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

CYCLE-AD：评估室内骑行对有阿尔茨海默病遗传风险的健康老年人延缓疾病进展的功效的随机对照试验

• 批准号: 10328952
• 负责人: JAY L. ALBERTS
• 金额: $ 142.36万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-15 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10328952
• 关键词: Accelerometer; Aerobic Exercise; Age; Alleles; Alzheimer' s Disease; Alzheimer' s disease risk; Amyloid; Anti-Inflammatory Agents; Auditory; Biological Markers; Biomechanics; Blinded; Brain; Brain imaging; Brain scan; Caring; Cerebrum; Characteristics; Clinical; Cognition; Cognitive; Dementia; Deterioration; Diagnosis; Diffuse; Disease; Disease Progression; Effectiveness; Elderly; Episodic memory; Exercise; Exhibits; Functional Magnetic Resonance Imaging; Gait; Genetic Risk; Goals; Health; Health Care Costs; Heart Rate; Hippocampus (Brain); Home; Homeostasis; Image; Impaired cognition; Individual; Inflammatory; Interval training; Intervention; Late Onset Alzheimer Disease; Link; Lipids; Literature; Longitudinal observational study; Magnetic Resonance Imaging; Measures; Memory; Moderate Exercise; Monitor; Neurons; Neuropsychological Tests; Onset of illness; Other Genetics; Outcome; Outcome Measure; Participant; Patient Self-Report; Patient-Focused Outcomes; Performance; Perfusion; Phenotype; Physical Exercise; Physical Fitness; Physical Function; Physical activity; Plasma; Play; Posture; Property; Quality of life; Radial; Randomized; Randomized Controlled Trials; Role; Series; System; Testing; Time; Translations; Vascular Dementia; Verbal Learning; World Health Organization; apolipoprotein E-4; base; brain magnetic resonance imaging; brain volume; cardiorespiratory fitness; clinically significant; cognitive function; cognitive testing; executive function; exercise intensity; exercise intervention; exercise regimen; experience; fitness; fitness test; follow-up; genetic risk factor; group intervention; improved; lifestyle factors; neuroinflammation; primary outcome; processing speed; programs; recruit; sedentary; white matter

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.

项目概要/摘要 载脂蛋白 E epsilon 4 (APOE 4) 等位基因是晚发型最重要的遗传风险因素 世界卫生组织最近的一项审查强调了阿尔茨海默病（AD）的潜力。 身体活动和锻炼对认知能力下降、全因痴呆、阿尔茨海默病和血管性痴呆的保护作用 在一项为期 18 个月的纵向观察研究中，我们发现久坐不动 4。 与 4 携带者相比，携带者的情景记忆和海马体积显着下降 重要的是，在 4 非携带者中，没有显着的纵向变化。 观察非携带者是否久坐或从事中度活动的认知和脑成像 PA，表明 PA 在延缓 4 携带者 AD 进展方面具有特定的神经保护作用。 根据我们的结果，一项具有盲法临床和影像学结果的务实、随机对照试验是 提议确定家庭高强度运动干预对健康、认知能力的影响 年龄在 65 至 80 岁之间的完整 4 携带者 CYCLE-AD（循环以停止或限制影响） 阿尔茨海默病）试验将招募其他健康的二级携带者，随机分配到两组中的一组 （每组 n=75）： 1） 一个室内自行车（IC）组，参加高强度间歇训练（HIIT；60-90% 心率储备）在家中通过市售的 Peloton® 骑行系统或 2) 常规和 习惯护理 (UCC) 小组，参与者参与其习惯水平的 PA。 18 个月的高强度有氧运动方案将减缓久坐的 AD 相关疾病进展 有 AD 遗传风险的老年人。干预组的参与者将每周进行 3 次锻炼（至少）。 每周 90 分钟），持续 18 个月，在研究开始时和 18 个月时获得主要结果指标。 包括全面的认知测试和脑部磁共振成像，以评估疾病进展和 全面的PA/体能评估，衡量高强度运动导致的体能变化程度 CYCLE-AD 试验的总体目标是确定长期、有氧运动的作用。 高强度运动可减缓或延迟 4 认知和 AD 相关大脑变化的发生 成功翻译并展示了可扩展的家庭演习的有效性。 能够减缓或延迟疾病发作的干预措施将改变 AD 治疗，改善患者状况 成果和生活质量，并降低医疗保健成本。