Cognitive Impairment in Chronic Kidney Disease: Pathophysiological Mechanisms and Potential Modulatory Effects of...

Chronic kidney disease (CKD) is a prevalent systemic disorder associated with cognitive impairment affecting memory, executive function, and attention, reflecting a disruption of the kidney-brain axis. This narrative review synthesizes current evidence regarding the pathophysiological mechanisms underlying CKD-associated cognitive decline and evaluates the therapeutic potential of resveratrol as a neuroprotective strategy. Cognitive impairment in CKD arises from uremic toxin accumulation, chronic inflammation, oxidative stress, and cerebrovascular dysfunction, leading to disruption of the blood-brain barrier and impaired synaptic plasticity. Additional contributors include glymphatic dysfunction, mitochondrial impairment, and Klotho deficiency. Preclinical evidence indicates that resveratrol mitigates oxidative stress and neuroinflammation, enhances mitochondrial function via sirtuin-1/peroxisome proliferator-activated receptor gamma coactivator-1 signaling, improves endothelial function, and restores Klotho expression. However, clinical evidence remains limited and sometimes inconsistent. Resveratrol represents a biologically plausible therapeutic approach for CKD-related cognitive impairment, although further well-designed clinical studies are required to establish its efficacy and translational potential.