Association of Serum Manganese Levels with  Alzheimer's Disease and Mild Cognitive Impairment:  A Systematic Review and Meta-Analysis

Manganese (Mn) is one of the most studied environmental heavy metals linked to Alzheimer's disease (AD). However, it remains unclear whether serum Mn levels are associated with AD and mild cognition impairment (MCI, a prodromal stage of AD). We conducted a metaanalysis to analyze the serum Mn levels in patients with AD and MCI. A systematic database search of PubMed, Web of Science, and the China National Knowledge Infrastructure (CNKI) identified 17 studies, including 836 cases and 1254 health controls (HC). Random-effects meta-analysis showed that patients with AD had significantly reduced serum Mn levels compared with HC subjects (SMD = -0.39; 95% CI (-0.71, -0.08); p = 0.015). MCI individuals had a tendency toward reduced serum Mn levels compared with HC subjects (SMD = -0.31; 95% CI (-0.70, 0.08); p = 0.117). A significant decrease in serum Mn levels was found in patients with cognitive impairment (including both AD patients and MCI patients) (SMD = -0.37, 95% CI (-0.60; -0.13); p = 0.002). Finally, no significant differences were observed between AD and MCI patients in serum levels (SMD = 0.24; 95% CI (-0.23, 0.72); p = 0.310). Our findings show that the serum Mn levels are lower in AD patients, and Mn deficiency may be a risk factor for AD.