TPSAlz - Transcranial Pulse Stimulation in Alzheimer's Disease

The incidence of dementia is increasing worldwide, and great research efforts have been pointing towards novel therapeutic strategies to slow down or treat the occurrence of dementia. Among non-invasive brain stimulation techniques, transcranial pulse stimulation (TPS) has recently demonstrated its potential in modulating brain functions and improving cognitive performances in Alzheimer's disease (AD) patients. Little is known on its effect on brain network organization/plasticity, particularly in prodromal stages of AD, such as Mild Cognitive Impairment (MCI). The proposal aims to evaluate whether TPS treatment may show positive effects on cognition, neuronal plasticity, and anatomical patterns in MCI due to AD and AD. In the present placebo-controlled study, at least 26 individuals with MCI due to AD and 26 with AD will be recruited. These two groups will be matched by age, gender and years of education. The data collection will be performed at baseline, at 1-month follow-up and at 8-month follow-up. At the baseline, all subjects will perform a complete neuropsychological assessment to evaluate cognitive functions, a high-density electroencephalogram (EEG) recording (128 channel) for the evaluation of the brain connectivity through graph theory indices, and a volumetric 3 Tesla brain Magnetic Resonance Imaging (MRI) to investigate anatomical features including volumetry and structural connectivity. Demographic and clinical data will be also collected. Then, every participant will be treated with a session of TPS for four weeks. Both MCI and AD will be divided into two different comparable groups of treatment: real TPS (treated) and placebo TPS (sham-treated). At 1-month and at 8-month follow-up visits, all subjects will undergo neuropsychological, high-density EEG and MRI evaluations. TPS has previously been evaluated for its efficacy in improving cognition in AD patients. As a novelty, this proposal will consider whether TPS may be a potential treatment also for MCI stage. Additionally, this non-invasive technique will be assessed for its potential positive impact on functional connectivity and anatomical measurements.