A daily dose of growth hormone-releasing hormone (GHRH) may help to improve memory and reasoning abilities in older people, whether or not they have mild problems with cognition. In a small randomized trial conducted by a University of Washington research team, people who received daily injections of GHRH did better on tests of mental function than those who received a fake shot, or placebo.
Investigators led by Laura Baker of the University of Washington & VA Puget Sound Health Care System in Seattle reported these results in the August 6 issue of the journal Archives of Neurology.
Alzheimer’s disease and other forms of dementia compose a significant public health problem. The advocacy and research group Alzheimer’s Disease International Worldwide projects that more than 65 million people will have dementia by the year 2030. That number is expected to top 115 million by the year 2050.
Some drugs have been developed that may slow the progress of the disease temporarily in some people. However, Alzheimer’s remains incurable. And while evidence is growing that a healthful diet, exercise, and challenging mental activities may help to stave off Alzheimer’s, there’s still no clear evidence about how to prevent it.
In most people who develop dementia, serious cognitive decline is preceded by a period of mild cognitive impairment (MCI). People with MCI have more problems with memory and reasoning than others their age, but their cognitive problems do not interfere with activities of daily living.
MCI affects an estimated 10 to 30 percent of people aged 65 years and older. Not everyone who develops MCI will go on to develop dementia, and some may even get better. However, people with MCI are at three to five times greater risk of developing dementia than are their cognitively normal peers.
GHRH comes into play because it causes a sequence of hormones to be released, called a cascade, all of which have an effect on the brain. GHRH, as its name implies, prompts the pituitary gland to release growth hormone. Growth hormone is necessary for growth and plays an important role in metabolism and brain function. In turn, growth hormone stimulates the liver to release a chemical called insulinlike growth factor 1.
A growing body of research suggests that GHRH and the cascade of hormones it causes the body to release play an important role in maintaining cognitive function. “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,” the authors write as background information in the study.
Because levels of GHRH decline with age, Baker’s team theorized that older people would benefit from the hormone. In 2011, Baker and colleagues presented research showing GHRH improved reasoning and memory in healthy older adults. However, up until this study, no one had investigated the potential effects of GHRH on people who already show signs of cognitive decline.
What the Researchers Did
Investigators initially enrolled 152 adults ages 55 to 87 years in the study. The majority – 137 – completed the five-month study. When the study began, 76 of the study “completers” were healthy, and 61 had MCI.
Researchers first tested the participants for cognitive function, then assigned them to two groups. One group received “dummy” shots, or placebo. One group received daily injections of GHRH in the form of tesamorlin (brand name Egrifta). The FDA approved Tesamorelin in 2010 for people with HIV to help with abnormal distribution of body fat that often occurs because of other HIV treatment drugs.
The authors tested the participants’ blood and cognitive function again at 10 and 20 weeks of treatment, and then after another 10 weeks without treatment.
What the Researchers Found
Study participants who received GHRH improved their cognitive performance, whether or not they had MCI. Although people who started the study healthy did better on tests than those who started with memory problems, both groups improved by about the same amount.
Healthy adults improved their brain function dramatically, performing about 200 percent better than their peers on tests of executive function. Executive function is the group of mental processes we use to connect present actions to past experiences. It allows us to plan, strategize, notice and remember details, and navigate time and space.
Executive function continued to slip in participants with MCI who were treated with tesamorelin, but at a much slower rate than those treated with placebo.
Although 68 percent of the treatment group experienced side effects or other problems, none were serious. Almost 4o percent of the control group also experienced adverse events during the study treatment period.
Problems in the treatment group consisted mostly of local skin reactions such as redness, itching, or stinging and increased muscle and joint pain. Less frequently, participants experienced stomach trouble, numbness, or tingling in the hands, weight gain, and fluid retention. Researchers noted that increased fluid retention could potentially lead to or worsen symptoms of congestive heart failure and high blood pressure; however, no study participants experienced heart attack or stroke.
People treated with GHRH also had higher levels of insulinlike growth factor 1 – 117% higher. In people with MCI, fasting insulin levels increased by 35 percent but remained in the normal range. Insulin levels did not increase in participants without MCI.
Insulin, the hormone that controls blood sugar levels, also plays an important role in the keeping nerves healthy in the brain. Insulin both protects existing nerves and stimulates new nerves to grow. As we age, insulin levels in the brain decrease. Earlier research has shown that people with Alzheimer’s disease have especially low levels of insulin.
As an added benefit, the treatment group also lost body fat and increase lean muscle mass, although these physiological changes did not appear to affect cognitive performance.
“Our results replicate and expand our earlier positive findings, demonstrating that GHRH administration has favorable effects on cognitive function not only in healthy older adults but also in adults at increased risk of cognitive decline and dementia,” the authors wrote.
Researchers noted several limitations to their study, including its small sample size, short duration, and relatively high educational level of participants. In addition, 90 percent of participants were white. Results may differ in populations of different ethnic, educational, and socioeconomic backgrounds. The short duration of the study – GHRH was administered for only 5 months – does not provide much information about the safety and effectiveness of long-term administration of the drugs.
What it Means for You
So if you’re concerned about memory loss, should you run out and ask your doctor for a prescription for tesamorelin? Not so fast. At close to $750 a daily dose, it’s not likely that your health insurance company would pay for off-label use of the drug.
This research, Baker cautioned, is highly preliminary. “Larger and longer-duration treatment trials are needed to firmly establish the therapeutic potential of GHRH administration to promote brain health in normal aging and ‘pathological aging,’” the authors wrote.
Nor are over-the-counter supplements of growth hormone a safe or effective option. They could be dangerous, cautioned Baker. In addition, there’s no evidence that oral or inhaled forms of the hormone have any effect.
Still, people concerned about preserving memory and cognitive function do have another alternative – and it’s one that might be just as effective, cheaper, safer, and offer other health benefits: Exercise.
Yes, exercise. A growing body of research suggests that exercise, especially aerobic exercise such as running, walking, bicycling, or swimming, may be one of the most effective ways to preserve memory. In 2010, Baker’s team published results of a study of the effects of intense aerobic activity on cognition in older adults. People in the study engaged in 45 to 60 minutes of aerobic exercise at least four times a week for six months. Although the sample size was very small – 33 older adults – participants’ improvements in executive function were similar to those seen with Tesamorelin.
The researchers reported no conflicts of interest. Tesamorelin and placebo were provided at no cost to the study by Theratechnologies, Inc. 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 conduced through 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.