Long-term Effect of TMS in Primary Progressive Aphasia (RECONNECT)

There are very few treatments for neurodegenerative disorders, and the efficacy of these treatments is generally modest. Recent studies have shown a short-term positive effect of non-invasive neuromodulation techniques such as transcranial magnetic stimulation (TMS) in primary progressive aphasia (PPA). PPA is a clinical syndrome associated with Alzheimer's disease and Frontotemporal degeneration. The aim of this study is to compare the effect of TMS and language therapy versus language therapy and sham TMS in patients with PPA during 6 months. A prospective, randomized, controlled, double-blind and parallel clinical trial will be conducted. The changes in brain metabolism using FDG-PET, language, neuropsychiatric symptoms, and daily-living activities will be assessed. Connectivity changes using electroencephalography will also be examined. In addition, a subgroup of patients will be assessed with multimodal MRI (structural and functional), and blood biomarkers. As a result of this project, valuable information about the long-term efficacy of non-invasive brain stimulation in PPA will be obtained, as well as the mechanisms of the therapy and clinical and neuroimaging factors associated with therapy response.

TMS (active) using theta burst protocol over the left dorsolateral prefrontal cortex. Daily sessions for two weeks followed by one session per week during 6 months. Each TMS session is followed by language training.

TMS (sham) using theta burst protocol over the left dorsolateral prefrontal cortex. Daily sessions for two weeks followed by one session per week during 6 months. Each TMS session is followed by language training.

Theta-burst transcranial magnetic stimulation (active) delivered over the left dorsolateral prefrontal cortex. Daily sessions for two weeks followed by 1 session per week.

Language therapy immediately after each TMS session. Daily sessions for two weeks followed by 1 session per week.

Theta-burst transcranial magnetic stimulation (sham) delivered over the left dorsolateral prefrontal cortex. Daily sessions for two weeks followed by 1 session per week.

Inclusion Criteria: Diagnosis of PPA (Gorno-Tempini et al. 2011 criteria supported by neuroimaging) CDR Language is the most prominent symptom Exclusion Criteria: Clinical Dementia Rating scale > 1 History of epilepsy or epileptiform activity in EEG Another disorder causing aphasia Any contraindication for TMS Pregnancy Medical disorder with a life expectancy of less than one year Malignancy in the last two years Alcohol or drug abuse Major psychiatric disorder Inability to communicate (mutism) Use of anticonvulsants, benzodiazepines, donepezil/galantamine/rivastigmine, memantine, antidepressants and neuroleptics is permitted if they are at stable doses in the last three months.