Light, metabolic syndrome and Alzheimer's disease: a non-pharmacological approach

光、代谢综合征和阿尔茨海默病：非药物方法

• 批准号: 10442504
• 负责人: CHRISTOPH BUETTNER
• 金额: $ 91.52万
• 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: 2021-03-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10442504
• 关键词: Aging; Agitation; Alzheimer' s Disease; Alzheimer' s disease patient; Alzheimer' s disease related dementia; Assisted Living Facilities; Behavior; Brain; Calibration; Caregivers; Circadian Dysregulation; Circadian Rhythms; Clinical; Cognitive; Controlled Environment; Cross-Over Studies; Darkness; Data; Dementia; Development; Disease; Elderly; Endocrinology; Epidemiology; Exposure to; General Population; Geriatric Psychiatry; Glucose; Glucose tolerance test; Goals; Home; Homeostasis; Hour; Human; Impairment; Inflammation; Insulin; Insulin Resistance; Intervention; Investigation; Light; Lighting; Link; Lipids; Literature; Manufacturer; Measures; Melatonin; Mental Depression; Metabolic; Metabolic Control; Metabolic Diseases; Metabolic syndrome; Metabolism; Moods; Mus; Non-Insulin-Dependent Diabetes Mellitus; Nursing Homes; OGTT; Obesity; Outcome; Patients; Pattern; Phototherapy; Pittsburgh Sleep Quality Index; Placebo Control; Population; Predisposition; Quality of life; Questionnaires; Randomized; Research; Resistance development; Rest; Risk; Safety; Sampling; Sleep; Sleep disturbances; Societies; System; Testing; Work; actigraphy; arm; blood glucose regulation; burden of illness; circadian; comparison control; depressive symptoms; design; diabetes risk; efficacy testing; glucose disposal; glucose tolerance; improved; improvement on sleep; inflammatory marker; information gathering; innovation; insight; instrument; insulin sensitivity; light effects; metabolic abnormality assessment; meter; mild cognitive impairment; novel; placebo controlled study; recruit; therapy design; urinary

Project Summary/Abstract This study's main hypothesis is that a delivering a tailored lighting intervention (TLI) will provide a successful means for promoting circadian entrainment and treating metabolic disease and inflammation in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) and Alzheimer's disease and related dementias (ADRD). As such, the proposed studies have the potential to provide important insights into the link between AD/ADRD and type 2 diabetes (T2DM) by identifying the disruption of circadian rhythms as a key component in the metabolic impairment. It would open new avenues of investigation, as it would raise the possibility that brain insulin resistance is indeed a consequence of disrupted circadian rhythm. Preliminary data from ongoing studies demonstrates a beneficial effect of light treatment on sleep and depression. If positive results are observed, the potential also exists to transform the manner in which homes, assisted living facilities, and nursing homes are lighted by delivering a simple, practical, non-pharmacological intervention to promote entrainment, improve sleep, and reduce metabolic disease in AD and mild AD MCI patients. The specific aims of the proposed research are two-fold. First, a randomized, placebo-controlled, crossover study involving 60 AD/ADRD patients who live in controlled environments (i.e., assisted living facilities and nursing homes), will investigate whether 8 weeks of exposure to a TLI designed to increase circadian entrainment (measured via urinary melatonin) improves sleep (actigraphy and questionnaires), mood (questionnaire), inflammatory markers, and metabolic control (oral glucose tolerance tests) compared to a control, circadian-inactive light. Second, using a single-arm, between-subjects design, placebo- controlled study we will investigate if long-term (6-month) exposure to TLI improves glucose homeostasis and insulin sensitivity in 30 patients with mild AD/ADRD and sleep disturbances, who will be recruited from the Mount Sinai AD research center (ADRC) and randomized to receive TLI (or dim light control treatment) at home. We will test if the TLI improves insulin sensitivity (SI) and glucose disposal (SG) as assessed through the frequently sampled IV glucose tolerance test (FSIVGTT) to dissect mechanisms through which circadian re-entrainment improves metabolism. The strengths of this project are considerable, especially given the unavailability of instruments for measuring personal circadian light exposure patterns. If successful, the study will open the way for a practical, effective non-pharmacological treatment for significantly reducing the two diseases' burden on society and, more directly, on caregivers. The unique, diverse research team is composed of experts in the fields of geriatric psychiatry, endocrinology, and light and circadian research, all of whom have direct access to the clinical population. This project is also highly translational, as the PIs will use the information gathered through this research to work with manufacturers in the development of lighting fixtures for this application.

项目概要/摘要 这项研究的主要假设是，提供量身定制的照明干预 (TLI) 将提供成功的 用于促进昼夜节律牵引并治疗患有以下疾病的患者的代谢性疾病和炎症的方法 轻度认知障碍 (MCI) 和阿尔茨海默病 (AD) 以及阿尔茨海默病和相关痴呆症 （ADRD）。因此，拟议的研究有可能为了解两者之间的联系提供重要见解。 通过将昼夜节律破坏确定为 AD/ADRD 和 2 型糖尿病 (T2DM) 的关键组成部分 代谢障碍。它将开辟新的调查途径，因为这将增加以下可能性： 大脑胰岛素抵抗确实是昼夜节律紊乱的结果。正在进行的初步数据 研究表明光疗对睡眠和抑郁症有有益作用。如果结果呈阳性 据观察，改变家庭、辅助生活设施和服务的方式也存在潜力。 通过提供简单、实用、非药物的干预措施来促进疗养院的健康 AD 和轻度 AD MCI 患者的夹带、改善睡眠并减少代谢性疾病。 拟议研究的具体目标有两个。首先，随机、安慰剂对照、交叉 这项研究涉及 60 名生活在受控环境（即辅助生活设施和 疗养院），将调查是否暴露于旨在增加昼夜节律的 TLI 8 周 夹带（通过尿褪黑激素测量）改善睡眠（体动记录仪和问卷调查）、情绪 （问卷）、炎症标志物和代谢控制（口服葡萄糖耐量试验）进行比较 控制、昼夜节律不活动的光。其次，使用单臂、受试者间设计、安慰剂 在对照研究中，我们将调查长期（6 个月）暴露于 TLI 是否可以改善葡萄糖稳态并 30 名患有轻度 AD/ADRD 和睡眠障碍的患者的胰岛素敏感性，这些患者将从 西奈山 AD 研究中心 (ADRC) 并随机接受 TLI（或弱光控制治疗） 家。我们将测试 TLI 是否改善评估的胰岛素敏感性 (SI) 和葡萄糖处理 (SG) 通过频繁采样的 IV 葡萄糖耐量试验 (FSIVGTT) 来剖析机制 昼夜节律重新夹带可改善新陈代谢。 该项目的优势是相当大的，特别是考虑到没有测量仪器 个人昼夜节律光照模式。如果成功，这项研究将为实用、有效的研究开辟道路。 非药物治疗可显着减轻这两种疾病对社会的负担，更多 直接针对护理人员。独特、多元化的研究团队由老年医学领域的专家组成 精神病学、内分泌学以及光和昼夜节律研究，所有这些都可以直接接触临床 人口。该项目也具有高度转化性，因为 PI 将使用通过该项目收集的信息 研究与制造商合作开发适用于该应用的照明灯具。