Elevated neurofilament light chain (NfL) in blood and CSF as a biomarker for Parkinson's disease cognitive impairment: A meta-analysis.

BACKGROUND: Parkinson’s disease (PD), a progressive neurodegenerative disorder, is linked to cognitive impairment. Neurofilament light chain (NfL) may serve as a biomarker, but its association with cognitive decline in PD remains inconsistent. METHODS: We searched PubMed, Embase, Scopus and Web of Science, identifying 19 eligible studies based on predefined criteria. Methodological quality was assessed using Newcastle–Ottawa Scale (NOS). Diagnostic discriminative performance of NfL was quantified through area under the curve (AUC) with 95% confidence intervals (CI) as effect measure. Meta-analysis employed random-effects models, followed by subgroup analysis, meta-regression, bias risk assessment, and sensitivity analysis. RESULTS: NfL demonstrated moderate-to-high diagnostic accuracy across three PD cognitive states (pooled AUC = 0.74, 95% CI: 0.70–0.79, P < 0.001), with NfL levels progressively increasing alongside worsening cognitive impairment—from PD with no cognitive impairment (PD-NC) to PD with mild cognitive impairment (PD-MCI) and PD dementia (PDD). Pairwise comparisons revealed AUC values of 0.70 (95% CI: 0.64–0.76) for PD-NC vs. PD-MCI, 0.75 (95% CI: 0.65–0.85) for PD-MCI vs. PDD, and 0.79 (95% CI: 0.73–0.86) for PD-NC vs. PDD. Plasma NfL (AUC = 0.75, 95% CI: 0.70–0.81, P < 0.001) slightly outperformed cerebrospinal fluid NfL (AUC = 0.72, 95% CI: 0.69–0.75, P < 0.001) in reflecting cognitive status and Mini-Mental State Examination (MMSE) scale showed superior utility over Montreal Cognitive Assessment (MoCA) evaluating NfL-cognitive impairment relationship. CONCLUSION: NfL levels are closely associated with severity of cognitive impairment in PD patients and may be a potential biomarker for evaluating cognitive decline.