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.

项目摘要/摘要 数据表明，在阿尔茨海默氏症的估计550万（65岁以上）的美国人中，约有40％ 轻度认知患者的轻松（AD）患有睡眠效果和昼夜节律系统的严重功能障碍 损害（MCI）是痴呆症的“有风险”或潜在的前驱阶段，睡眠醒来的灾难在UP中得到了证明 至60％的患者。我们的团队发表了各种研究，表明对睡眠，情绪和 量身定制的照明干预措施（TLI）的行为，旨在促进ALZ-的昼夜节律入口 海默氏病和相关痴呆症（ADRD）。另外，连贯的40 Hz神经振荡，显示为 对于健康的大脑活动很重要，在神经退行性疾病的患者中会减少。研究表明 暴露于40 Hz的节奏光（RL）降低Aβ水平以及在A中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飞行员数据 表明在40 Hz时调制的光调节会增加伽马功率和伽马/theta耦合，这两者都与 记忆和认知的增加。该提案的主要目标是调查组合的影响 促进昼夜节入口和光的光线 居住在社区中的MCI和温和广告患者的认知。在AIM 1中，我们将研究光的传递方式 - 40 Hz促进伽马波入口（有节奏的光[RL]），会影响主观睡眠和认知 在对照实验室研究中。实验室研究将使我们能够收集脑电图（EEG） 与健康对照相比，数据，执行认知测试并观察MCI患者的反应 组（HC）。在AIM 2中，我们将在一个随机的安慰剂对照现场研究中交付。 节日，提供昼夜节律的光（TLI）和伽马电源的光（40 Hz） RL），持续8周，测量夜间褪黑激素（昼夜节入口的标志），睡眠， 和认知。我们假设由综合干预措施（TLI + RL）产生的更好的睡眠将会 提高夜间褪黑激素水平并改善居住在MCI和轻度AD患者的认知 社区。我们将第一次证明一种实用，有效，量身定制的，非药理学中的 使用促进昼夜节入口（TLI）并提供神经刺激（40 Hz RL）的光线可以是 用于改善MCI和温和广告的老年人的睡眠和认知，在家里或独立或独立或 辅助生活设施。这种方法有可能减轻大量财务和社会攻击 巢穴，包括降低该人群的认知恶化。此外，鉴于最近有证据与 睡眠在AD发展中的重要性，拟议的研究可能会对研究产生重大影响 MCI和轻度AD的疾病。我们具有招募该部分的经验，专业知识和能力 - 研究的裤子。