The Systemic Immune-Inflammation Index and the Risk of Parkinson’s Disease in the U.S.: A Cross-Sectional Study

<b>Background</b>: Inflammation is reportedly related to Parkinson's disease (PD). However, the relationship between the systemic immune-inflammation index (SII) and PD remains unexplored. This study aimed to explore the potential relationship between the SII and PD. <b>Methods</b>: This retrospective cross-sectional study analyzed data from the National Health and Nutrition Examination Survey (NHANES) covering the years 2003 to 2020. We analyzed patients over 40 years of age after excluding those with missing SII, PD and covariate data. Logistic regression, subgroup analysis, and restricted cubic spline models were subsequently conducted to evaluate the associations between the SII and PD. <b>Results</b>: Finally, 30,638 participants were included in this study, of whom 416 (1.36%) were identified as having PD. Weighted multivariate regression analysis, adjusted for all covariates, revealed that participants with elevated in-transform (SII) values had a higher likelihood of PD [OR 1.39; 95% CI (1.02, 1.91), <i>p</i> = 0.039] compared to those with lower SII values. The fully adjusted restricted cubic spline curve revealed that the SII/100 was positively and linearly associated with the incidence of PD (<i>p</i> for nonlinearity > 0.05). Additionally, subgroup analysis revealed a stronger correlation between the SII and PD in female participants [OR = 1.06, 95% CI (1.03, 1.08)] compared to male participants [OR = 1.02, 95% CI (1.00, 1.03)] (<i>p</i> for interaction = 0.01). <b>Conclusions</b>: The SII showed a positive correlation with the incidence of PD, particularly in females. Further large-scale prospective studies are necessary to confirm these findings and explore the causal factors that may contribute to the early prevention of PD.