Fourteen randomised placebo-controlled trials (28,621 participants), nine observational studies (various designs 319,636 participants), one case series and five case reports were included.
Eleven trials investigated the effect of statins compared with placebo on cognition as a primary endpoint. One trial found that simvastatin had a negative impact on cognitive effects in tests that had previously been shown to be statin-sensitive. One trial reported significant cognitive improvements in a number of cognitive measures with placebo but only an improvement in memory recall with lovastatin. Two trials reported significant improvements in cognition with lovastatin, pravastatin and atorvastatin. The other seven trials did not report any significant differences between statins and placebo on measures of cognition. Three trials measured cognition as a secondary endpoint: one reported an improvement in verbal memory with atorvastatin but no effect on cognitive function; the other two reported no significant differences in cognitive decline between pravastatin or simvastatin and placebo.
Four of the nine observational studies reported possible protective or beneficial effects of statins, three reported no effects of statins on cognition and one study reported an increased risk of delirium. The case reports included people who took simvastatin, atorvastatin and rosuvastatin and reported symptoms of memory loss, behavioural changes, impaired concentration and attention, paranoia and anxiety that started between five days and nine months after starting statin therapy. All made a full recovery after stopping statins. Drug surveillance data from the US Food and Drug Administration over a five-year period reported 60 cases of memory loss (most involved simvastatin and atorvastatin) that developed within two months of the treatment in around half of the cases.