Prospective studies on Parkinson's disease

帕金森病的前瞻性研究

• 批准号: 8336633
• 负责人: HONGLEI CHEN
• 金额: $ 83.06万
• 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/8336633
• 关键词: Affect; Age; Agriculture; American; Ancillary Study; Atherosclerosis; Baseline Surveys; Biological Markers; Blood; Cancer Prevention Study II; Cardiovascular system; Caring; Clinical; Clinical Management; Cognitive; Cohort Studies; Collaborations; Collection; Communities; Data; Data Collection; Diabetes Mellitus; Disease; Elderly; Environment; Environmental Risk Factor; Extramural Activities; Genes; Genetic; Genetic Materials; Genetic Risk; Goals; Health; Health Professional; Life Style; Measures; Mental Depression; Napping; Neurodegenerative Disorders; Neurology; Nurses' Health Study; Parkinson Disease; Participant; Patients; Physical activity; Population; Prospective Studies; Psyche structure; Recruitment Activity; Reporting; Research; Research Personnel; Resources; Risk; Risk Factors; Sister; Smoking; Sweden; Symptoms; Universities; Woman; Women' s Health; Work; anticancer research; base; cohort; disability; disorder prevention; disorder risk; follow-up; high risk; nutrition; pre-clinical; prevent; prospective

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).

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，并通过研究非运动症状和生物标志物来表征高风险人群。我目前有三个正在进行的项目来实现这些目标。 帕金森的基因和环境（页面）研究：页面研究建立在最初用于癌症研究的大型前瞻性队列中。该队列在1990年代中期收集了大约50万美国老年人的大量饮食和生活方式数据。在这项研究中，我们成功地从约1,100名PD患者和1,900个对照中收集了遗传物质，其中大多数还提供了同类基线调查中无法获得的其他暴露信息。 这项研究报告了一些重要的发现：1）吸烟持续时间而不是强度对于解释吸烟 - 帕金森关系很重要（Neurology，2010年）； 2）抑郁症（MOV Disord 2010）和较长的白天小睡（Am J Epidemiol，2011年）可能是PD的早期非运动症状之一； 3）较高的体育活动可能会降低PD的风险（Neurology，2010年）； 4）糖尿病可能会增加PD的风险（糖尿病护理，2011年）。最后，与其他人合作，我们为与PD风险相关的多个遗传基因座的鉴定做出了贡献（Nat Genetics，2009，Lancet 2011和PLOS Genetics 2011）。 上海帕金森研究（SPS）：SPS也基于大型前瞻性队列 - 上海妇女健康研究（SWHS）建造。这项研究很重要，因为在1997 - 2000年的基线上，SWH在妇女中进行了很少的PD研究，而SWHS收集了生物测量。在这项研究中，我们旨在识别和临床确认帕金森患者，并检查女性PD的潜在危险因素和早期生物标志物。我们在2010年春末进行了一名飞行员，并于今年开始了主要数据收集，这可能会持续数年。 帕金森氏症研究中的动脉粥样硬化风险研究（ARIC）研究：ARIC研究是最成功的基于社区的心血管研究研究之一。该队列成立于1980年代后期，并从四个美国社区招募了15,000多名45-64岁的参与者。借助多个队列的血液收集，丰富的暴露数据，大量辅助研究，超过20年的随访以及持续的认知评估，ARIC COHORT是帕金森研究的绝佳资源。因此，我们计划确认PD病例，从而在这项公认的队列中启动一项长期的帕金森氏症研究。 PD研究将在该队列中有两个主要目的，以检查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，我的小组还与壁外研究人员合作研究了其他一些项目，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（卫生专业人员后续研究，护士健康研究，预防癌症研究II营养队列），NIHES（农业健康研究和姊妹研究）以及瑞典的Karolinska Institutet（国民全国患者登记册）。