Characterizing the Association Between Prenatal and Early Postnatal Metal Exposure and Later Adulthood Cognitive Function in the St. Louis Baby Tooth – Later Life Health Study

Abstract

Early exposure to a number of metals is associated with early cognitive outcomes, however, the evidence linking these early exposures to cognitive function in adulthood or later is limited. Furthermore, the options to address deleterious exposures that have already occurred are poorly understood. This dissertation set out to address three key gaps in our understanding of the long-term impacts of early metal exposure: (1) the association between prenatal and early postnatal lead exposure on later adulthood cognitive function; (2) effect modification of the prior association by level of childhood cognitively stimulating activities; and (3) the association between prenatal and early postnatal zinc exposure and later adulthood cognitive function. We addressed the three gaps by leveraging the novel St. Louis Baby Tooth – Later Life Health Study (SLBT). This cohort study was formed of individuals primarily from the St. Louis, Missouri, USA area who donated their deciduous (baby) teeth in 1958-1972. Using information provided at the time of tooth donation, participants were re-contacted and completed surveys and cognitive testing beginning in 2021. Using metal concentrations in the deciduous teeth, representing metal exposure from the second trimester through the first postnatal months, we were able to address the question of whether early metal levels were associated with cognitive function at an average age of 62 years, and whether these associations were dependent on childhood cognitively stimulating activities. The first study (Chapter 2) addressed research gap 1 and found that early lead exposure, particularly during the second trimester, was associated with poorer cognitive function in later adulthood. We further found that these associations were dependent on sex, with stronger negative associations found in females. The second study (Chapter 3) addressed research gap 2 and found that the effects of prenatal and early postnatal lead exposure on later adulthood cognitive function were dependent on level of cognitively stimulating activities in childhood. For those with low levels of cognitively stimulating activities, particularly at age 6 and 18, lead exposure was negatively associated with cognitive function, while among those with high levels of cognitively stimulating activities, lead exposure was generally not associated with cognitive function. The third study (Chapter 4) addressed research gap 3 and found that tooth zinc concentrations in the prenatal and early postnatal periods were non-linearly associated with cognitive function in later adulthood. Tooth concentrations of zinc in the middle of the distribution were generally associated with the greatest levels of cognitive function, while particularly low or high levels of tooth zinc were associated with poorer late adulthood cognitive function. This dissertation addresses a largely unexplored area of the impacts of early exposure to metals on cognitive function decades later. While it is a sobering reminder of the long reach of lead exposure, it also provides a possible avenue for intervention after lead exposure by encouraging participation in cognitively stimulating activities in childhood.