Cholesterol bad for brain too, UCSF study says

March 14, 2002

Higher cholesterol levels are not only bad for the heart and blood vessels, they increase the risk of cognitive impairment, the precursor to Alzheimer's disease, according to a study of elderly women by UCSF researchers.

Also, women who used cholesterol-lowering drugs called statins scored higher on tests of basic cognitive skills, such as memory, attention, and language, according to lead author Kristine Yaffe, MD, UCSF assistant professor of psychology, neurology and epidemiology, and chief of geriatric psychiatry at San Francisco Veterans Affairs Medical Center.

"The higher cholesterol these women had, the worse they did on cognitive testing. And using statins, which reduce cholesterol, seemed to be beneficial to their performance on these tests," Yaffe said. Declining scores on cognitive tests are a symptom of early stage Alzheimer's disease, she said.

"These results fit with other studies showing that statins may help to prevent Alzheimer's disease," Yaffe added. Although statins have not been proven to help the brain in a clinical trial, she explained, studies that have looked back at patients who took statins suggest they can reduce risk of Alzheimer's. The current study is published in the latest issue of Archives of Neurology.

To look at cholesterol's effects on the brain, Yaffe and her colleagues analyzed data retrospectively on 1037 women who had participated in the HERS clinical trial of hormone replacement therapy, because the trial had collected data on both cholesterol levels over time and tests of cognitive function. The women completed tasks that measured their abilities in memory, attention, language, orientation, and visual-spatial skills.

Women with the highest LDL-cholesterol levels, and those with the highest total cholesterol levels, had significantly poorer test scores, even after statistically correcting for differences such as age, education, and their use of hormone replacement therapy. Also, women whose cholesterol levels decreased over the four years of the study were less likely to suffer from cognitive impairment, defined as scoring especially low on the tests.

Cholesterol in general, and LDL cholesterol in particular, are well known for their sinister effects on the heart and blood vessels - high levels lead to narrowing of the arteries and increased risk of heart disease. HDL cholesterol is known as "good" cholesterol because high levels seem to protect against heart attack.

In addition to clogging arteries, and possibly leading to vascular changes in the brain, cholesterol may promote the clumping of a protein called beta-amyloid, which is believed to damage the brain in Alzheimer's disease patients.

Yaffe doesn't encourage people to start taking statins to prevent Alzheimer's. "Until we see the results of a randomized clinical trial, people shouldn't be taking statins for that purpose. However, if someone has high LDL or total cholesterol, they may be prescribed statins anyway to prevent heart disease," she said. Adopting a low cholesterol diet is the other proven and highly recommended way for people to reduce cholesterol to healthier levels, she added.
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Co-investigators on the study included: Deborah Grady, MD, MPH, UCSF professor and vice chair of epidemiology and biostatistics, and SFVAMC physician; Feng Lin, statistician in UCSF's department of epidemiology and biostatistics; and Elizabeth Barrett-Connor, MD, professor in the department of community and family medicine at University of California, San Diego.

The study was supported by grants from Wyeth-Ayerst, Inc., and the National Institutes of Health.

The San Francisco Veterans Affairs Medical Center has been a primary affiliate of University of California San Francisco since 1974. The UCSF School of Medicine and the SFVAMC collaborate to provide education and training programs for medical students and residents at SFVAMC. SFVAMC maintains full responsibility for patient care and facility management of the medical center. Physicians at SFVAMC are employed by the Department of Veterans Affairs and also hold UCSF faculty appointments.

University of California - San Francisco

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