Long-Acting Intranasal Insulin Detemir Improves Cognition for Adults with Mild Cognitive Impairment or Early-Stage Alzheimer's Disease Dementia
Long-Acting Intranasal Insulin Detemir Improves Cognition for Adults with Mild Cognitive Impairment or Early-Stage Alzheimer's Disease Dementia
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DOI：
10.3233/jad-141791
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发表时间：
2015-01-01
影响因子：
4
通讯作者：
Craft, Suzanne
中科院分区：
文献类型：
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作者：
Claxton, Amy;Baker, Laura D.;Craft, Suzanne
先前的试验显示，鼻内注射胰岛素对患有阿尔茨海默氏病痴呆（AD）或遗忘型轻度认知障碍（MCI）的成年人有很好的效果。这些试验使用常规胰岛素，与长效胰岛素类似物（如地特胰岛素）相比，其半衰期较短。目前的试验检查了鼻内地特胰岛素是否能改善MCI或AD成人的认知或日常功能。60名诊断为MCI或轻度至中度AD的成年人接受安慰剂（n = 20）、20 IU地特胰岛素（n = 21）或40 IU地特胰岛素（n = 19）21天，通过鼻内给药装置给药。结果显示，与安慰剂组相比，40 IU组的记忆复合物具有治疗效果（p < 0.05）。APOE状态（p < 0.05）缓解了这种效应，反映了APOE-β 4携带者的改善（p < 0.02）和非携带者的恶化（p < 0.02）。基线时胰岛素抵抗越高，40 IU剂量的改善越大（r = 0.54，p < 0.02）。对于言语工作记忆（p < 0.03）和视觉空间工作记忆（p < 0.04），显著的治疗效果也很明显，反映了接受高剂量鼻内地特胰岛素的受试者的改善。日常功能和执行功能无显著差异。总之，40 IU地特胰岛素每日治疗可调节AD或MCI成人的认知，主要记忆复合终点的治疗反应存在APOE相关差异。需要进一步研究APOE相关治疗差异的机制基础，并进一步评估鼻内地特胰岛素的疗效和安全性。
Previous trials have shown promising effects of intranasally administered insulin for adults with Alzheimer's disease dementia (AD) or amnestic mild cognitive impairment (MCI). These trials used regular insulin, which has a shorter half-life compared to long-lasting insulin analogues such as insulin detemir. The current trial examined whether intranasal insulin detemir improves cognition or daily functioning for adults with MCI or AD. Sixty adults diagnosed with MCI or mild to moderate AD received placebo (n = 20), 20 IU of insulin detemir (n = 21), or 40 IU of insulin detemir (n = 19) for 21 days, administered with a nasal drug delivery device. Results revealed a treatment effect for the memory composite for the 40 IU group compared with placebo (p < 0.05). This effect was moderated by APOE status (p < 0.05), reflecting improvement for APOE-epsilon 4 carriers (p < 0.02), and worsening for non-carriers (p < 0.02). Higher insulin resistance at baseline predicted greater improvement with the 40 IU dose (r = 0.54, p < 0.02). Significant treatment effects were also apparent for verbal working memory (p < 0.03) and visuospatial working memory (p < 0.04), reflecting improvement for subjects who received the high dose of intranasal insulin detemir. No significant differences were found for daily functioning or executive functioning. In conclusion, daily treatment with 40 IU insulin detemir modulated cognition for adults with AD or MCI, with APOE-related differences in treatment response for the primary memory composite. Future research is needed to examine the mechanistic basis of APOE-related treatment differences, and to further assess the efficacy and safety of intranasal insulin detemir.