Effects of Anesthesia on Alzheimer’s Disease–Related Biomarkers and Postoperative Cognitive Outcomes: A Review

Cognitive changes after surgery, including postoperative delirium and postoperative neurocognitive dysfunction, are common in older adults. These observations have raised concerns that anesthetic exposure may interact with biological pathways associated with Alzheimer’s disease (AD). This review summarizes in vitro, preclinical, and clinical studies examining the relationship between anesthetic exposure, amyloid-beta, tau-related measures, and postoperative cognitive outcomes. Experimental studies suggest that selected volatile anesthetics can influence amyloid-beta aggregation, tau phosphorylation, phosphatase activity, and neuronal signaling. However, these effects vary according to the anesthetic agent, exposure conditions, temperature, animal model, and underlying susceptibility. Human studies have yielded conflicting results. Some report short-term changes in cerebrospinal fluid or blood biomarkers, whereas others find no sustained changes in AD-related biomarkers or no association between postoperative biomarker trajectories and cognitive decline. Interpretation is further complicated because amyloid-beta and phosphorylated tau are not specific to AD and may also reflect other neurodegenerative diseases, neuronal injury, inflammation, altered clearance, or perioperative physiological stress. Current evidence does not establish that anesthesia accelerates AD progression in humans. Nevertheless, pre-existing neurodegenerative vulnerability may increase the risk of postoperative delirium or cognitive decline. Larger longitudinal studies using multimodal biomarkers, nonsurgical controls, standardized cognitive outcomes, and long-term follow-up are needed to determine whether perioperative exposures influence AD-specific pathology or primarily produce transient and nonspecific markers of brain stress.