Study: Statins Reduce the Risk of Dementia

The cholesterol-lowering drugs known as statins, taken by more than 15 million Americans, have proven to be a powerful weapon in the battle against heart disease. Now, new research indicates that statins may benefit the brain as well. A study appearing Monday in the journal Neurology found that statins dramatically reduced the risk of developing dementia and Alzheimer's disease among a group of subjects 60 years and older. "It suggests that if you took statins before dementia set in, you might be 50% less likely to develop the condition," says Mary Haan, an epidemiology professor at the University of Michigan and the study's lead author. "That's a really big effect."

The potential of statins to treat dementia and Alzheimer's has been the subject of investigation for years, but to date the results have been mixed. While no clear benefit has been established for the treatment of existing dementia, studies gauging the ability of statins to prevent the disease in cognitively healthy people have been slightly more promising. But exactly how statins affect cognition remains a mystery. And experts say it's one of several puzzles that must be solved before doctors and patients can harness the full potential of these drugs, which have already become a staple of the American medicine cabinet.

Haan and her colleagues followed 1,674 elderly Mexican Americans for five years, all of whom were dementia-free at the start of the study. They monitored both mental and physical health every 12 to15 months. After adjusting for factors like education, smoking status and genetic pre-disposition, statin users were found to have a 50% lower risk of developing dementia than those not taking the drugs.

But much more research will be needed before doctors routinely prescribe statins to prevent dementia. While epidemiological studies like Haan's have been generally positive, randomized clinical trials—the benchmark of clinical research—have, for the most part, failed to show any cognitive benefits. Researchers aren't sure which data to trust.

It's possible that cognitive benefits only come with years of statin use. If that's the case, clinical trials that last but a few months would not reveal such benefits. On the other hand, epidemiological studies are not randomized and those who wind up taking statins in such studies may be resistant to cognitive decline for reasons other than statin use. "It could be a false positive," says Benjamin Wolozin, a neurologist at Boston University who studies statins and cognition. "Distinguishing between these two possibilities is exceedingly difficult."

More clues may come from a prospective, double-blind, placebo-controlled clinical trial of the statin Zocor that is nearing completion. Unlike Lipitor, which was used in previous trials that did not find cognitive benefits, Zocor actually crosses the blood-brain barrier and enters the brain. "Brain permeant statins might be far more effective than statins that don't get into the brain," says Wolozin. "The reality is that many people take statins already. The key question might be which statin produces cognitive benefits?" Haan's subjects took a range of statins, including both Zocor and Lipitor.

Wolozin says that more clinical trials are essential but will be prohibitively expensive, especially when it comes to measuring preventative benefits—because the duration of such trials would have to be much longer than is typical. "Because of the cost," he says, "we might never be able to fully test whether statins reduce the incidence of Alzheimer's disease or dementia."
But why would we look to statins to treat cognitive health in the first place? The drugs have several characteristics that make them good candidates. By reducing cholesterol—which is what they were designed to do—statins help maintain a strong blood supply to the brain.

Researchers also believe that less cholesterol means less beta-amyloid, a small protein that accumulates in the brains of Alzheimer's patients. In addition to their effects on cholesterol, statins also inhibit inflammation, another plus for the vasculature of the brain. It's also possible that statins work to inhibit some insulin pathways; high insulin levels in the brain have been associated with Alzheimer's disease. "We know that they have these properties and that they may work differently in different populations," says Haan. "But we don't really know which of the pathways the cognitive benefits come from."

Until that question is answered, she says, it's too soon to say whether people can or should take statins for general cognitive health. In fact, too little cholesterol can be just as damaging to cognition as too much. The brain makes its own cholesterol, and reducing that natural synthesis might actually promote cognitive decline. "We need to answer many questions before we can promote statins for preventative cognitive health," says Wolozin. "We are not there yet."

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