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      Factors Associated With Short and Long Term Cognitive Changes in Patients With Sepsis

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          Abstract

          This study aimed to assess cognition in patients with severe sepsis or septic shock and whether cognitive impairment was associated with clinical and laboratory parameters. We conducted a cohort study of patients with severe sepsis and septic shock evaluated within 24 h and one year after ICU discharge. Demographic, clinical and laboratory data were analyzed, and the following neuropsychological tests were applied: Consortium to Establish Registry for Alzheimer’s Disease, Mini-Mental State Examination, and Trail Making Test forms A and B. We included 33 patients, mean age of 49, 19% were female. Patients underperformed on most measures 24 h after ICU discharge, with improvement on follow-up. IQCODE, APACHE II scores, NSE and IFN-γ levels at ICU discharge were associated with poor cognitive performance, while higher educational level was associated with good cognitive performance. The time to first antibiotic dose, accumulated dose of haloperidol during UCI stay and mean glycemia were also associated with poor cognitive outcome. In general, patients with severe sepsis or septic shock have cognitive impairment that can improve over time. This improvement was associated with factors identified during their ICU stay, such as cognitive reserve, educational level, mean glycemia during ICU stay and NSE level.

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          Most cited references33

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          The Informant Questionnaire on cognitive decline in the elderly (IQCODE): a review.

          The IQCODE is widely used as a screening test for dementia, particularly where the subject is unable to undergo direct cognitive testing or for screening in populations with low levels of education and literacy. This review draws together research on the psychometric properties and validity of the IQCODE. A systematic search of the literature was carried out using three databases. The review shows that the questionnaire has high reliability and measures a single general factor of cognitive decline. It validly reflects past cognitive decline, performs at least as well at screening as conventional cognitive screening tests, predicts incident dementia, and correlates with a wide range of cognitive tests. A particular strength is that the IQCODE is relatively unaffected by education and pre-morbid ability or by proficiency in the culture's dominant language. The disadvantage of the IQCODE is that it is affected by informant characteristics such as depression and anxiety in the informant and the quality of the relationship between the informant and the subject. Because the IQCODE provides information complementary to brief cognitive tests, harnessing them together can improve screening accuracy.
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            Evidence for a cytokine model of cognitive function.

            Aiming at a formulation of a cytokine model of cognitive function under immunologically unchallenged physiological conditions, this article reviews the cytokine biology in the central nervous system (CNS) and recent developments in normal cytokine functions within the CNS that subserve cognitive processes. Currently available evidence shows that the cytokines IL-1beta, IL-6 and TNF-alpha play a role in complex cognitive processes at the molecular level, such as synaptic plasticity, neurogenesis, as well as neuromodulation. Such findings provide evidence for a cytokine model of cognitive function, which shows that cytokines play an intimate role in the molecular and cellular mechanisms subserving learning, memory and cognition under physiological conditions. These cytokine-mediated cognitive processes have implications in the long-term development and pathogenesis of specific neuropsychiatric disorders such as major depression and dementia. The identification of this central role of cytokines in various brain activities during health provides greater insight into normal brain functions, especially synaptic plasticity, memory and cognition, and facilitates the understanding of specific biological mechanisms involved in neuropsychiatric diseases, such as dementia and depression. In order to extend the suggested cytokine model of cognitive function onto other members of the cytokine family, future research is required to investigate the physiological effects of other cytokines such as interferon-gamma (IFNgamma), alpha(1)-antichymotrypsin and IL-2 on cognitive function at the molecular level under immunologically unchallenged conditions.
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              Hippocampal Insulin Resistance Impairs Spatial Learning and Synaptic Plasticity

              Insulin receptors (IRs) are expressed in discrete neuronal populations in the central nervous system, including the hippocampus. To elucidate the functional role of hippocampal IRs independent of metabolic function, we generated a model of hippocampal-specific insulin resistance using a lentiviral vector expressing an IR antisense sequence (LV-IRAS). LV-IRAS effectively downregulates IR expression in the rat hippocampus without affecting body weight, adiposity, or peripheral glucose homeostasis. Nevertheless, hippocampal neuroplasticity was impaired in LV-IRAS–treated rats. High-frequency stimulation, which evoked robust long-term potentiation (LTP) in brain slices from LV control rats, failed to evoke LTP in LV-IRAS–treated rats. GluN2B subunit levels, as well as the basal level of phosphorylation of GluA1, were reduced in the hippocampus of LV-IRAS rats. Moreover, these deficits in synaptic transmission were associated with impairments in spatial learning. We suggest that alterations in the expression and phosphorylation of glutamate receptor subunits underlie the alterations in LTP and that these changes are responsible for the impairment in hippocampal-dependent learning. Importantly, these learning deficits are strikingly similar to the impairments in complex task performance observed in patients with diabetes, which strengthens the hypothesis that hippocampal insulin resistance is a key mediator of cognitive deficits independent of glycemic control.
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                Author and article information

                Contributors
                allancalsavara@medicina.ufop.br
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                14 March 2018
                14 March 2018
                2018
                : 8
                : 4509
                Affiliations
                [1 ]ISNI 0000 0004 0488 4317, GRID grid.411213.4, School of Medicine, Universidade Federal de Ouro Preto, ; Ouro Preto, MG Brazil
                [2 ]ISNI 0000 0001 2181 4888, GRID grid.8430.f, Postgraduate Program in Health Sciences: Infectious Diseases and Tropical Medicine, School of Medicine, Universidade Federal de Minas Gerais, ; Belo Horizonte, MG Brazil
                [3 ]Núcleo Interdisciplinar de Investigação em Medicina Intensiva - NIIMI, Belo Horizonte, MG Brazil
                [4 ]ISNI 0000 0000 9206 2401, GRID grid.267308.8, Neuropsychiatry Program & Immuno-Psychiatry Lab, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston, ; Houston, TX USA
                Article
                22754
                10.1038/s41598-018-22754-3
                5852240
                29540719
                ae32544e-b8a0-4d23-b0b5-4272e96d5eff
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 2 January 2018
                : 26 February 2018
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