Alzheimer's alarm over anesthetics

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GIVING elderly patients certain general anaesthetics could increase their risk of developing Alzheimer's disease and other memory and attention problems.

The suggestion arises from recent test tube and animal experiments. They also indicate that anaesthetists need to log more carefully the combinations and doses of the anaesthetics they give to patients, to allow the risks to be properly assessed.
The link between surgery and cognitive problems was first noted during the 1950s, but it was never clear whether postoperative cognitive dysfunction (POCD) was the result of the surgery itself or the anaesthetics, says Pravat Mandal of the University of Pittsburgh Medical School in Pennsylvania. It has been suggested that heart bypass surgery in particular could make the protective blood-brain barrier leaky, allowing immune tissue or unwanted debris into the brain.
Now animals studies and test tube experiments are beginning to show that certain anaesthetics reduce the rate at which brain cells are born and develop, a factor that seems to be important to normal memory function. They may also directly affect the rate at which beta amyloid proteins bind together. This could be worrying, as the formation of clumps or "plaques" of these proteins is characteristic of Alzheimer's disease and may contribute to brain cell death.
Last week at the annual meeting of the Society for Neuroscience in Atlanta, Georgia, Mandal revealed that the inhaled anaesthetics halothane and isoflurane encourage clumping of beta amyloid protein, as does the commonly used intravenous anaesthetic propofol, at least at higher concentrations. The findings back up a previous study in which Mandal used NMR spectroscopy to show that halothane interacts directly with a pocket in the beta amyloid protein, changing its shape and encouraging neighbouring proteins to bind. Just 6 hours of exposure to halothane is sufficient to trigger protein clumping similar to that seen in people with Alzheimer's, he says.
Although halothane is rarely used in North America or Europe, it is commonly used in Asia and Africa because it is very cheap. "It is a seriously deadly combination when an older person receives halothane," says Mandal, because as we get older we all have more beta amyloid in our brains. The other anaesthetics studied are more widely used in the US and Europe, often in combination, though these seem to take longer to exert their potentially deadly effects. The good news is that the intravenous anaesthetic thiopental (known as thiopentone in the UK) appears to have no effect on the proteins.
Andy Jenkins of Emory University in Atlanta, Georgia, who studies the mechanisms of anaesthetic action, agrees that there are now plenty of anecdotal reports about elderly relatives never being quite the same after going in for surgery.
The problems seem to be most often associated with elderly patients undergoing long procedures such as heart bypass surgery or hip replacement. The new findings are important, he says, because doctors have not always carefully recorded which anaesthetics are used for each patient, nor are the follow-up methods for recording cognitive decline standardised.
At the same meeting, Jeffrey Sall from the University of California, San Francisco, showed that giving isoflurane to 7-day-old rat pups had effects on memory that lasted until adulthood. Fewer new brain cells developed in the memory regions of anaesthetised rats compared with control rats, suggesting that a decline in the rate of new cell birth – which seems vital for normal memory function – may persist long after receiving anaesthetics.
Now the warning has been sounded, Mandal hopes that the dangers and benefits of each anaesthetic will be urgently studied. "The main focus should now be using an anaesthetic that does not have any undesirable and deadly effects," he says.