Arch Neurol. 2012 Aug 6;:1-10
Baker LD, Barsness SM, Borson S, Merriam GR, Friedman SD, Craft S, Vitiello MV
Abstract
BACKGROUND 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).
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 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.
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.
PMID: 22869065
GHRH May Help Keep Seniors Mentally Sharp
And even though the healthy adults outperformed those with mild cognitive impairment overall, the cognitive benefit of GHRH relative to placebo was comparable for both groups. And while not quite statistically significant, a similar pattern of results emerged for verbal memory.
“This is a well-conducted trial by an outstanding group of investigators with expertise in cognitive disorders of later life,” Dilip Jeste, M.D., chair in aging at the University of California, San Diego, and president of APA, told Psychiatric News. “The results are highly promising.”
This is a very important study since it was done by a well-regarded, well-known group of investigators who are experts in cognitive disorder.
Growth-Hormone Releasing-Hormone is a very promising treatment to improve cognition in adults and to treat cognitive illnesses including early Alzheimer’s disease. It does not have as many limitations as treatment with growth hormone itself.
I would like to see the study extended to all adults.
Of concern is the increase in insulin – though this may be outweighed by the reduction in body fat. The increase in insulin was primarily on those with Mild Cognitive Impairment where pre-diabetes and diabetes may already be a concern.
Even Dilip Jeste, MD was impressed by the study. He often is pessimistic in seminar presentations about treatments to improve cognition in adults given limited response to treatments of Alzheimer’s disease.
The loss of body fat was significant. People who are obese often are low in growth hormone. Increasing growth hormone helps restore normal body composition, promoting visceral and general fat loss. Optimization of thyroid hormone needs to be done first since there are fewer growth hormone receptors in the liver with a deficit in thyroid hormone, limiting the effectiveness of increasing growth hormone.