Cathodal tDCS in MCI: A Randomized, Double-Blind, Sham-Controlled Pilot Study

• Sponsor: Mayo Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT03521089
• Collaborator: (none)
• Enrollment: 16
• Location: 1
• Arms: 2
• Actual Duration (Months): 15.3
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

This study evaluates the application of non-invasive brain stimulation in the treatment of Mild Cognitive Impairment (MCI) in adults aged 55-85. Half of the participants will receive transcranial direct current stimulation (tDCS), while the other half will receive sham (like placebo) stimulation.

Condition or Disease	Intervention/Treatment	Phase
Mild Cognitive Impairment; Cognitive Impairment; Neurocognitive Dysfunction	Device: Soterix Medical 1x1 Low Intensity Transcranial Electrical Stimulator (tES) Model 2001	N/A

Detailed Description

The purpose of this study is to investigate whether giving transcranial direct current stimulation (tDCS) treatment using an investigational device called the Soterix tES Device (tDCS device) on the right side of the brain can improve performance on cognitive tests. Investigational means that the tDCS device is not approved by the U.S. Food and Drug Administration (FDA) for the use in this study.

tDCS is a non-invasive way to electrically stimulate the brain. The tDCS device is portable and runs on two 9-volt batteries. Electrodes from the tDCS device carry weak electrical current through the scalp and skull and into the brain. When the direction of the electric current flow is called cathodal, the brain under the site of stimulation reduces its activity.

When tasks are performed, certain parts of the brain are activated. Research studies have shown that younger adults and older adults activate similar parts of the brain when performing the same task (a memory task, for example). However, other researchers found older adults who scored worse on memory tasks, and those with Mild Cognitive Impairment, activated an additional part of the brain so both sides of the brain are activated. Researchers are not sure whether this additional activation is helpful or not. Investigators in this study believe that this extra activation may be contributing to worse performance on tasks.

It may be possible to use tDCS to reduce the brain activity on the extra activation (right) side in older adults, to resemble an activation pattern seen in younger adults (or higher scoring cohort). Using cathodal tDCS to reduce brain activity might help the brain in performing tasks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized 1:1 to active or sham transcranial direct current stimulation (tDCS) interventionRandomized 1:1 to active or sham transcranial direct current stimulation (tDCS) intervention
• Masking: Double (Participant, Investigator)
• Masking Description: Double-blind
• Primary Purpose: Treatment
• Official Title: Cathodal Transcranial Direct Current Stimulation (tDCS) in Mild Cognitive Impairment (MCI): A Randomized, Double-Blind, Sham-Controlled Pilot Study
• Actual Study Start Date: Feb 20, 2018
• Actual Primary Completion Date: May 31, 2019
• Actual Study Completion Date: May 31, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Active tDCS Active tDCS uses the Soterix Medical 1x1 Low Intensity Transcranial Electrical Stimulator (tES) Model 2001. The active tDCS intervention include stimulation for 15 minutes at 1mA. The cathode electrode will be placed over the right dorsolateral prefrontal cortex with reference electrode (anode) over the left dorsolateral prefrontal cortex. Both electrodes are covered by saline-soaked sponges that are held against the scalp by a pair of large, adjustable head straps. Treatment sessions will last for 15 minutes. 5 consecutive treatment sessions will be completed within 1 week.	Device: Soterix Medical 1x1 Low Intensity Transcranial Electrical Stimulator (tES) Model 2001; Transcranial direct current stimulation works by sending constant, low direct current through the electrodes. When these electrodes are placed in the region of interest, the current induces intracerebral current flow. This current flow then either increases or decreases the neuronal excitability in the specific area being stimulated based on which type of stimulation is being used. This change of neuronal excitability leads to alteration of brain function, which can be used in various therapies as well as to provide more information about the functioning of the human brain.; Other Names: Soterix tDCS Transcranial direct current stimulation Non-invasive brain stimulation Cathodal tDCS
Sham Comparator: Sham tDCS Sham tDCS uses the Soterix Medical 1x1 Low Intensity Transcranial Electrical Stimulator (tES) Model 2001. The sham tDCS intervention lasts for 15 minutes. The cathode electrode will be placed over the right dorsolateral prefrontal cortex with reference electrode (anode) over the left dorsolateral prefrontal cortex. Both electrodes are covered by saline-soaked sponges that are held against the scalp by a pair of large, adjustable head straps. Treatment sessions will last for 15 minutes. 5 consecutive treatment sessions will be completed within 1 week.	Device: Soterix Medical 1x1 Low Intensity Transcranial Electrical Stimulator (tES) Model 2001; Transcranial direct current stimulation works by sending constant, low direct current through the electrodes. When these electrodes are placed in the region of interest, the current induces intracerebral current flow. This current flow then either increases or decreases the neuronal excitability in the specific area being stimulated based on which type of stimulation is being used. This change of neuronal excitability leads to alteration of brain function, which can be used in various therapies as well as to provide more information about the functioning of the human brain.; Other Names: Soterix tDCS Transcranial direct current stimulation Non-invasive brain stimulation Cathodal tDCS

