Benefits of Nicotinamide Riboside Upon Cognition and Sleep

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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The Benefits of Nicotinamide Riboside Upon Cognition and Sleep in Older Veterans

Conditions
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Cognitive Impairment, Sleep Quality

Intervention / Treatment
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* Dietary Supplement: Nicotinamide riboside
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sleep Quality. Pittsburgh Sleep Quality Index (PSQI) global score >5 Exclusion Criteria: Dementia. Veteran Affairs - St. Louis University Mental Status questionnaire (VA-SLUMS) score <20

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A clinical trial, randomized controlled trial, double-blinded. Participants will be assigned to intervention (NR supplementation) or placebo groups.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Participants in the intervention group will receive 500mg of NR twice daily | Dietary Supplement: Nicotinamide riboside<br>* Nicotinamide riboside (NR) is a form of vitamin B3, which is found in fruits, vegetables, meat, and milk. NR is converted into nicotinamide adenosine dinucleotide NAD+. Low NAD+ levels have been linked to Alzheimer's disease and sleep disturbances.<br>* Other names: NR, vitamin B3;|
| Placebo Comparator: Placebo<br>Participants in the intervention group will receive 500mg of sham placebo twice daily | Dietary Supplement: Placebo<br>* The placebo pill will contain micro cellulose powder.<br>* Other names: Placebo pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sleep Quality Assessment | Sleep quality will be assessed with the Pittsburgh Sleep Quality Index , where global score >5 indicates poor sleep quality and global score <5 indicates good sleep quality. | Change from baseline to endpoint at 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive function | Cognitive function will be assessed with the Veterans Affairs St. Louis University Mental Health Status (VA-SLUMS), which contains 11 items designed to measure orientation, memory, attention, and executive function. Scores range from 0-30 with categories of unimpaired, mildly impaired, and impaired. | Change from baseline to endpoint at 12 weeks |