MCI
Conditions
Keywords
MCI, EEG, tES, Personalized treatment, Closed-loop
Brief summary
This research study investigates the feasibility and efficacy of a personalized, closed-loop electroencephalogram-transcranial electrical stimulation (EEG-tES) intervention for individuals with mild cognitive impairment (MCI), addressing the inconsistent results of generic brain stimulation protocols. By integrating artificial intelligence (AI)-derived insights with real-time data, the study aims to customize transcranial electrical stimulation (tES) parameters, including electrode placement, intensity, and frequency to target the specific brain regions responsible for abnormal signaling in each participant. Over the intervention period paired with computerized cognitive training, the project will evaluate improvements in learning, memory, and functional connectivity, while simultaneously identifying clinical and physiological predictors to determine the viability of transitioning this low-cost, non-invasive technology into a remotely supervised, home-based therapy setting. The study duration will be a total of 6-8 weeks.
Interventions
DEVICEActive tES
This three-week, closed-loop program integrates personalized tES with computerized cognitive training to drive neuroplasticity. Following baseline electroencephalogram (EEG) mapping, participants undergo daily 30-minute sessions consisting of four "loops." Each loop begins with an AI-analyzed EEG to calibrate stimulation parameters, followed by 5-minute stimulation periods.
BEHAVIORALCognitive Interventions
In between tES treatment loops, the participants will be asked to complete cognitive exercises. By pairing real-time brain modulation with targeted executive function exercises, the intervention aims to improve language skills and clinical outcomes through precise, data-driven cortical targeting.
Sponsors
Johns Hopkins University
Mackler-Goding Foundation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
45 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
* Must be between 45-85 years of age. * Must be proficient in English. * Must have a minimum of high-school education. * Must be diagnosed with 'probable Alzheimer's Disease (AD)' in specialized diagnostic centers with neuropsychological (e.g., RAVLT) and AD biomarkers according to 2011 guidelines. * The investigators will also perform extensive testing in the investigators' test battery including the Mnemonic Similarity Test (MST) that discriminates and measures the most salient hippocampal deficit-pattern separation (PS).
Exclusion criteria
* People with previous neurological disease including vascular dementia (e.g., stroke, developmental dyslexia, dysgraphia or attentional deficit). * People with hearing loss (\> 25 decibel, using audiometric hearing screen). * People with uncorrected visual acuity loss. * People with advanced dementia or severe language impairments (MMSE \<15, or Montreal Cognitive Assessment \<10, or language Frontotemporal Dementia-specific Clinical Dementia Rating (FTD-CDR) =3). * People with pre-existing psychiatric disorders such as behavioral disturbances, severe depression, or schizophrenia that do not allow these people to comply or follow the study schedule and requirements such as repeated evaluation and therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in auditory recall accuracy based on the sum of words recalled in Trials 1-5 of semantically related - trained word-lists | Before intervention, immediately after intervention and 1 month post intervention | Each trained word-list (practiced during the intervention period) will consist of 12 semantically related words (e.g., birds). Word lists will be constructed using psycholinguistic databases. There will be 5 Trials to learn each list. The investigators will compute the raw score of items correctly recalled by summing all scores from Trial 1 to Trial 5 and transforming to percent correct (range: 0-100%) at each time point of the study. Higher score is better. Increase in scores is considered a benefit. |
| Change in auditory delayed recall accuracy of semantically related - trained word-lists | Before intervention, immediately after intervention and 1 month post intervention | Each trained word-list (practiced during the intervention period) will consist of 12 semantically related words (e.g., birds). Word lists will be constructed using psycholinguistic databases. There will be 5 Trials to recall each list, and then participants will be asked to recall that list 20 minutes later (delayed recall). The investigators will compute the raw score of items correctly recalled (delayed recall) and transform to percent correct (range: 0-100%) at each time point of the study. Increase in scores is considered a benefit.Higher score is better. |
| Change in auditory recall accuracy based on the sum of words recalled in Trials 1-5 of semantically unrelated - trained word-lists | Before intervention, immediately after intervention and 1 month post intervention | Each trained word-list (practiced during the intervention period) will consist of 12 semantically unrelated words as in Rey Auditory-Verbal Learning Test (RAVLT). Word lists will be constructed using psycholinguistic databases. There will be 5 Trials to learn each list. The investigators will compute the raw score of items correctly recalled by summing all scores from Trial 1 to Trial 5 and transforming to percent correct (range: 0-100%) at each time point of the study. Increase in scores is considered a benefit. Higher score is better. |
