Esketamine for Treatment of Cognitive Decline in Alzheimer’s Disease: A Scoping Review of Pre-clinical Studies

Background/Objectives: Alzheimer's disease is a progressive neurodegenerative disorder leading to progressive cognitive decline. While the current pharmacological treatments provide some relief for other symptom domains, the cognitive decline remains a challenging symptom. This systematic review investigates preclinical and clinical literature supporting the use of esketamine for Alzheimer’s disease-associated cognitive decline (ADAC). Methods We searched PubMed, Google Scholar, Web of Science, Scopus, Embase, and Cochrane for relevant studies. Results We identified four preclinical studies supporting the use of esketamine in ADAC. These studies suggest that esketamine exerts its cognitive-enhancing effect through the activation of the Cannabinoid-2 receptor, the activation of the Brain-Derived Neurotrophic Factor signaling pathway, and the reduction of hippocampal Aβ42 and phosphorylated tau levels. Our search did not yield any clinical evidence to support this claim. Conclusion Preclinical studies suggest that esketamine holds promise as a potential therapeutic agent for ADAC due to its anti-inflammatory and neuroprotective properties. However, clinical studies are needed to confirm its efficacy and safety in human subjects before it can be considered for clinical application.