The available published evidence does not seem to support a link between statins and cognitive impairment, despite an FDA warning to that effect, according to a new systematic review.
Researchers searched PubMed, Embase, and the Cochrane Library through October 2012 for randomized, controlled trials (RCTs) and cohort, case-control and cross-sectional studies that assessed cognition in patients taking statins. They also searched FDA databases from January 1986 through March 2012 to identify reports of adverse events related to statins. Their study was meant to address whether the available published literature indicates that statins impair cognitive function and whether the FDA's postmarketing surveillance databases indicate a higher cognitive risk with statins than with other drugs commonly used for cardiovascular disease.
Results of the review, which received no external funding, were published in the Nov. 19 Annals of Internal Medicine.
A total of 57 studies (19 RCTs, 26 cohort studies, 6 case-control studies and 6 cross-sectional studies) were selected, and of these, 27 (3 RCTs, 16 cohort studies, 4 case-control studies and 4 cross-sectional studies) were included in meta-analyses. Criteria for the lowest risk of bias were met in 4 RCTs, 4 cohort studies and 2 case-control studies. However, most of the RCTs didn't provide enough information to judge the risk of bias from such factors as sequence generation, allocation concealment and selective outcome reporting. Poor representativeness and inadequate follow-up were seen in 11 cohort studies each, while 8 cohort studies had limited comparability. Three of the case-control studies, meanwhile, had limited exposure ascertainment.
Based on these data, the review authors found that low-quality evidence suggested no increase in Alzheimer's disease incidence with statin use. In addition, no difference was seen in procedural memory, attention or motor speed related to statin use. According to moderate-quality evidence, statins did not appear to increase incidence of dementia or mild cognitive impairment or change global cognitive scores, executive function, declarative memory, processing speed or visuoperception. The rate of cognitive-related adverse events in the FDA postmarketing databases was low for statins and was similar to rates reported for other common cardiovascular drugs.
The authors acknowledged that no highly powered RCTs were available for most outcomes and that the strength of the evidence in their study was therefore moderate or low. They also noted that the results for several outcomes were imprecise and inconsistent, that risk of bias was present, and that data on high-dose statins were especially limited. However, they concluded that the currently available evidence does not support the theory that statins have negative cognitive effects. “Larger and better-designed studies are needed to draw unequivocal conclusions about the effect of statins on cognition,” they wrote.