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Association Between Sepsis and Microvascular Brain Injury

Ehlenbach, William J. MD, MSc1; Sonnen, Joshua A. MD2; Montine, Thomas J. MD, PhD3; Larson, Eric B. MD, MPH4

doi: 10.1097/CCM.0000000000003924
Clinical Investigation: PDF Only

Objectives: Many survivors of sepsis suffer long-term cognitive impairment, but the mechanisms of this association remain unknown. The objective of this study was to determine whether sepsis is associated with cerebral microinfarcts on brain autopsy.

Design: Retrospective cohort study.

Setting and Subjects: Five-hundred twenty-nine participants of the Adult Changes in Thought, a population-based prospective cohort study of older adults carried out in Kaiser Permanente Washington greater than or equal to 65 years old without dementia at study entry and who underwent brain autopsy.

Measurements and Main Results: Late-life sepsis hospitalization was identified using administrative data. We identified 89 individuals with greater than or equal to 1 sepsis hospitalization during study participation, 80 of whom survived hospitalization and died a median of 169 days after discharge. Thirty percent of participants with one or more sepsis hospitalization had greater than two microinfarcts, compared with 19% participants without (χ2p = 0.02); 20% of those with sepsis hospitalization had greater than two microinfarcts in the cerebral cortex, compared with 10% of those without (χ2p = 0.01). The adjusted relative risk of greater than two microinfarcts was 1.61 (95% CI, 1.01–2.57; p = 0.04); the relative risk for having greater than two microinfarcts in the cerebral cortex was 2.12 (95% CI, 1.12–4.02; p = 0.02). There was no difference in Braak stage for neurofibrillary tangles or consortium to establish a registry for Alzheimer’s disease score for neuritic plaques between, but Lewy bodies were less significantly common in those with sepsis.

Conclusions: Sepsis was specifically associated with moderate to severe vascular brain injury as assessed by microvascular infarcts. This association was stronger for microinfarcts within the cerebral cortex, with those who experienced severe sepsis hospitalization being more than twice as likely to have evidence of moderate to severe cerebral cortical injury in adjusted analyses. Further study to identify mechanisms for the association of sepsis and microinfarcts is needed.

1Department of Medicine, University of Wisconsin, Madison, WI.

2Department of Pathology, University of Utah, Salt Lake City, UT.

3Department of Pathology, Stanford University, Stanford, CA.

4Kaiser Permanente Washington Health Research Institute, Seattle, WA.

Dr. Ehlenbach had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Dr. Ehlenbach helped in study concept and design, statistical analysis, and drafting of the article. Drs. Ehlenbach and Larson helped in administrative, technical, or material support and study supervision of the article. Drs. Ehlenbach, Montine, and Larson helped in obtained funding. All authors helped in acquisition, analysis, or interpretation of data and critical revision of the article for important intellectual content.

Supported, in part, by the National Institutes of Health (NIH), National Institute of Aging, The Atlantic Philanthropies, The John A. Hartford Foundation, and the Starr Foundation (K23AG038352, principal investigator [PI] Dr. Ehlenbach). Additional support provided by P50AG005136 (PI Dr. Grabowski) and NIH U01AG006781 (PI Dr. Larson).

Dr. Ehlenbach’s institution received funding from the National Institutes of Health (NIH). Dr. Larson’s institution received funding from the National Institute on Aging, and he received funding from UptoDate (royalties). Drs. Ehlenbach, Sonnen, Montine, and Larson report grants from the NIH paid to their institutions.

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