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Peripheral inflammatory markers during an acute bacterial infection in older patients with and without cognitive dysfunction: A case control study
Dementia is a known risk factor for acute bacterial infections which may also play a significant role in promoting or accelerating cognitive impairment. Pneumonia and urinary tract infections are the main cause of hospitalisation of dementia patients and infections are a major precipitant of deliriu...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9460160/ https://www.ncbi.nlm.nih.gov/pubmed/36093438 http://dx.doi.org/10.1016/j.bbih.2022.100503 |
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author | Regueira, Patrícia Silva, Ana Rita Cardoso, Ana Luísa Cardoso, Ana Maria Baldeiras, Inês Santana, Isabel Cerejeira, Joaquim |
author_facet | Regueira, Patrícia Silva, Ana Rita Cardoso, Ana Luísa Cardoso, Ana Maria Baldeiras, Inês Santana, Isabel Cerejeira, Joaquim |
author_sort | Regueira, Patrícia |
collection | PubMed |
description | Dementia is a known risk factor for acute bacterial infections which may also play a significant role in promoting or accelerating cognitive impairment. Pneumonia and urinary tract infections are the main cause of hospitalisation of dementia patients and infections are a major precipitant of delirium. It is well established that peripheral immune signals induce a neuroinflammatory response largely mediated by microglial cells which is amplified with advanced age, neurodegenerative disorders and genetic characteristics. Reversely, the innate immune response to acute bacterial infection is tightly regulated by the brain. It remains unclear whether dysfunctional neural circuits affected by dementia and/or delirium could alter systemic innate immune responses at the periphery. The current study aims to determine if dementia and/or delirium are associated with an altered systemic inflammatory response to an acute bacterial infection. We recruited 46 hospitalised older patients with acute bacterial infections. From these, 29 participants had cognitive dysfunction (6 with delirium, 12 with dementia and 11 with delirium superimposed on dementia) and 17 had normal cognition. We also included a control group of 11 patients with dementia but with no current infection matched for age and educational status. Baseline characteristics were tested between groups using Kruskal-Wallis test and pairwise comparisons were subsequently assessed with Bonferroni correction for multiple comparisons for continuous variables. Chi square test was used to assess differences between groups in categorical data and correlations between peripheral inflammatory parameters were assessed with Spearman's test. The 4 groups with infection and the control group with no infection had similar characteristics except for cognitive function and functionality which was higher for the group of infected cognitively healthy participants. Levels of C-reactive protein were similar between the infected groups and higher than the non-infected dementia group. Infected patients with cognitive dysfunction (delirium and/or dementia) had higher serum levels of IL-6, TNF-alpha and IL-1beta. These participants had reduced expression of miR-145 in circulating exosomes which correlated negatively with miR-155 levels (r = −0.411, p = 0.027). Expression of CR1 in circulating CD14(+) monocytes was higher in infected participants with cognitive dysfunction and, in this group, PICALM correlated both with TNF-alpha and IL-6. In contrast to what was observed in participants with normal cognition, expression of CR1 did not correlate with DAP12 in infected participants with cognitive dysfunction. Taken together, our findings suggest that cognitive dysfunction is associated with an exaggerated proinflammatory response during acute bacterial infection with deregulation of several molecular signalling pathways in circulating exosomes and in monocytes. |
format | Online Article Text |
id | pubmed-9460160 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-94601602022-09-10 Peripheral inflammatory markers during an acute bacterial infection in older patients with and without cognitive dysfunction: A case control study Regueira, Patrícia Silva, Ana Rita Cardoso, Ana Luísa Cardoso, Ana Maria Baldeiras, Inês Santana, Isabel Cerejeira, Joaquim Brain Behav Immun Health Full Length Article Dementia is a known risk factor for acute bacterial infections which may also play a significant role in promoting or accelerating cognitive impairment. Pneumonia and urinary tract infections are the main cause of hospitalisation of dementia patients and infections are a major precipitant of delirium. It is well established that peripheral immune signals induce a neuroinflammatory response largely mediated by microglial cells which is amplified with advanced age, neurodegenerative disorders and genetic characteristics. Reversely, the innate immune response to acute bacterial infection is tightly regulated by the brain. It remains unclear whether dysfunctional neural circuits affected by dementia and/or delirium could alter systemic innate immune responses at the periphery. The current study aims to determine if dementia and/or delirium are associated with an altered systemic inflammatory response to an acute bacterial infection. We recruited 46 hospitalised older patients with acute bacterial infections. From these, 29 participants had cognitive dysfunction (6 with delirium, 12 with dementia and 11 with delirium superimposed on dementia) and 17 had normal cognition. We also included a control group of 11 patients with dementia but with no current infection matched for age and educational status. Baseline characteristics were tested between groups using Kruskal-Wallis test and pairwise comparisons were subsequently assessed with Bonferroni correction for multiple comparisons for continuous variables. Chi square test was used to assess differences between groups in categorical data and correlations between peripheral inflammatory parameters were assessed with Spearman's test. The 4 groups with infection and the control group with no infection had similar characteristics except for cognitive function and functionality which was higher for the group of infected cognitively healthy participants. Levels of C-reactive protein were similar between the infected groups and higher than the non-infected dementia group. Infected patients with cognitive dysfunction (delirium and/or dementia) had higher serum levels of IL-6, TNF-alpha and IL-1beta. These participants had reduced expression of miR-145 in circulating exosomes which correlated negatively with miR-155 levels (r = −0.411, p = 0.027). Expression of CR1 in circulating CD14(+) monocytes was higher in infected participants with cognitive dysfunction and, in this group, PICALM correlated both with TNF-alpha and IL-6. In contrast to what was observed in participants with normal cognition, expression of CR1 did not correlate with DAP12 in infected participants with cognitive dysfunction. Taken together, our findings suggest that cognitive dysfunction is associated with an exaggerated proinflammatory response during acute bacterial infection with deregulation of several molecular signalling pathways in circulating exosomes and in monocytes. Elsevier 2022-08-27 /pmc/articles/PMC9460160/ /pubmed/36093438 http://dx.doi.org/10.1016/j.bbih.2022.100503 Text en © 2022 Published by Elsevier Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Full Length Article Regueira, Patrícia Silva, Ana Rita Cardoso, Ana Luísa Cardoso, Ana Maria Baldeiras, Inês Santana, Isabel Cerejeira, Joaquim Peripheral inflammatory markers during an acute bacterial infection in older patients with and without cognitive dysfunction: A case control study |
title | Peripheral inflammatory markers during an acute bacterial infection in older patients with and without cognitive dysfunction: A case control study |
title_full | Peripheral inflammatory markers during an acute bacterial infection in older patients with and without cognitive dysfunction: A case control study |
title_fullStr | Peripheral inflammatory markers during an acute bacterial infection in older patients with and without cognitive dysfunction: A case control study |
title_full_unstemmed | Peripheral inflammatory markers during an acute bacterial infection in older patients with and without cognitive dysfunction: A case control study |
title_short | Peripheral inflammatory markers during an acute bacterial infection in older patients with and without cognitive dysfunction: A case control study |
title_sort | peripheral inflammatory markers during an acute bacterial infection in older patients with and without cognitive dysfunction: a case control study |
topic | Full Length Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9460160/ https://www.ncbi.nlm.nih.gov/pubmed/36093438 http://dx.doi.org/10.1016/j.bbih.2022.100503 |
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