A systematic review of the therapeutic potential of nicotinamide adenine dinucleotide precursors for cognitive diseases in preclinical rodent models

Abstract

This systematic review sought to assess the impact of nicotinamide adenine dinucleotide (NAD⁺) precursors on cognitive impairments in several diseases in rat/mouse models. Accumulating evidence suggests that inflammation, apoptosis, oxidative stress responses, and mitochondrial dysfunction are potential factors of cognitive deficits in aging, Alzheimer's disease (AD), diabetes, traumatic brain injury (TBI), vascular dementia (VAD), and schizophrenia. NAD⁺ precursors have received increased interest due to their unique molecular structure targets antioxidant and inflammatory pathways and mitochondrial function. The PubMed, Scopus, Google Scholar, Embase, and Web of Science databases were searched through May 30, 2024. Studies investigating the effect of NAD⁺ precursors on cognitive impairments in rodent models were included. Two reviewers independently extracted and evaluated the data. The PRISMA guidelines for reporting systematic reviews were followed. Thirty preclinical studies were included in the review. Studies have revealed that treatment with NAD⁺ rescues cognitive deficits by inhibiting inflammation, oxidative stress, and apoptosis and improving mitochondrial function. Preclinical evidence has demonstrated that treatment with NAD⁺ precursors may be more effective in learning and memory recovery in AD, TBI, diabetes, aging, VAD, and schizophrenia. The outcomes of this investigation may lead to additional studies on the use of NAD⁺ precursors for treating human cognitive decline.