Adina Zeki Al Hazzouri1, Neal Jawadekar1, Leslie Grasset2, Paulina Kaiser3, Katrina Kezios1, Sebastian Calonico4, Maria Glymour5, Calvin Hirsch6, Alice M Arnold7, Ravi Varadhan8, Michelle C Odden9. 1. Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA. 2. University of Bordeaux, Inserm, Bordeaux Population Health Research Center, Team VINTAGE, UMR 1219 and Inserm, CIC1401-EC, France. 3. College of Public Health and Human Sciences, Oregon State University, Corvallis, USA. 4. Department of Health Policy and Management, Mailman School of Public Health, Columbia University, New York, New York, USA. 5. Department of Epidemiology & Biostatistics, University of California San Francisco, USA. 6. Center for Healthcare Policy and Research, Division of General Medicine, University of California Davis Medical Center, Sacramento, USA. 7. Department of Biostatistics, School of Public Health, University of Washington, Seattle, USA. 8. Division of Biostatistics and Bioinformatics, Sidney Kimmel Cancer Care Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. 9. Department of Epidemiology and Population Health, Stanford University, California, USA.
Abstract
BACKGROUND: Despite their well-established benefits for the prevention of cardiovascular disease, robust evidence on the effects of statins on cognition is largely inconclusive. We apply various study designs and analytical approaches to mimic randomized controlled trial effects from observational data. METHODS: We used observational data from 5 580 participants enrolled in the Cardiovascular Health Study from 1989/1990 to 1999/2000. We conceptualized the cohort as an overlapping sequence of nonrandomized trials. We compared multiple selection (eligible population, prevalent users, new users) and analytic approaches (multivariable adjustment, inverse-probability treatment weights, propensity score matching) to evaluate the association between statin use and 5-year change in global cognitive function, assessed using the Modified Mini-Mental State Examination (3MSE). RESULTS: When comparing prevalent users to nonusers (N = 2 772), statin use was associated with slower cognitive decline over 5 years (adjusted annual change in 3MSE = 0.34 points/year; 95% CI: 0.05-0.63). Compared to prevalent user design, estimates from new user designs (eg, comparing eligible statin initiators to noninitiators) were attenuated showing either null or negative association, though not significant. For example, in a propensity score-matched sample of statin-eligible individuals (N = 454), the annual 3MS change comparing statin initiators to noninitiators was -0.21 points/year (95% CI: -0.81 to 0.39). CONCLUSIONS: The association of statin use and cognitive decline is attenuated toward the null when using rigorous analytical approaches that more closely mimic randomized controlled trials. Point estimates, even within the same study, may vary depending on the analytical methods used. Further studies that leverage natural or quasi experiments around statin use are needed to replicate our findings.
BACKGROUND: Despite their well-established benefits for the prevention of cardiovascular disease, robust evidence on the effects of statins on cognition is largely inconclusive. We apply various study designs and analytical approaches to mimic randomized controlled trial effects from observational data. METHODS: We used observational data from 5 580 participants enrolled in the Cardiovascular Health Study from 1989/1990 to 1999/2000. We conceptualized the cohort as an overlapping sequence of nonrandomized trials. We compared multiple selection (eligible population, prevalent users, new users) and analytic approaches (multivariable adjustment, inverse-probability treatment weights, propensity score matching) to evaluate the association between statin use and 5-year change in global cognitive function, assessed using the Modified Mini-Mental State Examination (3MSE). RESULTS: When comparing prevalent users to nonusers (N = 2 772), statin use was associated with slower cognitive decline over 5 years (adjusted annual change in 3MSE = 0.34 points/year; 95% CI: 0.05-0.63). Compared to prevalent user design, estimates from new user designs (eg, comparing eligible statin initiators to noninitiators) were attenuated showing either null or negative association, though not significant. For example, in a propensity score-matched sample of statin-eligible individuals (N = 454), the annual 3MS change comparing statin initiators to noninitiators was -0.21 points/year (95% CI: -0.81 to 0.39). CONCLUSIONS: The association of statin use and cognitive decline is attenuated toward the null when using rigorous analytical approaches that more closely mimic randomized controlled trials. Point estimates, even within the same study, may vary depending on the analytical methods used. Further studies that leverage natural or quasi experiments around statin use are needed to replicate our findings.
Authors: Paulina Kaiser; Alice M Arnold; David Benkeser; Adina Zeki Al Hazzouri; Calvin H Hirsch; Bruce M Psaty; Michelle C Odden Journal: Int J Epidemiol Date: 2018-02-01 Impact factor: 7.196
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Authors: Philip B Gorelick; Angelo Scuteri; Sandra E Black; Charles Decarli; Steven M Greenberg; Costantino Iadecola; Lenore J Launer; Stephane Laurent; Oscar L Lopez; David Nyenhuis; Ronald C Petersen; Julie A Schneider; Christophe Tzourio; Donna K Arnett; David A Bennett; Helena C Chui; Randall T Higashida; Ruth Lindquist; Peter M Nilsson; Gustavo C Roman; Frank W Sellke; Sudha Seshadri Journal: Stroke Date: 2011-07-21 Impact factor: 7.914
Authors: Mandavi Kashyap; Sylvie Belleville; Benoit H Mulsant; Sarah N Hilmer; Amelie Paquette; Le Mai Tu; Cara Tannenbaum Journal: J Am Geriatr Soc Date: 2014-01-13 Impact factor: 5.562