The mediation effects of white matter microstructural abnormalities on the associations between cerebral small vessel disease burden and cognitive impairment

White matter (WM) microstructural deterioration is associated with a higher total cerebral small vessel disease (CSVD) burden, as assessed by magnetic resonance imaging (MRI) markers, and with more pronounced cognitive decline in CSVD patients. However, the relationships among CSVD burden, cognitive impairment and WM changes remain unclear. We aimed to characterize WM microstructural abnormalities in patients with different CSVD burdens and investigate the mechanism linking different CSVD burdens to cognitive decline. This study included 56 patients with severe CSVD burden (CSVD-s), 109 patients with mild CSVD burden (CSVD-m) and 81 healthy controls. We used diffusion tensor imaging (DTI) and tract-based spatial statistics to detect WM diffusion changes between groups and then explored the relationships between different CSVD burdens, WM diffusion changes and cognitive function, especially to quantitatively analyze the possible mediating effect of WM microstructural alterations on CSVD burden and cognitive function. The CSVD-s group presented significantly decreased FA and increased AD, RD and MD in the forceps minor, bilateral anterior thalamic radiation (ATR), superior longitudinal fasciculus (SLF), corticospinal tract (CST) and inferior fronto-occipital fasciculus (IFOF). The simple mediation model revealed that the mean MD value of forceps minor and right IFOF, the mean FA value of the left CST and right IFOF, and the mean RD value of the left CST, SLF and right IFOF partially mediated the correlations between the CSVD burden and multiple cognitive scores. Our findings offer potential neuroimaging targets for intervening in and improving cognitive dysfunction in patients with different CSVD burdens.