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Statins and cognitive decline in the Cardiovascular Health Study: A comparison of different analytical approaches.

TitleStatins and cognitive decline in the Cardiovascular Health Study: A comparison of different analytical approaches.
Publication TypeJournal Article
Year of Publication2021
AuthorsHazzouri, AZeki Al, Jawadekar, N, Grasset, L, Kaiser, P, Kezios, K, Calonico, S, M Glymour, M, Hirsch, C, Arnold, AM, Varadhan, R, Opoodden, MC
JournalJ Gerontol A Biol Sci Med Sci
Date Published2021 Jul 31
ISSN1758-535X
Abstract<p><b>BACKGROUND: </b>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 (RCT) effects from observational data.</p><p><b>METHODS: </b>We used observational data from 5,580 participants enrolled in the Cardiovascular Health Study from 1989/90 to 1999/2000. We conceptualized the cohort as an overlapping sequence of non-randomized 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 (3MS) examination.</p><p><b>RESULTS: </b>When comparing prevalent users to non-users (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 (e.g. comparing eligible statin initiators to non-initiators) 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), annual 3MS change comparing statin initiators to non-initiators was -0.21 points/year (95% CI:-0.81;0.39).</p><p><b>CONCLUSIONS: </b>The association of statin use and cognitive decline is attenuated towards the null when using rigorous analytical approaches that more closely mimic RCTs. 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.</p>
DOI10.1093/gerona/glab220
Alternate JournalJ Gerontol A Biol Sci Med Sci
PubMed ID34331536
ePub date: 
21/07