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

使用节律光疗法来调节阿尔茨海默病和相关痴呆症 (ADRD) 患者的伽马振荡和昼夜节律系统

• 批准号: 10459413
• 负责人: Mariana Gross Figueiro
• 金额: $ 80.05万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10459413
• 关键词: 6-sulfatoxymelatonin; AD transgenic mice; Adult; Affect; Age; Agitation; Alzheimer' s Disease; Alzheimer' s disease patient; Alzheimer' s disease related dementia; American; Amyloid beta-42; Amyloid beta-Protein; Animals; Area; Assisted Living Facilities; Attention; Behavior; Biological Markers; Brain; Brain Diseases; Brain region; Caregiver Burden; Clinical; Cognition; Cognitive; Communities; Control Groups; Coupling; Data; Data Analyses; Degenerative Disorder; Dementia; Deterioration; Development; Devices; Disease Progression; Drowsiness; Elderly; Electroencephalogram; Excessive Daytime Sleepiness; Exposure to; Frequencies; Funding; Goals; Home; Human; Independent Living; Intervention; Laboratory Study; Lead; Light; Lighting; Link; Measures; Melatonin; Memory; Moods; Mus; Neurodegenerative Disorders; Participant; Pathology; Patient Recruitments; Patients; Periodicity; Persons; Phase; Phototherapy; Placebo Control; Placebos; Play; Population; Publishing; Questionnaires; Randomized; Research; Risk; Role; Short-Term Memory; Sleep; Sleep Disorders; Somnambulism; Standardization; System; Testing; The Sun; Time; Urine; Visual Cortex; actigraphy; circadian; cognitive performance; cognitive testing; cohort; design; experience; field study; improved; member; mild cognitive impairment; mouse model; operation; recruit; relating to nervous system; response; social; therapy design

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.

项目概要/摘要 数据表明，估计有 550 万老年（65 岁以上）美国人中约有 40% 患有阿尔茨海默病 轻度认知障碍患者患有严重的睡眠-觉醒和昼夜节律系统功能障碍（AD） 损伤（MCI），痴呆症的“危险”或潜在前驱阶段，睡眠-觉醒障碍在 至 60% 的患者。我们的团队发表了多项研究，显示对睡眠、情绪和睡眠的积极影响 旨在促进阿尔茨海默氏症患者昼夜节律的定制照明干预（TLI）行为 海默氏病和相关痴呆症（ADRD）。此外，相干 40 Hz 神经振荡，被证明是 对于健康的大脑活动很重要，但患有神经退行性疾病的人会减少。研究表明 暴露于 40 Hz 节律光 (RL) 会降低 Aβ 水平以及视觉皮层中的斑块病理学 6个月大的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 40 Hz 的光调制会增加伽马功率和伽马/θ 耦合，两者都与 增加记忆力和认知能力。该提案的主要目标是调查组合的影响 用于促进昼夜节律夹带的光和用于促进睡眠和伽玛振荡夹带的光 生活在社区的 MCI 和轻度 AD 患者的认知能力。在目标 1 中，我们将研究光如何传递- 荷兰国际集团40赫兹促进伽马波夹带（节奏光[RL]），影响主观睡眠和认知 化在受控实验室研究中。实验室研究将使我们能够收集脑电图 (EEG) 数据，进行认知测试，并观察 MCI 患者与健康对照者的反应 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综合的 in- 干预，提供用于昼夜节律夹带（TLI）的光和用于伽马功率夹带的光（40 Hz RL），为期 8 周，测量夜间褪黑激素（昼夜节律的标志物）、睡眠、 和认知。我们假设联合干预（TLI + RL）会带来更好的睡眠 增加夜间褪黑激素水平并改善居住在 MCI 和轻度 AD 患者的认知能力 社区。我们将首次证明，一种实用的、有效的、量身定制的、非药物的方法—— 使用促进昼夜节律 (TLI) 并提供神经刺激 (40 Hz RL) 的光进行干预 用于改善患有 MCI 和轻度 AD 的老年人的睡眠和认知能力，这些老年人生活在家里或独立或独立的环境中 辅助生活设施。这种方法有可能减轻重大的财务和社会负担 巢穴，包括减少该人群的认知退化。此外，鉴于最近的证据表明 睡眠在 AD 发展中的重要性，拟议的研究可以对亲 MCI 和轻度 AD 疾病的进展。我们有经验、专业知识和能力招募参与者 学习用的裤子。