The association between delirium and the apolipoprotein E ε4 allele in the elderly

Objective As not all patients with similar risk factors and eliciting conditions develop delirium; it may be hypothesized that genetic variation may play a role in the risk of delirium. On the basis of the relationship between dementia, respectively reduced cholinergic activity, and the APOE epsilon 4-aliele, and the similarities between dementia and delirium in reduced cholinergic activity, the APOE epsilon A-allele is a rational candidate-gene for delirium. This study examined the association between APOE epsilon 4-allele and delirium in elderly patients. Methods Acutely admitted patients to the Department of Medicine of 65 years and over were included during a 27-month time period. Delirium was scored by the confusion assessment method. Cognitive impairment was diagnosed by Mini Mental State Examination and informant questionnaire on cognitive decline. Genotyping was done with matrix-assisted laser-desorption/ionization time-of flight mass spectrometry. Results Of 415 included patients, a random sample of 264 patients was genotyped for APOE. The patients who met the criteria for delirium (35%) were significantly older and more frequently had preexisting functional and cognitive impairment. APOE genotype was borderline significantly associated with cognitive impairment in patients below 75 years (P= 0.057). The odds ratio for carriers of an APOE epsilon 4-allele compared with patients without an APOE epsilon 4-allele for developing delirium was 1.17 (95% confidence interval (Cl): 0.49-2.78) in the cognitively intact patients and 0.42 (95% Cl: 0.14-1.30) in the cognitively impaired patients. No relation existed between the total number of APOE epsilon 4-alleles and the different delirium subtypes (P= 0.12). Conclusions We found no convincing evidence that carriers of the APOE epsilon A-allele have a higher risk of delirium.