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

项目总结 阿尔茨海默病和相关痴呆(ADRD)的患病率不断上升是一项重大的公共卫生和 在美国的临床挑战。确定ADRD原因，以便为预防和政策提供信息 以最有效的方式应对这些挑战。到目前为止，大多数研究都集中在识别基因 然而，最近的人口规模研究表明，环境暴露，如 铅和镉也会导致ADRD风险和病因。关于与以下因素有关的环境因素的初步发现 ADRD风险是有希望的，但人类证据有限。广泛的环境暴露(曝光组) 从未就ADRD事件进行过系统评估。虽然有越来越多的需求 更准确地预测ADR的未来风险，暴露数据在改进ADRD风险预测方面的作用 从未被评估过。为了解决这些差距，我们提出了一项前瞻性队列研究，通过利用 现有的大规模、具有全国代表性的、基于多种族人口的数据。《国家报》 健康和营养检查调查(NHANES，1998-2010，n&gt；15,000)有多种 环境化学品暴露测量、行为风险因素和临床表型，以及何时 链接到联邦医疗保险数据，提供长达25年的事故ADRD。我们的目标是(1)进行生物 基于假设的方法检验慢性铅和镉暴露与事故的关系 ADRD；(2)进行数据驱动的全环境关联研究，系统地评估广泛的 发生ADRD事件的环境毒物；以及(3)开发和验证基于暴露组的风险 基于机器学习方法的ADRD预测模型。这项拟议的研究将推进科学研究 理解可改变的和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提高对未来疾病风险的预测和 更准确地定义弱势群体。这项研究将突出个人层面和人口层面 有效预防或降低美国人口中ADRD风险的干预措施(即精准健康)。

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.