RISK FACTORS FOR MSA

MSA 的风险因素

• 批准号: 7553788
• 负责人: Caroline M. Tanner
• 金额: $ 19.52万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7553788
• 关键词: Parkinson' s disease; alcoholic beverage consumption; antiinflammatory agents; antioxidants; atrophy; brain injury; caffeine; case history; cell aggregation; chemicals; clinical research; dietary constituent; disease /disorder proneness /risk; environmental exposure; family genetics; human subject; interview; neural degeneration; occupational hazard; postmortem; questionnaires; tobacco abuse

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.

很少有研究探讨 MSA 的决定因素。除年龄外，尚未明确确定任何危险因素。该提案的目标是利用病例对照方法，迈出第一步，确定与 MSA 相关的因素。我们的假设不仅取决于对 MSA 目前理解的调查，还取决于有关其他晚年神经退行性疾病的决定因素和发病机制的当前理论，特别是帕金森病 (PD)，它与 ​​MSA 一样，具有 α-含有突触核蛋白的内含物。此外，还将研究神经退行性疾病的危险因素，这些因素与蛋白质聚集具有更普遍的发现。该应用程序的一个独特优势是使用 临床上可能患有 MSA 的特征明确的人群，将对他们进行临床跟踪，并在尸检中对一些人进行研究。核心 A 中注册的所有病例 (n = 175) 和对照 (n = 350) 将参与项目 I。将解决四个具体目标： SA 1：检验特定职业暴露或职业化学品暴露相关的假设MSA 风险增加； SA 2：检验特定饮食因素对 MSA 风险有直接影响的假设； SA 3：检验与 PD 或阿尔茨海默病 (AD) 相关的某些危险因素会改变 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、抗炎药物（风险较低）；头部外伤、使用兴奋剂（风险较高）； SA 4：确定是否存在 MSA 家族聚集或 MSA 症状，或 MSA 与其他神经退行性疾病（PD、AD、运动神经元疾病）的关系。为了 根据每个假设，被认为与 MSA 存在因果关系的暴露在 MSA 患者中比在对照组中更为常见。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，这些调查构成了试图描述 MSA 决定因素特征的必要探索步骤。