Abstract Details

Title Small Vessel and Glymphatic Dysfunction In Asymptomatic Intracranial Atherosclerosis Relates to Cognition and Predicts Decline

Topic Cerebrovascular Disease and Interventional Neurology

Presentation(s) P3 - Poster Session 3 (5:00 PM-6:00 PM)

Poster/Presentation
Number 4-020

Objective Test whether imaging indicators of small-vessel and glymphatic dysfunction biomarkers relate to cognition in asymptomatic intracranial atherosclerotic stenosis (aICAS) and predict subsequent decline.

Background aICAS is linked to cognitive impairment, but mechanisms remain unresolved. Small-vessel injury and impaired perivascular/glymphatic clearance are leading candidates. We quantified this burden using harmonized multimodal MRI and integrated plasma markers to evaluate cognitive associations and prognostic value.

Design/Methods In a multicenter cohort of aICAS patients (n=147) and matched controls (n=68), participants received 3T MRI and a standardized cognitive battery. Imaging markers included diffusion-based glymphatic index (DTI analysis along perivascular space, ALPS), white-matter free water, perivascular-space volume, and white-matter hyperintensity volume, processed with harmonized pipelines. Analyses covered group comparisons, associations with cognitive performance and plasma biomarkers, and structural equation model specified a latent CSVD/Glymphatic Burden to test mediation from an Atherogenic Lipids factor to cognition, Cox models were also used for follow-up decline.

Results Compared with controls, patients showed a lower ALPS index and higher global free water. In subgroup analyses, free water within stenosed perfusion territories was significantly higher in aICAS patients than in normal controls (p<0.05). Within patients, free water was also higher in stenosed compared with non-stenosed territories (p<0.01). Across the cohort, a greater glymphatic burden was associated with worse global cognitive performance and deficits in specific domain z-scores, and these associations remained robust after adjustment for demographic covariates. The CSVD/glymphatic burden mediated 58.4% of the adverse effect of atherogenic lipids on MoCA (p=0.010) and correlated with glial fibrillary acidic protein. Furthermore, baseline ALPS index is associated with subsequent cognitive decline (HR<0.01, p=0.025).

Conclusions Small-vessel and glymphatic dysfunction is linked to cognitive deficits in aICAS, constitutes an indirect pathway from lipids to cognition. These findings address the mechanism linking atherosclerosis to cognitive impairment and support a multi-indicator imaging-plus-plasma approach for risk stratification and mechanistic targeting.

Authors/Disclosures
Yinxi Zou, MD, PhD PRESENTER	Dr. Zou has nothing to disclose.
Weizhuang Yuan (The First Affiliated Hospital, Sun Yat-sen University)	No disclosure on file
Anqi Cheng (Peking union medical college hospital)	No disclosure on file
Mi Zhou, MD, PhD (Penn State Hershey Medical Center)	Dr. Zhou has nothing to disclose.
Daisy Liu	Miss Liu has received personal compensation for serving as an employee of Analysis Group.
Ningyuan Liu (Peking union medical college hospital)	No disclosure on file
HaoYao Guo (Peking Union Hospital)	Mr. Guo has nothing to disclose.
Linwen Liu (Peking union medical college hospital)	No disclosure on file
Fan Zhang	Dr. Zhang has nothing to disclose.
yue wang, MD	Dr. wang has nothing to disclose.
Shiwen Wu	No disclosure on file
Zhongrui Yan, MD, PhD	Prof. Yan has nothing to disclose.
Zhibing Ai (Taihe Hospital, Hubei University of Medicine)	No disclosure on file
Mingli Li (Peking union medical college hospital)	No disclosure on file
CAI-YAN LIU	Dr. LIU has nothing to disclose.
Weihai Xu (Peking union medical college hospital)	No disclosure on file

��ɫ��

��ɫ��