Feb. 9, 1999 NASHVILLE, Feb. 6 -- For several years, scientists have known that people who have inherited the E-4 variant of the apolipoprotein (apo) gene are at high risk for developing Alzheimers disease. Now they say that having the gene may also signal a higher likelihood of having stroke or another vascular disease in the brain.
The study's lead scientist, Charles DeCarli, M.D., says that people who have the apoE-4 gene variant and high blood pressure have smaller brain volumes and more abnormal white matter in the brain and thus may be more susceptible to silent strokes, which take a toll over time.
The research findings were presented here today at the 24th American Heart Association International Conference on Stroke and Cerebral Circulation.
Not only do the brain changes lead to a gradual deterioration of memory and motor skills, they also may place the person at risk for Alzheimer's disease, he says.
"When you go swimming, you wear a bathing suit instead of pants so that you wont be weighed down when you get in the water," explains DeCarli, of the University of Kansas Medical Center, Kansas City, Kan. "By the same token, a smaller brain volume, excess white matter abnormalities or silent stroke, can weigh you down and make you more susceptible to the effects of early Alzheimer's disease."
DeCarli says people who have the apoE-4 gene variant and high blood pressure or other vascular risk factors are at particularly high risk of having a stroke. Vascular disease affects the blood vessels in the brain, says DeCarli.
"People who do not have vascular disease and apoE-4 are not harmed, but if you have high blood pressure or other vascular disease and this apoE-4 gene allele, it really hurts your brain," says DeCarli. "It sets you up for some cognitive impairment. It reinforces the genetic risk for brain injury related to hypertension and vascular disease as you age."
Researchers are not sure how apoE-4 affects the brain, but DeCarli notes, "The apoE-4 may impair brain recovery from injury of any type, whether its Alzheimers or other vascular disease or head trauma. Having apoE-4, therefore, may increase ones chances of a poor outcome following any brain injury."
Scientists studied 414 men participating in the National Heart, Lung, and Blood Institutes Twin Study. Researchers used magnetic resonance imaging (MRI) to determine the study participants who had silent strokes, abnormalities in the white matter of the brain -- called white matter hyperintensities -- or smaller brains.
"The difference between using MRI and not using MRI to measure the amount of brain is significant," says DeCarli. "With MRI, you're going to catch more of the strokes and white matter disease. We can get a better idea of whats going on in the brain."
In silent strokes, people don't have any of the classic warning signs such as sudden headaches, dizziness or loss of motor skills. Silent strokes occur when smaller blood vessels in the brain are blocked or rupture. Silent strokes arent as damaging, at least initially, as strokes that occur when the carotid arteries in the neck are blocked or burst.
But silent strokes do take their toll over time. When the smaller vessels are unable to deliver oxygen and blood to the brain, cells die. Over time, brain cells that control functions such as memory and motor skills die off, leading to difficulty in memory, concentration and even walking. The researchers do not recommend screening people for apoE-4.
"This is one part of the bigger picture that needs to be examined further," says DeCarli. "It may be worth testing people for risk factors and controlling those rather than seeing if they have the apoE-4 or not."
The average age of the men in the study was 72 years. Those who had at least one copy of apoE-4 had smaller brain volumes when compared to those who did not have the gene variant. DeCarli says there were not enough people in the study with two copies of the variant to assess that effect.
On average, those studied who had at least one copy of apoE-4 had a brain volume of 919.4 cubic centimeters. Those who were free of apoE-4 had an average brain volume of 949.1 cubic centimeters.
There was also a significant difference in the volume of white matter hyperintensities between the two groups. Men who did not have the gene variant had 3.3 cubic centimeters of their brains affected by silent stroke. Those who had apoE-4 had more than three times -- 10.4 cubic centimeters -- the amount of white matter hyperintensities in their brain.
Co-authors are Terry Reed, Ph.D., of the University of Indiana, Indianapolis, Ind.; Phillip A. Wolf, M.D., Boston University; Bruce L. Miller M.D., University of California at San Francisco; Gary E. Swan Ph.D.; and Dorit Carmelli Ph.D., SRI International, Menlo Park, Calif.
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