title: Cytokines and Postoperative Delirium in Older Patients Undergoing Major Elective Surgery.
abstract: BACKGROUND
  A proinflammatory state has been associated with several age-associated conditions; however, the inflammatory mechanisms of delirium remain poorly characterized.
  
  
  METHODS
  Using the Successful Aging after Elective Surgery Study of adults age ≥70 undergoing major noncardiac surgery, 12 cytokines were measured at four timepoints: preoperative, postanesthesia care unit, postoperative day 2 (POD2) and 30 days later (POD1M). We conducted a nested, longitudinal matched (on age, sex, surgery type, baseline cognition, vascular comorbidity, and Apolipoprotein E genotype) case-control study: delirium cases and no-delirium controls were selected from the overall cohort (N = 566; 24% delirium). Analyses were independently conducted in discovery, replication, and pooled cohorts (39, 36, 75 matched pairs, respectively). Nonparametric signed-rank tests evaluating differences in cytokine levels between matched pairs were used to identify delirium-associated cytokines.
  
  
  RESULTS
  In the discovery and replication cohorts, matching variables were similar in cases and controls. Compared to controls, cases had (*p < .05, **p < .01) significantly higher interleukin-6 on POD2 in the discovery, replication, and pooled cohorts (median difference [pg/mL] 50.44**, 20.17*, 39.35**, respectively). In the pooled cohort, cases were higher than controls for interleukin-2 (0.99*, 0.77*, 1.07**, 0.73* at preoperative, postanesthesia care unit, POD2, POD1M, respectively), vascular endothelial growth factor (4.10* at POD2), and tumor necrosis factor-alpha (3.10* at POD1M), while cases had lower interleukin-12 at POD1M (-4.24*).
  
  
  CONCLUSIONS
  In this large, well-characterized cohort assessed at multiple timepoints, we observed an inflammatory signature of delirium involving elevated interleukin-6 at POD2, which may be an important disease marker for delirium. We also observed preliminary evidence for involvement of other cytokines.
authors.affiliation: Harvard Medical School, Boston, Massachusetts. Aging Brain Center, Institute for Aging Research, Hebrew SeniorLife, Boston, Massachusetts. Department of Medicine, and.
authors.forename: Sarinnapha M
authors.initials: SM
authors.lastname: Vasunilashorn
authors.affiliation: Harvard Medical School, Boston, Massachusetts. Department of Medicine, and.
authors.forename: Long
authors.initials: L
authors.lastname: Ngo
authors.affiliation: Harvard Medical School, Boston, Massachusetts. Aging Brain Center, Institute for Aging Research, Hebrew SeniorLife, Boston, Massachusetts. Department of Medicine, and.
authors.forename: Sharon K
authors.initials: SK
authors.lastname: Inouye
authors.affiliation: Harvard Medical School, Boston, Massachusetts. Department of Medicine, and.
authors.forename: Towia A
authors.initials: TA
authors.lastname: Libermann
authors.affiliation: Aging Brain Center, Institute for Aging Research, Hebrew SeniorLife, Boston, Massachusetts. Department of Psychiatry and Human Behavior, Warren Alpert Medical School, Brown University, Providence, Rhode Island.
authors.forename: Richard N
authors.initials: RN
authors.lastname: Jones
authors.affiliation: Aging Brain Center, Institute for Aging Research, Hebrew SeniorLife, Boston, Massachusetts. Department of Radiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: David C
authors.initials: DC
authors.lastname: Alsop
authors.affiliation: Department of Medicine, and.
authors.forename: Jamey
authors.initials: J
authors.lastname: Guess
authors.affiliation: UConn Center on Aging, University of Connecticut Health Center, Farmington.
authors.forename: Sandra
authors.initials: S
authors.lastname: Jastrzebski
authors.affiliation: Advanced Medical Research Institute of Canada, Sudbury, Ontario, Canada.
authors.forename: Janet E
authors.initials: JE
authors.lastname: McElhaney
authors.affiliation: UConn Center on Aging, University of Connecticut Health Center, Farmington.
authors.forename: George A
authors.initials: GA
authors.lastname: Kuchel
authors.affiliation: Harvard Medical School, Boston, Massachusetts. Aging Brain Center, Institute for Aging Research, Hebrew SeniorLife, Boston, Massachusetts. Department of Medicine, and.
authors.forename: Edward R
authors.initials: ER
authors.lastname: Marcantonio
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood*; D003693:Delirium / Q000097:blood / Q000209:etiology*; D017558:Elective Surgical Procedures; D005260:Female; D006801:Humans; D008297:Male; D011183:Postoperative Complications / Q000097:blood / Q000209:etiology*; D011446:Prospective Studies; D012306:Risk
chemical_list: D016207:Cytokines
keywords: Delirium; Inflammation; Postoperative