From CellBiology



Biomarkers for delirium--a review

J Am Geriatr Soc. 2011 Nov;59 Suppl 2:S256-61. doi: 10.1111/j.1532-5415.2011.03702.x.

Khan BA, Zawahiri M, Campbell NL, Boustani MA. Source Division of Pulmonary and Critical Care, Department of Medicine, School of Medicine, Indiana University, Indianapolis, USA.

Abstract To improve delirium recognition and care, numerous serum biomarkers have been investigated as potential tools for risk stratification, diagnosis, monitoring, and prognostication of delirium. The literature was reviewed, and no evidence was found to support the clinical use of any delirium biomarker, although certain biomarkers such as S-100 beta and insulin-like growth factor-1 and inflammatory markers have shown some promising results that need to be evaluated in future studies with appropriate sample size, prospective designs, and in a more-generalizable population. © 2011, Copyright the Authors Journal compilation © 2011, The American Geriatrics Society.

PMID 22091570

A review of recent clinical trials and guidelines on the prevention and management of delirium in hospitalized older patients

Hosp Pract (Minneap). 2011 Oct;39(4):96-106.

Rathier MO, Baker WL. Source University of Connecticut Health Center, Center on Aging, Farmington, CT, USA.


Treatment of acute illness in older adults is frequently complicated by the presence of delirium. Delirium is characterized by the development of an altered mental status over the course of hours to days, and can have a fluctuating course. Patients with delirium have difficulty paying attention to their environment, have disorganized thinking, and usually have an altered level of consciousness. While scientists continue to elucidate the pathophysiologic mechanisms associated with delirium, clinicians can identify patients at risk for delirium and diagnose it using valid instruments, such as the Confusion Assessment Method and Confusion Assessment Method for the Intensive Care Unit. Delirium is an independent risk factor for death, institutionalization, and dementia, and resolves in many patients by the time of hospital discharge. For patients admitted to medical units, optimal management of delirium includes reassessment of medications, pain, sleep, nutrition, mobility, need for physical restraints, and bowel and bladder function. The use of antipsychotic medication to sedate delirious patients should be restricted to patients in danger of harming themselves or others and should be used when nonpharmacologic means fail. Multicomponent interventions performed by the hospital care team that address risk factors can prevent delirium in patients in medical units and those undergoing hip fracture repair. This includes attention to the depth of sedation during spinal anesthesia and the addition of regional nerve blocks to patient-controlled analgesia in orthopedic patients, both of which may reduce postoperative delirium. Perioperative use of antipsychotics may further reduce the incidence of delirium, although hospital length of stay has not been routinely reduced. Appropriate management of analgesia, sedation, and delirium in the intensive care unit is also associated with reduced duration of mechanical ventilation, as well as intensive care unit and hospital length of stay. The use of dexmedetomidine, an α-adrenergic receptor agonist, for sedation may reduce intensive care unit length of stay when compared with use of benzodiazepines.

PMID 22056829

Patients' and nurses' experiences of delirium: a review of qualitative studies

Nurs Crit Care. 2011 Nov-Dec;16(6):303-15. doi: 10.1111/j.1478-5153.2011.00454.x. Epub 2011 Jul 19.

Bélanger L, Ducharme F. Source University of Montreal, Chemin Queen-Mary, Québec, Canada.


BACKGROUND: Knowledge of delirium accumulated over the past two decades has focused more on its characteristics, pathophysiology, incidence, aetiology and prognosis as well as interventions for preventing, detecting, evaluating or managing this syndrome and less so on how patients and nurses who care for them experience it. AIMS: To present the state of knowledge derived from qualitative studies of the experiences of persons who suffered delirium and of nurses who cared for them to guide critical care practice. RESULTS: Delirious patients experience incomprehension and various feelings of discomfort. Understanding, support, believing what they are experiencing, explanations, the presence of family/friends and the possibility of talking about the lived experience are interventions that might help them get through such episodes more easily. Nurses who tend to delirious patients fail to comprehend the utterances and behaviours of the persons cared for and experience various feelings of discomfort as well. Nevertheless, they intervene following different goals and intervention strategies that seem to vary as a function of their culture and values. CONCLUSION: Qualitative studies conducted on persons who suffered delirium and on nurses who cared for them have shed light on their lived experience and provide insight on how to improve critical care practice. RELEVANCE TO CLINICAL PRACTICE: The findings suggest that nurses must acknowledge the lived experience of the persons cared for and they must seek out the meaning that patients ascribe to this experience to understand the situation and thus conduct interventions that meet the needs expressed. © 2011 The Authors. Nursing in Critical Care © 2011 British Association of Critical Care Nurses.

PMID 21999421

CNS recruitment of CD8+ T lymphocytes specific for a peripheral virus infection triggers neuropathogenesis during polymicrobial challenge

PLoS Pathog. 2011 Dec;7(12):e1002462. Epub 2011 Dec 22.

Matullo CM, O'Regan KJ, Curtis M, Rall GF. Source Fox Chase Cancer Center, Division of Basic Science, Program in Immune Cell Development and Host Defense, Philadelphia, Pennsylvania, United States of America.


