Study shows increased Alzheimer's biomarkers in patients after anesthesia and surgery

October 4, 2011, University of Pennsylvania School of Medicine

(Medical Xpress) -- The possibility that anesthesia and surgery produces lasting cognitive losses has gained attention over past decades, but direct evidence has remained ambiguous and controversial. Now, researchers at the Perelman School of Medicine at the University of Pennsylvania provide further evidence that Alzheimer's pathology may be increased in patients after surgery. The new research is published in the October 2011 issue of the journal Anesthesiology.

"We have long sought a clearer picture of the true impact of anesthesia and surgery on the central nervous system," said lead study author Roderic Eckenhoff, MD, Austin Lamont Professor of Anesthesia at Penn. "Although not definitive, this human study gives some credibility to the notion that anesthesia and surgery produce an inflammatory insult on the brain and accelerate chronic like Alzheimer's."

Clinical observation of postoperative in patients and studies in animals have long suggested that anesthetics could interact with Alzheimer , but the decades-long refractory period, when Alzheimer pathology is developing in the absence of detectable , has made research difficult.

With advances in diagnostic tests led by Penn Medicine's Leslie Shaw, PhD, professor of Pathology and Laboratory Medicine, there is now a validated biomarker test that is able to detect the presence of Alzheimer's disease (AD) biomarkers found in cerebral spinal fluid (CSF). This 'signature' combination of Alzheimer's disease indicators – amyloid beta and tau protein – can find disease markers before Alzheimer's symptoms appear and reliably predicts which patients will progress from mild cognitive impairment to full blown Alzheimer's disease. Generally speaking, highly increased CSF tau protein and decreased beta-amyloid are indicative of AD pathology.

To further examine the impact of anesthesia and surgery on CSF in real time, Dr. Eckenhoff and colleagues at Penn set out to analyze the 'signature' indicators of Alzheimer's disease by collecting CSF from patients undergoing routine surgical procedures. A total of 11 patients, all undergoing endoscopic nasal surgery, were included in the study.

At the beginning of the study, there was no evidence of cognitive impairment and infection, and no patients were taking (CNS)-active medications. The first, or baseline, CSF sample was taken at the beginning of the procedure. Another CSF sample was taken at the end of the procedure, and additional samples were taken at 6, 24, and 48 hours after that.

Mean CSF amyloid beta concentrations fluctuated by less than 10 percent in either direction and were statistically unchanged throughout the 48 hour postoperative period. However, total tau was significantly increased after 6 hours, and was still increasing at 48 hours when most of the spinal catheters were removed. An injury biomarker, S100B, and inflammatory biomarkers Interleukin-10, IL-6, and tumor necrosis factor, were also significantly increased over time after surgery suggesting neuroinflammation as a possible mechanism.

These findings together suggest significant changes in CSF biomarkers in a direction that is consistent with Alzheimer's disease progression and enhanced neuroinflammation.

The researchers also found that the use of the inhaled volatile anesthetic sevoflurane was associated with significantly higher CSF concentrations of inflammatory biomarkers than was associated with injectable anesthetics such as propofol and remifentanil. Although this suggests anesthetic management might make a difference in post-surgery neuroinflammation, the authors caution the study was too small to make a definitive connection; larger studies are needed to examine this concept.

"The evidence for anesthesia per se being responsible for the changes we saw in this study is not definitive – in fact, our work in animal models of Alzheimer's is beginning to suggest that the surgical procedure itself produces a larger effect than ," said Dr. Eckenhoff. "The next step in this line of research is to determine whether anesthetic management can modulate the neuroinflammation caused by surgery, whether this brief inflammatory insult can actually change the trajectory of something like AD, and given that is usually not strictly elective, development of a strategy to reduce the inflammatory insult to the brain.

More information:

Related Stories

Recommended for you

Rocky start for Alzheimer's drug research in 2018

January 19, 2018
The year 2018, barely underway, has already dealt a series of disheartening blows to the quest for an Alzheimer's cure.

Alzheimer's disease: Neuronal loss very limited

January 17, 2018
Frequently encountered in the elderly, Alzheimer's is considered a neurodegenerative disease, which means that it is accompanied by a significant, progressive loss of neurons and their nerve endings, or synapses. A joint ...

Anxiety: An early indicator of Alzheimer's disease?

January 12, 2018
A new study suggests an association between elevated amyloid beta levels and the worsening of anxiety symptoms. The findings support the hypothesis that neuropsychiatric symptoms could represent the early manifestation of ...

One of the most promising drugs for Alzheimer's disease fails in clinical trials

January 11, 2018
To the roughly 400 clinical trials that have tested some experimental treatment for Alzheimer's disease and come up short, we can now add three more.

Different disease types associated with distinct amyloid-beta prion strains found in Alzheimer's patients

January 9, 2018
An international team of researchers has found different disease type associations with distinct amyloid-beta prion strains in the brains of dead Alzheimer's patients. In their paper published in Proceedings of the National ...

Advances in brain imaging settle debate over spread of key protein in Alzheimer's

January 5, 2018
Recent advances in brain imaging have enabled scientists to show for the first time that a key protein which causes nerve cell death spreads throughout the brain in Alzheimer's disease - and hence that blocking its spread ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.