AUTHOR=Feng Weishun , Lei Xinjun , Xu Shida , Xu Zhihua 

TITLE=Association between white matter hyperintensities and gray matter volume in cerebral small vessel disease: insights from periventricular and deep white matter lesions

JOURNAL=Frontiers in Neurology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1590997

DOI=10.3389/fneur.2025.1590997

ISSN=1664-2295

ABSTRACT=ObjectiveTo investigate the relationship between the severity of periventricular white matter hyperintensities (PWMH) and deep white matter hyperintensities (DWMH) and gray matter volume in cerebral small vessel disease (CSVD) patients.MethodsClinical and imaging data from 125 CSVD patients, collected between April and December 2022, were analyzed. The severity of PWMH and DWMH was assessed using the Fazekas scale. 3D T1-weighted images were processed with FSL software to segment gray matter and intracranial volume. The normalized gray matter volume (GM_n) was computed as the proportional ratio of gray matter volume relative to total intracranial volume.ResultsGroup-level analysis revealed significant differences in GM_n were observed across various Fazekas scores for both DWMH (p = 0.041) and PWMH (p < 0.001). Post hoc analysis with false discovery rate (FDR) correction showed that PWMH severity was associated with significantly lower GM_n in scores 2 and 3 compared to score 1 (FDR-adjusted p = 0.001 and 0.004, respectively), though no difference was observed between scores 2 and 3 (p > 0.05). For DWMH, no pairwise comparisons survived FDR correction, though a non-significant trend toward reduced GM_n was noted in score 3 versus scores 0–1 (FDR-adjusted p = 0.08). After multivariate analysis adjusting for vascular risk factors, PWMH severity was found to be independently associated with GM_n [p < 0.05, β (95% CI): Age −0.212 (−0.412, −0.011), PWMH score −0.408 (−0.605, −0.210)], while DWMH severity showed no independent association with GM_n (p > 0.05). Mediation analysis revealed PWMH significantly mediated 39.1% of the total effect of age on GM_n (indirect effect = −0.136; 95% CI: −0.265 to −0.053).ConclusionPWMH, but not DWMH, is independently associated with gray matter volume and partially mediates the age-related decline in GM volume. These findings highlight the topographical and mechanistic heterogeneity of WMH subtypes and underscore PWMH as a potential imaging marker for early intervention in CSVD-related neurodegeneration.