Plasma Neurofilament Light Chain as a Predictive Biomarker for Post-stroke Cognitive Impairment: A Prospective Cohort Study

Abstract

Background: Plasma neurofilaments light chain (pNfL) is a marker of axonal injury. The purpose of this study was to examine the role of pNfL as a predictive biomarker for post-stroke cognitive impairment (PSCI). Methods: A prospective single-center observational cohort study was conducted at the General Hospital of Western Theater Command between July 1, 2017 and December 31, 2019. Consecutive patients ≥18 years with first-ever acute ischemic stroke (AIS) of anterior circulation within 24 h of symptom onset were included. PSCI was defined by the Montreal Cognitive Assessment (MOCA) (MOCA < 26) at 90 days after stroke onset. Results: A total of 1,694 patients [male, 893 (52.70%); median age, 64 (16) years] were enrolled in the cohort analysis, and 1,029 (60.70%) were diagnosed with PSCI. Patients with PSCI had significantly higher pNfL [median (IQR), 55.96 (36.13) vs. 35.73 (17.57) pg/ml; P < 0.001] than Non-PSCI. pNfL was valuable for the prediction of PSCI (OR 1.044, 95% CI 1.038–1.049, P < 0.001) after a logistic regression analysis, even after adjusting for conventional risk factors including age, sex, education level, NIHSS, TOAST classification, and infarction volume (OR 1.041, 95% CI 1.034–1.047, P < 0.001). The optimal cutoff value of the pNfL concentration was 46.12 pg/ml, which yielded a sensitivity of 71.0% and a specificity of 81.5%, with the area under the curve (AUC) at 0.785 (95% CI 0.762–0.808, P < 0.001). Conclusion: This prospective cohort study showed that the pNfL concentration within 48 h of onset was an independent risk factor for PSCI 90 days after an anterior circulation stroke, even after being adjusted for potential influencing factors regarded as clinically relevant. Clinical Trial Registration: www.chictr.org.cn, identifier ChiCTR1800020330.