RISK FACTORS FOR MSA

很少有研究探讨了MSA的决定因素。除年龄外，没有明确的风险因素。本提案的目标将是采取第一步，确定与MSA相关的因素，使用病例对照方法。我们的假设将确定不仅通过调查目前的理解有关MSA，但也通过目前的理论有关的决定因素和其他晚年神经退行性疾病，特别是帕金森氏病（PD），其中，像MSA，有α-突触核蛋白含有夹杂物的发病机制。此外，还将研究神经退行性疾病的风险因素，这些风险因素与蛋白质聚集的更普遍结果相同。该应用程序的一个独特优势是使用 临床上很可能患有MSA的特征良好的人群，将对他们进行临床随访，并对一些人进行尸检研究。入组核心A的所有病例（n = 175）和对照（n = 350）将参加项目I。四个具体的目标将被解决：SA 1：测试的假设，暴露于特定的职业或职业化学品暴露与MSA的风险增加; SA 2：测试的假设，特定的饮食因素有一个直接影响的风险MSA; SA 3：测试的假设，某些风险因素与PD或阿尔茨海默病（AD）改变MSA的风险。关注的风险因素包括：使用烟草、咖啡因、酒精、抗炎药（风险较低）;头部创伤、使用兴奋剂（风险较高）; SA 4：确定是否存在MSA或MSA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。为 每种假设，认为与MSA有因果关系的暴露预计在MSA患者中比对照组更常见。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，这些调查构成了必要的探索性步骤，试图描述MSA的决定因素。

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.