Outcome Measures

Primary Outcome Measures

1. Change in Flanker Inhibitory Control and Attention Test Scores [Baseline, 1-month post intervention]

   Post-intervention score comparison between the intervention and control group measured by the NIH Toolbox Cognition Battery Test. The NIH Toolbox Cognition Battery Test is a comprehensive set of neuro behavioral measurements used to assess cognitive, sensory and motor functions where a higher composite score equals better cognitive performance. The NIH Toolbox Cognitive Scores used the Fully Adjusted Scale score (also referred to as the fully corrected T-score) with a mean of 50 and standard deviation of 10.

2. Change in Picture Vocabulary Test Scores [Baseline, 1 month post intervention]

   Post-intervention score comparison between the intervention and control group measured by the NIH Toolbox Cognition Battery Test. The NIH Toolbox Cognition Battery Test is a comprehensive set of neuro behavioral measurements used to assess cognitive, sensory and motor functions where a higher composite score equals better cognitive performance. The NIH Toolbox Cognitive Scores used the Fully Adjusted Scale score (also referred to as the fully corrected T-score) with a mean of 50 and standard deviation of 10.

3. Change in List Sorting Working Memory Test Scores [Baseline, 1 month post intervention]

   Post-intervention score comparison between the intervention and control group measured by the NIH Toolbox Cognition Battery Test. The NIH Toolbox Cognition Battery Test is a comprehensive set of neuro behavioral measurements used to assess cognitive, sensory and motor functions where a higher composite score equals better cognitive performance. The NIH Toolbox Cognitive Scores used the Fully Adjusted Scale score (also referred to as the fully corrected T-score) with a mean of 50 and standard deviation of 10.

4. Change in Dimensional Change Card Sort Test [Baseline, 1 month post intervention]

   Post-intervention score comparison between the intervention and control group measured by the NIH Toolbox Cognition Battery Test. The NIH Toolbox Cognition Battery Test is a comprehensive set of neuro behavioral measurements used to assess cognitive, sensory and motor functions where a higher composite score equals better cognitive performance. The NIH Toolbox Cognitive Scores used the Fully Adjusted Scale score (also referred to as the fully corrected T-score) with a mean of 50 and standard deviation of 10.

5. Change in Pattern Comparison Processing Speed Test Scores [Baseline, 1 month post intervention]

   Post-intervention score comparison between the intervention and control group measured by the NIH Toolbox Cognition Battery Test. The NIH Toolbox Cognition Battery Test is a comprehensive set of neuro behavioral measurements used to assess cognitive, sensory and motor functions where a higher composite score equals better cognitive performance. The NIH Toolbox Cognitive Scores used the Fully Adjusted Scale score (also referred to as the fully corrected T-score) with a mean of 50 and standard deviation of 10.

6. Change in Picture Sequence Memory Test v2.1 Score [Baseline, 1 month post intervention]

   Post-intervention score comparison between the intervention and control group measured by the NIH Toolbox Cognition Battery Test. The NIH Toolbox Cognition Battery Test is a comprehensive set of neuro behavioral measurements used to assess cognitive, sensory and motor functions where a higher composite score equals better cognitive performance. The NIH Toolbox Cognitive Scores used the Fully Adjusted Scale score (also referred to as the fully corrected T-score) with a mean of 50 and standard deviation of 10.

