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

Abstract

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.

Keywords: BDNF; biological; delirium of mixed origin; marker.

Fig 1

Spaghetti plot of intraoperative change in BDNF from baseline for each hour of surgery for (A) subjects with postoperative delirium and (B) subjects without postoperative delirium.

Fig 2

Lowess smoothed curve showing estimated probability of delirium by decline in BDNF levels from baseline. Dots on the top and bottom of the graph indicate actual values (1=delirious, 0=not delirious) in association with the change in BDNF level. Decline in BDNF levels is characterized in three ways: (A) percent change in BDNF from baseline, (B) maximum change in BDNF from baseline, and (C) average change in BDNF from baseline.