A randomized placebo-controlled trial of nicotinamide riboside in older adults with mild cognitive impairment.
Dementia
Geroscience
Mild cognitive impairment
NAD
Nicotinamide riboside
Placebo-controlled trial
Journal
GeroScience
ISSN: 2509-2723
Titre abrégé: Geroscience
Pays: Switzerland
ID NLM: 101686284
Informations de publication
Date de publication:
23 Nov 2023
23 Nov 2023
Historique:
received:
04
09
2023
accepted:
24
10
2023
medline:
23
11
2023
pubmed:
23
11
2023
entrez:
23
11
2023
Statut:
aheadofprint
Résumé
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.
Identifiants
pubmed: 37994989
doi: 10.1007/s11357-023-00999-9
pii: 10.1007/s11357-023-00999-9
doi:
Banques de données
ClinicalTrials.gov
['NCT02942888']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NCATS NIH HHS
ID : TL1TR002647
Pays : United States
Organisme : NIA NIH HHS
ID : P30AG044271
Pays : United States
Informations de copyright
© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
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