Sex differences and postoperative cognitive dysfunction: Unveiling biological mechanisms

Postoperative cognitive dysfunction (POCD) is a common neurological complication following surgery, particularly in older patients, with significant impacts on recovery, quality of life, and societal burden. As the aging population undergoes more surgical procedures, understanding the multifactorial risks associated with POCD is increasingly critical. While factors such as age, education level, and preexisting cognitive conditions are established risks, the role of biological sex in POCD remains underexplored. Emerging evidence highlights distinct sex differences in brain morphology, hormonal regulation, and neuroinflammatory responses, which may alter susceptibility to POCD. For instance, estrogen has been shown to exert neuroprotective effects under stress, and women may present greater vulnerability to inflammation-driven brain atrophy. Additionally, male carriers of the APOE4 allele exhibit worse postoperative cognitive outcomes, while female carriers appear relatively protected. This review aims to explore the interaction between biological sex and neuroinflammatory processes in the development of POCD. By delving into these mechanisms, the review seeks to shed light on sex-based disparities in POCD incidence and progression, offering new insights into its pathogenesis. Understanding these differences is vital for developing targeted prevention and treatment strategies, ultimately improving outcomes for both male and female patients while alleviating the strain on healthcare systems.