JAMA study confirms drug can help improve memory and cognition in advanced Alzheimer's patients

January 20, 2004

A study in the current issue of the Journal of the American Medical Association (JAMA) indicates that there is good reason for the recent attention surrounding the drug memantine for the treatment of Alzheimer's disease. A multi-center study directed by University of Rochester Medical Center faculty concluded that memantine, when taken with the commonly prescribed Alzheimer's drug donepezil, helped moderate to severe Alzheimer's patients maintain or in some cases, improve their memory and other intellectual functions, and helped to preserve activities of daily living during the study period. This represents the first medication approved by the FDA to treat advanced Alzheimer's patients, as well as a new category of medication to treat the disease.

Lead investigator Pierre N. Tariot, M.D., professor of psychiatry at the University of Rochester Medical Center, said that the study was significant not only because it validates a new class of drugs for the treatment of Alzheimer's, but also because it was the first time positive results have been seen combining two Alzheimer's drugs.

"To find a new medication that can provide substantial benefit to patients at this stage of the disease, either alone or in combination with another Alzheimer's drug, is certainly good news," Tariot said.

Thirty-seven institutions participated in the study between June 11, 2001 and June 3, 2002. The study compared the efficacy and safety of memantine versus placebo (sugar pill) in patients with moderate to severe AD already taking the cholinesterase inhibitor, donepezil. A total of 404 patients were enrolled, and 322 patients (80 percent) completed the clinical trial.

According to Tariot, patients who took the memantine and donepezil versus those on placebo showed statistically significant improvement in cognition, memory, and overall daily functioning.

"Family members tended to say things like, 'Gee, he's more like himself; he participates in and can follow a conversation; he can talk on the phone; he does not get as upset.' Or, 'He doesn't appear to be declining the way he did before,'" Tariot added. "While memantine is not a cure for Alzheimer's, if it helps to keep a person with Alzheimer's at home for six months or one year longer, then it is a victory."

The two medications target two separate cell mechanisms. Memantine is known as a "low to moderate affinity NMDA receptor antagonist," which overstimulates glutamate, a brain chemical implicated in nerve cell death when produced in high quantities. On the other hand, donepezil is an "acetylcholinesterase inhibitor," and works by preventing the break down of acetylcholine, a chemical messenger in the brain that is important for memory and other thinking skills. Before the FDA approved memantine in October 2003, the only medications approved for Alzheimer's treatments were all acetylcholinesterase inhibitors.

"We were pleasantly surprised to see that the two drugs worked well together," Tariot said. "Memantine is significant, since it provides an entirely new medication option for the 2.5 million people currently suffering at the advanced stage of Alzheimer's."

Today, more than 4.5 million Americans suffer with Alzheimer's, a progressive disease of the brain that is the most common type of dementia (a term used to describe the progressive loss of cognitive, intellectual or functional abilities). That number is expected to quadruple by 2050. Of those currently living with Alzheimer's disease, half are in the moderate to severe stages.

University of Rochester Medical Center

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