Experts recently have shed light on the link between general anesthetics and cognitive problems.
Anesthetics have been thought to cause cognitive dysfunction for a long time — the link was first highlighted in the 1950s. But it was never clear whether “postoperative cognitive dysfunction” was the result of the anesthetics or a side effect of the surgery. Further study has implicated the anesthetics themselves.
New research suggests that inhaled anesthetics bring a greater risk of Alzheimer’s disease than those given intravenously. This is because inhaled anesthetics are linked more closely with the formation of Alzheimer’s-related plaques in the brain.
A research team from the University of Pittsburgh Medical Center examined possible links between anesthetics and plaques on the molecular level, using nuclear magnetic resonance (NMR) spectroscopy. By employing this technique, Pravat K. Mandal Ph.D. and colleagues could observe the molecular buildup of amyloid beta peptide when animals in lab tests were given different anesthetics commonly used in surgery.
Mandal noted that “[O]ur prior research had shown in molecular models that anesthetics may play a role by causing amyloid beta peptides to clump together. Amyloid beta peptide is the major component of senile plaques, which accumulate in the brain of a patient with Alzheimer’s disease. In this study, we set out to see why this was happening and to determine if any one form of anesthesia might be a safer option than another.”
The researchers looked at the inhaled anesthetics halothane and isoflurane, and the intravenous anesthetics propofol and thiopental. Halothane is an older anesthetic and is not commonly used in the United States or Europe but is used in some other countries because it is relatively cheap. Isoflurane use is now starting to decline, often being replaced with propofol. However, it is economical, as it is no longer patented.
The intravenous anesthetic propofol, also called Diprivan, is commonly used today. In this study, it was linked to beta amyloid protein buildup only at concentrations higher than normally used on patients for anesthesia. Thiopental, a rapid-acting barbiturate, is widely used during the first step (induction) of anesthesia, and considered safe.
Study results, published in the journal Biochemistry were “strikingly different” between the inhaled and injected anesthetics. The inhaled drugs (halothane and isoflurane) caused much higher levels of amyloid beta buildup. Halothane appeared to interact with a specific location on the beta amyloid protein, encouraging other proteins to bind. Propofol had this effect only at high concentrations, and thiopental did not have this effect at all, even at high concentrations. The paper also outlines the exact molecular process of the interaction between anesthetics and amyloid beta peptide.
The researchers called for clinical studies on the interaction between anesthetics and amyloid beta. If the same pattern is true for humans, they said, this adds to the evidence that anesthetics may lead to amyloid plaques, which may trigger earlier memory problems.
Earlier findings
Scientists at the 2006 Annual Meeting of the Society for Neuroscience in Atlanta concluded that halothane and isoflurane — and propofol, in higher concentrations — can reduce the rate at which brain cells are “born” and develop as well as affect the rate of beta amyloid buildup. It is believed that this also affects memory centers in the brain.
References
Mandal P. K., Williams J. P. and Mandal R. Molecular understanding of alphabeta peptide interaction with isoflurane, propofol, and thiopental: NMR spectroscopic study. Biochemistry, Vol. 46, January 23, 2007, pp. 762-71.
Philips H. Alzheimer’s alert over anaesthetics. New Scientist, Issue No. 2575, October 28, 2006.
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