7. Change in Oral Reading Recognition Test Score [Baseline, 1 month post intervention]

   Post-intervention score comparison between the intervention and control group measured by the NIH Toolbox Cognition Battery Test. The NIH Toolbox Cognition Battery Test is a comprehensive set of neuro behavioral measurements used to assess cognitive, sensory and motor functions where a higher composite score equals better cognitive performance. The NIH Toolbox Cognitive Scores used the Fully Adjusted Scale score (also referred to as the fully corrected T-score) with a mean of 50 and standard deviation of 10.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 55 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female outpatients with confirmed MCI diagnosis

• Age 55-85

• Right handed (tested using the Edinburgh handedness inventory)

• Total PHQ-8 of ≤ 16 which signifies no severe depression

• All participants and/or caregivers must be able to provide informed consent

Exclusion Criteria:

• Neurodegenerative disease (e.g. Parkinson's, Huntington's, Multiple Sclerosis) other than MCI

• Previous brain lesion

• Intracranial abnormality such as prior stroke

• History of seizure disorder or epilepsy

• A "true" positive response, after patient clarification, to any question on the modified TMS/tDCS Adult Safety Screen questionnaire that would impact patient safety

• Any history of brain stimulation treatment (e.g., electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS), vagal nerve therapy (VNS), deep brain stimulation (DBS))

• Use of any investigational drug within 4 weeks

• Cardiac pacemakers, implanted medication pumps, intracardiac lines; acute or unstable cardiac disease; intracranial implants (e.g., aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head (exception: mouth/dental work) that cannot be safely removed

• Known or suspected pregnancy (extremely unlikely as the age range for this study is 55-85 years)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic in Arizona	Scottsdale	Arizona	United States	85259

Sponsors and Collaborators

• Mayo Clinic

Investigators

• Principal Investigator: Yonas E Geda, MD, MSc, Mayo Clinic

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 19, 2017

More Information

Additional Information:

• Mayo Clinic Clinical Trials

Publications

None provided.

• Responsible Party: Yonas E Geda, MD, Professor of Neurology and Psychiatry, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT03521089
• Other Study ID Numbers: 16-007478
• First Posted: May 11, 2018
• Last Update Posted: Mar 25, 2020
• Last Verified: Mar 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Keywords provided by Yonas E Geda, MD, Professor of Neurology and Psychiatry, Mayo Clinic: Mild Cognitive Impairment (MCI); Transcranial Direct Current Stimulation (tDCS)
• Additional relevant MeSH terms: Cognitive Dysfunction

Study Results

Participant Flow

Arm/Group Title	Active tDCS	Sham tDCS
Arm/Group Description	Active tDCS uses the Soterix Medical 1x1 Low Intensity Transcranial Electrical Stimulator (tES) Model 2001. The active tDCS intervention include stimulation for 15 minutes at 1mA. The cathode electrode will be placed over the right dorsolateral prefrontal cortex with reference electrode (anode) over the left dorsolateral prefrontal cortex. Both electrodes are covered by saline-soaked sponges that are held against the scalp by a pair of large, adjustable head straps. Treatment sessions will last for 15 minutes. 5 consecutive treatment sessions will be completed within 1 week.	Sham tDCS uses the Soterix Medical 1x1 Low Intensity Transcranial Electrical Stimulator (tES) Model 2001. The sham tDCS intervention lasts for 15 minutes. The cathode electrode will be placed over the right dorsolateral prefrontal cortex with reference electrode (anode) over the left dorsolateral prefrontal cortex. Both electrodes are covered by saline-soaked sponges that are held against the scalp by a pair of large, adjustable head straps. Treatment sessions will last for 15 minutes. 5 consecutive treatment sessions will be completed within 1 week.
Period Title: Overall Study
STARTED	8	8
COMPLETED	8	8
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Active tDCS	Sham tDCS	Total
Arm/Group Description	Active tDCS uses the Soterix Medical 1x1 Low Intensity Transcranial Electrical Stimulator (tES) Model 2001. The active tDCS intervention include stimulation for 15 minutes at 1mA. The cathode electrode will be placed over the right dorsolateral prefrontal cortex with reference electrode (anode) over the left dorsolateral prefrontal cortex. Both electrodes are covered by saline-soaked sponges that are held against the scalp by a pair of large, adjustable head straps. Treatment sessions will last for 15 minutes. 5 consecutive treatment sessions will be completed within 1 week.	Sham tDCS uses the Soterix Medical 1x1 Low Intensity Transcranial Electrical Stimulator (tES) Model 2001. The sham tDCS intervention lasts for 15 minutes. The cathode electrode will be placed over the right dorsolateral prefrontal cortex with reference electrode (anode) over the left dorsolateral prefrontal cortex. Both electrodes are covered by saline-soaked sponges that are held against the scalp by a pair of large, adjustable head straps. Treatment sessions will last for 15 minutes. 5 consecutive treatment sessions will be completed within 1 week.	Total of all reporting groups
Overall Participants	8	8	16
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	70.0 (5.7)	70.0 (9.5)	70.0 (7.5)
Sex: Female, Male (Count of Participants)
Female	2 25%	7 87.5%	9 56.3%
Male	6 75%	1 12.5%	7 43.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 12.5%	0 0%	1 6.3%
Not Hispanic or Latino	7 87.5%	8 100%	15 93.8%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	8 100%	8 100%	16 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	8 100%	8 100%	16 100%

