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Drug Slows Progression of Moderate to Severe Alzheimer’s Disease

By Tammy Gay

 

Memantine blocks the activity of a brain chemical called glutamate, which excites neurons. In recent years, researchers have learned that when neurons become over stimulated because of excess glutamate, the nerve cells can become damaged or die and this "excitotoxicity" has been linked to death of neurons. Nerve cells that respond to glutamate are involved in memory and learning.

 

April 2, 2003 (Lexington, Ky.) -- A drug that suppresses the activity of a key brain chemical could be the first effective treatment for patients in the later stages of Alzheimer's disease (AD), according to the results of a large multi-center clinical study published in the April 3 issue of the New England Journal of Medicine.

The drug, memantine, slows the mental and physical deterioration of patients with moderate to severe AD, according to Frederick Schmitt, Ph.D., professor, Department of Neurology, University of Kentucky College of Medicine.

UK Sanders-Brown Center on Aging, directed by William R. Markesbery, M.D., participated in the study led by Barry Reisberg, M.D., professor of psychiatry at New York University School of Medicine.

“Although this drug stabilizes and slows progression, cells are still dying,” Schmitt said. “However, this drug may result in delaying nursing home placement from six months to a year. We now are looking at memantine for early Alzheimer’s disease.”

"These patients seem to be declining much less, about half as much as ordinarily expected, over a six-month period," Reisberg said. "This medication will slow down the otherwise inexorable progress of this disease, and it is remarkably free of side effects."

AD is the most common form of dementia affecting people over age 65. Some four million Americans have the mind-robbing disease, and it is the major reason people are institutionalized in the United States. There are no treatments for slowing the later disease stages, in which patients begin to lose the ability to care for themselves.

Memantine blocks the activity of a brain chemical called glutamate, which excites neurons. In recent years, researchers have learned that when neurons become over stimulated because of excess glutamate, the nerve cells can become damaged or die and this "excitotoxicity" has been linked to death of neurons. Nerve cells that respond to glutamate are involved in memory and learning.

Approved medications for mild to moderate AD in America are aimed at a different chemical system in the brain. These drugs strengthen the activity of brain cells that use the brain chemical acetylcholine, which is also for improving memory.

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 randomized, double-blind 28-week study, patients received either memantine or a placebo twice a day. Behavioral, cognitive and functional tests were used to evaluate patients at the beginning and end of 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. The side effects from the drug were minimal.

“Even though we need medications to treat Alzheimer’s disease, we also have to keep up the efforts to prevent the disease. The future is looking better for treatment and prevention of Alzheimer’s disease,” said Greg Cooper, M.D., Ph.D., assistant professor, Department of Neurology, UK College of Medicine, and medical director of the UK Alzheimer’s Disease Research Center’s outreach clinic at Lexington Clinic.

In fact, UK Sanders-Brown Center on Aging researchers are working on the largest prevention trial in the university’s history. PREADVISE (Prevention of Alzheimer’s Disease by Vitamin E and Selenium) will link with SELECT (Selenium and Vitamin E Cancer Prevention Trial) in a large National Cancer Institute-supported study looking at the effects of vitamin E and selenium in preventing prostate cancer.

Memantine is manufactured by Merz Pharmaceuticals, based in Frankfurt, Germany. In the United States, Forrest Pharmaceuticals Inc., based in New York City, has licensed the drug from Merz. The Food and Drug Administration is reviewing the drug. Grants from Merz Pharmaceuticals and the National Institute on Aging supported the study.

For more information about memantine and AD, call (866) 321-5323. For more information about other AD clinical and prevention research trials at UK Sanders-Brown Center on Aging, call (859) 323-6729.


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