DNA methylation in the TNF-alpha gene decreases along with aging among delirium inpatients

Delirium is an acute disorder of attention and cognition in elderly people (ie, those aged 65 years or older) that is common, serious, costly, under-recognised, and often fatal. A formal cognitive assessment and history of acute onset of symptoms are necessary for diagnosis. In view of the complex multifactorial causes of delirium, multicomponent non-pharmacological risk factor approaches are the most effective strategy for prevention. No convincing evidence shows that pharmacological prevention or treatment is effective. Drug reduction for sedation and analgesia and non-pharmacological approaches are recommended. Delirium offers opportunities to elucidate brain pathophysiology--it serves both as a marker of brain vulnerability with decreased reserve and as a potential mechanism for permanent cognitive damage. As a potent indicator of patients' safety, delirium provides a target for system-wide process improvements. Public health priorities include improvements in coding, reimbursement from insurers, and research funding, and widespread education for clinicians and the public about the importance of delirium. Copyright © 2014 Elsevier Ltd. All rights reserved.

Monocytes originate from progenitors in the bone marrow and traffic via the bloodstream to peripheral tissues. During both homeostasis and inflammation, circulating monocytes leave the bloodstream and migrate into tissues where, following conditioning by local growth factors, pro-inflammatory cytokines and microbial products, they differentiate into macrophage or dendritic cell populations. Recruitment of monocytes is essential for effective control and clearance of viral, bacterial, fungal and protozoal infections, but recruited monocytes also contribute to the pathogenesis of inflammatory and degenerative diseases. The mechanisms that control monocyte trafficking under homeostatic, infectious and inflammatory conditions are being unravelled and are the focus of this Review.

Survivors of critical illness often have a prolonged and disabling form of cognitive impairment that remains inadequately characterized. We enrolled adults with respiratory failure or shock in the medical or surgical intensive care unit (ICU), evaluated them for in-hospital delirium, and assessed global cognition and executive function 3 and 12 months after discharge with the use of the Repeatable Battery for the Assessment of Neuropsychological Status (population age-adjusted mean [±SD] score, 100±15, with lower values indicating worse global cognition) and the Trail Making Test, Part B (population age-, sex-, and education-adjusted mean score, 50±10, with lower scores indicating worse executive function). Associations of the duration of delirium and the use of sedative or analgesic agents with the outcomes were assessed with the use of linear regression, with adjustment for potential confounders. Of the 821 patients enrolled, 6% had cognitive impairment at baseline, and delirium developed in 74% during the hospital stay. At 3 months, 40% of the patients had global cognition scores that were 1.5 SD below the population means (similar to scores for patients with moderate traumatic brain injury), and 26% had scores 2 SD below the population means (similar to scores for patients with mild Alzheimer's disease). Deficits occurred in both older and younger patients and persisted, with 34% and 24% of all patients with assessments at 12 months that were similar to scores for patients with moderate traumatic brain injury and scores for patients with mild Alzheimer's disease, respectively. A longer duration of delirium was independently associated with worse global cognition at 3 and 12 months (P=0.001 and P=0.04, respectively) and worse executive function at 3 and 12 months (P=0.004 and P=0.007, respectively). Use of sedative or analgesic medications was not consistently associated with cognitive impairment at 3 and 12 months. Patients in medical and surgical ICUs are at high risk for long-term cognitive impairment. A longer duration of delirium in the hospital was associated with worse global cognition and executive function scores at 3 and 12 months. (Funded by the National Institutes of Health and others; BRAIN-ICU ClinicalTrials.gov number, NCT00392795.).