Associations of the Hemoglobin-to-red blood cell distribution width ratio with Parkinson's Disease: the mediating role of systemic inflammation response index

Neuroinflammation and immune system dysregulation are critical contributors to the pathogenesis of Parkinson’s disease (PD). Although emerging inflammatory biomarkers, such as the hemoglobin-to-red blood cell distribution width ratio (HRR) and systemic inflammation response index (SIRI), may be significantly relevant, their relationship with PD has not been thoroughly explored. This study aimed to investigate the association between HRR and PD risk in middle-aged and older adults and evaluate the potential mediating role of SIRI in this association. A cross-sectional study was performed using data from 24,019 participants in the National Health and Nutrition Examination Survey (NHANES) 2005–2018. To investigate the relationship between HRR and PD prevalence, multivariable logistic regression models, restricted cubic spline (RCS) analyses, and subgroup analyses were employed. Additionally, a mediational analysis was performed to evaluate the potential mediating effect of the SIRI on this association. In a cohort of 24,019 participants, 347 individuals (1.4%) were diagnosed with PD. Multivariable-adjusted logistic regression demonstrated that each one-unit increase in HRR was associated with an 88% reduction in the odds of PD (odds ratio [OR] = 0.12, 95% confidence interval: 0.05-0.30). Conversely, each one-unit increase in the SIRI corresponded to a 15% increase in the odds of PD (OR = 1.15, 95% confidence interval: 1.03-1.28). RCS analysis revealed a crucial inverse linear association between HRR and PD. Subgroup analyses confirmed the robustness of the inverse association between HRR and PD. Additionally, analysis of the mediational effects revealed that the SIRI mediated 4.85% of the association between HRR and PD (p < 0.05). These findings demonstrate a crucial inverse correlation between reduced HRR and higher PD prevalence, with SIRI acting as a partial mediator. The results revealed a potential correlation among HRR, SIRI, and PD, suggesting that monitoring and managing HRR and SIRI levels may constitute a potential approach for mitigating PD prevalence.