Promoting Adaptive Neuroplasticity in Mild Cognitive Impairment

Study Overview
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Brief Summary
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The aging US population threatens to overwhelm our healthcare infrastructure, especially since the rate of Alzheimer's disease (AD) alone is expected to triple in the coming decades. Memory cause functional impairment, reduced quality of life, increased caregiver burnout, and eventual institutionalization. The diagnosis of mild cognitive impairment (MCI) identifies those with memory deficits but who remain relatively independent in everyday life. MCI provides a window for interventions that target memory functioning. The proposed study focuses specifically on a groundbreaking combination of mnemonic rehabilitation and non-invasive brain stimulation. The main idea is that brain stimulation can enhance functioning in the specific brain regions/networks, thereby increasing the patients' ability to benefit from different types of memory rehabilitation. This will be a randomized, double-blind study (active vs. fake brain stimulation), that provides multiple treatment session. Outcome will be examined using both laboratory-based and real-world memory testing as well as brain imaging. This first-of-its-kind study has the potential to meaningfully translate more basic science findings into neuroanatomically targeted and functionally meaningful treatments for our aging population.

Detailed Description
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Enrollment and interactions/interventions are temporarily paused due to COVID-19 and are expected to resume in the future. This is not a suspension of IRB approval. The proposed study focuses specifically on a groundbreaking combination of mnemonic rehabilitation and non-invasive brain stimulation. The main idea is that brain stimulation can enhance functioning in the specific brain regions/networks, thereby increasing the patients' ability to benefit from memory rehabilitation. This will be a randomized, double-blind study (active vs. fake brain stimulation), that provides multiple treatment session. Outcome will be examined using both laboratory-based and real-world memory testing as well as brain imaging. This first-of-its-kind study has the potential to meaningfully translate more basic science findings into neuroanatomically targeted and functionally meaningful treatments for our aging population. The general purpose of this study is to examine the effects of two types of treatments for memory impairment in those with mild cognitive impairment (MCI). One form of treatment is cognitive rehabilitation, which involves teaching new ways to learn and remember information. The second form of treatment uses a type of electrical brain stimulation called transcranial direct current stimulation (tDCS) to increase activity in certain brain areas that may be involved with memory. We will use brain imaging to see whether these treatments changed how individuals learn and remember information. We will also use cognitive tests and questionnaires to examine whether memory (and related abilities) changed because of treatment. Values were updated in February 2023 after discovering coding errors in the original database. An exploratory outcome variable (effect of brain volumes) was removed at that time since the electrical field analyses are fundamentally dependent on brain volumes - the EF outcome measure remained but was modified to remove the two sham conditions since, by design, they did not receive any electric field (i.e., sham) and the statistical corrections could not be performed.

Official Title
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Promoting Adaptive Neuroplasticity in Mild Cognitive Impairment

Conditions
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Mild Cognitive Impairment, Alzheimer's Disease

Intervention / Treatment
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* Device: Transcranial direct current stimulation (tDCS) Soterix Medical Inc. tDCS unit
* Device: Transcranial direct current stimulation (tDCS) Soterix Medical Inc. tDCS unit


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: General inclusion criteria (all patients): All medications stable for approximately 2-3 months; No history of severe mental illness; No current untreated alcohol or substance abuse/dependence; English as native and preferred language; MRI-compatible if taking part in fMRI studies Able to give informed consent. MCI Inclusion Criteria: - Diagnosis of amnestic MCI based on criteria set forth by Petersen (2004). Additionally, other potential causes of cognitive deficit ruled out by the referring physician Exclusion Criteria: History of neurological disease or injury History of severe mental illness Current untreated alcohol or substance abuse Other conditions may exclude; please discuss with contact

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 88 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: active tDCS + mnemonic strategy training<br>Group receives active brain stimulation plus memory rehabilitation | Device: Transcranial direct current stimulation (tDCS) Soterix Medical Inc. tDCS unit<br>* Active brain stimulation<br>|
| Active Comparator: sham tDCS + mnemonic strategy training<br>Group receives sham brain stimulation plus memory rehabilitation | Device: Transcranial direct current stimulation (tDCS) Soterix Medical Inc. tDCS unit<br>* Sham (placebo)<br>|
| Active Comparator: active tDCS + autobiographical memory recall<br>Group receives active brain stimulation plus reminiscence training | Device: Transcranial direct current stimulation (tDCS) Soterix Medical Inc. tDCS unit<br>* Active brain stimulation<br>|
| Active Comparator: sham tDCS + autobiographical memory recall<br>Group receives sham brain stimulation plus reminiscence training | Device: Transcranial direct current stimulation (tDCS) Soterix Medical Inc. tDCS unit<br>* Sham (placebo)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Face-name Memory Test Performance | Raw number of face-name pairs correctly recalled with a maximum of 15 points; higher values are better at each time point. Change at post-session 5 (day 5 after baseline)) calculated relative to baseline performance (positive differences indicate improvement; negative values indicate decline). Data coding errors were identified and accurate values were reported 2/6/2023. | change from baseline to post session 5 (day 5 after baseline) | 
| Object Location Association Memory Test Performance - Recognition Condition | Performance measured using number of correctly identified locations (3 locations per stimulus; 15 total stimuli). Higher values indicate better performance. Change at post-session 5 (day 5 after baseline) calculated relative to baseline performance (positive differences indicate improvement; negative values indicate decline). Data coding errors were identified and accurate data were updated 2/6/2023. | change from baseline to post session 5 (day 5 after baseline) | 
| fMRI Betaweight Change | Changes in task related blood oxygen dependent signal (BOLD) activation for the face-name (novel post > novel pre) contrast in the left inferior frontal gyrus (pars triangularis, pars orbitalis, pars opercularis). Data are preliminary betaweights for the above noted contrast. Positive values reflect increased BOLD signal while negative values represent reduced BOLD signal. Not all participants were able to complete fMRI, which explains sample size discrepancies with other outcome measures. Data coding errors were discovered and accurate, updated data reported on 2/6/2023 | change from baseline to post session 5 (day 5 after baseline) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prose Memory | Performance on the Ecological Memory Simulations- Medical Instructions subtest. Raw points where higher values reflect better performance at each time point (0-15 possible points at each time point). Reported values reflect change from baseline (i.e., post-session day 5 vs. baseline) where positive values represent improvement and negative values represent decline. Corrected values are now included (2/23) that account for age, sex, and baseline neuropsychological abilities. | change from baseline to post Session 5 (day 5 after baseline) | 
| MMQ - Strategy Subscale | Changes on the Multifactorial Memory Questionnaire - strategy subscale. Raw points where higher values reflect better performance at each time point (0-76 possible points at each time point). Reported values reflect change from baseline (i.e., post-session day 5 vs. baseline) where positive values represent improvement and negative values represent decline. | change from baseline to post session 5 (day 5 after baseline) | 
| Spatial Navigation | Performance on Ecological Memory Simulations routes subtest (serial order). Higher values indicate better performance at each time point (0-9 possible points at each time point). Change from baseline is reported (post-session day 5 vs. baseline) so higher values indicate better recall while negative values indicate decline. Corrected data are now reported (2/23) accounting for age, sex, and baseline neuropsychological abilities. | change from baseline to post session 5 (day 5 after baseline) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aging, Alzheimer's Disease/Dementia, Cognitive Disorders, Imaging, Magnetic Resonance Imaging (MRI), Neurology, Physical Medicine & Rehabilitation, transcranial direct current stimulation