NCT05984446

Targeting Default Mode Network Dysfunction in Persons At Risk of Alzheimer's Disease with Non-invasive Techniques

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 86 (actual)
• Sponsor: IRCCS Centro San Giovanni di Dio Fatebenefratelli · Academic / Other
• Sex: All
• Age: 60 Years
• Healthy volunteers: Accepted

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.

Conditions

• Alzheimer Disease

Interventions

Type	Name	Description
DEVICE	real-rTMS	Each subject will undergo 4 rTMS sessions using a 70-mm figure-eight coil (20Hz for 25 minutes). Target localization will be performed with a stereotaxic neuronavigation system.
DEVICE	sham-rTMS	The sham condition will match the real-rTMS protocol, but a sham coil will be used.

Timeline

• Start date: 2019-12-05
• Primary completion: 2024-07-30
• Completion: 2024-12-04
• First posted: 2023-08-09
• Last updated: 2025-01-16

Locations

1 site across 1 country: Italy