MICRONUTRIENT SUPPLEMENTATION AND FUNCTIONAL FOODS: Edited by Nathalie M. Delzenne and Henry C. LukaskiCan nicotinamide riboside protect against cognitive impairment?Braidy, Nady; Liu, YueAuthor Information Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia Correspondence to Nady Braidy, School of Psychiatry, Level 1, AGSM (G27 Gate, 11 Botany St, Kensington NSW 2052. Tel: +61 2 9385 8494; fax: +61 2 9382 3774; e-mail: [email protected] Current Opinion in Clinical Nutrition and Metabolic Care: November 2020 - Volume 23 - Issue 6 - p 413-420 doi: 10.1097/MCO.0000000000000691 Buy Metrics Abstract 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. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.