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 Three independent reviewers assessed each article. Quality scoring was conducted, and the extracted data were analysed using STATA. Risk of bias was evaluated using the Newcastle–Ottawa Scale. Meta-analytical model selection was guided by the I 2 statistic, with I 2 ≤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.