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Surgery more profound effect than anesthesia on brain pathology, cognition in Alzheimer's mice
Date:9/14/2012

ociated 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.

"On the other hand," cautions Maryellen Eckenhoff, PhD, a neuroscientist on the team, "the brain vulnerability seen in the AD mice may not translate well to people." The AD mice used, like all current mouse models of Alzheimer disease, more closely resemble the situation in familial Alzheimer disease, which constitutes only a small minority of patients. She points out that it is not yet clear whether results from AD mouse models will represent patients who eventually get late-onset, or "sporadic" Alzheimer disease. These mice are, however, the current standard of choice for screening new drugs and have yielded considerable insight into Alzheimer pathogenesis.

The mechanism linking surgery and the cognitive effects seems to be inflammation. An inflammatory process is well known to occur as a result of surgery, at least outside the central nervous system. How this inflammatory process gains access to the brain, and accelerates AD pathology in a persistent way is still unclear.

Postoperative cognitive decline has not been convincingly demonstrated to persist after three months in most people, and whether it predicts later dementia is still unclear. This study suggests that in the setting of a vulnerable brain, the cognitive deficits after surgery might be irreversible.

However, the finding that inflammation is the underlying mechanism, immediately suggests a strategy for mitigating injury. "Human studies will
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert  

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Surgery more profound effect than anesthesia on brain pathology, cognition in Alzheimer's mice
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