Associations between white matter hyperintensities and physical activity: A sectional study in UK Biobank participants.

White matter hyperintensities (WMH) are key markers of cerebral small vessel disease (CSVD) linked to increased risks of stroke, dementia, and cognitive decline. Physical activity (PA) has been hypothesized to reduce WMH burden and preserve brain health, yet findings across studies remain mixed. This study examines the association between PA and WMH burden, as well as white matter integrity using diffusion tensor imaging (DTI) metrics, in a cohort of 10,868 participants from the UK Biobank. Participants were categorized into low, intermediate, and high PA tertiles based on accelerometer data. WMH volumes, normalized for head size, were classified into quintiles. Multilevel ordered logistic regression models revealed that high PA levels were significantly associated with reduced WMH burden (OR = 0.956, p = 0.026), while low PA levels increased the likelihood of higher WMH burden (OR = 1.148, p < 0.001). Subtype analyses indicated stronger associations between PA and periventricular WMH compared to deep WMH. Furthermore, DTI metrics demonstrated that higher PA levels were correlated with improved fractional anisotropy (FA) and reduced mean diffusivity (MD) in key white matter tracts, such as the corpus callosum and fornix, suggesting better white matter integrity. Our findings emphasize the potential neuroprotective effects of PA, particularly in mitigating WMH progression and preserving cognitive and motor functions. These results underscore the importance of promoting PA, especially in older adults, as a strategy to reduce the burden of CSVD and support brain health. Future longitudinal studies are needed to confirm causality and elucidate underlying mechanisms.