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| ID | Type | Description | Link |
|---|---|---|---|
| 1R01AG058724 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute on Aging (NIA) | NIH |
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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).
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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sham Stimulation | Sham Comparator | Sham (placebo) dose of HD-tDCS treatment for 30 minutes, for between 5-30 sessions. |
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| 1 mA Dosage Stimulation | Experimental | 1 milliAmp dose of HD-tDCS treatment for 30 minutes, for between 5-30 sessions. |
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| 2 mA Dosage Stimulation | Experimental | 2 milliAmp dose of HD-tDCS treatment for 30 minutes, for between 5-30 sessions. |
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| 3 mA Dosage Stimulation | Experimental | 3 milliAmp dose of HD-tDCS treatment for 30 minutes, for between 5-30 sessions. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 1 mA HD-tDCS | Device | Participants will receive HD-tDCS at 1 mA for 30 minutes, for between 5-30 sessions. |
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| Measure | Description | Time Frame |
|---|---|---|
| Change in Lateral Temporal Cortex Connectivity | Primary outcome focuses on default mode network (DMN) between-network functional connectivity because the lateral temporal cortex is a core component of the DMN. Between-network functional connectivity is estimated from fMRI data as strength of temporal coupling between the DMN and other high-level (association) brain networks. For each participant and time point, correlation-based connectivity (Pearson r; Fisher r-to-z transformed; arbitrary units) computed between DMN regions and other regions of the association cortex defined using standard functional atlas. Higher values reflect stronger functional connectivity between DMN and other regions. A Z-score's range is infinite. Expected value is between -3 to 3. Analyses conducted separately for amyloid negative (A-) and amyloid positive (A+) participants. Post Intervention data collection was on day 5 of treatment. Post-Expansion (PE) appointments were not consecutive. Mean time between enrollment and PE was 10 wks, longest was 43 wks. | Change from Baseline to Post-Intervention (after tDCS Session 5 - day 5 of treatment) and from Baseline to Post-Expansion (after the participant's final tDCS session beyond Session 5, up to 43 weeks). |
| Measure | Description | Time Frame |
|---|---|---|
| Self-Report of Contentment With Memory | The Multifactorial Memory Questionnaire (MMQ) consists of three scales measuring separate aspects of metamemory. Items are rated on a 5-point Likert scale (0-4) based on the test taker's experiences over the previous two weeks. MMQ-Satisfaction (formerly called MMQ-Contentment) scale measures satisfaction, concern, and overall appraisal of one's own memory. Each of 18 statements is rated based on degree of agreement. The score range is 0 to 72, with higher scores indicating a higher degree of satisfaction. Post Intervention data collection was on day 5 of treatment. Post-Expansion (PE) appointments were not consecutive. Mean time between enrollment and PE was 10 wks, longest was 43 wks. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Inhibition Ability | A priori intent to measure through change in the NIH Toolbox Flanker Inhibitory Control and Attention Test Score | Baseline and post-intervention (after tDCS sessions 5 & 30) |
| Change in Conceptualization Ability |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Benjamin Hampstead, PhD | Associate Professor | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Michigan | Ann Arbor | Michigan | 48105 | United States |
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Number enrolled reflects the number of people who consented and were determined to be eligible for participation.
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| ID | Title | Description |
|---|---|---|
| FG000 | Sham Stimulation | Sham (placebo) dose of HD-tDCS treatment for 30 minutes, for between 5-30 sessions. Sham: Participants will receive sham (placebo) HD-tDCS for 30 minutes, for between 5-30 sessions. |
| FG001 | 1 mA Dosage Stimulation | 1 milliAmp dose of HD-tDCS treatment for 30 minutes, for between 5-30 sessions. 1 mA HD-tDCS: Participants will receive HD-tDCS at 1 mA for 30 minutes, for between 5-30 sessions. |
| FG002 | 2 mA Dosage Stimulation | 2 milliAmp dose of HD-tDCS treatment for 30 minutes, for between 5-30 sessions. 2 mA HD-tDCS: Participants will receive HD-tDCS at 2 mA for 30 minutes, for between 5-30 sessions. |
| FG003 | 3 mA Dosage Stimulation | 3 milliAmp dose of HD-tDCS treatment for 30 minutes, for between 5-30 sessions. 3 mA HD-tDCS: Participants will receive HD-tDCS at 3 mA for 30 minutes, for between 5-30 sessions. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Main Study |
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| Voluntary Study Expansion |
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| ID | Title | Description |
|---|---|---|
| BG000 | Sham Stimulation | Sham (placebo) dose of HD-tDCS treatment for 30 minutes, for between 5-30 sessions. Sham: Participants will receive sham (placebo) HD-tDCS for 30 minutes, for between 5-30 sessions. |
| BG001 | 1 mA Dosage Stimulation |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Lateral Temporal Cortex Connectivity | Primary outcome focuses on default mode network (DMN) between-network functional connectivity because the lateral temporal cortex is a core component of the DMN. Between-network functional connectivity is estimated from fMRI data as strength of temporal coupling between the DMN and other high-level (association) brain networks. For each participant and time point, correlation-based connectivity (Pearson r; Fisher r-to-z transformed; arbitrary units) computed between DMN regions and other regions of the association cortex defined using standard functional atlas. Higher values reflect stronger functional connectivity between DMN and other regions. A Z-score's range is infinite. Expected value is between -3 to 3. Analyses conducted separately for amyloid negative (A-) and amyloid positive (A+) participants. Post Intervention data collection was on day 5 of treatment. Post-Expansion (PE) appointments were not consecutive. Mean time between enrollment and PE was 10 wks, longest was 43 wks. | Analysis included all randomized participants with usable MRI data and available amyloid PET biomarker data from either baseline, relevant end point, or both. Data was analyzed using a mixed model, rather than paired analysis. Therefore, in some cases, number analyzed exceeds number of participants in expansion period. Participants were excluded when MRI data could not be reliably processed (segmentation/quality failures or excessive head motion) or amyloid PET data was not acquired. | Posted | Mean | 95% Confidence Interval | Fisher z-transformed Pearson correlation |
Up to 43 weeks)
Participants were followed during their participation in the trial. This duration varied significantly between participants due to participant availability and COVID restrictions.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Sham Stimulation | Sham (placebo) dose of HD-tDCS treatment for 30 minutes, for between 5-30 sessions. Sham: Participants will receive sham (placebo) HD-tDCS for 30 minutes, for between 5-30 sessions. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Fall post enrollment and prior to stimulation treatment | General disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | General disorders | Systematic Assessment | This data was collected via questionnaire prior to and after each treatment. Data represents all symptoms reported by participants at any time point. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Benjamin Hampstead | University of Michigan | 734-936-6185 | bhampste@med.umich.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 23, 2025 | Dec 5, 2025 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jan 23, 2025 | Dec 5, 2025 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D060825 | Cognitive Dysfunction |
| D003704 | Dementia |
| ID | Term |
|---|---|
| D003072 | Cognition Disorders |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D001927 | Brain Diseases |
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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.
