Activation of H3Rs mediates a series of intracellular signaling pathways that are involved in the pathogenesis of AD, including the Gαi/o-protein-coupled inhibition of AC (Lovenberg et al., 1999), downstream exaggeration of cognitive decline through transduction of cAMP/CREB (Moreno et al., 2011), and activation of PI3K/AKT/GSK3β signaling (Rapanelli et al., 2016). This evidence concerns the gene CREB1 and Mental deterioration.