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

点击翻译按钮获取中文摘要

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.