Cognition after Sepsis

Abstract & Commentary

By Joseph Safdieh, MD, Assistant Professor of Neurology, Weill Medical College, Cornell University. Dr. Safdieh reports no financial relationships relevant to the field of study.This article originally appeared in the December 2010 issue of Neurology Alert. It was edited by Matthew E. Fink, MD, and peer reviewed by Alan Z. Segal, MD. Dr. Fink is Interim Chair and Neurologist in Chief, Department of Neurology and Neuroscience, Weill Cornell Medical College, New York Presbyterian Hospital, and Dr. Segal is Associate Professor of Clinical Neurology, Specialty Area. Drs. Fink and Beal report no financial relationships relevant to this field of study.

Synopsis: Episodes of severe sepsis in older adults is associated with worsening cognition and functional status.Source: Iwashyna TJ, et al. Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA 2010;304:1787-94.

It has been suspected, based on observations and small case series, that after surviving an episode of severe sepsis, some patients develop a new, but not previously well defined, decline in their levels of cognitive and physical functions. In this large study, the investigators set out to answer whether there indeed is a worsening of cognitive function and functional ability after an episode of severe sepsis. The study data were derived from a large, prospectively collected database of U.S. residents from 1998-2006 called the Health and Retirement study; 9,223 subjects had baseline cognitive and functional assessment. Based on review of Medicare claims, 516 survived a hospitalization for severe sepsis and 4,517 survived hospitalization for another reason. All of the subjects had follow-up cognitive and functional assessments.

The investigators demonstrated that the prevalence of moderate to severe cognitive impairment increased by an absolute risk of 10.6% (OR, 3.34) in patients who survived hospitalization for sepsis. Without an episode of sepsis, hospital survivors had a 6.1% rate of moderate to severe cognitive impairment after discharge, which increased to 16.7% if there was an episode of severe sepsis. Non-sepsis-related hospitalizations were not associated with cognitive decline. Sepsis-related hospitalizations also significantly worsened functional ability, causing an average of 1.57 new functional limitations in activities of daily living in subjects who were previously at a normal functional baseline.


Neurologists and other physicians often notice that when older patients are discharged from the hospital after a critical illness, they are "not the same as before." This study rigorously confirms this observation. Not only do patients hospitalized for severe sepsis develop cognitive deterioration, but they also decline in multiple functional abilities. This study demonstrates these clinical observations by using a reliable, prospective database.

What is the actual impact of sepsis on patients and their families? The study demonstrates that severe sepsis causes a functional loss of an average of 1.57 components of activities of daily living, post-hospitalization. Lost functions include walking, dressing, bathing, eating, getting into and out of bed, toileting, preparing a hot meal, grocery shopping, making phone calls, taking medications, and managing money. Each of these 11 items is critically important for independent function, and the loss of 1-2 of them after hospitalization can be devastating for a patient and increases the cost of care and the burden on caregivers. A significant question raised, but not answered in this study is "What is the mechanism of the development of cognitive impairment and functional disability in severe sepsis?" Many factors may play a role, including generalized inflammation and injury from cytokines, metabolic dysfunction, hypotension, cerebral hypoperfusion, coagulation disorders and cerebral infarction, among others. Clearly, this study has identified a common and serious problem. The next step is to develop better therapies for patients with sepsis and to evaluate cognitive and functional outcomes, not just survival.