title: Neuroinflammation in delirium: a postmortem case-control study.
abstract: 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-1β (IL-1β), IL-6,β-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-1β 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.
authors: Department of Internal Medicine, Academic Medical Center, University of Amsterdam, P.O. Box 22660, 1100 DD Amsterdam, The Netherlands. b.c.vanmunster@amc.uva.nl
authors: Barbara C van
authors: BC
authors: Munster
authors: Eleonora
authors: E
authors: Aronica
authors: Aeilko H
authors: AH
authors: Zwinderman
authors: Piet
authors: P
authors: Eikelenboom
authors: Colm
authors: C
authors: Cunningham
authors: Sophia E J A de
authors: SE
authors: Rooij
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000096:biosynthesis; D015703:Antigens, CD / Q000096:biosynthesis; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis; D001344:Autopsy; D001921:Brain / Q000473:pathology; D016022:Case-Control Studies; D003693:Delirium / Q000473:pathology*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology*; D053583:Interleukin-1beta / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000473:pathology; D016875:tau Proteins / Q000096:biosynthesis; D000097382:CD68 Molecule
chemical_list: D016229:Amyloid beta-Peptides; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D005904:Glial Fibrillary Acidic Protein; D006684:HLA-DR Antigens; D053583:Interleukin-1beta; D015850:Interleukin-6; D016875:tau Proteins; C067980:CD68 antigen, human; D000097382:CD68 Molecule