Effects of growth hormone–releasing hormone on cognitive function in adults with mild cognitive impairment and healthy older adults: results of a controlled trial.
Effects of growth hormone–releasing hormone on cognitive function in adults with mild cognitive impairment and healthy older adults: results of a controlled trial.
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DOI：
10.1001/archneurol.2012.1970
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发表时间：
2012-11
影响因子：
--
通讯作者：
Vitiello, Michael V.
中科院分区：
文献类型：
--
作者：
Baker, Laura D.;Barsness, Suzanne M.;Borson, Soo;Merriam, George R.;Friedman, Seth D.;Craft, Suzanne;Vitiello, Michael V.
生长激素释放激素（GHRH）、生长激素和胰岛素样生长因子1对脑功能有强有力的影响，它们的水平随着年龄的增长而下降，它们可能在阿尔茨海默病的发病机制中发挥作用。此前，我们报告了短期GHRH给药对健康老年人的良好认知效果，并提供了初步证据，表明轻度认知障碍（MCI）成人也有类似的益处。研究GHRH对健康老年人和MCI成人认知功能的影响。随机、双盲、安慰剂对照试验。临床研究中心，华盛顿大学医学院在西雅图。共有152名成人（66名MCI患者），年龄范围为55至87岁（平均年龄68岁）; 137名成人（76名健康受试者和61名MCI受试者）成功完成了研究。参与者在睡前30分钟自我给药每日皮下注射tesamorelin（Theratechnologies Inc），一种稳定的人类GHRH类似物（1 mg/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，采集血液样本，并进行认知成套测验的平行版本。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射线吸收扫描，以测量身体成分。使用方差分析分析主要认知结果，包括反映执行功能、言语记忆和视觉记忆的3个复合物。执行功能采用Stroop色词干扰、任务转换、自我排序指向测验和词语流畅性进行评估，言语记忆采用故事回忆和霍普金斯言语学习测验进行评估，视觉记忆采用视觉空间学习测验和延迟匹配样本进行评估。意向治疗分析表明，GHRH对认知的有利影响（P= 0.03），在MCI成人和健康老年人中具有可比性。完成者分析显示了类似的模式，具有更强的GHRH效应（P=.002）。随后的分析表明，GHRH对执行功能有积极的影响（P=.005），并且在非文字记忆方面显示出类似的治疗相关益处（P=.08）。GHRH治疗使胰岛素样生长因子1水平增加117%（P<.001），保持在生理范围内，并使体脂百分比降低7.4%（P<.001）。GHRH治疗使MCI成人的空腹胰岛素水平在正常范围内增加了35%（P<0.001），但在健康成人中没有增加。不良事件是轻微的，68%的GHRH治疗的成年人和36%的安慰剂治疗的成年人报告了不良事件。20周的GHRH给药对MCI成人和健康老年人的认知都有良好的影响。需要进行更长时间的治疗试验，以进一步研究GHRH给药对正常衰老和“病理性衰老”期间大脑健康的治疗潜力。clinicaltrials.gov标识符：NCT 00257712
Growth hormone–releasing hormone (GHRH), growth hormone, and insulinlike 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). To examine the effects of GHRH on cognitive function in healthy older adults and in adults with MCI. Randomized, double-blind, placebo-controlled trial. Clinical Research Center, University of Washington School of Medicine in Seattle. 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. 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. 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. 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 insulinlike 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. 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.” clinicaltrials.gov Identifier: NCT00257712
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