Current research is focused on perioperative neurocognitive disorders in a vulnerable brain. Our recent studies have shown that surgery produces long-term cognitive impairment in pre-symptomatic Alzheimer mice, possibly due to the transient increase in neuroinflammation and an impaired immune response. However, this effect can be modulated by the anesthetic, with propofol resulting in less cognitive dysfunction than the inhaled anesthetic, isoflurane. In humans, we found significant changes in Alzheimer biomarkers in the CSF of older patients during the perioperative period. Further research is underway to examine ways to modulate neuroinflammation after surgery and major illness.