A non-pharmacological multi-modal therapy to improve sleep and cognition and reduce mild cognitive impairment risk

一种非药物多模式疗法，可改善睡眠和认知并降低轻度认知障碍风险

• 批准号: 10010093
• 负责人: Daniel Gartenberg
• 金额: $ 124.35万
• 依托单位: PROACTIVE LIFE, INC.
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-05-01 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10010093
• 关键词: Accidents; Acoustic Stimulation; Acoustics; Address; Adult; Affect; Aftercare; Age; Algorithms; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Amyloid; Apple watch; Arizona; Arousal; Artificial Intelligence; Attention; Big Data; Biological Markers; Businesses; Cardiovascular Diseases; Cellular Phone; Chronic; Circadian Rhythms; Client; Clinical; Clinical Treatment; Cognition; Cognitive Therapy; Combined Modality Therapy; Communities; Comorbid Insomnia; Computer software; Consumption; Custom; Data Display; Data Set; Detection; Devices; Diabetes Mellitus; Disease; Drowsiness; Elderly; Environment; Feedback; Future; Goals; Gold; Grant; Health; Health Services Accessibility; Healthcare; Healthcare Systems; Hippocampus (Brain); Hypertension; Illness Days; Impaired cognition; Independent Living; Individual; Internet of Things; Intervention; Laboratory Study; Legal patent; Letters; Light; Link; Longitudinal Studies; Maintenance; Malignant Neoplasms; Masks; Measures; Medical; Medicine; Memory; Memory impairment; Meta-Analysis; Modeling; Mood Disorders; Mus; Neocortex; Nerve Degeneration; Noise; Older Population; Outcome; Pathology; Patients; Performance; Pharmaceutical Preparations; Pharmacological Treatment; Pharmacology; Phase; Physiological; Pittsburgh Compound-B; Play; Population; Positron-Emission Tomography; Primary Insomnia; Process; Productivity; Property; Public Health; Randomized Clinical Trials; Relaxation; Research; Risk; Risk Factors; Role; Running; Sales; Scanning; Science; Services; Signal Transduction; Sleep; Sleep Deprivation; Sleep Stages; Sleep disturbances; Sleeplessness; Slow-Wave Sleep; Solid; Sonication; Stroke; Symptoms; System; Technology; Telemedicine; Testing; Thalamic structure; Time; Training; Universities; Validation; Work; abeta deposition; actigraphy; active method; aged; base; behavior change; beta amyloid pathology; biomarker panel; cognitive function; cognitive performance; cognitive task; cognitive testing; cost; diaries; evidence base; executive function; fitbit; functional disability; human old age (65+); hypnotic; imaging study; improved; improvement on sleep; intervention effect; middle age; mild cognitive impairment; multimodality; neuroimaging; new technology; non rapid eye movement; novel; personalized intervention; post intervention; primary outcome; randomized placebo controlled trial; regenerative; secondary outcome; side effect; sleep health; sleep quality; sleep regulation; software development; sound; standard care; statistics; tau Proteins

