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: 10542444
• 负责人: JAY L. ALBERTS
• 金额: $ 154.43万
• 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/10542444
• 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; Disease; Disease Progression; Effectiveness; Elderly; Episodic memory; Exercise; Exhibits; Functional Magnetic Resonance Imaging; Gait; Genetic Risk; Goals; Health; Health Care Costs; Heart Rate; Hippocampus; 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; Posture; Property; Quality of life; Radial; Randomized; Randomized, Controlled Trials; Role; Series; System; Testing; Time; Translations; VO2max; Vascular Dementia; Verbal Learning; World Health Organization; apolipoprotein E-4; brain magnetic resonance imaging; brain volume; cardiorespiratory fitness; clinically significant; cognitive function; cognitive testing; efficacy evaluation; executive function; exercise intensity; exercise intervention; exercise regimen; experience; fitness; fitness test; follow-up; genetic risk factor; group intervention; improved; lifestyle factors; neuroinflammation; neuroprotection; patient engagement; 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.

项目总结/摘要 载脂蛋白E <$4（APOE <$4）等位基因是晚发型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 体力活动和锻炼对认知能力下降、全因痴呆、AD和血管性痴呆的保护作用 健康人的痴呆症在一项为期18个月的纵向观察研究中，我们发现久坐不动的人 携带者与携带者相比，情景记忆和海马体积显著下降 谁从事适度的PA。重要的是，在2004年非携带者中， 无论非携带者是久坐还是从事中度运动， PA，提示PA在延缓AD进展中具有特异性神经保护作用。 基于我们的研究结果，一项实用的、随机对照的临床盲法和影像学结局试验， 建议确定家庭为基础的高强度运动干预对健康、认知和心理健康的影响。 年龄在65岁到80岁之间的完整的104名携带者。CYCLE-AD（停止或限制影响的循环） 阿尔茨海默氏症）试验将招募其他健康的久坐携带者随机分为两组 （每组n=75）：1）参加高强度间歇训练（HIIT; 60-90%的 心率储备）在他们的家中通过市售Peloton®自行车系统或2）自行车和 习惯护理（UCC）组，参与者参与其习惯水平的PA。我们假设 18个月的高强度有氧运动方案将减缓AD相关疾病的进展， 有遗传风险的老年人。干预组的参与者将每周进行3次锻炼（最少 90分钟/周）18个月。在研究入组时和18个月时获得的主要结局指标将 包括全面认知测试和脑部MR成像，以评估疾病进展， 全面的PA/健身评估，以衡量身体素质的变化程度，由于高 高强度有氧运动。CYCLE-AD试验的总体目标是确定长期， 高强度运动减缓或延迟认知和AD相关脑变化的发生 载波成功翻译并展示可扩展的家庭练习的有效性 能够减缓或延迟疾病发作干预将改变AD治疗，改善患者 结果和生活质量，并降低医疗保健成本。