Although viruses have been implicated in central nervous system (CNS) diseases of unknown etiology, including multiple sclerosis and amyotrophic lateral sclerosis, the reproducible identification of viral triggers in such diseases has been largely unsuccessful. Here, we explore the hypothesis that viruses need not replicate in the tissue in which they cause disease; specifically, that a peripheral infection might trigger CNS pathology. To test this idea, we utilized a transgenic mouse model in which we found that immune cells responding to a peripheral infection are recruited to the CNS, where they trigger neurological damage. In this model, mice are infected with both CNS-restricted measles virus (MV) and peripherally restricted lymphocytic choriomeningitis virus (LCMV). While infection with either virus alone resulted in no illness, infection with both viruses caused disease in all mice, with ∼50% dying following seizures. Co-infection resulted in a 12-fold increase in the number of CD8+ T cells in the brain as compared to MV infection alone. Tetramer analysis revealed that a substantial proportion (>35%) of these infiltrating CD8+ lymphocytes were LCMV-specific, despite no detectable LCMV in CNS tissues. Mechanistically, CNS disease was due to edema, induced in a CD8-dependent but perforin-independent manner, and brain herniation, similar to that observed in mice challenged intracerebrally with LCMV. These results indicate that T cell trafficking can be influenced by other ongoing immune challenges, and that CD8+ T cell recruitment to the brain can trigger CNS disease in the apparent absence of cognate antigen. By extrapolation, human CNS diseases of unknown etiology need not be associated with infection with any particular agent; rather, a condition that compromises and activates the blood-brain barrier and adjacent brain parenchyma can render the CNS susceptible to pathogen-independent immune attack.

PMID 22216008


Serum S100B in elderly patients with and without delirium

Int J Geriatr Psychiatry. 2010 Mar;25(3):234-9.

van Munster BC, Korevaar JC, Korse CM, Bonfrer JM, Zwinderman AH, de Rooij SE. Source Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Centre, University of Amsterdam, the Netherlands. Abstract OBJECTIVE: Elevation of S100B has been shown after various neurologic diseases with cognitive dysfunction. The aim of this study was to compare the serum level of S100B of patients with and without delirium and investigate the possible associations with different subtypes of delirium. METHODS: Acutely admitted medical patients aged 65 years or more were included from 2005 through 2008. Delirium was diagnosed by Confusion Assessment Method, delirium subtype by Delirium Symptom Interview and preexistent global cognitive function by the 'Informant Questionnaire on Cognitive Decline-short form'. S100B levels were determined in serum by electrochemiluminescence immunoassay. RESULTS: Samples of 412 patients were included, 91 during delirium, 35 after delirium and 286 of patients without delirium. Patients with delirium (31%) were significantly older, 81.5 versus 76.6 years (p < 0.001) and experienced significantly more often preexistent cognitive and functional impairment (p < 0.001). S100B level differed significantly (p = 0.004) between the three groups: median 0.07 microg/L (inter-quartile ranges: 0.05-0.14 microg/L) during delirium, 0.12 microg/L (0.05-0.29 microg/L) after delirium and 0.06 microg/L (0.03-0.10 microg/L) in patients without delirium. Combining the impact of cognitive impairment, infection and age on S100B, highest S100B was observed in the oldest patients after delirium with preexistent cognitive impaired and infection. Delirium subtype and S100B level were not significantly correlated. CONCLUSION: Higher S100B levels were found in patients with delirium than in patients without delirium, with highest levels of S100B in samples taken after delirium. Future studies are needed to elucidate the mechanism responsible for the increase of S100B and the possible association with long term cognitive impairment.

PMID 19575407


Pre-operative inflammatory markers and the risk of postoperative delirium in elderly patients

Int J Geriatr Psychiatry. 2008 Sep;23(9):943-8.

Lemstra AW, Kalisvaart KJ, Vreeswijk R, van Gool WA, Eikelenboom P. Source Department of Neurology, Academic Medical Centre, Amsterdam, The Netherlands. Abstract OBJECTIVE: Pathophysiological mechanisms leading to delirium are not clear. Age is a known risk factor and hypothesised to be accompanied by a low-grade inflammatory state. Previous studies have shown an association between delirium and circulating proinflammatory markers in acutely ill and postoperative patients. In light of the ageing/inflammation theory, we investigated the association of these markers with delirium in not acutely ill, elderly patients. METHODS: In a prospective nested case-control study levels of C-reactive protein (CRP), interleukin 6 (Il-6), insulin growth factor 1 (IGF-1) were measured pre-operatively in elderly patients admitted for hip-surgery. These levels were compared between patients who later developed a post-operative delirium and patients who did not. Patients were matched for age and disease severity. RESULTS: Eighteen patients who developed delirium post-operatively were matched with 50 controls. Median APACHE-scores were below 16 in both groups. Pre-operative serum concentrations of CRP, Il-6 and IGF-1 did not differ between groups. IL-6 levels were associated with a measure of cognitive impairment. CONCLUSION: In the present study no relationship was found between levels of pre-operative circulating pro-inflammatory markers and post-operative delirium in elderly patients, who were free from acute or severe disease.

PMID 18481319


Serum biomarkers for delirium

J Gerontol A Biol Sci Med Sci. 2006 Dec;61(12):1281-6.

Marcantonio ER, Rudolph JL, Culley D, Crosby G, Alsop D, Inouye SK. Source Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02446, USA.


This narrative review examines serum biomarkers for the diagnosis and monitoring of delirium. Serum biomarkers for delirium fall into three major groups: 1) those that are present or elevated prior to disease onset-risk markers, 2) those that rise with onset and fall with recovery-disease markers, and 3) those that rise in proportion to the consequences of disease-end products. As risk markers, we examine serum chemistries and genetic risk markers. As disease markers, we examine serum anticholinergic activity, amino acids, melatonin, cytokines, cortisol, and gene expression. As end products of delirium, we examine markers of neuronal injury. Finally, we discuss methodological and biostatistical considerations for future biomarker studies. Identifying accurate biomarkers for delirium may shed further light into its pathophysiology and on the interrelationship between delirium and dementia.

PMID 17234821