Micronutrient Deficiency, Arsenic Exposure, and Cognitive Function Outcomes in Adolescents

慢性砷暴露目前影响着70多万人中的1.4亿人 它还影响到210万使用国内井水的美国人。这个 大多数受地下水砷污染影响的国家都是低收入或中等收入国家； 微量营养素缺乏在这些国家很常见，因为他们通常没有食物强化 程序。例如，叶酸、B12和胆碱缺乏在孟加拉国很普遍。这些 微量营养素是神经发育所必需的，也是合成神经递质所必需的 还有髓磷脂。它们也是合成关键的甲基供体(S-腺苷甲硫氨酸)所必需的，即 AS甲基化和尿液排出所必需的。 青少年极易受到环境神经毒性暴露(如砷或 微量营养素缺乏)，因为青春期是神经发育的时期，伴随着强烈的神经 修剪--这也是执行功能技能成熟的神经发育期。对于青少年来说， 砷暴露和微量营养素缺乏对认知的影响可能会有严重的长期影响 对整体健康、生产力和生活质量的影响。 目的和方法：本提案的目的是检验以下假设：(1)叶酸缺乏， B12，胆碱会导致青少年认知功能测试得分较低，(2)砷暴露 会导致青少年在认知功能测试中得分较低，以及(3)接触有毒砷 代谢物会导致青少年在认知功能测试中得分较低。最后的探索 本研究的假设是：(4)营养缺乏可能会改变和加剧砷暴露的影响 关于青少年的认知结果。这项研究将利用现有的生物样品和样本数据 在738名孟加拉青少年(14-17岁)中，有广泛的当前和 水砷暴露的终生历史；这些青少年可用的背景数据和协变量数据 是极其丰富的，将使我们能够开发复杂的模型并提供对上下文的特定见解 导致这些不良认知结果的因素。 创新和未来方向：这项研究将为微量营养素的影响提供洞察 青少年缺乏(叶酸、B12、胆碱)、砷暴露和有毒砷代谢产物暴露 认知功能。这项研究的发现可能会为开发低成本、低风险的干预措施提供参考。 例如微量营养素补充、食品强化计划或行为/教育干预，以 缓解与AS相关的执行功能相关认知能力的下降，特别是在低/中等水平 微营养素缺乏症和暴露量高的收入国家。

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.