Role of CRP, TNF-a, and IGF-1 in Delirium Pathophysiology

Çinar, Mehmet Alper; Balıkçı, Adem; Sertoğlu, Erdim; Mehmet, A K; Serdar, Muhittin; Özmenler, Kami̇l Nahi̇t

doi:10.5152/npa.2014.6999

Cited by 15 publications

(14 citation statements)

References 41 publications

(49 reference statements)

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“…The authors conclude that the direct relationship between the magnitude of non-infective inflammatory response and incidence of POCD has not been established. This is consistent with the data reported by Çinar et al that CRP, although elevated, cannot be considered as an independent risk factor in the development of POD [ 98 ]. On the other hand, a study, including the CRP levels performed by Kotfis et al, showed a correlation between increased CRP levels and delirium [ 62 ].…”

Section: Inflammation-related Biomarkerssupporting

confidence: 93%

“…Kazmierski et al showed an elevation of IL-2 and TNF-α levels in the postoperative period in coronary artery bypass graft (CABG) patients with delirium, and these results were independent of patient-related factors like age and gender, as well as their psychiatric and physical state and co-morbidities or perioperative factors like CPB time or duration of surgery [ 99 ]. According to Çinar et al, it is difficult to consider the postoperative value of TNF-α or CRP as an independent risk factor for POD [ 98 ]. However, Androsova et al mentioned that SIRS is the key factor, which may affect the brain and lead to neuroinflammation with IL-6 and TNF-α as biomarkers in predicting delirium [ 51 ].…”

Section: Inflammation-related Biomarkersmentioning

confidence: 99%

“…The role of IGF-1 is neuroprotective as it inhibits the cytotoxic cytokines (e.g., TNF-α). In a study by Çinar et al, the authors found that low levels of IGF-1 before the cardiac operation were risk factors for developing POD [ 98 ]. Neurotransmitter-based and other biomarkers are summarized in Table 4 .…”

Section: Neurotransmitter-based and Other Biomarkersmentioning

confidence: 99%

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Current Evidence Regarding Biomarkers Used to Aid Postoperative Delirium Diagnosis in the Field of Cardiac Surgery—Review

Majewski¹,

Zegan-Barańska

Karolak

et al. 2020

Medicina

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Postoperative cognitive disorders after cardiac surgery may manifest as postoperative delirium (POD) or later as postoperative cognitive dysfunction (POCD). The incidence of POD after cardiac surgery ranges from 16% to 73%. In contrast to POD, POCD is usually diagnosed after the discharge from hospital, with an incidence of 30 to 70% of cases, very often noticed only by close relative or friends, decreasing after six (20–30%) and twelve (15–25%) months after surgery. Perioperative cognitive disorders are associated with adverse short- and long-term effects, including increased morbidity and mortality. Due to the complexity of delirium pathomechanisms and the difficulties in the diagnosis, researchers have not yet found a clear answer to the question of which patient will be at a higher risk of developing delirium. The risk for POD and POCD in older patients with numerous comorbidities like hypertension, diabetes, and previous ischemic stroke is relatively high, and the predisposing cognitive profile for both conditions is important. The aim of this narrative review was to identify and describe biomarkers used in the diagnosis of delirium after cardiac surgery by presenting a search through studies regarding this subject, which have been published during the last ten years. The authors discussed brain-derived biomarkers, inflammation-related biomarkers, neurotransmitter-based biomarkers, and others. Work based on inflammation-related biomarkers, which are characterized by the low cost of implementation and the effectiveness of delirium diagnosis, seems to be the closest to the goal of discovering an inexpensive and effective marker. Currently, the use of a panel of tests, and not a single biomarker, brings us closer to the discovery of a test, or rather a set of tests ideal for the diagnosis of delirium after cardiac surgery.

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Section: Inflammation-related Biomarkerssupporting

confidence: 93%

Section: Inflammation-related Biomarkersmentioning

confidence: 99%

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Current Evidence Regarding Biomarkers Used to Aid Postoperative Delirium Diagnosis in the Field of Cardiac Surgery—Review

Majewski¹,

Zegan-Barańska

Karolak

et al. 2020

Medicina

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“…Twenty-five studies applied CAM to define POD [ 22 – 27 , 29 – 31 , 33 – 36 , 38 – 40 , 42 – 50 ] of which three were assessed with CAM and confirmed with the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision; DSM-IV-TR) [ 25 – 27 ], and one was evaluated through CAM and the Delirium Rating Scale [ 24 ] (DRS: sensitivity of 82% and specificity of 94%, cut-off score of 10 [ 15 ]). Two studies used DRS to define delirium [ 21 , 28 ]. In one study, delirium was diagnosed using DSM-IV and DRS [ 32 ].…”

Section: Resultsmentioning

confidence: 99%

Inflammatory markers in postoperative delirium (POD) and cognitive dysfunction (POCD): A meta-analysis of observational studies

