Apolipoprotein E genotype and the association between C-reactive protein and postoperative delirium: Importance of gene-protein interactions

Alzheimers Dement. 2020 Mar;16(3):572-580. doi: 10.1016/j.jalz.2019.09.080. Epub 2020 Jan 4.


Introduction: Apolipoprotein E (APOE) status may modify the risk of postoperative delirium conferred by inflammation.

Methods: We tested whether APOE modifies the established association between C-reactive protein (CRP) and delirium incidence, severity, and duration in 553 noncardiac surgical patients aged 70 and older. High postoperative plasma CRP (≥234.12 mg/L) was defined by the highest sample-based quartile. Delirium was determined using the Confusion Assessment Method and chart review, and severity was determined by the Confusion Assessment Method-Severity score.

Results: APOE ε4 carrier prevalence was 19%, and postoperative delirium occurred in 24%. The relationship between CRP and delirium incidence, severity, and duration differed by ε4 status. Among ε4 carriers, there was a strong relationship between high CRP (vs. low CRP) and delirium incidence (relative risk [95% confidence interval], 3.0 [1.4-6.7]); however, no significant association was observed among non-ε4 carriers (relative risk [95% CI], 1.2 [0.8-1.7]).

Discussion: Our findings raise the possibility that APOE ε4 carrier status may modify the relationship between postoperative day 2 CRP levels and postoperative delirium.

Keywords: Apolipoprotein E; C-reactive protein; Delirium; Gene-protein interaction; Inflammation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alleles
  • Apolipoprotein E4
  • Apolipoproteins E / genetics*
  • C-Reactive Protein / analysis*
  • Delirium* / epidemiology
  • Delirium* / etiology
  • Epistasis, Genetic*
  • Female
  • Genotype
  • Humans
  • Postoperative Complications*


  • Apolipoprotein E4
  • Apolipoproteins E
  • C-Reactive Protein