Background: There is limited information regarding exercise training and brain health in people with multiple sclerosis (MS). This study investigated body weight as a moderator of exercise training effects on CNS volume and metabolism. Methods: Sixty people with MS were randomly selected (based on sex and weight classification) and allocated into exercise training (n = 30) or control (n = 30) conditions considering weight classification (normal weight vs. overweight/obese). The exercise training program consisted of 6 months of home-based exercise. Whole brain and regions-of-interest (ROI) volumes and metabolites were assessed using magnetic resonance imaging (MRI) and spectroscopy (MRS), respectively. Results: There were significant improvements in levels of Nacetylaspartate/creatine (NAA/Cr: marker of neural integrity and cell energy state flow) in all ROIs (p < 0.05) following exercise training, and excess body weight moderated the beneficial effects of exercise training in thalamus, anterior cingulate cortex and medial prefrontal cortex (p < 0.05). Additionally, brain-derived neurotrophic factor, platelet-derived growth factor and kynurenine pathway metabolites were significantly improved following exercise training (p < 0.05). Discussion: Current findings provide novel evidence for the beneficial effects of exercise training on CNS health in MS, and further suggest that excessive body weight might moderate some of the beneficial effects of exercise training in MS.
