Associations of cardiorespiratory fitness with brain white matter microstructural integrity and white matter hyperintensity volume across the adult lifespan

Higher cardiorespiratory fitness (CRF) is associated with less deterioration in brain microstructural white matter (WM) integrity in older adults assessed with MRI diffusion tensor imaging (DTI) and brain WM hyperintensities (WMH) volume measured with fluid-attenuated-inversion-recovery (FLAIR) imaging. This study investigated associations of CRF measured with peak oxygen consumption (V̇O_2peak) with brain WM microstructural integrity and WMH in healthy individuals across the adult lifespan. We hypothesized that higher CRF is associated with less deterioration in WM microstructural integrity and WMH across the adult lifespan, which in turn is associated with better cognitive performance. A total of 177 healthy adults underwent treadmill exercise testing to measure V̇O_2peak, MRI scan to measure free water (FW)–corrected DTI metrics and whole-brain WMH volume, and a comprehensive cognitive test battery. Linear regression models were used to examine the associations of DTI metrics and WMH volume with age, V̇O_2peak, and age × V̇O_2peak interaction. Higher CRF was associated with lower FW. Age × V̇O_2peak interactions were observed in FW of the corpus callosum (CC) and WMH volume, such that the positive regression slopes of FW and WMH volume with age were lower in those with higher V̇O_2peak than those with lower V̇O_2peak. Lower WMH volume and FW in the CC were associated with better fluid cognition composite score. In conclusion, higher CRF is associated with less deteriorations in brain WM integrity and better cognitive function across the adult lifespan. These findings highlight the importance of maintaining and improving CRF to slow brain aging.