Association of circulating manganese levels with Parkinson's disease: A meta-analysis

Whether systemic manganese (Mn) dysfunctions in Parkinson's Disease (PD) is still under ongoing debate. The recent reported studies on the circulating Mn levels in PD showed inconsistent results. A meta-analysis study was conducted to evaluate the association of circulating Mn levels with PD, and to clarify whether Mn should be considered as a potential risk factor for PD. A systematic searching was performed based on PubMed, web of science, and China National Knowledge Infrastructure (CNKI). Finally, 22 studies were identified, involving 637 PD patients and 802 health controls (HC) individuals for serum Mn, 1258 PD patients and 1304 HC individuals for peripheral blood Mn, and 195 PD patients and 196 HC individuals for cerebrospinal fluid (CSF) Mn. Forest plots were adopted to represent the comparison of the groups by assessing standardized mean difference with random effects model. This meta-analysis revealed a significantly increased serum Mn levels in PD patients (SMD = 0.78; 95% CI [0.32, 1.24]; P = 0.001), and it was further confirmed when serum, plasma and whole blood studies were analyzed together (SMD = 0.58; 95% CI [0.25, 0.91]; P = 0.001). Instead, no significant differences of CSF Mn were observed between PD patients and HC individuals (SMD = −0.09; 95% CI [−0.47, 0.29]; P = 0.644). These results supported the notion that elevated Mn level should be a potential risk factor for PD, although the high heterogeneity and methodological limitations recommended caution in the interpretations for the present findings.