Prospective studies on Parkinson's disease

帕金森病的前瞻性研究

• 批准号: 7330698
• 负责人: HONGLEI CHEN
• 金额: --
• 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/7330698
• 关键词: Prospective; studies; Parkinson; disease

Parkinson?s disease (PD) is the second most prevalent neurodegenerative disease in the elderly population and its causes are largely unknown. Although several genes have been identified to be responsible for some of the early onset familial cases, the causes of most PD cases remained unexplained. Epidemiological studies on PD environmental risk factors are proved difficult, due to the low incidence, the insidious onset and the clinical course of the disease. In collaboration with Dr. Alberto Ascherio?s group at Harvard School of Public Health, I have been investigating dietary and lifestyle risk factors in relation to PD risk in three well established prospective cohorts: the Health Professionals? Follow-up Study, the Nurses? Health Study, and the Cancer Prevention Study II Nutrition Cohort from American Cancer Society. The prospective design is important in PD epidemiological research as it avoids many of the potential biases that the previous case-control studies had. Further, these three cohrots are to date the largest prospective studies on PD and have generated some interesting results that need to be validated in future investigations. Consistent findings from these studies included a positive association between dairy consumption and risk of PD and an inverse association between non-aspirin NSAIDs use and PD risk. Recently, we were also able to provide to date the strongest prospective evidence linking pesticide use and a higher PD risk. Further, I am also developing a new research project on PD (the Parkinson?s Genes and Environment Study (PAGE)) to investigate environmental and genetic risk factors for PD in the NIH-AARP Diet and Health Study, which is a large prospective cohort that was initiated in mid-1990s by Dr. Arthur Schatzkin at NCI for cancer research. Over half a million US men and women 50 years or older participated in the baseline surveys in 1995 and 1996 and a follow-up survey is now underway to document the occurrence of chronic diseases, including PD. Therefore, this cohort provides an excellent infrastructure for PD research. The PAGE study includes two phases: PAGE 1 is a longitudinal study to investigate whether diet/lifestyle are related to PD risk, using exposure information collected at baseline and PD cases identified in the follow-up. PAGE 2 will be a case-control study to examine other environmental/occupational risk factors in relation to PD and will require further retrospective exposure data collection from both cases and selected controls. For both projects, the key is to do an accurate diagnostic confirmation of PD cases, and an intrinsic component of both projects is DNA collection, which will allow us to conduct case-control analyses of diet-gene / environment-gene interactions. Therefore, PD diagnostic confirmation and DNA collection will be carried out as part of PAGE 1. In PAGE2, we will conduct retrospective data collection using computer assisted telephone interview (CATI). Of particular interest are exposures to pesticides, heavy metals, medication, and history of infectious diseases. Eventually, we expect to confirm approximately 1,000 incident PD cases (1996-2004) based on the age- and gender-specific incidence from other large prospective cohorts with similar design. This will make the study the largest longitudinal study on PD to date and thus contribute significantly to our understanding of the environmental and genetic causes of late onset sporadic PD. We just started data collection for the PAGE study.

帕金森-S病(PD)是老年人群中第二常见的神经退行性疾病，其病因目前尚不清楚。尽管一些早发性家族性病例已被发现与几个基因有关，但大多数帕金森病病例的病因仍未得到解释。由于帕金森病发病率低、发病隐匿、临床病程长，对帕金森病环境危险因素的流行病学研究比较困难。 与哈佛大学公共卫生学院的阿尔贝托·阿谢里奥？S博士合作，我一直在三个已建立的前瞻性队列中调查饮食和生活方式风险因素与帕金森病风险的关系：卫生专业人员？护士们的后续研究？健康研究，以及来自美国癌症协会的癌症预防研究II营养队列。前瞻性设计在帕金森病流行病学研究中很重要，因为它避免了先前病例对照研究中的许多潜在偏见。此外，这三项研究是迄今为止关于帕金森病的最大规模的前瞻性研究，并产生了一些有趣的结果，需要在未来的研究中得到验证。这些研究的一致发现包括乳制品摄入量与帕金森病风险之间的正相关，以及非阿司匹林非类固醇抗炎药的使用与帕金森病风险之间的负关联。最近，我们还能够提供迄今为止最有力的前瞻性证据，将杀虫剂的使用与较高的帕金森病风险联系起来。 此外，我还在开发一个关于帕金森病的新研究项目(帕金森？S基因与环境研究(PAGE))，以在美国国立卫生研究院-美国退休人员协会饮食与健康研究中调查环境和遗传风险因素，这是一个大型前瞻性队列，由美国国立卫生研究院的Arthur Schatzkin博士于20世纪90年代中期发起，用于癌症研究。超过50万50岁或50岁以上的美国男性和女性参加了1995年和1996年的基线调查，目前正在进行后续调查，以记录包括帕金森病在内的慢性病的发生情况。因此，这一队列为帕金森病的研究提供了良好的基础设施。 PAGE研究包括两个阶段：PAGE 1是一项纵向研究，利用基线收集的暴露信息和后续确定的PD病例，调查饮食/生活方式是否与PD风险有关。第2页将是一项病例对照研究，以检查与帕金森病有关的其他环境/职业风险因素，并将需要从病例和选定的对照中进一步追溯暴露数据收集。对于这两个项目，关键是对PD病例进行准确的诊断确认，而这两个项目的一个内在组成部分是DNA收集，这将使我们能够对饮食-基因/环境-基因相互作用进行病例对照分析。因此，帕金森病诊断确认和DNA采集将作为第1页的一部分进行。在第2页，我们将使用计算机辅助电话访谈(CATI)进行回顾性数据收集。特别令人感兴趣的是接触杀虫剂、重金属、药物和传染病病史。 最终，我们预计将根据其他具有类似设计的大型前瞻性队列中年龄和性别特定的发病率，确认大约1000例帕金森病事件(1996-2004年)。这将使这项研究成为迄今为止关于帕金森病的最大规模的纵向研究，从而有助于我们理解晚发型散发性帕金森病的环境和遗传原因。 我们刚刚开始为页面研究收集数据。