Cerebral Artery Stenosis, Glymphatic Dysfunction, and Cognitive Trajectories: A Longitudinal Cohort Study of Community-Dwelling Older Adults.

AIMS: We aimed to investigate the role of glymphatic dysfunction in the association between stenosis and cognition.

METHODS

Older adults from a longitudinal cohort underwent magnetic resonance angiography to quantify cerebral artery stenosis burden. Glymphatic function was evaluated using diffusion tensor imaging-analysis along the perivascular space (DTI-ALPS) and free water in white matter (FW-WM). Global cognitive performance was assessed using the Mini-Mental State Examination (MMSE) and the Clinical Dementia Rating-Sum of Boxes (CDR-SB). Mediation analyses examined indirect effects, and longitudinal cognitive outcomes were analyzed using linear mixed-effects and Cox proportional hazards models.

RESULTS

Among 346 participants, 87 (25.1%) had at least one stenotic cerebral artery. Stenosis burden was associated with a lower DTI-ALPS index (β = -0.04, p = 0.003) and higher FW-WM (β = 0.01, p = 0.022). Both DTI-ALPS and FW-WM significantly mediated the association between stenosis burden and baseline MMSE, accounting for 13.06%-17.19% of the total effect. In longitudinal analyses, participants with stenosis and impaired glymphatic function had a higher risk of CDR-SB worsening relative to those with stenosis but preserved glymphatic function (hazard ratios 1.35-2.96) and those without stenosis (hazard ratios 3.27-4.70).

CONCLUSION

These findings suggest that glymphatic dysfunction may contribute to the association between cerebral artery stenosis and cognitive deterioration.