Sex-specific associations between exposure to multiple metals and visuospatial memory skills in adolescents

Abstract

OPS 40: Metals: neurological effects, Room 412, Floor 4, August 28, 2019, 10:30 AM - 12:00 PM Background/Aim: In rodents, visuospatial memory deficits following metal exposure have been measured with the radial arm maze (RAM) task. In humans, the virtual radial arm maze (VRAM), is the computerized analogue developed to assess visuospatial memory in children. The goal of this study was to examine associations between exposure to metals and performance on the VRAM among adolecents that can be utilized to plan future translational studies using RAM. Methods: Manganese (Mn), lead (Pb), chromium (Cr) and copper (Cu) were measured in blood, urine, hair, nails and saliva of 184 participants (84 girls; 11-15 years of age) enrolled in the PHIME study (Public Health Impact of Manganese Exposure) who resided near a ferroalloy plant in Italy. VRAM performance was assessed as the time required to complete the task. Using generalized weighted quartile sum (gWQS) regression, we investigated associations between a mixture of four metals in all matrices and VRAM performance, controlling for covariates. We estimated metal mixture weights and effects for the whole cohort and for each sex individually. Results: A higher metal mixture index was associated with poorer VRAM performance (β: 0.28; p=0.02). Upon stratification, this association was observed in girls (β: 0.65; p<0.001) and not boys. Urine Mn and blood Cu contributed 27% and 13% respectively to the overall mixture effect. Mn in all 5 matrices combined contributed to 54% to the overall mixture effect. In post-hoc analyses, no associations were observed between exposure to each metal separately and VRAM performance. Conclusions: Exposure to this metal mixture during adolescence may disrupt visuospatial skill acquisition in females. Our results can inform translational research that may address underlying neurotoxic mechanisms and guide additional studies on which metals to focus in future research.