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来描述农药在与年龄相关的疾病中的作用 嗅觉障碍（OI），并检查其与神经退行性疾病前驱发育的相关性 大约 15-25% 的美国老年人患有阿尔茨海默病 (AD) 和帕金森病 (PD) 等疾病。 患有不同程度的成骨不全症，这是一种感觉障碍，但大多数人甚至没有意识到自己患有成骨不全症。 独立预测短期和长期死亡率，并对营养、安全和质量产生不利影响 成骨不全症也是 AD 和 PD 的最重要的早期症状之一。 与较高的 PD 风险和潜在的 AD 相关，但对农药暴露的可靠评估 以人群为基础的研究一直是推动这一领域科学发展的主要障碍。 由流行病学家、生物统计学家、暴露评估专家、临床科学家和 神经毒理学家将通过剖析杀虫剂、年龄相关的药物之间的联系，在这一领域开辟新天地 我们将利用世界上最大的人类收藏资源。 关于急性和慢性农药接触的数据，农业健康研究 (AHS)，成立于 1993 年，至今仍在 大多数 AHS 参与者现在年龄≥60 岁，因此面临神经退行性疾病的风险。 客观测试约 2,700 名 AHS 农民的嗅觉，并进行家庭临床评估 约 600 名农民，我们希望为拟议的研究及其他方面建立一个大型、独特且持久的资源。 我们的具体目标是： 1) 描绘农民长期接触农药与成骨不全症之间的关系； 2) 分析与成骨不全相关的高农药暴露事件；以及 3) 评估成骨不全是否是一个重要的介导因素 大样本量、现状保证了该项目的科学严谨性。 科学曝光和结果评估、精心策划的统计分析以及经验丰富的专家 创新：该项目将显着推进我们的研究。 了解农药暴露的长期神经感觉和神经退行性后果 在特征明确的农业人口中培养 20 年的广泛数据收集意义：我们将。 为农药暴露与成骨不全症之间的关系带来新的见解，并增加对成骨不全症的理解 作为与农药接触相关的 AD 和 PD 发展的早期预警标志。 为未来的生物标志物纵向研究（例如基于神经影像或基于液体）奠定坚实的基础 最终确定各种农药在与年龄相关的成骨不全症和神经退行性疾病中的作用和机制。