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

Abstract

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: We followed 6992 participants of the prospective, population-based Rotterdam Study, from baseline (1990-1993) until January 2005 for incident AD. Data on all filled prescriptions came from pharmacy records. At each date an 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. We distinguished between statin, lipophilic and hydrophilic statins, and non-statin cholesterol-lowering drugs. Data were analysed with Cox-regression analysis, adjusting for sex, age and potential confounders.

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

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