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| 2 mA HD-tDCS | Device | Participants will receive HD-tDCS at 2 mA for 30 minutes, for between 5-30 sessions. |
|
| 3 mA HD-tDCS | Device | Participants will receive HD-tDCS at 3 mA for 30 minutes, for between 5-30 sessions. |
|
| Sham | Device | Participants will receive sham (placebo) HD-tDCS for 30 minutes, for between 5-30 sessions. |
|
| Change from Baseline to Post-Intervention (after tDCS Session 5 - day 5 of treatment) and from Baseline to Post-Expansion (after the participant's final tDCS session beyond Session 5, up to 43 weeks). |
| Self-Report of Memory Mistakes | Multifactorial Memory Questionnaire (MMQ) Ability Score - This scale measures self-perception of everyday memory ability. Respondents rate how often they experienced each of 20 common memory mistakes over the previous two weeks. The score range is 0 to 80, with higher scores indicating better self-reported memory ability. Post Intervention data collection was on day 5 of treatment. Post-Expansion (PE) appointments were not consecutive. Mean time between enrollment and PE was 10 wks, longest was 43 wks. | Change from Baseline to Post-Intervention (after tDCS Session 5 - day 5 of treatment) and from Baseline to Post-Expansion (after the participant's final tDCS session beyond Session 5, up to 43 weeks). |
| Self-Report of Memory Strategies Used | Multifactorial Memory Questionnaire (MMQ) Strategies Score - This scale measures the use of practical memory strategies and aids in day-to-day life. Respondents rate how often they used each of 19 memory strategies over the previous two weeks. The score range is 0 to 76, with higher scores indicating greater use of memory strategies. Post Intervention data collection was on day 5 of treatment. Post-Expansion (PE) appointments were not consecutive. Mean time between enrollment and PE was 10 wks, longest was 43 wks. | Change from Baseline to Post-Intervention (after tDCS Session 5 - day 5 of treatment) and from Baseline to Post-Expansion (after the participant's final tDCS session beyond Session 5, up to 43 weeks). |
| Change in Memory Functioning | The Repeatable Battery of the Assessment of Neuropsychological Status (RBANS) is a comprehensive neuropsychological battery for the evaluation of global cognition. The delayed memory section is a measure of delayed recall and recognition for verbal and visual information. It includes the subtests List Recall, List Recognition, Story Memory, and Figure Recall. Low scores on this index indicate difficulties with recognition and retrieval of information from long-term memory stores This index is composed of both auditory and visual measures; therefore, a severe deficit in language, auditory processing, or visual functioning may impact one of the measures more than the other. Analysis included the sum of the raw scores for each of the delayed memory subtests, with possible scores ranging from 0 to 62. Post Intervention data collection was on day 5 of treatment. Post-Expansion (PE) appointments were not consecutive. Mean time between enrollment and PE was 10 wks, longest was 43 wks. | Change from Baseline to Post-Intervention (after tDCS Session 5 - day 5 of treatment) and from Baseline to Post-Expansion (after the participant's final tDCS session beyond Session 5, up to 43 weeks). |
| Change in Overall Fluid Cognitive Abilities | Cognitive function was determined using the NIH Toolbox-Cognition Battery computerized tests, specifically the Fluid composite score. It is derived by averaging the subtests in the Fluid domain to achieve an overall standard score. Fully Corrected T-scores are adjusted for for age, gender, race/ethnicity, and educational attainment. The score compares the score of the participant to those in the NIH Toolbox nationally representative normative sampling. The T-score has a mean of 50 in the general population and a SD of 10. Scores higher than the mean indicate better performance. Post Intervention data collection was on day 5 of treatment. Post-Expansion (PE) appointments were not consecutive. Mean time between enrollment and PE was 10 wks, longest was 43 wks. | Change from Baseline to Post-Intervention (after tDCS Session 5 - day 5 of treatment) and from Baseline to Post-Expansion (after the participant's final tDCS session beyond Session 5, up to 43 weeks). |
| Cumulative Working Memory Effects of HD-tDCS Across Treatment Sessions | The n-back test is a working memory task where participants identify stimulus that matches stimulus experienced "n" steps back. Participants performed a 2-back test, in which they were asked to remember and press a button when shown a stimulus that appeared 2 steps before the current one (e.g. square, circle, square). The number of correct and incorrect identifications are normalized (z-score). Total score is the z-score of correct button presses minus the z-score of incorrect button presses. A higher score (d') reflects better working memory performance. Possible scores range from -4.85 to 4.85. Positive change (increase) in 2-back score across treatment sessions indicates improvement in working memory performance. Data is shown as the mean slope calculation of participants across first 5 days of treatment and across all treatments, x=days of treatment, y=n-back score. Post-Expansion (PE) appointments were not consecutive. Mean time between enrollment and PE was 10 wks. | Change from Baseline to Post-Intervention (after tDCS Session 5 - day 5 of treatment) and from Baseline to Post-Expansion (after the participant's final tDCS session beyond Session 5, up to 43 weeks). |
| Cumulative Memory Accuracy Effects of HD-tDCS Across Treatment Sessions | Paired Associates task is a verbal memory task that asks participants to learn a list of word pairs. After a delay, participants are shown correct and mismatched word pairs one at a time and asked to identify if the displayed word pair was from the list they were asked to learn or not. Total accuracy is a proportion (total correct responses divided by total trials completed) ranging from 0 to 1 that measures the accuracy of a participant's responses to both correct and mismatched word pairs. Higher scores indicate better verbal memory performance, and positive changes over time indicate an improvement in verbal memory performance, measured after baseline (Session 1) and every intervention session (Sessions 2-5) Data is shown as the mean slope calculation of participants across first 5 days of treatment and across all treatments, x=days of treatment, y= total accuracy. Post-Expansion (PE) appointments were not consecutive. Mean time between enrollment and PE was 10 wks. | Change from Baseline to Post-Intervention (after tDCS Session 5 - day 5 of treatment) and from Baseline to Post-Expansion (after the participant's final tDCS session beyond Session 5, up to 43 weeks). |
| Cumulative Memory Sensitivity Effects of HD-tDCS Across Daily Sessions | Verbal memory performance for computerized Paired Associates task, summarized with a computational model (linear ballistic accumulator decision model). The model uses each participant's accuracy and reaction times across trials to estimate how efficiently they accumulate information to distinguish previously studied (target) word pairs from new (lure) pairs. Reported outcome is the average memory sensitivity score at baseline, expressed as unitless model values (scores on a scale) where higher scores indicate better discrimination, scores near zero indicate chance-level performance, and negative scores (if present) indicate performance worse than chance. | Baseline |
