Cortical and subcortical gray matter alterations link cerebral small vessel disease burden to motor slowing: A cross-sectional and longitudinal study

BACKGROUND: Cerebral small vessel disease (CSVD) causes cortical atrophy and motor decline, but the specific cortical regions involved and their mediating role remain unclear. We aimed to determine whether regional cortical thickness mediates the association between CSVD severity and motor function. METHODS AND MATERIALS: isotropic) and motor testing (TUG and 3-m walk test). Cortical thickness was quantified using FreeSurfer v6.0 with longitudinal processing for follow-up scans. General linear models tested cross-sectional associations, linear mixed-effects models examined longitudinal effects, and mediation analysis assessed indirect effects. RESULTS: Significant negative associations were observed between cortical thickness and CSVD severity in the right insula, left rostral anterior cingulate cortex, and left lateral occipital cortex. Additionally, significant associations were found between cortical thickness at multiple time points in the right insula (β = 0.594, P = 0.024) and TUG test scores. The thickness of the right insular cortex mediated the relationship between CSVD severity and TUG performance (mean [SE] indirect effect, 0.085 [0.045]; 95 % CI, 0.015-0.197). CONCLUSIONS: CSVD severity was associated with cortical thinning in specific cortical regions, and right insular cortical thickness levels were related to motor performance and partially mediated the association between CSVD severity and mobility impairment. ETHICS APPROVAL AND CONSENT TO PARTICIPATE: All study procedures were approved by the Ethical Committee of the Institutional Review Board (IRB) of the Shandong Institute of Medical Imaging (2019-002). The study was conducted in accordance with the Declaration of Helsinki. All participants signed an informed consent form before the commencement of the study.