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利用血清胰岛素样生长因子-I水平预测阿尔茨海默病患者对多奈哌齐的精神方面无反应情况。

Use of serum insulin-like growth factor-I levels to predict psychiatric non-response to donepezil in patients with Alzheimer's disease.

作者信息

Tei Eitetsu, Yamamoto Hideki, Watanabe Takuya, Miyazaki Akira, Nakadate Toshio, Kato Nobumasa, Mimura Masaru

机构信息

Department of Neuropsychiatry, Showa University School of Medicine, Tokyo, Japan.

出版信息

Growth Horm IGF Res. 2008 Feb;18(1):47-54. doi: 10.1016/j.ghir.2007.07.006. Epub 2007 Aug 21.

Abstract

OBJECTIVE

Insulin-like growth factor-I (IGF-I) deficiency may be involved in cognitive deficits seen with aging and in neurodegenerative diseases such as Alzheimer's disease (AD). This study was aimed at investigating whether non-responder to donepezil could be predicted using decreased serum levels of IGF-I in AD patients.

DESIGN

This study involved 106 elderly subjects: 50 patients with AD and 56 age-matched controls without dementia. In patients with AD, donepezil was given orally 3 mg/day for 4 weeks and 5 mg/day for another 12 weeks. AD patients were divided into responders and non-responders based on the changes in mini-mental state examination (MMSE) scores before and 16 weeks after treatment with donepezil. Serum levels of IGF-I and atherogenic biomarkers were determined.

RESULTS

Before treatment with donepezil, there was a significant positive correlation between serum IGF-I levels and the MMSE scores in all subjects. Serum IGF-I levels and the MMSE scores were significantly lower in AD patients than in non-demented controls and were the lowest in non-responders to donepezil. Atherogenic biomarkers (LDL cholesterol, triglycerides, lipoprotein(a), lipid peroxide, apolipoprotein E, and glucose levels) did not differ significantly among these groups. On multiple logistic regression, non-responders to donepezil showed decreased serum IGF-I levels <110 ng/ml and MMSE scores <15 points before treatment.

CONCLUSIONS

These findings suggest that decreased levels of serum IGF-I combined with MMSE scores before treatment could predict non-responders to donepezil among AD patients, which may be a simple and practical method for selecting patients expected to show a response to treatment.

摘要

目的

胰岛素样生长因子-I(IGF-I)缺乏可能与衰老相关的认知缺陷以及阿尔茨海默病(AD)等神经退行性疾病有关。本研究旨在调查是否可以通过AD患者血清IGF-I水平降低来预测对多奈哌齐无反应者。

设计

本研究纳入106名老年受试者:50例AD患者和56名年龄匹配的无痴呆对照者。AD患者口服多奈哌齐,3毫克/天,共4周,然后5毫克/天,再持续12周。根据多奈哌齐治疗前和治疗16周后简易精神状态检查表(MMSE)评分的变化,将AD患者分为反应者和无反应者。测定血清IGF-I水平和动脉粥样硬化生物标志物。

结果

在多奈哌齐治疗前,所有受试者的血清IGF-I水平与MMSE评分之间存在显著正相关。AD患者的血清IGF-I水平和MMSE评分显著低于非痴呆对照者,且在多奈哌齐无反应者中最低。这些组之间的动脉粥样硬化生物标志物(低密度脂蛋白胆固醇、甘油三酯、脂蛋白(a)、脂质过氧化物、载脂蛋白E和血糖水平)无显著差异。多元逻辑回归分析显示,多奈哌齐无反应者在治疗前血清IGF-I水平<110纳克/毫升且MMSE评分<15分。

结论

这些发现表明,治疗前血清IGF-I水平降低与MMSE评分相结合可以预测AD患者中对多奈哌齐无反应者,这可能是一种选择预期对治疗有反应患者的简单实用方法。

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