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Statins are associated with a reduced risk of Alzheimer disease regardless of lipophilicity. The Rotterdam Study

M D M Haag¹, A Hofman¹, P J Koudstaal², B H C Stricker^1,3,4 and M M B Breteler¹

¹ Department of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands
² Department of Neurology, Erasmus Medical Centre, Rotterdam, The Netherlands
³ Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands
⁴ Inspectorate for Health Care, The Hague, The Netherlands

Correspondence to:
Professor M M B Breteler, Department of Epidemiology, Erasmus Medical Centre, PO Box 2040, 3000 CA Rotterdam, The Netherlands; m.breteler{at}erasmusmc.nl

Background: Cross-sectional reports suggest that statin users are less likely to have Alzheimer disease (AD). Prospective studies have provided inconsistent evidence. Moreover, it is unclear whether the association differs for lipohilic statins, those that could more easily pass the blood–brain barrier and hydrophilic statins.

Objectives: To prospectively evaluate whether use of statins is associated with the risk of AD, and to determine whether associations differ for lipophilic and hydrophilic statins.

Method: 6992 participants of the prospective, population-based Rotterdam Study were followed, from baseline (1990–1993) until January 2005 for incident AD. Data on all filled prescriptions came from pharmacy records. For each date on which each event occurred, cholesterol-lowering drug use for the person who experienced the event and all remaining persons in the cohort was categorised as "any" or "never" use. A distinction was made between statin, lipophilic and hydrophilic statins, and non-statin cholesterol-lowering drugs. Data were analysed with the Cox regression analysis, adjusting for sex, age and potential confounders.

Results: During follow-up (mean 9 years), 582 persons developed AD. Compared with never use of cholesterol-lowering drugs, statin use was associated with a decreased risk of AD (HR 0.57; 95% CI 0.37 to 0.90), but non-statin cholesterol-lowering drug use was not (HR 1.05; 95% CI 0.45 to 2.44). HRs were equal for lipophilic (HR 0.54; 95% CI 0.32 to 0.89) and hydrophilic statins (HR 0.54; 95% CI 0.26 to 1.11).

Conclusion: In the general population, the use of statins, but not of non-statin cholesterol-lowering drugs, was associated with a lower risk of AD compared with never use of cholesterol-lowering drugs. The protective effect was independent of the lipophilicity of statins.

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