Childhood Pb-induced cognitive dysfunction: structural equation modeling of hot and cold executive functions.

Background: Childhood lead [Pb] exposure has been consistently linked to neurotoxic effects related to the prefrontal cortex, a critical mediating structure involved in decision-making, planning, problem-solving, and specific aspects of short-term memory, i.e., the components of executive functions [EFs]. Limited studies have taken a deeper phenotyping approach that assess Pb's effects across multiple EF dimensions simultaneously, which can be organized into hot [e.g., reward, motivation] and cold [e.g., primary cognitive processing] dimensions.

Objective: We investigated whether childhood Pb exposure affects hot and cold EF dimensions and assessed any sexually dimorphic effects.

Methods: Leveraging a longitudinal birth cohort based in Mexico City, children's (n = 602) whole blood Pb levels (mean 23.66 μg/L) were measured at ages 4-6 and they were administered several EF tasks at ages 6-9. Confirmatory factor analysis confirmed that six EF tests estimated two latent variables representing hot and cold EF dimensions. Structural equation modeling [SEM] estimated the neurotoxic effect of childhood Pb exposure on latent variables of hot [higher scores indicate improved performance] and cold [higher scores indicate poorer performance] EFs. Subsequently, a multi-group SEM explored potential effect modifications by child sex.

Results: Pb exposure was significantly associated with negative impacts on hot EF performance [b = -0.129, p = 0.004]. In both males (b = -0.128, p = 0.032) and females (b = -0.132, p = 0.027), childhood Pb exposure was significantly associated with a reduction in hot EF performance, with no evidence of an interaction with sex. Additionally, we found no association between Pb exposure and cold EF performance [b = 0.063, p = 0.392] and no notable sex differences.

Impact: The present study leverages a sophisticated SEM framework as an exploratory tool and a neurotoxic framework to analyze multidimensional cognitive data, aiming to delineate hot and cold EFs. Our findings are consistent with neurotoxicity secondary to childhood Pb exposure impacting hot EF performance more than cold EF, though comparable trends were noted in cold EF performance for both sexes. Our approach uniquely captures hot EF, the more emotional and self-regulatory aspect of EF, adding a novel dimension to the literature on Pb exposure and cognitive development.