Abstract
Mitigating the loss of brain tissue due to age is a major problem for an ageing population. Improving cardiorespiratory fitness has been suggested as a possible strategy, but the influenceon brain morphology has not been fully characterized. To investigate the dependent shifts in brain tissue distribution as a function of cardiorespiratory fitness, we used a 3D transport-based morphometry approach. In this study of 172 inactive older adults aged 58-81 (66.5 ± 5.7) years, cardiorespiratory fitness was determined by V O2 peak (ml/kg/min) during graded exercise and brain morphology was assessed through structural magnetic resonance imaging. After correcting for covariates including age (in the fitness model), gender and level of education, we compared dependent tissue shifts with age to those due to VO2 peak . We found a significant association between cardiorespiratory fitness and brain tissue distribution (white matter, r = 0.30, P = 0.003; grey matter, r = 0.40, P < 0.001) facilitated by direct visualization of the brain tissue shifts due to cardiorespiratory fitness through inverse transformation-a key capability of 3D transport-based morphometry. A strong statistical correlation was found between brain tissue changes related to ageing and those associated with lower cardiorespiratory fitness (white matter, r = 0.62, P < 0.001; grey matter, r = 0.74, P < 0.001). In both cases, frontotemporal regions shifted the most while basal ganglia shifted the least. Our results highlight the importance of cardiorespiratory fitness in maintaining brain health later in life. Furthermore, this work demonstrates 3D transport-based morphometry as a novel neuroinformatic technology that may aid assessment of therapeutic approaches for brain ageing and neurodegenerative diseases.