Effects of Orally Administered Nicotinamide Riboside on Bioenergetic Metabolism, Oxidative Stress and Cognition in Mild Cognitive Impairment and Mild Alzheimer's Dementia

项目摘要/摘要 这项研究将作为对目前NIA资助的研究的补充，即口服给药的影响 烟酰胺核苷对轻度认知障碍患者能量代谢、氧化应激及认知功能的影响 损害和轻度阿尔茨海默氏症“。初步研究将评估NR补充剂对 氧化烟酰胺腺嘌呤二核苷酸(NAD+)水平与线粒体功能下游标志物 轻度认知障碍(MCI)和轻度阿尔茨海默病患者的脑内氧化应激 (Ad)。这项研究将使用NAD+和氧化还原比率的变化作为主要结果和CK/ATPase的变化 大脑中的活性和谷胱甘肽水平是次要结果。家长研究还将评估 补充NR对情绪和功能的影响，通过标准化的情绪，认知， 和日常运作。然而，这些临床和功能状态标记物的结果衡量标准是 受到相关限制的所有自我报告或观察员报告的衡量标准，包括较少的数据点， 召回偏差，响应者偏差，需要观察员在场和参与，不包括以下措施 通过活体连续测量捕捉变异。 我们提出了一种新的方法来利用连续的传感器数据来增强当前的结果度量 为了方便使用名为Emerald的传感器对功能和情绪进行数字表型分析。翡翠使用无线电 信号映射AD患者的运动、空间位置和睡眠模式，不需要直接交互 或联系，并可以收集连续的被动行为数据。定制的机器学习算法将 摘录(I)睡眠效率、(Ii)步态速度和(Iii)昼夜节律。Emerald设备还可以跟踪空间 在生活环境中的位置，并量化运动的水平和模式，这反过来又是 精神运动活动。这些变量将促进持续的、时间密集的和高度生态有效的 对日常运作变化进行评估，以加强目前收集的数据。传感器数据 还将允许连续绘制行为/功能变化的纵向图，并比较 每个单独变量的变化。 我们将在同意研究对象的生活环境中部署Emerald设备并收集数据 在他们参加父母试验期间，对睡眠和行为的影响。虽然这项研究需要访问 基线，6周和12周，翡翠将跟踪功能和两次访问之间的情绪，按时间顺序 NR给药后的行为模式和功能变化。翡翠设备将是 部署在40名研究参与者中。由于样本量较小，这是探索性的，但生成的数据 使用数字表型将使我们能够开发和测试关于NR之间关系的假说 补充剂、生物能量学/氧化应激、成像标志物和真实世界功能/临床结果 在未来对AD和轻度认知障碍的研究中。

Project Summary/Abstract This study will serve as a supplement to the current NIA funded study “Effects of Orally Administered Nicotinamide Riboside (NR) on Bioenergetic Metabolism, Oxidative Stress and Cognition in Mild Cognitive Impairment and Mild Alzheimer’s Dementia”. The primary study will assess the effect of NR supplementation on oxidized nicotinamide adenine dinucleotide (NAD+) levels and downstream markers of mitochondrial function and oxidative stress in the brain of patients with mild cognitive impairment (MCI) and mild Alzheimer’s Disease (AD). The study will use NAD+ and redox ratio changes as the primary outcome and changes in CK/ATPase activity and glutathione levels in the brain as the secondary outcome. The parent study will also assess the impact of NR supplementation on mood and functioning as measured by standardized tests of mood, cognition, and daily functioning. However, these outcome measures for these markers of clinical and functional status are all self- or observer-reported measures that are subject to associated limitations, including fewer data points, recall bias, responder bias, require the presence and engagement of an observer, and include no measures to capture variations using continuous measurement in vivo. We propose a novel approach to augment the current outcome measures with continuous sensor data to facilitate digital phenotyping of functioning and mood using a sensor called Emerald. Emerald uses radio signals to map motion, spatial location and sleep patterns in patients with AD and requires no direct interaction or contact and can collect continuous passive behavioral data. Customized machine-learning algorithms will extract (i) sleep efficiency, (ii) gait speed, and (iii) diurnal rhythm. The Emerald device can also track spatial location within the living environment and quantify levels and patterns of motion, which in turn are markers of psychomotor activity. These variables will facilitate a continuous, temporally dense and highly ecologically valid assessment of day-to-day variations in functioning to augment the data currently being collected. Sensor data will also allow continuous longitudinal mapping of behavioral/functional changes and comparison of trends of change in each individual variable. We will deploy the Emerald device in the living environment of consenting study subjects and collect data on sleep and behavior for the duration of their enrolment in the parent trial. While the study requires visits at baseline, 6 weeks and 12 weeks, the Emerald will track functioning and mood between visits, chronological patterns of behavior, and functional change in response to NR administration. The Emerald device will be deployed in forty study participants. Due to the small sample size, this is exploratory, but the data generated using digital phenotyping will enable us to develop and test hypotheses about the relationship between NR supplementation, bioenergetics/oxidative stress, imaging markers, and real-world functioning/clinical outcomes in future studies of AD and mild cognitive impairment.