Exploring the interactions of urinary metals and the mediating role of oxidative stress in Parkinson's disease risk: an epidemiological study in the elderly†

Abstract

Parkinson's disease (PD) ranks as the second most prevalent neurodegenerative disorder, often leading to significant disability in affected individuals. Metal exposure has been implicated in PD, but the overall role, interactions among metal mixtures, and underlying mechanisms remain unclear. In this study, we measured 8 essential and 2 potentially harmful metal trace elements in urine samples from PD patients (n = 96) and healthy controls (n = 162). The concentration of 8-hydroxy-2′-deoxyguanosine (8-OHdG), a marker of oxidative damage, was also measured. Logistic regression and restricted cubic spline (RCS) regression analyses revealed that both increased exposure to manganese (Mn) and lead (Pb), and insufficient intake of chromium (Cr), nickel (Ni), selenium (Se), and cadmium (Cd) may increase the risk of PD. However, smoking may mediate the relationship between Cd and PD, and Cd itself may not exert a protective effect against PD. Bayesian kernel machine regression (BKMR) and quantile-based g-calculation (QGC) models demonstrated that both metal deficiencies and excesses could increase the risk of PD, with Mn (73.7%) and Pb (9.3%) identified as the main contributors to PD risk. Furthermore, we observed an interaction between Mn and Cr, with Cr amplifying the promoting effect of Mn. Mediation analysis indicated that 8-OHdG mediated 11.6% of the total effect of Mn and Pb exposure on PD risk. Further research is required to explore specific metals' protective mechanisms and elucidate the interactions among different metals. Further longitudinal and cohort studies are required to better verify the causal link between metal exposure and PD.