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Commentary |

Statins and Brain DysfunctionStatins and Brain Dysfunction: A Hypothesis to Reduce the Burden of Cognitive Impairment in Patients Who Are Critically Ill

Alessandro Morandi, MD, MPH; Christopher G. Hughes, MD; Timothy D. Girard, MD, MSCI; Danny F. McAuley, MD; E. Wesley Ely, MD, MPH, FCCP; Pratik P. Pandharipande, MD, MSCI
Author and Funding Information

From the Center for Quality of Aging (Drs Morandi, Girard, and Ely), the Center for Health Services Research (Drs Morandi, Girard, and Ely), the Division of Allergy, Pulmonary, and Critical Care Medicine, the Department of Medicine (Drs Morandi, Girard, and Ely), and the Department of Anesthesiology, Division of Critical Care Medicine (Drs Hughes and Pandharipande), Vanderbilt University School of Medicine; the Anesthesia Service (Dr Pandharipande) and the Geriatric Research, Education, and Clinical Center Service (Drs Girard and Ely), Department of Veterans Affairs Medical Center, Tennessee Valley Healthcare System, Nashville, TN; and the Regional Intensive Care Unit (Dr McAuley), Royal Victoria Hospital, and the Centre for Infection and Immunity (Dr McAuley), the Queen’s University of Belfast, Belfast, Northern Ireland.

Correspondence to: Alessandro Morandi, MD, MPH, 1211 21st Ave S, Ste 6100, Nashville, TN 37212; e-mail: morandi.alessandro@gmail.com


Funding/Support: Dr Hughes is supported by the Foundation for Anesthesia Education and Research Mentored Research Training Grant. Dr Girard is supported by the National Institutes of Health [Grant AG034257]. Dr McAuley is supported by the Northern Ireland Public Health Agency Research and Development Division Translational Research Group for Critical Care. Dr Ely is supported by the US Department of Veterans Affairs Clinical Science Research and Development Service [Merit Review Award] and the National Institutes of Health [Grant AG027472]. Drs Ely and Girard are both supported by the US Department of Veterans Affairs Tennessee Valley Geriatric Research, Education, and Clinical Center. Dr Pandharipande is supported by the US Department of Veterans Affairs Clinical Science Research and Development Service [Career Development Award].

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


© 2011 American College of Chest Physicians


Chest. 2011;140(3):580-585. doi:10.1378/chest.10-3065
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Delirium is a frequent form of acute brain dysfunction in patients who are critically ill and is associated with poor clinical outcomes, including a critical illness brain injury that may last for months to years. Despite widespread recognition of significant adverse outcomes, pharmacologic approaches to prevent or treat delirium during critical illness remain unproven. We hypothesize that commonly prescribed statin medications may prevent and treat delirium by targeting molecular pathways of inflammation (peripheral and central) and microglial activation that are central to the pathogenesis of delirium. Systemic inflammation, a principal mechanism of injury, for example, in sepsis, acute respiratory distress syndrome, and other critical illnesses, can cause neuronal apoptosis, blood-brain barrier injury, brain ischemia, and microglial activation. We hypothesize that the known pleiotropic effects of statins, which attenuate such neuroinflammation, may redirect microglial activation and promote an antiinflammatory phenotype, thereby offering the potential to reduce the public health burden of delirium and its associated long-term cognitive injury.

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