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

金属混合物和铁状态在青少年早期认知中的作用

• 批准号: 10461495
• 负责人: Samantha Schildroth
• 金额: $ 3.65万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10461495
• 关键词: Address; Adolescence; Adolescent; Affect; Alloys; Arsenic; Attention; Biological Markers; Biological Monitoring; Biometry; Blood; Brain; Brain region; California; Child; Chromium; Cognition; Cognitive; Communities; Complex; Copper; Data; Deposition; Dietary Factors; Elements; Environmental Epidemiology; Environmental Exposure; Environmental Risk Factor; Etiology; Exposure to; Ferritin; Foundations; Future; Geographic Locations; Hair; Health; Hematocrit procedure; Hemoglobin; Hippocampus (Brain); Human; Individual; Industrialization; Industry; Iron; Italy; Joints; Knowledge; Lead; Longevity; Manganese; Measures; Mediating; Mediation; Mediator of activation protein; Memory; Mental Health; Mentorship; Metabolism; Metal exposure; Metals; Modification; Nail plate; Neurodevelopmental Disability; Neurodevelopmental Disorder; Neurotoxins; Nutritional; Nutritional status; Outcome; Pathway interactions; Performance; Play; Predisposition; Prevalence; Province; Public Health; Research; Role; Saliva; Science; Serum; Serum Iron Level; Testing; Toxic effect; Toxicology; Training; Transferrin; Urine; Verbal Learning; Whole Blood; absorption; aged; animal data; base; brain tissue; career; cognitive function; cohort; community living; disability; early adolescence; early life exposure; economic cost; enhancing factor; epidemiologic data; ferro-manganese alloy; health goals; improved; metal poisoning; multidisciplinary; neurobehavioral; neuron development; neurotoxicity; nutritional epidemiology; physical conditioning; public health intervention; public health research; rapid growth; recruit; skills

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.

项目总结/摘要 金属是已知的儿童神经毒物，但较少关注金属混合物的影响 对认知功能的影响此外，很少有关于金属的研究探讨了铁状态对认知功能的作用。 青少年的结果。我们的研究旨在描述一种工业相关金属混合物的神经毒性 (Mn铅、铜、铬）对青少年注意和言语学习记忆的影响， 亚群，可能有更大的易感性，通过阐明铁的地位，在金属- 诱导毒性。这项拟议的研究将使用以前收集的数据，从公共卫生影响的混合 元素暴露（PHIME）研究，720名10-14岁的意大利儿童的队列。PHIME的孩子们 从布雷西亚省三个不同的地理区域招募， 锰铁合金工业在一个多学科专家小组的指导下， 流行病学，生物统计学，暴露科学，神经行为毒理学和混合物，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的关联， 青少年的语言学习和记忆; 2）评估铁状态作为a）金属修饰剂的作用 改变金属混合物和认知之间的关联的神经毒性，和B） 受到金属混合物的冲击，影响认知。在多种生物标志物中测量PHIME中的金属 (hair指甲、血液、唾液、尿）和全血中的铁状态参数（铁蛋白， 转铁蛋白和血红蛋白）和使用血细胞比容/血清铁水平。认知功能的客观测量 用于评估注意力（Conners-Wells等级量表）和语言学习和记忆（加州 言语学习测试）。我们将使用国家的最先进的统计方法的混合物，包括贝叶斯 核机器回归和基于分位数的g计算，以实现我们提出的目标。研究 在这个建议中概述的将有助于我们目前的金属混合物的神经毒性的理解 与铁合金排放附近的社区相关，这是一个正在全球扩张的行业， 这两个领域是儿童整体认知功能所必需的，并将检查铁状态作为一种潜在的 敏感性因子拟议的培训和研究将扩大申请人的坚实基础， 环境流行病学，并为她提供额外的技能，需要研究的联合影响， 金属对认知的影响，同时考虑铁的状况。这项研究将1）解决健康方面的巨大数据缺口 金属混合物对青少年的影响，2）有助于描述可改变的环境因素，包括 饮食因素，如铁的状况，在青春期，可能是未来的公共卫生干预的目标。