Abstract
BACKGROUND: Brain structural abnormalities have been associated with cognitive impairment in individuals with small cerebral vascular disease (CSVD). However, the molecular and cellular factors making the different brain structural regions more vulnerable to CSVD-related cognitive impairment remain largely unknown. MATERIALS AND METHODS: Voxel-based morphology (VBM) was performed on the structural magnetic resonance imaging data of 46 CSVD-related cognitive impairment and 73 healthy controls to analyze and compare the gray matter volume (GMV) between the 2 groups. Transcriptome-neuroimaging spatial correlation analysis was carried out in combination with the Allen Human Brain Atlas to explore gene expression profiles associated with changes in cortical morphology in CSVD-related cognitive impairment. RESULTS: VBM analysis demonstrated extensive decreased GMV in CSVD-related cognitive impairment in the bilateral temporal lobe and thalamus, especially the hippocampus, thalamus, parahippocampus, and fusiform, and the left temporal lobe showed a more severe atrophy than the right temporal lobe. These brain structural alterations were closely related to memory and executive function deficits in CSVD-related cognitive impairment. Furthermore, a total of 1,580 genes were revealed to be significantly associated with regional change in GMV. The negatively and positively GMV-linked gene expression profiles were mainly enriched in RNA polymerase II, catalytic activity acting on a nucleic acid, aminoacyltransferase activity, axonogenesis, Golgi membrane, and cell junction organization. CONCLUSION: Our findings suggest that brain morphological abnormalities in CSVD-related cognitive impairment are linked to molecular changes involving complex polygenic mechanisms, highlighting the interplay between genetic influences and structural alterations relevant to CSVD-related cognitive impairment.