APOE and cytokines as biological markers for recovery of prevalent delirium in elderly medical inpatients

Int J Geriatr Psychiatry. 2007 Jul;22(7):688-94. doi: 10.1002/gps.1732.


Background: Delirium frequently occurs in the context of infection and other inflammatory conditions associated with elevated levels of cytokines. Cytokines used therapeutically can induce symptoms of delirium as an adverse effect. We hypothesized that a causal relationship might exist between delirium and cytokine production during illness. Further, we speculated that the APOE genotype of patients might influence their rate of recovery from delirium given that APOE is associated with amyloid deposition, increased susceptibility to exogenous neurotoxins, and can affect the immune response.

Methods: A cohort of 164 acutely ill patients, 70 years or older, admitted to an elderly medical unit were studied within 3 days of hospital admission and re-assessed twice weekly until their discharge, to identify and follow the clinical course of delirium. The APOE genotype and the level of circulating cytokines were determined for 116 and 60 patients respectively.

Results: Prevalent delirium was significantly (p < 0.05) associated with a previous history of dementia, age, illness severity, disability and low levels of circulating IGF-I. Recovery was significantly associated (p < 0.05) with lack of APOE 4 allele and higher initial IFN-gamma. A model incorporating gender, APOE epsilon 4 status and IGF-I levels predicted recovery or not from delirium in 76.5% of cases, with a sensitivity 0.77 and specificity 0.75.

Conclusions: A relationship between delirium with APOE genotype, IFN-gamma, and IGF-I, but not with IL-6, IL-1, TNF-alpha, and LIF was found. A predictive model of recovery was derived from gender, APOE status, and IGF-I levels. This model needs replication with further studies.

MeSH terms

  • Acute Disease
  • Aged
  • Aged, 80 and over
  • Alleles
  • Alzheimer Disease / blood
  • Alzheimer Disease / epidemiology
  • Alzheimer Disease / genetics
  • Apolipoprotein E4 / blood
  • Apolipoprotein E4 / genetics
  • Apolipoproteins E / blood
  • Apolipoproteins E / genetics*
  • Cross-Sectional Studies
  • Cytokines / blood
  • Cytokines / genetics*
  • Delirium / blood
  • Delirium / epidemiology
  • Delirium / genetics*
  • Disability Evaluation
  • Female
  • Genetic Markers / genetics
  • Genotype
  • Hospitalization*
  • Humans
  • Insulin-Like Growth Factor I / genetics
  • Interferon-gamma / blood
  • Interferon-gamma / genetics
  • Male
  • Mental Status Schedule
  • Prognosis
  • Recurrence
  • Risk Factors


  • Apolipoprotein E4
  • Apolipoproteins E
  • Cytokines
  • Genetic Markers
  • Insulin-Like Growth Factor I
  • Interferon-gamma