ARTICLE IN BRIEF
Investigators reported that people with atrial fibrillation were more likely to experience lower memory and thinking scores at earlier ages than people with no history of atrial fibrillation.
For years, doctors have known there was a connection between atrial fibrillation (AF) and cognitive decline. But a new study found that patients with incident AF began hitting dementia benchmarks on cognitive decline exams about an average of two years earlier than those with no history of the common heart disorder.
Several studies have looked at atrial fibrillation and cognitive decline. Some focused on a specific point in time and examined whether those patients with AF scored lower on cognitive tests. Other studies followed people over time, looking at those with AF and studying to see how many of those people were diagnosed with dementia.
This study, published in the June 5 online issue of Neurology, used a longitudinal design to focus on cognitive test scores over an average of seven years and how they changed over time. In addition to looking at the specific numbers, researchers focused on how fast those scores changed, said Evan L. Thacker, PhD, a statistician at the University of Alabama at Birmingham who did the research as part of his dissertation at the University of Washington in Seattle.
“People tend to score lower over time as they age,” said Dr. Thacker. “Our study allowed us to see that this decline happens a little more rapidly in those with atrial fibrillation.”
Steven M. Greenberg, MD, PhD, professor of neurology at Harvard Medical School, said the study shows how much has changed from the once-held view that Alzheimer's disease was an isolated neurological problem. Now, studies such as these are showing that risk factors that should have nothing to do with cognitive decline have major impacts.
“This is another strong piece of evidence that cardiovascular disease plays a role in brain function,” said Dr. Greenberg, who was not involved with the study. “It's a strong, robust study.”
The study received funding from the NIH National Heart Lung and Blood Institute, National Institute of Neurological Disorders and Stroke, and the National Institute on Aging.
The investigators followed 5,150 participants over age 65 for a mean of seven years who did not have AF or a history of stroke at the beginning of the study. About 10.7 percent of the group developed incident AF, a common heart disorder which presents in an irregular and often rapid heart rate. It often results in poor blood flow to the rest of the body.
Researchers looked at the patients' scores on the 100-point Modified Mini-Mental State Examination (3MSE), which measures cognitive ability. Those diagnosed with AF declined faster after their heart condition developed than those who did not.
For example, the predicted five-year decline in mean 3MSE score from age 80 to age 85 was ?6.4 points (95% CI: ?7.0, ?5.9) for participants without a history of atrial fibrillation, but was 10.3 points (95% CI: ?11.8, ?8.9) for participants experiencing incident atrial fibrillation at age 80, a five-year difference of ?3.9 points (95% CI: ?5.3, ?2.5).
“This was a marked result,” said Dr. Thacker. “There was a clear difference between people with atrial fibrillation and those without.”
While the association between the heart disorder and cognitive decline was not surprising, the rate of decline was, said several experts not involved with the study. The next step, they said, was to determine the physical correlation between the two.
S. Claiborne Johnston, MD, PhD, director of the Clinical and Translational Science Institute at the University of California, San Francisco (UCSF), said: “We can't say that atrial fibrillation is the cause of the cognitive decline, but maybe there are infarctions that aren't so apparent,” said Dr. Johnston. “It's also possible that AF happens in a group of people who are older and sicker and have vascular issues that are risk factors and those underlying causes are the reason for the decline.”
Part of the challenge with the study is that AF is rarely the only health issue in older patients, he said. Although the study adjusted for other factors such as hypertension and diabetes, adjustments are never perfect, he noted. For example, the patients with uncontrolled diabetes might have other complications than those who are taking medication to control the disease.
Michael Sharma, MD, associate professor of neurology at McMaster University in Ontario, said it's well established that AF is a risk factor for stroke, which increases as patients age. “The study has some implications for how we should think about aging and dementia and the role of screening for atrial fibrillation,” Dr. Sharma said. “For individuals with dementia, should we screen for atrial fibrillation, particularly if there are already vascular risk factors such as hypertension?
“There are a few steps we need to take before making these recommendations,” he continued. “We need to know the mechanism causing the problem before we decide what we would do about it.”
Dr. Sharma said he considered three possibilities for the link between AF and cognitive decline. He suspected that the accumulation of covert infarctions — or tiny strokes — might impair brain function, particularly if they are located in certain areas of the brain, like those that control language and memory.
It is also possible, he said, that the vascular changes that result in atrial fibrillation might be linked to vascular changes in the brain. Finally, the decreased blood flow associated with AF might result in the brain being less well-perfused than needed.
Dr. Johnston, of UCSF, said it would be important to follow up on imaging studies looking at the infarction issue. “It's worrisome,” he said. “We know that for every stroke we identify, there are a bunch of infarctions we don't — some studies show 2-to-1 and others up to 10-to-1. It would not be too surprising that there are relatively silent or covert infarctions that could add up to cognitive decline.”
Dr. Greenberg, of Harvard Medical School, also considered the infarction accumulation and the profusion problems in the brain, pointing out that underlying diseases of the blood vessels might lead to diseases in the brain in a cause-and-effect manner.
Dr. Greenberg, who is director of the Hemorrhagic Stroke Research at Massachusetts General Hospital's Stroke Research Center, said it would be interesting to know if anticoagulation medications had an impact on the test scores.
“We need to identify atrial fibrillation in people before it causes problems,” he said. “It's definitely a recommendation that, whenever someone is being seen in general primary care, [the physician] check their pulse and those with irregularities have EKGs.”
“There are many people who could benefit from being on anticoagulants who are not receiving them,” said Dr. Johnston.
The neurologists said they would be interested in looking at some of the recent trials of new anticoagulants to see if there were additional data showing the infarction occurrence for those with AF who were taking anticoagulants and correlating these numbers with cognitive decline.
Dr. Thacker, the lead author of the study, said the researchers did not address the use of anticoagulants. It would be difficult to do a randomized trial of patients with atrial fibrillation and anticoagulants, he said. He noted that because anticoagulants are known to be beneficial for preventing strokes, it would be unethical to put half the patients on a placebo.
The next step, he said, would be to narrow down the mechanism causing the link between the heart disorder and cognitive decline using imaging studies.
“If the link between AF and cognitive decline does have to do with small blood clots causing small infarction, we could use that information to reduce the risk of cognitive decline,” said Dr. Thacker. “This is an important question and we'd love to find the answer.”
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