Prospective studies on Parkinson's disease

帕金森病的前瞻性研究

• 批准号: 8929788
• 负责人: HONGLEI CHEN
• 金额: $ 112.03万
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8929788
• 关键词: Affect; Age; Aging; Agriculture; American; Area; Atherosclerosis; Biological Markers; Caffeine; Case-Control Studies; Characteristics; Clinical; Clinical Management; Coffee; Collaborations; Communities; Constipation; Country; Data; Dementia; Development; Diet; Disease; Elderly; Environment; Environmental Health; Environmental Risk Factor; Epidemiologic Studies; Epidemiology; Estrogens; Etiology; Genes; Genetic; Goals; Health; Ibuprofen; Individual; Infection; Institutes; Intake; Joints; Journals; Link; Longevity; Measures; Mental Depression; Motor; National Health and Nutrition Examination Survey; Natural History; Nature; Neurodegenerative Disorders; Outcome; Paper; Parkinson Disease; Patients; Pharmaceutical Preparations; Population; Prevalence; Principal Investigator; Prospective Studies; Psyche structure; Psychotic Disorders; Public Health; Public Health Schools; Publishing; Reporting; Reproductive History; Research; Research Personnel; Risk; Risk Factors; Role; Scientist; Series; Sister; Sleep disturbances; Smell Perception; Smoking; Symptoms; Time; United States National Institutes of Health; Woman; Women' s Health; alpha synuclein; base; burden of illness; clinical Diagnosis; cohort; cost effective; disability; disease diagnosis; disorder prevention; disorder risk; drinking; follow-up; genetic risk factor; high risk; hormone therapy; hyposmia; interest; melanoma; member; men; non-motor symptom; pesticide exposure; prospective

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease and affects more than one million elderly Americans. As the population ages, the burden of PD is expected to increase. Although there are effective measures to control the symptoms of PD, patients eventually develop severe physical and mental disabilities and often die of complications. My research aims to ascertain the environmental and genetic causes of PD and to characterize high-risk populations through research on pre-motor symptoms and biomarkers. Genes and environmental factors, alone or in combination, contribute to PD development. Over years, our research has contributed to a better understanding of the role of environmental factors in Parkinson's etiology, for example, on smoking, coffee drinking, infections, and use of certain medications. In the past year, we investigated some other potential risk factors for PD. PD is more common in men than in women; accordingly it has been hypothesized that estrogen may be protective. However, using data from the Parkinson's Genes and Environmental Studies, we did not identify associations between hormonal therapy or reproductive factors and PD risk (Mov Disord 2014). We previously reported that melanoma and PD tended to co-occur; our further research however did not support the hypothesis that the link could be potentially explained by genetic risk factors for melanoma (Neurobiol Aging, 2014) In addition, we are also part of a larger consortium to search for genetic causes of PD (e.g. Nat Gene 2014). Another important area of my research is the epidemiology of PD pre-motor symptoms. Clinicians and scientists have known for years that in addition to the characteristic motor signs, PD patients suffer from non-motor symptoms ranging from hyposmia (poor sense of smell) to dementia and psychosis. Although these symptoms can develop both before and after the clinical diagnosis of PD, I am interested in several symptoms that may develop prior to disease diagnosis by years. Examples of these symptoms include hyposmia, constipation, depression and certain sleep disturbances. These pre-motor symptoms may greatly facilitate research to identify populations at higher risk for PD and to understand early PD etiology. In the past, we have examined several individual symptoms in relation to PD risk. I am now conducting epidemiological studies to better characterize pre-motor symptoms in various populations and to understand their relevance to the natural history and etiology of PD. Our specific hypotheses are that 1) the presence of multiple pre-motor symptoms in the same individual predicts higher risk of PD; 2) environmental (e.g. smoking, caffeine intake, pesticide exposure, ibuprofen use) and genetic (e.g. SNCA, MAPT) factors affect the presence of these pre-motor symptoms and/or modify their progression to overt PD. We have summarized these ideas in a recent paper on the journal of Environmental Health Perspectives (2014). Further, using national representative data from NHANES, we demonstrated that the joint prevalence of non-motor symptoms is low in the general US population throughout the lifespan (Mov Disord, 2014). I am the principal Investigator on several PD studies that were built on large prospective cohorts. I have focused on prospective cohorts over case-control studies because they are relatively less prone to recall bias and reverse causation. Since PD is a rare outcome, large cohorts and long follow-up times are needed; research built on existing cohorts allows for relatively efficient and cost-effective case-identification. Further, by its nature, pre-motor research requires prospective studies. My ongoing projects include the Parkinson's Genes and Environment Study based on the NIH-AARP Diet and Health cohort, the PD project in the Atherosclerosis Risk In Communities study, and the Shanghai Parkinson's Study in the Shanghai Women's Health Study. Further, in collaboration with Branch colleagues, I am developing PD research in the Agricultural Health Study and the Sister Study. Finally, I have been continuing a longstanding collaboration with colleagues from the Harvard School of Public Health, and have developed a new collaboration with investigators at the Karolinska Institute. While these studies have different specific foci, they share a common theme of revealing the causes of PD and characterizing high risk populations for the purpose of disease prevention. In addition to PD research, I am also a member of the Global Burden of Disease group that estimated the public health burdens of a wide range of diseases across countries in the world. Primary findings were published in a series of papers on Lancet and JAMA.

