Metal Mixtures and the Role of Iron Status in Early Adolescent Cognition

项目摘要/摘要 金属是已知的儿童神经毒物，但人们对金属混合物的影响关注较少。 关于认知功能。此外，很少有关于金属的研究考察铁状态对认知的影响。 青少年的结果。我们的研究旨在描述一种与工业相关的金属混合物的神经毒性。 (锰、铅、铜、铬)对青少年注意和言语学习记忆领域的影响，并确定 通过阐明铁在金属中的地位所起的作用，可能对金属有更大敏感性的亚群- 诱导毒性。这项拟议的研究将使用之前从混合病毒对公共健康的影响收集的数据 元素暴露(PHIME)研究，对720名10-14岁的意大利儿童进行队列研究。PHIME的孩子们 从布雷西亚省的三个不同地理区域招募，暴露在不同的空气中 锰铁合金工业。在多学科环境专家团队的指导下 流行病学、生物统计学、暴露科学、神经行为毒理学和混合学，萨曼莎·希尔德罗斯 (PI)提出了以下目标：1)描述金属混合物与注意功能和 青少年的言语学习和记忆；2)评估铁作为一种金属修饰物的作用 改变金属混合物和认知之间联系的神经毒性，以及b)一种 受到金属混合物的影响，并影响认知。PHIME中的金属在多个生物标志物中进行了测量 (头发、指甲、血液、唾液、尿液)和全血中的铁状态参数(铁蛋白， 转铁蛋白和血红蛋白)，并使用红细胞压积/血清铁水平。认知功能的客观测量 被用来评估注意力(Conners-Wells评价量表)和言语学习和记忆(加利福尼亚州 口语学习测试)。我们将对混合物使用最先进的统计方法，包括贝叶斯 核机器回归和基于分位数的g计算，以满足我们提出的目标。这项研究 将有助于我们目前对金属混合物的神经毒性的理解 与居住在铁合金排放物附近的社区相关，铁合金排放是一个正在全球扩张的行业， 儿童整体认知功能所必需的两个领域，并将作为潜在的铁状态进行检查 易感因素。拟议的培训和研究将扩大申请人在以下领域的坚实基础 环境流行病学，并为她提供了研究多种疾病联合影响所需的额外技能 金属对认知的影响，同时考虑铁的状态。这项研究将1)解决健康方面的巨大数据差距 金属混合物对青少年的影响，以及2)有助于确定可改变的环境因素，包括 青春期的饮食因素，如铁的状况，可能是未来公共卫生干预的目标。

Project Summary/Abstract Metals are known neurotoxicants in children, but less attention has been given to the impact of metal mixtures on cognitive function. Further, few studies of metals have examined the role of iron status on cognitive outcomes in adolescents. Our study aims to describe the neurotoxicity of an industrial-relevant metal mixture (Mn, Pb, Cu, Cr) on the domains of attention and verbal learning and memory in adolescents, and to identify subpopulations that may have greater susceptibility to metals by elucidating the role of iron status in metal- induced toxicity. This proposed study will use previously collected data from the Public Health Impact of Mixed element Exposure (PHIME) study, a cohort of 720 Italian children aged 10-14 years. Children in PHIME were recruited from three distinct geographic regions of the Brescia Province with varying exposure to airborne ferromanganese alloy industry. Under the mentorship of a multidisciplinary team of experts in environmental epidemiology, biostatistics, exposure science, neurobehavioral toxicology, and mixtures, Samantha Schildroth (PI) proposes the following aims: 1) describe associations of metal mixtures with attentional function and verbal learning and memory in adolescents; 2) assess the role of iron status as a) a modifier of metals neurotoxicity that alters associations between the metal mixture and cognition, and b) a mediator that is impacted by the metal mixture and affects cognition. Metals in PHIME were measured in multiple biomarkers (hair, nails, blood, saliva, urine) and iron status parameters were measured in whole blood (ferritin, transferrin, and hemoglobin) and using hematocrit/serum iron levels. Objective measures of cognitive function were used to assess attention (Conners-Wells Rating Scales) and verbal learning and memory (California Verbal Learning Test). We will use state-of-the-art statistical approaches for mixtures, including Bayesian Kernel Machine Regression and quantile-based g-computation, to address our proposed aims. The research outlined in this proposal will contribute to our current understanding of the neurotoxicity of a metal mixture relevant for communities living in proximity to ferroalloy emissions, an industry that is expanding globally, on two domains necessary for the overall cognitive function of children and will examine iron status as a potential susceptibility factor. The proposed training and research will expand upon the applicant's strong foundation in environmental epidemiology and provide her with additional skills needed to study the joint effects of multiple metals on cognition, while considering iron status. This research will 1) address the large data gap on health effects of metal mixtures in adolescents, and 2) help characterize modifiable environmental factors, including dietary factors like iron status, in adolescence that may be targets for future public health intervention.