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Two Agents Fail to Fight Off Alzheimer's

Little or no benefit seen from Aricept or Vitamin E in much-awaited trial

WEDNESDAY, April 13, 2005 (HealthDay News) -- Two compounds that experts had hoped might slow or prevent Alzheimer's disease apparently have little or no effect.

The results from a long-awaited trial found vitamin E did not slow progression from mild cognitive impairment to Alzheimer's, as had been hoped. Nor did donepezil (Aricept) display any benefit over three years, although it was associated with a lower rate of progression to Alzheimer's over the first year of use.

"Everyone thought vitamin E would work better earlier, but there's nothing there," said Dr. Deborah Blacker, author of an editorial which accompanies the article in the June 9 issue of the New England Journal of Medicine.

"That's tremendously disappointing," she said.

The Aricept findings were not so absolutely negative but, according to Blacker, "there's no resounding sense that it's beneficial. There is some benefit, and patients could certainly choose to discuss it with their doctor."

"It's sort of a moderate disappointment," added Dr. Thomas M. Wisniewski, an associate professor of neurology, pathology and psychiatry at New York University School of Medicine. "We weren't expecting vitamin E to have much of an effect, and Aricept was likely to have a little bit of an effect."

The findings are being released early to coincide with a presentation being made April 13 at the annual meeting of the American Academy of Neurology in Miami Beach, Fla. The study was funded by the National Institute on Aging and by drug makers Pfizer Inc. and Eisai Inc., which together market Aricept.

Mild cognitive impairment (MCI) is generally considered to be a transitional state between normal aging and early dementia, particularly Alzheimer's disease. The focus of this study was the "amnestic" subtype of MCI, which is characterized primarily by memory problems.

About 10 percent to 15 percent of people with the amnestic form of MCI are diagnosed with Alzheimer's each year, compared with just 1 percent to 2 percent among normally functioning elderly people. About 80 percent of those with amnestic MCI will develop Alzheimer's within six years.

Right now, the cholinesterase inhibitor family of drugs, which includes Aricept, are recommended for mild to moderate Alzheimer's. One previous study suggested that vitamin E might also slow the progression of Alzheimer's.

This study was designed to see if either compound had an effect on delaying the progression of amnestic MCI to Alzheimer's.

A total of 769 participants with this type of MCI were randomly assigned to receive 2,000 IU of vitamin E per day, 10 milligrams of Aricept per day or a placebo, over the course of three years.

A total of 212 participants developed possible or probable Alzheimer's during the study period. About 16 percent developed Alzheimer's each year, but researchers found no significant differences between the three study groups in terms of progression to Alzheimer's over the three years.

Over the first year, people taking Aricept did display a reduced likelihood of progressing to Alzheimer's. That benefit was wiped out by the end of the third year, however.

"We're probably seeing a real effect that is transient," Blacker said. "It's hard to know what the reason is." The effect, she added, was probably due to temporarily slowed progression of the disease rather than any actual improvement in symptoms.

Aricept and related medicines probably don't have much of an effect on the basic mechanisms driving Alzheimer's, Wisniewski added. This would also account for why the effect was small and temporary.

Most of the benefit seen with Aricept occurred among people with the APOE e4 gene, which studies have linked to an increased risk for Alzheimer's disease.

While there still may be some use for Aricept, this study essentially dashes any hopes that vitamin E might be able to delay or prevent Alzheimer's, especially when other recent studies are considered, as well. Those studies have suggested that daily Vitamin E supplementation has more side effects than originally thought.

"It makes you less confident that it was totally harmless, which was one of the selling points," Blacker said. "We used to think it was good for general health and all of those things are being undermined."

The one hopeful note in all of this is that the researchers were able to pinpoint a group of people for use in future studies.

"We now have a method to define a group that is at high risk for progression, and there are a lot of drugs in the pipeline and we can now test them in this stage as well as later stages," Blacker said. "We're ready to hit the ground running to test things as they come along."

More information

Learn about efforts to treat Alzheimer's disease from the Alzheimer's Association.

SOURCES: Deborah Blacker, M.D., Sc.D., director, gerontology research unit, Massachusetts General Hospital, and associate professor, psychiatry, Harvard Medical School, both in Boston; Thomas M. Wisniewski, M.D., associate professor, neurology, pathology and psychiatry, New York University School of Medicine, New York City; June 9, 2005, New England Journal of Medicine early release
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