| Change in auditory delayed recall accuracy of semantically unrelated - trained word-lists | Before intervention, immediately after intervention and 1 month post intervention | Each trained word-list (practiced during the intervention period) will consist of 12 semantically unrelated words (as in RAVLT). Word lists will be constructed using psycholinguistic databases. There will be 5 Trials to recall each list, and then participants will be asked to recall that list 20 minutes later (delayed recall). The investigators will compute the raw score of items correctly recalled (delayed recall) and transform to percent correct (range: 0-100%) at each time point of the study. Increase in scores is considered a benefit. Higher score is better. |
| Change in auditory recall accuracy based the sum of words recalled in Trials 1-5 of semantically related - untrained word-lists | Before intervention, immediately after intervention and 1 month post intervention | Each untrained word-list (not practiced during the intervention period) will consist of 12 semantically related words (e.g., birds). Word lists will be constructed using psycholinguistic databases. There will be 5 Trials to learn each list. The investigators will compute the raw score of items correctly recalled by summing all scores from Trial 1 to Trial 5 and transforming to percent correct (range: 0-100%) at each time point of the study. Increase in scores is considered a benefit. Higher score is better. |
| Change in auditory delayed recall accuracy of semantically related - untrained word-lists | Before intervention, immediately after intervention and 1 month post intervention | Each untrained word-list (not practiced during the intervention period) will consist of 12 semantically related words (e.g., birds). Word lists will be constructed using psycholinguistic databases. There will be 5 Trials to recall each list, and then participants will be asked to recall that list 20 minutes later (delayed recall). The investigators will compute the raw score of items correctly recalled (delayed recall) and transform to percent correct (range: 0-100%) at each time point of the study. Increase in scores is considered a benefit. Higher score is better. |
| Change in auditory recall accuracy based on the sum of words recalled in Trials 1-5 of semantically unrelated - untrained word-lists | Before intervention, immediately after intervention and 1 month post intervention | Each untrained word-list (not practiced during the intervention period) will consist of 12 semantically unrelated words (as in RAVLT). Word lists will be constructed using psycholinguistic databases. There will be 5 Trials to learn each list. The investigators will compute the raw score of items correctly recalled by summing all scores from Trial 1 to Trial 5 and transforming to percent correct (range: 0-100%) at each time point of the study. Increase in scores is considered a benefit. Higher score is better. |
| Change in auditory delayed recall accuracy of semantically unrelated - untrained word-lists | Before intervention, immediately after intervention and 1 month post intervention | Each untrained word-list (not practiced during the intervention period) will consist of 12 semantically unrelated words (as in RAVLT). Word lists will be constructed using psycholinguistic databases. There will be 5 Trials to recall each list, and then participants will be asked to recall that list 20 minutes later (delayed recall). The investigators will compute the raw score of items correctly recalled (delayed recall) and transform to percent correct (range: 0-100%) at each time point of the study. Increase in scores is considered a benefit. Higher score is better. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Rey Auditory-Verbal Learning Test (RAVLT) score | Before intervention, immediately after intervention and 1 month post intervention | RAVLT is a well-established verbal memory test. RAVLT includes a 5-trial presentation of a 15-word list (List A), a single presentation of an interference list (List B)(Trial 6), two post-interference recall trials (one immediate - Trial 7, one delayed - Trial 8) and recognition of the target words in the orthographic modality with distractors (Trial 9). Scoring includes the percent score of Trial 1, Trial 5, Trial 8 and Trial 9 as well as the sum of Trial 1 through 5, and the difference between Trial 5 and Trial 1 computed as the percent difference between the scores before intervention and each time point after. Increase in score is considered a benefit. Higher score is better. |
| Change in Mini Mental State Examination (MMSE) | Before intervention, immediately after intervention and 1 month post intervention | MMSE is a well-established cognitive assessment test. It examines functions including registration (repeating named prompts), attention and calculation, recall, language, ability to follow simple commands and orientation. The total raw score is out of 30 points. The investigators will compute the raw score of items correct and transform to percent correct (range: 0-100%), computing change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit. Higher score is better. |
