Postoperative delirium and postoperative cognitive dysfunction: updates in pathophysiology, potential translational approaches to clinical practice and further research perspectives

Postoperative delirium, the onset of confusion/delirium during the early postoperative phase, is the most common postoperative complication in older adults and represents a medical emergency that requires immediate assessment and treatment. On the other hand, the term postoperative cognitive decline or dysfunction refers to a wide spectrum of clinical conditions featuring a decline in a variety of neuropsychological domains including memory, executive functioning, and speed of processing emerging week to months after anesthesia and surgery. Postoperative delirium and postoperative cognitive decline represent two distinct clinical entities along the continuum of cognitive impairment after anesthesia and surgery. All patients experiencing delirium does however not develop postoperative dysfunction and likewise all patients showing various degree of postoperative decline have not explicitly exhibited postoperative delirium. Although neuroinflammation seems to be main cause, the exact pathophysiology of both phenomena is very difficult to ascertain because it involves the crossroads of many mechanisms. This paper aimed to provide an update in the pathophysiology of these conditions with special attention to the roles of the neuroinflammation, the microglia activation, the surgical stress response, the impairment of neurotransmitter systems, and the direct neurotoxic effect of general anesthetic drugs. Potential translational approaches to clinical practice and further research perspectives are also given.