title: Randomized trial of the effects of simvastatin on cognitive functioning in hypercholesterolemic adults.
abstract: OBJECTIVE
  In our initial study of the potential effects of cholesterol-lowering interventions on cognitive functioning, treatment with lovastatin as compared with placebo caused performance decrements on several neuropsychological tests, whereas scores on other tests were unaffected. The current study was designed to confirm and extend those findings.
  
  
  METHODS
  The study comprised 308 hypercholesterolemic adults between 35 and 70 years of age. Employing a randomized double-blind design, we assigned participants to daily treatment with placebo, 10 mg of simvastatin, or 40 mg of simvastatin for 6 months. A neuropsychological test battery was administered to assess cognitive functioning at baseline and at the end of the treatment period.
  
  
  RESULTS
  A total of 283 subjects completed the study: 94 subjects on placebo, 96 taking 10 mg of simvastatin, and 93 taking 40 mg of simvastatin. Compared with placebo, decremental effects of simvastatin treatment were found on tests previously observed to be sensitive to statins (P = 0.008; difference in summary z scores = 0.18; 95% confidence interval [CI]: 0.07 to 0.29) and on tests not previously administered (P = 0.04; difference in summary z scores = 0.17; 95% CI: 0.05 to 0.29), but not on tests previously observed to be insensitive to statins (P = 0.84; difference in summary z scores = 0.02; 95% CI: -0.07 to 0.10). For the three tests specifically affected by simvastatin, effects on cognitive performance were small, manifest only as failure to improve during the 6 months of treatment (compared with placebo), and were confounded by baseline differences on one test.
  
  
  CONCLUSIONS
  This study provides partial support for minor decrements in cognitive functioning with statins. Whether such effects have any long-term sequelae or occur with other cholesterol-lowering interventions is not known.
authors.affiliation: Center for Clinical Pharmacology, University of Pittsburgh, Pennsylvania 15260, USA. mfm10@pitt.edu
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Muldoon
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Ryan
authors.forename: Susan M
authors.initials: SM
authors.lastname: Sereika
authors.forename: Janine D
authors.initials: JD
authors.lastname: Flory
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Manuck
mesh_terms: D000328:Adult; D000368:Aged; D003071:Cognition / Q000187:drug effects*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000523:psychology; D008297:Male; D008875:Middle Aged; D019821:Simvastatin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D019821:Simvastatin