Aerobic Exercise Training, Brain White Matter Free Water, And Cognitive Function In Older Adults

Free water (FW) in the brain white matter (WM) is sensitive to microstructural alteration and may reflect axonal degeneration or damage. Aerobic exercise and cardiorespiratory fitness are associated with improved WM microstructural integrity assessed with conventional diffusion tensor imaging (DTI), but their effects on FW and FW-corrected DTI metrics remain unclear. PURPOSE: To determine the effect of 1-year aerobic exercise on FW and FW-corrected DTI metrics and to explore the associations of FW with aerobic fitness and cognitive function in sedentary healthy older adults. METHODS: We conducted a 1-year randomized controlled trial allocating 73 sedentary healthy older adults (68 ± 5 years, 75% women) to aerobic exercise (n = 36) and stretching (n = 37) programs. FW and FW-corrected fractional anisotropy (fwcFA) were calculated from single-shell DTI data. A cognitive composite score of fluid intelligence was calculated from a validated neuropsychological battery while aerobic fitness was assessed by maximal oxygen uptake (VO2max). RESULTS: Aerobic exercise for one year did not have a significant effect on FW, fwcFA, or cognitive composite score compared to the stretching group, while VO2max improved after aerobic exercise training (p < 0.05). Tract-based spatial statistics (TBSS) revealed that higher VO2max at baseline was associated with lower FW levels at baseline and 1-year follow-up across all groups (p < 0.05). In addition, lower FW at baseline was associated with higher cognitive composite scores at baseline and 1-year follow-up (p < 0.05). Significant FW voxels were detected in the anterior regions of the corpus callosum, corona radiata, and internal capsule. fwcFA was not correlated with VO2max or cognitive composite score at baseline or follow-up. CONCLUSIONS: Higher cardiorespiratory fitness is associated with lower FW content in the brain WM in older adults, although FW content and cognitive performance remain unchanged with 1-year exercise training. National Institutes of Health (R01-HL-102457)