Chronic hypertension may shrink the brain.

High blood pressure, even if well controlled by medication, may cause the brain to shrink, according to a new report. The significance of brain atrophy remains unclear; however, researchers worry that long-standing hypertension could lead to cognitive difficulties.

"We think these healthy males with hypertension have brains that are aging at an accelerated rate," says Declan G.M. Murphy, co-author of the report in the September issue of HYPERTENSION and a researcher at the National Institute on Aging in Bethesda, Md. "The question is how much more brain tissue they need to lose before they become affected clinically"

This is not the first time scientists have demonstrated changes in the brains of people with hypertension. A 1984 study by a team of Japanese researchers showed that older men with hypertension had more brain atrophy than controls. However, that study relied on a technology called computerized tomography to obtain images of the brain. To get a sharper picture, Murphy and his colleagues used a newer technique called magnetic resonance imaging (MRI).

The U.S. researchers wanted to find very early changes in brain structure, so they recruited 18 otherwise healthy men age 51 to 80 who had suffered from hypertension for at least a decade, says study co-author Judith A. Salerno, also at the National Institute on Aging. The team recruited 17 healthy men within the same age range without hypertension to serve as controls.

MRI was used to obtain three-dimensional brain images of each participant. Next, the researchers used a mathematical method to calculate the percentage of brain matter and of fluid in the ventricles, large spaces in the brain that act as "gutters"to drain cerebrospinal fluid, Murphy says.

The group discovered that men with hypertension had smaller brains than the controls. Their analysis also revealed that men with hypertension had enlarged ventricles, a sign of brain atrophy, Salerno adds.

Most of the men with hypertension had extensive medical records dating back to the time of their diagnosis; Salerno notes. In addition, most took medication to keep their blood pressure under control.

The MRI data don't pinpoint the brain region most affected by chronic hypertension. However, Murphy thinks that high blood pressure may injure the so-called wiring portion of the brain known as white matter. The white matter consists of neurons, or nerve cells, that connect the brains computers (gray matter) to each other and to the rest of the body, Murphy says.

The volunteers in this study showed no sign of cognitive problems. All scored normal on tests of cognitive function, Salerno notes. However, the researchers believe the MRI picks up changes in the brain at an early stage, before cognitive difficulties show up. Even so, Salerno said she was surprised that some of the more severely affected men showed no symptoms of cognitive problems.

Nobody knows the mechanism by which hypertension might lead to brain atrophy. One theory holds that high pressure causes the muscle lining the brain arteries to thicken, thus reducing blood flow to the brain. With less blood getting through, some neurons die, causing portions of the brain to die. Some researchers believe that although it may take years, such a process eventually leads to a type of dementia characterized by problems with memory, arithmetic, and spatial tasks.

On the other hand, the high pressure may simply lead to compression of the brain and swelling of the ventricles, a process that doesn't necessarily impair the brains function, says Vladimir Hachinski of the University of Western Ontario in London.

Hachinski calls the team's findings "intriguing" but says further research must determine whether hypertension causes brain atrophy, "It was an in-depth study of a small number of patients, I'd like to see it confirmed," agrees Salerno.

Despite the small sample size, Hachinski says the study was well conducted. "I think it's a good beginning," he says.

A multicenter study of 5,000 men and women age 65 and older may soon provide scientists with more definitive data regarding hypertensions effect on the brain. Timothy J. Miller, a neuroradiologist at johns Hopkins Hospital in Baltimore, and his colleagues will look for signs of brain atrophy and enlarged ventricles in the MRI scans taken from otherwise healthy hypertensive volunteers. Miller says he expects to get preliminary results from that study within the next two years.

-K.A. Fackelrnann