Deep Medullary Vein Disruption and Glymphatic Dysfunction Are Associated With Cognitive Impairment and Imaging Burden in Cerebral Small-Vessel Disease

Abstract

Background and Purpose Cerebral small-vessel disease (CSVD) is a major cause of cognitive impairment, but its underlying mechanisms remain incompletely understood. This study investigated the interrelationships among deep medullary vein (DMV) disruption, glymphatic dysfunction as assessed using the diffusion-tensor imaging analysis along the perivascular space (DTI-ALPS) index, CSVD imaging markers, and cognitive impairment. Methods Fifty CSVD patients were enrolled from Chengdu Second People’s Hospital between January 2022 and December 2024, while 29 healthy controls (HCs) were recruited from the local community. DMV disruption was assessed using susceptibility-weighted imaging, while glymphatic function was evaluated using the DTI-ALPS index. Clinical characteristics, Mini-Mental State Examination (MMSE) scores, and CSVD imaging markers were collected, and regression and mediation analyses were performed. Results Compared with HCs, CSVD patients showed significantly lower DTI-ALPS indices, higher DMV scores, and worse cognition (all p<0.05). Higher DMV scores were independently associated with lower MMSE scores (p=0.006) and greater CSVD burden. Lower DTI-ALPS indices were associated with greater CSVD burden and showed a tendency toward an association with MMSE scores (p=0.070). DMV scores were negatively correlated with DTI-ALPS indices (p=0.024). The mediation analyses showed that glymphatic dysfunction did not exert a significant indirect effect on the relationship between DMV disruption and cognition, whereas there was a significant direct effect of DMV disruption on cognition. Conclusions This study found that DMV disruption and glymphatic dysfunction were associated with the CSVD imaging burden. Cognitive impairment was strongly associated with DMV disruption but weakly associated with glymphatic dysfunction. Combined assessments may provide complementary imaging markers for the CSVD severity and cognitive decline.