The neutrophil-to-lymphocyte ratio in Parkinson's disease: a systematic review and meta-analysis of its association with differential diagnosis, severity, and prognosis

Background and aim This study aimed to systematically review and meta-analyze the evidence on the association of the neutrophil-to-lymphocyte ratio (NLR) with clinical parameters in Parkinson's disease (PD), specifically its role in group differentiation (from healthy controls and other neurodegenerative diseases), disease severity, and prognosis. Methods In this study, a systematic review and meta-analysis were performed according to the PRISMA guidelines. A search conducted in PubMed, Embase, Scopus, Web of Science, and Google Scholar up to June 2024 was undertaken, providing observational studies that reported NLR in PD. The random-effects models pooled the mean differences of PD versus controls and PD versus multiple system atrophy (MSA), and pooled for UPDRS subscale correlation coefficients, total UPDRS, and Hoehn & Yahr (H&Y) stage. Constipation, depressive symptomatology, and mild cognitive impairment (MCI) markers were also analyzed. Results Twenty-eight studies were included. The NLR was significantly higher in patients with PD than in healthy controls (MD, 0.38; 95% CI 0.22–0.53; I 2 = 90%; moderate certainty). No significant difference was observed between PD and MSA. NLR showed moderate positive correlations with UPDRS I ( r = 0.42), UPDRS II ( r = 0.34), UPDRS III ( r = 0.27), total UPDRS ( r = 0.67), and H&Y stage ( r = 0.33). Associations were significant for depressive symptoms (high certainty) but not for constipation. For MCI, the NLR was lower rather than higher in patients who developed impairment, with modest discriminatory performance (moderate certainty). Conclusion NLR is higher in PD and correlates with clinical severity and depressive symptoms, but it does not discriminate PD from MSA or between motor subtypes, and it was not associated with incident mild cognitive impairment in the expected direction.