title: Proinflammatory cytokines, sickness behavior, and Alzheimer disease.
abstract: BACKGROUND
  In Alzheimer disease (AD), systemic inflammation is known to give rise to a delirium. However, systemic inflammation also gives rise to other centrally mediated symptoms in the absence of a delirium, a concept known as sickness behavior. Systemic inflammation is characterized by the systemic production of the proinflammatory cytokines tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6) that mediate immune to brain communication and the development of sickness behavior.
  
  
  OBJECTIVE
  To determine if raised serum TNFα or IL-6 are associated with the presence of sickness behavior symptoms, independent of the development of delirium, in a prospective cohort study of subjects with AD.
  
  
  METHODS
  A total of 300 subjects with mild to severe AD were cognitively assessed at baseline and a blood sample taken for inflammatory markers. Cognitive assessments, including assessments to detect the development of a delirium, and blood samples were repeated at 2, 4, and 6 months. The development of neuropsychiatric symptoms in the subject with AD over the 6-month follow-up period was assessed independently by carer interview at 2, 4, and 6 months.
  
  
  RESULTS
  Raised serum TNFα and IL-6, but not CRP, were associated with an approximately 2-fold increased frequency of neuropsychiatric symptoms characteristic of sickness behavior. These relationships are independent of the development of delirium.
  
  
  CONCLUSIONS
  Increased serum proinflammatory cytokines are associated with the presence of symptoms characteristic of sickness behavior, which are common neuropsychiatric features found in AD. This association was independent of the presence of delirium.
authors.affiliation: University of Southampton, Memory Assessment and Research Centre, Botley Rd, Southampton, UK, SO30 3JB. ch4@soton.ac.uk
authors.forename: C
authors.initials: C
authors.lastname: Holmes
authors.forename: C
authors.initials: C
authors.lastname: Cunningham
authors.forename: E
authors.initials: E
authors.lastname: Zotova
authors.forename: D
authors.initials: D
authors.lastname: Culliford
authors.forename: V H
authors.initials: VH
authors.lastname: Perry
mesh_terms: D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000503:physiopathology*; D002097:C-Reactive Protein / Q000378:metabolism; D016009:Chi-Square Distribution; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood*; D003693:Delirium / Q000209:etiology; D005260:Female; D006801:Humans; D055809:Illness Behavior / Q000502:physiology*; D008297:Male; D009483:Neuropsychological Tests; D011569:Psychiatric Status Rating Scales; D012111:Residence Characteristics; D012189:Retrospective Studies
chemical_list: D016207:Cytokines; D002097:C-Reactive Protein