Citicoline and NMN synergistically attenuate BCCAO-induced white matter damage and cognitive impairment by activating the SIRT1/TORC1/CREB pathway. They inhibit microglia activations, reduce proinflammatory cytokines (IL-1β, IL-6, and TNF-α), and increase anti-inflammatory mediators (e.g., IL-10). These findings highlight the neuroprotective effect of this combination. This evidence concerns the gene CREB1 and Cognitive impairment.