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Why Do Our Brains Betray Us?
Now on the Market: The First Drug Shown to Slow Alzheimer's

by Jeff Worley

A new drug on the market may be excellent news for people with mild to severe Alzheimer's disease and their families, says Frederick Schmitt, a professor with the UK Department of Neurology and Sanders-Brown Center on Aging. The drug, memantine (brand name Namenda™), is the first medication approved in the United States to treat moderate to severe Alzheimer's disease. Namenda™ was given the FDA stamp of approval last October and has been available by prescription since January.

Schmitt and Wes Ashford (now at Stanford University), working through Sanders-Brown and the ADRC, headed up UK's part of a large, multi-center clinical study of memantine, which was shown to suppress the activity of a key brain chemical involved in mental deterioration. The results of the study, which was funded by the drug's German manufacturer, Merz Pharmaceuticals, and the National Institute of Aging, were published in The New England Journal of Medicine in April 2003.

Illustration of neurofibrillary tanglesA healthy neuron (top right) contrasted with a damaged neuron (note its shriveled state and the presence around the nucleus of neurofibrillary tangles)

Tom Dolan, UK Medical Illustrator

The study involved 32 medical centers nationwide and enrolled 252 patients who lived independently. All had difficulty with daily activities, but could still speak and walk. During the 28-week study, patients received either memantine or a placebo twice a day. Neither the patients nor their physicians knew which pill they received. Behavioral, cognitive and functional tests were used to evaluate patients throughout the study.

Overall, the study found that the patients who were taking memantine showed significantly less deterioration in cognition and ability to perform daily life activities.

"These patients seem to be declining much less, about half as much as ordinarily expected, over a six-month period," says Barry Reisberg, a professor of psychiatry at New York University School of Medicine, who led the study. "This medication will slow down the otherwise inexorable progress of this disease, and it is remarkably free of side effects." A few patients did report dizziness, confusion, headache, and constipation.

"Although this drug stabilizes and slows progression, brain cells are still dying," Schmitt says. "However, memantine may result in delaying nursing home placement by six months to a year or longer. We now are looking at this drug for early Alzheimer's disease." Studies led by Schmitt and Greg Cooper (UK neurology, Sanders-Brown Center on Aging, and Lexington Clinic) are now under way to determine whether this drug or a similar drug known as neramexane will help these patients.

Memantine blocks the activity of a brain chemical called glutamate, which excites neurons, Schmitt explains. "In the past few years, we've learned that when neurons become over-stimulated because of excess glutamate, the nerve cells can become damaged or they can die. Neurons are literally excited to death." Many brain cells that respond to glutamate are involved in memory and learning.

One reason for doing clinical trials such as this one is obviously to further medical knowledge and hope that it translates into effective drug development, Schmitt says. But he says there is another important motivation.

"It allows you to spend more time with patients than might be possible in a typical, busy clinical practice. In these studies, patients get quality care from a whole team—researchers, physicians, a social worker, and a nurse," Schmitt says. [For more see Memantine User Says UK Study Has Changed Her Life]

Is memantine the wonder drug everyone's been looking for?

"We need to stress that although this is a wonderful scientific finding, it isn't a cure," Schmitt says. "It's another step in treating a very complex disease."

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For more information about Alzheimer's disease clinical trials at the UK Sanders-Brown Center on Aging, call 859/323-6729 or visit

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