Fish oil & alpha lipoic acid in mild Alzheimer's disease

描述（由申请人提供）：与阿尔茨海默病（AD）病理学相关的生物学机制的异质性使得可以靶向多种作用机制而不是单一机制的疗法成为延迟或预防疾病进展的有吸引力的候选者。氧化应激与阿尔茨海默病病理学密切相关，最近的研究表明，炎症和胆固醇（分别）的增加与AD病理学之间也存在关联。鱼油和α-硫辛酸还具有降低氧化应激、炎症和脂质水平的能力，使它们成为减缓阿尔茨海默病进展的治疗剂的强有力的候选者。这些补充剂也很少有报道的副作用。基于它们的作用机制，两种补充剂的组合具有在延迟AD进展方面最大化治疗益处的潜力。拟议的研究将是一项试点试验，旨在收集初步数据，以帮助设计一项更大的临床试验，以评估两种治疗对AD病理学相关机制和AD病理学临床标志物的影响。本初步研究设计为3组、平行组、双盲安慰剂对照试验。被诊断为可能患有AD并具有轻度认知障碍的>55岁的受试者将被随机分配到三组之一（13名受试者/组）：鱼油，2。鱼油加α-硫辛酸，3.安慰剂治疗干预将持续1年。我们的主要目的，目标1，是通过测量尿F2-异丙烷水平来评估治疗对氧化应激的影响。我们还将收集治疗对血脂水平和高敏C反应蛋白影响的初步数据。我们的次要目标（目标2）是收集AD相关临床结局指标的初步数据，包括：阿尔茨海默病评估量表-认知子量表（ADAS-cog）、临床痴呆评定量表（CDR）、简易精神状态检查（MMSE）、阿尔茨海默病合作研究日常生活活动量表、SF-36和逻辑记忆I 1。我们的三级目标，Aim 3，通过每月监测不良事件和实验室检查（代谢检查，包括肝功能检查和血小板功能测定）评估治疗安全性。鱼油补充的依从性将通过红细胞膜脂肪酸分析进行评估。

DESCRIPTION (provided by applicant): The heterogeneous nature of the biological mechanisms associated with Alzheimer's disease (AD) pathology make therapies that can target multiple mechanisms of action rather than a single mechanism attractive candidates to delay or prevent disease progression. Oxidative stress has been highly implicated in Alzheimer's disease pathology and recent studies show there is also an association between an increase in inflammation and cholesterol (respectively), and AD pathology. Fish oil and alpha lipoic also have the ability to decrease oxidative stress, inflammation, and lipid levels, making them strong candidates as therapeutic agents in slowing the progression of Alzheimer's disease. These supplements also have few reported side effects. Based on their mechanisms of action, a combination of the two supplements has the potential to maximize the therapeutic benefit in delaying the progression in AD. The proposed study will be a pilot trial designed to collect preliminary data to aid in the design of a larger clinical trial powered to assess both treatments' effect on mechanisms associated with AD pathology and clinical markers of AD pathology. This pilot study is designed as a 3-arm, parallel group, double-blind placebo-controlled trial. Subjects >55 yrs. diagnosed with probable AD and having mild cognitive impairment will be randomized to one of three groups (13 subjects/group): 1. fish oil alone, 2. fish oil plus alpha lipoic acid, 3. placebo. The treatment intervention will be for 1-year. Our primary objective, Aim 1, is to assess the treatments' effect on oxidative stress by measuring urine F2-isoprotane levels. We will also collect preliminary data on the treatments' effect on plasma lipid levels and high-sensitivity C-reactive protein. Our secondary objective, Aim 2, is to collect preliminary data on AD-related clinical outcome measures which will include: the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), Clinical Dementia Rating scale (CDR), Mini Mental State Examination (MMSE), Alzheimer's Disease Cooperative Study Activities of Daily Living Scale, SF-36, and Logical Memory I1.Our tertiary objective, Aim 3, is to assess treatment safety by a monthly monitoring of adverse events and laboratory tests (metabolic panel, including liver function tests and platelet function assay). Compliance of fish oil supplementation will be assessed by red blood cell membrane fatty acid analysis.