DENVER—Statins may help reduce the risk of Alzheimer’s disease, according to preliminary results reported at the 54th Annual Meeting of the American Academy of Neurology. The data, from a large, family-based, case-control study known as the Multi-Institutional Research in Alzheimer’s Genetic Epidemiology (MIRAGE) trial, showed that statin treatment was associated with a 79% decrease in Alzheimer’s disease risk.

“While the data are encouraging, we emphasize that we cannot advocate the use of statins to prevent or treat Alzheimer’s disease until the findings have been confirmed prospectively,” Robert C. Green, MD, advised. Dr. Green is Associate Professor of Neurology, Genetics, and Epidemiology, and Associate Director of the Alzheimer’s Disease Center at Boston University School of Medicine.

He was quick to point out, however, that shortcomings in the earlier trials’ designs made the results questionable. “In both studies, cases and non-cases were classified in non-standardized fashion by clinicians in practice rather than by research criteria, and the temporal relationship between statin use and the onset of dementia was not clear,” he said. “In addition, the earlier investigations did not include African-Americans, did not control for educational background, and did not evaluate the effect of apolipoprotein E [APOE] genotype.”

In an effort to rectify some of these inequities, the MIRAGE trial initiated the largest investigation conducted to date into the relationship between statins and Alzheimer’s disease. A total of 2,581 subjects, of which 614 were African-American, were enrolled at 15 research centers from 1996 to 2001. Subjects included 912 persons with probable or definite Alzheimer’s disease according to research criteria and 1,669 of their non-demented relatives (usually spouses and siblings). “Both groups were reasonably well matched for age, were fairly highly educated, and had almost exactly the same percentage of heart disease,” Dr. Green noted.

The relationship between statin use and the risk of Alzheimer’s disease was evaluated using generalized estimating equations that controlled for age, sex, and ethnicity; history of heart disease, stroke, or diabetes; and APOE genotype. Results showed that statin use was associated with a reduced risk of Alzheimer’s disease (adjusted odds ratio [OR], 0.21). Antihypercholesterolemic medications other than statins had a modest but insignificant effect on Alzheimer’s disease risk (adjusted OR, 0.73). Neither African-American ethnicity nor APOE genotype altered the association between the risk of Alzheimer’s disease and statin use. In addition, there was essentially no difference in the protective effect of natural and synthetic statins, Dr. Green reported.

Regardless of these possibilities, “a prospective prevention trial that confirms our data is crucial before it can be considered sound clinical practice to recommend statins for preventing Alzheimer’s.” Dr. Green cautioned, “We must remember that we can be fooled by the results of retrospective studies. For example, everyone felt that estrogen protected against heart disease based on the results of retrospective studies; however, a later prospective study looking at secondary heart disease showed that estrogen actually increased cardiac death.”

NR