EXERCISE TRAIL

ADCS U01更新申请的项目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，可以改善患有轻度认知障碍(MCI)的老年人以及疾病早期的认知衰退、慢性脑萎缩和有利地改变阿尔茨海默氏症的病理。完成了两项短期干预研究。到目前为止，运动对MCI的认知增强作用提供了初步支持。这项拟议的试验将利用MRI检查结构化和监督12个月的中到高强度有氧运动干预与拉伸对脑脊液(CSF)和脑结构中AD病理的认知和生物标志物的影响。久坐不动的老年人(60-85岁)患有遗忘性MCI(n=300，CDR=0.5)将纳入研究。干预的两个分支都将在社区锻炼设施中进行，在最初的几周内将逐渐增加体力活动，然后在12个月的其余试验中保持目标持续时间和心率强度。参与者将受益于使用其他成功的多地点运动试验的既定方法进行的密切监督，正在进行的健康教育，以及由工作人员、健身教练提供的多样化支持系统，以及供同行支持的运动“伙伴”。每周，干预者将在锻炼设施与参与者会面，以监督活动常规，审查研究目标和进展，确定和解决与继续坚持相关的问题，提供鼓励和情感支持，并制定下一周的锻炼计划。在基线、6个月和12个月收集的认知和功能结果，以及在干预6个月无监督延长后再次收集的结果，将包括ADAS-Cog13，并辅之以其他执行功能测试，执行功能和情景记忆的全球(综合)衡量标准，临床痴呆症评定量表(框和)。MCI的独立生活活动和老年抑郁量表。此外，参与者将在监督的锻炼期间完成一项简短的认知测试和关于情绪和睡眠的问卷调查。在基线和12个月收集的运动疗效生物标记物将包括脑脊液中衰老和AD病理的测量，以及整体和局部脑容量。尽管经常锻炼被广泛接受和推荐，以保持最佳的身体健康，并预防各种疾病，如心血管疾病和糖尿病，但人们开出的锻炼处方并不是为了保持最佳的认知健康或预防与认知能力下降相关的疾病。这项研究的结果将提供关于有氧运动改善认知和有利地改变阿尔茨海默病病理标记物的有效性的关键数据。

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.