Association between statin use and cognitive function: A systematic review of randomized clinical trials and observational studies.

The US Food and Drug Administration issued a black box warning in 2012 regarding the association of statin use with cognitive impairment. This may deter patients and practitioners from using statins for guideline-directed indications. Large studies have not shown an increase in cognitive impairment with statin use. MEDLINE, EMBASE, and Cochrane databases were searched up to October 2019. We present an up-to-date systematic review of randomized controlled trials (RCTs) and prospective observational studies examining the association between statin use and cognitive status in a population aged ≥60 years. Twenty-four studies with 1,404,459 participants were included in the review. Twenty-one were prospective observational studies, and 3 were RCTs. All 3 RCTs, which ranged from 3.2 to 5.6 years of follow-up, showed no significant association between statin use and adverse cognitive effects (odds ratio [OR] 1.03 [0.82-1.30]) and (OR 1.0 [0.61-1.65]). The mean difference in the Mini-Mental State Examination was insignificant (0.06 [-0.04 to 0.16]) in the third RCT. The follow-up for observational studies ranged from 3 to 15 years. Ten observational studies showed reduced incidence of dementia. Seven showed no association with incident dementia. Three studies showed decline in cognition was similar, whereas one showed slower decline with statin use. There was no evidence of adverse cognitive effects, including incidence of dementia, deterioration in global cognition, or specific cognitive domains associated with statin use in individuals aged ≥60 years. Future studies should examine this association in studies with longer follow-up periods.