Researchers Find Association Between Alzheimer's Gene And Mental Impairment After Cardiac Surgery

September 16, 1997

DURHAM, N.C. -- Physicians at Duke University Medical Center have found that patients who experience mental impairment after open heart surgery are more likely to carry the gene that predisposes people to Alzheimer's disease.

While up to three-quarters of all heart surgery patients experience some degree of cognitive impairment following surgery using heart-lung bypass machines, patients with the Alzheimer's- related gene apoliprotein E-4 (APOE-4), are more susceptible to this damage, a preliminary study of 65 patients found.

Since normal APOE is involved in nerve cell repair, they believe the variant APOE-4 is unable to make such repairs efficiently, as evidenced in patients with Alzheimer's disease. The study findings were published Tuesday in the September issue of the Annals of Thoracic Surgery. The study was supported by grants from the National Institutes of Health, National Institute on Aging, the American Heart Association and the Anesthesia Patient Safety Foundation.

"We noticed that after major heart surgery, the neurologic deficits of many patients -- attention, concentration and memory problems -- were very much like the early symptoms of Alzheimer's disease," said Duke's Dr. Mark Newman, chief of cardiothoracic anesthesiology and the study leader. "After controlling for other characteristics, we found a statistically significant correlation between patients with the APOE variant and neurological damage after surgery.

"Patients with the APOE variant were more susceptible to neurological damage than the other patients," Newman said. "The fact that this association was found in such a small study population leads us to believe the results will be borne out in larger studies."

Physicians say that while they can do nothing now to offset this susceptibility, it may be possible to develop drugs or other strategies to protect brain cells in these patients.

During major heart surgery, little blood clots and/or tiny fragments of atherosclerotic plaques can be dislodged and travel to the brain, leading to potential neurologic problems. The researchers believe that since the normal APOE gene is involved in nerve cell repair, the variant versions of the gene are unable to repair the subtle physiological changes caused by surgery, Newman said

Each year, more than 400,000 patients undergo open heart surgery requiring cardiopulmonary bypass, and as many as 75 percent suffer neurological complications, ranging from transient cognitive changes to stroke. While the elderly are known to be at higher risk, in more than half the cases the underlying predisposition for impairment is not known.

In the study patients were given a battery of cognitive tests prior to surgery and 6 weeks after surgery.

The study also showed that a higher level of education is protective of cognitive decline.

"We don't know the exact reason for this, but it is probably that more well-educated people have a greater functional reserve of brain cells, have more experience in test-taking, and may have developed more alternative neurological pathways," Newman said.

While these findings do not explain every case of cognitive decline following heart surgery, Newman said that they will be important in developing protective strategies for susceptible heart patients. At this point, the situation is similar to that of Alzheimer's disease -- physicians can determine who is the most susceptible, but, there are no current treatments.

Newman believes that these findings give more information to patients and their physicians as they weigh the risks and benefits of heart surgery.

He stressed that further studies with more patients are needed to prove a definite link between cognitive decline and the APOE variant. Newman and colleagues plan to follow heart patients for five years to determine how their cognitive status changes.

Joining Newman in the study were Dr. Barbara Tardiff, Ann Saunders, Ph.D., Dr. Warren Strittmatter, James Blumenthal, Ph.D., William White, Narda Croughwell, Dr. Duane Davis, Dr. Allen Roses and Dr. J.G. Reves, as well as the entire Neurological Outcome Research Group of the Duke Heart Center.
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Duke University

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