Claxton Amy, Baker Laura D, Hanson Angela, Trittschuh Emily H, Cholerton Brenna, Morgan Amy, Callaghan Maureen, Arbuckle Matthew, Behl Colin, Craft Suzanne
Geriatric Research, Education, & Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA Department of Psychiatry & Behavioral Science, University of Washington School of Medicine, Seattle, Washington, USA.
Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
J Alzheimers Dis. 2015;44(3):897-906. doi: 10.3233/JAD-141791.
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-ε4 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.
先前的试验表明，经鼻给予胰岛素对患有阿尔茨海默病痴呆（AD）或遗忘型轻度认知障碍（MCI）的成年人具有显著疗效。这些试验使用的是常规胰岛素，与长效胰岛素类似物（如地特胰岛素）相比，其半衰期较短。当前的试验旨在研究经鼻给予地特胰岛素是否能改善患有MCI或AD的成年人的认知或日常功能。60名被诊断为MCI或轻度至中度AD的成年人接受了安慰剂（n = 20）、20 IU地特胰岛素（n = 21）或40 IU地特胰岛素（n = 19）治疗，为期21天，通过鼻腔给药装置给药。结果显示，与安慰剂相比，40 IU组在记忆综合评分方面有治疗效果（p < 0.05）。这种效果受APOE状态的调节（p < 0.05），表明APOE-ε4携带者有所改善（p < 0.02），而非携带者则有所恶化（p < 0.02）。基线时较高的胰岛素抵抗预示着40 IU剂量会带来更大改善（r = 0.54，p < 0.02）。在言语工作记忆（p < 0.03）和视觉空间工作记忆（p < 0.04）方面也有显著的治疗效果，这反映出接受高剂量经鼻地特胰岛素治疗的受试者有所改善。在日常功能或执行功能方面未发现显著差异。总之，每日给予40 IU地特胰岛素可调节患有AD或MCI的成年人的认知，在主要记忆综合评分的治疗反应上存在与APOE相关的差异。未来需要进行研究，以探讨与APOE相关的治疗差异的机制基础，并进一步评估经鼻地特胰岛素的疗效和安全性。