Outcome Measures

1. Primary Outcome

Title	Change in Flanker Inhibitory Control and Attention Test Scores
Description	Post-intervention score comparison between the intervention and control group measured by the NIH Toolbox Cognition Battery Test. The NIH Toolbox Cognition Battery Test is a comprehensive set of neuro behavioral measurements used to assess cognitive, sensory and motor functions where a higher composite score equals better cognitive performance. The NIH Toolbox Cognitive Scores used the Fully Adjusted Scale score (also referred to as the fully corrected T-score) with a mean of 50 and standard deviation of 10.
Time Frame	Baseline, 1-month post intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active tDCS	Sham tDCS
Arm/Group Description	Active tDCS uses the Soterix Medical 1x1 Low Intensity Transcranial Electrical Stimulator (tES) Model 2001. The active tDCS intervention include stimulation for 15 minutes at 1mA. The cathode electrode will be placed over the right dorsolateral prefrontal cortex with reference electrode (anode) over the left dorsolateral prefrontal cortex. Both electrodes are covered by saline-soaked sponges that are held against the scalp by a pair of large, adjustable head straps. Treatment sessions will last for 15 minutes. 5 consecutive treatment sessions will be completed within 1 week.	Sham tDCS uses the Soterix Medical 1x1 Low Intensity Transcranial Electrical Stimulator (tES) Model 2001. The sham tDCS intervention lasts for 15 minutes. The cathode electrode will be placed over the right dorsolateral prefrontal cortex with reference electrode (anode) over the left dorsolateral prefrontal cortex. Both electrodes are covered by saline-soaked sponges that are held against the scalp by a pair of large, adjustable head straps. Treatment sessions will last for 15 minutes. 5 consecutive treatment sessions will be completed within 1 week.
Measure Participants	8	8
Least Squares Mean (Standard Error) [score on a scale]	35.1 (1.3)	41.5 (1.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Active tDCS, Sham tDCS
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0039
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Active tDCS
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.00
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Sham tDCS
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0156
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Primary Outcome

