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

描述（由申请人提供）：尽管帕金森氏症（PD）于1817年首次被描述，但其病因仍不清楚。大量的实验证据表明，多巴胺能神经元的破坏可能是由一系列相互关联的机制引起的，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）等药物是有效的抗氧化剂和抗炎化合物，可能在调节与氧化应激和炎症相关的毒性过程中发挥重要作用。本研究的具体目的是研究阿司匹林和其他非甾体抗炎药是否与PD风险降低有关，并确定炎症（如生物标志物所示）是否与PD风险增加有关。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——心血管健康研究的现有数据，该研究自1989年以来每年收集5888名65岁及以上受试者的药物使用和医生诊断的PD信息。每年在随访检查期间收集的当前药物清单将用于评估处方和非处方非甾体抗炎药的暴露情况。炎症的六个基线生物标志物也将用于评估炎症的存在。将使用相对风险估计值和95%置信区间作为关联度量。这项拟议的研究将有助于我们了解炎症是否与PD风险增加有关，以及非甾体抗炎药是否可能代表可以预防或降低PD风险的常用药物，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，但其病因仍然不清楚。拟议的研究将有助于我们了解阿司匹林和类似药物（非甾体抗炎药）是否可能代表可以预防或减少患帕金森病风险的常用药物，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.