February 2004

American Heart Association

Cholesterol drugs may lower risk for mental impairment after stroke

American Stroke Association meeting report

SAN DIEGO, Feb. 6 – High cholesterol may increase the risk of stroke, but cholesterol-lowering drugs might reduce the risk of impaired brain function after a stroke, according to a study presented today at the American Stroke Association's 29th International Stroke Conference.

Patients with a history of high cholesterol had a lower risk of cognitive impairment three to six months after stroke. However, the finding likely relates to high cholesterol treatment, rather than a protective or helpful effect of cholesterol. About 45 percent of the patients were being treated with cholesterol-lowering drugs known as statins before their stroke, said Eugenia Gencheva, M.D., a research fellow at the University of Illinois at Chicago (UIC) Center for Stroke Research. The research was conducted at Rush Medical College in Chicago.

"We're certainly not saying that the high cholesterol itself is protective," added David Nyenhuis, Ph.D., associate professor of neurology and rehabilitation at UIC. "Patients who had elevated cholesterol levels were more likely to be treated with statin drugs. We believe that perhaps statins were exerting the protective effect."

Elevated cholesterol is a risk factor for atherosclerotic vascular disease. In this observational study, hypercholesterolemia was determined by self-report and verification of current medication. Participants taking cholesterol-lowering drugs were defined as hypercholesterolemic, although their cholesterol levels might have been within acceptable limits as a result of their treatment.

Several observational studies have indicated that statin therapy is associated with a reduced risk of Alzheimer's disease and vascular dementia. However, the precise mechanisms by which statins might affect cognitive impairment are poorly understood, Gencheva said.

"Other research has shown that the effect of statins might be mediated by direct cholesterol-lowering properties, causing a reduction in cholesterol production and turnover in the brain," she said. "Statins also might reduce the concentration of proteins linked with dementia that accumulate in the brain in Alzheimer's patients."

Cognitive impairment – or loss of memory or other aspects of brain function – often occurs after stroke. Cardiovascular risk factors such as hypertension, diabetes, and obesity are widely assumed to influence cognitive impairment after stroke. But, the assumption hasn't been documented in medical literature, Gencheva said.

At the UIC Center for Stroke Research, an ongoing study led by Philip B. Gorelick, M.D, M.P.H., focuses on identifying markers for dementia after stroke through brain scans with magnetic resonance imaging. As an extension of that research, investigators evaluated demographic factors and cardiovascular risk factors as potential predictors of stroke-related cognitive impairment.

Ischemic strokes, which are caused by clots that disrupt blood flow to the brain, can result in various brain disorders known collectively as vascular cognitive impairment. The mildest disorder is vascular cognitive impairment-no dementia (VCIND); at the opposite end of the spectrum is vascular dementia, the most severe form of stroke-related brain dysfunction. The prevalence of VCIND is not known but vascular dementia may occur in up to one third of stroke survivors, researchers said.

This study focused on VCIND. Researchers studied 103 consecutive ischemic stroke patients – 41 diagnosed with VCIND and 62 who had no evidence of cognitive impairment after their strokes. All patients completed interviews that included questions about potential risk factors for cognitive impairment, and underwent neuropsychological testing. Information about cholesterol levels, blood pressure, and other vascular risk factors was self-reported and not based on actual measurement when patients were evaluated.

An initial analysis of different variables identified three statistically significant predictors of cognitive impairment: the patient's level of education, the presence of heart disease (defined as a history of heart attack, heart failure, disease of the heart muscle, disease of the heart valve, and abnormal heart rhythm); and a history of high cholesterol (hypercholesterolemia).

In a second analysis, heart disease and hypercholesterolemia remained significant predictors of cognitive impairment when results were not adjusted for education level. Increased education and hypercholesterolemia were associated with a reduced risk of cognitive impairment after stroke. When the researchers performed an analysis that controlled for the confounding effects of education, only hypercholesterolemia remained as a statistically significant predictor of the risk for cognitive impairment.

"Education is a well-known protective factor for cognitive impairment, and after adjusting for the effects of education, only hypercholesterolemia as defined in the study was statistically significant in the multivariate model," Gencheva said.

A major strength of the main study is that patients are being followed over time, including annual neurocognitive testing and MRI scans, Nyenhuis said. Continued evaluation of the patients eventually could lead to identification of changes in brain regions or structures that predict cognitive impairment.

Co-authors are Gorelick and Sally Freels, Ph.D. The National Institutes of Health supported the study.

Abstract P335

NR04-1206 (ISC04/Gencheva)