Targeting Default Mode Network Dysfunction in Persons At Risk of Alzheimer's Disease with Non-invasive Techniques
- Conditions
- Alzheimer Disease
- Interventions
- Device: real-rTMSDevice: sham-rTMS
- Registration Number
- NCT05984446
- Lead Sponsor
- IRCCS Centro San Giovanni di Dio Fatebenefratelli
- Brief Summary
Default mode network (DMN) dysfunction is a well-established feature of Alzheimer's Disease (AD) and is already present in preclinical stages and in subjects at risk for AD, thus offering a potential target for early intervention. Non-invasive stimulation techniques are candidate approaches to modulate network dysfunction, however interventions specifically targeting subjects at risk for AD are lacking. This project will test a non-invasive intervention to modulate the DMN in cognitively healthy older adults carrying the main genetic risk factor for AD, the APOE e4 allele. The proposal will non-invasively stimulate the DMN in at risk subjects and will assess the neuronal-cognitive effect of this approach with multimodal neuroimaging and neurophysiological techniques.
- Detailed Description
Sixty-four participants will be enrolled (n=32 APOE e4 carriers, 32 non-carriers as reference group) and will undergo rTMS stimulation, TMS with concurrent electroencephalography (TMS-EEG), multimodal imaging (resting-state and task functional MRI, and diffusion tensor imaging) and cognitive assessment at baseline, after the intervention (week 1) and after 2 months. Participants will be randomized to 2 groups: active DMN stimulation (real-rTMS) or placebo (sham-rTMS). Each subject will undergo a rs-fMRI scan before the intervention to derive individualized DMN stimulation targets. rTMS will be applied over the left inferior parietal lobule node of the DMN.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 86
- Age: 60 years and older
- MMSE score > 24
- Pathological scores in at least two standardized cognitive tests
- Participation in other interventional studies
- Known carriers of an autosomal dominant genetic mutation associated to AD
- Neurological, psychiatric or medical conditions not compatible with the study
Exclusion Criteria for MRI and rTMS:
- metal implants, pace-makers, prosthetic heart valves
- claustrophobia
- history of epilepsy
- pregnancy
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description real-rTMS real-rTMS 4 daily 25-minutes high-frequency rTMS sessions over one week sham-rTMS sham-rTMS 4 daily 25-minutes sham-rTMS sessions over one week
- Primary Outcome Measures
Name Time Method Change in DMN connectivity on TMS-EEG following real-rTMS compared to sham-rTMS in APOE4 carriers Baseline, post rTMS (1 week) Single pulse TMS will be applied with concurrent EEG to derive online measures of cortical excitability and connectivity. The response in the natural frequency of the target area will index cortical excitability. Effective connectivity will be measured through amplitude and latency of TEPs.
Change in DMN connectivity on rs-fMRI following real-rTMS compared to sham-rTMS in APOE4 carriers Baseline, post rTMS (1 week) Default mode network (DMN) mean functional connectivity is assessed on resting state functional MRI. Higher values denote greater functional connectivity. A positive change at post rTMS compared to baseline represents an increase in resting-state functional connectivity.
- Secondary Outcome Measures
Name Time Method Change in task-fMRI associative memory performance following real-rTMS compared to sham-rTMS in APOE4 carriers Baseline, post rTMS (1 week) Memory is assessed on task fMRI using a face-name associative paradigm
Trial Locations
- Locations (1)
IRCCS Centro San Giovanni di Dio Fatebenefratelli
🇮🇹Brescia, Italy