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C-Reactive protein and cognition: Mediation analyses with brain morphology in the UK Biobank

Cognitive impairments and abnormal immune activity are both associated with various clinical disorders. The association between C-Reactive protein (CRP), a marker associated with inflammation, and cognitive performance remains unclear. Further, mechanisms potentially linking CRP to cognition are not...

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Autores principales: Mendelson, Daniel, Mizrahi, Romina, Lepage, Martin, Lavigne, Katie M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10362544/
https://www.ncbi.nlm.nih.gov/pubmed/37484195
http://dx.doi.org/10.1016/j.bbih.2023.100664
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author Mendelson, Daniel
Mizrahi, Romina
Lepage, Martin
Lavigne, Katie M.
author_facet Mendelson, Daniel
Mizrahi, Romina
Lepage, Martin
Lavigne, Katie M.
author_sort Mendelson, Daniel
collection PubMed
description Cognitive impairments and abnormal immune activity are both associated with various clinical disorders. The association between C-Reactive protein (CRP), a marker associated with inflammation, and cognitive performance remains unclear. Further, mechanisms potentially linking CRP to cognition are not yet established. Brain structure may well mediate this relationship: immune processes play crucial roles in shaping and maintaining brain structure, with brain structure and function driving cognition. The United Kingdom Biobank (UKBB) is a large cohort study with extensive assessments, including high-sensitivity serum CRP levels, brain imaging, and various cognitive tasks. With data from 39,200 UKBB participants, we aimed first to determine the relationship between CRP and cognitive performance, and second, to assess metrics of brain morphology as potential mediators in this relationship. Participants were aged 40 to 70 at initial assessment and were mostly Caucasian. After accounting for potential covariates (e.g., age, sex, medical diagnoses, use of selective-serotonin reuptake inhibitors), we found CRP levels to have small, negative associations with fluid intelligence (b = −0.03, 95%CI[-0.05,-0.02], t(14381) = −3.62, p(cor) = .004), and numeric memory (b = −0.03, 95%CI[-0.05,-0.01], t(14366) = −3.31, p(cor) = .007). We found no evidence of brain morphology mediating these relationships (all |ab| < 0.001, all p(cor) > .55). Our findings from this large sample suggest that serum-assessed CRP is of marginal importance for cognitive performance in mid-to-late aged Caucasians; the small effect sizes of statistically significant associations provide context to previous inconsistent results. The seeming lack of involvement of brain morphology suggests that other brain metrics (e.g., connectivity, functional activation) may be more pertinent to this relationship. Future work should also consider CRP levels measured in the central nervous system and/or other cytokines that may better predict cognitive performance in this population.
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spelling pubmed-103625442023-07-23 C-Reactive protein and cognition: Mediation analyses with brain morphology in the UK Biobank Mendelson, Daniel Mizrahi, Romina Lepage, Martin Lavigne, Katie M. Brain Behav Immun Health Full Length Article Cognitive impairments and abnormal immune activity are both associated with various clinical disorders. The association between C-Reactive protein (CRP), a marker associated with inflammation, and cognitive performance remains unclear. Further, mechanisms potentially linking CRP to cognition are not yet established. Brain structure may well mediate this relationship: immune processes play crucial roles in shaping and maintaining brain structure, with brain structure and function driving cognition. The United Kingdom Biobank (UKBB) is a large cohort study with extensive assessments, including high-sensitivity serum CRP levels, brain imaging, and various cognitive tasks. With data from 39,200 UKBB participants, we aimed first to determine the relationship between CRP and cognitive performance, and second, to assess metrics of brain morphology as potential mediators in this relationship. Participants were aged 40 to 70 at initial assessment and were mostly Caucasian. After accounting for potential covariates (e.g., age, sex, medical diagnoses, use of selective-serotonin reuptake inhibitors), we found CRP levels to have small, negative associations with fluid intelligence (b = −0.03, 95%CI[-0.05,-0.02], t(14381) = −3.62, p(cor) = .004), and numeric memory (b = −0.03, 95%CI[-0.05,-0.01], t(14366) = −3.31, p(cor) = .007). We found no evidence of brain morphology mediating these relationships (all |ab| < 0.001, all p(cor) > .55). Our findings from this large sample suggest that serum-assessed CRP is of marginal importance for cognitive performance in mid-to-late aged Caucasians; the small effect sizes of statistically significant associations provide context to previous inconsistent results. The seeming lack of involvement of brain morphology suggests that other brain metrics (e.g., connectivity, functional activation) may be more pertinent to this relationship. Future work should also consider CRP levels measured in the central nervous system and/or other cytokines that may better predict cognitive performance in this population. Elsevier 2023-06-29 /pmc/articles/PMC10362544/ /pubmed/37484195 http://dx.doi.org/10.1016/j.bbih.2023.100664 Text en © 2023 The Authors 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
Mendelson, Daniel
Mizrahi, Romina
Lepage, Martin
Lavigne, Katie M.
C-Reactive protein and cognition: Mediation analyses with brain morphology in the UK Biobank
title C-Reactive protein and cognition: Mediation analyses with brain morphology in the UK Biobank
title_full C-Reactive protein and cognition: Mediation analyses with brain morphology in the UK Biobank
title_fullStr C-Reactive protein and cognition: Mediation analyses with brain morphology in the UK Biobank
title_full_unstemmed C-Reactive protein and cognition: Mediation analyses with brain morphology in the UK Biobank
title_short C-Reactive protein and cognition: Mediation analyses with brain morphology in the UK Biobank
title_sort c-reactive protein and cognition: mediation analyses with brain morphology in the uk biobank
topic Full Length Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10362544/
https://www.ncbi.nlm.nih.gov/pubmed/37484195
http://dx.doi.org/10.1016/j.bbih.2023.100664
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