Statins and Cognitive Function: A Systematic Review

Study Questions:

Is there an effect of statins on cognition?


Randomized controlled trials as well as cohort, case-control, and cross-sectional studies evaluating cognition in patients receiving statins were obtained using a systematic review of statins and cognitive function from the available literature via electronic libraries through October 2012, and Food and Drug Administration (FDA) databases from January 1986 through March 2012. Two reviewers extracted data; one reviewer assessed study risk of bias, and one reviewer checked all assessments. GRADE of evidence by the opinion of the reviewers representing their level of certainty or confidence in the evidence base for the given outcome included: 1) High: further research is very unlikely to change confidence in the estimate of effect; 2) Moderate: further research is likely to affect confidence in the estimate of effect and may change the estimate; 3) Low: further research is very likely to affect confidence in the estimate of effect and is likely to change the estimate; and 4) Very low: any estimate of effect is very uncertain


Among statin users, low-quality evidence suggested no increased incidence of Alzheimer disease and no difference in cognitive performance related to procedural memory, attention, or motor speed. Moderate-quality evidence suggested no increased incidence of dementia or mild cognitive impairment or any change in cognitive performance related to global cognitive performance scores, executive function, declarative memory, processing speed, or visuoperception. Examination of the FDA postmarketing surveillance databases revealed a low reporting rate for cognitive-related adverse events with statins that was similar to the rates seen with other commonly prescribed cardiovascular medications. Imprecision, inconsistency, and risk of bias also limited the strength of findings.


The authors concluded that larger and better-designed studies are needed to draw unequivocal conclusions about the effect of statins on cognition. Published data do not suggest an adverse effect of statins on cognition; however, the strength of available evidence is limited, particularly with regard to high-dose statins.


Recently, the FDA issued a warning cautioning that statins may be associated with memory loss or confusion. The FDA website provides the expanded advice on statin risks as quoted from Dr. A.G. Egan, a deputy director of safety at the FDA: ‘In general, the symptoms were not serious and were reversible within a few weeks after the patient stopped using the statin. Some people affected in this way had been taking the medicine for a day; others had been taking it for years.’ What should patients do if they fear that statin use could be clouding their thinking? ‘Talk to your health care professional,’ Egan says. ‘Don’t stop taking the medication; the consequences to your heart could be far greater.’ I have a hard enough time convincing many patients of the value of statins that has been demonstrated in innumerable placebo-controlled trials. What is the source of evidence that may impact patients’ decisions, and has the FDA decision to warn patients about cognitive impairment been discussed with a medical advisory committee of experts?

Clinical Topics: Dyslipidemia, Nonstatins, Novel Agents, Statins

Keywords: Cognition, United States Food and Drug Administration, Hydroxymethylglutaryl-CoA Reductase Inhibitors

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