Cortical and subcortical gray matter alterations link cerebral small vessel disease burden to motor slowing: A...

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.

We recruited 354 participants with CSVD (mean age 57.2 ± 11.4 years), of whom 55 had 16-month follow-up. Participants underwent 3.0 T MRI with 3D T1-weighted MPRAGE (1 mm³ 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.

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).

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.

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.