Prospective studies on Parkinson's disease

帕金森病（PD）是第二大流行的神经退行性疾病，影响着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，并通过对非运动症状和生物标志物的研究来表征高危人群。目前，我有几个正在进行的项目来实现这些目标。 帕金森基因和环境（PAGE）研究：PAGE研究是在一个大型前瞻性队列中建立的，该队列最初是为癌症研究建立的。该队列收集了20世纪90年代中期约50万美国老年人的广泛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1,100名PD患者和1,900名对照的遗传物质，其中大多数还提供了队列基线调查中无法获得的额外暴露信息。 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，在解释吸烟与帕金森病的关系方面很重要（神经病学，2010）; 2）抑郁症（MovDisord 2010）和更长的白天小睡（Am J Epidemiol，2011）可能是PD的早期非运动症状; 3）较高的体力活动可能降低PD的风险（Neurology，2010）;和4）糖尿病可能增加PD的风险（Diabetes Care，2011）。最后，我们与其他人合作，鉴定了与PD风险相关的多个遗传基因座（Nat Genetics，2009，Lancet 2011和PLoS Genetics 2011）。 上海帕金森研究（SPS）：SPS也是基于一个大型前瞻性队列-上海妇女健康研究（SWHS）。这项研究很重要，因为在妇女中进行的PD研究很少，SWHS在1997-2000年的基线收集了生物标本。在这项研究中，我们的目标是识别和临床确认帕金森病患者，并检查女性PD的潜在危险因素和早期生物标志物。随着队列随访的继续，正在分批进行病例确认。我们刚刚在2012年初通过第四次随访完成了第一轮病例确认。 帕金森研究在社区动脉粥样硬化风险（ARIC）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，招募了来自美国四个社区的15，000多名年龄在45至64岁之间的参与者。凭借多个队列范围内的血液采集，丰富的暴露数据，众多的辅助研究，超过20年的随访和持续的认知评估，ARIC队列是帕金森研究的绝佳资源。因此，我们计划确认PD病例，从而在这个成熟的队列中启动长期帕金森研究。在这个队列中，PD研究有两个主要目标：1）检查PD的遗传和环境风险因素; 2）检查PD的临床前非运动症状。 此外，我的团队还与校内和校外的研究人员合作开展了一些其他项目，以寻找PD和其他神经退行性疾病的原因。合作者来自哈佛大学（卫生专业人员随访研究、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）。最后，我们还与上海和北京的主要医院的研究人员合作，研究PD的非运动症状。

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 several 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. Case confirmation is being conducted in batches as cohorts follow-up continues. We just finished the first round of case confirmation through the fourth follow-up in early 2012. 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). Finally, we are also collaborating with investigators from major hospitals in Shanghai and Beijing to study PD nonmotor symptoms.