Cerebral Artery Stenosis, Glymphatic Dysfunction, and Cognitive Trajectories: A Longitudinal Cohort Study of Community‐Dwelling Older Adults
Weizhuang Yuan, Xingyang Niu, Linfang Lan, Xinran ChenABSTRACT
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.