Systemic Inflammatory Markers in Parkinson's Disease: Correlations with Disease Severity and Neuropsychiatric...

Objective: Chronic neuroinflammation is a recognized driver of Parkinson's disease (PD) pathophysiology, in which systemic inflammation may also participate. This study evaluated composite inflammatory indices in peripheral blood and investigated their associations with disease severity, motor symptoms, and non-motor symptoms. Methods: A retrospective study was conducted using routinely collected clinical and laboratory data. A total of 315 PD patients and 125 healthy controls (HCs) were enrolled. All PD patients underwent motor and non-motor symptom assessments. Differences in peripheral inflammatory indices were compared between the PD and HC groups, and across Hoehn-Yahr (H-Y) stages. Multinomial logistic regression was used for factors associated with disease severity. Multivariable linear regression examined correlations with clinical measures. Benjamini-Hochberg false discovery rate (FDR) correction was applied to PD vs. HC comparisons, H-Y group comparisons, and all symptom-related analyses. Results: Levels of the systemic inflammation response index (SIRI), monocyte-to-lymphocyte ratio (MLR), and monocyte-to-high-density lipoprotein cholesterol ratio (MHR) were significantly elevated in PD after FDR correction. In the multinomial logistic regression model, disease duration was significantly associated with both H-Y < 3 vs. H-Y > 3 (OR = 0.940, 95% CI: 0.894, 0.989; p = 0.016) and H-Y = 3 vs. H-Y > 3 (OR = 0.961, 95% CI: 0.925, 0.999; p = 0.043). Hypertension was associated only with H-Y < 3 vs. H-Y > 3 (OR = 0.468, 95% CI: 0.226, 0.970; p = 0.041). Platelet-to-lymphocyte ratio (PLR) was significantly associated with H-Y = 3 vs. H-Y > 3 (OR = 0.989, 95% CI: 0.980, 0.997; p = 0.012) but not with H-Y < 3 vs. H-Y > 3 (p = 0.167). Systemic immune-inflammation index (SII) was not significantly associated with either comparison. SII × sex (p = 0.496) and PLR × sex (p = 0.048, Bonferroni-corrected p > 0.025) interaction terms were not significant. After FDR correction, no inflammatory indices were significantly associated with motor or non-motor symptom (all q > 0.05). Conclusions: After rigorous adjustment, previously reported associations between peripheral inflammatory indices and PD severity were not replicated. Disease duration and hypertension were the primary correlates of higher H-Y staging. Elevated inflammatory indices should be interpreted with caution, as they may be associated with longer disease duration or vascular comorbidity.