Effects of Growth Hormone–Releasing Hormone on Cognitive Function in Adults With Mild Cognitive Impairment and Healthy Older Adults: Results of a Controlled Trial
Open accessAbstract
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
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GHRH supplementation in healthy elderly individuals and patients with mild cognitive impairment has favourable effects on cognition and metabolism.
“GHRH supplementation in healthy elderly individuals and patients with mild cognitive impairment, and this treatment has favourable effects on cognition and metabolism.532”
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- Authors
- Baker, L. D., Barsness, S. M., Borson, S., Merriam, G. R., Friedman, S. D., Craft, S., & Vitiello, M. V.
- Affiliations
- University of Washington (US)
- Seattle Children's Hospital (US)
- Corresponding author
- Baker, Laura D.
- Venue
- Archives of Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2012-11-01
- Volume
- 69
- Issue
- 11
- Pages
- 1420
- ISSN
- 0003-9942 (ISSN-L)
- PMC
- PMC3764914
- OpenAlex
- W2133969927
- Cited by
- 138
- References
- 87
- Citations by year
- 2026: 5 · 2025: 13 · 2024: 12 · 2023: 7 · 2022: 9 · 2021: 11 · 2020: 9 · 2019: 10 · 2018: 11 · 2017: 6 · 2016: 14 · 2015: 11 · 2014: 7 · 2013: 11 · 2012: 2
- FWCI
- 7.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Archives of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Veterans Affairs
- University of Washington
- National Institutes of Health
- U.S. Public Health Service (ULRR025014)
- National Institute on Aging (R01AG030484, AG025515, AG030484, R01AG025515)
- National Center for Research Resources (M01RR000037)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- growth hormone-releasing hormone, tesamorelin, mild cognitive impairment, cognitive function, executive function, verbal memory, visual memory, older adults, Alzheimer's disease, growth hormone, insulin-like growth factor I, brain aging, body composition, glucose tolerance, cognitive aging interventions
- MeSH terms
- Affect, Aged, Aged, 80 and over, Body Composition, Double-Blind Method, Female, Follow-Up Studies, Glucose Tolerance Test, Hormones, Humans, Insulin-Like Growth Factor I, Male, Middle Aged, Neuropsychological Tests, Sleep, Growth Hormone-Releasing Hormone, Absorptiometry, Photon, Case-Control Studies, Executive Function, Cognitive Dysfunction, Memory, Episodic
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