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

口服烟酰胺核苷对轻度认知障碍和轻度阿尔茨海默氏痴呆患者生物能代谢、氧化应激和认知的影响

• 批准号: 10394467
• 负责人: FEI DU
• 金额: $ 31.4万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10394467
• 关键词: ATP phosphohydrolase; Administrative Supplement; Alzheimer' s Disease; Area; Assisted Living Facilities; Bed Occupancy; Behavior; Behavioral; Bioenergetics; Biological Assay; Blood; Brain; COVID-19; Chronology; Clinical; Cognition; Cognitive; Color; Communities; Consent; Custom; Data; Dementia; Devices; Diurnal Rhythm; Environment; Funding; Future; Gait speed; Glutathione; Hour; Image; Individual; Location; Maps; Measurement; Measures; Metabolism; Mitochondria; Monitor; Moods; Motion; NADH; Nicotinamide adenine dinucleotide; Oral; Outcome; Outcome Measure; Oxidation-Reduction; Oxidative Stress; Oxides; Parents; Participant; Patients; Pattern; Persons; Phenotype; Physiological; Protocols documentation; Questionnaires; Radio; Reporting; Research Personnel; Sample Size; Signal Transduction; Sleep; Standardization; Study Subject; Technology; Testing; Time; Variant; Visit; Work; base; daily functioning; digital; functional independence; functional status; handheld mobile device; imaging biomarker; improved; in vivo; machine learning algorithm; mild cognitive impairment; neuroimaging; nicotinamide riboside supplementation; nicotinamide-beta-riboside; novel strategies; primary outcome; response; secondary outcome; sensor; serial imaging; sleep behavior; sleep pattern; standardize measure; tool; trend; wearable device

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.

项目总结/摘要 这项研究将作为目前NIA资助的研究“口服给药的影响”的补充。 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 损伤和轻度阿尔茨海默氏痴呆症”。主要研究将评估NR补充剂对 氧化型烟酰胺腺嘌呤二核苷酸（NAD+）水平和线粒体功能的下游标志物 轻度认知障碍（MCI）和轻度阿尔茨海默病患者大脑中的氧化应激 （AD）。本研究将使用NAD+和氧化还原比率变化作为主要结局， 活动和谷胱甘肽水平作为次要结果。母研究还将评估 NR补充剂对情绪和功能的影响，通过情绪，认知， 和日常功能。然而，这些临床和功能状态标志物的这些结果测量是 所有自我报告或自我报告的测量都受到相关限制，包括数据点较少， 回忆偏差，反应者偏差，需要观察者的存在和参与，并且不包括任何措施， 使用体内连续测量捕获变化。 我们提出了一种新的方法，以增加目前的结果措施与连续的传感器数据 用一种叫做Emerald的传感器来帮助对功能和情绪进行数字表型分析。翡翠使用无线电 信号来映射AD患者的运动、空间位置和睡眠模式，并且不需要直接交互 或者接触，并且可以收集连续的被动行为数据。定制的机器学习算法将 提取（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 心理活动这些变量将促进一个连续的，时间密集的和高度生态有效的 评估日常运作变化，以增加目前正在收集的数据。传感器数据 还将允许行为/功能变化的连续纵向映射和 每个变量的变化。 我们将在知情同意的研究受试者的生活环境中部署Emerald设备并收集数据 在父母试验期间的睡眠和行为。虽然这项研究需要访问 基线、6周和12周时，Emerald将按时间顺序跟踪访视之间的功能和情绪 行为模式和对NR给药的功能变化。Emerald设备将 在40名研究参与者中部署。由于样本量小，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有关NR之间关系的假设， 补充剂、生物能量学/氧化应激、成像标记物和真实世界功能/临床结局 在未来的AD和轻度认知障碍的研究中。