CYCLE-AD: Randomized Controlled Trial to Assess the Efficacy of Indoor Cycling in Slowing Disease Progression in Healthy Older Persons at Genetic Risk for Alzheimers Disease

项目摘要/摘要 载脂蛋白E epsilon 4(apoE4)等位基因是晚发性疾病最重要的遗传危险因素 阿尔茨海默病(AD)。世界卫生组织最近的一项审查强调了这种潜在的 体力活动和锻炼对认知功能减退、全因痴呆症、AD和血管疾病的保护作用 健康人群中的痴呆症。在一项为期18个月的纵向观察研究中，我们发现久坐的4 与4携带者相比，携带者的情景记忆和海马体体积显著下降 那些从事中度PA的人。重要的是，在4非携带者中， 观察非携带者是否久坐或从事中度运动的认知和脑成像。 提示PA在延缓-4携带者AD进展中具有特殊的神经保护作用。 根据我们的结果，一项务实的随机对照试验，临床和成像结果为 建议确定以家庭为基础的、高强度运动干预对健康、认知的影响 完整的4携带者年龄在65岁到80岁之间。循环-AD(循环以停止或限制效果 阿尔茨海默病)试验将招募其他健康的久坐携带者，随机分为两组 (n=75)：1)参加高强度间歇训练(HIIT；60%-90%)的室内自行车(IC)组 心率储备)在家中通过市售的Peloton®自行车系统或2)通常和 习惯护理(UCC)组，参与者参与他们的习惯性PA水平。我们假设 为期18个月的高强度有氧运动将减缓久坐不动的AD相关疾病的进展 面临阿尔茨海默病遗传风险的老年人。干预组的参与者将进行每周3次的锻炼(至少 每周90分钟)，为期18个月。在研究开始时和18个月时获得的主要结果衡量标准将 包括全面认知测试和脑磁共振成像，以评估疾病进展和 综合PA/体能评估，以衡量因高体能而导致的体能变化程度 高强度的有氧运动。Cycle-AD试验的总体目标是确定长期、 大强度运动延缓或延缓-4中认知和AD相关脑变化的发生 承运人。成功翻译并展示了可扩展的家庭练习的有效性 能够减缓或推迟疾病发作的干预将改变AD的治疗，改善患者 结果和生活质量，并降低医疗保健成本。

PROJECT SUMMARY/ABSTRACT The apolipoprotein E epsilon 4 (APOE 4) allele is the most important genetic risk factor for late onset Alzheimer's disease (AD). A recent review by the World Health Organization highlighted the potential protective role of physical activity and exercise against cognitive decline, all-cause dementia, AD, and vascular dementia in healthy individuals. In an 18-month longitudinal observational study, we showed that sedentary 4 carriers experience significant declines in episodic memory and hippocampal volume compared to 4 carriers who engaged in moderate PA. Importantly, among 4 non-carriers, no significant longitudinal changes in cognition and brain imaging were observed whether the non-carriers were sedentary or engaged in moderate PA, suggesting that PA has a specific neuroprotective role in delaying the progression of AD in 4 carriers. Based on our results, a pragmatic, randomized controlled trial with blinded clinical and imaging outcomes is proposed to determine the impact of a home based, high intensity exercise intervention in healthy, cognitively intact 4 carriers between the ages of 65 and 80 years. The CYCLE-AD (CYcling to Cease or Limit the Effects of Alzheimer's Disease) trial will recruit otherwise healthy sedentary carriers randomized to one of two groups (n=75 each): 1) an Indoor Cycling (IC) group that participates in high-intensity interval training (HIIT; 60-90% of heart rate reserve) in their home via the commercially available Peloton® cycling system or 2) a Usual and Customary Care (UCC) group, in which participants engage in their habitual level of PA. We hypothesize that an 18-month high-intensity aerobic exercise regimen will slow AD-related disease progression in sedentary elders at genetic risk for AD. Participants in the intervention group will engage in exercise 3x/week (minimum 90 minutes/week) for 18 months. Primary outcome measures, obtained at study entry and at 18 months, will include comprehensive cognitive testing and brain MR imaging to assess disease progression and a comprehensive PA/fitness assessment to measure the degree of change in physical fitness due to high intensity aerobic exercise. The overall goal of the CYCLE-AD trial is to determine the role of long-term, high intensity exercise in slowing or delaying the onset of cognitive and AD-related brain changes in 4 carriers. Successful translation and demonstration of the effectiveness of a scalable home-based exercise intervention capable of slowing or delaying disease onset will transform AD treatment, improve patient outcomes and quality of life, and reduce health care costs.