title: Statins and brain dysfunction: a hypothesis to reduce the burden of cognitive impairment in patients who are critically ill.
abstract: 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.
authors: Center for Quality of Aging, Vanderbilt University School of Medicine; Center for Health Services Research, Vanderbilt University School of Medicine; Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine. Electronic address: morandi.alessandro@gmail.com.
authors: Alessandro
authors: A
authors: Morandi
authors: Department of Anesthesiology, Division of Critical Care Medicine, Vanderbilt University School of Medicine.
authors: Christopher G
authors: CG
authors: Hughes
authors: Center for Quality of Aging, Vanderbilt University School of Medicine; Center for Health Services Research, Vanderbilt University School of Medicine; Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine; Geriatric Research, Education, and Clinical Center Service, Department of Veterans Affairs Medical Center, Tennessee Valley Healthcare System, Nashville, TN.
authors: Timothy D
authors: TD
authors: Girard
authors: Regional Intensive Care Unit, the Queen's University of Belfast, Belfast, Northern Ireland; Royal Victoria Hospital, and the Centre for Infection and Immunity, the Queen's University of Belfast, Belfast, Northern Ireland.
authors: Danny F
authors: DF
authors: McAuley
authors: Center for Quality of Aging, Vanderbilt University School of Medicine; Center for Health Services Research, Vanderbilt University School of Medicine; Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine; Geriatric Research, Education, and Clinical Center Service, Department of Veterans Affairs Medical Center, Tennessee Valley Healthcare System, Nashville, TN.
authors: E Wesley
authors: EW
authors: Ely
authors: Department of Anesthesiology, Division of Critical Care Medicine, Vanderbilt University School of Medicine; Anesthesia Service, Department of Veterans Affairs Medical Center, Tennessee Valley Healthcare System, Nashville, TN.
authors: Pratik P
authors: PP
authors: Pandharipande
mesh_terms: D003072:Cognition Disorders / Q000188:drug therapy*; D016638:Critical Illness; D003693:Delirium / Q000188:drug therapy* / Q000517:prevention & control; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology; D017628:Microglia / Q000502:physiology
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors