Chronic high-level manganese (Mn)-induced neurotoxicity has been associated with Mn accumulation in the basal ganglia and higher risk for developing parkinsonism. Recent studies in Mn-exposed animals revealed Mn accumulation in the hippocampus, the presence of Aβ diffuse plaques, and deficits in associative learning, the latter being hallmarks of Alzheimer's disease (AD) or related disorders. This and recent evidence of hippocampal Mn accumulation in welders prompted us to test the hypothesis that welders with chronic Mn exposure would display changes in the hippocampus. Subjects with (welders; n = 42) or without (controls; n = 31) welding history were studied. Mn exposure was estimated by occupational questionnaires, whole blood Mn, and R1 imaging (estimate of short-term brain Mn accumulation). Hippocampal diffusion tensor imaging (DTI; estimate of microstructural brain changes) and volume were determined. Compared with controls, welders displayed no significant difference in hippocampal volume (p =.165). Welders, however, exhibited higher DTI hippocampal mean diffusivity (MD) values compared with controls (p =.035) that was evident particularly in older welders (>50 years, p =.002). Hippocampal MD was associated significantly with age in welders (R = 0.59; p <.001) but not in controls (p =.16). Moreover, higher hippocampal MD values (age adjusted) were associated with long-term cumulative Mn exposure (R = 0.36, p =.021). Welders with chronic exposure have higher MD values in the hippocampus that become greater with increasing age, a brain change that is similar to that observed in those at risk for AD. The current results suggest that Mn exposure, coupled with aging, may make welders more vulnerable to AD or AD-like changes.
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