DIMENSIONS Autumn 2004

Spotlight on Research: Do Cholesterol-Lowering Medications Reduce Alzheimer’s Disease?

by Robert G. Riekse, MD

photo of Rieske research group

With the introduction of cholesterol-lowering medications called “statins,” it has been shown that the risk for heart disease and stroke can be reduced. The same risk factors that are involved in the development of heart disease or stroke, including high cholesterol, may also be important factors in the development of Alzheimer’s disease (AD). For example, persons who have high cholesterol in mid-life are almost three times as likely to develop Alzheimer’s disease, compared to those who have normal cholesterol.

Two large epidemiological studies have shown that statin medications may significantly reduce the risk for developing Alzheimer’s disease. In one study, statin medications were compared to other medications used in the treatment of heart disease and stroke, such as beta-blockers, diuretics and ACE inhibitors. Subjects who were taking statin medications had a 70% decreased prevalence of Alzheimer’s disease, compared to those who were taking the other medications. In another study, statin medications were compared to other cholesterol-lowering medications such as niacin and gemfibrozil. Again, only statin medications were associated with a reduced risk for Alzheimer’s disease. Therefore, it is thought that statins may prevent the development of Alzheimer’s disease not only by lowering cholesterol but also through other mechanisms.

Animal studies have indicated that statins are able to reduce a key protein involved in the development of Alzheimer’s disease. This protein, A-beta, is a precursor of the amyloid plaque, a pathological hallmark of Alzheimer’s disease. When animals were treated with a statin medication, simvastatin, over a relatively short period of time, there was more than a 40% reduction in the amount of this protein. It is not known if these medications will have the same effect in humans.

There are currently six statins available in the United States. These include simvastatin (Zocor®), prava-statin (Pravachol®), atorvastatin (Lipitor®), lovastatin (Mevacor®), fluvastatin (Lescol®), and rosuvastatin (Crestor®). Statins have been available for clinical use since the early 1990s and have well-established safety and tolerability profiles. Each inhibits a key enzyme necessary to produce cholesterol. Some are more potent, having a greater ability to reduce total and LDL cholesterol, the “bad form” of cholesterol. For example, atorva-statin and rosuva-statin are able to reduce total cholesterol and LDL cholesterol by more than 50% while raising HDL, the “good form” of cholesterol, by 10%. Some statins are able to pass into the brain whereas others act more peripherally. It is not known if the benefit derived from a statin is related to its ability to affect these various sources of cholesterol.

Throughout the past year, at the Alzheimer’s Disease Research Center located at the Seattle VAPSHCS, we have been recruiting subjects for three studies that are investigating the impact statins may have in the development of Alzheimer’s disease. Two studies, the Pfizer LEADe and the Alzheimer’s Disease Cooperative Study, involve subjects who have been previously diagnosed with Alzheimer’s disease and have normal cholesterol. These subjects are randomized to either a statin medication or placebo to investigate the possible use of statins in treating Alzheimer’s disease and possibly delaying its progression.

Another study, the Riekse Statin Study, is investigating the impact statins may have in those with normal cognition but who may be at increased risk for developing Alz-heimer’s disease because of high cholesterol. In this study, subjects who have normal cognition are randomized to one of two study medications, either simvastatin (Zocor®) or pravastatin (Pravachol®). Measurements are made before and after three months of treatment. Since recent research has suggested that persons who have high cholesterol in mid-life may be at high risk for developing Alzheimer’s disease, it is hoped that treating these individuals may prevent the development of AD.

Increasing evidence suggests that the same risk factors involved in coronary or cerebrovascular disease may also be involved in the development of Alzheimer’s disease. Consequently, treatment with statin medications may either reduce risk or delay the progression of Alzheimer’s disease. We are continuing to recruit subjects for all three studies to investigate this possibility. If you are interested and would like further information or know of someone who may qualify for one of our studies, please contact us at 1-800-317-5382 or 206-764-2069.


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