Glymphatic dysfunction in relapsing-remitting multiple sclerosis and its association with brain structural damage and cognitive impairment

Objective

To explore the glymphatic dysfunction in relapsing-remitting multiple sclerosis (RRMS) and its potential associations with brain structural damage, clinical disability, and cognitive impairment (Co-I).

Methods

The study involved 70 patients with RRMS and 44 healthy controls. Neurological and MRI assessments were performed, and cognitive performance was assessed via the Brief Repeatable Battery of Neuropsychological Tests (BRB-N). To assess the glymphatic function, we calculated the choroid plexus volume (CPV) and diffusion tensor imaging along perivascular spaces (DTI-ALPS) index. Multivariable linear regression analyses were used to examine correlations between glymphatic dysfunction and MRI-derived brain damage metrics. Additionally, we utilised random forest analysis to identify predictors of Co-I and assessed the mediating role of DTI-ALPS.

Results

Patients with RRMS, particularly those with Co-I, exhibited a low DTI-ALPS index and large CPV. A lower DTI-ALPS index was associated with longer disease duration, greater disability, larger lesion volume (LV), mean diffusivity (MD), and CPV, as well as lower fractional anisotropy (FA) (all FDR-p < 0.05). Moreover, DTI-ALPS mediated 27.21 % and 43.75 % of CPV effects on information processing speed and visuospatial memory, respectively. Random forest analysis indicated that lower education (relative importance [RI] = 100 %), higher CPV (RI = 95.8 %), lower DTI-ALPS index (RI = 80.7 %), higher MD (RI = 61.3 %), lower FA (RI = 60.5 %), older age (RI = 54.6 %), and higher EDSS score (RI = 45.4 %) are predictors of Co-I.

Conclusion

The study implied that glymphatic dysfunction may contribute to brain structural damage, clinical disability, and cognitive impairment in RRMS, indicating that glymphatic dysfunction may play a key role in the pathogenesis of RRMS.