Modulation of Cognition and Brain Connectivity by Noninvasive Brain Stimulation in Patients With Mild Cognitive Impairment Due to Alzheimer's Disease

Study Overview
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Brief Summary
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Alzheimer's disease (AD) has a detrimental impact on cognitive functions. Based on pilot studies results in patients with neurodegenerative brain diseases the investigators aim for promoting the brain plasticity and improving cognition by noninvasive brain stimulation (NIBS) in healthy young, healthy aged and subjects with mild cognitive impairment due to AD. Mild cognitive impairment (MCI) is an intermediate stage between the expected cognitive decline of normal aging and the more-serious decline of dementia. Different new brain targets, cognitive tasks and stimulation protocols will be tested and optimized for specific subject groups. Design of a functional MRI (fMRI) - repetitive transcranial magnetic stimulation (rTMS) - fMRI study will enable us to explore and identify effect of age, presence of the disease and genetic risk factor (APOE4) on repetitive transcranial magnetic stimulation (rTMS)-induced changes in cognition and related brain connectivity/activations. The study results will improve our understanding of healthy and pathological brain aging and will provide novel information about the usefulness of NIBS in specific subject groups. These results will have an important impact on future non-pharmacological treatment strategies.

Detailed Description
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Intensified intermittent theta-burst stimulation (iTBS) protocol will be applied in the MCI study group. A two-parallel-group, randomized, placebo controlled design will be used. Ten MCI subjects will be stimulated in a week-long therapeutical sessions. Other ten MCI subjects will be stimulated with the same protocol using sham stimulation. The investigators will study the change in subjects immediately after and again at a two-weeks follow-up visit after the end of the last stimulation session.

Official Title
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Modulation of Cognition and Brain Connectivity by Noninvasive Brain Stimulation in Patients With Mild Cognitive Impairment Due to Alzheimer's Disease

Conditions
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Mild Cognitive Impairment

Intervention / Treatment
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* Device: Transcranial magnetic stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: amnestic single or multi-domain mild cognitive impairment patients in accordance with diagnostic criteria (Albert et al., 2011) Exclusion Criteria: psychiatric disorders, including major depression, major vascular lesions, and other brain pathologies detected by MRI that might present with cognitive decline a cardio pacemaker or any MRI-incompatible metal in the body epilepsy any diagnosed psychiatric disorder alcohol/drug abuse lack of cooperation presence of dementia

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active Comparator: MCI patients with real iTBS<br>Patients will receive real iTBS in a week-long sessions. | Device: Transcranial magnetic stimulation<br>* Transcranial magnetic stimulation device will be used. Short protocol iTBS will be applied.<br>|
| Sham Comparator: Sham Comparator: MCI patients with sham iTBS<br>Patients will receive sham iTBS in a week-long sessions. | Device: Transcranial magnetic stimulation<br>* Transcranial magnetic stimulation device will be used. Short protocol iTBS will be applied.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual-attention task accuracy and reaction times | Stroop task will be presented in fMRI | On the beginning of the study, after completion of week stimulation a two weeks after completion of stimulation sessions. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resting state measurement | The effect of stimulation on the resting state networks will be studied using fMRI measurement. | On the beginning of the study, after completion of week stimulation a two weeks after completion of stimulation sessions. |