Statins and cognition: What can we learn from existing randomized trials?

Background: Statins are being developed as treatments for Alzheimer's dementia based on evidence from preclinical and observational studies. However, cholesterol plays an integral role in cell membrane signal transduction and suboptimal cholesterol level could potentially impair neuronal function. Additionally, results of observational nonrandomized studies may have been affected by treatment bias. Methods: We performed a systematic literature review in MEDLINE from January 1966 to July 2004 and included published prospective, randomized, and placebo-controlled human studies that examined the cognitive effects of statins. Results: Nine studies with sample sizes ranging from 22 to 20,000 and duration of 3 weeks to 5 years, met criteria for review. Study populations and cognitive outcomes varied. Four studies were >= 6 months or longer. Overall, none of these studies reported finding a positive benefit for any statin on cognition in non-demented subjects although there was inconsistent evidence for acute cognitive worsening in some studies. Conclusion: While statins intuitively have appeal for the prevention or treatment of dementia, any conclusions about their efficacy should await more deflnitive evidence from on-going prospective clinical trials