An interventional study of Transcranial pulse stimulation (TPS) in Alzheimer Disease and Mild Cognitive Impairment, sponsored by IRCCS San Raffaele Roma. Completed at 1 site in Italy. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-20.
Sponsored by IRCCS San Raffaele Roma · Not applicable, Interventional, and Treatment
The goal of this study is to evaluate the effects of transcranial pulse stimulation (TPS) in modulating cognitive functions as well as structural and functional connectivity in individuals with mild cognitive impairment and early Alzheimer's disease. The main outcome measure is to confirm whether TPS may be considered as an effective treatment to improve memory in a large cohort of participants and investigating its long-term effects. Then, secondary measurements are to evaluate if TPS may induce neuronal connectivity changes and may confirm previous results exploring whether this innovative technique may induce, in a long and short-term period, possible effects on cortical atrophy and structural connectivity. An additional outcomes is to evaluate if TPS may have a positive impact on global cognitive functioning and behavioral profile.
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.
3,765 studies on the registry are indexed under Alzheimer Disease; 881 are open to participants now.
This study's enrollment of 52 is below the median of 68 across 2,861 interventional studies indexed under Alzheimer Disease.
Browse Alzheimer Disease studies →IRCCS San Raffaele Roma is the lead sponsor of 68 studies on the registry; 27 are open to participants now.
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Inclusion Criteria:
Inclusion criteria for MCI due to AD will be as follows:
Inclusion criteria for AD will be as follows:
Exclusion Criteria:
Exclusion criteria for both MCI due to AD and AD will be the following:
A sham TPS is performed once a day for five days/weekly for four weeks in the sham group. Each daily TPS session takes about 30 minutes.
Device: Transcranial pulse stimulation (TPS)
A real TPS is performed once a day for five days/weekly for four weeks in the sham group. Each daily TPS session takes about 30 minutes.
Device: Transcranial pulse stimulation (TPS)
All patients will receive either real TPS or sham treatment once a day for five days/weekly for four weeks. Each daily TPS session takes approximately 30 minutes. TPS produces single ultrashort pulses with a frequency spectrum ranging from 1 to 8 Hz. Ultrasound pulses will be applied using a NEUROLITH TPS generator. Technical parameters will be set as follows: 0.2-0.25 mJ mm2 energy flux density, pulse repetition frequency of 3.5 Hz, 6000 pulses per session. Before the stimulation, individual 3D T1 isometric voxel MRI scans will be performed to allow TPS neuronavigation. Therefore, regions of interest (ROIs) from each participant will be defined by a trained neurologist to target brain areas, as frontal lobe, parietal lobe, precuneus and left/right hippocampus, typically involved in AD pathology.
Episodic Memory Score (EMS)
The stability/improvement of the memory profile in MCI and mild AD patients subjected to TPS treatment, in the short and long term, will be evaluated using Episodic Memory Score (EMS). (integrated neuropsychological assessment tool designed to evaluate verbal and visual episodic memory and predict the progression from amnestic Mild Cognitive Impairment (aMCI) to Alzheimer's disease) Range: from 4 (worst performance) to 12 (best performance).
Time frame: Before TPS sessions, at 1-month follow-up and at 8-months follow-up
EEG functional connectivity
To evaluate the changes in electrophysiological indices of functional connectivity, applying graph theory, in MCI and mild AD patients treated with real TPS compared to those treated with placebo TPS, both in the short and long term; Furthermore, identify neurophysiological measurements capable of predicting a positive response to treatment.
Time frame: Before TPS sessions, at 1-month follow-up and at 8-months follow-up
Cortical thickness
To evaluate the changes in cortical thickness using radiological data, in the MCI and mild AD groups treated with real TPS compared to the MCI and mild AD groups treated with placebo, both in the short and long term.
Time frame: Before TPS sessions, at 1-month follow-up and at 8-months follow-up
Structural connectivity
To evaluate the changes structural connectivity, using radiological data, in the MCI and mild AD groups treated with real TPS compared to the MCI and mild AD groups treated with placebo, both in the short and long term.
Time frame: Before TPS sessions, at 1-month follow-up and at 8-months follow-up
Rey Auditory Verbal Learning Test (RAVLT)
neuropsychological tests
Time frame: Before TPS sessions, at 1-month follow-up and at 8-months follow-up
Rey Osterrieth Complex Figure (ROCF) - copy and recall tasks
neuropsychological tests
Time frame: Before TPS sessions, at 1-month follow-up and at 8-months follow-up
Episodic Memory Score (EMS)
neuropsychological tests
Time frame: Before TPS sessions, at 1-month follow-up and at 8-months follow-up
Digit Span forward and backward
neuropsychological tests
Time frame: Before TPS sessions, at 1-month follow-up and at 8-months follow-up
Trail Making Test (TMT), part A and B
neuropsychological tests
Time frame: Before TPS sessions, at 1-month follow-up and at 8-months follow-up
Phonemic and semantic verbal fluency
neuropsychological tests
Time frame: Before TPS sessions, at 1-month follow-up and at 8-months follow-up
Object namnaming task
neuropsychological tests
Time frame: Before TPS sessions, at 1-month follow-up and at 8-months follow-up
Neuropsychiatric Inventory Questionnaire (NPI)
neuropsychological tests
Time frame: Before TPS sessions, at 1-month follow-up and at 8-months follow-up
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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IRCCS San Raffaele Roma