A pilot study of invasive vagus nerve stimulation in Chinese patients with Alzheimer’s disease: preliminary results on safety, cognition, and biomarkers

Introduction Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with no curative therapies, and vagus nerve stimulation (VNS) has emerged as a promising neuromodulatory approach. This prospective, open-label pilot study aimed to evaluate the feasibility, safety, and preliminary cognitive, psychological, inflammatory, and AD biomarker effects of invasive VNS (iVNS) in Chinese AD patients. Methods Five AD patients (mean age: 62.4 ± 4.0 years) underwent iVNS implantation, with assessments at baseline, 3, and 6 months postoperatively (one patient did not complete the 6-month follow-up). Cognitive function (MMSE, CDR, VFT, BNT), psychological/behavioral symptoms (CMAI, HAMA, HAMD), sleep/daily-living status (ESS, ADL), serum inflammatory factors, and AD biomarkers were measured. Results Among cognitive outcomes, MMSE increased by 1 point at both follow-ups and VFT rose by 5.2 and 4.25 points at 3 and 6 months, respectively, although none of these changes reached statistical significance; global CDR remained unchanged. HAMA and HAMD scores decreased, and ESS scores declined by 25–27%, without reaching significance. Serum pro-inflammatory Eotaxin and CCL5 were significantly reduced ( p = 0.026 and p = 0.045, respectively), whereas CXCL10 levels showed a non-significant numerical increase. Although the Aβ42 and Aβ42/Aβ40 ratio showed numerical increases (by 126.4% and 75.3%) and pTau181, pTau217, and NfL showed numerical decreases, these changes were not statistically significant. Only transient hoarseness was reported. Discussion These preliminary findings suggest that iVNS is feasible and associated with early signals of cognitive, psychological, inflammatory, and biomarker changes in AD patients, which warrant confirmation in larger, randomized, sham-controlled trials.