Neurofilament-Light Chain and Glial Fibrillary Acidic Protein as Blood-Based Delirium Risk Markers: A Multicohort Study

Postoperative delirium (POD) is often under-recognized in clinical practice. Blood-based markers could facilitate delirium detection and risk stratification. Neurofilament-Light chain (NfL) and Glial Fibrillary Acidic Protein (GFAP) are promising blood-based markers for neurodegenerative diseases and potential candidates for delirium. This study explored their role as blood-based risk markers for POD in older patients undergoing hip fracture surgery. In this prospective multicohort study, preoperative blood and intraoperative cerebrospinal fluid (CSF) samples were collected from patients aged ≥65 years with hip fractures. POD was assessed daily using the 4AT scale. NfL and GFAP concentrations in both blood and CSF were compared between POD and Non-POD groups, further stratifying by dementia status. Logistic regression models adjusted for covariates were used to assess associations. A total of 143 patients (median age, 85 years; 76.9% female) were included, with POD occurring in 38 patients (26.6%). Blood NfL and GFAP concentrations were significantly higher in the POD group than in Non-POD (64.55 vs. 44.6 pg/mL and 22 vs. 14.8 pg/mL, P&;lt0.001). CSF NfL levels were also elevated in POD (2154 vs. 1565 pg/mL, P=0.007), but no significant difference was observed for CSF GFAP levels. Higher preoperative blood NfL and GFAP levels independently predicted POD after adjusting for age, sex, dementia, frailty, and Interleukin-6 (Odds Ratio, OR: 3.21, 95% Confidence Interval, CI: 1.26-8.21, and OR: 3.66, 95% CI: 1.38-9.68, respectively). Although further research is needed, our findings support the role of NfL and GFAP as blood-based risk markers for POD in older patients undergoing hip fracture surgery.