| Tolerability of HD-tDCS | Tolerability was assessed using the HD-tDCS Safety Questionnaire, an 11-item symptom checklist. The questionnaire assesses the presence (yes/no) of 10 specific self-reported symptoms (Itching, Burning, Tingling, Scalp Pain, Trouble Concentrating, Sleep problems, Headache, Mood Change, Neck Pain, and Other symptoms) and 1 oberserved symptom, Skin Redness. Skin Redness was excluded from this analysis as it is not related to the participant's perception of tolerability. The total score (symptom burden) was calculated by summing the number of symptoms present across the 10 items for each session. Score range: 0 to 10 symptoms, where 0 = no symptoms present and 10 = all symptoms present. Higher scores indicate worse tolerability (more symptoms experienced). Values represent the mean number of symptoms per session, calculated by averaging symptom burden scores across all post-stimulation assessments within each treatment group. | Assessed immediately after each HD-tDCS session (participants received up to 30 sessions over approximately 1-12 weeks); values represent mean symptom burden averaged across all post-stimulation assessments |
| Effectiveness of Blinding of HD-tDCS | Participant's perception of treatment assignment assessed after each stimulation session using a 3-category ordinal scale. Participants guessed whether they received: (0) Sham stimulation, (1) Don't Know, or (2) Active stimulation. The scale is ordinal with Sham < Don't Know < Active. Effective blinding is indicated by no significant difference in the distribution of perceived assignment between active and sham groups (i.e., participants in active groups cannot reliably distinguish their treatment from sham). Higher proportional odds ratios would indicate active group participants were more likely to guess "active"; lower ratios would indicate sham participants were more likely to guess "active" (paradoxical pattern suggesting convincing sham condition). | Assessed immediately after each HD-tDCS session (participants received up to 30 sessions over approximately 1-12 weeks) |
| Change in Default Mode Network Connectivity | The outcome focuses on default mode network (DMN) within-network functional connectivity. Within-network functional connectivity is estimated from fMRI data as strength of temporal coupling within DMN regions (nodes). For each participant and time point, correlation-based connectivity (Pearson r; Fisher r-to-z transformed; arbitrary units) was computed between DMN regions defined using a standard functional atlas. Higher values reflect stronger functional connectivity within DMN. A Z-score's range is infinite. Expected value is around -3 to 3. Analyses are conducted separately for amyloid negative (A-) and amyloid positive (A+) participants. Post Intervention data collection was on day 5 of treatment. Post-Expansion (PE) appointments were not consecutive. Mean time between enrollment and PE was 10 wks, longest was 43 wks. | Change from Baseline to Post-Intervention (after tDCS Session 5 - day 5 of treatment) and from Baseline to Post-Expansion (after the participant's final tDCS session beyond Session 5, up to 43 weeks). |
| Cumulative Cognitive Change Across Daily Consecutive Sessions | Measured through change in Cogstate or other comparable computerized cognitive testing scores across consecutive daily sessions. | Change from Baseline to Post-Intervention (after tDCS Session 5 - day 5 of treatment) and from Baseline to Post-Expansion (after the participant's final tDCS session beyond Session 5, up to 43 weeks). |
| Change in Global Cognition | The Repeatable Battery of the Assessment of Neuropsychological Status (RBANS) is a comprehensive neuropsychological battery for the evaluation of global cognition and has been validated in subjects with mild cognitive impairment, moderate to severe traumatic brain injuries, vascular dementias, and Alzheimer's disease. Data was analyzed using the sum of the subtest raw scores, which is an indicator of the general cognitive functioning of the examinee. Low scores suggest general cognitive impairment even when some individual subtest scores may be within normal limits. Individuals with low scores on this measure exhibit problems with attention, memory, language, and construction skills. Possible scores range from 0 to 321. Post Intervention data collection was on day 5 of treatment. Post-Expansion (PE) appointments were not consecutive. Mean time between enrollment and PE was 10 wks, longest was 43 wks. | Change from Baseline to Post-Intervention (after tDCS Session 5 - day 5 of treatment) and from Baseline to Post-Expansion (after the participant's final tDCS session beyond Session 5, up to 43 weeks). |
A priori intent to measure through change in the NIH Toolbox Dimensional Change Card Sort Test Score
| Baseline and post-intervention (after tDCS sessions 5 & 30) |
| Change in Picture Sequence Memory | A priori intent to measure through change in the NIH Toolbox Picture Sequence Memory Test Score | Baseline and post-intervention (after tDCS sessions 5 & 30) |
| Change in Working Memory Ability | A priori intent to measure through change in the NIH Toolbox List Sorting Working Memory Test Score | Baseline and post-intervention (after tDCS sessions 5 & 30) |
| Change in Processing Speed | A priori intent to measure through change in the NIH Toolbox Pattern Comparison Processing Speed Test Score | Baseline and post-intervention (after tDCS sessions 5 & 30) |
| Change in Visuospatial Functioning | Measured through change in the RBANS Visuospatial Index score | Baseline and post-intervention (after tDCS sessions 5 & 30) |
| Change in Language Functioning | Measured through change in the RBANS Language Index score | Baseline and post-intervention (after tDCS sessions 5 & 30) |
| Change in Attention | Measured through change in the RBANS Attention Index score | Baseline and post-intervention (after tDCS sessions 5 & 30) |
| Change in Memory Functioning | Measured through change in the RBANS Immediate Memory Index score | Baseline and post-intervention (after tDCS sessions 5 & 30) |
| Change in Cognitive Functioning | A priori intent to measure through changes in RBANS subtest scores | Baseline and post-intervention (after tDCS sessions 5 & 30) |
| Paused due to non-related illness, then became medically ineligible during pause |
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| COMPLETED | Attended at least the 6th visit, with the option of attending up to 30 visits. Participants who attended the 6th visit are considered to have completed the expansion regardless of whether or not they continued on to attend more optional visits. |
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| NOT COMPLETED |
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1 milliAmp dose of HD-tDCS treatment for 30 minutes, for between 5-30 sessions.