帕金森病（PD）是第二大流行的神经退行性疾病，影响超过一百万的美国老年人。随着人口老龄化，PD的负担预计会增加。虽然有有效的措施来控制PD的症状，但患者最终会发展为严重的身体和精神残疾，并经常死于并发症。我的研究旨在确定PD的环境和遗传原因，并通过对运动前症状和生物标志物的研究来表征高危人群。 基因和环境因素，单独或组合，有助于PD的发展。多年来，我们的研究有助于更好地了解环境因素在帕金森病病因中的作用，例如吸烟，喝咖啡，感染和使用某些药物。在过去的一年中，我们调查了PD的其他一些潜在风险因素。PD在男性中比在女性中更常见;因此，已经假设雌激素可能具有保护作用。然而，使用帕金森氏症基因和环境研究的数据，我们没有确定激素治疗或生殖因素与PD风险之间的相关性（MovDisord 2014）。我们之前报道了黑色素瘤和PD倾向于同时发生;然而，我们的进一步研究不支持这种联系可能由黑色素瘤的遗传风险因素解释的假设（Neurobiol Aging，2014）。此外，我们也是一个更大的联盟的一部分，以寻找PD的遗传原因（例如Nat Gene 2014）。 我研究的另一个重要领域是PD运动前症状的流行病学。多年来，临床医生和科学家已经知道，除了特征性的运动体征外，PD患者还患有非运动症状，从嗅觉减退（嗅觉差）到痴呆和精神病。虽然这些症状可以在PD临床诊断之前和之后发生，但我对可能在疾病诊断之前几年发生的几种症状感兴趣。这些症状的例子包括嗅觉减退、便秘、抑郁和某些睡眠障碍。这些运动前症状可能极大地促进研究，以确定PD的高风险人群，并了解早期PD病因。在过去，我们已经检查了与PD风险相关的几种个体症状。我现在正在进行流行病学研究，以更好地描述不同人群的运动前症状，并了解其与PD自然史和病因的相关性。我们的具体假设是：1）同一个体中存在多种运动前症状预测PD的风险较高; 2）环境（例如吸烟，咖啡因摄入，农药暴露，布洛芬使用）和遗传（例如SNCA，MAPT）因素影响这些运动前症状的存在和/或改变其进展为明显的PD。我们在最近发表在《环境健康展望》杂志（2014）上的一篇论文中总结了这些想法。此外，使用来自NHANES的国家代表性数据，我们证明了在整个生命周期中，美国普通人群中非运动症状的联合患病率较低（Mov Disord，2014）。 我是几项基于大型前瞻性队列的PD研究的主要研究者。我关注的是前瞻性队列研究，而不是病例对照研究，因为它们相对不容易出现回忆偏差和反向因果关系。由于PD是一种罕见的结果，需要大的队列和长的随访时间;建立在现有队列基础上的研究允许相对有效和具有成本效益的病例识别。此外，就其性质而言，前运动研究需要前瞻性研究。我正在进行的项目包括基于NIH-AARP饮食和健康队列的帕金森氏症基因和环境研究，社区研究中的动脉粥样硬化风险的PD项目，以及上海妇女健康研究中的上海帕金森氏症研究。此外，我正在与分支同事合作，在农业健康研究和姐妹研究中开展PD研究。最后，我一直在继续与哈佛公共卫生学院的同事们进行长期合作，并与卡罗林斯卡研究所的研究人员开展了新的合作。虽然这些研究有不同的具体重点，但它们都有一个共同的主题，即揭示PD的原因并描述高危人群以预防疾病。 除了PD研究，我还是全球疾病负担小组的成员，该小组估计了世界各国各种疾病的公共卫生负担。主要研究结果发表在《柳叶刀》和《美国医学会杂志》上的一系列论文中。