Title	Change in Picture Vocabulary Test Scores
Description	Post-intervention score comparison between the intervention and control group measured by the NIH Toolbox Cognition Battery Test. The NIH Toolbox Cognition Battery Test is a comprehensive set of neuro behavioral measurements used to assess cognitive, sensory and motor functions where a higher composite score equals better cognitive performance. The NIH Toolbox Cognitive Scores used the Fully Adjusted Scale score (also referred to as the fully corrected T-score) with a mean of 50 and standard deviation of 10.
Time Frame	Baseline, 1 month post intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active tDCS	Sham tDCS
Arm/Group Description	Active tDCS uses the Soterix Medical 1x1 Low Intensity Transcranial Electrical Stimulator (tES) Model 2001. The active tDCS intervention include stimulation for 15 minutes at 1mA. The cathode electrode will be placed over the right dorsolateral prefrontal cortex with reference electrode (anode) over the left dorsolateral prefrontal cortex. Both electrodes are covered by saline-soaked sponges that are held against the scalp by a pair of large, adjustable head straps. Treatment sessions will last for 15 minutes. 5 consecutive treatment sessions will be completed within 1 week.	Sham tDCS uses the Soterix Medical 1x1 Low Intensity Transcranial Electrical Stimulator (tES) Model 2001. The sham tDCS intervention lasts for 15 minutes. The cathode electrode will be placed over the right dorsolateral prefrontal cortex with reference electrode (anode) over the left dorsolateral prefrontal cortex. Both electrodes are covered by saline-soaked sponges that are held against the scalp by a pair of large, adjustable head straps. Treatment sessions will last for 15 minutes. 5 consecutive treatment sessions will be completed within 1 week.
Measure Participants	8	8
Least Squares Mean (Standard Error) [score on a scale]	52.0 (1.2)	52.0 (1.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Active tDCS, Sham tDCS
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9674
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Active tDCS
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0938
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Sham tDCS
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2500
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

3. Primary Outcome

Title	Change in List Sorting Working Memory Test Scores
Description	Post-intervention score comparison between the intervention and control group measured by the NIH Toolbox Cognition Battery Test. The NIH Toolbox Cognition Battery Test is a comprehensive set of neuro behavioral measurements used to assess cognitive, sensory and motor functions where a higher composite score equals better cognitive performance. The NIH Toolbox Cognitive Scores used the Fully Adjusted Scale score (also referred to as the fully corrected T-score) with a mean of 50 and standard deviation of 10.
Time Frame	Baseline, 1 month post intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active tDCS	Sham tDCS
Arm/Group Description	Active tDCS uses the Soterix Medical 1x1 Low Intensity Transcranial Electrical Stimulator (tES) Model 2001. The active tDCS intervention include stimulation for 15 minutes at 1mA. The cathode electrode will be placed over the right dorsolateral prefrontal cortex with reference electrode (anode) over the left dorsolateral prefrontal cortex. Both electrodes are covered by saline-soaked sponges that are held against the scalp by a pair of large, adjustable head straps. Treatment sessions will last for 15 minutes. 5 consecutive treatment sessions will be completed within 1 week.	Sham tDCS uses the Soterix Medical 1x1 Low Intensity Transcranial Electrical Stimulator (tES) Model 2001. The sham tDCS intervention lasts for 15 minutes. The cathode electrode will be placed over the right dorsolateral prefrontal cortex with reference electrode (anode) over the left dorsolateral prefrontal cortex. Both electrodes are covered by saline-soaked sponges that are held against the scalp by a pair of large, adjustable head straps. Treatment sessions will last for 15 minutes. 5 consecutive treatment sessions will be completed within 1 week.
Measure Participants	8	8
Least Squares Mean (Standard Error) [score on a scale]	60.5 (1.9)	51.8 (1.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Active tDCS, Sham tDCS
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0067
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Active tDCS
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0313
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Sham tDCS
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7500
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

4. Primary Outcome

Title	Change in Dimensional Change Card Sort Test
Description	Post-intervention score comparison between the intervention and control group measured by the NIH Toolbox Cognition Battery Test. The NIH Toolbox Cognition Battery Test is a comprehensive set of neuro behavioral measurements used to assess cognitive, sensory and motor functions where a higher composite score equals better cognitive performance. The NIH Toolbox Cognitive Scores used the Fully Adjusted Scale score (also referred to as the fully corrected T-score) with a mean of 50 and standard deviation of 10.
Time Frame	Baseline, 1 month post intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active tDCS	Sham tDCS
Arm/Group Description	Active tDCS uses the Soterix Medical 1x1 Low Intensity Transcranial Electrical Stimulator (tES) Model 2001. The active tDCS intervention include stimulation for 15 minutes at 1mA. The cathode electrode will be placed over the right dorsolateral prefrontal cortex with reference electrode (anode) over the left dorsolateral prefrontal cortex. Both electrodes are covered by saline-soaked sponges that are held against the scalp by a pair of large, adjustable head straps. Treatment sessions will last for 15 minutes. 5 consecutive treatment sessions will be completed within 1 week.	Sham tDCS uses the Soterix Medical 1x1 Low Intensity Transcranial Electrical Stimulator (tES) Model 2001. The sham tDCS intervention lasts for 15 minutes. The cathode electrode will be placed over the right dorsolateral prefrontal cortex with reference electrode (anode) over the left dorsolateral prefrontal cortex. Both electrodes are covered by saline-soaked sponges that are held against the scalp by a pair of large, adjustable head straps. Treatment sessions will last for 15 minutes. 5 consecutive treatment sessions will be completed within 1 week.
Measure Participants	8	8
Least Squares Mean (Standard Error) [score on a scale]	43.7 (2.8)	48.0 (2.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Active tDCS, Sham tDCS
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3069
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Active tDCS
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1875
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Sham tDCS
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7188
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

