Statins Show Promise in Protecting Against Alzheimer's

So far, clinical trials have failed to demonstrate that cholesterol-lowering drugs called statins can stop the progression of Alzheimer's disease or even the conversion of mild cognitive impairment to Alzheimer's.

However, statins might be able to protect against Alzheimer's earlier in the disease process in persons who do not yet have any cognitive impairment, a new large, prospective study has found. It was conducted by Dutch scientists and published in the Journal of Neurology, Neurosurgery, and Psychiatry on October 17.

Some 7,000 subjects, average age 69 and without Alzheimer's, were followed for up to 15 years (for nine years on average). The researchers tracked all prescriptions for cholesterol-lowering drugs, including those for statins, issued to the subjects during the follow-up period. The researchers also noted which subjects—some 600 of them—developed Alzheimer's during the follow-up period. Finally the researchers looked to see whether the use of cholesterol-lowering drugs was associated with a lower risk of getting Alzheimer's even when age, gender, education level, smoking, total serum cholesterol level, apolipoprotein E (APOE) genotype, and other possibly confounding factors were considered.

There was no association for nonstatin cholesterol-lowering drugs. However, there was for statins. Compared with the nonuse of cholesterol-lowering drugs, statin use was associated with a 43 percent lower risk of Alzheimer's.

Notably, the link between statin use and a reduced risk of Alzheimer's was the same whether the statins were lipophilic (having an affinity for lipids and probably capable of easily crossing the blood-brain barrier into the brain) or hydrophilic (having an affinity for water and probably not so adept at crossing the barrier). Further, the protective effect was observed regardless of statin dosage or duration of use.

So statins might help protect people against Alzheimer's, the lead investigator, Monique Breteler, M.D., Ph.D., and colleagues concluded in their study report. Breteler is both a professor of neuroepidemiology at Erasmus University in Rotterdam and an adjunct professor of epidemiology at Harvard University School of Public Health.

“Before we conducted the study, we were skeptical about the hypothesis that statins would be associated with a decreased risk of dementia and Alzheimer's disease,” Breteler told Psychiatric News.“ So the fact that we did find a decreased risk, and especially that the effect seemed so strong, came as a surprise.”

“Our study underscores once more, in considering possible preventive interventions for Alzheimer's, that one has to take into account the exposure window,” she continued. “[Even though] clinical trials ... did not find evidence that statin use could stop progression of Alzheimer's, or conversion from mild cognitive impairment to Alzheimer's, they do not speak to the potential usefulness of statins in preventing disease [before any cognitive impairment starts].”

In other words, she concluded, “Our study calls for a very careful distinction between potential efficacy in primary, secondary, and tertiary prevention and suggests that statins should be evaluated for their usefulness in primary prevention.”

The study was funded by the Erasmus Medical Center, the Netherlands Organization for Health Research and Development, and other government agencies.

An abstract of “Statins Are Associated With a Reduced Risk of Alzheimer Disease Regardless of Lipophilicity. The Rotterdam Study” is posted at<http://jnnp.bmj.com/cgi/content/abstract/jnnp.2008.150433v1>.▪