Neurofilament Light Chain as a Prognostic Biomarker for Post-Stroke Cognitive Impairment: A Systematic Review of Prospective Cohort Studies

Background: Post-stroke cognitive impairment (PSCI) is a common complication affecting a substantial proportion of stroke survivors and is associated with reduced functional independence, poorer rehabilitation outcomes, and increased caregiver burden. Early identification of patients at risk remains challenging. Neurofilament Light Chain (NfL), a marker of neuroaxonal injury, has emerged as a potential blood-based biomarker in neurological disorders.Objective: To systematically evaluate prospective evidence on NfL as a predictor of cognitive impairment following ischemic or hemorrhagic stroke.Methods: A systematic review was conducted in accordance with PRISMA Guidelines. PubMed, Cochrane Library, and ScienceDirect were searched for prospective cohort studies assessing plasma or serum NfL levels and subsequent cognitive outcomes in adult stroke patients. Eligible studies evaluated cognitive outcomes using validated assessment tools during follow-up. Due to methodological heterogeneity across studies, findings were synthesized narratively due to methodological heterogeneity.Results: Seven prospective cohort studies involving 2,907 stroke patients were included. Most studies measured NfL within 24-48 hours after stroke onset and assessed cognitive outcomes between 3 and 12 months. Across studies, elevated baseline NfL levels were consistently associated with an increased risk of PSCI and lower cognitive scores. In multivariable analyses, NfL remained independently predictive after adjustment for age, stroke severity, and infarct volume. Reported discriminative performance ranged from AUC 0.672 to 0.865, indicating moderate to good predictive ability.Conclusion: Blood-based NfL measurement is consistently associated with post-stroke cognitive impairment. These findings support circulating Nfl as a promising biomarker for early risk stratification of PSCI in stroke survivors.