Therapy of Alzheimer's Disease With Neurofeedback

Study Overview
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Brief Summary
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The project aims to investigate in patients of Alzheimer's disease in a prodromal state (early state of the disease) compared to healthy subjects whether neurofeedback training with functional MRI (fMRI) can improve cognitive ability. It is of interest if voluntary modulation of brain activation with real-time (rt) fMRI as a novel method affects cognitive ability, as well as functional and structural measures of the brain. Over the course of the study subjects will learn a real-world footpath. During neurofeedback training subjects are then asked to recall this footpath while simultaneously trying to modulate their own brain activation based on feedback. Feedback is given about the parahippocampal gyrus - a region of the brain associated with episodic and visuo-spatial memory, which is known to be affected early by Alzheimer's disease pathology. Before and after the training cognitive ability is assessed using neuropsychological tests mainly measuring numerous domains of memory. The investigators hypothesise that the training leads to an improvement of the trained cognitive domain, but also induces changes in brain structure and function.

Official Title
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Neurofeedback and Follow-up With Real-time fMRI to Investigate Cognitive Function in Patients of Mild Cognitive Impairment (MCI) or Alzheimer's Disease (AD)

Conditions
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Alzheimer Dementia (AD), Elderly

Intervention / Treatment
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* Other: rtfMRI neurofeedback training
* Device: 3T MRI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Native speakers of German Naive to neurofeedback experiments Ability to provide written informed consent Exclusion Criteria: Metallic implants (MR-safety) Neurological/psychiatric disease (except Alzheimer's disease in the patient group) Use of psychoactive medication (expect medication for Alzheimer's disease) Familiarity with the study site

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The design is a pre-test/post-test study with an intervention of three parallel groups. The groups are a healthy elderly experimental group, a patient group and a healthy elderly sham-feedback group.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Healthy elderly experimental group<br>Feedback of the parahippocampal gyrus using rtfMRI neurofeedback training (using 3T MRI). | Other: rtfMRI neurofeedback training<br>* Information about the state of brain activation was given to subjects. That information was visualised as a thermometer bar. Subjects tried to modulate that activation while performing a mental imagery task.<br>Device: 3T MRI<br>* A 3T Siemens MRI scanner was used to implement rtfMRI neurofeedback training.<br>|
| Experimental: Patient group<br>Feedback of the parahippocampal gyrus using rtfMRI neurofeedback training (using 3T MRI). | Other: rtfMRI neurofeedback training<br>* Information about the state of brain activation was given to subjects. That information was visualised as a thermometer bar. Subjects tried to modulate that activation while performing a mental imagery task.<br>Device: 3T MRI<br>* A 3T Siemens MRI scanner was used to implement rtfMRI neurofeedback training.<br>|
| Sham Comparator: Healthy elderly sham-feedback group<br>Feedback of the postcentral gyrus using rtfMRI neurofeedback training (using 3T MRI). | Other: rtfMRI neurofeedback training<br>* Information about the state of brain activation was given to subjects. That information was visualised as a thermometer bar. Subjects tried to modulate that activation while performing a mental imagery task.<br>Device: 3T MRI<br>* A 3T Siemens MRI scanner was used to implement rtfMRI neurofeedback training.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual and Verbal Memory Test (VVM) | Neuropsychological assessment including visuo-spatial memory | 2.5 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Montreal Cognitive Assessment (MoCA) | Neuropsychological instrument for a general cognitive screening | 2.5 weeks | 
| Wechsler Memory Scale Revised (WMS-R) | Subtests from the WMS-R were used to assess several domains of memory | 2.5 weeks | 
| Trail Making Test (TMT) | TMT-A and -B were used to assess cognitive processing speed and task switching capabilities. | 2.5 weeks | 
| Visual Patterns Test (VPT) | The VPT was used to assess visual working memory capabilities. | 2.5 weeks | 
| Parahippocampal activation | Activation of the parahippocampal gyrus during neurofeedback training as measured with fMRI | 2.5 weeks | 
| Memory-related functional connectivity using Granger Causality Analysis (GCA) | Change of functional connectivity mainly between memory-associated brain regions over the course of neurofeedback training characterised by GCA | 2.5 weeks | 
| Change of brain structure | Assessment of grey matter volume in the entire brain | 2.5 weeks | 
| Change of brain function | Assessment of activation in the entire brain | 2.5 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neurofeedback, real-time functional MRI, parahippocampus