Efficacy and Mechanisms of Combined Aerobic Exercise and Cognitive Training in MCI

有氧运动与认知训练相结合对 MCI 的疗效及机制

• 批准号: 10368684
• 负责人: Feng Vankee Lin
• 金额: $ 71.77万
• 依托单位: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10368684
• 关键词: Address; Aerobic Exercise; Affect; Alzheimer associated neurodegeneration; Alzheimer disease prevention; Alzheimer' s Disease; American; Auditory; Brain; Clinical; Cognition; Cognitive; Deterioration; Disease Progression; Dose; Educational Intervention; Elderly; Epidemic; Episodic memory; Family member; Functional Magnetic Resonance Imaging; Future; Goals; Hour; Intention; Intervention; Intervention Studies; Long-Term Effects; Magnetic Resonance Imaging; Measures; Mediating; Memory; Metabolic; Modeling; Nervous system structure; Neurons; Neurophysiology - biologic function; Onset of illness; Outcome; Participant; Pathologic; Pharmaceutical Preparations; Phase; Prevention Research; Process; Randomized; Randomized Controlled Trials; Regimen; Reporting; Rest; Sampling; Single-Blind Study; Structure; Symptoms; Testing; Thick; Time; Training; Training Programs; United States; United States National Institutes of Health; Verbal Learning; Visuospatial; Work; amnestic mild cognitive impairment; arm; attentional control; base; brain metabolism; cognitive change; cognitive training; design; efficacy evaluation; efficacy testing; executive function; exercise training; feasibility testing; high risk population; improved; mild cognitive impairment; novel; prevent; processing speed; programs; relating to nervous system

Because almost all drug trials for Alzheimer's disease (AD) have failed, developing non-pharmacological interventions with strong potential to prevent or delay the onset of AD in high-risk populations (e.g., those with mild cognitive impairment [MCI]) is critically important. Aerobic exercise and cognitive training are 2 promising interventions for preventing AD. Aerobic exercise increases aerobic fitness, which in turn improves brain structure and function, while cognitive training improves selective neural function intensively. Hence, combined Aerobic exercise and Cognitive Training (ACT) may very well have an additive or synergistic effect on cognition by complementary strengthening of different neural functions. Few studies have tested ACT's effects, and those studies have reported discrepant findings, largely due to varying ACT programs. The purpose of this single-blinded, 2×2 factorial Phase II randomized controlled trial (RCT) is to test the efficacy and additive/synergistic effects of a 6-month combined cycling and speed of processing (SOP) training intervention on cognition and relevant mechanisms (aerobic fitness, AD signature cortical thickness, and functional connectivity in the default mode network [DMN]) in older adults with amnestic MCI (aMCI). Our preliminary studies have shown that enhanced aerobic fitness is associated with better cognition and resting-state functional connectivity in the DMN in AD, and ~20 hours of SOP training improves executive function and maintains functional connectivity in the DMN in aMCI. This RCT will randomize 128 participants equally to 4 arms: ACT, cycling only, SOP training only, or attention control for 6 months, and then follow them for another 12 months. Cognition and aerobic fitness will be assessed at baseline, 3, 6, 12, and 18 months; AD signature cortical thickness and functional connectivity in the DMN at baseline, 6, 12, and 18 months; AD conversion at 3, 6, 12, and 18 months. The specific aims are to: Aim I. Determine the efficacy and additive/synergistic effects of ACT on cognition over 6 months. H1: ACT will have the greatest effects on executive function and episodic memory compared with other groups. Aim II. Examine the underlying mechanisms of ACT over 6 months. H2a: ACT will have the greatest effects on AD signature cortical thickness, functional connectivity in the DMN, and aerobic fitness compared with other groups. H2b: Changes in the mechanistic measures are related to cognitive changes. H2c: Changes in AD signature cortical thickness and DMN mediate aerobic fitness' effects on cognition. Aim III (exploratory). Calculate the long-term effect sizes of ACT on cognition and clinical and pathological AD conversion to inform future Phase III RCTs. Analysis will use intention-to-treat and linear mixed-effect modeling. This trial will be the first to test the synergistic effects on cognition and mechanisms (relevant to AD-associated neurodegeneration) of a uniquely conceptualized and rigorously designed ACT in older adults with aMCI. It will advance AD prevention research by providing precise effect-size estimates of the ACT intervention. Our long-term goal is to delay AD onset and slow AD progression.

因为几乎所有阿尔茨海默氏病（AD）的药物试验都失败了，因此出现了非药物 具有强大潜力的干预措施，以防止或延迟高风险人群中的AD发作（例如 轻度认知障碍[MCI]）至关重要。有氧运动和认知培训是2个承诺 预防广告的干预措施。有氧运动增加了有氧运动，从而改善了大脑 结构和功能，而认知训练则大大提高了选择性神经功能。因此，合并 有氧运动和认知训练（ACT）很可能对认知具有添加剂或协同作用 通过互补的增强不同的神经功能。很少有研究测试了行动的影响，并且 这些研究报告了差异发现，这主要是由于行动计划的不同。这个目的 单盲，2×2阶段II阶段II随机对照试验（RCT）是为了测试效率和 6个月组合循环和加工速度（SOP）训练干预的添加/协同作用 关于认知和相关机制（有氧健身，AD标志性皮质厚度和功能性 在患有Amnestic MCI（AMCI）的老年人中，默认模式网络中的连通性[DMN]）。我们的初步 研究表明，增强的有氧健身与更好的认知和静息状态有关 DMN在AD中的功能连接性，SOP培训的约20小时可改善执行功能和 在AMCI中保持DMN中的功能连通性。该RCT将随机将128个参与者等于4 武器：ACT，仅骑自行车，仅SOP训练或注意力控制6个月，然后跟随他们进行另一个 12个月。认知和有氧健身将在基线，3、6、12和18个月进行评估；广告签名 基线，6、12和18个月的DMN的皮质厚度和功能连通性； AD转换为3， 6、12和18个月。具体目的是：目标I。确定效率和添加剂/协同作用 在6个月内采取认知行动。 H1：ACT将对执行功能和情节产生最大的影响 与其他组相比，记忆。目标II。检查6个月内ACT的潜在机制。 H2A： ACT将对AD标志性皮质厚度，DMN的功能连通性具有最大的影响，并且 有氧健身与其他组相比。 H2B：机械措施的变化与 认知变化。 H2C：AD标志性皮质厚度和DMN的变化介导有氧健身的效果 关于认知。 AIM III（探索性）。计算ACT对认知和临床的长期效应大小以及 病理广告转化以告知未来的III阶段RCT。分析将使用意向治疗和线性 混合效应建模。该试验将是第一个测试对认知和机制的协同影响的试验。 （与广告相关的神经变性有关）独特概念化和严格设计的行为 AMCI的老年人。它将通过提供精确的效应尺寸估计值来推动AD预防研究 ACT干预。我们的长期目标是延迟AD发作并减缓AD的进展。