ABSTRACT NUMBER: ESOC2026A2083 EARLY PLASMA NFL PREDICTS COGNITIVE OUTCOMES 5 YEARS AFTER STROKE

Abstract Background and aims Cognitive impairment is common after stroke, yet early risk stratification remains challenging. Blood-based biomarkers of neuroaxonal and astroglial injury, such as neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP), may help identify patients at high risk for cognitive impairment. Methods In a prospective multicentre cohort of dementia-free patients with ischaemic or haemorrhagic stroke (n = 558; median NIHSS 3 [IQR 1–5]; DEMDAS), plasma samples were collected at a median of 3 days post-stroke (IQR 2-5). NfL and GFAP were measured using single-molecule detection technology. Neuropsychological assessments were conducted at 6, 12, 36, and 60 months. The primary outcome was post-stroke cognitive impairment (PSCI; ≥1 domain <-1.5 SD) within five years. Secondary outcomes included global cognitive performance and domain-specific outcomes. Associations with longitudinal outcomes were assessed using mixed-effects models, adjusted for relevant confounders. Results Higher NfL was associated with greater white matter hyperintensity volume and infarct volume. NfL, but not GFAP, predicted PSCI over 5 years (OR = 1.57, 1.28–1.91, P < 0.0001; Figure, Panel A), lower global cognitive scores (Figure, Panel B), and poorer attention and executive function. Machine-learning models consistently ranked NfL among the top predictors of PSCI (Figure, Panel C), outperforming GFAP and conventional stroke-related factors such as infarct volume and NIHSS. Conclusions Plasma NfL measured shortly after stroke robustly predicts long-term cognitive impairment, particularly in executive domains. It likely captures brain injury not fully explained by clinical or imaging markers and may improve early risk identification, targeted monitoring, and post-stroke trial enrichment. Conflict of interest The authors declare no conflicts of interest. Figure 1 - belongs to Conclusions