Statins are associated with a reduced risk of Alzheimer disease regardless of lipophilicity. The Rotterdam Study
Statins are associated with a reduced risk of Alzheimer disease regardless of lipophilicity. The Rotterdam Study
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DOI：
10.1136/jnnp.2008.150433
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发表时间：
2009-01-01
影响因子：
11
通讯作者：
Breteler, M. M. B.
中科院分区：
文献类型：
--
作者：
Haag, M. D. M.;Hofman, A.;Breteler, M. M. B.
背景：横断面报告表明，他汀类药物使用者不太可能患阿尔茨海默病（AD）。前瞻性研究提供了不一致的证据。此外，尚不清楚亲脂性他汀类药物（更容易通过血脑屏障的药物）和亲水性他汀类药物之间的关联是否不同。目的：前瞻性评估他汀类药物的使用是否与AD的风险相关，并确定亲脂性和亲水性他汀类药物之间的关联是否不同。从基线（1990-1993）至2005年1月，对6992例前瞻性、基于人群的鹿特丹研究参与者进行了AD事件随访。所有已填写处方的数据均来自药房记录。对于每起事件发生的每个日期，发生事件的人和队列中所有其他人的降胆固醇药物使用被归类为“任何”或“从未”使用。对他汀类药物、亲脂性和亲水性他汀类药物以及非他汀类降胆固醇药物进行了区分。数据进行了分析与考克斯回归分析，调整性别，年龄和潜在的confersers.Results：在后续行动（平均9年），582人开发AD。与从不使用降胆固醇药物相比，使用他汀类药物与AD风险降低相关（HR 0.57; 95% CI 0.37 - 0.90），但使用非他汀类降胆固醇药物与AD风险降低无关（HR 1.05; 95% CI 0.45 - 2.44）。亲脂性（HR 0.54; 95%CI 0.32至0.89）和亲水性他汀类药物（HR 0.54; 95%CI 0.26至1.11）的HR相等。结论：在一般人群中，与从未使用降胆固醇药物相比，使用他汀类药物（而非他汀类降胆固醇药物）与AD风险降低相关。这种保护作用与他汀类药物的亲脂性无关。
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.