Correlation Between Serum TGF-β1 Levels, Intracranial Atherosclerotic Plaque Parameters and Post-Stroke Cognitive Impairment

Yu-ge Zhang,1,2,* Peng-fei Yang,3,* Bing-jie Liu,1,2 Shuo Wang,1 Kun-yan Li,1 Hua Zhong,4 Yi-ren Jiang,1,2 Bin Yuan1,21Department of Neurology II, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, People’s Republic of China; 2Henan Key Laboratory of Neural Regeneration, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, People’s Republic of China; 3School of Pharmacy, Xinxiang Medical University, Xinxiang, People’s Republic of China; 4Department of Clinical Laboratory, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bin Yuan, Department of Neurology II, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, People’s Republic of China, Tel /Fax +86-0373-4404351, Email [email protected]: This study aimed to investigate the relationships between serum transforming growth factor-β 1 (TGF-β 1), plaque features on high-resolution magnetic resonance vessel wall imaging (HR-VWI) and post-stroke cognitive impairment (PSCI) in symptomatic intracranial atherosclerotic stenosis (sICAS), test the diagnostic value of single and combined biomarkers, and elucidate their internal interaction mechanism.Methods: A prospective cohort recruited 182 consecutive hospitalized sICAS patients from October 2023 to October 2024. Baseline clinical, laboratory and vascular wall imaging data were collected, and cognitive function was evaluated via Montreal Cognitive Assessment (MoCA) six months after stroke. Subjects were divided into the PSCI group (75 cases) and non-PSCI group (107 cases). Multivariate logistic regression was used to identify independent predictors of PSCI. ROC curves combined with Bootstrap and cross-validation evaluated model diagnostic stability, and two-way mediation analysis clarified the pathway among TGF-β 1, plaque enhancement and PSCI.Results: The PSCI group had older age, shorter education duration, more stroke history, lower BMI and serum TGF-β 1, higher plaque enhancement rate and lower plaque eccentricity index (all P< 0.05). Age, plaque enhancement and infarct volume were independent risk factors for PSCI, while TGF-β 1 was an independent protective factor. Single indicators showed moderate diagnostic efficacy for PSCI, and the combined model reached an AUC of 0.801 with stable performance in internal validation. Plaque enhancement aggravated PSCI by reducing TGF-β 1 levels, with a mediating effect ratio of 24.04% (P=0.026), while the reverse pathway had no statistical significance. Multiple cognitive subdomains were damaged in PSCI patients.Conclusion: Age, plaque enhancement and serum TGF-β 1 independently affect PSCI in sICAS patients, and their combination shows good diagnostic discrimination. Plaque enhancement worsens PSCI through downregulating serum TGF-β 1, offering theoretical support for PSCI mechanism study and therapeutic target screening.Keywords: symptomatic intracranial atherosclerotic stenosis, post-stroke cognitive impairment, high-resolution magnetic resonance vessel wall imaging, plaque enhancement, transforming growth factor-β 1