5. Primary Outcome

Title	Change in Pattern Comparison Processing Speed Test Scores
Description	Post-intervention score comparison between the intervention and control group measured by the NIH Toolbox Cognition Battery Test. The NIH Toolbox Cognition Battery Test is a comprehensive set of neuro behavioral measurements used to assess cognitive, sensory and motor functions where a higher composite score equals better cognitive performance. The NIH Toolbox Cognitive Scores used the Fully Adjusted Scale score (also referred to as the fully corrected T-score) with a mean of 50 and standard deviation of 10.
Time Frame	Baseline, 1 month post intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active tDCS	Sham tDCS
Arm/Group Description	Active tDCS uses the Soterix Medical 1x1 Low Intensity Transcranial Electrical Stimulator (tES) Model 2001. The active tDCS intervention include stimulation for 15 minutes at 1mA. The cathode electrode will be placed over the right dorsolateral prefrontal cortex with reference electrode (anode) over the left dorsolateral prefrontal cortex. Both electrodes are covered by saline-soaked sponges that are held against the scalp by a pair of large, adjustable head straps. Treatment sessions will last for 15 minutes. 5 consecutive treatment sessions will be completed within 1 week.	Sham tDCS uses the Soterix Medical 1x1 Low Intensity Transcranial Electrical Stimulator (tES) Model 2001. The sham tDCS intervention lasts for 15 minutes. The cathode electrode will be placed over the right dorsolateral prefrontal cortex with reference electrode (anode) over the left dorsolateral prefrontal cortex. Both electrodes are covered by saline-soaked sponges that are held against the scalp by a pair of large, adjustable head straps. Treatment sessions will last for 15 minutes. 5 consecutive treatment sessions will be completed within 1 week.
Measure Participants	8	8
Least Squares Mean (Standard Error) [score on a scale]	46.6 (3.0)	51.6 (3.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Active tDCS, Sham tDCS
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2609
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Active tDCS
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0313
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Sham tDCS
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0156
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

6. Primary Outcome

Title	Change in Picture Sequence Memory Test v2.1 Score
Description	Post-intervention score comparison between the intervention and control group measured by the NIH Toolbox Cognition Battery Test. The NIH Toolbox Cognition Battery Test is a comprehensive set of neuro behavioral measurements used to assess cognitive, sensory and motor functions where a higher composite score equals better cognitive performance. The NIH Toolbox Cognitive Scores used the Fully Adjusted Scale score (also referred to as the fully corrected T-score) with a mean of 50 and standard deviation of 10.
Time Frame	Baseline, 1 month post intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active tDCS	Sham tDCS
Arm/Group Description	Active tDCS uses the Soterix Medical 1x1 Low Intensity Transcranial Electrical Stimulator (tES) Model 2001. The active tDCS intervention include stimulation for 15 minutes at 1mA. The cathode electrode will be placed over the right dorsolateral prefrontal cortex with reference electrode (anode) over the left dorsolateral prefrontal cortex. Both electrodes are covered by saline-soaked sponges that are held against the scalp by a pair of large, adjustable head straps. Treatment sessions will last for 15 minutes. 5 consecutive treatment sessions will be completed within 1 week.	Sham tDCS uses the Soterix Medical 1x1 Low Intensity Transcranial Electrical Stimulator (tES) Model 2001. The sham tDCS intervention lasts for 15 minutes. The cathode electrode will be placed over the right dorsolateral prefrontal cortex with reference electrode (anode) over the left dorsolateral prefrontal cortex. Both electrodes are covered by saline-soaked sponges that are held against the scalp by a pair of large, adjustable head straps. Treatment sessions will last for 15 minutes. 5 consecutive treatment sessions will be completed within 1 week.
Measure Participants	8	8
Least Squares Mean (Standard Error) [score on a scale]	45.2 (3.8)	42.8 (3.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Active tDCS, Sham tDCS
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6951
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Active tDCS
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0938
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Sham tDCS
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0938
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

