Prospective studies on Parkinson's disease

帕金森病(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非运动性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。我目前有三个正在进行的项目来实现这些目标。 帕金森病基因和环境研究(PAGE)：PAGE研究是在最初为癌症研究而建立的大型前瞻性队列中进行的。该队列在20世纪90年代中期从大约50万美国老年人那里收集了广泛的饮食和生活方式数据。在这项研究中，我们成功地收集了大约1100名PD患者和1900名对照的遗传物质，其中大多数人还提供了队列基线调查中没有的额外暴露信息。这项研究报告了几个重要的发现：1)吸烟持续时间，而不是强度，在解释吸烟和帕金森之间的关系方面很重要(神经病学，2010年)；2)抑郁症(Mov Disord，2010年)和白天更长的午睡(Am J Epidinool，2011年)可能是PD的早期非运动症状之一；3)较高的体力活动可能降低患PD的风险(神经病学，2010年)；以及4)糖尿病可能增加PD的风险(糖尿病护理，2011年)。最后，我们与其他人合作，为识别与PD风险相关的多个基因座做出了贡献(NAT Genetics，2009，Lancet 2011，和PLoS Genetics 2011)。 上海帕金森研究(SPS)：上海妇女健康研究(SWHS)也建立在一个大型前瞻性队列的基础上。这项研究很重要，因为在女性中进行的帕金森病研究很少，而SWHS在1997-2000年的基线上收集了生物胺。在这项研究中，我们的目标是识别和临床确认帕金森患者，并检查女性帕金森病的潜在危险因素和早期生物标志物。我们在2010年春末进行了试点，并于今年开始主要数据收集，可能会持续几年。 社区动脉粥样硬化风险(ARIC)研究中的帕金森研究：ARIC研究是最成功的基于社区的心血管研究队列研究之一。该队列成立于20世纪80年代末，从美国四个社区招募了15,000多名参与者，年龄45岁-。ARIC队列具有多个队列范围的血液采集、丰富的暴露数据、大量的辅助研究、20多年的随访和持续的认知评估，是帕金森研究的极好资源。因此，我们计划确认帕金森病病例，从而在这一成熟的队列中启动一项长期的帕金森研究。在这个队列中，帕金森病研究将有两个主要目的：1)检查帕金森病的遗传和环境危险因素；2)检查帕金森病的临床前非运动症状。 此外，我的团队还在与内部和外部调查人员合作开展其他几个项目，以寻找帕金森病和其他神经退行性疾病的原因。合作者来自哈佛大学(卫生专业人员跟踪研究、护士健康研究、癌症预防研究II营养队列)、NIHES(农业健康研究和姐妹研究)和瑞典卡罗林斯卡研究所(全国患者登记)。

Parkinson 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 nonmotor symptoms and biomarkers. I currently have three ongoing projects to accomplish these goals. Parkinson's Genes and Environment (PAGE) Study: The PAGE study was built within a large prospective cohort that was initially established for cancer research. The cohort had collected extensive dietary and lifestyle data from approximately 0.5 million US older adults in mid-1990s. In this study, we have successfully collected genetic material from approximately 1,100 PD patients and 1,900 controls, and majority of them also provided additional exposure information that was not available from the cohort's baseline survey. This study has reported several important findings: 1) smoking duration, rather than intensity, is important in explaining the smoking-Parkinson relationship (Neurology, 2010); 2) depression (Mov Disord 2010) and longer daytime napping (Am J Epidemiol, 2011) may be among the early nonmotor symptoms of PD; 3) higher physical activity may lower the risk for PD (Neurology, 2010); and 4) diabetes may increase the risk for PD (Diabetes Care, 2011). Finally, in collaboration with others, we contributed to the identification of multiple genetic loci that were associated with PD risk (Nat Genetics, 2009, Lancet 2011, and PLoS Genetics 2011). The Shanghai Parkinson Study (SPS): The SPS is also being built based on a large prospective cohort - the Shanghai Women's Health Study (SWHS). The study is important because little PD research has been conducted among women, and the SWHS collected biospecimen at its baseline in 1997-2000. In this study, we aim to identify and clinically confirm Parkinson patients and to examine potential risk factors and early biomarkers for PD among women. We carried out a pilot in the late spring of 2010 and started main data collection this year which may last for several years. Parkinson Research in the Atherosclerosis Risk In Communities (ARIC) Study: The ARIC study is one of the most successful community-based cohort studies on cardiovascular research. The cohort was established in late 1980s and recruited over 15,000 participants, ages 45-64, from four US communities. With multiple cohort-wide blood collections, rich exposure data, numerous ancillary studies, more than 20 years of follow-up, and ongoing cognitive assessment, the ARIC cohort is an excellent resource for Parkinson research. We therefore plan to confirm PD cases and thus initiate a long-term Parkinson study in this well-established cohort. There will be two major aims of PD research in this cohort 1) to examine genetic and environmental risk factors for PD; 2) to examine preclinical nonmotor symptoms of PD. In addition, my group is also working on a few other projects in collaboration with intra- and extramural investigators to search for causes of PD and other neurodegenerative diseases. Collaborators are from the Harvard University (the Health Professionals Follow-up Study, the Nurses Health Study, the Cancer Prevention Study II Nutrition Cohort), NIHES (the Agricultural Health Study and the Sister Study), and the Karolinska Institutet in Sweden (national-wide patient register).