1 mA HD-tDCS: Participants will receive HD-tDCS at 1 mA for 30 minutes, for between 5-30 sessions.
| BG002 | 2 mA Dosage Stimulation | 2 milliAmp dose of HD-tDCS treatment for 30 minutes, for between 5-30 sessions. 2 mA HD-tDCS: Participants will receive HD-tDCS at 2 mA for 30 minutes, for between 5-30 sessions. |
| BG003 | 3 mA Dosage Stimulation | 3 milliAmp dose of HD-tDCS treatment for 30 minutes, for between 5-30 sessions. 3 mA HD-tDCS: Participants will receive HD-tDCS at 3 mA for 30 minutes, for between 5-30 sessions. |
| BG004 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Multifactorial Memory Questionnaire (MMQ) Subsections | The Multifactorial Memory Questionnaire (MMQ) consists of three scales measuring separate aspects of metamemory. Items are rated on a 5-point Likert scale (0-4) based on the test taker's experiences over the previous two weeks. Subsections: Contentment/Satisfaction: Score range 0-72, higher scores indicate higher degree of satisfaction Ability: Score range 0-80, higher scores indicate better self-reported memory ability. Strategies: Score range is 0 to 76, higher scores indicate greater use of memory strategies. | Analysis included all randomized participants with MMQ data and available amyloid PET biomarker data. Participants were excluded when MMQ data or amyloid PET data was not acquired. | Mean | Standard Deviation | score on a scale |
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| Baseline RBANS total | Analysis included all randomized participants with RBANS data and available amyloid PET biomarker data. Participants were excluded when RBANS data or amyloid PET data was not acquired. | Mean | Standard Deviation | Score on a scale |
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| RBANS delayed recall subscale | Analysis included all randomized participants with RBANS data and available amyloid PET biomarker data. Participants were excluded when RBANS data or amyloid PET data was not acquired. | Mean | Standard Deviation | Score on a scale |
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| NIH Toolbox Cognition Fluid Composite Score | Analysis included all randomized participants with the NIH Toolbox Cognition Fluid Composite Score and available amyloid PET biomarker data. Participants were excluded when the composite score or amyloid PET data was not acquired. | Mean | Standard Deviation | score on a scale |
|
| Lateral Temporal Cortex Connectivity | Default mode network (DMN) between-network functional connectivity from resting-state fMRI, estimated as temporal coupling between DMN and the other high-level association networks. Pearson correlations (r) between fMRI time series from DMN regions and association-cortex regions (standard functional atlas) were Fisher r-to-z transformed (Unit: Fisher z; dimensionless). Higher Fisher z=stronger positive coupling; 0=none; negative=anticorrelation. Not a psychometric T-score (not scaled to mean=50, SD=10); no clinical cutoffs. Analyses conducted separately for amyloid- and amyloid+ participants. | Analysis included all randomized participants with usable MRI data and available amyloid PET biomarker data. Participants were excluded when MRI data could not be reliably processed (segmentation/quality failures or excessive head motion) or amyloid PET data was not acquired. | Mean | Standard Deviation | Fisher z-transformed Pearson correlation |
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| Default Mode Network Connectivity | Default mode network (DMN) within-network functional connectivity from resting-state fMRI, estimated as temporal coupling among DMN regions (nodes). Pearson correlations (r) between fMRI time series from DMN regions (standard functional atlas) were computed and Fisher r-to-z transformed (Unit: Fisher z; dimensionless). Higher Fisher z=stronger positive within-DMN coupling; 0=none; negative=anticorrelation. Not a psychometric T-score (not scaled to mean=50, SD=10); no clinical cutoffs. Analyses conducted separately for amyloid- and amyloid+ participants. | Analysis included all randomized participants with usable MRI data and available amyloid PET biomarker data. Participants were excluded when MRI data could not be reliably processed (segmentation/quality failures or excessive head motion) or amyloid PET data was not acquired. | Mean | Standard Deviation | Fisher z-transformed Pearson correlation |
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| Working Memory (0-back) | Signal-detection measure of ability to discriminate targets from non-targets. d' = Z(hit rate) - Z(false alarm rate), where Z is the standard normal transform of proportions. d'=0 indicates chance-level discrimination; higher d' indicates better performance (better outcome). No established clinical cutoffs. | Analysis included all randomized participants with N-back data and available amyloid PET biomarker data. Participants were excluded when N-back data or amyloid PET data was not acquired. | Mean | Standard Deviation | d' (dimensionless) |
|
| Working Memory (2-back) | Signal-detection measure of ability to discriminate targets from non-targets. d' = Z(hit rate) - Z(false alarm rate), where Z is the standard normal transform of proportions. d'=0 indicates chance-level discrimination; higher d' indicates better performance (better outcome). No established clinical cutoffs. | Analysis included all randomized participants with N-back data and available amyloid PET biomarker data. Participants were excluded when N-back data or amyloid PET data was not acquired. | Mean | Standard Deviation | d' (dimensionless) |
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| Paired Associates Task | Total accuracy is a proportion (total correct responses divided by total trials completed) ranging from zero to one that measures the accuracy of a participant's responses to both correct and mismatched word pairs. | Analysis included all randomized participants with Paired Associates data and available amyloid PET biomarker data. Participants were excluded when Paired Associates data or amyloid PET data was not acquired. | Mean | Standard Deviation | Proportion of correct responses |
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| Change from Baseline to Post-Intervention (after tDCS Session 5 - day 5 of treatment) and from Baseline to Post-Expansion (after the participant's final tDCS session beyond Session 5, up to 43 weeks). |
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| Secondary | Self-Report of Contentment With Memory | The Multifactorial Memory Questionnaire (MMQ) consists of three scales measuring separate aspects of metamemory. Items are rated on a 5-point Likert scale (0-4) based on the test taker's experiences over the previous two weeks. MMQ-Satisfaction (formerly called MMQ-Contentment) scale measures satisfaction, concern, and overall appraisal of one's own memory. Each of 18 statements is rated based on degree of agreement. The score range is 0 to 72, with higher scores indicating a higher degree of satisfaction. Post Intervention data collection was on day 5 of treatment. Post-Expansion (PE) appointments were not consecutive. Mean time between enrollment and PE was 10 wks, longest was 43 wks. | Analysis included all randomized participants with recorded outcome measure and available amyloid PET biomarker data from either baseline, relevant end point, or both. Data was analyzed using a mixed model, rather than paired analysis. Therefore, in some cases, number analyzed exceeds number of participants in expansion period. Participants were excluded when outcome was not recorded or amyloid PET data was not acquired. | Posted | Mean | 95% Confidence Interval | score on a scale | Change from Baseline to Post-Intervention (after tDCS Session 5 - day 5 of treatment) and from Baseline to Post-Expansion (after the participant's final tDCS session beyond Session 5, up to 43 weeks). |
