Risk of Parkinson's Diseases Associated with Aspirin and Other NSAIDs

描述(申请人提供)：虽然帕金森氏病(PD)在1817年首次被描述，但病因仍然不明。大量的实验证据表明，多巴胺能神经元的破坏可能是一系列相互关联的机制的结果，包括小胶质细胞的激活、炎症介质的上调以及与氧化应激源的相互作用。非甾体抗炎药(NSAIDs)是一类有效的抗氧化剂和抗炎化合物，在调节与氧化应激和炎症相关的毒性过程中可能发挥重要作用。这项拟议研究的具体目的是检查阿司匹林和其他非类固醇抗炎药是否与较低的帕金森病风险相关，并确定炎症(由生物标记物指示)是否可能与帕金森病风险的增加相关。为了实现这些目标，我们建议分析一项纵向多中心队列研究的现有数据，该研究名为心血管健康研究，自1989年以来，每年收集5888名65岁及以上的受试者的用药情况和医生诊断的帕金森病的信息。在后续检查期间每年收集的当前药物库存将用于评估对处方药和非处方药的暴露情况。六个炎症的基线生物标志物也将被用来评估炎症的存在。相对风险估计和95%的可信区间将被用作关联性的衡量标准。这项拟议的研究将有助于我们了解炎症是否与帕金森病风险增加有关，以及非类固醇抗炎药是否可能是可以预防或降低帕金森病发病风险的常见药物，从而减轻这种神经系统疾病在人群中的负担。公共卫生相关性：尽管帕金森氏病(PD)在1817年首次被描述，但病因仍然不明。这项拟议的研究将有助于我们了解阿司匹林和类似药物(NSAIDs)是否代表可以预防或降低患帕金森病风险的常见药物，从而减轻这种神经系统疾病在人群中的负担。

DESCRIPTION (provided by applicant): Although Parkinson's disease (PD) was first described in 1817, the cause still remains obscure. A large body of experimental evidence indicates that destruction of dopaminergic neurons may result from a series of inter-related mechanisms involving microglial activation, up-regulation of inflammatory mediators, and interactions with oxidative stressors. Medications such as nonsteroidal anti-inflammatory drugs (NSAIDs) are potent anti-oxidants and anti-inflammatory compounds that may play an important role in modulating toxic processes associated with oxidative stress and inflammation. The specific aims of this proposed study are to examine whether aspirin and other NSAIDs are associated with a lower risk of PD, and to determine whether inflammation (as indicated by biological markers) may be associated with increased PD risk. To achieve these goals, we propose to analyze existing data from a longitudinal multicenter cohort study, Cardiovascular Health Study, in which information on medication use and physician- diagnosed PD was collected every year among 5,888 subjects 65 years and older since 1989. Inventories of current medications collected yearly during follow-up examinations will be used to assess exposure to prescription and over-the-counter NSAIDs. Six baseline biological markers of inflammation will also be used to assess the presence of inflammation. Relative risk estimates and 95% confidence intervals will be used as measures of association. The proposed study would contribute to our understanding of whether inflammation is associated with an increased risk of PD and whether NSAIDs may represent common medicines that could prevent or reduce the risk of developing PD, thereby reducing the burden of this neurological disease in the population. PUBLIC HEALTH RELEVANCE: Although Parkinson's disease (PD) was first described in 1817, the cause still remains obscure. The proposed study will contribute to our understanding of whether aspirin and similar medications (NSAIDs) may represent common drugs that could prevent or reduce the risk of developing PD, thereby reducing the burden of this neurological disease in the population.