Cognitive Outcomes of Brain Stimulation As a Later-in-Life Treatment

Study Overview
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Brief Summary
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This is a pilot study being done to attempt to improve episodic memory problems in persons with mild cognitive impairment (MCI) or dementia. The pre-supplemental motor area (preSMA) and dorsal anterior cingulate cortex (dACC) have been shown to play a role in episodic memory and language retrieval. Prior studies have suggested that neurostimulation targeting this region can improve episodic memory and word recall. The purpose of this study is to examine the efficacy of high-definition transcranial direct current stimulation (HD-tDCS) to the preSMA/dACC region and its influence on word retrieval and other cognitive functions in patients with MCI or dementia. Entraining the preSMA/dACC circuit with 10 sessions of HD-tDCS will allow us to study whether neurostimulation may be an effective treatment.

Detailed Description
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The research objective of this study is to examine the efficacy of HD-tDCS to the preSMa/DaCC region and its influence on word retrieval and other cognitive functions in patients with MCI or dementia after 10 sessions of HD-tDCS. There will be two treatment arms: active HD-tDCS (1 mA) and a sham group. For Phase 1, participants will receive 10 sessions of active stimulation (1 mA anodal HD-tDCS targeting preSMA/dACC for 20 min) or sham across 2 weeks. Word retrieval and other cognitive tasks will be completed at baseline, immediate follow-up after session 10, and a 2-month follow-up. For Phase 2, participants randomized into the sham group will have the opportunity to return after 2 months and receive the active treatment while being unblinded to their treatment condition. Following 10 active treatment sessions, word retrieval and other cognitive tasks will again be completed immediately following the last HD-tDCS session and then a 2-month follow-up.

Official Title
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Cognitive Outcomes of Brain Stimulation As a Later-in-Life Treatment

Conditions
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Mild Cognitive Impairment, Dementia, Amnestic Mild Cognitive Impairment - aMCI

Intervention / Treatment
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* Device: NeuroElectric StarStim
* Device: Sham Treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Active diagnosis of mild cognitive impairment or dementia, Female and male subjects, All races/ethnicities, Age 55 years and older, Fluent in English, Exclusion Criteria: Lifetime history of major neurologic syndromes (e.g., epilepsy, brain tumor, etc), Substance use disorder within the past year, Has metal fragments in skull/head, Current vision or hearing impairment that interferes with testing, Current medication use known to alter HD-tDCS reactivity

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: Crossover Assignment
Interventional Model Description: In Phase 1, there will be two treatment arms (active and sham). All subjects will have the option to complete active stimulation of HD-tDCS. Those assigned to the sham condition group will have the option to return for active treatment in Phase 2. Each HD-tDCS condition is comprised of 10 days of active or sham stimulation targeting the pre-SMA (supplemental motor area)/sACC (subgenual anterior cingulate cortex) followed by neuropsychological testing after completion of the last session.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Phase 1: Active Treatment<br>Participants will receive 10 sessions of active stimulation (1 mA anodal HD-tDCS targeting preSMA/dACC for 20 min) across 2 weeks. Word retrieval and other cognitive tasks will be completed at baseline, immediate follow-up after session 10, and a 2-month follow-up | Device: NeuroElectric StarStim<br>* 10 sessions of active stimulation (1 mA anodal HD-tDCS targeting preSMA/dACC for 20 min) across 2 weeks<br>* Other names: Phase 1/2 Active;|
| Sham Comparator: Phase 1: Sham Treatment<br>Participants will receive 10 sessions of sham stimulation across 2 weeks. Word retrieval and other cognitive tasks will be completed at baseline, immediate follow-up after session 10, and a 2-month follow-up | Device: Sham Treatment<br>* Sham stimulation for 10 sessions over 2 weeks<br>|
| Active Comparator: Phase 2: Active Treatment<br>For Phase 2, participants randomized into the sham group will have the opportunity to return after 2 months from completing Phase 1. They will receive the active treatment while being unblinded to their treatment condition. Following 10 active treatment sessions, word retrieval and other cognitive tasks will again be completed immediately following the last HD-tDCS session and then a 2-month follow-up. | Device: NeuroElectric StarStim<br>* 10 sessions of active stimulation (1 mA anodal HD-tDCS targeting preSMA/dACC for 20 min) across 2 weeks<br>* Other names: Phase 1/2 Active;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Rey Auditory Verbal Learning Test Score | The RAVLT is a verbal episodic memory test that is sensitive to mesial and lateral verbal episodic memory circuit dysfunction. The primary outcome measure for this task is the total number of items immediately recalled during the learning trials and after the 20 minute delayed recall trial. Changes in scores from baseline to testing immediately following the completion of the condition will be examined as well as from baseline to 8 months post-treatment. RAVLT : Rey Auditory Verbal Learning Test, 0-15 score for each trial, higher scores reflect better performance | Pre-treatment, post-treatment (an average of 2 weeks), and 8 weeks post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Delis Kaplan Executive Function System (DKEFS) Verbal Fluency Test | The DKEFS Verbal Fluency Test is a measure of word retrieval. The task has 3 conditions each lasting 60 seconds, requiring the subject to name words by phonemes, semantic categories, and then switching between two semantic categories. The outcome measure for this task is the total words named for each of the 3 conditions. Changes in scores from baseline to testing immediately following the completion of each condition will be examined as well as from baseline to 8 months post-treatment. DKEFS: Delis-Kaplan Executive Function System Verbal Fluency Test, 0-no upper limit for each trial, higher scores reflect better performance | Pre-treatment, post-treatment (an average of 2 weeks), and 8 weeks post-treatment | 
| Changes in Boston Naming Test Short Form | The Boston Naming Test Short Form has 30 pictures of common objects that upon seeing each picture, individuals need to name the object as soon as one can. The outcome measure for this task is the number of correctly named items. Changes in scores from baseline to testing immediately following the completion of condition will be examined as well as from baseline to 8 months post-treatment. BNT: Boston Naming Test - Short Form, 0-30 score, higher scores reflect better performance | Pre-treatment, post-treatment (an average of 2 weeks), and 8 weeks post-treatment |