PREVENTION OF ALZHEIMER'S BY VITAMIN E AND SELENIUM

通过维生素 E 和硒预防阿尔茨海默病

• 批准号: 6533913
• 负责人: WILLIAM R MARKESBERY
• 金额: $ 88.38万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6533913
• 关键词: Alzheimer's disease; aging; clinical trials; cognition disorders; combination therapy; dementia; diet therapy; dietary mineral; disease /disorder onset; disease /disorder prevention /control; genotype; human subject; human therapy evaluation; longitudinal human study; mental disorder diagnosis; neural degeneration; neuropsychological tests; nutrition related tag; outcomes research; patient oriented research; polymerase chain reaction; progressive supranuclear palsy; selenium; statistics /biometry; tocopherols; vitamin therapy

DESCRIPTION: Alzheimer's disease (AD), is a major health problem in the United States, where it affects approximately four million older individuals. There is no effective treatment of AD and prevention is the key to this disorder. Oxidative stress, in the form of lipid, protein, carbohydrate and DNA oxidation plays a significant role in the pathogenesis of neuron degeneration in AD and serves as a potential therapeutic target for slowing the onset or preventing the disease. The present application, termed PREADVISE, is based on the hypothesis that early treatment with vitamin E and selenium (Se) in the presymptomatic stage of the disease may delay the onset or prevent AD. These two agents have strong antioxidant properties and have not been used together in a large human study. This proposed evaluation of AD prevention will be added to the Selenium and Vitamin E Chemoprevention Trial (SELECT), a NCI-supported, phase III, double-blind, placebo-controlled 2X2 factorial study that assesses the combined and single effect of these two antioxidants on the reduction of the incidence of prostate cancer in 32,400 healthy men 55 or older (50 or older if African American). The duration of SELECT will be 12 years with a five-year uniform accrual period. PREADVISE is open to men 65 or older (60 or older if a minority) and it is estimated that 10,368 participants will be enrolled. They will be randomized to one of four arms: vitamin E plus Se, vitamin E plus Se placebo, Se plus vitamin E placebo, or vitamin E and Se placebos. They will undergo a memory impairment screening examination as part of the initial and annual SELECT evaluation, and those that fall below the cutoff point will undergo a more thorough cognitive evaluation using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) battery of cognitive tests. Participants who fail the CERAD battery will receive a thorough dementia medical evaluation for diagnosis and be reviewed in a consensus conference by neurologists and a neuropsychologist with lengthy experience in dementia. It is estimated that the relative risk for AD (relative risk 0.60) is detectable with 80 percent power in this trial. The study offers an inexpensive opportunity to evaluate the long-term effect of two antioxidant agents in slowing the onset or preventing AD in a large number of subjects. The study also will evaluate the sensitivity and specificity of the screening measure in a matched sample of normals. In addition, it will evaluate the effect of antioxidant therapy in a group of 200 elderly longitudinally followed normal controls.

描述：阿尔茨海默氏病（AD），是曼联的主要健康问题 在影响大约400万年长的情况下。有 没有有效的AD和预防治疗方法是这种疾病的关键。 氧化应激，脂质，蛋白质，碳水化合物和DNA氧化的形式 在AD中神经元变性的发病机理中起重要作用 作为减慢或预防的潜在治疗靶标 疾病。目前的应用程序称为前提，是基于 假设早期用维生素E和硒（SE）治疗 疾病的预症状阶段可能会延迟发作或预防AD。这些 两种代理具有强大的抗氧化特性，尚未一起使用 在一项大型人类研究中。将添加此拟议的对AD预防评估的评估 硒和维生素E化学预防试验（SELECT），NCI支持的， 第三阶段，双盲，安慰剂对照的2x2阶乘研究，评估 这两种抗氧化剂对还原的合并和单一影响 32,400名55岁或55岁以上健康男性的前列腺癌发生率（50岁或以上） 如果非裔美国人）。选择的持续时间为12年，五年 统一的应计时期。预防对65岁或65岁以上的男性开放（如果A 少数民族），据估计将入学10,368名参与者。他们 将被随机分为四个臂之一：维生素E Plus SE，维生素E Plus SE 安慰剂，SE加上维生素E安慰剂，或维生素E和SE安慰剂。他们会的 作为初始和 年度选择评估，降至截止点以下的评估将 使用财团进行更彻底的认知评估以建立 阿尔茨海默氏病（CERAD）的认知测试量表。 失败的Cerad电池的参与者将获得彻底的痴呆症 诊断的医学评估，并在共识会议上进行审查 神经科医生和神经心理学家在痴呆症中有悠久的经验。这是 估计可以检测到AD的相对风险（相对风险0.60） 该试验中的80％的功率。该研究提供了廉价的机会 评估两种抗氧化剂在减慢发作或 防止大量受试者中的广告。该研究还将评估 在匹配的样本中筛选度量的敏感性和特异性 正常。此外，它将评估抗氧化剂在A中的作用 200名老年人纵向遵循正常对照。