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COGNITIVE DECLINE AFTER BYPASS GRAFTING STUDIED

San Antonio, TX — There are counter-balancing factors that determine the neurological and cognitive outcomes after coronary bypass grafting (CABG). “On one hand, surgery and anesthesia are improving, but on the other, a higher risk population is having the operation. As more patients have stent failures and come to surgery, we can expect to see more cases of cognitive decline,” said Guy McKhann, MD, Professor of Medicine at Johns Hopkins University School of Medicine, in Baltimore. Dr. McKhann spoke here in February at the 27th International Annual Meeting of the American Stroke Association.

There are both short-term and long-term losses of cognitive functions. The loss of cognitive function, according to one study, might affect up to 37 percent of the approximately 400,000 Americans who undergo the CABG procedure each year (New England Journal of Medicine 2001; 344 (6): 395–402).

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Dr. Guy McKhann: “We have gone back to ask this question: Why would somebody decline three to four years after surgery? Have we selected a group of patients with Alzheimer disease? Is this normal aging? Is this vascular disease with some of these effects superimposed on top?”

LONG-TERM DECLINE

The study, which was conducted at Duke University in Durham, NC, between 1989 and 1993, found that while 53 percent of patients had cognitive decline immediately after surgery, 24 percent of them seemed to rebound over the first six months. Their level of cognitive functioning declined again toward the end of the five-year follow-up.

A similar study conducted at Johns Hopkins in 2000 – for which Dr. McKhann was one of the investigators – also found an immediate cognitive decline after CABG, followed by a significant rebound and then a more prolonged decline (Archives of Neurology 2001; 58: 598–604). Significantly, the subjects in the Johns Hopkins study were in much poorer health at baseline.

Patients in the Johns Hopkins study performed a battery of cognitive tests at baseline and at one year and five years. Between baseline (surgery) and one year, there were statistically significant improvements on five out of eight cognitive domains (verbal memory, visual memory, executive function, motor speed, and psychomotor speed) with insignificant changes in language, attention, and visual construction.

However, after three years of follow-up, the same patients showed a significant decline on six of the eight domains. Motor function and executive function were the only two domains that did not change significantly.

Dr. McKhann said: “We have gone back to ask these questions: Why would somebody decline three to four years after surgery? Have we selected a group of patients with Alzheimer disease? Is this normal aging? Is this vascular disease with some of these effects superimposed on top?”

ENCEPHALOPATHY IS FACTOR

The issue of neurological complications following CABG has not been studied widely, he added, pointing out that postoperative encephalopathy – a diffuse change in brain functions, including delirium, confusion, coma, and seizures – can affect 10 percent of the CABG population, as well.

Predictive factors for encephalopathy include hypertension, age, history of vascular disease, and diabetes. A more important factor, however, appears to be the length of time the patient is on the cardiopulmonary bypass pump.

Dr. McKhann explained that during the CABG procedure, the lipid-filled microemboli cause small ischemic lesions in the brain, which increase their number by 90 percent for each 60 minutes of surgery time.

When low-risk patients – who do not have diabetes, carotid bruit, hypertension, or previous stroke – undergo a 60-minute bypass procedure, they would have a two percent risk of developing encephalopathy, he said. But if these same patients' surgery took 180 minutes, the risk of encephalopathy would increase to 4.5 percent.

At the same time, if patients were in a high-risk group – over the age of 65, with carotid bruits, hypertension, and diabetes – their increased risk would be 31 percent if their surgery lasted 60 minutes, but would jump to 50 percent if the procedure lasted 180 minutes.

COMPLICATED STUDY DESIGN

Dr. McKhann said investigators at Johns Hopkins are planning to explore these issues regarding post-CABG cognitive decline further. But, he said, they are trying to determine the appropriate study design, which is complicated by questions about who to include in the study – for example, whether they should include older people who have not had CABG, but have had other procedures such as stenting, and whether to include patients who have the procedure “off-pump” and therefore would not be at the same risk for developing encephalopathy-related cognitive decline.

Dr. McKhann and his colleagues hypothesize that those with pre-existing cerebrovascular disease are at greater risk for postoperative stroke, encephalopathy, and long-term cognitive change. They think this late decline may be the manifestation of vascular dementia augmented by the multiple ischemic events associated with microemboli during CABG.