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| Secondary | Self-Report of Memory Mistakes | Multifactorial Memory Questionnaire (MMQ) Ability Score - This scale measures self-perception of everyday memory ability. Respondents rate how often they experienced each of 20 common memory mistakes over the previous two weeks. The score range is 0 to 80, with higher scores indicating better self-reported memory ability. Post Intervention data collection was on day 5 of treatment. Post-Expansion (PE) appointments were not consecutive. Mean time between enrollment and PE was 10 wks, longest was 43 wks. | Analysis included all randomized participants with recorded outcome measure and available amyloid PET biomarker data from either baseline, relevant end point, or both. Data was analyzed using a mixed model, rather than paired analysis. Therefore, in some cases, number analyzed exceeds number of participants in expansion period. Participants were excluded when outcome was not recorded or amyloid PET data was not acquired. | Posted | Mean | 95% Confidence Interval | score on a scale | Change from Baseline to Post-Intervention (after tDCS Session 5 - day 5 of treatment) and from Baseline to Post-Expansion (after the participant's final tDCS session beyond Session 5, up to 43 weeks). |
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| Secondary | Self-Report of Memory Strategies Used | Multifactorial Memory Questionnaire (MMQ) Strategies Score - This scale measures the use of practical memory strategies and aids in day-to-day life. Respondents rate how often they used each of 19 memory strategies over the previous two weeks. The score range is 0 to 76, with higher scores indicating greater use of memory strategies. Post Intervention data collection was on day 5 of treatment. Post-Expansion (PE) appointments were not consecutive. Mean time between enrollment and PE was 10 wks, longest was 43 wks. | Analysis included all randomized participants with recorded outcome measure and available amyloid PET biomarker data from either baseline, relevant end point, or both. Data was analyzed using a mixed model, rather than paired analysis. Therefore, in some cases, number analyzed exceeds number of participants in expansion period. Participants were excluded when outcome was not recorded or amyloid PET data was not acquired. | Posted | Mean | 95% Confidence Interval | score on a scale | Change from Baseline to Post-Intervention (after tDCS Session 5 - day 5 of treatment) and from Baseline to Post-Expansion (after the participant's final tDCS session beyond Session 5, up to 43 weeks). |
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| Secondary | Change in Memory Functioning | The Repeatable Battery of the Assessment of Neuropsychological Status (RBANS) is a comprehensive neuropsychological battery for the evaluation of global cognition. The delayed memory section is a measure of delayed recall and recognition for verbal and visual information. It includes the subtests List Recall, List Recognition, Story Memory, and Figure Recall. Low scores on this index indicate difficulties with recognition and retrieval of information from long-term memory stores This index is composed of both auditory and visual measures; therefore, a severe deficit in language, auditory processing, or visual functioning may impact one of the measures more than the other. Analysis included the sum of the raw scores for each of the delayed memory subtests, with possible scores ranging from 0 to 62. Post Intervention data collection was on day 5 of treatment. Post-Expansion (PE) appointments were not consecutive. Mean time between enrollment and PE was 10 wks, longest was 43 wks. | Analysis included all randomized participants with RBANS data and available amyloid PET biomarker data from either baseline, relevant end point, or both. Data was analyzed using a mixed model, rather than paired analysis. Therefore, in some cases, number analyzed exceeds number of participants in expansion period. Participants were excluded when RBANS data or amyloid PET data was not acquired. | Posted | Mean | 95% Confidence Interval | score on a scale | Change from Baseline to Post-Intervention (after tDCS Session 5 - day 5 of treatment) and from Baseline to Post-Expansion (after the participant's final tDCS session beyond Session 5, up to 43 weeks). |
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| Secondary | Change in Overall Fluid Cognitive Abilities | Cognitive function was determined using the NIH Toolbox-Cognition Battery computerized tests, specifically the Fluid composite score. It is derived by averaging the subtests in the Fluid domain to achieve an overall standard score. Fully Corrected T-scores are adjusted for for age, gender, race/ethnicity, and educational attainment. The score compares the score of the participant to those in the NIH Toolbox nationally representative normative sampling. The T-score has a mean of 50 in the general population and a SD of 10. Scores higher than the mean indicate better performance. Post Intervention data collection was on day 5 of treatment. Post-Expansion (PE) appointments were not consecutive. Mean time between enrollment and PE was 10 wks, longest was 43 wks. | Analysis included all randomized participants with recorded outcome measure and available amyloid PET biomarker data from either baseline, relevant end point, or both. Data was analyzed using a mixed model, rather than paired analysis. Therefore, in some cases, number analyzed exceeds number of participants in expansion period. Participants were excluded when outcome was not recorded or amyloid PET data was not acquired. | Posted | Mean | 95% Confidence Interval | score on a scale | Change from Baseline to Post-Intervention (after tDCS Session 5 - day 5 of treatment) and from Baseline to Post-Expansion (after the participant's final tDCS session beyond Session 5, up to 43 weeks). |
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| Secondary | Cumulative Working Memory Effects of HD-tDCS Across Treatment Sessions | The n-back test is a working memory task where participants identify stimulus that matches stimulus experienced "n" steps back. Participants performed a 2-back test, in which they were asked to remember and press a button when shown a stimulus that appeared 2 steps before the current one (e.g. square, circle, square). The number of correct and incorrect identifications are normalized (z-score). Total score is the z-score of correct button presses minus the z-score of incorrect button presses. A higher score (d') reflects better working memory performance. Possible scores range from -4.85 to 4.85. Positive change (increase) in 2-back score across treatment sessions indicates improvement in working memory performance. Data is shown as the mean slope calculation of participants across first 5 days of treatment and across all treatments, x=days of treatment, y=n-back score. Post-Expansion (PE) appointments were not consecutive. Mean time between enrollment and PE was 10 wks. | Analysis included all randomized participants with Nback data and available amyloid PET biomarker data. Participants were excluded when Nback data or amyloid PET data was not acquired. | Posted | Mean | 95% Confidence Interval | d'/day | Change from Baseline to Post-Intervention (after tDCS Session 5 - day 5 of treatment) and from Baseline to Post-Expansion (after the participant's final tDCS session beyond Session 5, up to 43 weeks). |
