Metals and Developmental Origins of Late Life Cognitive Function

金属与晚年认知功能的发育起源

• 批准号: 10256790
• 负责人: Marc G Weisskopf
• 金额: $ 56.81万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-08 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10256790
• 关键词: Ablation; Accounting; Address; Adult; Age; Alzheimer' s Disease; American; Animal Experimentation; Animals; Biological Markers; Blood; Blood specimen; Cells; Child; Cognitive; Cognitive aging; Cohort Studies; Data; Dementia; Dental Enamel; Deposition; Development; Disease; Economic Burden; Elderly; Encapsulated; Enrollment; Environmental Exposure; Epigenetic Process; Exposure to; Fluorescence; Gene Expression; Genetic Transcription; Health; Human; Impaired cognition; Individual; Inductively Coupled Plasma Mass Spectrometry; Intervention; Lasers; Life; Link; Lipid Bilayers; Measures; Metal exposure; Metals; MicroRNAs; Modification; Neurons; Outcome; Participant; Pathology; Patients; Performance; Population; Prevention; Process; Public Health; Questionnaires; Risk; Risk Factors; Roentgen Rays; Role; Sampling; Serum; Signal Transduction; Structure of nail of toe; Testing; Time; Tooth structure; United States; Vulnerable Populations; Woman; Work; age related; aging brain; aging population; base; cognitive development; cognitive function; cognitive testing; cost estimate; early childhood; early detection biomarkers; early life exposure; economic cost; extracellular vesicles; human study; in utero; lead exposure; men; nanoscale; novel marker; particle; postnatal; prenatal; recruit

We propose to study the relation between prenatal, early postnatal, and adult exposure to metals and cognitive function in older age, and whether early life exposures modify effects of adult exposures. We will also explore whether those exposures and cognitive outcomes are associated with changes in blood-derived extracellular vesicle (EV) micro RNA expression (miRNA), which could represent epigenetic mechanisms underlying associations. We will conduct a cohort study among a subset of participants in the original St. Louis Baby Tooth (SLBT) study who donated their baby teeth in the 1950s and 1960s. Based on our pilot work, we anticipate easily being able to enroll 1,000 former SLBT participants (500 men and 500 women) who will have completed questionnaires and cognitive function testing, and from whom we will collect blood for miRNA analyses and repeated toenail samples for adult metal analyses. Prenatal and early postnatal exposure to several metals will be assessed by measuring metals in baby tooth enamel (using laser-ablation inductively coupled plasma mass spectrometry). Adult metal exposures will be assessed using X-Ray Fluorescence to measure metals in the toenail samples. EVs will be isolated from the blood samples and analyzed for EV miRNA expression levels. The SLBT provides a unique setting that will allow us to have individual-level biomarkers of early life and adult metal exposures in older adults on whom we can conduct cognitive function testing. This study setting allows us to have an unprecedented ability to examine whether early life exposures are related to late life cognitive health—a hypothesis suggested for metals exposure from animal research, but extremely hard to test in humans without the biomarker of such early exposure that the already collected baby teeth in the SLBT can provide.

我们建议研究产前，早期产后和成人接触金属与 老年的认知功能以及早期生活是否会导致成人暴露的改变。我们也会 探索这些暴露和认知结果是否与鲜血的变化有关 细胞外囊泡（EV）微RNA表达（miRNA），它可以代表表观遗传机理 基础协会。我们将在原始圣路易斯的一部分参与者中进行一项队列研究 在1950年代和1960年代捐赠了乳牙的婴儿牙（SLBT）研究。根据我们的飞行员工作，我们 预计将能够招募1,000名前SLBT参与者（500名男性和500名女性） 完成的问卷调查和认知功能测试，我们将收集miRNA的血液 分析和重复的脚趾甲样品进行成人金属分析。产前和早期暴露于 几种金属将通过测量婴儿牙齿搪瓷中的金属进行评估（使用激光燃烧效率 耦合等离子体质谱法）。成人金属暴露将使用X射线荧光评估 测量脚趾甲样品中的金属。电动汽车将从血液样本中分离出来并分析EV miRNA表达水平。 SLBT提供了一个独特的设置，使我们能够拥有个人级别 早期生活和成人金属暴露的生物标志物在我们可以进行认知功能的老年人中 测试。这项研究设置使我们具有前所未有的能力来检查早期生活是否暴露 与后期的认知健康有关，这是一个假设，暗示了来自动物研究的金属暴露，但 没有这种早期暴露的生物标志物，在人类中非常难以测试 SLBT中的牙齿可以提供。