Drug Combo Slows Alzheimer's Disease

Jan. 20, 2004 -- A combination drug treatment looks promising for people with advancing Alzheimer's disease -- greatly aiding memory, speech, and overall functioning in daily life.

The study, which appears in this week's issue of the Journal of the American Medical Association (JAMA), is the first to combine two drugs FDA-approved for treatment of Alzheimer's disease.

"It was really unexpected good news," researcher Pierre N. Tariot, MD, a psychiatrist and neurologist with the University of Rochester Medical Center in Rochester, N.Y., tells WebMD.

"Instead of declining week by week by week, the progression of decline was slowed considerably," he says. "But we should be clear -- this isn't a cure, it isn't a reversal. These are modest gains that translate into meaningful quality of life."

Brain Chemistry of Alzheimer's

Until last year, drugs such as donepezil were the only medications for people with mild to moderate Alzheimer's disease. They work by inhibiting the breakdown of acetylcholine, a chemical involved in learning and memory.

Unfortunately, upwards of 25% of Alzheimer's patients have gastrointestinal troubles with these drugs -- so they can't take them long-term, explains Tariot.

Memantine, which was FDA-approved late last year, is for patients with moderate to severe Alzheimer's. It belongs to a new class of medications known as N-methyl-p-aspartate (NMDA) receptor antagonists -- which means it inhibits certain brain receptors, thereby protecting brain cells against damage that leads to worsening Alzheimer's.

"The tolerability rate for memantine is considerably better," says Tariot. "That's the other good news, that this provides another option for people who cannot tolerate cholinergic inhibitors."

Dramatic Improvements

The 404 patients in Tariot's study had been taking donepezil some two years before the study began. For 24 weeks, half took donepezil plus memantine; half got a placebo instead of memantine.

Those in the donepezil-memantine group had significant benefit -- with some changes in everyday functioning as early as week four, reports Tariot.

Brain functions such as memory, language, and attention improved dramatically; the patients also had less confusion.

Activities of daily living -- such as eating, walking, grooming, using the telephone, hobbies, communicating, doing complex tasks, and interacting with others -- were also easier. Patients were also less depressed, less anxious, and less agitated.

The gastrointestinal effects associated with cholinergic drugs like donepezil were more commonly reported in the group that took the placebo.

Caregivers Notice Differences

"People who really 'get it' are the caregivers," Tariot explains. "Imagine if you're dealing with somebody who from moment to moment doesn't know what they should be doing and asks questions over and over again."

This medication combination "allows them to pay attention, to engage with family members at the dinner table, watch television, use a telephone for six months to a year longer," he tells WebMD. "Add that all together, and it adds up to a meaningful outcome. Even modest gains translate into meaningful quality of life."