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: 6319407
• 负责人: WILLIAM R MARKESBERY
• 金额: $ 82.58万
• 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/6319407
• 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 州，它影响了大约 400 万老年人。有 AD没有有效的治疗方法，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 在 AD 和神经元变性的发病机制中起重要作用 作为减缓发病或预防的潜在治疗靶点 这种疾病。本申请称为 PREADVISE，基于 假设早期使用维生素 E 和硒 (Se) 进行治疗 该疾病的症状前阶段可能会延迟发病或预防 AD。这些 两种药剂具有较强的抗氧化性能，未曾同时使用过 在一项大型人类研究中。将添加此提议的 AD 预防评估 硒和维生素 E 化学预防试验 (SELECT)，这是一项由 NCI 支持的、 III 期、双盲、安慰剂对照 2X2 析因研究评估 这两种抗氧化剂的联合作用和单独作用对减少 32,400 名 55 岁或以上的健康男性（50 岁或以上）前列腺癌的发病率 如果非裔美国人）。 SELECT 的期限为 12 年，其中 5 年 统一计提期限。 PREADVISE 向 65 岁或以上的男性开放（60 岁或以上，如果 少数民族），预计将有 10,368 名参与者参加。他们 将被随机分配到四个组之一：维生素 E 加 Se、维生素 E 加 Se 安慰剂、硒加维生素 E 安慰剂、或维生素 E 和硒安慰剂。他们会 接受记忆障碍筛查检查作为初始和 年度 SELECT 评估，那些低于截止点的将 使用联盟进行更彻底的认知评估，以建立 阿尔茨海默病登记处 (CERAD) 一系列认知测试。 CERAD 电池失效的参与者将患上彻底的痴呆症 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，在痴呆症方面拥有丰富的经验。这是 估计 AD 的相对风险（相对风险 0.60）可以通过以下方法检测到： 本次试验中功率为 80%。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发生方面的长期效果 预防大量受试者的 AD。该研究还将评估 匹配样本中筛查措施的敏感性和特异性 法线。此外，它将评估抗氧化疗法的效果 由 200 名老年人组成的小组纵向跟踪正常对照。