Risk Factors and Potential Protective Medications for Parkinson Disease

我们建议评估越战退伍军人患帕金森氏病(PD)的风险是否 通过接触除草剂、低胆固醇、糖尿病、较高的体重指数(BMI)和使用 他汀类(3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂)，非类固醇抗炎药 (非类固醇抗炎药)和抗高血压药物。如果特定的药物可以降低帕金森病的风险，那么他们就可以 在已知或怀疑患有帕金森病的退伍军人中，有可能被视为帕金森氏症的预防性治疗 患帕金森病的风险更高。拟议的调查将利用接触估计人口的机会 320万越战老兵。这一群体特别适合于解决特定的 除草剂参与帕金森病，因为他们广泛接触除草剂的水平远远高于任何 其他研究过这一问题的人群，以及是否存在复杂的暴露 基于部队位置信息的评估模型。此外，详细的医疗和药房 在像越战老兵这样庞大的人口中，记录将允许一些最强大、最没有偏见的人 迄今为止关于几种不同医疗条件和药物的作用的结果，同时提供了足够的 探索剂量-反应关系和其他分分析的能力。我们将确定帕金森病病例和对照 通过退伍军人病历，随机抽取700例患者和1400例对照。 假设1：接触橙剂和其他除草剂的时间越长，患帕金森病的风险越高。 假设2A：较高的胆固醇水平与较低的帕金森病风险相关。 假设2B：糖尿病与帕金森病风险增加有关。 假设2C：BMI越高，患帕金森病的风险越高。 假设3A：他汀类药物的使用与帕金森病风险降低相关。 假设3B：非甾体抗炎药的使用与帕金森病风险降低相关。 假设3C：钙通道阻滞剂的使用与帕金森病风险降低相关。 作为一个探索性的目标，我们还将研究除草剂-PD缔合的可能的效果修饰 在假设#2和#3中检查的医疗条件和药物使用变量，以及吸烟。 鉴于越南退伍军人接触除草剂的水平很高，而且风险很高 假设2A-2C在这一人群中的状况，了解这种接触的关系 像帕金森氏症这样的衰弱疾病与退伍军人管理局照顾退伍军人的使命高度相关。 此外，如果可以证明我们将检查的任何药物都可以降低帕金森病的风险或修改风险 可归因于除草剂的暴露，那么这些药物可能被认为是一种预防性药物 对已知或怀疑接触过除草剂的退伍军人进行帕金森病治疗。

We propose to assess whether the risk of Parkinson's disease (PD) among veterans of the Vietnam War is predicted by exposure to herbicides, lower cholesterol, diabetes, higher body mass index (BMI), and use of statins (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors), non-steroidal anti-inflammatory drugs (NSAIDs), and anti-hypertensive medications. If particular medications reduce the risk of PD, then they could potentially be considered as a prophylactic treatment against PD among veterans known or suspected to be at higher risk of PD. The proposed investigation will take advantage of access to a population of an estimated 3.2 million Vietnam veterans. This population is uniquely suited to address the question of the specific involvement of herbicides in PD because of their wide exposure to herbicides at levels much higher than in any other population in which this question has been studied, and the existence of a sophisticated exposure assessment model based on troop location information. In addition, the detailed medical and pharmacy records in a population as large as that of Vietnam veterans will allow for some of the strongest, least biased results to date on the role of several different medical conditions and medications, while providing sufficient power to explore dose-response relations and other subanalyses. We will identify PD cases and controls through VA medical records and randomly select 700 cases and 1,400 controls. Hypothesis 1: Higher exposure to Agent Orange and other herbicides is associated with increased risk of PD. Hypothesis 2A: Higher cholesterol levels are associated with a decreased risk of PD. Hypotheses 2B: Diabetes is associated with an increased risk of PD. Hypothesis 2C: Higher BMI is associated with an increased risk of PD. Hypothesis 3A: Statin use is associated with a decreased risk of PD. Hypothesis 3B: NSAID use is associated with a decreased risk of PD. Hypothesis 3C: Calcium channel blocker use is associated with a decreased risk of PD. As an exploratory aim, we will also examine possible effect modification of the herbicide-PD association by the medical conditions and medication use variables examined in Hypotheses #2 and #3, as well as by smoking. In light of the very high levels of herbicide exposure among Vietnam veterans and the frequency of the risk conditions of hypotheses 2A-2C among this population, understanding the relation of such exposures to a debilitating illness such as PD is highly relevant to the VA mission of caring for our combat veterans. Furthermore, if it can be shown that any of the medications we will examine reduce risk of PD or modifies risk attributable to herbicide exposure, then these medications could potentially be considered as a prophylactic treatment against PD among veterans known or suspected to have been exposed to herbicides.