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.

项目概要/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 (NR) 对轻度认知中生物能量代谢、氧化应激和认知的影响 损伤和轻度阿尔茨海默氏痴呆”。主要研究将评估 NR 补充剂对健康的影响。 氧化烟酰胺腺嘌呤二核苷酸 (NAD+) 水平和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大脑中的氧化应激 (AD)。该研究将使用 NAD+ 和氧化还原比的变化作为主要结果以及 CK/ATPase 的变化。 母研究还将评估大脑中的活性和谷胱甘肽水平作为次要结果。 NR 补充剂对情绪和功能的影响通过情绪、认知、 然而，这些临床和功能状态标志物的结果测量是 所有自我报告或观察者报告的措施均受到相关限制，包括较少的数据点， 回忆偏差、应答者偏差，需要观察者在场和参与，并且不包括任何措施 使用体内连续测量捕获变化。 我们提出了一种利用连续传感器数据来增强当前结果测量的新颖方法 使用名为 Emerald 的传感器来促进功能和情绪的数字表型分析。 信号可绘制 AD 患者的运动、空间位置和睡眠模式，无需直接交互 或联系并可以收集连续的被动行为数据。 提取（i）睡眠效率，（ii）步态速度，以及（iii）昼夜节律 Emerald 设备还可以跟踪空间。 生活环境中的位置以及运动的数量水平和模式，而这些又是 这些变量将促进连续的、时间密集的和高度生态有效的活动。 评估功能的日常变化以增强当前收集的数据。 还将允许行为/功能变化的连续纵向映射和趋势比较 每个单独变量的变化。 我们将在同意的研究对象的生活环境中部署 Emerald 设备并收集数据 尽管该研究需要在家长试验期间进行访问， 基线、6 周和 12 周，Emerald 将按时间顺序跟踪两次访问之间的功能和情绪 Emerald 设备的行为模式和功能变化将受到影响。 由于样本量较小，这是探索性的，但生成的数据。 使用数字表型分析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、成像标记物和现实世界功能/临床结果 在未来的 AD 和轻度认知障碍研究中。