Postoperative cognitive dysfunction and neurodegeneration: From inflammation to precision medicine.

Brain Res Bull 2026

Lin X, Luo Y, Zhu Q

Abstract

Postoperative cognitive dysfunction (POCD) is a prevalent neurocognitive complication in elderly surgical patients, marked by memory, attention, and executive function impairments. Its pathophysiology involves neuroinflammation, blood-brain barrier disruption, mitochondrial dysfunction, and Alzheimer’s disease (AD)-like pathologies, including amyloid-beta accumulation and tau hyperphosphorylation. Although often reversible, persistent POCD may accelerate neurodegeneration in high-risk individuals, underscoring the need for early biomarkers and targeted therapies. This review synthesizes current evidence on POCD mechanisms, risk factors, and management. Key findings highlight the role of neuroinflammatory mediators (e.g., cytokines, microglial activation) and shared pathways with AD, such as synaptic dysfunction and neurotrophic deficits. Major risk factors include advanced age, genetic susceptibility (e.g., ApoE4), and pre-existing cognitive decline. Emerging interventions-anti-inflammatory agents (minocycline, dexmedetomidine), neuroprotectants (melatonin, IGF-1), and non-pharmacological strategies (BIS-guided anesthesia, exercise)-show promise. Precision medicine approaches, including tailored anesthesia and repurposed AD therapeutics, could further improve outcomes. In conclusion, POCD lies at the intersection of acute perioperative stress and chronic neurodegeneration. Future research should prioritize biomarker validation, individualized prevention, and long-term cognitive monitoring to address the growing burden of POCD in aging populations.

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