7. Primary Outcome

Title	Change in Oral Reading Recognition Test Score
Description	Post-intervention score comparison between the intervention and control group measured by the NIH Toolbox Cognition Battery Test. The NIH Toolbox Cognition Battery Test is a comprehensive set of neuro behavioral measurements used to assess cognitive, sensory and motor functions where a higher composite score equals better cognitive performance. The NIH Toolbox Cognitive Scores used the Fully Adjusted Scale score (also referred to as the fully corrected T-score) with a mean of 50 and standard deviation of 10.
Time Frame	Baseline, 1 month post intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active tDCS	Sham tDCS
Arm/Group Description	Active tDCS uses the Soterix Medical 1x1 Low Intensity Transcranial Electrical Stimulator (tES) Model 2001. The active tDCS intervention include stimulation for 15 minutes at 1mA. The cathode electrode will be placed over the right dorsolateral prefrontal cortex with reference electrode (anode) over the left dorsolateral prefrontal cortex. Both electrodes are covered by saline-soaked sponges that are held against the scalp by a pair of large, adjustable head straps. Treatment sessions will last for 15 minutes. 5 consecutive treatment sessions will be completed within 1 week.	Sham tDCS uses the Soterix Medical 1x1 Low Intensity Transcranial Electrical Stimulator (tES) Model 2001. The sham tDCS intervention lasts for 15 minutes. The cathode electrode will be placed over the right dorsolateral prefrontal cortex with reference electrode (anode) over the left dorsolateral prefrontal cortex. Both electrodes are covered by saline-soaked sponges that are held against the scalp by a pair of large, adjustable head straps. Treatment sessions will last for 15 minutes. 5 consecutive treatment sessions will be completed within 1 week.
Measure Participants	8	8
Least Squares Mean (Standard Error) [score on a scale]	58.5 (1.7)	56.1 (1.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Active tDCS, Sham tDCS
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3592
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Active tDCS
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0625
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Sham tDCS
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.0000
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Adverse Events

Time Frame	A symptom-based questionnaire was used to measure adverse events and was administered at each intervention visit for the 5 consecutive days over a total study duration of 12 months.
Arm/Group Title	Active tDCS		Sham tDCS
Arm/Group Description	Active tDCS uses the Soterix Medical 1x1 Low Intensity Transcranial Electrical Stimulator (tES) Model 2001. The active tDCS intervention include stimulation for 15 minutes at 1mA. The cathode electrode will be placed over the right dorsolateral prefrontal cortex with reference electrode (anode) over the left dorsolateral prefrontal cortex. Both electrodes are covered by saline-soaked sponges that are held against the scalp by a pair of large, adjustable head straps. Treatment sessions will last for 15 minutes. 5 consecutive treatment sessions will be completed within 1 week.		Sham tDCS uses the Soterix Medical 1x1 Low Intensity Transcranial Electrical Stimulator (tES) Model 2001. The sham tDCS intervention lasts for 15 minutes. The cathode electrode will be placed over the right dorsolateral prefrontal cortex with reference electrode (anode) over the left dorsolateral prefrontal cortex. Both electrodes are covered by saline-soaked sponges that are held against the scalp by a pair of large, adjustable head straps. Treatment sessions will last for 15 minutes. 5 consecutive treatment sessions will be completed within 1 week.
All Cause Mortality
	Active tDCS		Sham tDCS
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)
Serious Adverse Events
	Active tDCS		Sham tDCS
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)
Other (Not Including Serious) Adverse Events
	Active tDCS		Sham tDCS
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.