Long-term transcranial magnetic stimulation plus language therapy may slow aphasia progression

Hospital Clínico San Carlos in Madrid-led research reports that intermittent theta-burst transcranial magnetic stimulation (TMS) paired with language therapy over six months was associated with positive outcomes in primary progressive aphasia (PPA). Improvements included less decline in regional brain metabolism and improvements in language abilities, functional independence, and neuropsychiatric symptoms.

Primary progressive aphasia is a neurodegenerative clinical syndrome with insidious onset characterized by prominent speech and/or language impairment. It is a syndrome that can be the mode in which common causes of dementia, Alzheimer’s disease and frontotemporal degeneration are initially present.

According to current international consensus criteria, three variants are recognized: nonfluent/agrammatic, semantic, and logopenic. Speech-language intervention has proven to be beneficial.

Noninvasive brain stimulation techniques, including transcranial magnetic stimulation, have also been explored in neurodegenerative diseases and in PPA, with previous studies examining short-term effects such as improvements in naming, cognitive tests, apathy, spontaneous speech, and regional cerebral metabolism. Longer-term effects have not been well documented.

In the study, “Long-Term Therapy With Transcranial Magnetic Stimulation in Primary Progressive Aphasia,” published in JAMA Network Open, researchers conducted a prospective, double-blind parallel-design randomized clinical trial to evaluate the efficacy, safety, and adherence of transcranial magnetic stimulation plus language therapy in participants with PPA over six months.

Sixty-three participants were tested at the Department of Neurology of Hospital Clínico San Carlos in Spain and randomized 2:1 to active TMS (n=42) or sham TMS (n=21), stratified by PPA variants (nonfluent/agrammatic, semantic, logopenic).

Participants and the assessor were blinded, and the researcher performing TMS sessions did not have access to assessment results. The intervention schedule consisted of a two-week intensive course of 10 daily sessions followed by a maintenance phase of one session per week for 22 weeks, with language therapy delivered immediately after each TMS or sham session.

All sessions used an intermittent theta-burst protocol: 600 pulses at 50 Hz, distributed across 20 cycles of three pulses with a 10-second interval, lasting approximately three minutes at 120% of the resting motor threshold with a maximum of 50% of the maximum stimulator output.

Language treatment involved an adapted form of lexical retrieval treatment with 50-minute sessions, training sets of five nouns per session drawn from 261 words across eight semantic categories, with homework using Copy and Recall Treatment.

The primary outcome focused on a brain-metabolism measure (SUVR) of the standardized uptake value ratio in a large region encompassing most of the left hemisphere. Secondary outcomes were the Mini-Linguistic State Examination, confrontation naming of trained objects, words per minute from a spontaneous speech task, the Interview for Deterioration in Daily Living Activities in Dementia, and the Neuropsychiatric Inventory.

SUVR measured 0.78 in the active group vs. 0.77 in the sham group at six months, indicating less reduction in SUVR in the active group.

Language ability based on the Mini-Linguistic State Examination had a mean adjusted difference of 7.71 points favoring active TMS, in part due to a worsening score in the sham group compared with the active group.

Naming of trained items rose to an adjusted mean of 143.81 in the active group vs. a drop to 119.99 in the sham group from baseline means of 122.21 and 127.12, respectively.

Daily functioning based on the Interview for Deterioration in Daily Living Activities in Dementia fell −5.39, indicating improvement favoring the active TMS group. Adjusted means were 43.54 in the active group vs. 48.94 in the sham group, from baseline means of 48.02 and 45.45, respectively, showing a downward shift in the active group and an upward shift in the sham group.

Speech rate, measured in words per minute, showed no significant difference between groups.

Overall, the study showed both improvement with and declines without the use of TMS. Safety data included two serious adverse events that occurred in the sham group, unrelated to the sham treatment itself.

The authors conclude that long-term TMS combined with language therapy may help slow the progression of PPA and offer a new approach for treating language disturbances due to neurodegenerative disorders.

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