Study reveals link between cardiovascular risk factors and cognitive decline

Elderly people with the metabolic syndrome—a constellation of cardiovascular risk factors including excessive fat around the abdomen, high blood pressure, and high blood glucose levels—are at greater risk for cognitive impairment and decline than those without the syndrome, according to a study led by a University of California, San Francisco (UCSF) researcher.

Elders with both the metabolic syndrome and high levels of inflammation in the blood are particularly at risk, according to the research, published in the November 10 issue of JAMA.

The findings, based on a five-year study of more than 2,600 elders, are the first to show a link between the metabolic syndrome and a decline in mental powers among the elderly.

The metabolic syndrome is on the rise in the United States, affecting an estimated one in four adults and 40 percent of people over the age of 40. It is defined as a cluster of five simultaneous disorders: abdominal obesity, high blood pressure, high blood triglycerides (fats), low levels of HDL—the so-called “good” cholesterol—and high blood glucose levels. Inflammation, as indicated by high levels of inflammatory markers in the blood, is often found in people with metabolic syndrome as well. Together, these conditions strongly increase the risk of coronary heart disease, vascular disease, stroke, and type II diabetes.

“What’s bad for the body turns out to be bad for the brain,” says Kristine Yaffe, MD, associate professor of psychiatry, neurology, and epidemiology at UCSF and chief of geriatric psychiatry at the San Francisco VA Medical Center (SFVAMC).

Yaffe led the five-year prospective study of elders in Tennessee and Pennsylvania. The elders were approximately evenly divided between males and females and blacks and whites. By the end of the study, a total of 26 percent of the elders with the metabolic syndrome exhibited significant cognitive decline, compared with 21 percent without the syndrome. The key factor, however, seemed to be the presence of inflammatory markers in the blood: 30 percent of elders who had both the syndrome and high inflammation showed cognitive decline at the end of five years, while only 23 percent with the syndrome and low inflammation demonstrated a similar decline.

Recent studies seem to indicate a yet-undetermined relationship between inflammation and Alzheimer’s disease, says Yaffe, which gives her results broader implications, she says. “When people think about risk factors for cardiovascular disease, they’re thinking about problems in terms of the heart, in terms of the body. But people usually don’t think about how this might affect cognitive function.” She says the results are particularly ominous in light of the increasing rate of obesity among Americans. “If we keep going, not only is the obesity epidemic going to lead to people having more strokes and heart disease and diabetes, but maybe it will [mean] a lot more people having dementia.”

The study participants, both with and without the syndrome, were all mentally healthy at the beginning of the study and showed no signs of cognitive problems. All started out with high scores—an average of 90 on a 100-point scale—on a standard cognitive test called the Teng Modified Mini-Mental State Examination, which measures orientation, concentration, memory, and other mental factors. The same test was administered at three and five years. Cognitive decline was defined as a score at least five points lower than the initial score. In day-to-day terms, explains Yaffe, “The kind of change we were looking at on this test is the kind of change that most people would notice, or their families would notice. This is a group of people who started off being very healthy [mentally]. So in somebody who’s declined this much, most people would be concerned.”

Yaffe points out that, on the positive side, the risk of dementia might be seen as an additional impetus for the prevention and treatment the metabolic syndrome. “What if you identified these people [with the syndrome] and you say, ‘You’ve got this constellation of problems. It would be really good if you lost weight and really carefully monitored your blood pressure and your glucose [and other risk factors], because otherwise, not only are you at risk for heart attacks, but you might be at risk for dementia.’ And seeing whether you can modify that trajectory by getting people to exercise, lose weight, and possibly reduce inflammation.”

The study draws no conclusions about the possible causes of cognitive decline in the presence of the metabolic syndrome and high inflammation. Interactions between the syndrome and inflammation are not yet clearly understood.

The study observed 2,632 elders with a mean age of 74 at community clinics in Memphis, Tennessee and Pittsburgh, Pennsylvania from 1997 to 2002. The study did not distinguish between cognitive decline related to Alzheimer’s disease and decline caused by stroke. Yaffe hopes to explore that difference in future research.

Other researchers who participated in the study were Dr. Alka Kanaya of the department of medicine and Karla Lindquist of the department of geriatrics at University of California, San Francisco, Eleanor M. Simonsick, Ph.D. and Dr. Tamara Harris of the National Institute on Aging, Dr. Ronald I. Shorr and Frances A. Tylavsky, Ph.D. of the department of preventive medicine at the University of Tennessee at Memphis, and Dr. Anne B. Newman of the department of epidemiology at the University of Pittsburgh School of Medicine.

The study was supported by grants from the National Institutes of Health.