Cognitive and Aerobic Resilience for the Brain

描述（由申请人提供）：痴呆症是一种与年龄有关的疾病，影响10%的70岁以上人口。它与丧失功能独立性和高昂的护理费用（2010年估计为1590亿美元）有关。在变得痴呆之前，大多数患者会经历一个被称为轻度认知障碍（MCI）的阶段，在这个阶段，缺陷是轻微的，护理费用较低。我们建议对轻度认知障碍患者进行行为干预的初步研究。如果拟议的试点研究能够实现其目标，它将为支持一项大型、多地点、随机临床试验（RCT）提供一个概念和实践基础，该试验将测试身体和认知联合训练在延迟痴呆症临床诊断时间方面的功效。一项2 × 2因子设计，包括基于家庭的认知干预（Cog-I）或认知控制（Cog-C）和基于家庭的体育锻炼干预（physical exercise intervention, physi）或体育锻炼控制（physical exercise control, physc），招募患有MCI的老年人，根据《美国老年人法案》第三章接受膳食。物理i干预包括45分钟的有氧和阻力训练。Cog-I干预包括以计算机为基础的模块，重点关注执行认知能力，持续45分钟。物理- c干预包括45分钟的伸展运动，而Cog-C干预包括45分钟的教育节目和完成拼图和文字游戏（Cog-C）。4种治疗条件中的每一种包括每周3次90分钟的疗程，持续12周（共36次）。目标是：1)确定可行性，监测干预措施和结果的依从性，并监测安全性和可接受性；2)确定联合治疗（Cog-I + physi）与对照组（Cog-C + physc）相比是否对认知测试成绩有积极影响；3)估计年龄、APOE、教育程度和基线认知状态是否与治疗反应相关；4)通过追踪营养因子（BDNF和VEGF）和炎症标志物（CRP, IL-6, tnf - α）的前后变化来检查实验干预的作用机制。确定延缓轻度认知损伤进展的治疗方法具有巨大的公共卫生意义，因为此类干预措施有可能延缓痴呆的发病及其伴随的功能和经济损失。

DESCRIPTION (provided by applicant): Dementia is an age-related condition that affects 10% of the population over age 70. It is associated with loss of functional independence and high care costs (estimated at $159 billion in 2010). Prior to becoming demented, most patients pass through a stage called Mild Cognitive Impairment (MCI) in which deficits are mild and care costs are lower. We are proposing a pilot study of a behavioral intervention in MCI patients. If the proposed pilot study, designed to be consistent with current recommended approaches to establishing trial feasibility, is able to achieve its aims, it will provide a conceptual and practcal rationale to support a large, multi-site, randomized clinical trial (RCT) that tests the efficacy o combined physical and cognitive training in delaying time to a clinical diagnosis of dementia. a 2 x 2 factorial design with a home-based cognitive intervention (Cog-I) or cognitive control (Cog-C) and a home-based physical exercise intervention (Phys-I) or physical exercise control (Phys-C) enrolling older adults with MCI receiving meals under Title III of the Older Americans Act. The Phys-I intervention includes physical exercise focused on aerobic and resistance training for 45 minutes. The Cog-I intervention consists of computer based modules focused on executive cognitive ability for 45 minutes. The Phys-C intervention consists of 45 minutes of stretching while the Cog-C intervention consists of 45 minutes of educational programs and completion of puzzles and word games (Cog-C). Each of the 4 treatment conditions consists of 3 90-minute per week sessions for 12 weeks (36 sessions total). The aims are: 1) establish feasibility, monitor adherence to interventions and outcomes, and monitor safety and acceptability; 2) determine if combined treatment (Cog-I + Phys-I) has a positive effect on cognitive test performance vs. control (Cog-C + Phys-C); 3) estimate whether age, APOE, education, and baseline cognitive status are associated with response to treatment; and 4) examine mechanisms of action of the experimental intervention by tracking pre-post changes in trophic factors (BDNF and VEGF) and inflammatory markers (CRP, IL-6, TNF-alpha). Identification of treatments that delay progression of MCI is of enormous public health significance as such interventions have potential to delay the onset of dementia and its attendant functional and financial losses.