Apolipoprotein E4 polymorphism as a genetic predisposition to delirium in critically ill patients*
- 1 January 2007
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Critical Care Medicine
- Vol. 35 (1), 112-117
- https://doi.org/10.1097/01.ccm.0000251925.18961.ca
Abstract
To test for an association between apolipoprotein E (APOE) genotypes and duration of intensive care unit delirium. Prospective, observational cohort study. A 541-bed, community-based teaching hospital. Fifty-three mechanically ventilated intensive care unit patients. None. All patients were managed with standardized sedation and ventilator weaning protocols as part of an ongoing clinical trial and were evaluated prospectively for delirium with the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). DNA was extracted from whole blood samples obtained on enrollment, and APOE genotype was determined using polymerase chain reaction followed by restriction enzyme digestion by investigators blinded to the clinical information. Delirium occurred in 47 (89%) patients at some point during the intensive care unit stay. Of the 53 patients, 12 (23%) had an APOE4 allele (APOE4+) and 41 (77%) had only APOE2 or APOE3 alleles (APOE4-). APOE4+ patients were younger (53.2 +/- 21.9 vs. 65.4 +/- 13.4, p = .08) and less often admitted for pneumonia (0% vs. 29.3%, p = .05) compared with APOE4- patients, yet they had a duration of delirium that was twice as long: median (interquartile range), 4 (3, 4.5) vs. 2 (1, 4) days (p = .05). No other clinical outcomes were significantly different between the APOE4+ and APOE4- patients. Using multivariable regression analysis to adjust for age, admission diagnosis of sepsis or acute respiratory distress syndrome or pneumonia, severity of illness, and duration of coma, the presence of APOE4 allele was the strongest predictor of delirium duration (odds ratio, 7.32; 95% confidence interval, 1.82-29.51, p = .005). APOE4 allele represents the first demonstrated genetic predisposition to longer duration of delirium in humans.This publication has 47 references indexed in Scilit:
- PREVALENCE OF DELIRIUM IN SURGICAL ICU PATIENTS.Critical Care Medicine, 2005
- Apolipoprotein E-Derived Peptides Block α7 Neuronal Nicotinic Acetylcholine Receptors Expressed inXenopusOocytesThe Journal of pharmacology and experimental therapeutics, 2005
- Delirium as a Predictor of Mortality in Mechanically Ventilated Patients in the Intensive Care UnitJAMA, 2004
- Current opinions regarding the importance, diagnosis, and management of delirium in the intensive care unit: A survey of 912 healthcare professionals*Critical Care Medicine, 2004
- Effect of apolipoprotein E genotype on in-hospital mortality following intracerebral haemorrhageActa Neurologica Scandinavica, 2003
- Apolipoprotein E PolymorphismStroke, 2000
- Gene Dose of Apolipoprotein E Type 4 Allele and the Risk of Alzheimer's Disease in Late Onset FamiliesScience, 1993
- The Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE): socio-demographic correlates, reliability, validity and some normsPsychological Medicine, 1989
- APACHE IICritical Care Medicine, 1985
- The central role of the propensity score in observational studies for causal effectsBiometrika, 1983