The Role of Lipid-Lowering Drugs in Cognitive Function: A Meta-Analysis of Observational Studies

Mahyar Etminan, Pharm.D., Sudeep Gill, M.D., FRCPC, Ali Samii, M.D., FRCPC


Pharmacotherapy. 2003;23(6):726-730. 

In This Article

Abstract and Introduction

Study Objective: To quantify the risk of cognitive impairment with use of lipid-lowering drugs.
Design and Data Sources: Literature search through MEDLINE and EMBASE databases; data from seven observational studies were analyzed.
Measurements and Main Results: We quantified the risk of cognitive impairment first with the use of any lipid-lowering drug, and then specifically with the statins, using the random effects model. We tested for heterogeneity using the Q statistic as well as quantitatively using the Ri statistic. All seven studies provided data for statin users, and five provided data only on use of lipid-lowering drugs. Compared with patients not receiving lipid-lowering drugs, the relative risk of cognitive impairment with any lipid-lowering drug was 0.62 but was not statistically significant (95% confidence interval [CI] 0.28-1.38), and the relative risk with statins was 0.43 and was statistically significant (95% CI 0.31-0.62).
Conclusion: Lipid-lowering drugs -- in particular, the statins -- seem to lower the odds of developing cognitive impairment. Randomized, controlled trials are needed to address the efficacy of these agents specifically in different types of dementia.

Observational studies show that lipid-lowering drugs may reduce the risk of Alzheimer's disease and improve cognitive function.[1,2] Several mechanisms may explain this potential protective effect. It is believed that cholesterol plays a pivotal role in formation of amyloid plaques, and reduction in cholesterol formation may slow the process of plaque formation.[3] It also is postulated that a cognitive benefit of lowering lipids may be specific to 3-hydroxy-3-methylglutaryl coenzyme A (CoA) reductase inhibitors (statins) and may relate to their antioxidant or antiinflammatory properties.[4] If this is the case, nonstatin lipid-lowering drugs may either have no protective benefit against cognitive impairment or have a reduced benefit compared with that of statins.


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