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      Cognitive performance during senescence in untreated congenital isolated GH deficiency

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          Abstract

          Individuals with untreated isolated GH deficiency (IGHD) due to a mutation in the GHRH receptor gene from Itabaianinha Brazil have increased insulin sensitivity, normal life expectancy, and an extended health span, i.e. the period of life free from disabilities. We hypothesize that their prolonged health span is accompanied by a delayed cognitive decline in senescence. To test this hypothesis, we have administered the Literacy-Independent Cognitive Assessment (LICA) to 15 IGHD individuals aged over 50 years and 15 controls matched by age, sex, years of education, and percentage of illiteracy. All individuals were negative for HIV and syphilis serology, and there were no differences in serum levels of folate, vitamin B12 and TSH between the two groups, while free T4 was higher in the IGHD group. IGHD subjects had a higher total LICA score than controls, 215 (22.7) vs 204.2 (18.1), without reaching statistical significance. Scores of memory, visuoconstruction, language and calculation were similar between the two groups, with better attention (9.5 (1.4) vs 8.3 (1.1), P = 0.01) and executive function (38.3 (4.8) vs 35.1 (2.5), P = 0.03) scores in IGHD. MANCOVA revealed that group (but no age) had a significant effect on the LICA variables (partial eta squared of 0.455, power of 0.812, P = 0.02). This effect is verified on attention (partial eta squared 0.216, power of 0.749, P = 0.01) and executive function (partial eta squared 0.154, power of 0.570, P = 0.03. In conclusion, IGHD in senescence is associated with similar total cognitive performance but better attention and executive function than controls.

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          Most cited references54

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          Guidelines for the Process of Cross-Cultural Adaptation of Self-Report Measures

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            Fatigue and Cognitive Impairment in Post-COVID-19 Syndrome: A Systematic Review and Meta-Analysis

            Importance COVID-19 is associated with clinically significant symptoms despite resolution of the acute infection (i.e., post-COVID-19 syndrome). Fatigue and cognitive impairment are amongst the most common and debilitating symptoms of post-COVID-19 syndrome. Objective To quantify the proportion of individuals experiencing fatigue and cognitive impairment 12 or more weeks following COVID-19 diagnosis, and to characterize the inflammatory correlates and functional consequences of post-COVID-19 syndrome. Data Sources Systematic searches were conducted without language restrictions from database inception to June 8, 2021 on PubMed/MEDLINE, The Cochrane Library, PsycInfo, Embase, Web of Science, Google/Google Scholar, and select reference lists. Study Selection Primary research articles which evaluated individuals at least 12 weeks after confirmed COVID-19 diagnosis and specifically reported on fatigue, cognitive impairment, inflammatory parameters, and/or functional outcomes were selected. Data Extraction & Synthesis Two reviewers independently extracted published summary data and assessed methodological quality and risk of bias. A meta-analysis of proportions was conducted to pool Freeman-Turkey double arcsine transformed proportions using the random-effects restricted maximum-likelihood model. Main Outcomes & Measures The co-primary outcomes were the proportions of individuals reporting fatigue and cognitive impairment, respectively, 12 or more weeks after COVID-19 infection. The secondary outcomes were inflammatory correlates and functional consequences of post-COVID-19 syndrome. Results The literature search yielded 10,979 studies, and 81 studies were selected for inclusion. The fatigue meta-analysis comprised 68 studies, the cognitive impairment meta-analysis comprised 43 studies, and 48 studies were included in the narrative synthesis. Meta-analysis revealed that the proportion of individuals experiencing fatigue 12 or more weeks following COVID-19 diagnosis was 0.32 (95% CI, 0.27, 0.37; p < 0.001; n = 25,268; I 2 =99.1%). The proportion of individuals exhibiting cognitive impairment was 0.22 (95% CI, 0.17, 0.28; p < 0.001; n = 13,232; I 2 =98.0). Moreover, narrative synthesis revealed elevations in proinflammatory markers and considerable functional impairment in a subset of individuals. Conclusions & Relevance A significant proportion of individuals experience persistent fatigue and/or cognitive impairment following resolution of acute COVID-19. The frequency and debilitating nature of the foregoing symptoms provides the impetus to characterize the underlying neurobiological substrates and how to best treat these phenomena. Study Registration PROSPERO (CRD42021256965)
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              Brain Insulin Resistance at the Crossroads of Metabolic and Cognitive Disorders in Humans.

              Ever since the brain was identified as an insulin-sensitive organ, evidence has rapidly accumulated that insulin action in the brain produces multiple behavioral and metabolic effects, influencing eating behavior, peripheral metabolism, and cognition. Disturbances in brain insulin action can be observed in obesity and type 2 diabetes (T2D), as well as in aging and dementia. Decreases in insulin sensitivity of central nervous pathways, i.e., brain insulin resistance, may therefore constitute a joint pathological feature of metabolic and cognitive dysfunctions. Modern neuroimaging methods have provided new means of probing brain insulin action, revealing the influence of insulin on both global and regional brain function. In this review, we highlight recent findings on brain insulin action in humans and its impact on metabolism and cognition. Furthermore, we elaborate on the most prominent factors associated with brain insulin resistance, i.e., obesity, T2D, genes, maternal metabolism, normal aging, inflammation, and dementia, and on their roles regarding causes and consequences of brain insulin resistance. We also describe the beneficial effects of enhanced brain insulin signaling on human eating behavior and cognition and discuss potential applications in the treatment of metabolic and cognitive disorders.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                21 December 2023
                29 November 2023
                01 January 2024
                : 13
                : 1
                : e230401
                Affiliations
                [1 ]Division of Psychiatry , Health Sciences Graduate Program, Federal University of Sergipe, Aracaju, Sergipe, Brazil
                [2 ]Department of Psychiatry and Psychotherapy , University Hospital Hamburg-Eppendorf, Hamburg, Germany and Technical University of Munich, Munich, Germany
                [3 ]Division of Endocrinology , Diabetes and Metabolism, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
                [4 ]Department of Psychology , Federal University of Sergipe, São Cristovão, Sergipe, Brazil
                [5 ]Postgraduate Program in Psychology , Federal University of Sergipe, São Cristovão, Sergipe, Brazil
                [6 ]Division of Endocrinology , Health Sciences Graduate Program, Federal University of Sergipe, Aracaju, Sergipe, Brazil
                [7 ]Statistics division , Health Sciences Graduate Program, Federal University of Sergipe, Aracaju, Sergipe, Brazil
                [8 ]Division of Geriatrics , Health Sciences Graduate Program, Federal University of Sergipe, Aracaju, Sergipe, Brazil
                Author notes
                Correspondence should be addressed to M Aguiar-Oliveira: herminio@ 123456infonet.com.br
                Author information
                http://orcid.org/0000-0002-9979-9881
                Article
                EC-23-0401
                10.1530/EC-23-0401
                10762558
                38019109
                5a28d2dc-c3d2-467f-b185-5af17569e777
                © the author(s)

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

                History
                : 27 September 2023
                : 29 November 2023
                Categories
                Research

                gh,ghrh receptor,cognition,senescence
                gh, ghrh receptor, cognition, senescence

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