Optimizing a closed-loop digital meditation intervention for remediating cognitive decline and reducing stress in older adults

摘要 认知控制的缺陷是许多老年人经历的认知能力下降的核心， 导致功能衰退并最终痴呆。人口中迅速增长的部分面临着 这种认知能力下降有可能对社会产生广泛的负面影响，据估计， 维持或改善老年人（OA）的认知能力可能会预防或延迟 估计有1000万新的阿尔茨海默病和其他痴呆症病例。由于缺乏成功， 发现有效的药理学或预防性疗法来预防痴呆症， 采取干预措施纠正认知缺陷至关重要。为此，我们开发了一种新颖的闭环数字 冥想干预（MediTrain），旨在改善健康OA的集中注意力调节。 在一项机制随机对照试验中，我们最近表明，MediTrain导致认知控制的广泛改善， 在具有认知缺陷的OA亚组中观察到的最大增益（即，MCI样）。此外，这次干预 导致应激反应降低和衰老细胞标志物的改善。本提案的目标是 通过在全国范围内招募的大样本中进行移动的随机对照试验（mRCT），扩大我们的干预范围， 将完全在移动的设备上完成研究的受试者，提供执行计划的统计功效 主持人和亚组分析，以了解治疗反应变异性的来源。另一 从我们最初的MediTrain在OA中的RCT中出现的一个重要问题是： 达到我们观察到的益处所需的干预剂量？因此，这项研究将解决 两个具体目标：首先，我们将在不同剂量治疗的OA中进行MediTrain的大型mRCT， 确定认知改善和减轻压力所需的最低有效剂量。二是 检查认知能力下降对治疗效果的调节作用。我们还将包括一个探索性的目标， 检查潜在的遗传（阿尔茨海默氏症多基因危害评分），生理（心血管） 风险）和社会（种族/民族）调节剂对治疗效果的影响。为了实现这些目标，我们将 一项在不同的全国性OA样本（N = 3240）中在移动的设备上部署MediTrain的大规模mRCT， 他们将完全在移动的设备上完成研究。这个大型的全国性队列将提供样本量 有必要在不同的治疗反应范围内检查个体和亚组差异。 一般人口。所有参与者将完成基线、即时随访和6个月随访 认知和功能结果的评估。我们预计，这种独特的方法和 实验设计将大大推进针对广泛的治疗方案的发展， 一系列的认知能力和临床人群，患有缺乏调节的注意力控制。

Abstract Deficits in cognitive control are at the core of much cognitive decline experienced by many older adults, often leading to functional decline and eventually dementia. The rapidly growing segment of the population facing such cognitive decline has the potential to negatively impact society broadly and it has been estimated that maintaining or improving cognition in older adults (OA) could potentially prevent or delay the onset of an estimated 10 million new cases of Alzheimer’s disease and other dementias. Given the lack of success in discovering effective pharmacological or preventative therapies to prevent dementias, developing targeted interventions to remediate cognitive deficits is vital. To this end, we developed a novel closed-loop, digital meditation intervention (MediTrain) that was designed to improve regulation of focused attention in healthy OA. In a mechanistic RCT, we recently showed that MediTrain lead to broad improvements in cognitive control, with the greatest gains seen in a subgroup of OA with cognitive deficits (i.e., MCI-like). In addition, this intervention led to reduced stress reactivity and improvements in cellular markers of aging. A goal of this proposal will be to extend the scope of our intervention by conducting a mobile RCT (mRCT) in a large sample, recruited nationally, who will complete the study entirely on mobile devices, providing the statistical power to perform planned moderator and subgroup analyses to understand the sources of variability in treatment response. Another important question that emerged from our initial RCT of MediTrain in OA was: what is the minimal and/or optimal dose of the intervention required to achieve the benefits we observed? Thus, this proposed research will tackle two specific aims: First, we will conduct in a large, mRCT of MediTrain in OA at varying doses of treatment to determine the minimum effective dose required for cognitive improvement and stress reduction. Second, we will examine the moderating effect of cognitive decline on treatment effects. We will also include an exploratory aim to examine the impact of potential genetic (Alzheimer’s polygenic hazard scores), physiological (cardiovascular risk), and social (race/ethnicity) moderators on the treatment effects. To accomplish these aims, we will conduct a large-scale mRCT of MediTrain deployed on mobile devices in a diverse, nation-wide sample of OA (N = 3240), who will complete the study entirely on mobile devices. This large, national cohort will provide the sample size necessary to examine individual and subgroup differences in treatment response across a diverse swath of the general population. All participants will complete baseline, immediate follow-up, and 6-month follow-up assessments of cognitive and functional outcomes. We anticipate that this unique methodological approach and experimental design will significantly advance the development of treatment programs directed at the broad range of cognitive abilities and clinical populations that suffer from deficient regulation of attentional control.