Association of intraoperative changes in brain-derived neurotrophic factor and postoperative delirium in older adults.

BACKGROUND: Delirium is common after surgery, although the aetiology is poorly defined. Brain-derived neurotrophic factor (BDNF) is a neurotrophin important in neurotransmission and neuroplasticity. Decreased levels of BDNF have been associated with poor cognitive outcomes, but few studies have characterized the role of BDNF perioperatively. We hypothesized that intraoperative decreases in BDNF levels are associated with postoperative delirium. METHODS: Patients undergoing spine surgery were enrolled in a prospective cohort study. Plasma BDNF was collected at baseline and at least hourly intraoperatively. Delirium was assessed using rigorous methods, including the Confusion Assessment Method (CAM) and CAM for the intensive care unit. Associations of changes in BDNF and delirium were examined using regression models. RESULTS: Postoperative delirium developed in 32 of 77 (42%) patients. The median baseline BDNF level was 7.6 ng ml -1 [interquartile range (IQR) 3.0-11.2] and generally declined intraoperatively [median decline 61% (IQR 31-80)]. There was no difference in baseline BDNF levels by delirium status. However, the percent decline in BDNF was greater in patients who developed delirium [median 74% (IQR 51-82)] vs in those who did not develop delirium [median 50% (IQR 14-79); P =0.03]. Each 1% decline in BDNF was associated with increased odds of delirium in unadjusted {odds ratio [OR] 1.02 [95% confidence interval (CI) 1.00-1.04]; P =0.01}, multivariable-adjusted [OR 1.02 (95% CI 1.00-1.03); P =0.03], and propensity score-adjusted models [OR 1.02 (95% CI 1.00-1.04); P =0.03]. CONCLUSIONS: We observed an association between intraoperative decline in plasma BDNF and delirium. These preliminary results need to be confirmed but suggest that plasma BDNF levels may be a biomarker for postoperative delirium.

Evidence of an association between brain cellular injury and cognitive decline after non-cardiac surgery.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is common after non-cardiac surgery, but the mechanism is unclear. We hypothesized that decrements in cognition 1 month after non-cardiac surgery would be associated with evidence of brain injury detected by elevation of plasma concentrations of S100ß, neuron-specific enolase (NSE), and/or the brain-specific protein glial fibrillary acid protein (GFAP). METHODS: One hundred and forty-nine patients undergoing shoulder surgery underwent neuropsychological testing before and then 1 month after surgery. Plasma was collected before and after anaesthesia. We determined the relationship between plasma biomarker concentrations and individual neuropsychological test results and a composite cognitive functioning score (mean Z-score). RESULTS: POCD (≥-1.5 sd decrement in Z-score from baseline) was present in 10.1% of patients 1 month after surgery. There was a negative relationship between higher plasma GFAP concentrations and lower postoperative composite Z-scores {estimated slope=-0.14 [95% confidence interval (CI) -0.24 to -0.04], P=0.005} and change from baseline in postoperative scores on the Rey Complex Figure Test copy trial (P=0.021), delayed recall trial (P=0.010), and the Symbol Digit Modalities Test (P=0.004) after adjustment for age, sex, history of hypertension and diabetes. A similar relationship was not observed with S100ß or NSE concentrations. CONCLUSIONS: Decline in cognition 1 month after shoulder surgery is associated with brain cellular injury as demonstrated by elevated plasma GFAP concentrations.