Abstract
With the rapidly aging population in Japan, the number of geriatric patients undergoing surgical procedures under anesthesia is expected to increase. Furthermore, postoperative neurocognitive disorders, such as postoperative delirium (POD) and cognitive dysfunction (POCD), are now well-recognized as the most frequent complications of surgery, especially in geriatric patients. More importantly, epidemiological studies consistently show that POD/POCD are not transient phenomena, but are associated with long-term disability and increased mortality rates. Although POD and POCD are considered distinct clinical entities, recent preclinical and clinical findings suggest that neuroinflammation is a common underlying mechanism involved in the development of these disorders. Neuroinflammation is characterized by microglia activation and under increased brain levels of pro-inflammatory cytokines, such as TNF-α and IL-1β. Particularly, microglia in a normal aged brain is reportedly shifted towards an inflammatory phenotype, known as “microglia priming”. The microglia priming in the hippocampus may make elderly surgical patients highly susceptible to the development of neuroinflammation and related cognitive disorders following a peripheral immune challenge. Furthermore, during the perioperative period, many factors including general anesthetics/sedatives, surgery-related systemic inflammation, an acute stress response, and nerve injury can contribute to the development of neuroinflammation via both neuronal and humoral pathways. Therefore, to prevent and manage postoperative neurocognitive disorders, it is crucially important to minimize these intrinsic or iatrogenic risk factors. This review provides a pathophysiological overview of postoperative neurocognitive disorders and current perspectives on prevention, treatment, and intervention strategies.
