Tei Eitetsu, Yamamoto Hideki, Watanabe Takuya, Miyazaki Akira, Nakadate Toshio, Kato Nobumasa, Mimura Masaru
Department of Neuropsychiatry, Showa University School of Medicine, Tokyo, Japan.
Growth Horm IGF Res. 2008 Feb;18(1):47-54. doi: 10.1016/j.ghir.2007.07.006. Epub 2007 Aug 21.
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.
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.
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.
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.
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。
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。
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。
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。