Dementia Care Research and Psychosocial Factors

Primary progressive aphasia (PPA) is a neurodegenerative syndrome characterized by language impairment there is currently no effective treatment. Non-invasive techniques like transcranial magnetic stimulation (TMS) have shown potential in improving symptoms, but their long-term effects in PPA are unknown. This study aimed to evaluate the efficacy of TMS combined with language therapy in PPA at 6 months.

This double-blinded, prospective, randomized, parallel clinical trial enrolled 63 PPA patients (24 nonfluent PPA (nfvPPA), 12 semantic PPA (svPPA) and 27 logopenic (lvPPA)). Participants were randomized in a 2:1 ratio to either active TMS or sham TMS. The intervention involved a 6-month intermittent theta-burst stimulation protocol over the left dorsolateral prefrontal cortex (DLPFC) followed by language therapy based on Lexical Retrieval Cascade Treatment. The primary outcome was the standardized uptake value (SUV) in a brain region associated with PPA progression, measured at baseline and at 6 months using FDG-PET. Secondary outcomes included language performance (Mini-Linguistic State Examination, word naming, words per minute in spontaneous speech), functional independence, and neuropsychiatric symptoms, assessed at baseline, 3 months, and 6 months.

The primary outcome showed a significant benefit in the active TMS group compared to the sham group at 6 months. Active TMS also improved secondary outcomes, including language abilities, functional independence, and neuropsychiatric symptoms, except in words per minute during spontaneous speech. Adherence was complete in 92% of participants.

Intermittent theta-burst stimulation combined with language therapy for 6 months was associated with reduced decline in regional brain metabolism and improvements in language performance, functional independence, and neuropsychiatric symptoms in patients with PPA.