title: Is statin-associated cognitive impairment clinically relevant? A narrative review and clinical recommendations.
abstract: OBJECTIVE
  To explore the impact of statin use on cognition.
  
  
  METHODS
  A literature search was performed using MEDLINE (1950-November 2011), EMBASE (1980-November 2011), and the Cochrane Library (1960-November 2011) using the search terms "cognition/drug effects," "delirium, dementia, amnestic, cognitive disorders/chemically induced," "memory disorders/chemically induced," "hydroxymethylglutaryl-CoA reductase inhibitors/adverse effects," and "hydroxymethylglutaryl-CoA reductase inhibitors." A bibliographic search on included references was also conducted.
  
  
  METHODS
  Studies were included for analysis if they were conducted in humans and examined the impact of statin use on cognition as either a primary or secondary endpoint; case reports and case series were also included for analysis.
  
  
  RESULTS
  Reports of statin-associated cognitive impairment were found primarily in observational studies (eg, case reports/series). One randomized controlled trial demonstrated that simvastatin impaired some measures of cognition compared to placebo. Conversely, in the majority of randomized controlled trials and observational studies, statins were found to have either a neutral or beneficial effect on cognition. Preliminary data suggest that statins that are less lipophilic (ie, pravastatin and rosuvastatin) may be less likely to contribute to cognitive impairment due to limited penetration across the blood-brain barrier. These drugs would be a logical alternative in cases where cognitive impairment secondary to another statin is suspected.
  
  
  CONCLUSIONS
  Despite several reports of statin-associated cognitive impairment, this adverse effect remains a rare occurrence among the totality of the literature. If statin-associated cognitive impairment is suspected, a trial discontinuation can reveal a temporal relationship. Switching from lipophilic to hydrophilic statins may resolve cognitive impairment. The vascular benefits and putative cognitive benefits outweigh the risk of cognitive impairment associated with statin use; therefore, the current evidence does not support changing practice with respect to statin use, given this adverse effect.
authors.affiliation: Geriatric Pharmacotherapy, School of Pharmacy, University of Waterloo, Waterloo, ON, Canada. carlos.rojas-fernandez@uwaterloo.ca
authors.forename: Carlos H
authors.initials: CH
authors.lastname: Rojas-Fernandez
authors.forename: Jean-Christy F
authors.initials: JC
authors.lastname: Cameron
mesh_terms: D001812:Blood-Brain Barrier / Q000378:metabolism; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects* / Q000737:chemistry / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors