New drug may slow Alzheimer's course

Anticipation of a dramatic increase in the numbers of Americans with Alzheimer's disease continues to propel research on treatment and prevention.

By Susan J. Landers, AMNews staff. May 12, 2003.

Washington -- A new drug that takes a different approach in combating Alzheimer's disease is showing promise at slowing decline in mental functioning -- a development researchers hope will improve the quality of life for people in the latter stages of the disease.

The drug, memantine, appears to regulate glutamate, one of the brain's specialized messenger chemicals that affects the activity of several different types of receptors. At normal concentrations, glutamate plays an essential role in learning and memory. However, its concentration often spikes or diminishes as a result of Alzheimer's. The hope is that by evening out this chemical's levels, the drug will slow the decline of memory functions, thus allowing people to care for themselves longer and reducing the caregiver burden.

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Available treatments for Alzheimer's that have proven effective at treating mild to moderate stages of the disease are aimed at a different chemical system in the brain, the cholinergic system.

Memantine has been approved for use in Germany for more than 10 years. The Food and Drug Administration is reviewing its safety and efficacy for possible U.S. sale by Forest Laboratories Inc. Approval could occur by this fall.

Findings from a randomized, double-blind study of the drug in 252 patients were published in the April 3 New England Journal of Medicine. Patients who took memantine seemed to decline about half as much during the six-month trial as would ordinarily be expected, said Barry Reisberg, MD, professor of psychiatry at New York University School of Medicine, who led the study.

The drug also appears free of significant side effects, said Dr. Reisberg.

The push for treatments and prevention is urgent. Four million Americans already have Alzheimer's disease and as many as 14 million are expected to be affected as the baby boomers age. The Alzheimer's Assn. predicts those numbers are likely to swamp the health care system and devastate millions of families financially and emotionally.

A preventive path would be a welcome find, and a heart-healthy diet is showing promising signs of being a head-healthy one, too.

Eliminating saturated fats and trans-unsaturated fats from diets may turn out to be the best way to avoid Alzheimer's. While the definitive trial has yet to be done, there is growing epidemiological evidence suggesting a relationship between diet and Alzheimer's, said Bill Thies, PhD, vice president for medical and scientific affairs at the Alzheimer's Assn.

"In fact there is an increasing body of knowledge that suggests there is a relationship between vascular risk factors and Alzheimer's disease," said Dr. Thies.

"Controlling weight, getting exercise and eating a diet higher in vegetables and lower in saturated fats are all going to benefit you in a lot of ways," said Dr. Thies. "Eventually we might find out it is also preventing Alzheimer's disease."

For example, a recent study from Rush-Presbyterian-St. Luke's Medical Center in Chicago found that participants whose diets were high in saturated fats and trans-unsaturated fats were more than twice as likely to develop Alzheimer's than were those whose diets were higher in unsaturated and unhydrogenated fats.

For nearly four years the researchers studied the dietary habits of 815 Chicago residents age 65 and older. At the end of the study, 131 subjects had developed Alzheimer's. The study was published in the February Archives of Neurology.

But despite promising results, it's too early to make dietary recommendations for Alzheimer's prevention, cautioned the study's lead author, Martha Clare Morris, ScD, assistant professor at Chicago's Rush Institute for Healthy Aging. "But what was neat about the findings is that it is the same fat composition that we've observed through years and years of research on diets that prevent heart disease."

"Diet is going to be shown to be a key part of our prevention strategy," said Neal Barnard, MD, president of the Physicians Committee for Responsible Medicine in Washington, D.C.

While research on fats and Alzheimer's disease are yielding some promising results, studies on the effects of antioxidants have been mixed. There have been studies showing a benefit to taking antioxidants, but a new study, also published in the February Archives of Neurology, found no evidence that the consumption of carotenes and vitamins C and E decreased the risk of Alzheimer's.

Jose Luchsinger, MD, assistant professor of medicine at New York's Columbia University and the lead author of the study, said he wasn't surprised that his study produced different results than other recent studies.

The differing findings could reflect a measurement error in diet or different characteristics in the population studied. Or, perhaps antioxidants actually have no appreciable effect, said Dr. Luchsinger.

Randomized trials of antioxidants are needed to demonstrate that they make a difference, he said. Currently, however, there is no body of evidence to support taking vitamins.

"I think because there is no cure and no prevention for Alzheimer's disease right now, people take a leap of faith and follow some medical hypothesis -- such as, in this case, antioxidants may help," said Dr. Luchsinger. "My recommendation would be that people can take their vitamins because they are fairly benign, but we have to wait for randomized trials of antioxidant vitamins to give us the real answer."

Another issue that must be teased out is whether antioxidants in a pill are as beneficial as those in food, noted Paula Bickford, PhD, professor of neurosurgery at the University of South Florida, Tampa. Whether supplements are synthetic or natural could also make a difference.

Copyright 2003 American Medical Association. All rights reserved.