Distinctive patterns of right-hemisphere vulnerability in cerebral small vessel disease: a gray matter asymmetry study.

Cerebral small vessel disease (CSVD) is a leading cause of vascular cognitive impairment (VCI), characteristically associated with gray matter (GM) loss. However, it remains unclear whether this GM loss exhibits regional interhemispheric asymmetry and how it relates to cognitive function. In this study, 56 CSVD patients and 56 demographically matched healthy controls were included, and structural MRI as well as cognitive and clinical data were collected. Voxel-based morphometry (VBM) and the GM Asymmetry Index (GMAI; calculated as (L-R)/(L + R), higher values indicate relatively greater left-sided GM) were performed using a study-specific symmetric template. Perivascular spaces were also estimated with a deep learning framework. Partial correlations were tested against multi-domain cognitive performance. Compared with controls, CSVD patients exhibited extensive GM reduction in the right superior and middle frontal gyri as well as in the left hippocampus and putamen. Regional GMAI analyses further suggested altered hemispheric GM loss, with leftward shifts (higher GMAI) in the middle temporal gyrus, superior frontal gyrus, and precuneus, and rightward shifts (lower GMAI) in the inferior temporal and fusiform gyri. Additionally, subcortical nuclei exhibited a corresponding leftward lateralization of perivascular space burden. Association analyses showed that right prefrontal volume was positively related to global cognitive scores, whereas left temporal asymmetry tracked cognitive decline. Of note, this right-dominant pattern in prefrontal-related regions is consistent with our activation likelihood estimation meta-analytic re-synthesis of prior VBM evidence and NeuroSynth mapping. Collectively, these findings suggest a distinct topographical vulnerability of the right hemisphere in CSVD and highlight GMAI as a neuroimaging marker for vascular cognitive decline.