Depending on how you slice the epidemiological pie, the use of cholesterol-lowering statins could appear to decrease, increase, or do nothing to the risk of developing Alzheimer disease, says a study published this week in the Archives of Neurology.
Using data from 2,798 older adults in the Cardiovascular Health Cognition study, Thomas Rea and colleagues at the University of Washington in Seattle and collaborators in several US cities found no change in the risk of AD or vascular dementia between people who had ever used statins compared to those who had never used the drugs. But a different analysis, comparing current users and never-users, gave a different result: The risk of dementia was cut in half in the current users. Yet another comparison, between former users compared to never-users, revealed a higher risk of dementia with statin use.
The results are consistent with previous studies showing that statin treatment is associated with a lower risk of AD when disease incidence is measured at one time in users vs. non-users (the case-control or cross-sectional study design), but that the benefit evaporates under the kind of prospective, follow-up design favored by Rea et al. (see ARF related news story). One proposed explanation for the inconsistent findings is that current statin use could, in fact, be a marker for good health among elders, while discontinuing statin use indicates declining health. The results provide a cautionary tale about the limitations of epidemiological studies and lead the authors to conclude that “additional investigation is needed to determine whether and for whom statin may affect dementia risk.
The gold standard of clinical investigation is, of course, the prospective, controlled trial, of which two small versions have yielded promising results for statins (see ARF related news story and Simons et al., 2002). The results of two larger studies, now underway, are eagerly awaited.—Pat McCaffrey
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