The goal of this clinical trial is to investigate the effect of non-invasive brain stimulation techniques in the progression of primary progressive aphasia for 6 months. We will compare three modalities of brain stimulation (TMS, tDCS, TMS+tDCS) against sham stimulation. All patients will receive also language therapy.
Transcranial Magnetic Stimulation will follow an intermitent theta-burst protocol targetting the left dorsolateral prefrontal cortex. Transcranial electrical stimulation will also follow an excitatory protocol over the same region. All brain stimulation procedures will be conducted under neuronavigation. Language therapy will follow the lexical retrieval cascade protocol and will be conducted after each brain stimulation session.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
80
Active TMS + sham tDCS. All patients will receive language therapy immediately after brain stimulation. The period of treatment will be 6 months, comprising 10 consecutive sessions in two weeks (intensive period) followed by once per week (maintenance period of 22 weeks)
sham TMS + active tDCS. All patients will receive language therapy immediately after brain stimulation. The period of treatment will be 6 months, comprising 10 consecutive sessions in two weeks (intensive period) followed by once per week (maintenance period of 22 weeks)
Sham TMS. All patients will receive language therapy immediately after brain stimulation. The period of treatment will be 6 months, comprising 10 consecutive sessions in two weeks (intensive period) followed by once per week (maintenance period of 22 weeks)
Hospital Clinico San Carlos
Madrid, Spain
RECRUITINGMini-Linguistic State Examination
Time frame: 6 months
Naming of trained words
It will be evaluated using a list of 261 words from eight semantic categories (animals, food, objects, places, furniture, clothing, transportation, and body parts)
Time frame: 6 monhts
ACE-III
General cognition
Time frame: 6 months
Interview for Deterioration in Daily Living Activities in Dementia (IDDD)
Functional activities
Time frame: 6 months
Communicative Effectiveness Index (CETI)
Functional communication questionnaire
Time frame: 6 months
CDR(R) plus NACC FTLD-SB
Clinical Dementia Rating
Time frame: 6 months
Neuropsychiatric Inventory (NPI)
Neuropsychiatric symptoms
Time frame: 6 months
FDG-PET imaging
Regional brain metabolism in a region of interest capturing a large part of the left hemisphere and associated with clinical decline in PPA (Fernandez-Romero et al. 2025)
Time frame: 6 months
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Sham tDCS. All patients will receive language therapy immediately after brain stimulation. The period of treatment will be 6 months, comprising 10 consecutive sessions in two weeks (intensive period) followed by once per week (maintenance period of 22 weeks)