The association of prenatal manganese exposure with problem-solving skills and its mediation by the building blocks...

Problem-solving skills build upon three core executive functions: inhibition, working memory, and cognitive flexibility. There is evidence of adverse associations of prenatal exposure to manganese (Mn) with core executive functions, but less is known about Mn associations with problem-solving or potential mediators of this association.

This study aimed to investigate the association of prenatal Mn exposure with problem-solving and to identify potential neuropsychological mechanisms through which this association may be mediated.

Study participants were 410 adolescents from the New Bedford Cohort (NBC) who have undergone periodic evaluations since their birth (1993-1998) to mothers residing near a Massachusetts Superfund site. We investigated the association of cord blood Mn with problem-solving measured by the Delis-Kaplan Executive Function System (D-KEFS) Sorting and Tower subtests (scores scaled to a mean ± SD of 10 ± 3) using multivariable linear regression. Inhibition and cognitive flexibility were also measured by the D-KEFS; working memory was measured with the Wide Range Assessment of Memory and Learning, 2nd edition. Regression-based causal mediation analysis was used to assess the proportion of the Mn-problem-solving association mediated by inhibition, working memory, and cognitive flexibility individually and jointly.

NBC adolescents (mean age 15.5 years) were socio-demographically diverse with 31 % in a low-income household at birth and had cord blood Mn concentrations similar to other general population samples. Mn was associated with Sorting but not Tower scores. Specifically, a doubling of cord blood Mn concentrations was associated with - 0.59 points lower (95 % CI: -1.16, -0.03) Sort Recognition score. In mediation analyses, there was suggestive evidence that inhibition, working memory, and cognitive flexibility combined mediated 30 % of the total effect of Mn on Sorting. When analyzed individually, working memory mediated a larger proportion (24 %) of the effect than inhibition or cognitive flexibility.

We observed adverse associations of cord blood Mn with problem-solving among adolescents. There was suggestive evidence that the building blocks of executive function jointly, and working memory individually, were potentially important mediators of this association.