Neurofilament light chain as a potential biomarker of perioperative neurocognitive disorders: a systematic review and meta-analysis

OBJECTIVES: Although neurofilament light chain (NfL) is used as a biomarker of neurodegenerative decline, its application in surgery- and anaesthesia-induced acute cognitive dysfunction remains uncertain. We aimed to synthesise existing evidence to evaluate the potential of NfL as a biomarker for perioperative neurocognitive disorder (PND). DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, EMBASE, MEDLINE, the Cochrane Library and the Cochrane Central Register of Clinical Trials were systematically searched up to March 2024. ELIGIBILITY CRITERIA: Observational studies-including cohort, case-control and cross-sectional designs-were included if they reported cerebrospinal fluid (CSF) or blood NfL levels in individuals with and without PND. DATA EXTRACTION AND SYNTHESIS: ≤40% indicating low heterogeneity and the use of a fixed-effect model; random-effects models were used when this threshold was exceeded. RESULTS: Within-group analyses showed significant postoperative increases in blood NfL levels in both the postoperative delirium (POD) group (standardised mean difference (SMD) = 0.49; 95% CI 0.34 to 0.64) and the no-POD group (SMD=0.67, 95% CI 0.53 to 0.81). Between-group comparisons revealed significantly higher preoperative CSF NfL levels in the POD group (SMD=0.27, 95% CI 0.07 to 0.47). Both preoperative and postoperative blood NfL levels were also significantly elevated in the POD group (SMD=0.53, 95% CI 0.40 to 0.66, and SMD=0.58, 95% CI 0.43 to 0.73, respectively). CONCLUSIONS: This meta-analysis suggests that NfL may be a potential biomarker for POD. Further research is needed to clarify the association between CSF and blood NfL levels and other forms of PND. PROSPERO REGISTRATION NUMBER: CRD42024516907.