EXERCISE TRAIL

ADCS U01续期申请的项目2将是一项关键的多地点随机对照试验，以评估有监督的有氧运动是否是一种有效的治疗选择，以改善轻度认知障碍（MCI）老年人的认知能力下降，减缓脑萎缩，并有利地改变阿尔茨海默病病理，从而在疾病的早期阶段。完成两项短期干预研究。为MCI中运动的认知增强作用提供了初步支持。拟议的试验将通过MRI检查有组织和监督的12个月中至高强度有氧运动干预与拉伸对认知和脑脊液（CSF）和脑结构中AD病理生物标志物的影响。研究纳入了患有遗忘性轻度认知障碍的久坐老年人（60-85岁）（n=300， CDR=0.5）。干预的两个部分都将在社区运动设施中进行，在最初的几周内，身体活动将逐渐增加，然后在接下来的12个月的试验中保持目标持续时间和心率强度。参与者将受益于严密的监督，使用其他成功的多地点运动试验的既定方法，持续的健康教育，以及由工作人员、健身教练和同伴支持的运动“伙伴”提供的多样化支持系统。每周，干预师将在锻炼设施与参与者会面，监督活动常规，回顾研究目标和进展，确定并解决与持续坚持相关的问题，提供鼓励和情感支持，并制定下周的锻炼计划。在基线、第6个月和第12个月以及在无监督的干预延长6个月后再次收集的认知和功能结果将包括ADAS-Cog13，并辅以执行功能的其他测试、执行功能和情景记忆的整体（复合）测量、临床痴呆评定量表（方框总和）。MCI的独立生活活动与老年抑郁量表。此外，参与者将完成一个简短的认知测试和关于情绪和睡眠的问卷调查，每周在监督锻炼期间。在基线和第12个月收集的运动功效的生物标志物将包括脑脊液中衰老和AD病理的测量，以及整个和局部脑容量。尽管定期锻炼被广泛接受和推荐，以保持最佳的身体健康，预防各种疾病，如心血管疾病和糖尿病，但锻炼并不是以同样的信念来规定的，以保持最佳的认知健康或预防与认知能力下降相关的疾病。这项研究的结果将为有氧运动改善认知和有利地改变阿尔茨海默病病理标志物的功效提供关键数据。

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.