August 8, 2012 — Treatment with human growth hormone–releasing hormone (GHRH) for 20 weeks had favorable effects on cognitive function in a randomized controlled trial of healthy older adults and those with mild cognitive impairment (MCI).
Compared with placebo, daily subcutaneous injections of tesamorelin (Egrifta, Theratechnologies, Inc) were associated with improvement on tests of executive function and possibly memory, the study team reports in an article published online August 6 in Archives of Neurology.
These findings “replicate and expand” the results of a 2006 study by the same researchers that found favorable effects of GHRH on executive function in healthy older adults.
“The 2006 study included what were presumed to be cognitively normal adults. This [latest] study included not only older adults with normal cognition for age, but also a group of adults with amnestic MCI,” Laura D. Baker, PhD, of the University of Washington School of Medicine and Veterans Affairs Puget Sound Health Care System, in Seattle, told Medscape Medical News.
“This study also used a different form of GHRH that is longer acting and is more effective at increasing circulating levels of IGF-1 [insulin-like growth factor 1], a presumed key hormone for our observed cognition-enhancing effects,” she added.
In the study, 152 adults (mean age, 68 years) gave themselves a daily subcutaneous injection of tesamorelin (1 mg/day) or placebo 30 minutes before bedtime for 20 weeks.
Investigators collected blood samples and administered standard tests of executive function and verbal and visual memory at baseline, at 10 and 20 weeks of treatment, and after a 10-week washout (30 weeks total).
They ordered an oral glucose tolerance test and performed dual-energy x-ray absorptiometry to measure body composition at baseline and after 20 weeks. A total of 137 participants (76 healthy patients and 61 patients with MCI) successfully completed the study.
“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 authors report. “The completer analysis showed a similar pattern, with a more robust GHRH effect (P = .002).”
In subsequent analyses, a positive effect of GHRH on executive function was noted (P = .005), along with a trend showing a similar treatment-related benefit for verbal memory (P = .08).
Treatment with GHRH increased IGF-1 levels by 117% (P < .001), which remained within the physiologic range, and reduced percent body fat by 7.4% (P < .001). Treatment with GHRH also 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 those receiving GHRH vs 36% of those receiving placebo. Adverse events largely consisted of local skin reactions and arthralgias. Gastrointestinal upset, numbness or tingling in the hands, weight gain, and fluid retention were seen less often.
More Study Needed
In an interview with Medscape Medical News, Heather M. Snyder, PhD, senior associate director of Medical & Scientific Relations at the Alzheimer’s Association, noted that 2 other studies have looked at growth hormone for cognition.
One study showed some benefit on cognition; the other did not show benefit. “This gives some indication that we do need to continue with this line of research to see if there is a potential benefit,” Dr. Snyder said.
“A caveat of the study is that it’s a small sample size, so it’s difficult to draw a huge number of conclusions,” she added.
The study team notes in its findings that GHRH and IGF-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.” Several prior studies have linked lower IGF-1 levels with poorer cognitive performance, they point out.
“At this point,” Dr. Snyder said, “we don’t really know what the potential mechanism might be, which is why it’s so important to continue to invest and commit to furthering Alzheimer’s disease research. The National Alzheimer’s Plan that was released earlier this year will hopefully help us move in that direction.”
“A follow-up study is planned to examine longer-duration treatment effects in a 12-month placebo-controlled trial,” Dr. Baker said. “We will include older adults with MCI and healthy adults with a first-degree family history of dementia. We will also examine treatment-related changes in brain structure and function.”
Tesamorelin and placebo were provided by Theratechnologies, Inc, at no cost to the study. This research was supported by National Institutes of Health/National Institute of Aging grants, and by the U.S. Department of Veterans Affairs. A portion of the work was conducted at the Clinical Research Center Facility at the University of Washington Medical Center, which is supported by a National Institutes of Health/National Center for Research Resources grant. The authors and Dr. Snyder have disclosed no relevant financial relationships.