Associations between cognitive reserve, glymphatic function and cognitive function in mild cognitive impairment

Objective To evaluate the association between cognitive reserve (CR) and glymphatic function in mild cognitive impairment (MCI), and to examine whether the relationship between CR and cognition is mediated by glymphatic function. Methods 113 MCI individuals and 91 healthy controls (HC) were enrolled to assess the glymphatic function by using diffusion tensor imaging along the perivascular space (DTI-ALPS), perivascular space (PVS) ratings, and choroid plexus volume (CPV). Cognitive reserve index questionnaire (CRIq) was employed to evaluate the comprehensive CR of participants in both groups. The glymphatic function was compared between the two groups and Spearman correlation analyses were performed among the CR, glymphatic function and cognition. Mediation analyses were further conducted to explore potential mediating effects. Results The MCI group had significantly lower bilateral ALPS index and mean ALPS index than the HC group, while the bilateral CPV, basal ganglia (BG)-PVS and centrum semiovale (CS)-PVS scores were significantly higher in the MCI group than the HC group. After controlling for age and sex, bilateral and mean ALPS index were positively correlated with MoCA, MMSE, and VFT scores; mean ALPS index and left ALPS index were positively correlated with AVLT-immediately performance. BG-PVS was negatively correlated with MMSE and VFT scores, and right CPV was negatively correlated with VFT scores. Meanwhile, CRIq was positively correlated with bilateral and mean ALPS index, but was negatively correlated with BG-PVS, and mean ALPS partially mediated the association between CRIq and cognition in the MCI group. Conclusion Mild cognitive impairment individuals exhibit reduced glymphatic activity relative to HC. Comprehensive CR is associated with cognitive function in MCI, with the mean ALPS index statistically mediating a portion of the CR–cognition association.