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: 9927956
• 负责人: CHRISTOPH BUETTNER
• 金额: $ 32.09万
• 依托单位: RENSSELAER POLYTECHNIC INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-15 至 2020-10-11
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9927956
• 关键词: Aging; Agitation; Alzheimer' s Disease; Alzheimer' s disease patient; Alzheimer' s disease related dementia; Assisted Living Facilities; Behavior; Brain; Caregivers; Circadian Dysregulation; Circadian Rhythms; Clinical; Cognitive; Controlled Environment; Cross-Over Studies; Data; Dementia; Development; Disease; Elderly; Endocrinology; Epidemiology; Exposure to; General Population; Geriatric Psychiatry; Glucose; Glucose tolerance test; Goals; Home environment; Homeostasis; Hour; Human; Impairment; Inflammation; Insulin; Insulin Resistance; Intervention; Investigation; Light; Lighting; Link; Lipids; Literature; Manufacturer Name; 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; Placebos; Population; Predisposition; Quality of life; Questionnaires; Randomized; Research; Resistance development; Rest; Risk; Safety; Sampling; Sleep; Sleep disturbances; Societies; System; Testing; Work; actigraphy; arm; base; blood glucose regulation; burden of illness; circadian; depressive symptoms; design; diabetes risk; efficacy testing; glucose disposal; glucose tolerance; improved; inflammatory marker; 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.

项目摘要/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 促进昼夜节律夹带和治疗代谢疾病和炎症的手段 轻度认知障碍（MCI）和阿尔茨海默氏病（AD）和阿尔茨海默氏病和相关痴呆症 （ADRD）。因此，拟议的研究有潜力提供对之间联系的重要见解 通过识别昼夜节律的破坏作为关键组成部分，AD/ADRD和2型糖尿病（T2DM） 代谢障碍。它将开放新的调查途径，因为它会增加 脑胰岛素抵抗确实是昼夜节律破坏的结果。正在进行的初步数据 研究表明，光治疗对睡眠和抑郁症的有益作用。如果积极的结果是 观察到的，潜力也存在，以改变房屋，辅助生活设施的方式以及 通过提供简单，实用，非药理学干预措施来促进疗养院 夹带，改善睡眠并减少AD和轻度AD MCI患者的代谢疾病。 拟议研究的具体目的是两倍。首先，一个随机，安慰剂对照的跨界 研究涉及60名公元/ADRD患者，他们生活在受控环境中（即辅助生活设施和 疗养院），将调查是否有8周的TLI暴露于昼夜节日 夹带（通过尿致褪黑激素测量）改善了睡眠（Actraphy和问卷），情绪 （问卷），炎症标记和代谢控制（口服葡萄糖耐量测试）比较 为了控制，昼夜节光。其次，使用单臂，受试者之间的设计，安慰剂 - 对照研究，我们将研究长期（6个月）暴露于TLI是否可以改善葡萄糖稳态和 30例轻度AD/ADRD和睡眠障碍患者的胰岛素敏感性，他们将从 西奈山广告研究中心（ADRC），随机接收TLI（或昏暗的光控制处理） 家。我们将测试TLI是否改善了胰岛素敏感性（SI）和葡萄糖处置（SG）（SG） 通过经常采样的静脉注射葡萄糖耐量测试（FSIVGTT）通过 昼夜节律的重新进入可以改善新陈代谢。 该项目的优势是相当大的，特别是考虑到衡量仪器 个人昼夜节律曝光模式。如果成功，这项研究将为实用，有效 非药物治疗可显着减轻两种疾病的社会负担，更多 直接对照料者。独特的，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，所有人都可以直接进入临床 人口。该项目也很高度转化，因为PI将使用通过此信息收集的信息 与制造商合作开发此应用的照明设备的研究。