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.

项目摘要/摘要 金属是儿童中已知的神经毒性，但对金属混合物的影响更少的关注 关于认知功能。此外，很少有金属研究检查铁状态在认知方面的作用 青少年的结果。我们的研究旨在描述与工业相关的金属混合物的神经毒性 （MN，PB，CU，CR）在青少年的注意力和言语学习和记忆的领域，并识别 通过阐明铁状态在金属中的作用，可能对金属具有更大敏感性的亚群 诱导的毒性。这项拟议的研究将使用以前收集的数据来自混合的公共卫生影响 元素暴露（Phime）研究，由720名意大利儿童组成的10-14岁儿童。菲姆的孩子是 从布雷斯西亚省的三个不同地理区域招募，暴露于空中 Ferromanganese合金行业。在一个多学科的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物，Samantha Schildroth （PI）提出以下目的：1）描述金属混合物与注意功能的关联和 青少年的言语学习和记忆； 2）评估铁状态作为a）金属修饰符的作用 神经毒性改变了金属混合物与认知之间的关联，b）介体是 受金属混合物的影响并影响认知。在多种生物标志物中测量了片中的金属 （头发，指甲，血液，唾液，尿液）和铁状态参数以全血（铁蛋白， 转铁蛋白和血红蛋白），并使用血细胞比容/血清铁水平。认知功能的客观度量 被用来评估注意力（Conners-Wells评级量表）和口头学习和记忆（加利福尼亚州 言语学习测试）。我们将使用最先进的统计方法进行混合物，包括贝叶斯 内核机器回归和基于刻痕的G计算，以解决我们提出的目标。研究 该提案中概述将有助于我们当前对金属混合物的神经毒性的理解 与居住在靠近铁合金排放的社区有关的社区，该行业在全球范围内不断扩展 儿童总体认知功能所需的两个领域，并将将铁状态视为潜力 易感因子。拟议的培训和研究将扩大申请人的强大基础 环境流行病学，并为她提供研究多重影响所需的其他技能 在考虑铁状态的同时，认知金属。这项研究将解决有关健康的巨大数据差距 金属混合物在青少年的影响，2）有助于特征可修改的环境因素，包括 诸如铁状态之类的饮食因素，在青春期可能是未来公共卫生干预的目标。