Left-lateralized glymphatic dysfunction is associated with MoCA-measured cognitive impairment in cerebral small...

Cerebral small vessel disease (CSVD) is a major cause of vascular cognitive impairment. Glymphatic dysfunction has been implicated in cognitive decline, but its relationship with CSVD-related cognitive impairment, particularly with regard to potential hemispheric differences, remains unclear.

Forty-eight CSVD patients and 56 matched healthy controls underwent brain MRI and cognitive assessment using the Montreal Cognitive Assessment (MoCA). Bilateral ALPS indices (ALPS-L and ALPS-R) were calculated to assess glymphatic function. Pearson and partial correlation analyses were performed to examine associations between ALPS indices and MoCA scores. Logistic regression models and receiver operating characteristic (ROC) analyses were used to evaluate the associations between hemispheric ALPS indices and cognitive impairment as measured by the MoCA and assess their performance in distinguishing CSVD patients from healthy controls.

Both ALPS-L and ALPS-R were significantly reduced in CSVD patients (p < 0.01). ALPS-L was positively correlated with MoCA scores (r = 0.307, p = 0.001), independent of demographic factors, whereas ALPS-R showed no significant association. ROC analyses demonstrated that incorporating ALPS indices improved the prediction of relatively lower cognitive performance measured by MoCA, with the model including ALPS-L showing higher predictive performance (AUC = 0.765) compared with the contrast model including ALPS-R (AUC = 0.737). The trend of these models in distinguishing CSVD from healthy controls is consistent.

CSVD patients exhibit bilateral lymphatic dysfunction. The left ALPS index showed a lateralized association with MoCA-measured cognitive impairment and may represent a potential imaging marker associated with cognitive performance in CSVD.