This is a randomized clinical trial of a treatment that combines non-invasive brain stimulation with computerized cognitive training (CCT) for people with mild cognitive impairment (MCI). The form of brain stimulation used in this study is accelerated intermittent theta burst stimulation (iTBS). All participants receive the same amount of iTBS and are randomly assigned to engage in one of two types of CCT. The goals of the study are to see if this combined treatment is feasible and acceptable to people with MCI and whether combined iTBS and CCT improves memory, thinking skills, mood, and daily function.
This is a randomized, sham-controlled trial of combined intermittent theta burst stimulation (iTBS) and computerized cognitive training (CCT) for people with mild cognitive impairment (MCI). The primary objectives of this study are to determine the feasibility, acceptability, and preliminary effect sizes of 3-day combined iTBS+CCT for improving neurocognitive and psychosocial function in MCI.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
50
A MagVenture MagPro Transcranial Magnetic Stimulation (TMS) System with Brainsight neuronavigation will be used. All participants will receive active treatment: 12 sessions (3 min each) of iTBS on each of 3 treatment days within an 8-day span. A single session = 600 pulses of 50 Hz iTBS triplets delivered every 200ms in 2s trains repeated every 10s (8s inter-train interval) for 190s. Stimulation intensity is 120% resting motor threshold (rMT) delivered at the left dorsolateral prefrontal cortex. Total pulses = 21,600. Inter-session intervals will be approx. 15 min.
CCT will be delivered through the online BrainHQ platform. Participants will engage in adaptive visual speed of processing training during the 15-min breaks between iTBS sessions (11 sessions on each treatment day, total CCT time = 495 min).
Sham CCT will be delivered through the online BrainHQ platform. Participants will engage in non-adaptive control games during the 15-min breaks between iTBS sessions (11 sessions on each treatment day, total sham CCT time = 495 min).
Medical University of South Carolina
Charleston, South Carolina, United States
RECRUITINGRetention
Percent of participants who completed all study procedures(i.e., Week 0 pre-treatment assessments, all treatment sessions, and Week 2 and Week 6 follow-up assessments). This will be calculated as a binary count (1=yes, 0=no) of completers divided by the total number of participants.
Time frame: From enrollment to the end of study at week 6 (1-month post-treatment assessment).
Adherence
Percent of treatment sessions completed. This will be calculated as the number of full iTBS and CCT sessions completed by each participant divided by the prescribed number of sessions.
Time frame: On each of the 3 treatment days during Week 1
Acceptability
Ratings of treatment acceptability on the Theoretical Framework of Acceptability (TFA) Questionnaire. The TFA is a self-report measure on which participants rate their perceptions of treatment acceptability via 5-point Likert-scale ratings on 8 items regarding the following: affective attitude, burden, perceived effectiveness, intervention coherence, self-efficacy, opportunity costs, ethicality, and general acceptability. Item scores will be averaged (ranging from 0-5), with higher scores indicating greater intervention acceptability.
Time frame: Week 0 (1 week pre-treatment), Week 2 (1 week post-treatment)
Change in NIH Toolbox-Cognition Battery (NIHTB-CB) Fluid Composite
The NIHTB-CB is a performance-based, iPad-administered \~30-minute suite of 7 tests that ascertain abilities in different cognitive domains (e.g. executive function, episodic memory, working memory, processing speed, language). It was developed using advanced psychometric techniques to minimize measurement error and produces normed subtest and composite scores. We will use the fully-corrected T-score (range T=0-100; Mean T=50, SD=10; higher scores indicate better cognition) of the Fluid Cognition Composite (normed for age and years of education).
Time frame: Week 0 (1 week pre-treatment), Week 2 (1 week post-treatment), and Week 6 (4 weeks post-treatment)
Change in Preclinical Alzheimer's Cognitive Composite (Mayo-PACC) Z-score
The Mayo-PACC is a composite derived from a brief battery of three neuropsychological tests of verbal episodic memory, processing speed, and semantic fluency. Z-scores will be computed for each test using a cognitively unimpaired normative reference; these will be averaged to create a single composite Z-score (Mean Z=0, SD=1; higher scores indicate better cognition).
Time frame: Week 0 (1 week pre-treatment), Week 2 (1 week post-treatment), and Week 6 (4 weeks post-treatment)
Change in Quick Dementia Rating System (QDRS) Total Score
The QDRS is an informant-rated measure used to evaluate changes in participants' memory, orientation, and functional abilities on a 5-point scale (0, 0.5, 1, 2, 3). Item scores are summed, and higher scores suggest greater impairment.
Time frame: Week 0 (1 week pre-treatment), Week 2 (1 week post-treatment), and Week 6 (4 weeks post-treatment)
Change in Informant-rated Everyday Cognition (ECog-II) Scale Total Score
The ECog-II scale is an informant-rated questionnaire of change in participants' everyday cognitive and functional abilities in six domains: memory, language, visuospatial function, and executive function. Each item is scored on a 4-point scale (0-"Better or no change", 1-Questionable/occasionally worse, 2-Consistnetly a little worse, 3-"Consistently much worse"). Each item also has a "I don't know" response option, which does not contribute to their score. Item scores will be averaged, with higher scores indicating greater impairment.
Time frame: Week 0 (1 week pre-treatment), Week 2 (1 week post-treatment), and Week 6 (4 weeks post-treatment)
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