Introduction: Metal exposure has been associated with higher risk of neurodegenerative disorders such as Alzheimer's disease (AD). We examined the potential link between welding-related metal co-exposure (e.g., Fe, Mn, Pb) and AD-related structural and neurobehavioral metrics. Methods: Subjects with (welders; n=42) or without (controls; n=31) a history of welding were examined. Metal exposure was estimated by exposure questionnaires and whole blood metal levels. Brain metal accumulations were estimated by MRI R1 (Mn) and R2* (Fe) in the caudate, putamen, globus pallidus, red nucleus (RN), and hippocampus. AD-related structural differences were assessed by volume and diffusion tensor imaging metrics in the hippocampus, and neurobehavioral aspects by learning/memory task scores. Results: Compared to controls, welders displayed higher blood metal levels (p values <0.004) and R2* values in the caudate and RN (p values <0.024). Caudate R2* values were associated with blood Fe (p=0.043), whereas RN R2* values were correlated with blood Pb (p=0.003). Welders had higher hippocampal mean diffusivity (MD; p=0.011) and lower Story Recall scores (p=0.049), but no difference in volume or domain-wise learning/memory performance (p values >0.117). Group differences in hippocampal MD and Story Recall scores were greater with higher RN R2* values (p values <0.016). Moreover, RN R2* values reflected an indirect link between blood Pb and hippocampal MD (p=0.036) across both groups. Discussion: Welders had hippocampal structural and learning/memory performance differences similar to those in AD-at-risk populations. These AD-like differences in welders may, in part, be linked to Pb exposure reflected by higher RN R2* levels at the brain level.

The authors have declared no competing interest.

This study was supported by NIH grants R01 ES019672, R01 NS060722, U01 NS082151 and NS112008, the Hershey Medical Center General Clinical Research Center (National Center for Research Resources, UL1 TR002014), the Penn State College of Medicine Translational Brain Research Center, the PA Department of Health Tobacco CURE Funds, and the National Research Foundation of Korea (2019R1G1A109957511).

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