Swiger KJ, Manalac RJ, Blumenthal RS, et al.
Mayo Clin Proc. 2013 Sep 27. doi: 10.1016/j.mayocp.2013.07.013. [Epub ahead of print]

Background

Statin use has been linked to cognitive effects, which led to the US Food and Drug Administration (FDA) to change the labelling for statins [1]. The FDA noted ‘ill-defined memory loss’ and ‘confusion’, based on observational studies and randomised controlled trials, a range of time of onset, and a reversible nature upon medication discontinuation.
However, in a narrative overview of statin safety literature, it was concluded that statin use does not yield an increased risk of cognitive decline, and that the FDA label change should not change clinical practice [2]. But the most recent Cochrane Review on statins for primary prevention of cardiovascular disease indicates a persistent concern that statins may have adverse effects on cognition [3].
With regard to long-term cognitive outcomes, two epidemiologic studies published in 2000 have reported a lower risk of dementia in those using statins [4,5]. Mixed results on this subject have been published thereafter. This systematic review and meta-analysis therefore aims to test the hypothesis that statins have short-term and/or long-term cognitive effects in adults without a history of cognitive dysfunction, using data of randomised controlled trials and high-quality prospective cohort studies.

Main results

• Eight studies met the quality criteria for quantitative analysis of effects on short-term cognition. Digit Symbol Substitution Test (DSST) score was used to assess short-term cognition, Three studies provided sufficient DSST data for quantitative synthesis. Change in mean DSST score was consistent among those studies with no adverse effect of statin therapy. A trend was seen towards a benefit of statin use (mean change: 1.65, 95%CI: -0.03 to 3.32).
• Eight studies met the quality criteria for quantitative synthesis of the effect on dementia, encompassing data of 23443 patients with mean statin exposure duration of 3 to 24.9 years. Three studies found no association between statin use and incident dementia, while five studies found a favourable effect for statins. Quantitative synthesis showed a 29% reduction in incident dementia in patients on statins (HR: 0.71, 95%CI: 0.61-0.82).
• Five studies with a mean follow-up of 6.2 years provided enough data to calculate an absolute risk reduction of 2% (95%CI: 1%-3%) and a number needed to treat of 50 (95%CI 33-100).

Conclusion

This systematic review and meta-analysis of statin use in adults without a history of cognitive dysfunction, does not provide evidence for adverse effects on short-term cognition. Analysis of the long-term effects even showed a protective effect of statins on dementia, with 29% relative reduction and 2% absolute risk reduction.
It is as yet uncertain how these results may apply to patients with cognitive dysfunction at baseline, or other patient subgroups. Nevertheless, this study provides reassuring information to take away possible concerns on the neurocognitive safety of statin therapy. According to this publication, there is no evidence to change practice guidelines.

References

1. FDA Drug Safety Communication: important safety label changes to cholesterol-lowering statin drugs. US FDA website. http://www. fda.gov/Drugs/DrugSafety/ucm293101.htm. Accessed August 15, 2013.
2. Jukema JW, Cannon CP, De Craen AJM, Westendorp RGJ, Trompet S. The controversies of statin therapy: weighing the evidence. J Am Coll Cardiol. 2012;60(10):875-881.
3. Taylor F, Huffman MD, Macedo AF, et al. Statins for the pri- mary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2013;1:CD004816.
4. Jick H, Zornberg G, Jick S. Statins and the risk of dementia. Lan- cet. 2000;356(9242):1627-1631.
5. Wolozin B, Kellman W, Ruosseau P, Celesia GG, Siegel G. Decreased prevalence of Alzheimer disease associated with 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors. Arch Neurol. 2000;57(10):1439-1443.

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