Prospective studies on Parkinson's disease

帕金森氏病(PD)是第二大最常见的神经退行性疾病，影响着100多万美国老年人。随着人口老龄化，帕金森病的负担预计会增加。虽然有有效的措施来控制帕金森病的症状，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。我的研究旨在通过对运动前症状和生物标志物的研究，确定帕金森病的环境和遗传原因，并确定高危人群的特征。 基因和环境因素单独或结合在一起，对帕金森病的发展起到了促进作用。多年来，我们的研究有助于更好地理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。在过去的一年里，我们调查了一些其他潜在的帕金森病危险因素。帕金森病在男性中比在女性中更常见；因此，人们假设雌激素可能具有保护作用。然而，使用帕金森基因和环境研究的数据，我们没有发现激素治疗或生殖因素与帕金森病风险之间的联系(Mov Disord 2014)。我们之前曾报道过黑色素瘤和帕金森病倾向于共存；然而，我们的进一步研究并不支持这种联系可能由黑色素瘤的遗传风险因素来解释的假设(Neurobiol Aging，2014)此外，我们还加入了一个更大的联盟，以寻找帕金森病的遗传原因(例如，NAT基因2014)。 我研究的另一个重要领域是帕金森病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，帕金森氏症患者还会出现非运动症状，从嗅觉减退(嗅觉不良)到痴呆症和精神病。虽然这些症状可以在帕金森病临床诊断之前和之后发展，但我对几个可能在疾病诊断之前多年发展的症状感兴趣。这些症状的例子包括营养不良、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，以确定帕金森病的高危人群，并了解早期帕金森病的病因。在过去，我们已经检查了几个与帕金森病风险相关的个体症状。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的自然病史和病因学的相关性。我们的具体假设是：1)同一人出现多种运动前症状预示着PD的风险更高；2)环境(例如吸烟、咖啡因摄取、农药暴露、布洛芬使用)和遗传因素(例如SNCA、MAPT)会影响这些运动前症状的存在和/或将它们的进展修改为显性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的全国代表性数据，我们证明了非运动症状的联合患病率在整个寿命周期内在美国普通人群中是低的(Mov Disord，2014)。 我是几项PD研究的首席研究员，这些研究建立在大型前瞻性队列的基础上。相比病例对照研究，我把重点放在了预期队列上，因为他们相对不太容易回忆、偏见和颠倒因果关系。由于帕金森病是一种罕见的结果，需要大量的队列和较长的随访时间；建立在现有队列基础上的研究可以相对有效和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，以及上海妇女健康研究中的上海帕金森研究。此外，我正在与科里的同事合作，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们长期合作，并与卡罗林斯卡研究所的研究人员发展了一种新的合作。虽然这些研究有不同的具体焦点，但它们都有一个共同的主题，即揭示帕金森病的原因，并以疾病预防为目的描述高危人群的特征。 除了PD研究，我也是全球疾病负担小组的成员，该小组评估了世界各国各种疾病的公共卫生负担。初步研究结果发表在《柳叶刀》和《美国医学会杂志》的一系列论文中。

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.