Dataset Information

Growth hormone-releasing hormone effects on brain ?-aminobutyric acid levels in mild cognitive impairment and healthy aging.

ABSTRACT: Growth hormone-releasing hormone (GHRH) has been previously shown to have cognition-enhancing effects. The role of neurotransmitter changes, measured by proton magnetic resonance spectroscopy, may inform the mechanisms for this response.To examine the neurochemical effects of GHRH in a subset of participants from the parent trial.Randomized, double-blind, placebo-controlled substudy of a larger trial.Clinical research unit at the University of Washington School of Medicine.Thirty adults (17 with mild cognitive impairment [MCI]), ranging in age from 55 to 87 years, were enrolled and successfully completed the study.Participants self-administered daily subcutaneous injections of tesamorelin (Theratechnologies Inc), a stabilized analogue of human GHRH (1 mg/d), or placebo 30 minutes before bedtime for 20 weeks. At baseline and weeks 10 and 20, participants underwent brain magnetic resonance imaging and spectroscopy protocols and cognitive testing and provided blood samples after fasting. Participants also underwent glucose tolerance tests before and after intervention.Brain levels of glutamate, inhibitory transmitters ?-aminobutyric acid (GABA) and N-acetylaspartylglutamate (NAAG), and myo-inositol (MI), an osmolyte linked to Alzheimer disease in humans, were measured in three 2?×?2?×?2-cm3 left-sided brain regions (dorsolateral frontal, posterior cingulate, and posterior parietal). Glutamate, GABA, and MI levels were expressed as ratios to creatine plus phosphocreatine, and NAAG was expressed as a ratio to N-acetylaspartate.After 20 weeks of GHRH administration, GABA levels were increased in all brain regions (P?

SUBMITTER: Friedman SD

PROVIDER: S-EPMC3764915 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Growth hormone-releasing hormone effects on brain γ-aminobutyric acid levels in mild cognitive impairment and healthy aging.

Friedman Seth D SD Baker Laura D LD Borson Soo S Jensen J Eric JE Barsness Suzanne M SM Craft Suzanne S Merriam George R GR Otto Randolph K RK Novotny Edward J EJ Vitiello Michael V MV

JAMA neurology 20130701 7

<h4>Importance</h4>Growth hormone-releasing hormone (GHRH) has been previously shown to have cognition-enhancing effects. The role of neurotransmitter changes, measured by proton magnetic resonance spectroscopy, may inform the mechanisms for this response.<h4>Objective</h4>To examine the neurochemical effects of GHRH in a subset of participants from the parent trial.<h4>Design</h4>Randomized, double-blind, placebo-controlled substudy of a larger trial.<h4>Setting</h4>Clinical research unit at th ...[more]

PMID: 23689947

Similar Datasets

Project description:Measures of cerebrovascular reactivity (CVR) are used to judge the health of the brain vasculature. In this study, we report the use of several different analyses of blood oxygen dependent (BOLD) fMRI responses to CO2 to provide a number of metrics of CVR based on the sigmoidal resistance response to CO2. To assess possible differences in these metrics with age, we compiled atlases reflecting voxel-wise means and standard deviations for four different age ranges and for a group of patients with mild cognitive impairment (MCI) and compared them. Sixty-seven subjects were recruited for this study and scanned at 3T field strength. Of those, 51 healthy control volunteers between the ages of 18-83 were recruited, and 16 (MCI) subjects between the ages of 61-83 were recruited. Testing was carried out using an automated computer-controlled gas blender to induce hypercapnia in a step and ramp paradigm while monitoring end-tidal partial pressures of CO2. Surprisingly, some resistance sigmoid parameters in the oldest control group were increased compared to the youngest control group. Resistance amplitude maps showed increases in clusters within the temporal cortex, thalamus, corpus callosum and brainstem, and resistance reserve maps showed increases in clusters within the cingulate cortex, frontal gyrus, and corpus callosum. These findings suggest that some aspects of vascular reactivity in parts of the brain are initially maintained with age but then may increase in later years. We found significant reductions in all resistance sigmoid parameters (amplitude, reserve, sensitivity, midpoint, and range) when comparing MCI patients to controls. Additionally, in controls and in MCI patients, amplitude, range, reserve, and sensitivity in white matter (WM) was significantly reduced compared to gray matter (GM). WM midpoints were significantly above those of GM. Our general conclusion is that vascular regulation in terms of cerebral blood flow (CBF) responsiveness to CO2 is not significantly affected by age, but is reduced in MCI. These changes in cerebrovascular regulation demonstrate the value of resistance metrics for mapping areas of dysregulated blood flow in individuals with MCI. They may also be of value in the investigation of patients with vascular risk factors at risk for developing vascular dementia.

Project description: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).To examine the effects of GHRH on cognitive function in healthy older adults and in adults with MCI.Randomized,double-blind,placebo-controlled trial.Clinical Research Center, University of Washington School of Medicine in Seattle.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.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.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.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.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.”clinicaltrials.gov Identifier: NCT00257712

Project description:Although subtle discourse declines in people with mild cognitive impairment (MCI) have been reported, heterogeneous measures and tasks among the MCI discourse studies have yielded widely varying outcomes. The present study aimed to first, identify discourse measures that aid the differentiation among people with amnestic MCI (aMCI), people with non-amnestic MCI (naMCI), and cognitively healthy control (HC) participants, and second, delineate the cognitive functions related to such discourse measures. Three discourse tasks (an episodic narrative, a planning task, and a picture description) were performed by 30 aMCI, 22 naMCI, and 21 HC participants. Samples were analyzed using six categories of 15 measures, namely coherence, cohesion, proposition, grammaticality, lexicality, and fluency. The statistical analyses included (1) a multivariate analysis of variance for group comparison; (2) binary simple logistic regression and receiver operating characteristic curve analysis for differentiation between two groups; (3) binary multiple logistic regression for being diagnosed with naMCI or aMCI with the minimum number of predictors; and (4) Pearson correlation analysis for identifying the cognitive functions associated with the discourse measures. The proportion of cohesive words and propositional density in aMCI participants were worse than those in naMCI participants. Global coherence, the proportion of cohesive words, and the proportion of dysfluencies and pauses in naMCI participants were lower than those in the HC participants. Global and local coherence and the proportion of cohesive words, cohesive ties per utterances, propositional density, and dysfluencies and pauses in aMCI participants were worse than those in the HC participants. The aforementioned measures were demonstrated to be effective predictors for classifying groups by receiver operating characteristic curve analysis. In addition, the proportions of cohesive words and pauses were common discourse measures for differentiation between naMCI and HC participants or between aMCI and HC participants using binary multiple logistic regression. According to the correlation analysis, memory and executive functions are needed for coherent, cohesive, and efficient discourse productions in MCI. The detailed description of discourse performances in this study will aid the characterization of the declined language abilities of MCI participants and also the understanding of the cognitive functions involved in discourse performance in MCI.

Dataset Information

Growth hormone-releasing hormone effects on brain ?-aminobutyric acid levels in mild cognitive impairment and healthy aging.

Publications

Growth hormone-releasing hormone effects on brain γ-aminobutyric acid levels in mild cognitive impairment and healthy aging.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets