Aerobic exercise is associated with region-specific changes in volumetric, tensor-based, and fixel-based measures of white matter integrity in healthy older adults

Abstract

White matter integrity and cognition have been found to decline with advancing adult age. Aerobic exercise may be effective in counteracting these declines. Generally, white matter integrity has been quantified using a volumetric measure (WMV) and with tensor-based parameters, such as fractional anisotropy (FA) and mean diffusivity (MD), the validity of which appears to be compromised in the presence of crossing fibers. Fixel-based analysis techniques claim to overcome this problem by yielding estimates of fiber density (FD), cross-section (FC), and their product (FDC) in multiple directions per voxel. In a sample of 61 healthy older adults (63-76 years old), we quantified changes in white matter integrity following an aerobic exercise intervention with the commonly used volumetric and tensor-based metrics (WMV, FA, MD) and with fixel-based metrics (FD, FC, FDC). We investigated the associations of changes in these white matter parameters with changes in cardiovascular fitness and Digit Symbol Substitution task (DSST) performance, a marker of perceptual speed. In line with previous findings, we observed maintained WMV in the corpus callosum of exercisers, and positive change-change correlations between WMV and fitness, and between WMV and perceptual speed. For FA and MD, group differences in change opposite to those hypothesized were found in the corpus callosum, posterior corona radiata, and superior longitudinal fasciculus at an uncorrected significance threshold. Likewise, regions in superficial WM in the prefrontal cortex showed group differences in FD and FDC change, uncorrected, with more positive change in controls and more negative change in exercisers. Finally, changes in FD and FDC were found to be inversely correlated to changes in fitness and DSST performance. The present results corroborate previous findings of WMV changes, but cast doubt on current physiological interpretations of both tensor-based and fixel-based indicators of white matter properties in the context of exercise intervention studies.

Keywords: Aerobic exercise; Aging; Cardiovascular fitness; Diffusion-weighted imaging; Perceptual speed; White matter integrity.

Fig. 1

Group differences in change in white matter volume (WMV), fractional anisotropy (FA), mean diffusivity (MD), fiber density (FD), fiber density and cross-section (FDC). Yellow/orange-colored clusters represent more positive changes in exercisers than controls, cyan-colored clusters represent more negative changes in exercisers than controls. WMV, FA, and MD are calculated and displayed in MNI space, whereas FD and FDC are calculated and displayed in a study-specific space. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig. 2

Significant correlations between percent change in VO₂peak, white matter integrity metrics extracted from clusters with significant time-by-group interactions, and Digit Symbol Substitution task score. Overall correlations are shown in opaque black for those correlations that do not show significant group differences (top row: left, center, right; bottom row: left); for these, group-wise correlations are shown as transparent color-coded lines. Correlations that differ significantly between groups are represented by opaque color-coded lines (bottom row: center, right); for these, overall correlations are shown as transparent black lines. WMV = white matter volume; FD = fiber density; FDC = fiber density and cross-section; dmPFC = dorsomedial prefrontal cortex; DSST = Digit Symbol Substitution task; ACR = anterior corona radiata; dlPFC = dorsolateral prefrontal cortex. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)