EXERCISE TRAIL

ADCS U 01更新申请的项目2将是一项关键的多中心随机对照试验，旨在评估监督下的有氧运动是否是改善轻度认知障碍（MCI）老年人认知能力下降、减缓脑萎缩并有利地改变阿尔茨海默病病理学的有效治疗选择，从而在疾病的最早阶段。完成了两项短期干预研究。迄今为止，提供了初步的支持认知增强效果的MCI运动。拟议的试验将使用MRI检查结构化和监督的12个月中高强度有氧运动干预与拉伸对脑脊液（CSF）和脑结构中AD病理学的认知和生物标志物的影响。将招募患有遗忘型MCI的久坐老年人（60-85岁）（n=300，CDR=0.5）。两组干预措施都将在社区运动设施中进行，在最初几周内逐渐增加体力活动，然后在12个月试验的剩余时间内保持目标持续时间和心率强度。参加者将受惠于其他成功的多地点运动试验的既定方法的密切监督，持续的健康教育，以及由员工、健身教练和运动伙伴提供的多元化支持系统。每周，干预者将在运动设施与参与者会面，监督活动常规，审查研究目标和进展，识别和解决与持续坚持相关的问题，提供鼓励和情感支持，并制定下周的运动计划。在基线、第6个月和第12个月以及在无监督延长干预6个月后再次收集的认知和功能结局将包括ADAS-Cog 13，并辅以其他执行功能测试、执行功能和情景记忆的总体（复合）测量、临床痴呆评定量表（方框总和）。MCI的独立生活活动和老年抑郁量表。此外，参与者将在监督锻炼期间每周完成一次简短的认知测试和关于情绪和睡眠的问卷调查。在基线和第12个月收集的运动功效的生物标志物将包括CSF中的老化和AD病理学以及全脑和局部脑体积的测量。虽然经常锻炼被广泛接受并推荐以保持最佳身体健康并预防各种医疗状况，如心血管疾病和糖尿病，但运动并没有被同样的信念用于保持最佳认知健康或预防与认知下降相关的疾病。本研究的结果将提供有关有氧运动改善认知能力并有利地改变阿尔茨海默病病理标志物的功效的关键数据。

Project 2 of the ADCS U01 renewal application will be a pivotal multi-site randomized controlled trial to assess whether supervised aerobic exercise is an effective therapeutic option to ameliorate cognitive decline, slow brain atrophy, and favorably alter Alzheimer pathology in older adults with mild cognitive impairment (MCI) and thus in the earliest stages of disease. Two short-term intervention studies completed . thus far provide preliminary support for a cognition-enhancing effect of exercise in MCI. The proposed trial will examine the effects of a structured and supervised 12-month moderate- to high-intensity aerobic exercise intervention versus stretching on cognition and biomarkers of AD pathology in cerebrospinal fluid (CSF) and brain structure using MRI. Sedentary older adults (60-85 yrs old) with amnestic MCI (n=300, CDR=0.5) will be enrolled. Both arms of the intervention will be carried out in community exercise facilities, and physical activity will be gradually increased over the first few weeks and then maintained at the targeted duration and heart rate intensity for the rest of the 12-month trial. Participants will benefit from close supervision using established methods from other successful multi-site exercise trials, on-going health education, and a diversified support system provided by staff, fitness trainers, and an exercise 'Buddy' for peer support. Each week, the interventionist will meet with the participant at the exercise facility to supervise the activity routine, review study goals and progress, identify and resolve issues related to continued adherence, provide encouragement and emotional support, and develop the exercise plan for the coming week. Cognitive and functional outcomes, collected at baseline, months 6 and 12, and again following a 6-month unsupervised extension of the intervention, will include the ADAS-Cog13, supplemented with other tests of executive function, a global (composite) measure of executive function and of episodic memory, the Clinical Dementia Rating scale (sum of boxes). Activities of Independent Living for MCI, and the Geriatric Depression Scale. In addition, participants will complete a brief cognitive test and questionnaire about mood and sleep each week during the supervised exercise session. Biomarkers of exercise efficacy, collected at baseline and month 12, will include measures of aging and AD pathology in CSF, and whole and regional brain volumes. Although regular exercise is widely accepted and recommended to maintain optimum physical health and prevent various medical conditions such as cardiovascular disease and diabetes, exercise is not prescribed with the same conviction to maintain optimum cognitive health or prevent diseases associated with cognitive decline. The results of this study will provide critical data regarding the efficacy of aerobic exercise to improve cognition and favorably alter markers of Alzheimer's disease pathology.