Cortisol, interleukins and S100B in delirium in the elderly.
ABSTRACT In independent studies delirium was associated with higher levels of cortisol, interleukin(IL)s, and S100B. The aim of this study was to simultaneously compare cortisol, IL-6, IL-8, and S100B levels in patients aged 65years and older admitted for hip fracture surgery with and without delirium. Cortisol, IL-6, IL-8, and S100B were assayed in repeated blood samples. 120 patients (mean age 84years, 62 patients with delirium) were included. Highest levels of IL-8 (27.1, 95% Confidence Interval (CI): 13.6-53.1pg/ml) and cortisol (666, 95% CI: 475-859nmol/L) were before delirium, but of IL-6 (84.3, 95% CI: 46.5-151.4pg/mL) and S100B (0.18, 95% CI: 0.12-0.24 microg/L) during delirium. In multivariable analysis cortisol, LogIL-6, and LogS100B were significantly associated with delirium, but adjusted for pre-existing cognitive impairment, only LogS100B remained significantly associated. Cortisol, IL-6 and S100B may have a role in the pathogenesis of delirium, but S100B is the strongest independent marker.
BMC Geriatrics 12/2015; 15(1). DOI:10.1186/s12877-015-0006-3 · 2.00 Impact Factor
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ABSTRACT: Acute hospitals have seen unprecedented demographic changes, where older age, frailty and cognitive impairment now characterise the majority of health service users. Delirium is very common in this setting, and adverse outcomes are well described. However, studies investigating cognitive outcomes after delirium in unselected samples have been lacking. This thesis had four objectives: (1) To estimate the prevalence of delirium in the general population (2) To assess the association of delirium with cognitive outcomes (3) To investigate how these associations relate to underlying dementia pathology (4) To develop novel methods for retrospectively ascertaining delirium. Methods: Data from three population-based neuropathology cohort studies were used: Vantaa 85+; Cambridge City over-75s Cohort (CC75C); MRC Cognitive Function and Ageing Study (CFAS). (1) To ascertain the prevalence of delirium in the general population, a measure of delirium was developed using data recorded in standardised interview schedules, with criterion validity evaluated through the association with mortality and dementia risk. (2) The association with cognitive outcomes was tested in a series of logistic regression models, where delirium was the exposure and dementia (or worsening dementia severity) was the outcome. In addition, the association with change in Mini-Mental Status Examination (MMSE) score was assessed using random-effects linear regression. (3) In brain donors from all three cohorts, the independent effects of delirium, dementia pathology, and their interaction, were investigated using the same approach. (4) A chart-based method for deriving a retrospective diagnosis for delirium was developed, validated against bedside psychiatrist diagnosis. Vignettes from the medical record were abstracted and delirium status decided by expert consensus panel. Results: (1) Age-specific prevalence in CFAS increased with age from 1.8% in the 65-69 year age group to 13.5% in the ≥90 age group (p<0.01 for trend). (2) Delirium was consistently associated with adverse cognitive outcomes: new dementia (OR 8.7, 95% CI 2.1 to 35); worsening dementia severity (OR 3.1, 95% CI 1.5 to 6.3); faster change in Mini-Mental Status Examination (MMSE) score (1.0 additional points/year, p<0.01) (3) In the neuropathology analyses, decline attributable to delirium was -0.37 MMSE points/year (p<0.01). Decline attributable to dementia pathology was -0.39 MMSE points/year (p<0.01). However, the combination of delirium and dementia pathology resulted in the greatest decline, where the interaction contributed a further -0.16 MMSE points/year (p=0.01), suggesting that delirium worsened cognitive trajectories in dementia, but through distinct pathophysiological pathways not accounted for by Alzheimer’s, vascular or Lewy body pathology. (4) The chart abstraction method yielded a sensitivity of 0.88 and specificity 0.75 for ‘possible delirium’, with lower sensitivity (0.58) and higher specificity (0.93) for ‘probable delirium’ (AUC 0.86, 95% CI 0.82 to 0.89). This thesis adds to the small body of work on delirium in prospective studies, with the first ever analyses conducted in whole populations. The findings suggest new possibilities regarding the pathology of cognitive impairment, positioning delirium and/or its precipitants as a critically inter-related mechanism.10/2013, Degree: PhD, Supervisor: Carol Brayne
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ABSTRACT: Besides brain injury and systemic infection, cognitive and concussion like sickness behaviour is associated with muscular trauma and perioperative patients, which represents a major obstacle to daily activities and rehabilitation. The neuroinflammatory response triggers glial activation and consequently the release of proinflammatory cytokines within the hippocampus. We review clinical studies that have investigated neurocognitive and psychosomatic symptoms related to muscular trauma and in perioperative conditions. These include impaired attention and executive and general cognitive functioning. The purpose of this literature review is to focus on the systemic inflammation and the role of proinflammatory cytokines IL1, IL6,and TNF and other inflammatory mediators which mediates the cognitive impairment and induces sickness behaviour. Moreover, this review will also help to determine if some patients could have long-term cognitive changes associated with musculoskeletal injuries or as a consequence of surgery and thereby will lead to efforts in reducing that risk.04/2014; 2014:671781. DOI:10.1155/2014/671781