A syndrome called "post-operative cognitive decline" has been coined to refer to the commonly reported loss of cognitive abilities, usually in older adults, in the days to weeks after surgery. In fact, some patients time the onset of their Alzheimer's disease symptoms from a surgical procedure. Exactly how the trio of anesthesia, surgery, and dementia interact is clinically inconclusive, yet of great concern to patients, their families and physicians.
A year ago, researchers at the Perelman School of Medicine at the University of Pennsylvania reported that Alzheimer's pathology, as reflected by cerebral spinal fluid biomarkers, might be increased in patients after surgery and anesthesia. However, it is not clear whether the anesthetic drugs or the surgical procedure itself was responsible. To separate these possibilities, the group turned to a mouse model of Alzheimer's disease.
The results, published online this month in the Annals of Surgery, shows that surgery itself, rather than anesthesia, has the more profound impact on a dementia-vulnerable brain.
The team, led by Roderic Eckenhoff, MD, Austin Lamont Professor of Anesthesia, exposed mice with human Alzheimer disease genes, to either anesthesia alone, or anesthesia and an abdominal surgery. The surgery was similar to appendectomy or colectomy, very common procedures in humans. They found that surgery causes a lasting increase in Alzheimer's pathology, primarily through a transient activation of brain inflammation. Also, a significant cognitive impairment persisted for at least 14 weeks after surgery compared to controls receiving anesthesia alone. Neither surgery nor anesthesia produced changes in normal non-transgenic animals.
"In the mice, there was a clear and persistent decrement in learning and memory caused by surgery as compared with inhalational anesthesia - but only in the context of a brain made vulnerable by human Alzheimer-associated transgenes," notes Eckenhoff.
He also notes that at the time of surgery, the AD mice showed no outward symptoms of AD, despite having subtle evidence of ongoing neuropathology. "This timeline is analogous to both the age range and cognitive status of many of our patients presenting for a surgical procedure and suggests the window of vulnerability to surgery of the Alzheimer's brain extends into this pre-symptomatic period," says Eckenhoff. This period might be analogous to what is now called prodromal AD.