Abstract
BACKGROUND: Postoperative delirium (POD) is a frequent and serious complication in older adults after cardiac surgery. Blood-brain barrier (BBB) dysfunction is implicated in cognitive decline, but its preoperative role in POD remains underexplored. This pilot study aimed to investigate the association between preoperative regional BBB permeability, assessed by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), and POD in older patients undergoing off-pump coronary artery bypass grafting (OPCABG). METHODS: This prospective observational pilot study, registered in the Chinese Clinical Trial Registry (ChiCTR2200063774), included patients aged ≥ 65 years scheduled for OPCABG. Preoperative BBB permeability (quantified as Ktrans) in the hippocampus, thalamus, frontal lobe, and temporal lobe, along with regional brain volumes and Montreal Cognitive Assessment-Basic (MoCA-B) scores, were assessed. POD was diagnosed using the 3-Minute Diagnostic Confusion Assessment Method (3D-CAM) or CAM-ICU for 5 postoperative days. Univariable and multivariable logistic regression analyses were performed to identify predictors of POD. Correlations between Ktrans, volume, and POD severity (CAM-S) were examined. RESULTS: Fifty patients (mean age 69.0 ± 3.3 years) were analyzed; 19 (38%) developed POD. In univariable analysis, higher preoperative Ktrans in the hippocampus (Odds Ratio [OR] 1.350, 95%CI 1.048-1.740, P = 0.020) and thalamus (OR 1.466, 95%CI 1.017-2.113, P = 0.040), lower MoCA-B scores (P = 0.020), and smaller hippocampal (OR 0.297, 95%CI 0.131-0.672, P = 0.004) and thalamic volumes (OR 0.304, 95%CI 0.121-0.766, P = 0.012) were associated with POD. However, in multivariable logistic regression including MoCA-B, Ktrans, and volumes, only lower MoCA-B scores (OR 0.697, 95%CI 0.513-0.947, P = 0.021) and smaller hippocampal volume (OR 0.322, 95%CI 0.105-0.992, P = 0.048) remained independent predictors of POD incidence. Preoperative hippocampal Ktrans correlated significantly with POD severity (CAM-S, r = 0.673, P = 0.002). CONCLUSION: In this pilot study, while increased preoperative BBB permeability in the hippocampus and thalamus was associated with POD univariably, baseline cognitive function and hippocampal volume were stronger independent preoperative predictors of POD incidence after OPCABG. Higher preoperative hippocampal BBB permeability was associated with greater POD severity, suggesting a role for pre-existing BBB vulnerability in exacerbating delirium. These preliminary and exploratory findings warrant validation in larger, adequately powered cohorts and highlight the complex interplay of pre-existing brain vulnerabilities in POD development. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2200063774; registered on 09/16/2022).