Pesticides, Olfaction, and Neurodegeneration Among US Farmers

美国农民的农药、嗅觉和神经退行性疾病

• 批准号: 10331301
• 负责人: HONGLEI CHEN
• 金额: $ 114.58万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10331301
• 关键词: Acute; Adult; Affect; Age-Years; Agricultural Health Study; Alzheimer' s Disease; Area; Biological Markers; Chemicals; Chronic; Clinical; Clinical assessments; Collection; Data; Data Collection; Development; Disease; Elderly; Enrollment; Epidemiologist; Etiology; Event; Exposure to; Foundations; Future; Goals; Home; Human; Impaired cognition; Impairment; Knowledge; Link; Liquid substance; Logistic Regressions; Mediation; Mediator of activation protein; Nerve Degeneration; Nested Case-Control Study; Neurodegenerative Disorders; Neurologic; Occupational; Olfactory dysfunction; Outcome Assessment; Parkinson Disease; Participant; Patient Self-Report; Peripheral; Pesticides; Population; Population Study; Public Health; Publications; Quality of life; Recording of previous events; Reporting; Reproducibility; Research; Resources; Risk; Risk Factors; Role; Route; Safety; Sample Size; Science; Scientist; Sensory; Smell Perception; Solid; Statistical Data Interpretation; Symptoms; Testing; age related; aged; aging brain; animal data; base; experience; farmer; high risk; human data; improved; innovation; insight; modifiable risk; mortality; motor impairment; multidisciplinary; neuroimaging; neurosensory; novel; nutrition; pesticide exposure; public health relevance

Abstract We propose the most comprehensive study ever undertaken to delineate roles of pesticides in age-related olfactory impairment (OI), and to examine their relevance to prodromal development of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). About 15-25% of older US adults have various levels of OI, a sensory impairment that most do not even realize they have. Nonetheless, OI independently predicts short-term and long-term mortality, and adversely affects nutrition, safety, and quality of life. OI is also one of the most important early symptoms of AD and PD. Pesticide exposure is ubiquitous and has been linked to a higher risk of PD and potentially to AD, but reliable assessment of pesticide exposure in population-based studies has been a major hurdle to advancing the science in this field. Our multidisciplinary team of epidemiologists, biostatisticians, exposure assessment experts, clinical scientists, and a neurotoxicologist will break new ground in this area by dissecting the connections among pesticides, age-related OI, and neurodegenerative diseases. We will leverage resources from the world's largest collection of human data on acute and chronic pesticide exposure, the Agricultural Health Study (AHS), established in 1993 and still ongoing. Most AHS participants are now aged ≥60 years and thus at risk for neurodegenerative diseases. By objectively testing the sense of smell of ~2,700 AHS farmers and conducting in-home clinical assessments for ~600 farmers, we expect to build a large, unique, and lasting resource for the proposed research and beyond. Our Specific Aims are to: 1) delineate the associations of chronic exposure to pesticides with OI among farmers; 2) analyze high pesticide exposure events in relation to OI; and 3) assess whether OI is an important mediator in pesticide-related AD and PD. The Scientific Rigor of this project is assured by the large sample size, state-of- the-science exposure and outcome assessments, carefully planned statistical analyses, and a very experienced multidisciplinary and multi-institutional research team. Innovation: This project will significantly advance our knowledge of long-term neurosensory and neurodegenerative consequences of pesticide exposures by cultivating 20 years of extensive data collection in a well-characterized farming population. Significance: We will bring new insights into the relationship between pesticide exposure and OI, and increase understanding of OI as an early warning marker for AD and PD development in association with pesticide exposure. This project will lay a solid foundation for future longitudinal research with biomarkers (e.g., neuroimaging-based or fluid-based) to conclusively define roles and mechanisms of various pesticides in age-related OI and neurodegeneration.

抽象的 我们提出了有史以来最全面的研究，用于描述与年龄有关的农药 嗅觉损害（OI），并检查它们与神经退行性的前驱性发展的相关性 阿尔茨海默氏病（AD）和帕金森氏病（PD）等疾病。大约15-25％的美国成年人 具有各种级别的OI，这是大多数人甚至都没有意识到的感觉障碍。尽管如此，OI 独立预测短期和长期死亡率，并对营养，安全性和质量产生不利影响 生活。 OI也是AD和PD最重要的早期症状之一。农药暴露无处不在， 与PD的风险更高，可能与AD相关，但可靠地评估农药暴露 基于人群的研究一直是推进该领域科学的主要障碍。我们的多学科 流行病学家，生物统计学家，暴露评估专家，临床科学家和A团队 神经毒理学家将通过剖析农药之间的联系，在这一领域打破新的地面 OI和神经退行性疾病。我们将利用世界上最大的人类收藏中的资源 关于急性和慢性农药暴露的数据，农业健康研究（AHS）于1993年建立，仍然 正在进行。大多数AHS参与者现在年龄≥60岁，因此有神经退行性疾病的风险。经过 客观地测试约2,700名AHS农民的气味，并进行家庭临床评估 〜600名农民，我们希望为拟议的研究及其他地区建立一个大型，独特而持久的资源。 我们的具体目的是：1）描述农民中长期暴露于农药与OI的相关性； 2）分析与OI有关的高农药暴露事件； 3）评估OI是否是重要的调解人 在与农药有关的AD和PD中。该项目的科学严谨是由大型样本量，最新的 科学的暴露和结果评估，仔细计划的统计分析以及经验丰富的 多学科和多机构研究团队。创新：这个项目将大大推动我们的 了解农药暴露于农药的长期神经感觉和神经退行性后果 在良好的农业人群中培养20年的广泛数据收集。意义：我们会的 对农药暴露与OI之间的关系带来新的见解，并增加对OI的理解 作为与农药暴露有关的AD和PD开发的预警标记。这个项目将 为生物标志物（例如，基于神经成像或基于流体的液体）的未来纵向研究奠定坚实的基础 最终定义了与年龄相关的OI和神经变性中各种农药的作用和机制。