Association Between Plasma Amyloid-Beta 42 Ratio and Postoperative Delirium in Elderly Patients Undergoing Major Abdominal Surgery: Secondary Analysis of a Randomized Controlled Trial

Introduction

Cerebrospinal fluid Aβ42 has been proposed as a potential indicator for cerebral β-amyloidosis and may be involved in the pathophysiology of delirium. Whether perioperative plasma Aβ42 alternation is associated with postoperative delirium risk among elderly patients remains unknown.

Methods

This was a secondary analysis of a randomized controlled trial evaluating the effects of acupuncture (intervention) compared to standard care (control) on the incidence of delirium in patients undergoing major abdominal surgery. Participants with blood samples collected were included in this cohort study. The exposure variable was the Aβ42 ratio, calculated with the plasma Aβ42 level immediately after surgery divided by the preoperative plasma Aβ42 level. The primary endpoint was the occurrence of delirium within the first 7 days following surgery or until hospital discharge, whichever happened first, evaluated using either the Confusion Assessment Method or the Confusion Assessment Method-intensive care unit for intubated patients. Delirium severity was a secondary outcome assessed by the Memorial Delirium Assessment Scale. The logistic regression models and a restricted cubic spline were performed to examine the association between the Aβ42 ratio and delirium incidence, with receiver operating characteristic curve (ROC) analysis for diagnostic power. The mediation effects of the matrix metalloproteinase-9 ratio were further explored by causal mediation analysis. The linear regression and generalized linear mixed models assessed the association between the Aβ42 ratio and delirium severity.

Results

A total of 195 patients with blood samples collected were included in the final analysis. Among them, the mean age was 70.2 ± 4.2 years; 134 were female (68.7%), and 26 (13.3%) patients experienced postoperative delirium. The plasma Aβ42 ratio was positively correlated with an increased delirium risk (adjusted odds ratio 3.21, 95% confidence interval 1.71–6.05, p < 0.001) and delirium severity, as measured by the highest postoperative Memorial Delirium Assessment Scale score (adjusted β coefficient 3.04, 95% confidence interval 0.9–5.18, p = 0.006) in the fully adjusted multivariable analysis models. The restricted cubic spline indicated a linear relationship between the plasma Aβ42 ratio and delirium incidence (p = 0.202). The ROC showed that the area under the curve for the Aβ42 ratio to predict delirium risk was 0.698 (95% CI, 0.582–0.814), with the optimal cut-off point of 0.137. Mediation analyses showed that the Aβ42 ratio does not mediate postoperative delirium through the matrix metalloproteinase-9 ratio (proportion: 1.3%).

Conclusions

This cohort study showed that a higher Aβ42 ratio was associated with an increased delirium risk and severity, and the association was linear. The plasma Aβ42 ratio might be a mini-invasive biomarker to identify postoperative delirium.