Diminishing accelerated long-term forgetting in mild cognitive impairment: Study protocol for a prospective, double-blind, placebo-controlled, randomized controlled trial.

Background: Harnessing the lifelong potential of the human brain for neuroplasticity may serve to maintain the viability of neural structures and postpone the onset of cognitive decline. The absence of effective pharmacological interventions to counter memory decline has encouraged scientists to test the possibility that noninvasive electrical stimulation may serve as an additional tool to improve memory abilities.Previous research showed that electrical stimulation of the greater occipital nerve enhances memory recall performance in young and older healthy subjects. This study aims to extend these findings to determine the effect of transcutaneous electrical stimulation of the greater occipital nerve on the improvement of episodic memory in individuals with amnestic Mild Cognitive Impairment (aMCI). Methods/design: This study is a prospective, double-blind, placebo-controlled, randomized parallel-group study. A total of 100 individuals with a diagnosis of aMCI according to NIA/AA will be recruited. Participants will be randomly assigned to one of four groups. One group will receive active non-invasive transcutaneous electrical stimulation of greater occipital nerve (NITESGON), while three groups will serve as controls (i.e., sham NITESGON, active NITESGON with local anesthesia, and active NITESGON on the C5/C6 nerve). The primary outcome, i.e., memory recall, will be determined by a word association task, and will be recorded at baseline, 7 days after NITESGON, and 28 days after NITESGON. The secondary outcome is neurophysiological changes determined by resting state EEG and will be assessed immediately before and after NITESGON. Discussion: The results will add new insights into improving episodic memory in individuals with aMCI. Trial registration: #NCT05289804 (clinicaltrial.gov). Protocol approval id: #SPREC102021-23 (Ethics Committee at Trinity College Dublin, School of Psychology).