MRI-based glymphatic markers and composite scoring for the discrimination of mild cognitive impairment in cerebral small vessel disease.

PURPOSE: Glymphatic system (GS) alterations has been increasingly associated with cognitive impairment in cerebral small vessel disease (CSVD). Comprehensive and quantifiable markers of GS function remain limited.

METHODS

GS was assessed using three non-invasive MRI-based metrics including analysis along perivascular space (ALPS) index, coupling between global blood-oxygen-level-dependent (gBOLD) signal and cerebrospinal fluid (CSF) movement, and choroid plexus volume (CPV). Correlations between GS metrics and CSVD markers were examined, along with their associations with cognition. A weighted glymphatic composite score (GCS) was subsequently derived based on relative cognitive contributions.

RESULTS

We recruited 350 participants (65.53 ± 7.65 years), with 160 CSVDs and 190 healthy controls (HC). Compared with CSVD-normal cognition (CSVD-NCI), the CSVD-mild cognitive impairment (CSVD-MCI) group exhibited significantly lower ALPS indices and higher CPV (p < 0.001). CSVD markers including periventricular (β = -0.350; β = 0.404) and deep (β = -0.330; β = 0.324) white matter hyperintensities, microbleeds (β= -0.255; β = 0.191), lacunes (β = -0.194; β = 0.177), and perivascular spaces (β = -0.335; β = 0.390) were associated with ALPS index and CPV (p < 0.01).Linear analyses revealed a significant interaction between ALPS and CSVD on cognition (p < 0.05), which remained robust after further adjustment for vascular risk factors. Compared to CSVD-NCI, CSVD-MCI exhibited significantly lower GCS (p < 0.05). The GCS was significantly associated with MCI status after adjustment for clinical factors (OR = 0.31, p = 0.024).

CONCLUSIONS

Combining multiple GS-related MRI markers into a composite index effectively reflects cognitive status in CSVD and may serve as a non-invasive biomarker for CSVD-MCI discrimination.