Neuromodulation for Mild Cognitive Impairment: Improvements in Spatial Navigation and Associative Memory with Acute Transcutaneous Vagus Nerve Stimulation: VINCI‐AD

Abstract

Background: New therapeutic strategies to treat Mild Cognitive Impairment (MCI) are urgently needed. Transcutaneous Vagus Nerve Stimulation (tVNS) is a neuromodulation technique which uses a handheld device to peripherally stimulate the afferent vagus nerve. tVNS has shown promise in augmenting memory in cognitively healthy populations but data in cognitively impaired populations is sparse. Method: VINCI‐ADis an investigator‐led, single‐blind, sham‐controlled crossover pilot study assessing the effects of tVNS in amnestic MCI. All participants have MCI (CDR global 0.5) with amnestic neuropsychological profile (RBANS delayed memory index >85). Participants are randomised over 3 study visits to baseline (no stimulation) active stimulation (at the CC of left ear) or sham stimulation (earlobe). Cognitive tests include Face‐Name Association Task (FNAT), Sustained Attention Response Test (SART) and Sea Hero Quest Navigation Test (SHQ) among others. Result: Interim data analysis of 28 participants is presented (mean age 71.5 (range 55‐85), 17 male, RBANS DMI 73.3 ±11.1). CSF AD biomarkers were positive for 75% (21/28) (AB‐42 460.4pg/ml (±83.3pg/ml) and p‐tau181 82.5pg/ml [±53.2pg/ml]) and 78% (22/28) of participants had a Charleston Comorbidity Index of ≥3. Mean tVNS stimulation time pre‐cognitive assessments was 21.2 minutes, with mean amplitude setting during active stimulation of 2.5mA (1.8‐4.5) and sham of 2.0mA (0.9‐3.1). During FNAT, active tVNS had no effect on facial recognition or reaction times, however recall accuracy was significantly improved (69.2% ±3.13) compared to baseline (44.7% ±3.51 p=0.016) and sham(50.1%±3.28 p=0.021) and during active tVNSspatial navigation (38.94sec [±1.68]) was quicker than baseline (51.49sec (±3.2) p = 0.0164) and sham (51.9sec (±3.15) p = 0.0038).We noted no significant improvements in SART or other cognitive tests performance during tVNS. Conclusion: tVNS may be a useful complementary tool to augment spatial and associative memory in MCI. Further larger studies are needed to delineate precise settings in this population.