New Alzheimer's Drug Warnings

Experimental drugs designed to preserve memory function lost to age or brain disease may do so at the expense of other forms of recall.

Researchers believe that regional differences in the brain could undercut the effectiveness of drugs that are being developed to enhance memory in people with Alzheimer's disease and other age-related dementia.

Understanding Memory

Two areas of the brain are associated with different types of memory. The hippocampus has been associated with long-term memory formation, while the prefrontal cortex has been associated with working or functional memory—such as remembering the phone number of your babysitter or remembering a phone number long enough to dial it.

In a healthy individual, the two brain systems work together. When a person gets older, however, both forms of memory can be adversely affected.

The prefrontal cortex—the working memory—naturally flags with normal aging, "so it's particularly important to see what this cortex loses, and give it back," says study author Amy FT. Arnsten, professor and director of graduate studies in neurobiology at Yale University School of Medicine.

"There's some deterioration in the hippocampus [the long-term memory function] with normal aging, but what really erodes the hippocampus is Alzheimer's."

Experts believe that increasing the activity of an enzyme called protein kinase A (PKA) in the hippocampus may improve memory and other cognitive deficits. There are drugs in development that may accomplish that.

The Problem With Drugs

The problem, according to Arnsten and her colleagues at Yale, is that a particular drug can have vastly different effects on different parts of the brain.

Their study found that drugs that might benefit the hippocampus might have deleterious effects on the prefrontal cortex.

"Different regions of the brain that control various kinds of learning and memory may be affected differently by drugs that are targeted at improving cognition," explains Paula Bickford, a professor of neurosurgery at the University of South Florida Center for Aging and Brain Repair in Tampa and a past president of the American Aging Association.

"They may improve one kind of cognition but impair a different type of cognition," according to Bickford.

The Study

The researchers did a series of tests in rats and monkeys using drugs to increase or decrease PKA activity.

Inhibiting PKA in the hippocampus actually improved functioning in the prefrontal cortex. PKA activation in the hippocampus impaired functioning in the prefrontal cortex.

As people age, PKA activity declines in the hippocampus but increases in the prefrontal cortex, suggesting that different measures are needed to improve the situation in each area of the brain.