Low-level arsenic exposure, childhood neighborhood disadvantage, and executive functions in adolescents from Montevideo, Uruguay

Introduction: Low-level arsenic (As) exposure is linked to cognitive deficits, but its impact on specific executive functions (EF) in adolescents is not well understood. Additionally, neighborhood socioeconomic context may interact with As exposure to influence cognitive outcomes. This study examines associations between blood As levels, neighborhood disadvantage, and EF performance in adolescents from Montevideo, Uruguay. Methods: We analyzed data from 344 adolescents in the Salud Ambiental Montevideo (SAM) cohort, where blood As levels were measured at two time points, with values averaged and log2-transformed for analysis. EFs, including working memory, inhibitory control, cognitive flexibility, and fluid cognition, were assessed using the NIH Cognitive Toolbox. Neighborhood disadvantage (ND) was represented as a factor encompassing sociodemographic indicators. Multiple imputation was used to handle missing data, and linear regression models tested associations between As exposure, EFs, and potential interactions with ND. Furthermore, we explored effect modification by age (young adolescents <11.6 years, older adolescents ≥11.6 years). Results: Based on multivariable models, there was no evidence for an association between blood As and EFs or fluid cognition or of interactions with neighborhood disadvantage. Exploratory analyses revealed evidence of effect modification by age, with inverse associations between As exposure and inhibitory control and working memory at younger ages. Conclusion: There was no evidence for an association between low-level blood As and EFs in adolescents overall, but age-related susceptibility to As was suggested for younger ages. Further research on low-level As exposure in adolescents is needed to better understand critical windows of susceptibility and socioeconomic contexts for neurotoxic effects of As.