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| Secondary | Cumulative Memory Accuracy Effects of HD-tDCS Across Treatment Sessions | Paired Associates task is a verbal memory task that asks participants to learn a list of word pairs. After a delay, participants are shown correct and mismatched word pairs one at a time and asked to identify if the displayed word pair was from the list they were asked to learn or not. Total accuracy is a proportion (total correct responses divided by total trials completed) ranging from 0 to 1 that measures the accuracy of a participant's responses to both correct and mismatched word pairs. Higher scores indicate better verbal memory performance, and positive changes over time indicate an improvement in verbal memory performance, measured after baseline (Session 1) and every intervention session (Sessions 2-5) Data is shown as the mean slope calculation of participants across first 5 days of treatment and across all treatments, x=days of treatment, y= total accuracy. Post-Expansion (PE) appointments were not consecutive. Mean time between enrollment and PE was 10 wks. | Analysis included all randomized participants who completed the baseline computerized paired-associates task, had available amyloid PET biomarker data, were not identified as outliers, and for whom a valid model-based memory sensitivity estimate (baseline average) could be obtained. Participants were excluded when paired-associates data, amyloid PET data, or a valid model-based memory sensitivity estimate was not available. | Posted | Mean | 95% Confidence Interval | proportion of correct responses/day | Change from Baseline to Post-Intervention (after tDCS Session 5 - day 5 of treatment) and from Baseline to Post-Expansion (after the participant's final tDCS session beyond Session 5, up to 43 weeks). |
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| Secondary | Cumulative Memory Sensitivity Effects of HD-tDCS Across Daily Sessions | Verbal memory performance for computerized Paired Associates task, summarized with a computational model (linear ballistic accumulator decision model). The model uses each participant's accuracy and reaction times across trials to estimate how efficiently they accumulate information to distinguish previously studied (target) word pairs from new (lure) pairs. Reported outcome is the average memory sensitivity score at baseline, expressed as unitless model values (scores on a scale) where higher scores indicate better discrimination, scores near zero indicate chance-level performance, and negative scores (if present) indicate performance worse than chance. | Analysis included all randomized participants who completed the baseline computerized paired-associates task, had available amyloid PET biomarker data, were not identified as outliers, and for whom a valid model-based memory sensitivity estimate (baseline average) could be obtained. Participants were excluded when paired-associates data, amyloid PET data, or a valid model-based memory sensitivity estimate was not available. | Posted | Mean | Standard Deviation | arbitrary units | Baseline |
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| Secondary | Tolerability of HD-tDCS | Tolerability was assessed using the HD-tDCS Safety Questionnaire, an 11-item symptom checklist. The questionnaire assesses the presence (yes/no) of 10 specific self-reported symptoms (Itching, Burning, Tingling, Scalp Pain, Trouble Concentrating, Sleep problems, Headache, Mood Change, Neck Pain, and Other symptoms) and 1 oberserved symptom, Skin Redness. Skin Redness was excluded from this analysis as it is not related to the participant's perception of tolerability. The total score (symptom burden) was calculated by summing the number of symptoms present across the 10 items for each session. Score range: 0 to 10 symptoms, where 0 = no symptoms present and 10 = all symptoms present. Higher scores indicate worse tolerability (more symptoms experienced). Values represent the mean number of symptoms per session, calculated by averaging symptom burden scores across all post-stimulation assessments within each treatment group. | Of 233 enrolled participants, 232 were included in the analysis (N=232 participants, 3196 sessions). One participant from the 2 mA group was excluded due to missing symptom data. Five individual sessions across all groups were excluded due to incomplete symptom assessments. | Posted | Mean | Standard Deviation | symptoms on a scale (0-10) | Assessed immediately after each HD-tDCS session (participants received up to 30 sessions over approximately 1-12 weeks); values represent mean symptom burden averaged across all post-stimulation assessments |
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| Secondary | Effectiveness of Blinding of HD-tDCS | Participant's perception of treatment assignment assessed after each stimulation session using a 3-category ordinal scale. Participants guessed whether they received: (0) Sham stimulation, (1) Don't Know, or (2) Active stimulation. The scale is ordinal with Sham < Don't Know < Active. Effective blinding is indicated by no significant difference in the distribution of perceived assignment between active and sham groups (i.e., participants in active groups cannot reliably distinguish their treatment from sham). Higher proportional odds ratios would indicate active group participants were more likely to guess "active"; lower ratios would indicate sham participants were more likely to guess "active" (paradoxical pattern suggesting convincing sham condition). | Of 233 enrolled participants, 232 were included in the blinding effectiveness analysis (N=232 participants, 3185 sessions). One participant was excluded due to having no valid blinding assessments. Sessions were excluded due to missing blinding responses. Missing sessions are due to participant refusal to answer and the blinding assessment not being administered. Cumulative link mixed model with participant as random effect was used to account for repeated measures. | Posted | Number | sessions | Assessed immediately after each HD-tDCS session (participants received up to 30 sessions over approximately 1-12 weeks) | tDCS sessions | tDCS sessions |
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| Secondary | Change in Default Mode Network Connectivity | The outcome focuses on default mode network (DMN) within-network functional connectivity. Within-network functional connectivity is estimated from fMRI data as strength of temporal coupling within DMN regions (nodes). For each participant and time point, correlation-based connectivity (Pearson r; Fisher r-to-z transformed; arbitrary units) was computed between DMN regions defined using a standard functional atlas. Higher values reflect stronger functional connectivity within DMN. A Z-score's range is infinite. Expected value is around -3 to 3. Analyses are conducted separately for amyloid negative (A-) and amyloid positive (A+) participants. Post Intervention data collection was on day 5 of treatment. Post-Expansion (PE) appointments were not consecutive. Mean time between enrollment and PE was 10 wks, longest was 43 wks. | Analysis included all randomized participants with usable MRI data and available amyloid PET biomarker data from either baseline, relevant end point, or both. Data was analyzed using a mixed model, rather than paired analysis. Therefore, in some cases, number analyzed exceeds number of participants in expansion period. Participants were excluded when MRI data could not be reliably processed (segmentation/quality failures or excessive head motion) or amyloid PET data was not acquired. | Posted | Mean | 95% Confidence Interval | Fisher z-transformed Pearson correlation | Change from Baseline to Post-Intervention (after tDCS Session 5 - day 5 of treatment) and from Baseline to Post-Expansion (after the participant's final tDCS session beyond Session 5, up to 43 weeks). |
