These findings suggest that glymphatic dysfunction may contribute to the association between cerebral artery stenosis and cognitive deterioration.
About one quarter of the 346 community-dwelling older adults had at least one stenotic cerebral artery.
Greater cerebral artery stenosis burden was associated with markers of poorer glymphatic function.
Glymphatic markers partially mediated the association between stenosis burden and baseline global cognition.
Participants with stenosis and impaired glymphatic function had a higher risk of CDR-SB worsening than those with stenosis but preserved glymphatic function.
Participants with stenosis and impaired glymphatic function had a much higher risk of CDR-SB worsening than those without stenosis.
The authors conclude that glymphatic dysfunction may contribute to the link between cerebral artery stenosis and cognitive decline.
This study followed 346 community-dwelling older adults to ask whether narrowing of the brain's arteries affects thinking abilities partly by impairing the brain's waste-clearance system, known as the glymphatic system. About a quarter of participants (87 people) had at least one narrowed brain artery on MRI angiography. Those with more narrowing showed MRI signs of poorer glymphatic function, measured with two imaging markers (DTI-ALPS and free water in white matter). Statistical mediation analyses suggested that these glymphatic markers accounted for roughly 13% to 17% of the association between artery narrowing and lower scores on a cognitive screening test (MMSE) at baseline. Over follow-up, people who had both artery narrowing and impaired glymphatic function were more likely to show worsening on a dementia rating scale (CDR-SB) than people who had narrowing but preserved glymphatic function, or people without narrowing. The risk was around 3 to 5 times higher compared with people without narrowing. This research suggests that the brain's clearance system may be one pathway through which narrowed arteries contribute to cognitive decline, and that glymphatic imaging markers might help identify people at higher risk. Because this is an observational study, it cannot prove that glymphatic dysfunction causes the decline, and the mediation accounted for only part of the association.
Yuan W, Niu X, Lan L, Chen X. (2026). Cerebral Artery Stenosis, Glymphatic Dysfunction, and Cognitive Trajectories: A Longitudinal Cohort Study of Community-Dwelling Older Adults.. CNS neuroscience & therapeutics. https://doi.org/10.1002/cns.71216