Common Heart Drugs May Slow Alzheimer's

Experts caution larger trial needed on ACE inhibitors

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HealthDay Reporter

WEDNESDAY, Oct. 13, 2004 (HealthDayNews) -- Standard blood pressure-lowering medications already used by millions of patients may also slow the mental decline seen in Alzheimer's disease, a small study suggests.

Long-term use of a specific type of the drugs called angiotensin-converting enzyme (ACE) inhibitors was associated with a dramatic slowing of memory and cognitive loss in elderly Alzheimer's patients, Japanese researchers report.

"Anything that purports to show a slowing down of progression is encouraging," said Dr. Steven DeKosky, director of the Alzheimer's Disease Research Center at the University of Pittsburgh.

However, he stressed that the study, published in the October issue of Neurology, is small and its results need to replicated in larger, more sophisticated trials.

"This is certainly not anything that someone would take action on right now, to start medicating differently," DeKosky said.

According to the National Institute on Aging, nearly 4.5 million Americans suffer from Alzheimer's disease, the causes of which remain largely unknown. While the slow buildup in brain tissue of protein deposits called amyloid plaques is thought to play a major role in the disease, many experts believe interruptions in brain blood flow may contribute to Alzheimer's as well.

"Cerebrovascular disease indirectly affects blood flow through mini-strokes or blood vessel blockages, and I think it's being recognized as having more of a role in Alzheimer's than was appreciated 10 or 20 years ago," explained the Mayo Clinic's Dr. David S. Knopman, whose commentary on the Japanese study appears in the same issue of the journal.

In that study, Dr. Takashi Ohrui and colleagues at Tohoku University assessed one-year changes in memory and thinking in 162 elderly nursing home residents diagnosed with both hypertension and mild to moderate Alzheimer's disease.

The patients were divided up into three groups: One group received a type of ACE inhibitor able to cross the blood-brain barrier and penetrate into the brain; a second group received an ACE inhibitor unable to penetrate the brain; and a third group received a different kind of blood-pressure medication, called a calcium channel blocker.

At the beginning of the study, all of the patients scored about 20 on a standard neurological test to measure memory and cognition, called the Mini-Mental State Exam (MMSE).

One year later, the scores of patients taking the calcium channel blocker had dropped by 4.9 points, on average, while those taking the non-brain-penetrating ACE inhibitors fell an average of 4.6 points.

However, patients taking either one of the two brain-penetrating ACE inhibitors, perindopril or captopril, remained relatively stable, with an MMSE decline of just 0.6 points on average.

DeKosky called the results "impressive," especially because these blood pressure drugs are "already approved and relatively safe."

However, he said, "there are a lot of questions with this particular study."

First of all, the steep declines in MMSE scores seen in the two groups not taking the brain-penetrating drugs were higher than usually seen in these types of trials, possibly skewing the results, DeKosky said.

And he noted the MMSE exam doesn't tell us much about changes in the brain's "executive" center -- the frontal lobe -- where so much of the neurological degeneration seen in Alzheimer's is thought to occur.

Furthermore, Knopman added, the study wasn't blinded, meaning that both patients and doctors knew who was getting what medication, possibly affecting the results.

For these and other reasons, "these results must be replicated, and by themselves can only be considered interesting," Knopman said. "I'd like to see studies with proper placebo controls that have a more extensive and reliable set of outcomes."

DeKosky said ACE inhibitors might still prove useful in improving brain function, because they target important chemicals regulating brain blood flow.

"There is some evidence, biochemically, that the ACE inhibitors that get into the brain have some effect on reversing, improving or delaying brain damage," he said. "I think this opens the door to look at the mechanisms, perhaps at specific medications."

Knopman agreed. "The interest will hopefully lead to a clinical trial being done in North America," he said.

More information

To learn more about Alzheimer's disease, go to the National Institute on Aging.

SOURCES: Steven DeKosky, M.D., professor and chairman, department of neurology, and director, Alzheimer's Disease Research Center, University of Pittsburgh; David S. Knopman, M.D., consultant, neurology, Mayo Clinic, Rochester, Minn.; October 2004 Neurology

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