Progressive structural alterations in the cerebral small vessel disease with cognitive impairment and vascular dementia

Background The progression of cerebral small vessel disease (CSVD) leads to cognitive decline, which can be categorized into subcortical vascular mild cognitive impairment (svMCI) and vascular dementia (VaD). Objective This research aimed to examine the structural changes in gray (GM) and white matter (WM) in the brain across the disease spectrum. Methods A total of 30 healthy controls (HC), 26 individuals with svMCI, and 29 individuals with VaD were included in study. All participants underwent MRI scans and clinical evaluations. Voxel-based morphometry (VBM), voxel-based analysis of diffusion tensor imaging (VBA-DTI), and fixel-based analysis (FBA) were utilized to examine progressive structural changes, with correlation analyses conducted to explore their relationship with clinical measures. Results VBM analysis revealed progressive GM atrophy in right dorsal cingulate gyrus, and right hippocampus in svMCI and VaD compared to HC. VBA-DTI results demonstrated alterations in fractional anisotropy (FA) values in the inferior longitudinal fasciculus, along with changes in mean diffusivity (MD) values in the inferior longitudinal fasciculus. FBA results identified significant WM alterations in superior corona radiata, and posterior corona radiata. As disease progressed, those with VaD showed more severe cognitive impairments and more pronounced changes in GM and WM of various brain regions. The correlation results indicated that structural changes in GM and WM, identified through VBM, FA, and MD analyses, were significantly associated with severity of cognitive and motor deficits. Conclusions Our study reveals notable alterations in GM and WM in brains of individuals with cognitive impairments associated with svMCI and VaD. These results provide a foundation for clinical observation of CSVD-related alterations and offer strong support for further in-depth exploration of neuropathological changes. Clinical Trial Registration ChiCTR2400093373.