Prospective studies on Parkinson's disease

帕金森病的前瞻性研究

• 批准号: 8734146
• 负责人: HONGLEI CHEN
• 金额: $ 102.87万
• 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/8734146
• 关键词: Affect; Age; Agriculture; Alcohol consumption; American; Area; Atherosclerosis; Beer; Biological Markers; Caffeine; Case-Control Studies; Characteristics; Clinical; Clinical Management; Coffee; Collaborations; Communities; Constipation; Country; Craniocerebral Trauma; Data; Dementia; Development; Diet; Disease; Elderly; Environment; Environmental Health; Environmental Risk Factor; Epidemiologic Studies; Epidemiology; Etiology; Future; Genes; Genetic; Genets; Goals; Health; Ibuprofen; Individual; Infection; Institutes; Intake; Journals; Link; Measures; Mental Depression; Motor; Natural History; Nature; Neurodegenerative Disorders; Outcome; Paper; Parkinson Disease; Patients; Pharmaceutical Preparations; Plasma; Population; Principal Investigator; Prospective Studies; Psyche structure; Psychotic Disorders; Public Health; Public Health Schools; Publishing; Reporting; Research; Research Personnel; Risk; Risk Factors; Role; Scientist; Series; Sister; Sleep disturbances; Smell Perception; Smoking; Symptoms; Time; United States National Institutes of Health; Urate; Women' s Health; alpha synuclein; base; burden of illness; clinical Diagnosis; cohort; cost effective; disability; disease diagnosis; disorder prevention; disorder risk; distilled alcoholic beverage; drinking; follow-up; genetic variant; high risk; hyposmia; interest; member; patient registry; pesticide exposure; prevent; prospective

Parkinsons 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 Parkinsons 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. Using data from the Parkinsons Genes and Environmental Studies, we prospectively investigated the association between alcohol drinking and future PD risk. We found that while moderate beer drinking was associated a lower risk for PD, liquor drinking was associated with a higher risk (PLoS One, 2013). Using data from the Swedish Patient Registry, we found that recent head injury was not related to a higher risk of PD (Mov Disord 2013). In the past, we have reported that higher plasma urate was associated with a lower risk of PD; we examined last year whether this association could be attributed to known genetic variants that are associated with plasma urate. We did not find a link between these genetic variants and PD (Transl Neurodegener, 2013). In addition, we are also part of a larger consortium to search for genetic causes of PD (e.g. Hum Mol Genet, 2012, 2013; PLoS Med 2013). 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. 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 Parkinsons 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 Parkinsons Study in the Shanghai Womens 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) 是第二常见的神经退行性疾病，影响超过一百万美国老年人。随着人口老龄化，PD的负担预计会增加。尽管有有效措施控制帕金森病的症状，但患者最终会出现严重的身体和精神残疾，并常常死于并发症。我的研究旨在确定帕金森病的环境和遗传原因，并通过对运动前症状和生物标志物的研究来描述高危人群的特征。 基因和环境因素单独或共同作用，有助于帕金森病的发生。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学中的作用，例如吸烟、喝咖啡、感染和使用某些药物。去年，我们调查了其他一些帕金森病的潜在危险因素。利用帕金森基因和环境研究的数据，我们前瞻性地研究了饮酒与未来帕金森病风险之间的关联。我们发现，虽然适量饮用啤酒与较低的帕金森病风险相关，但饮酒却与较高的帕金森病风险相关（PLoS One，2013）。使用瑞典患者登记处的数据，我们发现近期头部受伤与 PD 风险较高无关（Mov Disord 2013）。过去，我们曾报道过较高的血浆尿酸与较低的帕金森病风险相关；我们去年研究了这种关联是否可以归因于与血浆尿酸盐相关的已知遗传变异。我们没有发现这些遗传变异与帕金森病之间的联系（Transl Neurodegene，2013）。此外，我们也是寻找 PD 遗传原因的更大联盟的一部分（例如 Hum Mol Genet，2012、2013；PLoS Med 2013）。 我研究的另一个重要领域是 PD 运动前症状的流行病学。临床医生和科学家多年来已经知道，除了特有的运动体征外，PD 患者还患有非运动症状，包括嗅觉减退（嗅觉差）、痴呆和精神病。尽管这些症状在帕金森病临床诊断之前和之后都可能出现，但我对疾病诊断前数年可能出现的几种症状感兴趣。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会极大地促进研究，以确定帕金森病高风险人群并了解早期帕金森病的病因。过去，我们检查了与帕金森病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，并了解它们与帕金森病自然史和病因学的相关性。我们的具体假设是 1) 同一个体存在多种运动前症状预示 PD 风险较高； 2) 环境（例如吸烟、咖啡因摄入、杀虫剂暴露、布洛芬使用）和遗传（例如 SNCA、MAPT）因素会影响这些运动前症状的出现和/或改变其向明显 PD 的进展。我们在《环境健康展望》杂志上最近发表的一篇论文中总结了这些想法。 我是几项基于大型前瞻性队列的 PD 研究的首席研究员。我关注的是前瞻性队列而不是病例对照研究，因为他们相对不太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，因此需要大量的队列和较长的随访时间；基于现有队列的研究可以实现相对有效且具有成本效益的病例识别。此外，就其本质而言，运动前研究需要前瞻性研究。我正在进行的项目包括基于 NIH-AARP 饮食与健康队列的帕金森病基因和环境研究、社区动脉粥样硬化风险研究中的 PD 项目以及上海女性健康研究中的上海帕金森病研究。此外，我正在与分支机构的同事合作，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大学公共卫生学院的同事进行长期合作，并与卡罗林斯卡研究所的研究人员建立了新的合作关系。虽然这些研究有不同的具体重点，但它们有一个共同的主题，即揭示帕金森病的病因并描述高危人群的特征，以达到预防疾病的目的。 除了帕金森病研究之外，我还是全球疾病负担小组的成员，该小组估计了世界各国多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。