Aerobic Exercise for the Promotion of Healthy Aging: Changes in Brain Structure Assessed with New Methods

As the proportion of older individuals in the population increases, so does the scientific concern surrounding age-related deterioration of brain tissue and related cognitive decline. One modifiable lifestyle factor of interest in the pursuit to slow or even reverse age-related brain atrophy is aerobic exercise. A number of studies have already demonstrated that aerobic exercise in older age can induce maintenance (i.e., reduction of loss) of both gray and white matter volume, particularly in the frontal regions of the brain, which are vulnerable to shrinkage in older age. Other magnetic resonance imaging (MRI)-based techniques, such as quantitative MRI and diffusion-weighted MRI, have been used to measure age-related deterioration of gray and white matter integrity in both voxel-wise analyses as well as on the latent level, but whether these negative changes can be ameliorated through exercise has yet to be shown. The current dissertation includes three papers which used a number of both established and novel MRI-based metrics to quantify changes in brain tissue integrity resulting from aging, as well as to investigate whether these changes can be ameliorated through aerobic exercise. In Paper I (Wenger et al., 2022), we tested the reliability of quantitative MRI measures, namely longitudinal relaxation rate, effective transverse relaxation rate, proton density, and magnetization transfer saturation, by measuring them in a two-day, four-session design with repositioning in the scanner. Using the intra-class effect decomposition model, we found that magnetization transfer saturation could reliably detect individual differences, validating its use to investigate changes in brain structure longitudinally, as well as correlations with other variables of interest, such as change in cardiovascular fitness. In Paper II (Polk et al., 2022), we tested the effects of aerobic exercise on a latent factor of gray-matter structural integrity, comprising observed measures of gray-matter volume, magnetization transfer saturation, and mean diffusivity, in regions of interest that have previously shown volumetric effects of aerobic exercise. We found that gray-matter structural integrity was maintained in frontal and midline regions, and that change in gray-matter structural integrity in the right anterior cingulate cortex was positively correlated with change in cardiovascular fitness within exercising participants. These results suggest a causal relationship between aerobic exercise, cardiovascular fitness, and gray-matter structural integrity in this region. In Paper III (Polk et al., 2022), we tested the effects of aerobic exercise on white matter integrity, measured with both established and recently developed metrics. We were able to replicate findings from a previous study on the effects of aerobic exercise on white matter volume, and we also found change-change correlations between white matter volume and cardiovascular fitness as well as between white matter volume and performance on a test of perceptual speed. We also found unexpected exercise-induced changes in the diffusion weighted imaging-derived metrics of fractional anisotropy, mean diffusivity, fiber density, and fiber density and cross-section. Specifically, we found increases (or decreases in the case of mean diffusivity) within control participants and decreases (or increases in mean diffusivity) in exercisers. Furthermore, we found that percent change in fiber density and fiber density and cross-section correlated negatively with percent change in both cardiovascular fitness and cognitive performance. This casts doubt on the functional interpretation of these measures and suggests that the “more is better” principle may not be universally applicable when investigating age-related and exercise-induced changes in white matter integrity. In sum, this dissertation showed that regular at-home aerobic exercise, which may be more accessible for older individuals than supervised exercise, can be an effective tool to ameliorate age-related decreases in a latent measure of gray-matter structural integrity as well as white matter volume. It also illuminated potential limitations of other measures of white matter integrity in the context of aging and aerobic exercise, and calls for further research into these novel measures, especially when considering functional outcomes such as cognitive performance