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

摘要 认知控制缺陷是许多老年人认知能力下降的核心，通常 导致功能衰退，最终导致痴呆症。快速增长的人口部分面临着 这种认知能力的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推迟老年痴呆的发病。 据估计，阿尔茨海默病和其他痴呆症的新增病例为1000万例。鉴于在……方面缺乏成功 发现预防痴呆症的有效药物或预防性疗法，开发有针对性的 纠正认知缺陷的干预措施至关重要。为此，我们开发了一种新型的闭环系统，数字 冥想干预(MediTrain)，旨在改善健康骨性关节炎患者注意力集中的调节。 在一项机械性随机对照试验中，我们最近表明，MediTrain能够广泛改善认知控制， 在有认知缺陷(即，类似MCI的)的OA亚组中所见的最大收益。此外，这一干预 导致应激反应性降低和衰老细胞标志物的改善。这项提案的一个目标是 扩大我们的干预范围，在全国招募的大样本中进行流动随机对照试验(MRCT)， 世卫组织将完全在移动设备上完成研究，提供执行计划的统计能力 主持人和亚组分析，以了解治疗反应中可变性的来源。另一个 从我们最初在OA中进行的MediTrain RCT中出现的重要问题是：什么是最小和/或最优的 达到我们观察到的益处所需的干预剂量？因此，这项拟议的研究将解决 两个具体目标：首先，我们将在不同剂量的治疗下，在OA中进行大规模的MRCT，以 确定改善认知和减轻压力所需的最小有效剂量。第二，我们将 观察认知功能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 检查潜在的遗传因素(阿尔茨海默病多基因危险评分)、生理因素(心血管疾病)的影响 风险)和社会(种族/民族)调节因素对治疗效果的影响。为了实现这些目标，我们将进行 在移动设备上部署的大规模MediTrain MRCT在不同的全国范围内的OA样本中(N=3240)， 世卫组织将完全在移动设备上完成这项研究。这个庞大的全国队列将提供样本大小 有必要检查不同地区的个体和亚组治疗反应的差异 普通人口。所有参与者都将完成基线、即时随访和6个月的随访 对认知和功能结果的评估。我们预计，这种独特的方法和方法 实验设计将显著推动针对广泛的治疗方案的发展 注意力控制调节不足的认知能力和临床人群的范围。

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.