Postop Delirium More Frequent If Alzheimer's-Linked Allele Present

SAN FRANCISCO, Aug. 24 -- Older surgical patients who carry the (ApoE4) allele, a risk factor for early-onset Alzheimer's disease, are an at increased risk for postoperative delirium, according to researchers here.

Among patients over 65 who had major surgery other than cardiac procedures, a quarter of all those who had delirium on the first two postop days had at least one copy of the apolipoprotein (E4 ApoE4) allele, found Jacqueline M. Leung, M.D., M.P.H., of the University of California San Francisco, and colleagues.

The rate of postop delirium was nearly four-fold higher among the carriers of the risk allele compared with patients who had other versions of the gene, the investigators reported in the September issue of Anesthesiology.

"Postoperative delirium is common in older patients after noncardiac surgery, and is associated with increased rates of nursing home placement and hospital mortality," they wrote. "Despite this prevalence and clinical importance, no specific etiologic factor has been identified."

The authors conducted a nested-cohort study of 190 patients, mean age 72.5, who underwent major non-cardiac procedures requiring anesthesia to see whether there is a genetic predisposition to the postop delirium.

To determine the presence of delirium, the investigators interviewed patients by telephone before surgery using the Telephone Interview of Cognitive Status, a validated instrument adapted from the Mini Mental Status Examination. Prior to surgery and on each of the first two postop days, patients were interviewed and their level of delirium (or its lack) was assessed with the Confusion Assessment Method.

Apolipoprotein genotypes were determined from genomic DNA obtained from blood samples. The authors conducted bivariate tests of association between delirium and apolipoprotein genotypes and other potentially important risk factors, and created multivariate logistic regression models to further explore possible associations.

They found that 15.3% of patients had symptoms of delirium on both the first and second postop days, and of this group, 24.2% were found to have at least one copy of the E4 allele.

When they compared delirium rates in relation to genotype, they found that 28.3% of the ApoE4 carriers with at least one allele experienced delirium, compared with 11.1% of patients who carried other ApoE alleles.

A multivariate analysis adjusted for other delirium risk factors -- including older age, change in postoperative pain levels, and a history of central nervous system disorders -- showed that patients with at least one copy of ApoE4 still had a significantly increased risk for early postoperative delirium (odds ratio 3.64, 95% confidence interval 1.51 to 8.77).

The authors recommended that further studies examine possible mechanisms whereby ApoE4 can lead to postoperative delirium, including how the allele may interact with other possible risk factors.

The authors noted that they could not determine the mechanism linking apolipoprotein genotype with delirium, and that by focusing on early-onset delirium they may have missed late-onset cases. Also, the sample size was not large enough to examine other allelic combinations, they noted, and they pointed out that it is still not known whether postoperative delirium in ApoE4 carriers is predictive of cognitive impairment.