Research finds increased risk of dementia in patients who experience delirium after surgery

Delirium is common in elderly hospitalized patients, affecting an estimated 14 - 56% of patients. It frequently manifests as a sudden change in behavior, with patients suffering acute confusion, inattention, disorganized thinking and fluctuating mental status.

01 aug 2017--Pre-existing cognitive impairment or dementia in patients undergoing surgery are widely recognized as risk factors for postoperative delirium, increasing its likelihood and severity.
However, little previous research has focused on whether delirium itself portends or even accelerates a decline into dementia in patients who showed no previous signs of cognitive impairment.
Research published today in the British Journal of Anaesthesia focuses on patients over the age of 65 who were assessed as cognitively normal prior to surgery. This study, led by Professor Juraj Sprung of the Mayo Clinic in Minnesota, finds those who developed postoperative delirium were three times more likely to suffer permanent cognitive impairment or dementia.
Over a ten year period, patients over the age of 65 enrolled at the Mayo Clinic Study of Ageing in Olmsted County Minnesota who were exposed to general anesthesia were included in an investigation involving over two 2000 patients. Their cognitive status was evaluated in regular 15 month periods before and after surgery by neuropsychologic testing and clinical assessment. Out of 2014 patients, 1667 were deemed to be cognitively normal before surgery. Of the 1152 patients who returned for follow-up cognitive evaluation, 109 (9.5%) had developed mild cognitive impairment (pre-dementia) or dementia, and those who had suffered postoperative delirium were three times more likely to be subsequently diagnosed with permanent cognitive decline or dementia. This research is the first to focus on the association between delirium and long-term cognitive decline in patients with normal mental capacity before surgery.
While previous studies have highlighted cognitive decline in the elderly following postoperative delirium, no others have involved such a detailed neuro-cognitive assessment identifying those with normal pre-operative cognitive abilities who go on to develop dementia. In conclusion, researchers believe that postoperative delirium could be a warning sign of future permanent cognitive impairment (dementia) in patients who at the time of surgery were still just above the threshold for registering cognitive decline. Alternatively, postoperative delirium could itself produce injury, which per se accelerates the trajectory of decline into dementia.
"Our research shows that delirium after surgery is not only distressing for patients and their families, but also may be a warning that patients could later develop dementia, said Sprung. "We don't yet know whether taking steps to prevent postoperative delirium could also help prevent dementia - but we need to find out."
British Journal of Anaesthesia Editor-in-Chief Professor Hugh Hemmings said: "This important research identifies a significant risk factor for developing dementia postoperatively, and highlights the need for more research in preventing, identifying and treating postoperative delirium."

More information: J. Sprung et al, Postoperative delirium in elderly patients is associated with subsequent cognitive impairment, BJA: British Journal of Anaesthesia (2017). DOI: 10.1093/bja/aex130


Provided by Oxford University Press

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 at an 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.
The study was supported in part by the National Institute of Aging, Mildred V. Strouss Charitable Trust, and a grant from the Fondation Leducq. Authors' conflicts of interest were not listed.Primary source: AnesthesiologySource reference: Leung JM et al. "Apolipoprotein E e4 allele increases the risk of early postoperative delirium in older patients undergoing noncardiac surgery." Anesthesiology 2007. 107;3.