1.18.2007

Common Anesthetic linked to Alzheimer's
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The commonly used anesthetic isoflurane can lead to the death of brain cells and the production of amyloid-beta plaque, a hallmark of Alzheimer's disease, Harvard researchers report.

Their study appears in the January issue of the Journal of Gerontology, which is devoted to the problems of dementia and delirium. In the United States, delirium accounts for $7 billion per year in hospital expenses and more than $100 billion a year when rehabilitation, institutionalization and long-term care are added to the equation.

The Harvard study raises questions about the safety of isoflurane, which has been used for years for all ages of patients.

"Many people, especially the elderly, who have anesthesia suffer from postoperative cognitive dysfunction, scrambling and delirium that can last six hours or two weeks or months," said lead researcher Rudolph Tanzi, a professor of neurology at the Genetics and Aging Research Unit of the Massachusetts General Institute for Neurodegenerative Disease.

"To me, a big dose of isoflurane mimics a stroke or a bang to the head, and you don't want that as a risk factor for Alzheimer's disease at any age," Tanzi said.

In experiments with cells that had an amyloid-beta protein, Tanzi's team exposed them to isoflurane for six hours.

The researchers found that isoflurane caused these cells to die. "It also caused the cell to overproduce the toxic molecule responsible for the pathology of Alzheimer's disease, particularly amyloid-beta," Tanzi said.

This is a warning, Tanzi said. "Isoflurane may be one reason why the elderly are more prone to cognitive dysfunction following anesthesia," he said.

"Any trauma to the brain induces cell death. Isoflurane now joins that list of insults to the brain that can cause cell death and excessive production of this key molecule in Alzheimer's pathology," Tanzi. "This does increase the risk for Alzheimer's disease."

Tanzi believes that isoflurane should be avoided, when possible. "We don't have enough data yet to ban isoflurane," he said. "But I'm convinced enough that I won't let my mother have it. I would advise any family or friends to stay away from isoflurane," he said. "There is a lot of speculation here, and a lot of work needs to be done, but at this point I wouldn't take a chance."

Despite the findings, one expert doesn't agree that isoflurane is dangerous.

"Most of the studies that have been done have been done in isolated cell types," said Dr. Piyush Patel, a professor of anesthesiology at the University of California, San Diego. "Not only that, but the cells they are using are not normal cells."

Patel believes, however, that the findings are provocative enough that there needs to be further research on the issue. "Studies need to be done in cells that are closer to normal cells, and then in animals," he said.

Moreover, it isn't clear that this same effect would be seen in humans, Patel said. "Isoflurane has had a long history of safety in all aged patients, all the way from premature babies to octogenarians. There is absolutely no evidence right now in human beings that that drug is harmful," he said. "To extrapolate these findings to humans would be irresponsible."

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