Investigating Transcutaneous Vagus Nerve Stimulation in Amnestic Mild Cognitive Impairment

Abstract Background New treatments are urgently needed for individuals with Mild Cognitive Impairment (MCI) - in particular for those with amnestic MCI, of whom a high proportion have underlying Alzheimer's Disease (AD). Transcutaneous Vagus Nerve Stimulation (tVNS) is a non-invasive neuro-modulatory treatment which has not been extensively examined in older adults with amnestic MCI. Methods A single site, single-blind, randomised three-arm crossover pilot trial of acute (60 minutes) tVNS (baseline, sham or active stimulation) was conducted a Regional Specialist Memory Service. Forty participants (age 71.7 ±6.9; 22/40 male) with diagnosed amnestic MCI were recruited. Given the links between AD and neuro-cardiovascular instability, potential adverse effects of active tVNS were assessed using beat-to-beat peripheral (Blood Pressure (BP) and Heart Rate [HR]) and central (via Near Infra-red Spectroscopy) haemodynamic responses to Active Stand (AS). Cognition was assessed between 21.3 ±4.9 and 60.5 ±4.4 minutes using a domain-specific cognitive performance battery with results analysed using mixed-effects linear regression. Results In older adults with amnestic MCI, tVNS was safe, tolerable and acceptable with 98% of participants stating they would use the device again. There was no significant effect on BP, or HR responses to AS and cerebral oxygenation remained stable during AS. After tVNS stimulation, performance on tests of spatial navigation were significantly improved compared to both baseline (ß= -8.76; [-14.91, -2.56]; p=0.01) and sham (ß= -4.15; [-7.32, -0.99]; p=0.01) conditions. Conclusion tVNS is a safe and tolerable treatment modality in older adults with amnestic MCI. Future studies should explore sustained effects and feasibility of domiciliary use.