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| Secondary | Cumulative Cognitive Change Across Daily Consecutive Sessions | Measured through change in Cogstate or other comparable computerized cognitive testing scores across consecutive daily sessions. | Due to financial constraints, Cogstate software was not able to be used for this study and no data was collected for this measure. "Other comparable computerized cognitive testing scores" as described in the Outcome Measure Description are reported in Secondary Outcome 7 and 8. | Posted | Change from Baseline to Post-Intervention (after tDCS Session 5 - day 5 of treatment) and from Baseline to Post-Expansion (after the participant's final tDCS session beyond Session 5, up to 43 weeks). |
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| Secondary | Change in Global Cognition | The Repeatable Battery of the Assessment of Neuropsychological Status (RBANS) is a comprehensive neuropsychological battery for the evaluation of global cognition and has been validated in subjects with mild cognitive impairment, moderate to severe traumatic brain injuries, vascular dementias, and Alzheimer's disease. Data was analyzed using the sum of the subtest raw scores, which is an indicator of the general cognitive functioning of the examinee. Low scores suggest general cognitive impairment even when some individual subtest scores may be within normal limits. Individuals with low scores on this measure exhibit problems with attention, memory, language, and construction skills. Possible scores range from 0 to 321. Post Intervention data collection was on day 5 of treatment. Post-Expansion (PE) appointments were not consecutive. Mean time between enrollment and PE was 10 wks, longest was 43 wks. | Analysis included all randomized participants with recorded outcome measure and available amyloid PET biomarker data from either baseline, relevant end point, or both. Data was analyzed using a mixed model, rather than paired analysis. Therefore, in some cases, number analyzed exceeds number of participants in expansion period. Participants were excluded when outcome was not recorded or amyloid PET data was not acquired. | Posted | Mean | 95% Confidence Interval | score on a scale | Change from Baseline to Post-Intervention (after tDCS Session 5 - day 5 of treatment) and from Baseline to Post-Expansion (after the participant's final tDCS session beyond Session 5, up to 43 weeks). |
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| Other Pre-specified | Change in Inhibition Ability | A priori intent to measure through change in the NIH Toolbox Flanker Inhibitory Control and Attention Test Score | Not Posted | Baseline and post-intervention (after tDCS sessions 5 & 30) | Participants |
| Other Pre-specified | Change in Conceptualization Ability | A priori intent to measure through change in the NIH Toolbox Dimensional Change Card Sort Test Score | Not Posted | Baseline and post-intervention (after tDCS sessions 5 & 30) | Participants |
| Other Pre-specified | Change in Picture Sequence Memory | A priori intent to measure through change in the NIH Toolbox Picture Sequence Memory Test Score | Not Posted | Baseline and post-intervention (after tDCS sessions 5 & 30) | Participants |
| Other Pre-specified | Change in Working Memory Ability | A priori intent to measure through change in the NIH Toolbox List Sorting Working Memory Test Score | Not Posted | Baseline and post-intervention (after tDCS sessions 5 & 30) | Participants |
| Other Pre-specified | Change in Processing Speed | A priori intent to measure through change in the NIH Toolbox Pattern Comparison Processing Speed Test Score | Not Posted | Baseline and post-intervention (after tDCS sessions 5 & 30) | Participants |
| Other Pre-specified | Change in Visuospatial Functioning | Measured through change in the RBANS Visuospatial Index score | Not Posted | Baseline and post-intervention (after tDCS sessions 5 & 30) | Participants |
| Other Pre-specified | Change in Language Functioning | Measured through change in the RBANS Language Index score | Not Posted | Baseline and post-intervention (after tDCS sessions 5 & 30) | Participants |
| Other Pre-specified | Change in Attention | Measured through change in the RBANS Attention Index score | Not Posted | Baseline and post-intervention (after tDCS sessions 5 & 30) | Participants |
| Other Pre-specified | Change in Memory Functioning | Measured through change in the RBANS Immediate Memory Index score | Not Posted | Baseline and post-intervention (after tDCS sessions 5 & 30) | Participants |
| Other Pre-specified | Change in Cognitive Functioning | A priori intent to measure through changes in RBANS subtest scores | Not Posted | Baseline and post-intervention (after tDCS sessions 5 & 30) | Participants |
| 0 |
| 59 |
| 0 |
| 59 |
| 58 |
| 59 |
| EG001 | 1 mA Dosage Stimulation | 1 milliAmp dose of HD-tDCS treatment for 30 minutes, for between 5-30 sessions. 1 mA HD-tDCS: Participants will receive HD-tDCS at 1 mA for 30 minutes, for between 5-30 sessions. | 0 | 59 | 1 | 59 | 56 | 59 |
| EG002 | 2 mA Dosage Stimulation | 2 milliAmp dose of HD-tDCS treatment for 30 minutes, for between 5-30 sessions. 2 mA HD-tDCS: Participants will receive HD-tDCS at 2 mA for 30 minutes, for between 5-30 sessions. | 0 | 58 | 1 | 58 | 55 | 58 |
| EG003 | 3 mA Dosage Stimulation | 3 milliAmp dose of HD-tDCS treatment for 30 minutes, for between 5-30 sessions. 3 mA HD-tDCS: Participants will receive HD-tDCS at 3 mA for 30 minutes, for between 5-30 sessions. | 0 | 57 | 0 | 57 | 56 | 57 |
| Weakness between stimulation treatments | General disorders | Non-systematic Assessment |
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| Burning sensation on scalp | Skin and subcutaneous tissue disorders | Systematic Assessment | This data was collected via questionnaire prior to and after each treatment. Data represents all symptoms reported by participants at any time point. |
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| Itching | Skin and subcutaneous tissue disorders | Systematic Assessment | This data was collected via questionnaire prior to and after each treatment. Data represents all symptoms reported by participants at any time point. |
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| Tingling on scalp | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Pain on scalp | General disorders | Systematic Assessment | This data was collected via questionnaire prior to and after each treatment. Data represents all symptoms reported by participants at any time point. |
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| Trouble concentrating | General disorders | Systematic Assessment | This data was collected via questionnaire prior to and after each treatment. Data represents all symptoms reported by participants at any time point. |
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| Sleepiness | General disorders | Systematic Assessment | This data was collected via questionnaire prior to and after each treatment. Data represents all symptoms reported by participants at any time point. |
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| Mood change | General disorders | Systematic Assessment | This data was collected via questionnaire prior to and after each treatment. Data represents all symptoms reported by participants at any time point. |
