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Vascular Risk Factors May Signal Faster Cognitive Decline

ARTICLE IN BRIEF

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The greater a person's risk of having a first stroke over the next 10 years, the more accelerated the annual rate of cognitive decline, according to a new study.

NEW ORLEANS—Stroke risk factors, particularly left ventricular hypertrophy (LVH), diabetes, and high systolic blood pressure, may increase the rate of cognitive decline, according to a new study.

An analysis of data from the national longitudinal Reasons for Geographic and Racial Differences in Stroke (REGARDS) study showed that the greater a person's risk of having a first stroke over the next 10 years, the more accelerated the annual rate of cognitive decline.

“All of us are in a process of cognitive decline, so it's not a matter of whether it is happening, but of how fast it is happening,” said chief investigator George Howard, DrPH, professor and chair of the department of biostatistics at the University of Alabama at Birmingham.

“What we found is that people who have a high risk of having a stroke over the next 10 years decline twice as fast as people considered at average risk of stroke,” he said.

The study, which was funded by the NINDS, was described here at the American Stroke Association International Stroke Conference 2008.

STUDY METHODS, FINDINGS

To determine whether stroke risk factors predict cognitive decline, the investigators used data from the ongoing REGARDS study of 30,201 participants aged 45 and older randomly selected from the 48 contiguous states.

Half the participants were African-American, and half were white. Half of the participants are from the eight southeastern states that make up the “Stroke Belt” where stroke is more prevalent, and the rest are from other states. Men and men were equally represented.

Following a 45-minute computer-assisted health interview, each participant had had an in-home evaluation by a health professional that included anthropometric measures, venipuncture, and electrocardiograms. Participants received follow-up calls every six months to check their health status.

For the current analysis, cognitive function was assessed annually using a six-item subset of the Mini-Mental State Exam.

Of the total cohort, 17,626 participants who had never had a stroke or transient ischemic attack and who had two or more cognitive-function assessments were included in the final analysis.

The participants were an average age of 65.9 years and had an average systolic blood pressure of 127.9 mmHg. Fifty-six percent of them had hypertension; 19.3 percent had diabetes; 21.9 percent suffered from cardiovascular disease (CVD); 6.5 percent had LVH; and 13.1 percent smoked.

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DR. GEORGE HOWARD: “All of us are in a process of cognitive decline, so its not a matter of whether it is happening, but of how fast it is happening. What we found is that people who have a high risk of having a stroke over the next 10 years decline twice as fast as people considered at average risk of stroke.”

Stroke risk was assessed using the Framingham Stroke Risk Function (FSRF) index, which estimates a person's chance of having a stroke over the next 10 years based on systolic blood pressure, antihypertensive medication, diabetes, smoking status, history of CVD, atrial fibrillation, and LVH.

Dr. Howard said that the average person has about a 1 percent chance of having a stroke per year, or a Framingham stroke score of about 10. People with Framingham scores of 30 or higher are considered at high risk of stroke; about 5 percent of the cohort fell into this category.

After factoring in age, race, and gender, the mean rate of cognitive decline for a person at average risk for stroke was 0.06 points per year on the six-point scale.

Participants at high risk for stroke experienced a 0.12 point mean decline in cognitive function score annually — or twice that of the “average” person, Dr. Howard said.

The investigators then assessed the influence of the individual components that make up the FSRF on cognitive function. They found that people with high systolic blood pressure, diabetes, and left ventricular hypertrophy had significantly faster cognitive decline than people without these risk factors.

“LVH had the biggest effect on cognitive function,” Dr. Howard said. It was associated with about a 60 percent increase in the annual rate of decline. Diabetes was associated with about a 56 percent increase in the rate of cognitive decline.

For every 10 mmHg increase in systolic blood pressure, there was about a 20 percent increase in the rate of cognitive decline.

Dr. Howard said he found it interesting that even though higher systolic blood pressure was associated with accelerated cognitive decline, being on antihypertensive medication was not. This suggests, he said, that treatment to control blood pressure might be effective in slowing age-related cognitive dysfunction, although that needs to be tested in a clinical trial.

As in other studies that have suggested a negative association between nicotine and cognitive dysfunction, cigarette smoking appeared to be protective against cognitive decline, Dr. Howard said. However, the relationship did not reach statistical significance.

The researchers also looked at whether race, gender, depression, or education influenced the effect of stroke risk factors on cognitive function. The analysis showed no significant interactions by race and sex or by the presence or absence of depression.

However, they did find what Dr. Howard called “two confusing interactions” between education levels and stroke risk factors.

In people with a high school education or higher, atrial fibrillation and LVH were associated with faster cognitive decline, as in the entire cohort.

But in people who had not graduated from high school, atrial fibrillation and LVH did not appear to predict for cognitive decline, he said. “We would have expected even faster decline with less education,” he said, adding that further study is needed.

During the question-and-answer session, Dr. Howard said that the impact of geographical region on the association between FSRF and cognitive decline has also been analyzed. The results are “exciting” and will be presented at an upcoming scientific meeting, he said.

THE ROLE OF CEREBROVASCULAR RISK FACTORS

The study confirms growing evidence that cerebrovascular risk factors are associated with cognitive dysfunction, commented Jeffrey L. Saver, MD, vice chair of the American Heart Association Stroke Council, director of the University of California-Los Angeles (UCLA) Stroke Center, and professor of neurology at the David Geffen School of Medicine at UCLA.

The study's strengths include both its large size and the fact that individual risk factors most likely to affect cognitive function were identified, he said.

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DR. JEFFREY SAVER: “We should use the information to motivate patients to comply with their diabetes medication, their antihypertensive medication, and other vascular treatments, telling them they will not only be preventing a stroke, but protecting their brain capacity."

“We should use the information to motivate patients to comply with their diabetes medication, their antihypertensive medication, and other vascular treatments, telling them they will not only be preventing a stroke, but protecting their brain capacity.”

“As the population ages, better treatment of vascular risk factors will help avert not only stroke, but also an epidemic of late-life cognitive impairment,” Dr. Saver said.