Effects of growth hormone–releasing hormone on cognitive function in adults with mild cognitive impairment and healthy older adults: results of a controlled trial.

Laura D Baker, Suzanne M Barsness, Soo Borson, George R Merriam, Seth D Friedman, Suzanne Craft, Michael V Vitiello
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引用次数: 105

Abstract

Background: Growth hormone–releasing hormone(GHRH), growth hormone, and insulin like growth factor 1 have potent effects on brain function, their levels decrease with advancing age, and they likely play a role in the pathogenesis of Alzheimer disease. Previously, we reported favorable cognitive effects of short-term GHRH administration in healthy older adults and provided preliminary evidence to suggest a similar benefit in adults with mild cognitive impairment (MCI).

Objective: To examine the effects of GHRH on cognitive function in healthy older adults and in adults with MCI.

Design: Randomized,double-blind,placebo-controlled trial.

Setting: Clinical Research Center, University of Washington School of Medicine in Seattle.

Participants: A total of 152 adults (66 with MCI) ranging in age from 55 to 87 years (mean age, 68 years); 137 adults (76 healthy participants and 61 participants with MCI) successfully completed the study.

Intervention: Participants self-administered daily subcutaneous injections of tesamorelin (Theratechnologies Inc),a stabilized analog of human GHRH (1 mg/d), or placebo 30 minutes before bedtime for 20 weeks. At baseline, at weeks 10 and 20 of treatment, and after a 10-week washout(week 30), blood samples were collected, and parallel versions of a cognitive battery were administered. Before and after the 20-week intervention, participants completed an oral glucose tolerance test and a dual-energy x-ray absorptiometry scan to measure body composition.

Main outcome measures: Primary cognitive outcomes were analyzed using analysis of variance and included 3 composites reflecting executive function, verbal memory, and visual memory. Executive function was assessed with Stroop Color-Word Interference,Task Switching, the Self-Ordered Pointing Test, and Word Fluency, verbal memory was assessed with Story Recall and the Hopkins Verbal Learning Test,and visual memory was assessed with the Visual-Spatial Learning Test and Delayed Match-to-Sample.

Results: The intent-to-treat analysis indicated a favorable effect of GHRH on cognition (P=.03), which was comparable in adults with MCI and healthy older adults.The completer analysis showed a similar pattern, with a more robust GHRH effect (P=.002). Subsequent analyses indicated a positive GHRH effect on executive function (P=.005) and a trend showing a similar treatment-related benefit in verbal memory(P=.08). Treatment with GHRH increased insulin like growth factor 1 levels by 117 %(P.001), which remained within the physiological range, and reduced percent body fat by 7.4%(P.001). Treatment with GHRH increased fasting insulin levels within the normal range by 35%in adults with MCI (P.001) but not in healthy adults. Adverse events were mild and were reported by 68%of GHRH treated adults and 36% of those who received placebo.

Conclusions: Twenty weeks of GHRH administration had favorable effects on cognition in both adults with MCI and healthy older adults. Longer-duration treatment trials are needed to further examine the therapeutic potential of GHRH administration on brain health during normal aging and “pathological aging.”

Trial registration: clinicaltrials.gov Identifier: NCT00257712

Abstract Image

生长激素释放激素对轻度认知障碍成人和健康老年人认知功能的影响:一项对照试验的结果
背景:生长激素释放激素(GHRH)、生长激素和胰岛素样生长因子1对脑功能有显著影响,其水平随年龄增长而降低,可能在阿尔茨海默病的发病机制中起作用。之前,我们报道了健康老年人短期服用GHRH对认知的有利影响,并提供了初步证据表明轻度认知障碍(MCI)的成年人也有类似的益处。目的:探讨GHRH对健康老年人和轻度认知损伤成人认知功能的影响。设计:随机、双盲、安慰剂对照试验。单位:西雅图华盛顿大学医学院临床研究中心。参与者:共有152名成人(66名患有轻度认知障碍),年龄从55岁到87岁(平均年龄68岁);137名成年人(76名健康参与者和61名轻度认知障碍参与者)成功完成了这项研究。干预措施:参与者在睡前30分钟自行皮下注射替沙莫瑞林(therattechnologies Inc),一种稳定的人类GHRH类似物(1mg /d)或安慰剂,持续20周。在基线,治疗第10周和第20周,以及10周洗脱期(第30周)后,收集血液样本,并进行平行版本的认知电池。在20周的干预前后,参与者完成了口服葡萄糖耐量试验和双能x线吸收仪扫描,以测量身体成分。主要结果测量:采用方差分析对主要认知结果进行分析,包括反映执行功能、言语记忆和视觉记忆的3个组合。执行功能采用Stroop颜色-单词干扰、任务切换、自序指向测试和单词流畅性测试,言语记忆采用故事回忆和霍普金斯言语学习测试,视觉记忆采用视觉空间学习测试和延迟匹配样本测试。结果:意向治疗分析显示GHRH对认知有良好的影响(P=.03),在轻度认知障碍成人和健康老年人中具有可比性。完整的分析显示了类似的模式,具有更强的GHRH效应(P= 0.002)。随后的分析表明,GHRH对执行功能有积极的影响(P= 0.005),在言语记忆方面也有类似的治疗相关益处(P= 0.08)。GHRH治疗将胰岛素样生长因子1水平提高了117% (P.001),保持在生理范围内,并将体脂百分比降低了7.4%(P.001)。在MCI成人中,GHRH治疗使正常范围内的空腹胰岛素水平提高了35% (P.001),而在健康成人中则没有。不良事件是轻微的,68%接受GHRH治疗的成年人和36%接受安慰剂治疗的成年人报告了不良事件。结论:20周的GHRH治疗对轻度认知障碍成人和健康老年人的认知都有良好的影响。需要更长时间的治疗试验来进一步研究GHRH对正常衰老和“病理性衰老”期间大脑健康的治疗潜力。试验注册:clinicaltrials.gov标识符:NCT00257712
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Archives of neurology
Archives of neurology 医学-临床神经学
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