Sex and ApoE genotype differences in treatment response to two doses of intranasal insulin in adults with mild cognitive impairment or Alzheimer's disease.
Sex and ApoE genotype differences in treatment response to two doses of intranasal insulin in adults with mild cognitive impairment or Alzheimer's disease.
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DOI：
10.3233/jad-122308
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Craft S
中科院分区：
文献类型：
--
作者：
Claxton A;Baker LD;Wilkinson CW;Trittschuh EH;Chapman D;Watson GS;Cholerton B;Plymate SR;Arbuckle M;Craft S
之前的一项临床试验表明，四个月的鼻内胰岛素治疗可以改善阿尔茨海默病 (AD) 或轻度认知障碍 (MCI) 患者的认知和功能，但之前的研究表明，对胰岛素治疗的反应可能因性别和 ApoE ε4 携带情况而异。因此，对试验中的 104 名 MCI 或 AD 参与者完成了使用重复测量协方差分析的应答者分析，这些参与者接受安慰剂或 20 或 40 IU 胰岛素 4 个月，通过鼻腔输送装置给药。结果表明，有记忆障碍的男性和女性对鼻内胰岛素治疗的反应不同。关于故事记忆延迟，男性和女性在服用 20 IU 鼻内胰岛素时表现出认知改善，但只有男性在服用 40 IU 剂量时表现出认知改善。 ApoE ε4 阴性个体的性别差异最为明显。对于 40 IU 剂量，ApoE ε4 阴性男性有所改善，而 ApoE ε4 阴性女性则恶化。他们的 ApoE ε4 阳性对应者保持认知稳定。在功能测量中没有检测到这种性别效应。然而，与男性相比，使用任一剂量鼻内胰岛素的女性的功能能力相对保留。与之前针对年轻人的研究不同，接受鼻内胰岛素的男性和女性在 4 个月的治疗过程中体重均未出现显着变化。
A previous clinical trial demonstrated that four months of treatment with intranasal insulin improves cognition and function for patients with Alzheimer’s disease (AD) or mild cognitive impairment (MCI), but prior studies suggest that response to insulin treatment may differ by sex and ApoE ε4 carriage. Thus, responder analyses using repeated measures analysis of covariance were completed on the trial’s 104 participants with MCI or AD who received either placebo or 20 or 40 IU of insulin for 4 months, administered by a nasal delivery device. Results indicate that men and women with memory impairment responded differently to intranasal insulin treatment. On delayed story memory, men and women showed cognitive improvement when taking 20 IU of intranasal insulin, but only men showed cognitive improvement for the 40 IU dose. The sex difference was most apparent for ApoE ε4 negative individuals. For the 40 IU dose, ApoE ε4 negative men improved while ApoE ε4 negative women worsened. Their ApoE ε4 positive counterparts remained cognitively stable. This sex effect was not detected in functional measures. However, functional abilities were relatively preserved for women on either dose of intranasal insulin compared with men. Unlike previous studies with young adults, neither men nor women taking intranasal insulin exhibited a significant change in weight over 4 months of treatment.