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：阿尔茨海默病（AD）是美国的一个主要健康问题， 它影响到大约400万老年人。有 没有有效的治疗AD和预防是这种疾病的关键。 氧化应激，以脂质、蛋白质、碳水化合物和DNA氧化的形式存在 在AD神经元变性的发病机制中起重要作用， 作为一种潜在的治疗靶点， 这种疾病被称为PREADVISE的本申请是基于 早期应用维生素E和硒（Se） 症状前阶段的疾病可以延迟发病或预防AD。这些 两种药剂具有很强的抗氧化性能， 在一个大型的人类研究中。将增加这一拟议的AD预防评价 硒和维生素E化学预防试验（SELECT），一项由NCI支持的， 一项III期、双盲、安慰剂对照2X2析因研究，评估 这两种抗氧化剂的组合和单一作用对减少 32，400名55岁或以上（50岁或以上）健康男性的前列腺癌发病率 非裔美国人）。SELECT的期限为12年，其中5年为 统一的权责发生制。PREADVISE对65岁或以上的男性开放（60岁或以上，如果 少数民族），估计将有10 368人参加。他们 将被随机分为四组：维生素E加硒，维生素E加硒 安慰剂、Se加维生素E安慰剂或维生素E和Se安慰剂。他们将 接受记忆障碍筛查检查，作为初始和 年度选择评估，那些低于截止点将 使用Consortium to Establish进行更全面的认知评估 阿尔茨海默病登记处（CERAD）认知测试组合。 CERAD电池失败的参与者将接受彻底的痴呆症 诊断的医学评价，并在共识会议上进行审查， 神经学家和神经心理学家在痴呆症方面有长期的经验。是 估计AD的相对风险（相对风险0.60）可检测到， 在这次审判中有80%的把握。这项研究提供了一个廉价的机会， 评估两种抗氧化剂在减缓发病或 预防大量受试者的AD。该研究还将评估 筛选措施在匹配样本中的灵敏度和特异性 正常人此外，它还将评估抗氧化治疗在 200名老年人纵向跟踪正常对照组。