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| Neck pain | Musculoskeletal and connective tissue disorders | Systematic Assessment | This data was collected via questionnaire prior to and after each treatment. Data represents all symptoms reported by participants at any time point. |
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| Skin redness | Skin and subcutaneous tissue disorders | Systematic Assessment | This data was collected via questionnaire prior to and after each treatment. Data represents all symptoms reported by participants at any time point. |
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| Pulsing, tapping, tickling sensation | General disorders | Non-systematic Assessment | This data was collected via questionnaire prior to and after each treatment. Data represents all symptoms reported by participants at any time point. |
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| Pricking, probing sensation on scalp | Skin and subcutaneous tissue disorders | Non-systematic Assessment | This data was collected via questionnaire prior to and after each treatment. Data represents all symptoms reported by participants at any time point. |
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| Pressure in head | General disorders | Non-systematic Assessment | This data was collected via questionnaire prior to and after each treatment. Data represents all symptoms reported by participants at any time point. |
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Not provided
Not provided
| D002493 |
| Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| Change from baseline to post intervention- amyloid positive participants |
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| Change from baseline to end of expansion- amyloid negative-participants |
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| Change from baseline to end of expansion- amyloid positive-participants |
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| Change from baseline to post intervention - amyloid positive participants |
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| Change from baseline to post expansion- amyloid negative participants |
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| Change from baseline to post expansion- amyloid positive participants |
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| Change from baseline to post intervention - amyloid positive participants |
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| Change from baseline to post expansion- amyloid negative participants |
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| Change from baseline to post expansion- amyloid positive participants |
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| Change from baseline to post intervention - amyloid positive participants |
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| Change from baseline to end of expansion- amyloid negative-participants |
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| Change from baseline to end of expansion- amyloid positive-participant |
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| Change from baseline to post intervention - amyloid positive participants |
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| Change from baseline to end of expansion- amyloid negative-participants |
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| Change from baseline to end of expansion- amyloid positive-participants |
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| Slope across first 5 days of treatment for Amyloid Positive (A+) Participants |
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| Slope across entire treatment (up to 43 weeks) for Amyloid Negative (A-) Participants |
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| Slope across entire treatment (up to 43 weeks) for Amyloid Positive (A+) Participants |
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| Slope across first 5 days of treatment for Amyloid Positive (A+) Participants |
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| Slope across entire treatment (up to 43 weeks) for Amyloid Negative (A-) Participants |
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| Slope across entire treatment (up to 43 weeks) for Amyloid Positive (A+) Participants |
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| Amyloid Positive Participants |
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| 0.565 |
| Mean Difference (Final Values) |
| -0.101 |
| Standard Error of the Mean |
| 0.176 |
| 2-Sided |
| 95 |
| -0.448 |
| 0.245 |
| Superiority |
| Mixed Models Analysis | 0.167 | Mean Difference (Final Values) | -0.244 | Standard Error of the Mean | 0.176 | 2-Sided | 95 | -0.59 | 0.103 | Superiority |
| tDCS sessions |
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| Didn't know |
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| Chose active |
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| Superiority |
| Null Hypothesis: No difference in blinding effectiveness between 2 mA and Sham. Participants' perception of treatment assignment (ordinal: guessed sham < don't know < guessed active) is not associated with actual treatment assignment (2 mA vs Sham). | Mixed Models Analysis | CLMM with ordinal logistic regression. Random intercept for participant to account for repeated measures. GuessOrdinal ~ Group + (1|ParticipantID) | 0.0605 | Two-sided test with alpha=0.05. No adjustment for multiple comparisons; each dose is a planned pairwise comparison to the sham reference group. | Odds Ratio (OR) | 0.407 | Standard Error of the Mean | 0.480 | 2-Sided | 95 | 0.159 | 1.041 | Proportional odds ratio from CLMM. OR > 1 indicates higher odds of guessing "active" in the 2 mA group compared to Sham. OR = 1 indicates no difference. OR < 1 indicates paradoxically lower odds of guessing "active" in the active dose group. | Superiority |
| Null Hypothesis: No difference in blinding effectiveness between 3 mA and Sham. Participants' perception of treatment assignment (ordinal: guessed sham < don't know < guessed active) is not associated with actual treatment assignment (3 mA vs Sham). | Mixed Models Analysis | CLMM with ordinal logistic regression. Random intercept for participant to account for repeated measures. GuessOrdinal ~ Group + (1|ParticipantID) | 0.055 | Two-sided test with alpha=0.05. No adjustment for multiple comparisons; each dose is a planned pairwise comparison to the sham reference group. | Odds Ratio (OR) | 0.438 | Standard Error of the Mean | 0.431 | 2-Sided | 95 | 0.188 | 1.019 | Proportional odds ratio from CLMM. OR > 1 indicates higher odds of guessing "active" in the 3 mA group compared to Sham. OR = 1 indicates no difference. OR < 1 indicates paradoxically lower odds of guessing "active" in the active dose group. | Superiority |
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| Change from Baseline to Post-Intervention for Amyloid Positive (A+) Participants |
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| Change from Baseline to Post-Expansion for Amyloid Negative (A-) Participants |
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| Change from Baseline to Post-Expansion for Amyloid Positive (A+) Participants |
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| Change from baseline to post intervention - amyloid positive participants |
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| Change from baseline to end of expansion- amyloid negative-participants |
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| Change from baseline to end of expansion- amyloid positive-participants |
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