A randomized placebo-controlled trial of nicotinamide riboside in older adults with mild cognitive impairment
Miranda E Orr, Eithan Kotkowski, Paulino Ramirez, Darcy Bair-Kelps, Qianqian Liu, Charles Brenner, Mark S Schmidt, Peter T Fox et al.. GeroScience, 2023-11-23
Topic: Drug trials: efficacy and safety
Nicotinamide riboside (NR) increases blood levels of NAD+, a cofactor central to energy metabolism, and improves brain function in some rodent models of neurodegeneration. We conducted a placebo-controlled randomized pilot study with the primary objective of determining safety of NR in older adults with mild cognitive impairment (MCI). Twenty subjects with MCI were randomized to receive placebo or NR using dose escalation to achieve, and maintain, a final dose of 1 g/day over a 10-week study duration. The primary outcome was post-treatment change from baseline measures of cognition (Montreal Cognitive Assessment, MoCA). Predefined secondary outcomes included post-treatment changes in cerebral blood flow (CBF); blood NAD+ levels; and additional neurocognitive, psychometric, and physical performance tests. DNA methylation was assessed in peripheral blood mononuclear cells (PBMCs) as an exploratory outcome. The target NR dose was safely achieved as evidenced by a 2.6-fold increase in blood NAD+ in the NR group (p < 0.001, 95% CI [17.77, 43.49]) with no between-group difference in adverse event reporting. MoCA and other neurocognitive and psychometric metrics remained stable throughout the study. NR reduced CBF in the default mode network (DMN) with greatest differences observed in the left inferior parietal lobe (IPL) (DMN p = 0.013, μ = 0.92, 95% CI [0.23, 1.62]; left IPL p = 0.009, μ = 1.66, 95% CI [0.5, 2.82]). Walking speed in the placebo group significantly improved across the study duration suggestive of a practice effect but did not change in the NR group (p = 0.0402 and p = 0.4698, respectively). Other secondary outcome measures remained stable. Global methylation analyses indicated a modest NR-associated increase in DNA methylation and concomitant reduction in epigenetic age as measured by PhenoAge and GrimAge epigenetic clock analyses. In summary, NR significantly increased blood NAD+ concentrations in older adults with MCI. NR was well tolerated and did not alter cognition. While CBF was reduced by NR treatment, statistical significance would not have withstood multiple comparisons correction. A larger trial of longer duration is needed to determine the potential of NR as a strategy to improve cognition and alter CBF in older adults with MCI. ClinicalTrials.gov NCT02942888.
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APA 7th
Orr, M. E., Kotkowski, E., Ramirez, P., Bair-Kelps, D., Liu, Q., Brenner, C., et al. (2024). A randomized placebo-controlled trial of nicotinamide riboside in older adults with mild cognitive impairment. GeroScience. https://doi.org/10.1007/s11357-023-00999-9
Vancouver
Orr ME, Kotkowski E, Ramirez P, Bair-Kelps D, Liu Q, Brenner C, et al. A randomized placebo-controlled trial of nicotinamide riboside in older adults with mild cognitive impairment. GeroScience. 2024. doi:10.1007/s11357-023-00999-9. PMID: 37994989.
BibTeX
@article{orr2024-37994989,
author = {Orr, Miranda E and Kotkowski, Eithan and Ramirez, Paulino and Bair-Kelps, Darcy and Liu, Qianqian and Brenner, Charles and Schmidt, Mark S and Fox, Peter T and others},
title = {{A randomized placebo-controlled trial of nicotinamide riboside in older adults with mild cognitive impairment}},
journal = {GeroScience},
year = {2024},
doi = {10.1007/s11357-023-00999-9},
pmid = {37994989},
url = {https://doi.org/10.1007/s11357-023-00999-9}
}
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Key findings
- Walking speed in the placebo group significantly improved across the study duration suggestive of a practice effect but did not change in the NR group (p = 0.0402 and p = 0.4698, respectively).
- In summary, NR significantly increased blood NAD+ concentrations in older adults with MCI.
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Study details
- Evidence strengthHigh
How this study scored 79/100
Published in a peer-reviewed journal, and it is a randomised controlled trial. Scored zero for sample size and effect reported because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 44 of the 56 points we could judge it on, which is 79 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (GeroScience) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 11 / 12 | A randomised controlled trial (from PubMed type “Randomized Controlled Trial”) |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2024 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (pubmed indexes it as a clinical or observational study) |
| Randomised / blinded | 2 / 2 | Randomised and blinded or placebo-controlled (as stated in the record) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 37994989) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 44 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 44 of the 56 points we could judge it on is 79 out of 100. |
| Total | 79 / 100 | — |
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