Intermittent Theta Burst Stimulation Combined with Cognitive Training in Mild Cognitive Impairment: Protocol for an 18-Week Randomised, Double-Blind, Sham-Controlled Feasibility Pilot Study (The iCog.X Boost Trial).

Introduction

Mild cognitive impairment (MCI) is a transitional stage between normal ageing and dementia, affecting ~35% of adults aged 70+ and carrying a 15-18% annual risk of progression. Cognitive training (CT) shows promise but outcomes are variable and transfer to daily function is unclear; intermittent theta burst stimulation (iTBS) may enhance prefrontal neuroplasticity. Few studies have evaluated whether combining CT and iTBS in MCI is practical, acceptable, and safe.

Methods

This 18-week, randomised, double-blind, sham-controlled feasibility pilot trial will recruit 44 individuals with MCI, randomised 1:1 to CT + active iTBS or CT + sham iTBS. Participants complete 14 CT sessions over 10 weeks; accelerated iTBS is delivered in five sessions per day over five consecutive days at 75% resting motor threshold to the left DLPFC using neuronavigation, with reversed-coil sham. Primary outcomes are feasibility, acceptability, adherence, and safety; secondary (exploratory) outcomes are cognitive, functional, and psychological; tertiary (mechanistic) outcomes are EEG- and TMS-derived neurophysiological measures. The trial is not powered for efficacy: feasibility and neurophysiological outcomes will be analysed descriptively, while secondary outcomes will be analysed using linear mixed-effects models. Ethics and dissemination: Ethical approval has been granted by the Western Sydney University HREC (H16500); written informed consent will be obtained before enrolment. Trial registration number: ACTRN12625000952448.