Objective: We evaluated feasibility, safety, and preliminary efficacy of taVNS for motor and non-motor symptoms in mild to moderate PD.

Background: Neuronal loss in the locus coeruleus (LC) occurs early in PD, attenuating signaling from the substantia nigra (SN), accelerating SN degeneration, and ultimately producing cognitive and motor decline. In animal models, VNS has been shown to ameliorate motor deficits, reduce neuroinflammation, increase BDNF, and to protect LC and SN neurons. Furthermore, taVNS has emerged as a promising non-surgical method to stimulate the vagus nerve.

Method: We conducted a double-blind, sham controlled RCT of taVNS in 30 subjects with mild to moderate non-demented PD. Subjects received 10, 1-hour taVNS sessions (25Hz, suprathreshold) over a two-week period. The primary outcome was change in off-medication MDS-UPDRS III.

Results: Baseline characteristics of active and sham groups were similar for demographic and baseline measures (Table 1). All subjects tolerated the treatment well. Group differences on MDS-UPDRS III were not significantly different; however, clinically meaningful improvement of ³3 points in MDS-UPDRS III was observed in 8 in the active group [3-12] (53%) compared to 4 [3-11] in the sham group (26%). Most improved symptom in responders was bradykinesia, followed by tremor. Analysis of secondary outcomes revealed statistically significant group differences in semantic and phonemic fluency, with decline in active and improvement in sham. Notably, 4 of 8 motor responders manifested a clinically significant decline in fluency. No group differences were observed on other cognitive tests or subjective measures of cognitive functioning (Table 2).

Conclusion: taVNS was feasible and well-tolerated in PD subjects. Although efficacy was not demonstrated statistically on MDS-UPDRS III, clinically significant improvement was seen in a subset of treatment subjects. Interestingly, active taVNS was also associated with decline in verbal fluency compared to sham. Enhanced dopaminergic and noradrenergic functioning associated with taVNS may have led to motor improvements, while also causing prefrontal hyperactivity and diminished cognitive performance. Future studies increasing the number of daily taVNS sessions and overall treatment length, along with target engagement indicators and larger sample size, are planned to further assess the merit of taVNS for treatment of PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/transauricular-vagus-nerve-stimulation-tavns-for-mild-to-moderate-parkinsons-disease-pd/