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.

由于几乎所有的阿尔茨海默病（AD）药物试验都失败了，开发非药物 在高危人群中预防或延迟AD发作的潜在干预措施（例如，的人 轻度认知障碍（MCI）是非常重要的。有氧运动和认知训练是很有前途的 预防AD的措施。有氧运动增加有氧健身，这反过来又提高大脑 结构和功能，而认知训练改善选择性神经功能集中。因此，结合 有氧运动和认知训练（ACT）很可能对认知产生叠加或协同效应 通过不同神经功能的互补强化。很少有研究测试ACT的效果， 这些研究报告了不一致的发现，主要是由于不同的ACT项目。这样做的目的 一项单盲、2×2析因II期随机对照试验（RCT），旨在检测疗效， 6个月的循环和处理速度（SOP）联合训练干预的累加/协同效应 认知和相关机制（有氧健身，AD签名皮质厚度，和功能 默认模式网络[DMN]中的连通性）在患有遗忘型MCI（aMCI）的老年人中。我们的初步 研究表明，增强有氧健身与更好的认知和休息状态有关 AD中DMN的功能连接，以及约20小时的SOP培训可改善执行功能， 在aMCI中保持DMN中的功能连接。该RCT将随机分配128名参与者，平均分配4名 手臂：ACT，仅循环，仅SOP培训或注意力控制6个月，然后再随访一个月 12个月将在基线、3、6、12和18个月时评估认知和有氧健身; AD特征 基线、6、12和18个月时DMN的皮质厚度和功能连接; 3个月时AD转换， 6、12和18个月。具体目标是：确定以下物质的功效和累加/协同效应： ACT在认知上超过6个月。H1：ACT将对执行功能和情节产生最大影响 与其他群体相比。Aim II.检查ACT的潜在机制超过6个月。H2a： ACT将对AD特征皮质厚度、DMN中的功能连接性以及 有氧健身与其他组相比。H2 b：机制措施的变化与以下方面有关： 认知变化H2 c：AD特征皮质厚度和DMN的变化介导有氧健身的影响 关于认知。目标三（探索性）。计算ACT对认知和临床的长期效应量， 病理性AD转化，为未来的III期RCT提供信息。分析将使用意向治疗和线性 混合效果建模这项试验将是第一次测试对认知和机制的协同作用 （与AD相关的神经退行性变相关）的独特概念化和严格设计的ACT， 老年人aMCI它将通过提供精确的效应大小估计来推进AD预防研究。 ACT干预。我们的长期目标是延迟AD发作和减缓AD进展。