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.