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July 31, 2008 —一篇墨西哥裔美国人社区年长者族群基础的世代研究发现，在5年的追踪期间，statin类药物的使用者发生失智或者认知缺损的机会是其同侪的一半。
研究者对居住在加州Sacramento的1,674名年纪在60岁以上无失智的墨西哥裔美国人，评估使用statins类药物和发生失智与认知缺损之间的关联，这些人参加“Sacramento Area Latino Study on Aging (SALSA)”这项前溯世代研究。
本研究主要作者为密西根大学的Caryn Cramer博士及其同事，研究发表于7月29日的神经学(Neurology)期刊。
【研究并不意味Statins适用于每个人】
共同作者、密西根大学的Mary N. Haan博士向Medscape Psychiatry表示，该研究认为，服用statins药物的人 —用来减少低密度脂蛋白胆固醇，或者，如果是糖尿病患，用来减少心肌梗塞风险— 或许可以有降低失智或认知缺损风险的好处。
她强调，目前本研究并不意味大家要开始服用statins类药物来帮助治疗失智症或者认知缺损；她指出，有人担心这或许会增加statins的使用，我不认为我们已经了解statins如何影响神经退化，但我们的结果是令人鼓舞的。
这项研究是针对社区中有糖尿病高风险的某种族年长者进行；在其他族群，statins可能会有不同、较小的效果，或甚至没有效果；她指出，这需要进一步研究。
研究团队写道，使用降血脂药物与认知结果之间关联性的证据很复杂，他们使用SALSA研究的资料进行研究。
参与者在1998至1999年间被纳入进行中的SALSA研究，他们接受每年的认知和临床评估，包括确认statin之使用(检查参与者的药柜)。
目前的研究着眼于其中1,674名参与者的5年追踪结果，这些人在开始时并没有失智，也没有无失智的认知缺损。
总共有452名参与者(27%)在研究期间服用statins类药物，Statin类药物定义为任何一种的 3-hydroxy-3-methylglutaryl 辅酶A (HMG-CoA)-还原酶抑制剂，在这5年间有各种使用情况；举例来说，在第4次访视时(使用statin的截止点)，statin类药物使用情形如下：atorvastatin (104名参与者)、cerivastatin (0名参与者)、 fluvastatin (6名参与者)、lovastatin (104名参与者)、 pravastatin (28名参与者)、 rosuvastatin (5名参与者)、simvastatin (46名参与者)。
5年追踪结束之后，130名参与者发生失智：82 名可能是阿兹海默氏症，48名出现无失智的认知缺损。
Cox比例风险模型中，校正所有重要的共同变项(教育、抽烟状态、出现至少一个APOE-ε4 对偶基因、一开始有中风或者糖尿病史)，曾使用statins类药物的人，发生失智或者无失智的认知缺损风险，比未使用该类药物者低44% (风险率0.56; 95% CI, 0.37 – 0.87)。
Haan博士表示，其研究是显示statins类药物可以初步预防失智的最初研究之一，不过，由于这是一个观察研究，因此目前还不能作出完整结论。
她指出，我们仍不清楚statins作为初步预防治疗是否会优于其他药物，我们也还不完全了解statins类药物影响神经退化的方式，这些都还有待我们努力。
Cramer博士在她完成博士学位以及进行研究期间，受雇于生产atorvastatin (Lipitor)的Pfizer公司；Pfizer公司并未提供支持本研究的任何物质，也未参与研究设计、进行、管理、分析、诠释、回顾或者核准研究或撰稿；共同作者无人宣称有任何相关资金上的往来。
Statins Reduce Risk for Cognitive Impairment
By Marlene Busko
Medscape Medical News
July 31, 2008 — Statin users are about half as likely as nonusers to develop dementia or cognitive impairment without dementia, new research suggests. According to study investigator Mary N. Haan, DrPh, from the University of Michigan, in Ann Arbor, this is one of the first studies to show that statins could have value in the primary prevention of dementia.
The study suggests that people already taking statins — to decrease low-density-lipoprotein-cholesterol levels or, if they are diabetic, to lower their risk of myocardial infarction — might benefit from the reduced risk for dementia or cognitive impairment, Dr. Haan told Medscape Neurology and Neurosurgery.
However, she said, the observational nature of the research warrants caution: "This does not mean at this point that people should start using statins because it might help them with their dementia or cognitive impairment."
"There is some concern that this might initiate a greater use of statins. I don't think we are there yet in terms of understanding how statins affect neurodegeneration, but our results are encouraging," she added.
The findings are published in the July 29 issue of Neurology. Caryn Cramer, PhD, also from the University of Michigan, was lead author on the study.
The 5-year follow-up study examined 1674 Mexican Americans, aged 60 years and older, who were dementia-free at baseline and were participants in the Sacramento Area Latino Study on Aging (SALSA) prospective cohort study.
In this ongoing study designed to examine whether vascular and lifestyle risk factors increase the risk for dementia and decline in cognitive and physical functioning, the investigators set out to assess the possible link between statin use and the incidence of combined dementia and cognitive impairment without dementia.
Participants were enrolled in 1998 and 1999. They underwent yearly cognitive and clinical evaluations, which included the verification of statin use.
A total of 452 participants (27%) took statins at some point during the study. Statins were defined as any 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)-reductase inhibitor, and use varied over the 5 years. At visit 4, the cutoff for statin exposure, statin use was as follows: atorvastatin (104 participants), cerivastatin (0 participants), fluvastatin (6 participants), lovastatin (104 participants), pravastatin (28 participants), rosuvastatin (5 participants), and simvastatin (46 participants).
Over the 5-year follow-up, 130 participants developed dementia — 82 with likely Alzheimer's disease and 48 with cognitive impairment without dementia.
In a Cox proportional hazard model adjusted for education, smoking status, presence of at least 1 APOE-ε4 allele, and a history of stroke or diabetes at baseline, subjects who had used statins were 44% less likely than nonusers to develop dementia or cognitive impairment without dementia (hazard ratio, 0.56; 95% confidence interval, 0.37 – 0.87).
This study was conducted in community-dwelling elderly people from an ethnic group at high risk for diabetes. In other populations, statins could have different, smaller, or no effects. This needs to be investigated further, said Dr. Haan.
"We still don't know if some statins will be better than others in primary prevention, and we don't fully understand the way statins work to influence neurodegeneration. These are all things that people are working on," she added.
During the time the study was conducted, Dr. Cramer was employed by Pfizer Corporation, manufacturer of atorvastatin (Lipitor). Pfizer did not provide any material support for this study, and did not participate in the design, conduct, management, analysis, interpretation, review, or approval of the study or the manuscript. None of the other authors have disclosed any relevant financial relationships.
Neurology. 2008;71:505-513.