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A randomized placebo-controlled trial of nicotinamide riboside in older adults with mild cognitive impairment

Pilot RCT (n=20 MCI) of escalating oral NR to 1 g/day for 10 weeks versus placebo: blood NAD+ rose ~2.6-fold on NR with similar adverse-event reporting to placebo, while MoCA and other cognitive/psychometric primaries did not differ between groups.

Design

  • Population: 20 older adults with MCI (10 NR / 10 placebo)
  • Dose: escalating NR to 1 g/day maintained through 10 weeks
  • Primary: MoCA change; secondary: CBF, blood NAD+, other neurocognitive tests; exploratory: PBMC DNA methylation / epigenetic clocks

Headline outcomes (abstract)

  • Blood NAD+: ~2.6× increase in NR arm (p < 0.001; 95% CI for fold-change reported in abstract)
  • MoCA / neurocognitive metrics: no between-group cognitive benefit—stable in both arms per summary
  • CBF (DMN / left IPL): NR-associated reductions with p values that authors note would not survive multiplicity correction

Evidence hygiene

Pilot scale and industry-supplied NR—read alongside larger NR PAD and long-COVID trials on the same precursor protocol family.

Publication

Orr ME, et al. Geroscience. 2024 Feb;46(1):665-682. Epub 2023 Nov 23. PMID 37994989.

Outcomes

  • NAD+ Level
    160
    % (Percent Change)
  • MoCA and other primary neurocognitive metrics did not differ between NR and placebo through 10 weeks—no demonstrated cognitive efficacy despite NAD+ rise.
View original paper →