APOE and cytokines as biological markers for recovery of prevalent delirium in elderly medical inpatients

Adamis, Dimitrios; Treloar, Adrian; Martin, Finbarr C.; Gregson, N. A.; Hamilton, Gillian; Macdonald, Alastair

doi:10.1002/gps.1732

Cited by 99 publications

(125 citation statements)

References 32 publications

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“…66,67,69,[71][72][73][74] There is a growing body of literature supporting the role of inflammatory cytokines in delirium, yet there is no consensus at this time. 7,[75][76][77][78][79][80][81][82] Future prospective studies that employ polysomnography and measure the impact of CPAP therapy are needed to confirm the OSA-POD association and establish the mechanism by which OSA might increase the risk of POD. A limitation of our research is the possible role of undiagnosed OSA.…”

Section: Discussionmentioning

confidence: 99%

Obstructive Sleep Apnea and Incidence of Postoperative Delirium After Elective Knee Replacement in the Nondemented Elderly

Flink¹,

Rivelli²,

Cox³

et al. 2012

Survey of Anesthesiology

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Section: Discussionmentioning

confidence: 99%

Obstructive Sleep Apnea and Incidence of Postoperative Delirium After Elective Knee Replacement in the Nondemented Elderly

Flink¹,

Rivelli²,

Cox³

et al. 2012

Survey of Anesthesiology

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“…Elevated levels of plasma C-reactive protein have been reported in patients with delirium in medical or surgical settings [34,35] but this has not been confirmed by other studies [36,37,38]. Similarly, reports of higher plasma levels of IL-6, IL-8 and IL-10 in patients with delirium were not consistently replicated.…”

Section: Clinical Correlates Of Acute Neuroinflammationmentioning

confidence: 92%

The Immunology of Delirium

Cerejeira

Lagarto

Mukaetova‐Ladinska

2014

Neuroimmunomodulation

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Delirium is an acute neuropsychiatric syndrome characterized by acute-onset global cognitive deficits, perceptual and behavioural disturbances affecting mainly elderly subjects with underlying medical or surgical conditions. The pathophysiology of delirium is complex and inflammation is a relevant precipitant factor of this syndrome, although it remains unclear how acute systemic inflammation induces the clinical picture of delirium. The central nervous system is able to detect peripheral infection or tissue destruction through circulating immune mediators and neural ascending signs. Activated microglia is responsible for an acute neuroinflammatory reaction underlying the symptoms of sickness. In healthy conditions descending pathways from the paraventricular nucleus, locus coeruleus and dorsal motor nucleus organize a centralized response to influence the immune response at the periphery and restore homeostasis. In the context of ageing and chronic neurodegeneration, adaptive changes to acute insults are characterized by exaggerated production of pro-inflammatory cytokines by primed microglia coupled with dysfunction of brain-to-immune pathways. In animal models, these changes underlie a more severe manifestation of sickness behaviour with working memory deficits suggesting that inattention, a core feature of delirium, can be a clinical correlate of an increased neuroinflammatory reaction. In patients with delirium, higher levels of pro-inflammatory cytokines and cortisol were identified in plasma and cerebrospinal fluid. However, to date it has not been clarified how peripheral inflammatory or endocrine biomarkers can reflect the likelihood or severity of delirium symptoms. In the future, a better understanding of the interaction between the brain and peripheral organs and the exact mechanism by which systemic inflammation can lead to delirium, will allow the development of new therapeutic agents.

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“…In several studies, the potential role of the neuroprotective cytokine insulin-like growth factor-1 (IGF-1) has been investigated. Low IGF-1 levels have been associated with delirium in acutely ill elderly patients [8,19,20]. …”

Section: Introductionmentioning

confidence: 99%

Neopterin: A Potential Biomarker for Delirium in Elderly Patients

Egberts¹,

Wijnbeld²,

Fekkes³

et al. 2014

Dement Geriatr Cogn Disord

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Background/Aims: The diagnosis of delirium is not supported by specific biomarkers. In a previous study, high neopterin levels were found in patients with a postoperative delirium. In the present study, we investigated levels of neopterin, interleukin-6 (IL-6) and insulin-like growth factor-1 (IGF-1) in acutely ill admitted elderly patients with and without a delirium. Methods: Plasma/serum levels ofneopterin, IL-6 and IGF-1 were determined in patients aged ≥65 years admitted to the wards of Internal Medicine and Geriatrics. Differences in biomarker levels between patients with and without a delirium were investigated by the analysis of variance in models adjusted for age, gender, comorbidities and eGFR (when appropriate). Results: Eighty-six patients were included; 23 of them with a delirium. In adjusted models, higher mean levels of neopterin (70.5 vs. 45.9 nmol/l, p = 0.009) and IL-6 (43.1 vs. 18.5 pg/ml, p = 0.034) and lower mean levels of IGF-1 (6.3 vs. 9.3 nmol/l, p = 0.007) were found in patients with a delirium compared to those without. Conclusions: The findings of this study suggest that neopterin might be a potential biomarker for delirium which, through oxidative stress and activation of the immune system, may play a role in the pathophysiology of delirium. © 2014 S. Karger AG, Basel

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APOE and cytokines as biological markers for recovery of prevalent delirium in elderly medical inpatients

Abstract: A relationship between delirium with APOE genotype, IFN-gamma, and IGF-I, but not with IL-6, IL-1, TNF-alpha, and LIF was found. A predictive model of recovery was derived from gender, APOE status, and IGF-I levels. This model needs replication with further studies.

Cited by 99 publications

References 32 publications

Obstructive Sleep Apnea and Incidence of Postoperative Delirium After Elective Knee Replacement in the Nondemented Elderly

Obstructive Sleep Apnea and Incidence of Postoperative Delirium After Elective Knee Replacement in the Nondemented Elderly

The Immunology of Delirium

Neopterin: A Potential Biomarker for Delirium in Elderly Patients

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