| Change in digit span forward score | Before intervention, immediately after intervention and 1 month post intervention | Digit span forward involves the recall of a series of single digits (sets of 1-8 digits) in the same order the digits were presented. Scoring will be based on the number of consecutive digits correctly recalled. The investigators will compute the change in outcome between the time point before intervention and each time point after. Increase in score is considered a benefit. Higher score is better. |
| Change in Mnemonic Similarity Task (MST) score | Before intervention, immediately after intervention and 1 month post intervention | MST is a well-established test in order to assess high interference memory and general recognition memory via pattern separation. It involves differentiating between previously learned images and novel images. For the MST tasks, the Pattern Separation (PS) score will be calculated using two measures: a) the rate of similar items correctly identified minus the rate of similar items misidentified as new (S\|S-S\|N); b) the rate of similar items correctly identified minus the rate of similar items misidentified as old (S\|S-O\|S). The number of correct responses for each category of items (i.e., old, similar, new) and the type of errors (i.e., identifications of new items as similar; identification of similar items as old) will also be tracked. Change in outcome in percent difference will be computed between the scores before intervention and each time point after. Increase in scores is considered a benefit. Higher score is better. |
| Change in word repetition score | Before intervention, immediately after intervention and 1 month post intervention | Temple Assessment of Language and Short-Term Memory in Aphasia (TALSA) tasks include word repetition, with sets of 1-6 words. Scoring will be based on percent of words correctly repeated. The investigators will compute the raw score of items correct and transform to percent correct (range: 0-100%), computing change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit. Higher score is better. |
| Change in non-word repetition score | Before intervention, immediately after intervention and 1 month post intervention | TALSA tasks include non-word repetition, with sets of 1-6 non-words. Scoring will be based on percent of non-words correctly repeated. The investigators will compute the raw score of items correct and transform to percent correct (range: 0-100%), computing change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit. Higher score is better. |
| Change in sentence repetition score | Before intervention, immediately after intervention and 1 month post intervention | Sentence repetition tasks come from the TALSA, with scoring based on percent of words in sentences correctly repeated. The investigators will compute the raw score of items correct and transform to percent correct (range: 0-100%), computing change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit.Higher score is better. |
| Change in oral naming Boston Naming Test score | Before intervention, immediately after intervention and 1 month post intervention | Accuracy in oral picture naming (30-item Boston Naming Test). The Boston Naming Test is a widely used picture naming test that detects lexical retrieval deficits in the oral modality. The investigators will compute the raw score of items correct and transform to percent correct (range: 0-100%), computing change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit. Higher score is better. |
| Change in oral naming Philadelphia Naming Test score | Before intervention, immediately after intervention and 1 month post intervention | Accuracy in oral picture naming (Philadelphia Naming Test). The Philadelphia Naming Test is an extensive picture naming test that comprises 275 items from a wide range of frequencies and other psycholinguistic characteristics. The investigators will compute the raw score of items correct and transform to percent correct (range: 0-100%), computing change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit. Higher score is better. |
| Change in written naming as assessed by Boston Naming Test | Before intervention, immediately after intervention and 1 month post intervention | Accuracy in written picture naming (30-item Boston Naming Test). The investigators will compute the raw score of items correct and transform to percent correct (range: 0-100%), computing change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit. Higher score is better. |
| Change in written naming as assessed by Philadelphia Naming Test | Before intervention, immediately after intervention and 1 month post intervention | Accuracy in written picture naming (Philadelphia Naming Test). The investigators will compute the raw score of items correct and transform to percent correct (range: 0-100%), computing change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit. Higher score is better. |
