Abstract

This study aimed to determine the dose–response relationship between the levels of statin exposure and the incidence of Alzheimer’s disease (AD). We included 119,013 Korean adults (≥ 60 years old) using a database from the Korean National Health Insurance Service (2002–2013). Statin exposure was treated as a time-varying variable. Incidence of AD was defined by the first claim code for AD with anti-Alzheimer drugs. AD occurred in 9467 cases during a median 7.2 years of follow-up. Overall, statin use was not associated with an increased risk of AD incidence [adjusted hazard ratio (aHR) = 1.04; 95% confidence interval (CI) = 0.99–1.10]. When examined by level of statin exposure, statin prescription < 540 days during a 2-year window time was associated with a higher risk for incidence of AD compared to statin non-use. However, days of prescription ≥ 540 and cumulative defined daily dose ≥ 540 of statin were associated with decreased risk of AD [aHR (95% CI) = 0.87 (0.80–0.95) and 0.79 (0.68–0.92), respectively]. Our findings indicate that less persistent statin use is associated with increased risk of AD, whereas persistent and adherent statin use is associated with decreased risk of AD.

Highlights

  • This study aimed to determine the dose–response relationship between the levels of statin exposure and the incidence of Alzheimer’s disease (AD)

  • We aimed to evaluate the association of statin use with incidence of AD considering the time-varying status of statin use along with the dose–response relationship

  • The proportions of statin prescriptions ≥ 540 days and ≥ 540 cumulative defined daily dose (cDDD) among statin users during the 2-year time window increased from 9.1% and 0.4% in 2002–2003, respectively, to 14.4% and 44.4% in 2010–2011

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Summary

Introduction

This study aimed to determine the dose–response relationship between the levels of statin exposure and the incidence of Alzheimer’s disease (AD). When examined by level of statin exposure, statin prescription < 540 days during a 2-year window time was associated with a higher risk for incidence of AD compared to statin non-use. As one of the most commonly used drugs, there has been concern that statin use has a long-term adverse effect, including cognitive dysfunction and dementia. In 2012, the US Food and Drug Administration (FDA) raised concerns about the adverse cognitive effects of statins, such as memory loss, based on case r­ eports[6]. Previous studies on the effect of statin use on dementia outcome are limited in the following aspects: (1) Most studies classified subjects as either a statin user or non-user at baseline without considering the time-varying nature of statin c­ onsumption[12,13,14,16,18].

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