Targeting Autonomic Flexibility to Enhance Cognitive Training Outcomes in Older Adults with Mild Cognitive Impairment

摘要 我们最近完成的R01表明，面向加工速度和注意力(PS/A)的认知训练 (VSOP)对PS/A和工作记忆有很强的影响，但对认知控制或情景记忆没有影响。 长期影响总体上是温和的。在建议的R01更新计划中，我们建议物色其他 进一步增强PS/A训练在患有轻度遗忘症的老年人中的转移和长期效果 认知障碍(MCI)，通过解决支持适应性学习和 神经可塑性。第二阶段双盲随机试验的目标是测试是否增加了共振 对VSOP的频率呼吸(RFB)训练将加强适应能力的多个贡献者， 特别是自主神经系统(ANS)灵活性的中枢和外周通路，这将 加强VSOP训练对认知功能和脑功能的影响，延缓MCI痴呆的进展。我们的 中心假设是通过改善自主神经系统(ANS)来增强适应能力 灵活性，将增强神经可塑性和MCI痴呆的缓慢进展，因为适应能力是关键 对于VSOP的神经可塑性，但在神经退行性变过程中受到损害。老年MCI(n=114) 将随机分配到为期8周的联合干预(RFB VSOP)，VSOP与引导图像 放松(IR)控制和等待列表IR控制，并在后续定期进行助推器培训。 机械性的和远端的结果包括ANS的灵活性和痴呆进展的多个标志。数据将是 在14个月的时间内收集。两个主要目标是检查联合行动的长期影响 干预ANS灵活性(目标1)，以及认知、行为和功能能力(目标2)。这个 探索性目标将是确定联合干预的初步长期效果 神经退行性变。我们认为这是我们已完成的R01的合理更新计划，旨在确定 进一步提高认知训练在MCI中的迁移和长期效果的附加属性。这将是 在首批研究针对MCI适应能力的新的联合干预措施的随机对照试验中， 最终目标是减缓神经退行性变。拟议的工作与NINR战略计划保持一致，以推进 护理学，EPS。症状管理(在这种情况下，改善MCI的认知和功能症状) 使用非药物干预方法并了解相关机制。

Abstract Our recently completed R01 suggested that processing speed and attention (PS/A) oriented cognitive training (VSOP) produced robust effect on PS/A and working memory, but not in cognitive control or episodic memory, and long-term effects were overall modest. In the proposed R01 renewal, we propose to identify additional attributes to further enhance transferred and long-term effects of PS/A training in older adults with amnestic mild cognitive impairment (MCI) by addressing adaptation capacity that underpins adaptive learning and neuroplasticity. The goal of the stage II double-blinded randomized trial is to test whether adding resonance frequency breathing (RFB) training to VSOP will strengthen multiple contributors to adaptation capacity, particularly the central and peripheral pathways of autonomic nervous system (ANS) flexibility, which will strengthen VSOP training effect on cognitive and brain function and slow the progress of dementia in MCI. Our central hypothesis is that strengthening adaptation capacity, via improving autonomic nervous system (ANS) flexibility, will enhance neuroplasticity and slow progress of dementia in MCI, since adaptation capacity is critical for neuroplasticity of VSOP, but compromised in neurodegenerative process. Older adults with MCI (n = 114) will be randomly assigned to an 8-week combined intervention (RFB+VSOP), VSOP with guided imagery relaxation (IR) control, and a waitlist IR control, with periodical booster training sessions at follow-ups. Mechanistic and distal outcomes include ANS flexibility and multiple markers of dementia progress. Data will be collected across a 14-month period. The two primary aims are to examine long-term effects of the combined intervention on ANS flexibility (Aim 1), as well as the cognitive, behavioral, and functional capacity (Aim 2). The exploratory aim will be to determine the preliminary long-term effect of the combined intervention on neurodegeneration. We consider this a reasonable renewal plan from our completed R01, aiming to identify additional attributes to further enhance transferred and long-term effects of cognitive training in MCI. This will be among the first RCTs to examine a novel, combined intervention targeting adaptation capacity in MCI, with an ultimate goal for slowing neurodegeneration. The proposed work is aligned with NINR strategic plan to advance nursing science, eps. symptoms management (in this case, improving cognitive and functional symptoms in MCI) using a non-pharmacological intervention approach and understanding relevant mechanisms.