Neuroinflammation in Delirium: A Postmortem Case-Control Study

Background: Delirium can be hypothesized to be an extreme manifestation of sickness behavior in elderly persons with neurodegenerative disease. The purpose of this study was to investigate whether increased cerebral inflammation with microglial, astrocyte, and cytokine activation exists in patients with delirium compared to nondelirious patients. Methods: Postmortem brain tissue from 9 cases with delirium was compared to 6 age-matched controls without delirium. Human leukocyte antigen-DR (HLA-DR) and CD68 cell count and glial fibrillary acidic protein (GFAP), interleukin-1 beta (IL-1 beta), IL-6,beta-amyloid, and tau protein immunoreactivity were determined in hippocampus, frontal cortex, and white matter. Results: There were no significant differences in the patients with delirium compared to the controls with respect to age 73 versus 70.5 years (p = 0.72) or dementia (22% versus 0%, p = 0.22). Both markers for microglial activity showed significantly higher scores in delirium brain specimens than controls in the total brain score (HLA-DR 129 vs. 20 and CD68 30 vs. 8.5) as well as in the various brain areas separately. The immunoreactivity of astrocyte activity (GFAP) was higher in the total brain score in patients with delirium (5.2 vs. 4.0, p = 0.05), but in the various brain areas this was only significant in the dentate gyrus. IL-6 immunoreactivity was higher in patients with delirium in all brain areas and IL-1 beta was not detectable. Coexisting infectious disease or dementia did not influence the overall results. Conclusions: These preliminary study results show an association between human brain activity of microglia, astrocytes, and IL-6 and delirium in elderly patients and add to the accumulating evidence that inflammatory mechanisms are involved in delirium.