Hallschmid Manfred
Institute of Medical Psychology and Behavioral Neurobiology, University of Tübingen, Otfried-Müller-Str. 25, 72076, Tübingen, Germany.
German Center for Diabetes Research (DZD), Tübingen, Germany.
CNS Drugs. 2021 Jan;35(1):21-37. doi: 10.1007/s40263-020-00781-x. Epub 2021 Jan 30.
Brain insulin signaling contributes to memory function and might be a viable target in the prevention and treatment of memory impairments including Alzheimer's disease. This short narrative review explores the potential of central nervous system (CNS) insulin administration via the intranasal pathway to improve memory performance in health and disease, with a focus on the most recent results. Proof-of-concept studies and (pilot) clinical trials in individuals with mild cognitive impairment or Alzheimer's disease indicate that acute and prolonged intranasal insulin administration enhances memory performance, and suggest that brain insulin resistance is a pathophysiological factor in Alzheimer's disease with or without concomitant metabolic dysfunction. Intranasally administered insulin is assumed to trigger improvements in synaptic plasticity and regional glucose uptake as well as alleviations of Alzheimer's disease neuropathology; additional contributions of changes in hypothalamus-pituitary-adrenocortical axis activity and sleep-related mechanisms are discussed. While intranasal insulin delivery has been conclusively demonstrated to be effective and safe, the recent outcomes of large-scale clinical studies underline the need for further investigations, which might also yield new insights into sex differences in the response to intranasal insulin and contribute to the optimization of delivery devices to grasp the full potential of intranasal insulin for Alzheimer's disease.
大脑胰岛素信号传导有助于记忆功能，可能是预防和治疗包括阿尔茨海默病在内的记忆障碍的一个可行靶点。这篇简短的叙述性综述探讨了通过鼻内途径给予中枢神经系统（CNS）胰岛素以改善健康和疾病状态下记忆表现的潜力，重点关注最新研究结果。针对轻度认知障碍或阿尔茨海默病患者的概念验证研究和（先导）临床试验表明，急性和长期鼻内给予胰岛素可提高记忆表现，并提示脑胰岛素抵抗是阿尔茨海默病的一个病理生理因素，无论是否伴有代谢功能障碍。鼻内给予的胰岛素被认为可引发突触可塑性和局部葡萄糖摄取的改善以及阿尔茨海默病神经病理学的缓解；还讨论了下丘脑 - 垂体 - 肾上腺皮质轴活动变化和睡眠相关机制的额外作用。虽然鼻内胰岛素给药已被确凿证明是有效和安全的，但大规模临床研究的最新结果强调了进一步研究的必要性，这也可能为鼻内胰岛素反应中的性别差异带来新见解，并有助于优化给药装置，以充分发挥鼻内胰岛素治疗阿尔茨海默病的潜力。
