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Personalized repetitive transcranial magnetic stimulation for non‐fluent and semantic variants of primary progressive aphasia: Developments in clinical trials and cognitive assessment
Abstract Background Primary progressive aphasia (PPA) is a neurodegenerative syndrome characterized by the neurodegeneration of language brain regions and networks. As in many other neurodegenerative disorders, effective treatments are lacking or have limited efficacy. Repetitive transcranial magnet...
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| Published in: | Alzheimer's & dementia 2020-12, Vol.16 (S9) |
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| Main Authors: | , , , , , , , , , , |
| Format: | Article |
| Language: | English |
| Online Access: | Get full text |
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| Summary: | Abstract
Background
Primary progressive aphasia (PPA) is a neurodegenerative syndrome characterized by the neurodegeneration of language brain regions and networks. As in many other neurodegenerative disorders, effective treatments are lacking or have limited efficacy. Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a potential treatment for many neurological and psychiatric disorders, and lately also for neurodegenerative disorders. We aimed to assess the effect of rTMS, on language, global cognition, neuropsychiatric symptoms, and brain metabolism in patients with PPA using a personalized target.
Methods
We conducted a randomized, double‐blind, pilot study of patients with PPA receiving rTMS. Simple randomization was used to separate patients into 2 groups with a 3:2 ratio: i) active‐site rTMS therapy only (n = 12); ii) a cross‐over group (n = 8). In the latter group, subjects were randomly allocated 1:1 to receive therapeutic rTMS followed by control‐site rTMS, or vice versa. Fifteen sessions of neuronavigated rTMS with personalized targeting were delivered. The primary outcome was changes in spontaneous speech (word count using a story description task). Secondary outcomes included changes in other language tasks (object naming, story reading task, repetition), global cognition (Addenbrooke’s Cognitive Examination), global impression of change (patient and caregiver), neuropsychiatric symptoms (Neuropsychiatric Inventory), and brain metabolism (FDG‐PET).
Result
Twenty patients with PPA were enrolled (14 with nonfluent and 6 with semantic variant PPA). Compared to the control group, the group receiving active‐site rTMS 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
Our findings suggest that high‐frequency rTMS with personalized targeting improves language, patient and caregiver perception of change, apathy, and depression. The finding of increased regional brain metabolism suggests enhancement of synaptic activity with the treatment. This study provides a rationale and supports the consideration for conducting a phase III randomized cl |
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| ISSN: | 1552-5260 1552-5279 |
| DOI: | 10.1002/alz.047658 |