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他汀类药物、新发阿尔茨海默病、认知功能变化与神经病理学

Statins, incident Alzheimer disease, change in cognitive function, and neuropathology.

作者信息

Arvanitakis Z, Schneider J A, Wilson R S, Bienias J L, Kelly J F, Evans D A, Bennett D A

机构信息

Rush Alzheimer's Disease Center, Department of Neurological Sciences, 600 S. Paulina, Suite 1020, Rush University Medical Center, Chicago, IL 60612, USA.

出版信息

Neurology. 2008 May 6;70(19 Pt 2):1795-802. doi: 10.1212/01.wnl.0000288181.00826.63. Epub 2008 Jan 16.

Abstract

OBJECTIVE

To examine the relation of statins to incident Alzheimer disease (AD) and change in cognition and neuropathology.

METHODS

Participants were 929 older Catholic clergy (68.7% women, mean baseline age 74.9 years, education 18.2 years, Mini-Mental State Examination 28.5) free of dementia, enrolled in the Religious Orders Study, a longitudinal clinical-pathologic study of AD. All agreed to brain autopsy at time of death and underwent annual structured clinical evaluations, allowing for classification of AD and assessment of cognition (based on 19 neuropsychological tests). Statins were identified by direct medication inspection. Neuropathologic data were available on 262 participants. All macroscopic chronic cerebral infarctions were recorded. A measure of global AD pathology was derived from silver stain, and separate measures of amyloid and tangles were based on immunohistochemistry. We examined the relation of statins to incident AD using Cox proportional hazards, change in cognition using mixed effects models, and pathologic indices using logistic and linear regression.

RESULTS

Statin use at baseline (12.8%) was not associated with incident AD (191 persons, up to 12 follow-up years), change in global cognition, or five separate cognitive domains (all p values > 0.20). Statin use any time prior to death (17.9%) was not related to global AD pathology. Persons taking statins were less likely to have amyloid (p = 0.02). However, among those with amyloid, there was no relation of statins to amyloid load. Statins were not related to tangles or infarction.

CONCLUSIONS

Overall, statins were not related to incident Alzheimer disease (AD) or change in cognition, or continuous measures of AD pathology or infarction.

摘要

目的

研究他汀类药物与阿尔茨海默病(AD)发病、认知变化及神经病理学改变之间的关系。

方法

研究对象为929名老年天主教神职人员(女性占68.7%,平均基线年龄74.9岁,受教育年限18.2年,简易精神状态检查表评分为28.5),均无痴呆症,参与了宗教团体研究,这是一项关于AD的纵向临床病理研究。所有人均同意在死亡时进行脑尸检,并接受年度结构化临床评估,以对AD进行分类并评估认知情况(基于19项神经心理学测试)。通过直接检查药物来确定他汀类药物的使用情况。262名参与者有神经病理学数据。记录所有肉眼可见的慢性脑梗死情况。通过银染得出整体AD病理学指标,基于免疫组织化学分别得出淀粉样蛋白和神经原纤维缠结的指标。我们使用Cox比例风险模型研究他汀类药物与AD发病的关系,使用混合效应模型研究认知变化,使用逻辑回归和线性回归研究病理指标。

结果

基线时使用他汀类药物的比例为12.8%,与AD发病(191人,随访长达12年)、整体认知变化或五个独立认知领域均无关联(所有p值均>0.20)。死亡前任何时间使用他汀类药物的比例为17.9%,与整体AD病理学无关。服用他汀类药物的人出现淀粉样蛋白的可能性较小(p = 0.02)。然而,在有淀粉样蛋白的人群中,他汀类药物与淀粉样蛋白负荷无关。他汀类药物与神经原纤维缠结或梗死无关。

结论

总体而言,他汀类药物与阿尔茨海默病(AD)发病、认知变化、AD病理学或梗死的连续测量指标均无关。

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