Personalized Repetitive Transcranial Magnetic Stimulation for Primary Progressive Aphasia

Background: Primary progressive aphasia (PPA) is a neurodegenerative syndrome for which no effective treatment is available. Objective: We aimed to assess the effect of repetitive transcranial magnetic stimulation (rTMS), using personalized targeting. Methods: We conducted a randomized, double-blind, pilot study of patients with PPA receiving rTMS, with a subgroup of patients receiving active- versus control-site rTMS in a cross-over design. Target for active TMS varied among the cases and was determined during a pre-treatment phase from a list of potential regions. The primary outcome was changes in spontaneous speech (word count). Secondary outcomes included changes in other language tasks, global cognition, global impression of change, neuropsychiatric symptoms, and brain metabolism using FDG-PET. Results: Twenty patients with PPA were enrolled (14 with nonfluent and 6 with semantic variant PPA). For statistical analyses, data for the two variants were combined. Compared to the control group (n = 7), the group receiving active-site rTMS (n = 20) showed improvements in spontaneous speech, other language tasks, patient and caregiver global impression of change, apathy, and depression. This group also showed improvement or stabilization of results obtained in the baseline examination. Increased metabolism was observed in several brain regions after the therapy, particularly in the left frontal and parieto-temporal lobes and in the precuneus and posterior cingulate bilaterally. Conclusion: We found an improvement in language, patient and caregiver perception of change, apathy, and depression using high frequency rTMS. The increase of regional brain metabolism suggests enhancement of synaptic activity with the treatment. Trial registration: NCT03580954 (https://clinicaltrials.gov/ct2/show/NCT03580954)