Can nicotinamide riboside protect against cognitive impairment?

Curr Opin Clin Nutr Metab Care. 2020 Nov;23(6):413-420. doi: 10.1097/MCO.0000000000000691.


Purpose of review: The present review aims to address the clinical benefits of using nicotinamide riboside, a precursor to the essential pyridine nucleotide, nicotinamide adenine dinucleotide (NAD+) as a therapeutic agent to attenuate age-related cognitive decline.

Recent findings: Oral supplementation with nicotinamide riboside can inhibit the accumulation of pathological hallmarks of Alzheimer's disease and improve learning and memory in various murine models for dementia. Nicotinamide riboside can also reduce DNA damage, neuroinflammation, apoptosis, and improved hippocampal synaptic plasticity in diabetic mice, and another Alzheimer's disease mouse model. The cognitive benefits of nicotinamide riboside in Alzheimer's disease models may be modulated in part by upregulation of proliferator-activated-γ coactivator 1α-mediated β-secretase 1(BACE-1) ubiquitination and degradation, preventing Aβ production in the brain. Nicotinamide riboside also maintained blood-brain barrier integrity and maintained the gut microbiota in a mouse model for cerebral small vessel disease and alcohol-induced depression, respectively. Oral nicotinamide riboside has been shown to be bioavailable and well tolerated in humans with limited adverse effects compared to other NAD+ precursors.

Summary: Oral nicotinamide riboside may represent a promising stratagem to improve cognitive decline during 'normal' ageing, Alzheimer's disease and other diseases. Results from recent clinical trials are needed to enumerate the preclinical benefits in humans.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / prevention & control
  • Alzheimer Disease / therapy*
  • Amyloid Precursor Protein Secretases / metabolism
  • Animals
  • Aspartic Acid Endopeptidases / metabolism
  • Brain / metabolism
  • Cognitive Aging / physiology*
  • Cognitive Dysfunction / prevention & control
  • Cognitive Dysfunction / therapy*
  • Dietary Supplements*
  • Disease Models, Animal
  • Humans
  • Mice
  • Niacinamide / administration & dosage
  • Niacinamide / analogs & derivatives*
  • Pyridinium Compounds / administration & dosage*


  • Pyridinium Compounds
  • nicotinamide-beta-riboside
  • Niacinamide
  • Amyloid Precursor Protein Secretases
  • Aspartic Acid Endopeptidases
  • BACE1 protein, human