Stimulation to Improve Memory

Study Overview
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Brief Summary
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This study will test the effects of different doses of a form of non-invasive brain stimulation for the treatment of individuals with mild cognitive impairment (MCI) and dementia of the Alzheimer's Type (DAT).

Detailed Description
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This research study is being done to learn important information about the effects of weak electrical stimulation on brain functioning in those with mild cognitive impairment (MCI) and dementia of the Alzheimer's type (DAT). The findings will help determine how much stimulation is needed to enhance memory and thinking abilities, how it affects brain functioning, and who is most likely to benefit. Ultimately, this information may guide treatment efforts for those at various stages of Alzheimer's disease. The study will use brain imaging to see whether these treatments change how participants learn and remember information. Functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) scans will be used. The study will also use cognitive tests and questionnaires to examine whether participants' memory (and related abilities) change because of treatment. The study will enroll participants with a diagnosis of MCI or DAT. It is expected but not required that participants will be co-enrolled in the University of Michigan Memory and Aging Project (UM-MAP; HUM00000382).

Official Title
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Testing High Definition Transcranial Direct Current Stimulation (HD-tDCS) as Treatment of Mild Cognitive Impairment

Conditions
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Mild Cognitive Impairment, Dementia of Alzheimer Type

Intervention / Treatment
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* Device: 1 mA HD-tDCS
* Device: 2 mA HD-tDCS
* Device: 3 mA HD-tDCS
* Device: Sham


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Mild Cognitive Impairment (MCI) or dementia of the Alzheimer's type (DAT) Must be MRI compatible, criteria that also apply for High Definition transcranial direct current stimulation (HD-tDCS; e.g., absence of metallic or electronic implants in the upper body or head) Stable on relevant medications for at least 4 weeks prior to study enrollment Exclusion Criteria: Certain neurological diseases Certain psychiatric conditions Severe sensory impairment

Ages Eligible for Study
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Minimum Age: 55 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Eligible participants will be randomized 1:1:1:1 to receive either sham, 1mA, 2mA, or 3mA HD-tDCS for at least 5 sessions and up to 30 sessions using a blocked randomization design.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Sham Stimulation<br>Sham (placebo) dose of HD-tDCS treatment for 30 minutes, for between 5-30 sessions. | Device: Sham<br>* Participants will receive sham (placebo) HD-tDCS for 30 minutes, for between 5-30 sessions.<br>|
| Experimental: 1 mA Dosage Stimulation<br>1 milliAmp dose of HD-tDCS treatment for 30 minutes, for between 5-30 sessions. | Device: 1 mA HD-tDCS<br>* Participants will receive HD-tDCS at 1 mA for 30 minutes, for between 5-30 sessions.<br>|
| Experimental: 2 mA Dosage Stimulation<br>2 milliAmp dose of HD-tDCS treatment for 30 minutes, for between 5-30 sessions. | Device: 2 mA HD-tDCS<br>* Participants will receive HD-tDCS at 2 mA for 30 minutes, for between 5-30 sessions.<br>|
| Experimental: 3 mA Dosage Stimulation<br>3 milliAmp dose of HD-tDCS treatment for 30 minutes, for between 5-30 sessions. | Device: 3 mA HD-tDCS<br>* Participants will receive HD-tDCS at 3 mA for 30 minutes, for between 5-30 sessions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Lateral Temporal Cortex Connectivity | Graph Theory Analysis via fMRI using arbitrary units of connectivity strength | Baseline fMRI and post-intervention (after tDCS sessions 5 & 30) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Self-Report of Contentment with Memory | Multifactorial Memory Questionnaire (MMQ) Contentment Score | Baseline and post-intervention (after tDCS sessions 5 & 30) | 
| Self-Report of Memory Mistakes | Multifactorial Memory Questionnaire (MMQ) Ability Score | Baseline and post-intervention (after tDCS sessions 5 & 30) | 
| Self-Report of Memory Strategies Used | Multifactorial Memory Questionnaire (MMQ) Strategies Score | Baseline and post-intervention (after tDCS sessions 5 & 30) | 
| Change in Memory Functioning | Measured through change in the RBANS Delayed Memory Index | Baseline and post-intervention (after tDCS sessions 5 & 30) | 
| Change in Overall Fluid Cognitive Abilities | Measured through change in the NIH Toolbox Cognition Fluid Composite Score | Baseline and post-intervention (after tDCS sessions 5 & 30) | 
| Cumulative Working Memory Effects of HD-tDCS across daily sessions | Working memory accuracy measured by a discriminability ratio (2-back d' minus 0-back d') on a validated computerized N-Back task, measured after baseline (Session 1) and every intervention session (Sessions 2-6) | Baseline Session through Session 6 then weekly up to final session | 
| Cumulative Memory Accuracy Effects of HD-tDCS across daily sessions | Verbal memory accuracy measured by an accuracy score (percent correct) on a computerized Paired Associates task, measured after baseline (Session 1) and every intervention session (Sessions 2-6) | Baseline Session through Session 6 then weekly up to final session | 
| Cumulative Memory Reaction Time Effects of HD-tDCS across daily sessions | Verbal memory reaction time measured by a drift rate score (V; measured by the mean rate at which information is accumulated towards a boundary [correct or error response]) on a computerized Paired Associates task, measured after baseline (Session 1) and every intervention session (Sessions 2-6) | Baseline Session through Session 6 then weekly up to final session | 
| Tolerability of HD-tDCS | Evaluated using standard questionnaires that arose from comprehensive reviews of the tDCS literature, this questionnaire was recently refined to include pre- and post-HD-tDCS symptom assessment. This will be administered prior to and immediately after every brain stimulation session (including sham). | Prior to and immediately following each HD-tDCS session (<60 Minutes) | 
| Effectiveness of Blinding of HD-tDCS | Evaluated using a standard single question administered after every brain stimulation session (including sham). | Immediately following HD-tDCS sessions 5 and final session (<60 Minutes) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dementia, Memory, Cognitive Rehabilitation, PET scan, fMRI, Brain Stimulation