,10and specifically the hippocampal region4,5,8,11,as well as decreased white matter atrophy.10 Colcombe et al12 reported increased brain volume in older adults who engagedin aerobic exercise training, but did not see this effect for those randomizedto a stretching and toning condition. Further, PA selectively enhances anteriorhippocampal volume8 and affects volumetric changes in the hippocampus over time,5 though this relationship may differ between men and women.
13 Gender differences have similarly been found in cognitiveperformance.14 For example, Laurin and colleagues14 found that over a period of5 years increased levels of PA had a protective effect on cognition in womenbut not men. In additionto its effect on brain structure and cognition, PA has been shown to moderatethe effect of age11 and geneticrisk factors,15 such as apolipoproteinE (APOE) e4 status,16 on AD pathophysiological biomarkers.Okonkwo et al11 found anassociation between self-reported PA and the attenuation of age-relatedalterations in extant AD biomarkers of b-amyloid (Ab) burden, cerebral glucosemetabolism, and hippocampal volume. Interestingly, lower levels of plasma Ab has been observed only amongcarriers of the APOE e4 allelewho reported high levels of PA.17 Thus, themoderating effect of PA may be influenced by level of intensity.9,16-19Investigators have examined the effect of PA on AD biomarkers through the lensof meeting activity recommendations established by the Department of Health andHuman Services9 or the American HeartAssociation.11,16,18 Meeting thesePA recommendations has been associated with lower Ab burden,16,20 asmeasured by cortical binding of the C-Pittsburgh compound B (PiB) tracer inregions associated with cognitive decline such as the prefrontal cortex andlateral temporal lobe.18 Moreover, engagement inmoderate intensity PA, but not light or vigorous activity, has been associatedwith increased glucose metabolism in select brain regions such as the temporalgyri, angular gyri, and posterior cingulate.19 In summary, there is strongevidence for positive associations between PA and cognitive performance2-4, and PAand brain volume within AD-relevant structures.5-10 Furthermore,emerging evidence indicates that PA may also associate with pathophysiologicalmarkers of AD16-20 or modify therelationship between core AD risk factors (e.g., age and APOE e4 positivity) and biomarker status.11,15