Prospective studies on Parkinson's disease

帕金森病的前瞻性研究

• 批准号: 9143484
• 负责人: HONGLEI CHEN
• 金额: $ 116.12万
• 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/9143484
• 关键词: Affect; Age; Agriculture; American; Area; Atherosclerosis; Autonomic Dysfunction; Biological Markers; Caffeine; Cardiac; Case-Control Studies; Characteristics; Cholesterol; Clinical; Clinical Management; Coffee; Cohort Studies; Collaborations; Communities; Constipation; Country; Craniocerebral Trauma; Data; Dementia; Development; Diet; Disease; Elderly; Environment; Environmental Risk Factor; Epidemiologic Studies; Epidemiology; Etiology; Genes; Genetic; Genetic Variation; Goals; Health; Ibuprofen; Individual; Infection; Institutes; Intake; Life; Measures; Mental Depression; Meta-Analysis; Motor; Natural History; Nature; Neurodegenerative Disorders; Neurology; Outcome; Paper; Parkinson Disease; Patients; Pharmaceutical Preparations; Plasma; Population; Principal Investigator; Prospective Studies; Psyche structure; Psychotic Disorders; Public Health; Publications; 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; Women' s Health; alpha synuclein; base; burden of illness; cardiovascular health; case control; clinical Diagnosis; cohort; cost effective; design; disability; disease diagnosis; disorder prevention; disorder risk; drinking; follow-up; heart rate variability; high risk; hyposmia; interest; member; non-motor symptom; pesticide exposure; prospective

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. For example, previous epidemiological studies have shown that head injury may increase the risk of PD. We for the first time demonstrated in our analysis that this association was more likely due to head injury that occurred early in life (Parkinson Relat Disord, 2015). In the same publication, we also reported a potential interaction between head injury and a genetic variation. In 2015, we also examined plasma cholesterol levels in relation to PD risk (Mov Disord 2015). While higher total cholesterol is bad for cardiovascular health, our data suggest that it may be associated with a lower risk for PD. Another important area of my research is the epidemiology of pre-motor symptoms of PD. 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, certain sleep disturbances, and symptoms of autonomic dysfunction. 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 published 3 papers on this topic in 2015. We first conducted a meta-analysis and clearly demonstrated that these symptoms were much more prevalent in PD cases than in controls (Transl Neurodegener, 2015). Then using data from de novo PD patients and controls, we showed that a few nonmotor symptoms, poor sense of smell in particular, could efficiently differentiate PD cases from controls (Neurology, 2015). Finally, using data from a well-designed cohort study, we for the first time have demonstrated that low heart rate variability, a marker of cardiac autonomic dysfunction, was associated with a higher risk for PD (Ann Neurology, 2015). 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 an ongoing 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 the Lancet.

帕金森病（PD）是第二大流行的神经退行性疾病，影响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，并通过对运动前症状和生物标志物的研究来表征高危人群。 基因和环境因素，单独或组合，有助于PD的发展。多年来，我们的研究有助于更好地了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。在过去的一年中，我们调查了PD的其他一些潜在风险因素。例如，先前的流行病学研究表明，头部损伤可能会增加PD的风险。我们在分析中首次证明，这种关联更可能是由于生命早期发生的头部损伤（Parkinson Relat Disord，2015）。在同一出版物中，我们还报道了头部损伤和遗传变异之间的潜在相互作用。2015年，我们还检查了与PD风险相关的血浆胆固醇水平（MovDisord 2015）。虽然较高的总胆固醇对心血管健康不利，但我们的数据表明，它可能与较低的PD风险有关。 我研究的另一个重要领域是PD运动前症状的流行病学。多年来，临床医生和科学家已经知道，除了特征性的运动体征外，PD患者还患有非运动症状，从嗅觉减退（嗅觉差）到痴呆和精神病。虽然这些症状可以在PD临床诊断之前和之后发生，但我对可能在疾病诊断之前几年发生的几种症状感兴趣。这些症状的实例包括嗅觉减退、便秘、抑郁、某些睡眠障碍和自主神经功能障碍的症状。这些运动前症状可能极大地促进研究，以确定PD的高风险人群，并了解早期PD病因。在过去，我们已经检查了与PD风险相关的几种个体症状。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，并了解其与PD自然史和病因的相关性。我们的具体假设是：1）同一个体中存在多种运动前症状预测PD的风险较高; 2）环境（例如吸烟，咖啡因摄入，农药暴露，布洛芬使用）和遗传（例如SNCA，MAPT）因素影响这些运动前症状的存在和/或改变其进展为明显的PD。我们在2015年发表了3篇关于这个主题的论文。我们首先进行了一项荟萃分析，并清楚地证明了这些症状在PD病例中比对照组更普遍（Transl Neurodegener，2015）。然后使用来自原发PD患者和对照的数据，我们发现一些非运动症状，特别是嗅觉差，可以有效区分PD病例和对照（Neurology，2015）。最后，使用来自一项精心设计的队列研究的数据，我们首次证明了低心率变异性（心脏自主神经功能障碍的标志物）与PD风险较高相关（Ann Neurology，2015）。 我是几项基于大型前瞻性队列的PD研究的主要研究者。我关注的是前瞻性队列研究，而不是病例对照研究，因为它们相对不容易出现回忆偏差和反向因果关系。由于PD是一种罕见的结果，需要大的队列和长的随访时间;建立在现有队列基础上的研究允许相对有效和具有成本效益的病例识别。此外，就其性质而言，前运动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氏症基因和环境研究，社区研究中的动脉粥样硬化风险的PD项目，以及上海妇女健康研究中的上海帕金森氏症研究。此外，在与分支同事的合作下，我正在农业健康研究和姐妹研究中开展PD研究。最后，我与卡罗林斯卡研究所的研究人员正在进行合作。虽然这些研究有不同的具体重点，但它们都有一个共同的主题，即揭示PD的原因并描述高危人群以预防疾病。 除了PD研究，我还是全球疾病负担小组的成员，该小组估计了世界各国各种疾病的公共卫生负担。主要研究结果发表在《柳叶刀》上的一系列论文中。