RISK FACTORS FOR MSA

很少有研究探讨MSA的决定因素。除了年龄，还没有明确确定的风险因素。这项提案的目标将是利用病例对照方法，在确定与MSA有关的因素方面迈出第一步。我们的假设不仅取决于对目前对MSA的理解的调查，还取决于关于其他晚年神经退行性疾病的决定因素和发病机制的现有理论，特别是帕金森病(PD)，它像MSA一样，具有包含α-突触核蛋白的包涵体。此外，还将调查神经退行性疾病的风险因素，这些因素分享了更普遍的蛋白质聚集发现。此应用程序的一个独特优势是使用 临床上可能患有MSA的特征良好的人群，临床将对他们进行跟踪，一些人将在尸检中进行研究。在核心A中登记的所有病例(n=175)和对照(n=350)将参加项目I。将涉及四个具体目标：SA 1：测试暴露于特定职业或职业化学物质暴露与MSA风险增加相关的假设；SA 2：测试特定饮食因素对MSA风险有直接影响的假设；SA 3：测试与PD或阿尔茨海默病(AD)相关的某些风险因素改变MSA风险的假设。感兴趣的风险因素包括：使用烟草、咖啡因、酒精、抗炎药(风险较低)；头部创伤、兴奋剂使用(风险较高)；SA 4：确定是否存在MSA的家族聚集或MSA的症状，或MSA和其他神经退行性疾病(PD、AD、运动神经元疾病)的家族聚集性。为 每一种假设，被认为与MSA有因果关系的暴露在MSA患者中预计比在对照组中更常见。假设检验将使用经典方法进行病例对照研究的单变量和多变量分析。我们强调，这些调查是试图确定多发性硬化症决定因素的必要探索性步骤。

Few studies have explored the determinants of MSA. Apart from age, no risk factor has been definitively identified. The goal of this proposal will be to take the first step in identifying factors associated with MSA, using a case-control method. Our hypotheses will be determined not only by an investigation of current understandings about MSA, but also by current theories regarding the determinants and the pathogenesis of other late-life neurodegenerative diseases, particularly Parkinson's disease (PD), which, like MSA, has alpha-synuclein-containing inclusions. In addition, risk factors for neurodegenerative disorders sharing the more general finding of protein aggregation will be investigated. A unique advantage of this application is the use of a well-characterized population with clinically Probable MSA, who will be followed clinically and for some studied at autopsy. All cases (n = 175) and controls (n = 350) enrolled in Core A will participate in Project I. Four specific aims will be addressed: SA 1: To test the hypothesis that exposure to specific occupational or a vocational chemical exposure is associated with an increased risk of MSA; SA 2: To test the hypothesis that specific dietary factors have a direct effect on the risk of MSA; SA 3: To test the hypotheses that certain risk factors associated with PD or Alzheimer's disease (AD) alter the risk of MSA. Risk factors of interest include: use of tobacco, caffeine, alcohol, anti-inflammatory drugs (lower risk); head trauma, stimulant use (higher risk); SA 4:To determine whether there is familial aggregation of MSA or the symptoms of MSA, or of MSA and other neurodegenerative diseases (PD, AD, motor neuron disease). For each hypothesis, exposures believed to be causally associated with MSA are expected to be more common in persons with MSA than in controls. Hypothesis testing will use classical methods for univariate and multivariate analysis of case-control studies. We stress that these investigations constitute a necessary exploratory step in attempting to characterize the determinants of MSA.