Hippocampal microstructural and neurobehavioral differences in welders are related to higher R2* in the red nucleus

Abstract

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.