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LDL Cholesterol Increases Risk of

Dementia After Stroke

Lead researchers: Richard Mayeux and Joan T. Moroney

The "bad" form of cholesterol just got worse. Not only are high levels of the low-density lipoprotein (LDL) form of cholesterol a significant risk factor for heart disease, they also increase a person’s risk of developing dementia after a stroke, according to a study conducted by P&S researchers. The findings, reported in the July 21, 1999, issue of JAMA, provide insight on how high cholesterol levels may contribute to vascular dementia.

"In our study, people with the highest levels of LDL cholesterol had as much as a three-fold increase in the risk of dementia with stroke, called vascular dementia," says Dr. Richard Mayeux, the Gertrude H. Sergievsky Professor of Neurology, Psychiatry, and Public Health, and the study’s principal investigator. "Low-density lipoprotein cholesterol is an independent risk factor for vascular dementia, and that finding has important therapeutic implications."

Vascular dementia is the second most common form of dementia in the elderly, following Alzheimer’s disease. Dr. Mayeux and his colleagues previously reported that APOE-e4, one variant of a gene involved in lipid metabolism, is associated with an increased risk of vascular dementia. APOE-e4 also increases the risk of developing Alzheimer’s disease. Those findings inspired Dr. Mayeux and Dr. Joan T. Moroney, assistant professor of neurology, to directly investigate the effects of cholesterol levels on the risk of Alzheimer’s disease and vascular dementia.

Of the 1,111 people followed for an average of two years, 286 became demented. Of those, 225 developed Alzheimer’s disease and 61 developed vascular dementia. Another 61 people had strokes but did not develop dementia. Risk of vascular dementia was associated with both total cholesterol and LDL cholesterol but not any form of the APOE gene. The risk of Alzheimer’s disease was not associated with lipids but was associated with the APOE-e4 gene.

The people who developed dementia following stroke had an average LDL cholesterol level of 130 milligrams per deciliter (mg/dl), while stroke patients who did not develop dementia had an average LDL level of 118 mg/dl. An LDL level of lower than 130 mg/dl is considered to be healthy.

Dr. Mayeux and Dr. Moroney, the study’s lead author, say future studies will explain how high cholesterol levels may contribute to vascular dementia. "These findings raise lots of questions, more than they answer," says Dr. Moroney. She and Dr. Mayeux have begun a new study that includes more extensive monitoring of cholesterol levels and more extensive brain imaging of patients with stroke.

Both Drs. Mayeux and Moroney agree that lowering cholesterol may reduce the risk of vascular dementia. They are considering a test of that hypothesis with clinical trials of cholesterol-lowering drugs for stroke patients with high cholesterol levels.

P&S researchers Drs. Lars Berglund, Scott Small, Carol Merchant, Karen Bell, and Yaakov Stern also contributed to the research. So did Dr. Ming-Xin Tang of the Joseph L. Mailman School of Public Health at Columbia. The National Institute on Aging funded the study. The National Institute of Neurological Disorders and Stroke also provided support for Dr. Moroney.

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