The aim of the study is to evaluate the safety, feasibility, clinical and biological efficacy, and predictors of efficacy of an intervention consisting of transcranial alternating current stimulation (tACS) in patients with Frontotemporal Dementia (FTD).

In addition to typical symptoms, FTD also present alterations in brain oscillations. In animal models of neurodegeneration, restoration of oscillations via neuronal "entrainment" phenomena has demonstrated a significant reduction in toxic protein accumulation, resulting in improved cognitive function.

tACS is a neurophysiological noninvasive method of neuromodulation increasingly studied for its therapeutic potential. It has been shown to safely modulate the oscillatory frequencies underlying multiple cognitive functions, including verbal memory, perception, and working memory.

In light of this evidence, it is proposed to apply a single-session treatment of β-tACS stimulation in patients with FTD and to evaluate its clinical effects, oscillatory modifications by EEG, and changes in neurophysiological indices such as short intracortical inhibition (SICI) and intracortical facilitation (ICF), both compromised in the disease.

The study has a cross-over design (multicenter, randomized, placebo-controlled and double-blind), with FTD patients randomly assigned to one of the two arms: i) Group 1, who will receive a real tACS session first (1h); ii) Group 2, who will instead undergo a sham tACS session (1h). In the next phase (cross-over), one week after the first phase, the groups will reverse the treatment: Group 1 will receive tACS sham and Group 2 will receive real tACS.

The main objectives of the study are: [1] to evaluate the safety and tolerability of the single tACS treatment session; [2] to investigate the effects of the protocol on (short-term) cognitive performance in patients with FTD; [3] to verify intervention-induced changes in brain synchronization; [4] to evaluate changes in neurophysiological indices following treatment; and [5] evaluate any predictors of efficacy.

Inclusion Criteria:

• Male or female subjects aged over 40 years at the time of signing the informed consent form;
• Presence of a clinical diagnosis of Frontotemporal Dementia according to clinical criteria (Rascovsky et al., 2011; Gorno-Tempini et al., 2011).

Exclusion Criteria:

• Age younger than that stated in the inclusion criterion;
• Inability to understand;
• Contraindications for tACS and TMS: cardiac pacemaker carriers and metal implants that are not compatible with electric or magnetic fields, history of epilepsy, current pregnancy (Safety Questionnaire)