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

> **NIH NIH R01** · MCLEAN HOSPITAL · 2021 · $313,981

## Abstract

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 mark...

## Key facts

- **NIH application ID:** 10394467
- **Project number:** 3R01AG066670-02S1
- **Recipient organization:** MCLEAN HOSPITAL
- **Principal Investigator:** FEI DU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $313,981
- **Award type:** 3
- **Project period:** 2020-05-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10394467

## Citation

> US National Institutes of Health, RePORTER application 10394467, Effects of Orally Administered Nicotinamide Riboside on Bioenergetic Metabolism, Oxidative Stress and Cognition in Mild Cognitive Impairment and Mild Alzheimer's Dementia (3R01AG066670-02S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10394467. Licensed CC0.

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