title: Effects of growth hormone–releasing hormone on cognitive function in adults with mild cognitive impairment and healthy older adults: results of a controlled trial.
abstract: 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.
  
  
  METHODS
  Randomized,double-blind,placebo-controlled trial.
  
  
  METHODS
  Clinical Research Center, University of Washington School of Medicine in Seattle.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.”
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00257712
authors.affiliation: Department of Psychiatry and Behavioral Science, University of Washington School of Medicine, USA. ldbaker@uw.edu
authors.forename: Laura D
authors.initials: LD
authors.lastname: Baker
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Barsness
authors.forename: Soo
authors.initials: S
authors.lastname: Borson
authors.forename: George R
authors.initials: GR
authors.lastname: Merriam
authors.forename: Seth D
authors.initials: SD
authors.lastname: Friedman
authors.forename: Suzanne
authors.initials: S
authors.lastname: Craft
authors.forename: Michael V
authors.initials: MV
authors.lastname: Vitiello
mesh_terms: D015502:Absorptiometry, Photon; D000339:Affect / Q000187:drug effects; D000368:Aged; D000369:Aged, 80 and over; D001823:Body Composition / Q000187:drug effects; D016022:Case-Control Studies; D060825:Cognitive Dysfunction / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D056344:Executive Function / Q000187:drug effects; D005260:Female; D005500:Follow-Up Studies; D005951:Glucose Tolerance Test; D013007:Growth Hormone-Releasing Hormone / Q000627:therapeutic use*; D006728:Hormones / Q000627:therapeutic use*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D061212:Memory, Episodic; D008875:Middle Aged; D009483:Neuropsychological Tests; D012890:Sleep / Q000187:drug effects
chemical_list: D006728:Hormones; D007334:Insulin-Like Growth Factor I; D013007:Growth Hormone-Releasing Hormone