Risk Factors and Potential Protective Medications for Parkinson Disease

我们建议评估越南战争退伍军人中帕金森病（PD）的风险是否 通过暴露于除草剂，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），非甾体抗炎药 （NSAID）和抗高血压药物。如果特定的药物可以降低PD的风险，那么它们可以 可能被认为是已知或怀疑患有PD的退伍军人的预防性治疗。 PD风险更高。拟议的调查将利用对估计约1000万人口的访问， 3.2百万越战老兵这一群体特别适合于解决特定的 除草剂参与PD，因为他们广泛暴露于除草剂的水平远远高于任何 其他人群中，这个问题已经研究，并存在一个复杂的暴露 基于部队位置信息的评估模型。此外，详细的医疗和药房 像越战老兵这样庞大的人口记录将允许一些最强大的，最少偏见的 迄今为止的结果对几种不同的医疗条件和药物的作用，同时提供足够的 探索剂量反应关系和其他子分析的能力。我们将确定PD病例和对照 并随机抽取700例病例和1,400例对照。 假设1：较高的橙子剂和其他除草剂暴露与PD风险增加相关。 假设2A：较高的胆固醇水平与PD风险降低相关。 假设2B：糖尿病与PD风险增加相关。 假设2C：较高的BMI与PD风险增加相关。 假设3A：他汀类药物的使用与PD风险降低相关。 假设3B：NSAID使用与PD风险降低相关。 假设3C：钙通道阻滞剂的使用与PD风险降低相关。 作为一个探索性的目的，我们还将研究除草剂-PD关联的可能效果修改， 医疗条件和药物使用变量检查假设#2和#3，以及吸烟。 鉴于越战老兵接触除草剂的程度很高， 假设2A-2C的条件在这个人群中，了解这种接触的关系， 使人衰弱的疾病，如帕金森病，与退伍军人事务部照顾我们的战斗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可以降低PD的风险或改变风险， 由于除草剂暴露，那么这些药物可能被认为是一种预防性的药物。 在已知或怀疑暴露于除草剂的退伍军人中进行PD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.