Disrupted Brain Structure–Function Coupling and Its Mediating Effects on the Associations Between Cerebral Small Vessel Disease Burden and Cognitive Dysfunction

Aims We aimed to specify relationships among cerebral small vessel disease (CSVD) burden, cognitive dysfunction, and brain structure–function coupling changes. Methods A total of 108 patients with mild CSVD burden (CSVD‐m), 53 patients with severe CSVD burden (CSVD‐s), and 76 healthy controls (HC) were included in this study. The ratio of regional homogeneity (ReHo) or amplitude of low‐frequency fluctuation (ALFF) to gray matter volume (GMV) was calculated as an indicator of voxel‐wise structure–function coupling. Results Significantly decreased or increased ReHo–GMV and ALFF–GMV coupling values in patients with severe CSVD burden were primarily found in several brain regions, and the disrupted structure–function coupling in the right putamen mediated the relationship between CSVD burden and cognitive dysfunction. Conclusions Brain structure–function coupling characterized by ReHo–GMV and ALFF–GMV mediated the cognitive dysfunction caused by CSVD and was an innovative and effective brain imaging indicator for exploring the association between CSVD burden and cognitive dysfunction.