Summary Our long-term goal is to improve healthcare with non-pharmacological interventions that use the science of behavior change and new Internet of Things (IoT) devices to augment clinical treatment. When you go to the doctor of the future, instead of prescribing a drug, in many cases the doctor may prescribe a software intervention guiding the patient through a process of facilitated behavior change and environmental optimization. This software approach to healthcare addresses the high-priority of providing services to individuals with limited/no access to care and for addressing the public health issues of insomnia and conversion to Mild Cognitive Impairments (MCI) and Alzheimer's Disease (AD). These diseases are thought to cost the US Healthcare system more than $400 billion/year, with another $400 billion/year cost to U.S. businesses in lost productivity, sick days, and accidents. In our Phase I, we were the first research group to show that non-phase locked auditory stimulation can improve next day performance on attention measures without adversely impacting sleep organization, quality, or total sleep time. Our acoustic intervention increased the percentage and intensity of slow-wave sleep (SWS), the stage of sleep with many regenerative properties and which typically decreases with age. We have additional preliminary evidence that this sound-based intervention, played at the right time and volume during sleep, can enhance next day memory performance. Due to the accumulating support demonstrating the role that sleep quality and SWS play in conversion to MCI and AD from imaging studies, longitudinal studies, and cognitive assessments, our intervention may address both the public health issue of poor sleep quality and AD. In our Phase II, we propose to further address insomnia and AD risk by integrating our deep sleep enhancement intervention and sound masking intervetinos with additional IoT devices, such as the FitBit, Apple Watch, and Oura Ring for more accurately measuring sleep and delivering sleep improvement enhancements, such as smart light bulbs to entrain and strengthen circadian rhythms, and Amazon's Alexa to deliver relaxation interventions and reminders to address compliance. The developed software will include a sleep diary with all relevant sleep statistics viewable by a trained therapist in the gold standard treatment for insomnia, cognitive behavioral therapy for insomnia (CBTi). Displaying this data to the clinician can be used to deliver more personalized interventions and increase compliance with the treatment. We propose to conduct a randomized clinical trial on 65+ aged healthy individuals in an independent living facility that have symptoms for insomnia and compare our enhanced type of CBTi integrated with new IoT technology to typical CBTi and a passive control of sleep hygiene therapy. We hypothesize that our intervention is just as effective as the gold standard treatment for insomnia of CBTi as measured by sleep efficiency on a sleep diary (primary outcome). The system may also have the additional benefit of improving next day cognitive performance (secondary outcome), a meaningful indicator of cognitive decline and AD risk. Exploratory analyses further test the effects of the intervention on a neurodegeneration biomarker panel and additional cognitive performance measures.

总结 我们的长期目标是通过使用行为科学的非药物干预来改善医疗保健 改变和新的物联网（IoT）设备，以增强临床治疗。当你去看医生的时候， 未来，在许多情况下，医生可能会开一个软件干预来指导患者，而不是开一种药物。 患者通过促进行为改变和环境优化的过程。这种软件方法， 医疗保健解决了向有限/无法获得护理的个人提供服务的高度优先事项， 解决失眠和转化为轻度认知障碍（MCI）和阿尔茨海默氏症的公共卫生问题 疾病（AD）。这些疾病被认为每年花费美国医疗保健系统超过4000亿美元， 另外，美国企业每年因生产力损失、病假和事故而损失4000亿美元。在第一阶段，我们 是第一个证明非锁相听觉刺激可以改善第二天表现的研究小组 注意力测量，而不会对睡眠组织，质量或总睡眠时间产生不利影响。我们的声学 干预增加了慢波睡眠（SWS）的百分比和强度， 再生特性，并且其通常随年龄而降低。我们有额外的初步证据表明 在睡眠期间以正确的时间和音量播放基于声音的干预，可以增强第二天的记忆 性能由于越来越多的支持表明睡眠质量和SWS在转换中发挥的作用， 从影像学研究、纵向研究和认知评估中，我们的干预措施可以解决MCI和AD 睡眠质量差和AD的公共卫生问题。在第二阶段，我们建议进一步解决失眠问题， 通过将我们的深度睡眠增强干预和声音掩蔽干预与额外的物联网相结合来降低AD风险 设备，如FitBit，Apple Watch和Oura Ring，用于更准确地测量睡眠和提供睡眠 改进增强功能，例如智能灯泡，以引导和加强昼夜节律，以及亚马逊的 Alexa提供放松干预和提醒，以解决合规问题。开发的软件将包括一个 睡眠日记，其中所有相关的睡眠统计数据可由受过训练的治疗师在失眠的金标准治疗中查看， 失眠症认知行为疗法（cognitive behavioral therapy for insomnia，CBTi）将这些数据提供给临床医生， 个性化的干预措施，并提高对治疗的依从性。我们建议进行一项随机临床试验， 在独立生活设施中对65岁以上有失眠症状的健康老年人进行的试验， 我们的增强型CBTi与新的物联网技术集成到典型的CBTi和睡眠卫生的被动控制 疗法我们假设我们的干预措施与CBTi失眠的金标准治疗一样有效 如通过睡眠日记上的睡眠效率（主要结果）测量的。该系统还可以具有额外的好处， 改善第二天认知表现（次要结局），这是认知下降和AD的一个有意义的指标 风险探索性分析进一步测试了干预对神经变性生物标志物组的影响， 额外的认知表现测量。