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Peer-reviewedCC BYCNS neuroscience & therapeutics

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

  • Weizhuang Yuan1,2,3
  • Xingyang Niu1,2,3
  • Linfang Lan1,2,3
  • Xinran Chen1,2,3
  1. 1Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
  2. 2Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, Guangzhou, China.
  3. 3National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China.
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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.

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Cite

BibTeXRIS
BibTeX
@article{yuan2026cerebral,
  title = {{Cerebral Artery Stenosis, Glymphatic Dysfunction, and Cognitive Trajectories: A Longitudinal Cohort Study of Community-Dwelling Older Adults.}},
  author = {Weizhuang Yuan and Xingyang Niu and Linfang Lan and Xinran Chen},
  journal = {CNS neuroscience \& therapeutics},
  year = {2026},
  month = oct,
  doi = {10.1002/cns.71216},
  url = {https://europepmc.org/article/MED/42904869},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Cerebral Artery Stenosis, Glymphatic Dysfunction, and Cognitive Trajectories: A Longitudinal Cohort Study of Community-Dwelling Older Adults.
AU  - Weizhuang Yuan
AU  - Xingyang Niu
AU  - Linfang Lan
AU  - Xinran Chen
PY  - 2026
DA  - 2026/10/01
JO  - CNS neuroscience & therapeutics
DO  - 10.1002/cns.71216
UR  - https://europepmc.org/article/MED/42904869
AB  - 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.
SN  - 1755-5930
SN  - 1755-5949
ER  -