The Use of Rhythmic Light Therapy to Entrain Gamma Oscillations and the Circadian System in Patients with Alzheimer's Disease and Related Dementias (ADRD)

项目总结/摘要 数据表明，在估计的550万老年人（65岁以上）中，约有40%的美国阿尔茨海默氏症患者， 在轻度认知功能障碍的人群中， 在轻度认知功能障碍（MCI），一种“危险”或潜在的痴呆前驱期，睡眠-觉醒障碍在上 60%的患者。我们的团队已经发表了各种研究，显示了对睡眠，情绪和 定制照明干预（TLI）的行为，旨在促进Alz患者的昼夜节律夹带， 海默氏病及相关痴呆（ADRD）。此外，相干40 Hz神经振荡，显示为 对于健康的大脑活动很重要，在患有神经退行性疾病的人中减少。研究表明 暴露于40 Hz节律光（RL）可降低Aβ水平以及视皮层斑块病理学， 6月龄AD转基因小鼠模型。此外，我们最近收集并发布了令人兴奋的试点数据， 表明在40 Hz下的光调制增加了伽马功率和伽马/θ耦合，两者都与 增强记忆力和认知能力。本提案的主要目标是调查一个组合的影响 用于促进睡眠的昼夜节律夹带的光和用于促进睡眠的伽马振荡夹带的光， MCI和社区轻度AD患者的认知功能。在目标1中，我们将研究光如何传递- 刺激40 Hz以促进伽马波夹带（节律光[RL]），影响主观睡眠和认知， 在一项受控的实验室研究中。一项实验室研究将允许我们收集脑电图（EEG） 数据，进行认知测试，并观察MCI患者与健康对照组相比的反应 HC组。在目标2中，我们将在一项随机、安慰剂对照的田间研究中， 干预，递送用于昼夜节律夹带（TLI）的光和用于伽马功率夹带（40 Hz）的光 RL），为期8周，并测量夜间褪黑激素（昼夜节律诱导的标志物）、睡眠， 和认知。我们假设联合干预（TLI + RL）带来的更好的睡眠将 增加夜间褪黑激素水平，改善MCI和轻度AD患者的认知能力， 社区我们将首次证明，一个实用的，有效的，量身定制的，非药理学的- 使用促进昼夜节律夹带（TLI）并递送神经刺激（40 Hz RL）的光的干预可以是有效的。 用于改善MCI和轻度AD老年人的睡眠和认知， 辅助生活设施。这种方法有可能减轻重大的财政和社会负担。 包括减少这一人群的认知恶化。此外，鉴于最近的证据表明， 睡眠在AD发病中的重要性，拟议的研究可能会对AD的发病产生重大影响。 MCI和轻度AD的病情进展。我们有经验，专业知识和能力招募参与者- 学习的裤子。

Project Summary/Abstract Data suggest that approximately 40% of the estimated 5.5 million older (65+) Americans with Alzheimer's dis- ease (AD) suffer from severe dysfunction of sleep-wake and circadian systems In people with mild cognitive impairment (MCI), an “at risk” or potential prodromal stage of dementia, sleep-wake disturbance is evident in up to 60% of patients. Our team has published various studies showing the positive impact on sleep, mood, and behavior of a tailored lighting intervention (TLI) designed to promote circadian entrainment in persons with Alz- heimer’s disease and related dementias (ADRD). In addition, coherent 40 Hz neural oscillation, shown to be important for healthy brain activity, is reduced in those with neurodegenerative diseases. Research showed that exposure to 40 Hz rhythmic light (RL) decreased Aβ levels as well as plaque pathology in the visual cortex in a 6-month-old AD transgenic mouse model. In addition, we recently collected and published on exciting pilot data showing that light modulating at 40 Hz increases gamma power and gamma/theta coupling, both associated with increase in memory and cognition. The main goal of this proposal is to investigate the impact of a combination of light for promoting circadian entrainment and light for promoting gamma oscillation entrainment on sleep and cognition in MCI and mild AD patients living in the community. In Aim 1, we will investigate how light deliver- ing 40 Hz to promote gamma wave entrainment (rhythmic light [RL]), affects subjective sleep and cogni- tion in a controlled laboratory study. A lab study will allow us to collect electroencephalogram (EEG) data, perform cognitive tests, and observe the response in those with MCI compared to a healthy control group (HC). In Aim 2, we will deliver, in a randomized, placebo-controlled field study, the combined in- tervention, delivering light for circadian entrainment (TLI) and light for gamma power entrainment (40 Hz RL), for a period of 8 weeks and measure nocturnal melatonin (a marker of circadian entrainment), sleep, and cognition. We hypothesize that better sleep resulting from the combined intervention (TLI + RL) will increase nighttime melatonin levels and improve cognition in MCI and mild AD patients living in the community. We will, for the first time, demonstrate that a practical, effective, tailored, nonpharmacological in- tervention using light that promotes circadian entrainment (TLI) and delivers neurostimulation (40 Hz RL) can be used to improve sleep and cognition in older adults with MCI and mild AD living at home or in independent or assisted living facilities. This approach has the potential to thereby mitigate significant financial and social bur- dens, including decreasing cognitive deterioration in this population. Moreover, given recent evidence linking the importance of sleep in the development of AD, the proposed studies can have a significant impact on the pro- gression of the disease MCI and mild AD. We have the experience, expertise, and ability to recruit the partici- pants for the study.