Diminishing Accelerated Long-term Forgetting in Mild Cognitive Impairment: Study Protocol for a Prospective, Double-blind, Placebo-controlled, Randomized Controlled Trial

Patients 50 years of age and above with amnestic mild cognitive impairment (aMCI), will be recruited to the memory clinic at St. James and the Memory Assessment and Support Service Tallaght University Hospital. The investigators plan to include 100 English-speaking aMCI patients. To participate in this study, subjects should be able to provide an informed consent, have a confirmed aMCI diagnosis and have their medication stable for at least three months prior to baseline data collection. Prospective participants, who meet the criteria, will be sent an electronic copy of the consent form. Participants will only be asked to sign the consent form at the site after going over the form with the researcher where all aspects of the study protocol will be reviewed.

The study is designed to give us adequate power to detect clinically meaningful differences between the groups. Twenty individuals per group (total n = 80) would offer us a power of 80% to detect the difference between groups using Cohen's d estimation of effect size. A sample size of 80 will allow us to see a large effect size. Although The investigators do not expect attrition to be large, a dropout rate of no more than 10% is expected. This trial is longitudinal which could increase its drop-out rate. The investigators will thus oversample to a target sample size of 25 patients per group to assure that our power to detect effects is maintained. The overall sample will be 100. The investigators aim to recruit patients with aMCI and display pre-symptomatic signs of Alzheimer's disease (AD). An age ranging from 50 years and above is a good fit for this population.

The study consists of three in person sessions. Session 1 will consist of a word association memory task in which participants are instructed to memorize a subset of words. Participants will either receive active stimulation or control stimulation during the word-association task. Session 1 will also include demographic and mood related questionnaires, as well as EEG before and after memory testing. At the end of EEG testing, participants will fill out an exit questionnaire developed by Brunoni et al. to assess potential side-effects (headache, neck pain, scalp pain, tingling, itching, burning sensation, skin redness, sleepiness, trouble concentrating, mood changes) at the end of stimulation. One week after Session 1, Session 2 will take place. They will again complete the word association memory task. Three weeks after Session 2, Session 3 will take place and participants will complete the word association memory task and complete a blinding questionnaire at the end of the session.

During memory testing, participants will receive one of four interventions. Participants will encounter a second researcher who will take over for the first researcher in order to provide the blinded-stimulation protocol. They will be assigned randomly (like a flip of a coin) to one of four groups. Some groups will receive active stimulation and the other three groups will serve as controls. For sham stimulation, placement of the electrodes will be identical to active stimulation. A third group will receive stimulation, but with a topical skin anesthetic. For the fourth control group, the electrodes will be placed on the lower neck. For both the third and fourth control group, the current similar to active stimulation will be applied.

Participants will be paid at the end of the session and will be asked to sign a receipt of the money. If they successfully complete the study, they will be compensated for travel with 10 euros, if they wish to withdraw or are unable to proceed because of any in-eligibility in the in-person session, they will be compensated with 5 euros for travel.