Prospective studies on Parkinson's disease

帕金森？帕金森氏病（PD）是老年人群中第二大流行的神经退行性疾病，其原因在很大程度上是未知的。虽然已经确定了几个基因负责一些早发性家族性病例，大多数PD病例的原因仍然无法解释。由于帕金森病发病率低、起病隐匿、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Alberto Ascherio博士合作？作为哈佛公共卫生学院的一个研究小组的成员，我一直在研究饮食和生活方式与PD风险相关的三个成熟的前瞻性队列：卫生专业人员？后续研究，护士？健康研究和美国癌症协会癌症预防研究II营养队列。前瞻性设计在PD流行病学研究中很重要，因为它避免了以前病例对照研究中存在的许多潜在偏倚。此外，这三个cohrot是迄今为止最大的PD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进行验证。这些研究的一致结果包括乳制品消费与PD风险之间的正相关性以及非阿司匹林NSAID使用与PD风险之间的负相关性。最近，我们还能够提供迄今为止最有力的前瞻性证据，将农药使用与更高的PD风险联系起来。 此外，我还开发了一个新的研究项目对PD（帕金森？的基因和环境研究（PAGE）），以调查NIH-AARP饮食和健康研究中PD的环境和遗传风险因素，这是一项大型前瞻性队列研究，由NCI的亚瑟沙茨金博士于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，目前正在进行一项随访调查，以记录慢性疾病（包括PD）的发生。因此，该队列为PD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，使用基线时收集的暴露信息和随访中确定的PD病例，研究饮食/生活方式是否与PD风险相关。第2页将是一项病例对照研究，以检查与PD相关的其他环境/职业风险因素，并将需要从病例和选定的对照组中进一步收集回顾性暴露数据。对于这两个项目，关键是对PD病例进行准确的诊断确认，而这两个项目的内在组成部分是DNA采集，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，PD诊断确认和DNA采集将作为PAGE 1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。特别感兴趣的是接触杀虫剂，重金属，药物和传染病史。 最终，我们预计将确认约1,000例事件PD病例（1996-2004年）的基础上，年龄和性别特异性发病率从其他大型前瞻性队列类似的设计。这将使该研究成为迄今为止最大的PD纵向研究，从而对我们了解迟发性散发性PD的环境和遗传原因做出重大贡献。 我们刚开始收集PAGE研究的数据。

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.