Efficacy and Mechanisms of Combined Aerobic Exercise and Cognitive Training in MCI_The ACT Trial COVID Admin Sup

协议摘要(最多5,000个字符) 这项单盲、2×2析因第二阶段随机对照试验(RCT)的目的是检验 为期6个月的骑行和处理速度(SOP)联合训练的疗效和相加/协同效应 对认知和相关机制的干预(有氧适应、AD信号皮质厚度和 遗忘性MCI(AMCI)老年人的默认模式网络[DMN]中的功能连接)。我们的 初步研究表明，增强有氧体能与更好的认知和休息有关- AD患者DMN中的状态功能连接，以及约20小时的SOP培训可改善执行功能和 在aMCI中维护DMN中的功能连接。这项随机对照试验将128名参与者平均随机分配到4名 手臂：行动，仅骑自行车，仅SOP训练，或6个月的注意力控制，然后跟随他们另一个月 12个月。将在基线、3个月、6个月、12个月和18个月评估认知和有氧适应能力；AD签名 基线、6个月、12个月和18个月时DMN的皮质厚度和功能连接性； 3个月、6个月、12个月和18个月。具体目标是：目标一、确定药效和相加/协同效应 ACT对认知的影响超过6个月。H1：ACT将对执行功能和插曲产生最大影响 与其他组的记忆进行比较。目的II.研究ACT在6个月内的潜在机制。H_2A： ACT将对AD信号的皮质厚度、DMN中的功能连接性产生最大影响，以及 与其他组的有氧健身进行比较。H2B：机制措施的变化与以下方面有关 认知变化。H_2c：AD信号皮质厚度的变化和DMN介导有氧健身的影响 关于认知。目标三(探索性)。计算ACT对认知和临床的远期效应大小 病理性AD转换以通知未来的III期RCT。分析将使用意向处理和线性 混合效果建模。这项试验将首次测试在认知和机制上的协同效应 (与AD相关的神经退行性变相关)中独特的概念化和严格设计的ACT 患有急性心肌梗塞的老年人。它将通过提供准确的效果大小估计来推进AD预防研究 采取干预措施。我们的长期目标是延缓AD的发病和进展。

Brief Summary of Protocol (5,000 characters max) 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.