Mitochondrial dysfunction in postoperative cognitive dysfunction: From preclinical mechanisms to multimodal diagnostics and precision intervention

Abstract

Postoperative cognitive dysfunction (POCD) poses a significant clinical challenge with far-reaching implications for patient recovery and long-term quality of life. Growing evidence underscores the central role of mitochondrial dysfunction in the pathogenesis of POCD, uncovering an intricate interplay of molecular mechanisms that influence cognitive function. This study reviews the key mechanistic pathways involving mitochondria: bioenergetic impairment and metabolic irregularities, oxidative stress pathways and neuroinflammation, disruptions in calcium signaling, and deficiencies in mitochondrial quality control mechanisms-including kinetic abnormalities, defective mitophagy, and mitochondrial genetic material damage. Each of these pathways acts as a potential molecular nexus contributing to the cognitive decline in post-surgery, revealing the multifaceted nature of POCD progression. Furthermore, the review synthesizes recent advances in diagnostic and preventive strategies targeting mitochondrial dysfunction, bridging preclinical discoveries with clinical relevance. By delineating the role of mitochondria in the molecular landscape of POCD, this review not only clarifies the disease’s pathogenic foundations but also paves the way for future translational research in mitochondria-targeted diagnostics and interventions.