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

Year: 2026
Type: article
Study design: Observational Study
Abstract: 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.
DOI: 10.1002/cns.71216
Language: English
Field: Medicine
Open Access status: gold
Estimated APC paid: $4,140
Funders: Eli Lilly and Company, China Postdoctoral Science Foundation, Natural Science Foundation for Young Scientists of Shanxi Province, National Institutes of Health, Avid Radiopharmaceuticals, National Institute on Aging, National Institute of Biomedical Imaging and Bioengineering
Awards: DRIVING PERFORMANCE IN PRECLINICAL ALZHEIMER'S DISEASE, Healthy Aging and Senile Dementia, Washington University Institute of Clinical and Translational Sciences, G7831108753, G9000112288, G9000115080, Alzheimer's Disease Research Center, Washington University Institute of Clinical and Translational Sciences, THE XNAT IMAGING INFORMATICS PLATFORM, Antecedent Biomarkers for Alzheimer Disease: The Adult Children Study
OpenAlex ID: W7223104604
FWCI:
Cites: 31
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Related to: 10