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

Abstract

<h4>Objectives</h4>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).<h4>Design</h4>Systematic review and meta-analysis.<h4>Data sources</h4>PubMed, EMBASE, MEDLINE, the Cochrane Library and the Cochrane Central Register of Clinical Trials were systematically searched up to March 2024.<h4>Eligibility criteria</h4>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.<h4>Data extraction and synthesis</h4>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 I² statistic, with I²≤40% indicating low heterogeneity and the use of a fixed-effect model; random-effects models were used when this threshold was exceeded.<h4>Results</h4>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).<h4>Conclusions</h4>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.<h4>Prospero registration number</h4>CRD42024516907.