Chronic arsenic exposure currently affects >140 million people in 70+ countries (including Bangladesh); it also effects 2.1 million Americans who use domestic well water. The majority of countries afflicted by groundwater arsenic (As) contamination are low-income or middle-income; micronutrient deficiencies are common in these countries, as they don?t typically have food fortification programs. For example, deficiencies in folate, B12, and choline are widespread in Bangladesh. These micronutrients are essential for neural development and are necessary for the synthesis of neurotransmitters and myelin. They are also required for synthesis of a crucial methyl donor (s-adenosylmethionine) that is required for As methylation and urinary elimination. Adolescents are acutely vulnerable to environmental neurotoxic exposures (such as arsenic or micronutrient deficiency) because adolescence is a period of neurodevelopment associated with intense neural pruning ? it is also the neurodevelopmental period in which executive function skills mature. For adolescents, the cognitive effects of arsenic exposure and micronutrient deficiencies may have serious long-term consequences for overall health, productivity, and quality of life.
Aims and Methods: The goals of this proposal are to test the hypotheses that, (1) deficiencies in folate, B12, and choline will result in poorer scores on tests of cognitive function in adolescents, (2) arsenic exposure will result in poorer scores on tests of cognitive function in adolescents, and (3) exposure to toxic arsenic metabolites will result in poorer scores on tests of cognitive function in adolescents. The final exploratory hypothesis of this study is that (4) nutritional deficiencies may modify and exacerbate the effect of As exposure on cognitive outcomes for adolescents. This study will leverage existing biospecimens and data from a sample of 738 Bangladeshi adolescents (aged 14-17 years) with a broad range of well-characterized current and lifetime histories of water arsenic exposure; the contextual and covariate data available for these adolescents is extremely rich, and will allow us to develop complex models and provide specific insights into contextual factors contributing to these adverse cognitive outcomes. Innovation and Future Directions: This study will provide insight into the influences of micronutrient deficiencies (folate, B12, choline), arsenic exposure, and toxic arsenic metabolite exposure on adolescent cognitive function. Findings from this study could inform the development of low-cost, low-risk interventions, such as micronutrient supplementation, food fortification programs, or behavioral/educational interventions to mitigate As-related decrements in executive-function-related cognitive abilities, particularly in low/middle income countries that have a high prevalence of micronutrient deficiencies and As exposure.
Adverse cognitive outcomes have previously been associated with chronic arsenic exposure and toxic arsenic metabolite exposure in children and adults; these adverse outcomes may persist even after exposure has ended or has been reduced. Existing research has demonstrated that these effects are stronger in regions with high prevalence of micronutrient deficiencies, which have their own adverse cognitive health consequences; therefore, further research into arsenic exposures and micronutrient predictors is needed, particularly during important neurodevelopmental periods, such as adolescence, when critical executive function skills mature. This proposed research will provide insight into the relationships between micronutrient deficiency, arsenic exposure, toxic arsenic metabolite exposure and cognitive outcomes, which could inform future interventions for minimizing the health risks of these exposures via nutrient supplementation, food fortification, or behavioral intervention programs.
