Stimulation to Improve Memory

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

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.

Measured through change in Cogstate or other comparable computerized cognitive testing scores across consecutive daily sessions.

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.

A priori intent to measure through change in the NIH Toolbox Flanker Inhibitory Control and Attention Test Score

A priori intent to measure through change in the NIH Toolbox Dimensional Change Card Sort Test Score

A priori intent to measure through change in the NIH Toolbox Picture Sequence Memory Test Score

A priori intent to measure through change in the NIH Toolbox List Sorting Working Memory Test Score

A priori intent to measure through change in the NIH Toolbox Pattern Comparison Processing Speed Test Score

Measured through change in the RBANS Visuospatial Index score

Measured through change in the RBANS Language Index score

Measured through change in the RBANS Attention Index score

Measured through change in the RBANS Immediate Memory Index score

A priori intent to measure through changes in RBANS subtest scores