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.

帕金森氏病（PD）是第二大流行的神经退行性疾病，影响了超过一百万的美国人。随着人口年龄的增长，PD的负担预计将增加。尽管有有效的措施来控制PD的症状，但患者最终会出现严重的身体和精神残疾，并且常常死于并发症。我的研究旨在确定PD的环境和遗传原因，并通过研究前运动症状和生物标志物来表征高危人群。 基因和环境因素单独或结合起来有助于PD的发展。多年来，我们的研究有助于更好地理解环境因素在帕金森氏病学中的作用，例如在吸烟，咖啡饮用，感染和某些药物的使用方面。在过去的一年中，我们研究了PD的其他一些潜在危险因素。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PD风险之间的关联。我们发现，虽然适度的啤酒饮酒是PD的较低风险，但酒饮酒与较高的风险有关（PLOS One，2013年）。使用瑞典患者注册中心的数据，我们发现最近的头部受伤与PD的风险较高无关（Mov Disord 2013）。过去，我们报道了较高的血浆尿酸盐与PD的较低风险有关。去年，我们检查了这种关联是否可以归因于与血浆尿酸盐有关的已知遗传变异。我们没有找到这些遗传变异和PD之间的联系（Transl Neurodegener，2013年）。此外，我们还是一个较大的财团的一部分，用于寻找PD的遗传原因（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都知道，除了特征性的运动迹象外，PD患者还患有从低温（气味不良）到痴呆和精神病等非运动症状。尽管这些症状可以在PD临床诊断之前和之后发展，但我对可能在疾病诊断之前可能出现的几种症状感兴趣。这些症状的例子包括低血症，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PD风险较高的人群并了解早期PD病因。过去，我们检查了与PD风险有关的几个个体症状。我现在正在进行流行病学研究，以更好地表征各种人群中的运动前症状，并了解它们与PD的自然史和病因的相关性。我们的具体假设是1）同一个人中存在多种运动前症状的存在预测PD的风险更高； 2）环境（例如吸烟，咖啡因摄入量，农药暴露，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存在和/或将其进展为明显的PD。我们在有关环境健康观点杂志的最新论文中总结了这些想法。 我是基于大型潜在人群建立的几项PD研究的主要研究者。我专注于前瞻性队列，而不是病例对照研究，因为它们相对较不容易回忆起偏见和反向因果关系。由于PD是一个罕见的结果，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允许相对高效且具有成本效益的病例识别。此外，从本质上讲，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饮食和健康队列的帕金森基因和环境研究，社区研究中动脉粥样硬化风险的PD项目以及上海女子健康研究中的上海帕金森氏症研究。此外，与分支同事合作，我正在开发农业健康研究和姊妹研究中的PD研究。最后，我一直在与哈佛大学公共卫生学院的同事进行长期合作，并与Karolinska Institute的调查员建立了新的合作。尽管这些研究具有不同的特定焦点，但它们具有揭示PD原因和为预防疾病目的表征高风险种群的原因的共同主题。 除了PD研究外，我还是全球疾病组负担的成员，估计世界各国各种疾病的公共卫生负担。主要发现发表在有关柳叶刀和贾马的一系列论文中。