2018

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BackgroundThe aim of this study was to summarize and discuss the similarities and differences in inflammatory biomarkers in postoperative delirium (POD) and cognitive dysfunction (POCD).MethodsA systematic retrieval of literature up to June 2017 in PubMed, Embase, the Cochrane Library, the China National Knowledge Infrastructure database, and the Wanfang database was conducted. Extracted data were analyzed with STATA (version 14). The standardized mean difference (SMD) and the 95% confidence interval (95% CI) of each indicator were calculated using a random effect model. We also performed tests of heterogeneity, sensitivity analysis, assessments of bias, and meta-regression in this meta-analysis.ResultsA total of 54 observational studies were included. By meta-analysis we found significantly increased C-reactive protein (CRP) (9 studies, SMD 0.883, 95% CI 0.130 to 1.637, P = 0.022 in POD; 10 studies, SMD -0.133, 95% CI -0.512 to 0.246, P = 0.429 in POCD) and interleukin (IL)-6 (7 studies, SMD 0.386, 95% CI 0.054 to 0.717, P = 0.022 in POD; 16 studies, SMD 0.089, 95% CI -0.133 to 0.311, P = 0.433 in POCD) concentrations in both POD and POCD patients. We also found that the SMDs of CRP and IL-6 from POCD patients were positively correlated with surgery type in the meta-regression (CRP: Coefficient = 1.555365, P = 0.001, 10 studies; IL-6: Coefficient = -0.6455521, P = 0.086, 16 studies).ConclusionAvailable evidence from medium-to-high quality observational studies suggests that POD and POCD are indeed correlated with the concentration of peripheral and cerebrospinal fluid (CSF) inflammatory markers. Some of these markers, such as CRP and IL-6, play roles in both POD and POCD, while others are specific to either one of them.

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“…In fact, relationship between direct measurement of TNF-alpha level and delirium has been controversial. In patients with delirium, multiple study reported that TNF-alpha remain not significant (De Rooij et al, 2007 ; Çinar et al, 2014 ; Brum et al, 2015 ). Of note, sample sizes of delirium cases in these reports are less than 100 (64 cases, 15 cases, and 17 cases, respectively), thus the result might have been underpowered.…”

Section: Discussionmentioning

confidence: 99%

Epigenetics of Delirium and Aging: Potential Role of DNA Methylation Change on Cytokine Genes in Glia and Blood Along With Aging

Shinozaki

Braun

Hing

et al. 2018

Front. Aging Neurosci.

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Background: Delirium in elderly patients is common and dangerous. Major risk factors include aging and exogenous insults, such as infection or surgery. In animal models, aging enhances pro-inflammatory cytokine release from microglia in response to exogenous insults. The epigenetic mechanism DNA methylation (DNAm) regulates gene expression and changes with age. Older individuals may have methylation changes that influence the increased cytokine upon insult, but the degree to which aging affects DNAm of cytokine genes is not fully understood.Methods: The relationship between DNAm and aging of pro-inflammatory cytokine genes (TNF-alpha, IL1-beta, IL-6) was investigated using methylation array data in two cohorts. Brain and blood samples were collected from a neurosurgery cohort (NSG) of 21 subjects who underwent brain resection. A second cohort, the Grady Trauma Project (GTP), included blood samples from 265 subjects.Results: In the NSG cohort, a significant negative correlation between age and DNAm in brain was found at a CpG in IL-6. With the GTP dataset, significant negative correlations between age and DNAm were seen at most of the CpGs in TNF-alpha. Also, TNF-Alpha expression increases with age. These GTP DNAm correlations were also nominally significant in NSG blood samples. In neuronal negative NSG brain tissue, a similar negative trend was observed.Conclusions: With aging, a decrease in DNAm of cytokines gene CpGs in glia and blood was seen. As this can affect their expression, additional research is needed to fully elucidate the role of DNAm in aging and how it may influence the pathogenesis of delirium.

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Role of CRP, TNF-a, and IGF-1 in Delirium Pathophysiology

Abstract: Low IGF-1 levels can be used to predict delirium after surgery. However, the complex nature of cytokines and delirium itself make it difficult to utilize cytokines to predict delirium instead of psychometric tools.

Cited by 15 publications

References 41 publications

Current Evidence Regarding Biomarkers Used to Aid Postoperative Delirium Diagnosis in the Field of Cardiac Surgery—Review

Current Evidence Regarding Biomarkers Used to Aid Postoperative Delirium Diagnosis in the Field of Cardiac Surgery—Review

Inflammatory markers in postoperative delirium (POD) and cognitive dysfunction (POCD): A meta-analysis of observational studies

Epigenetics of Delirium and Aging: Potential Role of DNA Methylation Change on Cytokine Genes in Glia and Blood Along With Aging

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