264 Improvements in associative memory and spatial navigation with acute transcutaneous Vagus Nerve Stimulation in Mild Cognitive Impairment: preliminary data

Abstract Background 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 unimpaired populations but data in cognitively impaired populations is sparse. This investigation is timely as new therapeutic strategies to treat Mild Cognitive Impairment (MCI) are urgently needed. Methods VINCI-ad is an investigator-led, single-blind, sham-controlled crossover pilot study assessing the effects of tVNS in amnestic MCI. All participants have MCI (Clinical-Dementia Rating Scale—Global Score of 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. Results Interim data analysis of 28 participants (planned recruitment n = 40) 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-42460.4 pg/ml (± 83.3 pg/ml) and p-tau181 82.5 pg/ml [± 53.2 pg/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 2.5 mA (1.8–4.5) and sham of 2.0 mA (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 tVNS spatial navigation (38.94 sec [±1.68]) was quicker than baseline (51.49 sec (±3.2) p = 0.0164) and sham (51.9 sec (±3.15) p = 0 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.