| Change in oral naming of action as assessed by Hopkins Assessment of Naming Actions (HANA) | Before intervention, immediately after intervention and 1 month post intervention | Accuracy in oral naming of actions. The investigators will compute the raw score of items correct and transform to percent correct (range: 0-100%), computing change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit. Higher score is better. |
| Change in syntactic comprehension as assessed by Subject-relative, Object-relative, Active, Passive (S.O.A.P.) Syntactic Battery | Before intervention, immediately after intervention and 1 month post intervention | The 40-item Subject-relative, Object-relative, Active, Passive (S.O.A.P.) Syntactic Battery of various sub-tests will be used to assess argument structure comprehension and production. The investigators will compute the raw score of items correct and transform to percent correct (range: 0-100%), computing change in outcome in percent difference between baseline and each time point. Increase in score is considered benefit. Higher score is better. |
| Change in verbal fluency task score | Before intervention, immediately after intervention and 1 month post intervention | Verbal fluency tasks (semantic and letter fluency) involve generating as many words as possible in one minute. Scoring will be based on number of words generated per minute. The investigators will compute the raw score of items correct and compute change in outcome between baseline and each time point. Increase in score is considered benefit. Higher score is better. |
| Change in spelling as assessed by the Johns Hopkins Dysgraphia battery | Before intervention, immediately after intervention and 1 month post intervention | Accuracy in spelling using the Johns Hopkins Dysgraphia battery. The investigators will compute the raw score of items correct using a spelling scoring system accounting for additions, substitutions, and deletions, and transform to percent correct (range: 0-100%), computing change in outcome in percent difference before intervention and each time point after. Increase in score is considered a benefit. Higher score is better. |
| Change in digit span backward score | Before intervention, immediately after intervention and 1 month post intervention | Digit span backward involves the recall of a series of single digits (sets of 1-8 digits) in the reverse order than the digits were presented. Scoring will be based on the number of consecutive digits correctly recalled. The investigators will compute the change in outcome between the time point before intervention and each time point after. Increase in score is considered a benefit. Higher score is better. |
| Change in spatial span forward score | Before intervention, immediately after intervention and 1 month post intervention | Spatial span forward involves the recall of a series of positions on a board (sets of 1-9) in the same order the digits were presented. Scoring will be based on the number of consecutive positions correctly recalled. The investigators will compute the change in outcome between the time point before intervention and each time point after. Increase in score is considered a benefit. Higher score is better. |
| Change in spatial span backward score | Before intervention, immediately after intervention and 1 month post intervention | Spatial span backward involves the recall of a series of positions (sets of 1-8) in the reverse order than the digits were presented. Scoring will be based on the number of consecutive positions correctly recalled. The investigators will compute the change in outcome between the time point before intervention and each time point after. Increase in score is considered a benefit. Higher score is better. |
| Change in semantic content of connected speech (Cookie Theft) | Before intervention, immediately after intervention and 1 month post intervention | Using the Cookie Theft image from the Boston Diagnostic Aphasia Examination (BDAE) investigators will obtain representative language samples as participants describe the image. The investigators will combine the raw score of all items (semantics) correct from the image and transform to percent correct (range: 0-100%), computing change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit. Higher score is better. |
| Change in semantic content of connected speech (Circus) | Before intervention, immediately after intervention and 1 month post intervention | Using the Circus image from the Apraxia Battery for Adults (ABA) investigators will obtain representative language samples as participants describe the images. The investigators will combine the raw score of all items (semantics) correct from the image and transform to percent correct (range: 0-100%), computing change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit. Higher score is better. |
| Change in attention and manipulation of information scores | Before intervention, immediately after intervention and 1 month post intervention | Using the Trail Making Test (TMT) parts A and B, which include the sequential connection of letters/numbers in order to complete a trail, the investigators will obtain the time required by the participants to finish the tasks. Decrease in the time is considered a benefit. Higher score is better. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORKyrana Tsapkini, PhD
Johns Hopkins University
Outcome results
None listed