Supplementation with NAD+ and Its Precursors to Prevent Cognitive Decline across Disease Contexts

The preservation of cognitive ability by increasing nicotinamide adenine dinucleotide (NAD(+)) levels through supplementation with NAD(+) precursors has been identified as a promising treatment strategy for a number of conditions; principally, age-related cognitive decline (including Alzheimer's disease and vascular dementia), but also diabetes, stroke, and traumatic brain injury. Candidate factors have included NAD(+) itself, its reduced form NADH, nicotinamide (NAM), nicotinamide mononucleotide (NMN), nicotinamide riboside (NR), and niacin (or nicotinic acid). This review summarises the research findings for each source of cognitive impairment for which NAD(+) precursor supplementation has been investigated as a therapy. The findings are mostly positive but have been made primarily in animal models, with some reports of null or adverse effects. Given the increasing popularity and availability of these factors as nutritional supplements, further properly controlled clinical research is needed to provide definitive answers regarding this strategy's likely impact on human cognitive health when used to address different sources of impairment.