Benefits of Nicotinamide Riboside Upon Cognition and Sleep

Overview

Poor sleep quality and short sleep duration may be a mechanistic component of cognitive impairment in older adults, associated with a decline in brain-derived neurotrophic factor. Increasing the availability of nicotinamide adenine dinucleotide (NAD+) with supplementation of its precursor, nicotinamide riboside (NR), a form of vitamin B3 may increase the expression of brain-derived neurotrophic factor. This study proposes to examine the benefits of NR supplementation on sleep and cognitive function in older adults with comprehensive subjective and objective measures and to explore its impacts on serum brain-derived neurotrophic factor.

Ten percent of adults aged ≥ 65 years and fifty percent of adults ≥ 85 years exhibit cognitive impairment. Dementia treatment cost $277 billion in 2018 and is predicted to surpass $500 billion with the aged population reaching 70 million by 2030 in America. In addition, 50% of older adults experience poor sleep quality, including fragmented nighttime sleep, reduced sleep efficiency, and earlier bedtime and wake-up times. Consequently, millions of Americans are at risk for both cognitive impairment, including Alzheimer's Disease and other dementias, and disrupted sleep. Sleep disruptions alter underlying circadian rhythms and synaptic plasticity in the hippocampus, as well as reduce expression of brain-derived neurotrophic factor (BDNF) - elements associated with impaired memory, dementia, and Alzheimer's Disease. Importantly, sleep disturbances and mild cognitive impairment may appear several years before the development of clinical dementia. Therefore, interventions that improve sleep may prevent cognitive impairment and would have substantial clinical importance. Pre-clinical animal models suggest that enhancing the availability of nicotinamide adenine dinucleotide (NAD+) may reduce cognitive decline and support sleep quality by boosting mitochondrial function and BDNF expression. Additionally, supplementation with NAD+ precursor nicotinamide riboside (NR), a form of vitamin B3, improves cognition in aged mice. The hypothesis for this study is that NR supplementation will enhance cognition by improving objective sleep duration and sleep quality in older persons. To test the hypothesis, this study will measure the benefits of NR supplementation on sleep and cognition in older Veterans and determine the role of BNDF as a potential biomarker of sleep quality.