The Study of the Environment and Alzheimer's disease and related Dementias (SEAD)

环境与阿尔茨海默病和相关痴呆症的研究 (SEAD)

基本信息

批准号：
10371214
负责人：
Kelly Marie Bakulski
金额：
$ 66.65万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-03-15 至 2026-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10371214
关键词：
Address Affect Alzheimer&apos s Disease Alzheimer&apos s disease related dementia Alzheimer&apos s disease risk American Animal Model Behavioral Biological Biological Markers Biology Blood Cadmium Case-Control Studies Chemicals Clinical Cognition Cohort Studies Complex Data Development Diet Discrimination Early Intervention Environment Environmental Exposure Environmental Risk Factor Etiology Evaluation Exposure to Future Genetic Genotype Goals Human Individual Infection Intervention Lead Life Style Link Measurement Measures Medicare Modeling Modernization National Health and Nutrition Examination Survey National Institute on Aging Neurodegenerative Disorders Neurotoxins Participant Policies Population Precision Health Prevalence Prevention Prospective cohort study Public Health Recommendation Research Risk Risk Factors Role Scientific Advances and Accomplishments Strategic Planning Testing Time Toxic Environmental Substances United States Urine Vulnerable Populations abeta deposition advanced disease base bone chronic Pb exposure clinical phenotype dementia risk demographics disorder prevention disorder risk effective intervention environmental chemical environmental chemical exposure follow-up human population study improved lead exposure machine learning method modifiable risk molecular phenotype multi-ethnic neurotoxic neurotoxicity novel population based precision medicine prevent prospective risk prediction risk prediction model risk stratification symposium tau expression toxicant

项目摘要

PROJECT SUMMARY The rising prevalence of Alzheimer's disease and related dementias (ADRD) is a major public health and clinical challenge in the United States. Identification of ADRD causes to inform prevention and policy is the most efficient way to address these challenges. Most research to date has focused on identifying genetic causes of ADRD, however, recent population-scale studies have shown that environmental exposures, such as lead and cadmium, also contribute to ADRD risk and etiology. Initial findings on environmental factors linked to ADRD risk is promising, but human evidence is limited. A wide range of environmental exposures (exposome) have never been evaluated systematically in relation to incident ADRD. While there is a growing demand to predict future risk for ADRS more precisely, the role of exposomic data in improving ADRD risk prediction has never been evaluated. To address these gaps, we propose a prospective cohort study by capitalizing on existing large-scale, United States nationally representative, multi-ethnic population-based data. The National Health and Nutrition Examination Survey (NHANES, from 1998-2010, n>15,000) has a variety of environmental chemical exposure measurements, behavioral risk factors, and clinical phenotypes, and when linked to Medicare data, provides up to 25 years of incident ADRD. We aim to (1) conduct a biologic hypothesis-based approach to test the associations of chronic exposure to lead and cadmium with incident ADRD; (2) conduct a data-driven environment-wide association study to systematically evaluate a wide-range of environmental toxicants with incident ADRD; and (3) develop and validate an exposome-based risk prediction model for ADRD using machine learning methods. The proposed study will advance scientific understanding on how modifiable and currently ubiquitous environmental neurotoxicants can lead to the development of ADRD. This study assesses the exposome to improve prediction of future disease risk and define vulnerable populations more precisely. This research will highlight individual-level and population-level interventions (i.e. precision health) to effectively prevent or reduce the risk of ADRD in the US population.

项目概要阿尔茨海默病和相关痴呆症 (ADRD) 的患病率不断上升，是一个重大的公共卫生问题美国的临床挑战。确定 ADRD 原因，为预防和政策提供信息是关键应对这些挑战的最有效方法。迄今为止，大多数研究都集中在识别遗传然而，ADRD 的原因，最近的人口规模研究表明，环境暴露，例如铅和镉也会导致 ADRD 风险和病因。关于与环境因素相关的初步发现 ADRD 风险是有希望的，但人类证据有限。广泛的环境暴露（暴露）从未针对 ADRD 事件进行系统评估。尽管需求不断增长为了更准确地预测 ADRS 的未来风险，暴露数据在改善 ADRD 风险预测中的作用已经从未被评价过。为了解决这些差距，我们提出了一项前瞻性队列研究，利用现有的大规模、具有美国全国代表性、多种族人口的数据。国家报健康和营养检查调查（NHANES，1998-2010 年，n>15,000）有多种环境化学暴露测量、行为风险因素和临床表型，以及何时与 Medicare 数据关联，提供长达 25 年的 ADRD 事件记录。我们的目标是 (1) 进行生物学基于假设的方法来测试长期接触铅和镉与事故之间的关系 ADRD； (2) 开展数据驱动的全环境关联研究，系统评估广泛的环境关联性 ADRD 事件中的环境毒物； (3) 开发并验证基于暴露的风险使用机器学习方法的 ADRD 预测模型。拟议的研究将推动科学发展了解可改变且目前普遍存在的环境神经毒物如何导致 ADRD 的发展。这项研究评估了暴露组，以改善对未来疾病风险的预测和更准确地定义弱势群体。这项研究将重点关注个人层面和人口层面有效预防或降低美国人群 ADRD 风险的干预措施（即精准健康）。