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

项目摘要/摘要 数据显示，在大约550万患有阿尔茨海默氏症的美国老年人(65岁以上)中，约有40%的人患有阿尔茨海默氏症。 轻度认知障碍患者存在严重的睡眠-觉醒和昼夜节律系统功能障碍 损害(MCI)，痴呆的一个“危险”或潜在的前驱阶段，睡眠-觉醒障碍在UP中是明显的 到60%的患者。我们的团队已经发表了各种研究，表明这对睡眠、情绪和 旨在促进阿尔茨海默病患者昼夜节律携带的量身定制照明干预(TLI)的行为 海默病及相关痴呆(ADRD)。此外，相干的40赫兹神经振荡，显示为 对健康的大脑活动很重要，在患有神经退行性疾病的人中会减少。研究表明， 暴露于40赫兹节律光(RL)可降低A-β水平和视皮层斑块病理。 6个月龄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 显示在40赫兹的光调制增加了伽马功率和伽马/θ耦合，两者都与 提高记忆力和认知力。这项提案的主要目标是调查联合行动的影响 用于促进昼夜节律夹带的光和用于促进伽马振荡夹带的光对睡眠和 社区MCI和轻度AD患者认知功能的调查在目标1中，我们将研究光如何传递- 40赫兹促进伽马波夹带(节奏光[RL])，影响主观睡眠和认知- 在一项对照的实验室研究中。一项实验室研究将允许我们收集脑电(EEG) 数据，进行认知测试，并观察MCI患者与健康对照组的反应 组(HC)。在目标2中，我们将在一项随机、安慰剂对照的现场研究中提供- 发明，为昼夜夹带(TLI)和伽马功率夹带(40赫兹)提供光 RL)，为期8周，并测量夜间褪黑激素(昼夜携带的标志)，睡眠， 和认知力。我们假设，联合干预(TLI+RL)产生的更好的睡眠将 提高MCI和轻度AD患者夜间褪黑素水平和改善认知功能 社区。我们将首次展示一种实用的、有效的、量身定做的、非药理学的- 使用促进昼夜节律夹带(TLI)并提供神经刺激(40赫兹RL)的光可以 用于改善患有MCI和轻度AD的老年人的睡眠和认知能力，生活在家里或独立或 辅助生活设施。这种方法有可能因此缓解重大的财务和社会问题- 洞穴，包括减少这一人群的认知退化。此外，鉴于最近的证据表明 睡眠在阿尔茨海默病发展中的重要性，拟议的研究可以对PRO-PRO产生重大影响 轻度阿尔茨海默病和轻度阿尔茨海默病。我们有经验、专业知识和能力来招募参与者- 书房穿的裤子。

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.