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

项目总结/摘要 这项研究的主要假设是，提供定制的照明干预（TLI）将提供一个成功的 用于促进昼夜节律诱导和治疗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）和阿尔茨海默病及相关痴呆 （ADRD）。因此，拟议的研究有可能为以下方面的联系提供重要的见解： AD/ADRD和2型糖尿病（T2 DM），通过确定昼夜节律的破坏作为 代谢障碍这将开辟新的调查途径，因为这将增加以下可能性： 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，光治疗对睡眠和抑郁症有有益的影响。如果结果为阳性， 观察到，也存在着改变家庭，辅助生活设施， 疗养院通过提供简单，实用，非药物干预来促进 夹带，改善睡眠，并减少AD和轻度AD MCI患者代谢疾病。 拟议研究的具体目标有两个方面。首先，随机，安慰剂对照，交叉 一项涉及60名生活在受控环境中的AD/ADRD患者的研究（即，辅助生活设施和 疗养院），将调查是否8周暴露于TLI，旨在增加昼夜节律 夹带（通过尿褪黑激素测量）改善睡眠（活动记录和问卷调查），情绪 （问卷调查），炎症标志物和代谢控制（口服葡萄糖耐量试验）比较 到一个控制，昼夜节律不活跃的光。第二，采用单组受试者间设计，安慰剂- 对照研究，我们将研究长期（6个月）暴露于TLI是否改善葡萄糖稳态， 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AD研究中心（ADRC），并随机接受TLI（或昏暗灯光对照治疗）， 回家我们将测试TLI是否改善胰岛素敏感性（SI）和葡萄糖处置（SG） 通过频繁采样的IV葡萄糖耐量试验（FSIVGTT）， 这种昼夜节律的再夹带改善了新陈代谢。 这个项目的优势是相当大的，特别是考虑到没有测量仪器， 个人昼夜光照模式。如果成功的话，这项研究将为一项切实有效的 非药物治疗，以显着减少这两种疾病对社会的负担， 直接影响到看护者独特的、多样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，光和昼夜节律研究，所有这些都可以直接进入临床 人口这个项目也是高度翻译的，因为PI将使用通过这个项目收集的信息。 研究与制造商合作，开发用于此应用的照明灯具。

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.