Perioperative neurocognitive disorders: the importance of global systemic interactions

Perioperative neurocognitive disorders (PNDs) are a spectrum of cognitive impairments that can occur after anaesthesia and surgery, most often in older adults. They are linked to worse outcomes and higher mortality. Despite several proposed mechanisms, effective prevention and treatment remain limited, suggesting that key triggers of PNDs remain unknown or that our understanding of PND pathophysiology is incomplete. The review article by Ba and colleagues highlights the role of extrasynaptic γ-aminobutyric acid type A (GABA_A) receptors in PNDs, including their structure, function, and potential roles in PNDs after exposure to anaesthesia and surgery. Current experimental approaches focus on PND contributors in isolation. Further advances in understanding the complex systemic neurobehavioural interactions required to perform cognitive tasks, including integration of the known exposures and risk factors for PNDs with age- and pathology-related changes in the neural circuits underlying cognition, will facilitate development of mechanism-based treatments for PNDs.