Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, 185 Pilgrim Rd, Boston, MA, 02215, USA.
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
J Neurol. 2022 Sep;269(9):4817-4835. doi: 10.1007/s00415-022-11119-6. Epub 2022 Apr 28.
This study aimed at assessing the long-term effects of intranasal insulin (INI) on cognition and gait in older people with and without type 2 diabetes mellitus (T2DM).
Phase 2 randomized, double-blinded trial consisted of 24 week treatment with 40 IU of INI (Novolin R, off-label use) or placebo (sterile saline) once daily and 24 week follow-up. Primary outcomes were cognition, normal (NW), and dual-task (DTW) walking speeds. Of 244 randomized, 223 completed baseline (51 DM-INI, 55 DM-Placebo, 58 Control-INI, 59 Control-Placebo; 109 female, 65.8 ± 9.1; 50-85 years old); 174 completed treatment (84 DM, 90 Controls); 156 completed follow-up (69 DM).
DM-INI had faster NW (~ 7 cm/s; p = 0.025) and DTW on-treatment (p = 0.007; p = 0.812 adjusted for baseline difference) than DM-Placebo. Control-INI had better executive functioning on-treatment (p = 0.008) and post-treatment (p = 0.007) and verbal memory post-treatment (p = 0.004) than Control-Placebo. DM-INI increased cerebral blood flow in medio-prefrontal cortex (p < 0.001) on MRI. Better vasoreactivity was associated with faster DTW (p < 0.008). In DM-INI, plasma insulin (p = 0.006) and HOMA-IR (p < 0.013) decreased post-treatment. Overall INI effect demonstrated faster walking (p = 0.002) and better executive function (p = 0.002) and verbal memory (p = 0.02) (combined DM-INI and Control-INI cohort, hemoglobin A1c-adjusted). INI was not associated with serious adverse events, hypoglycemic episodes, or weight gain.
There is evidence for positive INI effects on cognition and gait. INI-treated T2DM participants walked faster, showed increased cerebral blood flow and decreased plasma insulin, while controls improved executive functioning and verbal memory. The MemAID trial provides proof-of-concept for preliminary safety and efficacy and supports future evaluation of INI role to treat T2DM and age-related functional decline.
本研究旨在评估鼻内胰岛素（INI）对有和没有 2 型糖尿病（T2DM）的老年人认知和步态的长期影响。
这是一项 2 期随机、双盲试验，包括 24 周的 40IU INI（诺和灵 R，超说明书使用）或安慰剂（无菌生理盐水）每日一次治疗和 24 周随访。主要结局为认知、正常（NW）和双重任务（DTW）行走速度。244 名随机患者中，223 名完成了基线检查（51 名 DM-INI、55 名 DM-Placebo、58 名 Control-INI、59 名 Control-Placebo；109 名女性，65.8±9.1 岁；50-85 岁）；174 名完成了治疗（84 名 DM，90 名对照）；156 名完成了随访（69 名 DM）。
与 DM-Placebo 相比，DM-INI 在 NW（~7cm/s；p=0.025）和 DTW 治疗时（p=0.007；p=0.812，调整基线差异）更快。与 Control-Placebo 相比，Control-INI 在治疗时（p=0.008）和治疗后（p=0.007）以及治疗后（p=0.004）的执行功能以及言语记忆方面表现更好。与 Control-Placebo 相比，DM-INI 增加了中前额皮质的脑血流（p<0.001）。更好的血管反应性与 DTW 更快相关（p<0.008）。在 DM-INI 中，治疗后血浆胰岛素（p=0.006）和 HOMA-IR（p<0.013）降低。总的来说，INI 治疗显示出更快的行走速度（p=0.002）和更好的执行功能（p=0.002）和言语记忆（p=0.02）（DM-INI 和 Control-INI 联合队列，血红蛋白 A1c 调整）。INI 与严重不良事件、低血糖发作或体重增加无关。
有证据表明 INI 对认知和步态有积极影响。接受 INI 治疗的 T2DM 参与者行走速度更快，脑血流增加，血浆胰岛素降低，而对照组的执行功能和言语记忆提高。MemAID 试验为 INI 治疗 T2DM 和与年龄相关的功能下降的初步安全性和有效性提供了证据支持，并支持进一步评估 INI 的作用。
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