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      Effect of low-normal and high-normal IGF-1 levels on memory and wellbeing during growth hormone replacement therapy: a randomized clinical trial in adult growth hormone deficiency

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          Abstract

          Background

          The aim of the present study was to investigate the effect of low-normal and high-normal levels of IGF-1 in growth hormone (GH) deficient adults on cognition and wellbeing during GH treatment.

          Methods

          A randomized, open-label, clinical trial including 32 subjects receiving GH therapy for at least 1 year. Subjects were randomized to receive either a decrease (IGF-1 target level of − 2 to − 1 SDS) or an increase of their daily GH dose (IGF-1 target level of 1 to 2 SDS) for a period of 24 weeks. Memory was measured by the Cambridge Neuropsychological Test Automated Battery, selecting the Pattern Recognition Memory task and the Spatial Working Memory. Wellbeing was measured as mood by the Profile of Moods States questionnaire, and quality of life by the Nottingham Health Profile and QoL Assessment in GH Deficiency in Adults questionnaires.

          Results

          Data from 30 subjects (65.6% male, mean age 46.6 (9.9 SD) years), who fulfilled the target levels, were analyzed. Females in the low dose treatment arm were found to have a better working memory and a better strategic memory control after 24 weeks as opposed to the females in the high treatment arm. With respect to mood, the decrease in IGF-1 levels in females within the low treatment arm was associated with more fatigue and less vigor.

          Conclusions

          The adjustment of GH dose in female patients seems to have a narrow window. A dose too high may impair prefrontal cognitive functioning, while a dose too low may result in decreased vigor.

          Trial registration

          This study is registered with ClinicalTrials.gov, number NCT01877512.

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          Most cited references44

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          Consensus guidelines for the diagnosis and treatment of adults with GH deficiency II: a statement of the GH Research Society in association with the European Society for Pediatric Endocrinology, Lawson Wilkins Society, European Society of Endocrinology, Japan Endocrine Society, and Endocrine Society of Australia.

          Ken Ho (2007)
          The GH Research Society held a Consensus Workshop in Sydney, Australia, 2007 to incorporate the important advances in the management of GH deficiency (GHD) in adults, which have taken place since the inaugural 1997 Consensus Workshop. Two commissioned review papers, previously published Consensus Statements of the Society and key questions were circulated before the Workshop, which comprised a rigorous structure of review with breakout discussion groups. A writing group transcribed the summary group reports for drafting in a plenary forum on the last day. All participants were sent a polished draft for additional comments and gave signed approval to the final revision. Testing for GHD should be extended from hypothalamic-pituitary disease and cranial irradiation to include traumatic brain injury. Testing may indicate isolated GHD; however, idiopathic isolated GHD occurring de novo in the adult is not a recognized entity. The insulin tolerance test, combined administration of GHRH with arginine or growth hormone-releasing peptide, and glucagon are validated GH stimulation tests in the adult. A low IGF-I is a reliable diagnostic indicator of GHD in the presence of hypopituitarism, but a normal IGF-I does not rule out GHD. GH status should be reevaluated in the transition age for continued treatment to complete somatic development. Interaction of GH with other axes may influence thyroid, glucocorticoid, and sex hormone requirements. Response should be assessed clinically by monitoring biochemistry, body composition, and quality of life. There is no evidence that GH replacement increases the risk of tumor recurrence or de novo malignancy.
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            Planning and spatial working memory following frontal lobe lesions in man

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              A comparative study of visuospatial memory and learning in Alzheimer-type dementia and Parkinson's disease.

              Groups of patients with dementia of Alzheimer type (DAT) and idiopathic Parkinson's disease, together with age and IQ-matched normal controls, were compared on several computerized tests of visuospatial memory and learning. Two different groups of parkinsonian patients were studied: (1) a newly diagnosed group, early in the course of the disease, not receiving medication (NMED) PD) and (2) a group later in the course of the disease, receiving medication (MED PD). The DAT and MED PD group were significantly impaired in both spatial and visual pattern recognition memory. The DAT group exhibited a delay-dependent deficit (over 0-16 s) in a delayed matching-to-sample procedure, but were not impaired at simultaneous-matching-to-sample. By contrast, the MED PD group showed delay-independent deficits in the delayed matching-to-sample test and both the MED PD and the NMED PD group were also significantly impaired in simultaneous matching. In a form of delayed response test, the subjects were required first to memorize and then to learn the locations of several abstract visual stimuli which varied progressively in number from 1 to 8. The DAT group were severely impaired in this conditional associative learning task. A significant proportion of patients, but none of the controls, in the NMED and MED PD group also failed the test at the levels of 6 or 8 items. There was a significant correlation between the performance on the first trial, memory score in the delayed response task and indices of clinical disability and disease duration in the patients with Parkinson's disease. The results are discussed in terms of the utility of the comparison between DAT and PD in characterizing the nature of the cognitive deficits in these conditions and their relation to those findings from animal neuropsychology which use comparable paradigms.
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                Author and article information

                Contributors
                0031 (0) 204444444 , c.vanbunderen@vumc.nl
                Journal
                Health Qual Life Outcomes
                Health Qual Life Outcomes
                Health and Quality of Life Outcomes
                BioMed Central (London )
                1477-7525
                6 July 2018
                6 July 2018
                2018
                : 16
                : 135
                Affiliations
                [1 ]ISNI 0000 0004 0435 165X, GRID grid.16872.3a, Department of Internal Medicine, section of Endocrinology, Neuroscience Campus Amsterdam, , VU University Medical Center, ; De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands
                [2 ]ISNI 0000 0004 1754 9227, GRID grid.12380.38, Department of Clinical Neuropsychology, , VU University, ; Amsterdam, the Netherlands
                Author information
                http://orcid.org/0000-0003-0006-7726
                Article
                963
                10.1186/s12955-018-0963-2
                6035403
                29980224
                8ca88369-e476-4dfc-b7f7-a425165d0e2b
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 8 January 2018
                : 2 July 2018
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001826, ZonMw;
                Award ID: 92003591
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100004319, Pfizer;
                Categories
                Research
                Custom metadata
                © The Author(s) 2018

                Health & Social care
                growth hormone deficiency,growth hormone treatment,cognition,memory,mood,insulin-like growth factor-1

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