Correlation between Blood Biomarkers and Post-Stroke Cognitive Impairment

Xianjun Liu^1,2,3Zhaoyang Lv^1,2Zhihong Shi^1,2Feng Liu^1,2Hao Wu^1,2*Shuai Liu^1,2*Yong Ji^1,2*

• ¹Department of Neurology,Huanhu Hospital Affiliated to Tianjin Medical University, Tianjin, China
• ²Tianjin Key Laboratory of Cerebrovascular and Neurodegenerative Diseases, Tianjin dementia institute, Tianjin Huanhu Hospital, Tianjin, China
• ³Department of Neurology, The Central Hospital of Yongzhou, Yongzhou, Hunan, China

Background: Post-stroke cognitive impairment (PSCI) is common and imposes a significant burden upon both families and society. There is limited information on biomarkers for PSCI. This study investigated the correlation between blood biomarkers and post-ischaemic stroke cognitive impairment, to identify potential blood biomarkers and their efficacy in predicting the disorder. Methods: This prospective study enrolled patients who had experienced their first acute ischaemic stroke between January 2024 and March 2025. Patients underwent blood tests within 24 hours of admission, which measured plasma levels of Aβ1-40, Aβ1-42, glial fibrillary acidic protein (GFAP), neurofilament light chain (NFL), p-Tau181, p-Tau217, Aβ42/40, and p-Tau217/Aβ1-42. The cognitive function of the patients was assessed at the three-month follow-up visit using the Montreal Cognitive Assessment (MOCA) scale. Participants were divided into a cognitive impairment group and a cognitively normal group with a MoCA cutoff score of 22. Results: A total of 128 patients who had experienced a first ischaemic stroke were included in the analysis. At the three-month post-stroke follow-up, 69 patients (53.9%) were allocated to the PSCI group, with 59 patients (46.1%) in the cognitively normal group. After univariate and multivariate logistic regression analyses, plasma GFAP (OR = 1.0027, 95% CI = 1.0002–1.0053, P = 0.038) and plasma NFL (OR = 1.0046, 95% CI = 1.0006–1.0086, P = 0.025) were identified as independent risk factors for cognitive impairment following ischaemic stroke. Receiver operating characteristic (ROC) curves indicated area under the curve (AUC) values of 0.779 (95% CI = 0.700–0.858, P < 0.001) for plasma GFAP and 0.809 (95% CI = 0.733–0.885, P < 0.001) for plasma NFL, indicating good predictive performance for both parameters. The AUC for GFAP+NFL was 0.855 (95% CI = 0.792–0.918, P < 0.001), indicating superior predictive performance of the GFAP and NFL combination for PSCI post-ischaemic stroke cognitive impairment. Conclusion: Elevated plasma GFAP and NFL levels are associated with an increased risk of post-ischaemic stroke cognitive impairment. Plasma GFAP and NFL may represent potential biological markers for PSCI. The combination of the two parameters showed superior predictive efficacy for PSCI.