Can Cholesterol-Lowering Drugs Prevent Alzheimer’s?...

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February 15, 2008

February 15, 2008

High cholesterol raises the risk of Alzheimer's disease and other forms of dementia. Because of this, scientists have wondered whether lowering cholesterol would have the opposite effect of lowering Alzheimer's risk.

Statin drugs, the popular cholesterol-lowering medications taken by millions, may be protective against Alzheimer's disease, according to numerous correlational studies that look back on people who have taken statins. However, because of limitations inherent in such studies, scientists have not yet come to a definitive conclusion about the potential benefits of statins in lowering the risk of Alzhiemer's disease.

A recent study has in fact questioned the conclusion that statins offer protection against Alzheimer's, although the drugs have proven benefits for heart health. The study appeared in Neurology, the medical journal of the American Academy of Neurology.

The findings, part of the large and ongoing Religious Orders Study -- also a correlational study -- involved 929 Catholic clergy members who were an average of 75 years old. All of the participants were free of dementia at the start of the study, and all agreed to a brain autopsy at the time of their death. They underwent annual memory and thinking skills tests for up to 12 years.

At the beginning of the study, 119 people were taking a statin drug.  During the 12-year follow-up period, 191 people developed Alzheimer's disease. Sixteen of those who developed Alzheimer's were using statins at the start of the study.

"Some studies have suggested people taking cholesterol-lowering drugs are less likely to have Alzheimer's disease, but our longitudinal findings found no relation between statin use and Alzheimer's," said study author Dr. Zoe Arvanitakis, Associate Professor of the Department of Neurological Sciences at Rush University Medical Center in Chicago. "The study also found no association between taking statins and a slower cognitive decline among older people."

In addition, researchers performed brain autopsies on more than 250 people who died during the study to examine the relation of statins to Alzheimer's disease pathology and stroke in the brain, the two common pathological causes of dementia.  The study found statin use at any time during the course of the study had no effect on brain changes related to Alzheimer's disease or strokes, although other studies contradict this finding.

Dr. Arvanitakis notes the study is limited in that there were relatively few statin users among those who died. She says future studies will need to look at the possibility of associations of statins with other pathologic changes of Alzheimer's disease not examined in this study.

Another limitation of this study is that the researchers did not list the cholesterol levels of the participants prior to their taking statins.  Presumably, those who took statins did so because they at one time had elevated cholesterol, a risk factor for Alzheimer's. Such individuals might have a higher risk of Alzheimer's than people with naturally lower cholesterol, but in this study they showed no higher risk than those who did not use statins. If one assumes that the participants who did not take statins had naturally lower cholesterol levels, then the results of this study might be interpreted differently. Statin use might have actually protected participants against Alzheimer's, causing them to have no greater risk than the non-statin users.

Mixed Results

Earlier studies have had mixed results on whether statin drugs benefit the brain. A preliminary study last fall from researchers from Group Health and the University of Washington, for example, found that popular cholesterol-lowering medicines like Zocor, Mevacor, and Altocor may have benefits for the brain. It found that seniors in their 60s and 70s who were taking statin drugs before they died had fewer of the twisted tangles commonly found in the brains of those with Alzheimer's disease. [See the article, "Can Cholesterol Pills Prevent Alzheimer's Disease."]

Doctors are unsure why, or even if, cholesterol drugs might benefit those with Alzheimer's disease. Some earlier research suggests that statins may lead to lower levels of beta-amyloid, the toxic protein that builds up in brains affected by Alzhemer's. High cholesterol may also promote inflammation and narrow arteries and blood vessels, including those that nourish brain cells essential for thinking and memory.

Some earlier studies also suggest that medicines that lower cholesterol may help to slow the relentless downward progression of those with Alzheimer's disease.  However, other studies have shown that drugs have little effect on keeping the memory sharp.

More research must be done to untangle the effects of cholesterol drugs on the brain. Currently, doctors do not know enough to recommend statins for the routine prevention or treatment of Alzheimer's disease, although such drugs have proven benefit for the heart.

The Fisher Center for Alzheimer's Research Foundation continues to fund vital research into the underlying causes of Alzheimer's disease, opening the way to new avenues of treatment and prevention.

By www.ALZinfo.org, The Alzheimer's Information Site. Reviewed by William J. Netzer, Ph.D., Fisher Center for Alzheimer's Research Foundation at The Rockefeller University.

Source:

Z. Arvanistakis, M.D., M.S., J. A. Schneider, M.D., M.S., R. S. Wilson Ph.D., et al: "Statins, Incident Alzheimer Disease, Change in Cognitive Function, and Neuropathology" Neurology, 16 January 2008.

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