Targeting Default Mode Network Dysfunction in Persons At Risk of Alzheimer's Disease with Non-invasive Techniques (NEST4AD)

IRCCS Centro San Giovanni di Dio Fatebenefratelli

Status: Completed

Conditions: Alzheimer Disease

Treatments: Device: sham-rTMS; Device: real-rTMS

Study type: Interventional

Funder types: Other

Identifiers

NCT05984446

GR-2018-12368250

Details and patient eligibility

About

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.

Full 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.

Enrollment: 86 patients

Sex: All

Ages: 60+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Age: 60 years and older
• MMSE score > 24

Exclusion criteria

• 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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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86 participants in 2 patient groups

real-rTMS

Experimental group

Description:

4 daily 25-minutes high-frequency rTMS sessions over one week

Treatment:

Device: real-rTMS

sham-rTMS

Sham Comparator group

Description:

4 daily 25-minutes sham-rTMS sessions over one week

Treatment:

Device: sham-rTMS