Beth A Taylor1, Alecia D Dager2, Gregory A Panza3, Amanda L Zaleski3, Shashwath Meda4, Gregory Book4, Michael C Stevens2, Sarah Tartar5, C Michael White6, Donna M Polk7, Godfrey D Pearlson2, Paul D Thompson8. 1. Department of Cardiology, Hartford Hospital, Hartford, CT; Department of Kinesiology, University of Connecticut, Storrs, CT. Electronic address: Beth.Taylor@uconn.edu. 2. Department of Psychiatry, Yale University, New Haven, CT; Olin Neuropsychiatry Center, Institute of Living, Hartford Hospital, Hartford, CT. 3. Department of Cardiology, Hartford Hospital, Hartford, CT; Department of Kinesiology, University of Connecticut, Storrs, CT. 4. Olin Neuropsychiatry Center, Institute of Living, Hartford Hospital, Hartford, CT. 5. Department of Psychiatry, Hartford Hospital, Hartford, CT. 6. University of Connecticut School of Medicine, Farmington, CT; Department of Pharmacy Practice, University of Connecticut, Storrs, CT. 7. Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA. 8. Department of Cardiology, Hartford Hospital, Hartford, CT; Department of Psychiatry, Hartford Hospital, Hartford, CT.
Abstract
BACKGROUND:Functional magnetic resonance imaging (fMRI) has not been used to assess the effects of statins on the brain. We assessed the effect of statins on cognition using standard neuropsychological assessments and brain neural activation with fMRI on two tasks. METHODS:Healthy statin-naïve men and women (48±15 years) were randomized to 80 mg/day atorvastatin (n=66; 27 men) or placebo (n=84; 48 men) for 6 months. Participants completed cognitive testing while on study drug and 2 months after treatment cessation using alternative test and task versions. RESULTS: There were few changes in standard neuropsychological tests with drug treatment (all P>.56). Total and delayed recall from the Hopkins Verbal Learning Test-Revised increased in both groups (P<.05). The Stroop Color-Word score increased (P<.01) and the 18-Point Clock Test decreased in the placebo group (P=.02) after drug cessation. There were, however, small but significant group-time interactions for each fMRI task: participants on placebo had greater activation in the right putamen/dorsal striatum during the maintenance phase of the Sternberg task while on placebo but the effect was reversed after drug washout (P<.001). Participants on atorvastatin had greater activation in the bilateral precuneus during the encoding phase of the Figural Memory task while on-drug but the effect was reversed after drug washout (P<.001). CONCLUSION: Six months of high dose atorvastatin therapy is not associated with measurable changes in neuropsychological test scores, but did evoke transient differences in brain activation patterns. Larger, longer-term clinical trials are necessary to confirm these findings and evaluate their clinical implications.
RCT Entities:
BACKGROUND: Functional magnetic resonance imaging (fMRI) has not been used to assess the effects of statins on the brain. We assessed the effect of statins on cognition using standard neuropsychological assessments and brain neural activation with fMRI on two tasks. METHODS: Healthy statin-naïve men and women (48±15 years) were randomized to 80 mg/day atorvastatin (n=66; 27 men) or placebo (n=84; 48 men) for 6 months. Participants completed cognitive testing while on study drug and 2 months after treatment cessation using alternative test and task versions. RESULTS: There were few changes in standard neuropsychological tests with drug treatment (all P>.56). Total and delayed recall from the Hopkins Verbal Learning Test-Revised increased in both groups (P<.05). The Stroop Color-Word score increased (P<.01) and the 18-Point Clock Test decreased in the placebo group (P=.02) after drug cessation. There were, however, small but significant group-time interactions for each fMRI task: participants on placebo had greater activation in the right putamen/dorsal striatum during the maintenance phase of the Sternberg task while on placebo but the effect was reversed after drug washout (P<.001). Participants on atorvastatin had greater activation in the bilateral precuneus during the encoding phase of the Figural Memory task while on-drug but the effect was reversed after drug washout (P<.001). CONCLUSION: Six months of high dose atorvastatin therapy is not associated with measurable changes in neuropsychological test scores, but did evoke transient differences in brain activation patterns. Larger, longer-term clinical trials are necessary to confirm these findings and evaluate their clinical implications.
Authors: Matthew F Muldoon; Christopher M Ryan; Susan M Sereika; Janine D Flory; Stephen B Manuck Journal: Am J Med Date: 2004-12-01 Impact factor: 4.965
Authors: Paul D Thompson; Beth A Parker; Priscilla M Clarkson; Linda S Pescatello; C Michael White; Adam S Grimaldi; Benjamin D Levine; Ronald G Haller; Eric P Hoffman Journal: Prev Cardiol Date: 2010
Authors: Brian R Ott; Lori A Daiello; Issa J Dahabreh; Beth A Springate; Kimberly Bixby; Manjari Murali; Thomas A Trikalinos Journal: J Gen Intern Med Date: 2015-01-10 Impact factor: 5.128
Authors: Steven E Nissen; Erik Stroes; Ricardo E Dent-Acosta; Robert S Rosenson; Sam J Lehman; Naveed Sattar; David Preiss; Eric Bruckert; Richard Ceška; Norman Lepor; Christie M Ballantyne; Ioanna Gouni-Berthold; Mary Elliott; Danielle M Brennan; Scott M Wasserman; Ransi Somaratne; Rob Scott; Evan A Stein Journal: JAMA Date: 2016-04-19 Impact factor: 56.272
Authors: Stella Trompet; Peter van Vliet; Anton J M de Craen; Jelle Jolles; Brendan M Buckley; Michael B Murphy; Ian Ford; Peter W Macfarlane; Naveed Sattar; Chris J Packard; David J Stott; Jim Shepherd; Eduard L E M Bollen; Gerard J Blauw; J Wouter Jukema; Rudi G J Westendorp Journal: J Neurol Date: 2009-08-04 Impact factor: 4.849