BioEd Online

One of the most commonly used anaesthetic drugs may cause chemical changes in the brain that promote Alzheimer's disease. Researchers have discovered that isofluorane, a widely used agent for general anaesthesia, triggers production of a protein linked to the disease when applied to cultured cells.

Although the results have not been replicated in the human body, they demonstrate how patients undergoing surgery would be at increased risk of dementia if the same chemical changes occur in their own brain cells.

"At this stage it is premature to tell everybody [that isofluorane] is dangerous to use," says Zhongcong Xie of the Institute for Neurodegenerative Disease at Massachusetts General Hospital in Charlestown, a member of the research team. He and his team are planning studies in mice as well as monitoring people to see whether anaesthetics do indeed raise the risk of Alzheimer's.

Patients undergoing general anaesthetic are typically knocked out and kept asleep using a combination of intravenous and inhaled, or 'volatile', drugs such as isofluorane. But even if a shadow were to fall over isofluorane, it wouldn't be a good idea to switch to just using intravenous drugs, Xie says, as this could be dangerous: it is much harder to make fine-scale adjustments to doses using this method.

Protein tangles

Xie and his colleagues treated cultured human neural cells with isofluorane, and found that the cells produced more of a protein called amyloid ß. In the brain, this protein accumulates and forms tangles that are linked to Alzheimer's. The researchers report their results in the Journal of Neuroscience¹.

Some elderly patients who have a general anaesthetic are known to develop 'post-operative cognitive dysfunction', in which they struggle to fully regain their mental faculties after their surgery, points out Mervyn Maze, an expert on anaesthetics at Imperial College, London.

The cause of this problem remains unclear, Maze adds. Previous surveys showed that elderly patients were likely to have cognitive problems after their surgery irrespective of whether they had received a local or general anaesthetic. And it may not be the anaesthetics to blame at all.

But the new findings swing the focus back onto volatile anaesthetics as a possible cause for this mental decline, Maze says. The symptoms, he notes, are similar to those of Alzheimer's.

Patient study

It will be essential to monitor patients to see whether they show similar signs of amyloid-ßproduction and mental decline after operations, Maze says. Cultured neural cells express different genes from those in the living brain, so you might not see the same results in patients. What's more, he adds, the effect might occur only in the most vulnerable brains, such as those of infants and the elderly.

Should further study confirm there is a problem, surgeons will have to seek an alternative volatile anaesthetic. One option is xenon gas, but this is much more expensive.

But worrying about alternatives might yet be premature, Xie argues. "I would say we should probably be alert, but we don't have any firm conclusions yet," he says. "We're working to get more data — the human data do not exist yet."