Transcutaneous auricular vagus nerve stimulation for prevention of postoperative cognitive dysfunction in older adults with gastrointestinal tumors: A randomized controlled trial.

INTRODUCTION

Postoperative cognitive dysfunction (POCD) is common in the perioperative period among older adults and has been linked to inflammatory responses, neural injury-related biomarkers, and mood changes. Evidence for safe, feasible, and effective non-pharmacological interventions remains limited. This prospective, double-blind, randomized controlled trial evaluated the association between transcutaneous auricular vagus nerve stimulation (taVNS) and postoperative cognitive test performance, and examined concomitant changes in inflammatory and neural injury-related biomarkers and mood.

MATERIALS AND

METHODS

A total of 103 older adults scheduled for elective laparoscopic gastrointestinal tumor resection were consecutively enrolled and randomly assigned to taVNS or sham stimulation; 99 participants completed follow-up and were included in the primary analysis. Cognitive function was assessed preoperatively and at postoperative day 1, day 7, month 1, and month 3 using the Montreal Cognitive Assessment (MoCA). Serum interleukin-1β (IL-1β) and S100β were measured preoperatively and on postoperative day 7. Mood was assessed preoperatively and on postoperative day 7 using the 24-item Hamilton Depression Scale (HAMD-24).

RESULTS

From postoperative day 7 onward, MoCA scores were higher in the taVNS group than in the sham group (p = 0.01), with differences maintained at postoperative months 1 and 3 (absolute between-group differences of 2.06 and 2.97 points, respectively; both p < 0.01). RM ANOVA and ANCOVA indicated significant main effects of time and a significant group × time interaction. On postoperative day 7, the taVNS group showed lower postoperative IL-1β and S100β levels than the control group (both p < 0.001) and a smaller worsening in HAMD-24 scores. ΔMoCA was negatively correlated with ΔIL-1β (r = -0.425), ΔS100β (r = -0.248), and ΔHAMD-24 (r = -0.234). Exploratory stratified analyses showed broadly consistent effect directions across subgroups. Adverse event rates were similar between groups (approximately 4.1% in each), and events were mild local reactions.

DISCUSSION: In this exploratory randomized controlled trial, perioperative taVNS was associated with a more favorable MoCA trajectory after laparoscopic gastrointestinal tumor surgery in older adults, with between-group differences in IL-1β, S100β, and HAMD-24 on postoperative day 7. Clinical significance and generalizability require confirmation in larger studies.