Background: Delirium, a clinical expression of acute encephalopathy, is associated with an increased risk of long-term cognitive impairment and dementia. Postoperative delirium is a frequent complication of elective surgery in elderly patients. Sedation, postoperative delirium and dementia are all associated with altered brain communication, specifically decreased functional connectivity strength and a disturbed network organization. We studied changes in the functional brain network over time after elective surgery and postoperative delirium, and analyzed if such changes are related to cognitive decline. Methods: Elderly patients (N=554) undergoing elective surgery underwent clinical assessments (including Trail Making Test B (TMT-B) and resting-state functional magnetic resonance imaging (rs-fMRI) before and three months after surgery. Delirium was assessed on the first seven postoperative days, using the Confusion Assessment Method for the Intensive Care Unit, the Nursing Delirium Screening Scale and chart review. After strict motion correction, rs-fMRI connectivity strength and network characteristics were calculated in 246 patients (35% female, age 65-87 years), of whom 38 (16%) developed postoperative delirium. Generalized linear mixed model analyses were performed to test for differences between baseline and follow-up, and between patients who developed postoperative delirium (POD+) and patients who did not (POD-). Results: Rs-fMRI functional connectivity strength increased after elective surgery in the total study population (beta=0.006, p=0.021), but decreased after postoperative delirium (beta=-0.014, p=0.026). No difference in TMT-B scores was found at follow-up between patients with and without postoperative delirium, but patients who decreased in functional connectivity strength (of whom 15.4% POD+) declined in TMT-B scores compared to the group that did not (of whom 10.3% POD+) (beta=11.04, p=0.034). Postoperative delirium was not associated with changes in functional network characteristics over time. Conclusions: Decreased functional connectivity strength may reflect longterm impact of delirium after the syndrome clinically resolves, and is associated with lasting cognitive deterioration.

The authors have declared no competing interest.

https://clinicaltrials.gov/ct2/results?cond=NCT02265263&term=&cntry=&state=&city=&dist=

This study was funded by the European Union Seventh Framework Program under Grant Agreement No. 602461 [FP7/2007 2013] and funding from the Dutch Organization for Health Research and Development (ZonMW) under Grant Agreement No. 606360098711.

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Ethics committee of University Medical Center (UMC) Utrecht and Charite Hospital at Berlin gave ethical approval for this work (ethical approval numbers 14-469 respectively EA2/092/14 )

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