Feasibility of Interleaving Computerized Cognitive Training With Repetitive Transcranial Magnetic Stimulation: Pilot Studies in Mild Cognitive Impairment Due to Alzheimer’s Disease and Stroke

Background Repetitive transcranial magnetic stimulation induces neural plasticity, which may be maximized via adjunctive interventions. Objective This study aimed to examine the feasibility and acceptability of interleaving computerized cognitive training (CCT) with accelerated intermittent theta burst (iTBS) repetitive transcranial magnetic stimulation in 2 open-label phase I trials of amnestic mild cognitive impairment (aMCI; NCT04503096) and poststroke mild cognitive impairment (psMCI; NCT04655963). Methods Participants (aMCI: n=21; and psMCI: n=14) received 24 sessions of accelerated iTBS over 3 days (8 sessions per day). During the 10‐ to 15-minute intervals between iTBS sessions, participants engaged in CCT via the BrainHQ platform. During the 4-week follow-up period, participants were asked to complete 20 minutes daily of BrainHQ. Both studies offered identical compensation for daily practice, but the aMCI group received weekly reminders, whereas the psMCI group did not. Study-specific questionnaires assessed BrainHQ acceptability (administered post-treatment and at follow-up). Results During in-laboratory treatment, the groups completed similar amounts of BrainHQ (aMCI: median 107, IQR 92-121 min; and psMCI: median 111, IQR 93-137 min; P =.51). However, engagement differed during the unmonitored follow-up (aMCI: median 450, IQR 167-581 min,; and psMCI: median 142, IQR 0-477 min); practice time increased in the aMCI group but decreased in the psMCI group over the 4 weeks ( P =.001). Both groups generally rated BrainHQ positively at both time points in terms of their experience with the platform, exercises, and perceived benefit for their mood and functioning. Conclusions Combined treatment with CCT and accelerated iTBS is feasible and acceptable in people with mild cognitive impairment. Standardized dosing of CCT is feasibly achieved when interleaved with iTBS sessions and completed in-laboratory, but ecological adherence to CCT in an unmonitored, self-directed context likely requires additional supports and may be influenced by patient characteristics.