Repetitive transcranial magnetic stimulation of orbitofrontal cortex for empathy enhancement in behavioural variant frontotemporal dementia: a randomized sham-controlled clinical trial to assess different intensities

Abstract

Background Dementias are the leading cause of disability in later life and, due the aging of the population, are predicted to increase its burden. Frontotemporal dementia is the second cause of early onset dementia, before Alzheimer’s disease. Empathy loss is one of the core features of its behavioural variant, which impairs their social relationships and consequently reduces the quality of life of their familiars and caregivers. No therapy is approved for this dementia, and its management its

mostly educational and symptomatic. Repetitive transcranial magnetic stimulation is a non- invasive, low-cost and available technique that is emerging as a potential therapeutic tool for

multiple neurological and psychiatric conditions, showing potential to become a possibility to ameliorate social cognition deficits in these patients. Objectives The main purpose of this study is to test if repetitive transcranial magnetic stimulation, applied on the bilateral OFC in people suffering from behavioural variant frontotemporal dementia, could enhance empathy, comparing three different intensity parameters: sub-threshold, supra-threshold and sham stimulation. Secondary objectives include evaluating its effect on other cognitive areas and neuropsychiatric symptoms and improvement in caregivers quality of life; it will be assessed if atrophy degree interferes in the stimulation result and registered the tolerability and safety of the process. Design and Methods This study will be a randomized, single-blinded, multicentric, sham-controlled clinical trial. It will recruit 153 patients using a consecutive non-probabilistic method. Participants will be randomized in 3 arms following a 1:1:1 ratio; arm A) will receive subthreshold stimulation, arm B) suprathreshold stimulation and arm C) sham stimulation, for 4 consecutive weeks. Empathy will be assessed using Reading Mind in the Eyes test and Faux Pas test. Patients will be followed 1 year to assess therapy after-effects