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：
10579862
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/10579862
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 Predisposition Prevalence Prevention Prospective, cohort study Public Health Recommendation Research Risk Risk Factors Risk Reduction Role Scientific Advances and Accomplishments Strategic Planning Testing Time Toxic Environmental Substances United States Urine Vulnerable Populations abeta deposition advanced disease 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.