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.
Age 60-85 (inclusive).
English as a first/primary language.
Adequate sensorimotor function and verbal expressive abilities to complete all assessments.
Must have a co-participant (e.g. spouse, adult child or relative, sibling, cohabitator, friend, caregiver) who has at least weekly in-person contact with the participant and is willing to participate in the study as a collateral informant.
Telephone Interview for Cognitive Status (TICS) score of ≤ 22 suggestive of dementia.
Prior diagnosis of Dementia (NIA-AA) or Major Neurocognitive Disorder (DSM-5).
Daily/weekly anticholinergic or sedative use. Stimulants may be allowed pending investigator review.
History of significant or unstable condition/s or treatments for these condition/s that may impact cognition (as determined by the study investigators) such as significant cardiac (e.g. heart failure), infectious (e.g. HIV, urinary tract infection), or metabolic disease (e.g. labile diabetes), cancer (e.g. brain cancer, chemotherapy-induced cognitive impairment), severe mental illness (e.g., bipolar disorder, psychoses), alcohol or substance use disorder, developmental disorder (e.g. autism spectrum disorder, intellectual disability), or other neurologic disease (e.g. movement disorder, multiple sclerosis, moderate to severe brain injury, seizures).
Parallel
Accelerated iTBS
DeviceA 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.
Computerized Cognitive Training
DeviceCCT 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 Computerized Cognitive Training
DeviceSham 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).
Retention
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.
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.
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.
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).
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.
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-"Consistently a little worse", 3-"Consistently much worse"). Each item also has an "I don't know" response option, which does not contribute to their score. Item scores will be averaged (range: 0-3), with higher scores indicating greater impairment.
Change in PROMIS Cognitive Function, Depression, Anxiety, Sleep Disturbance, and Fatigue T-scores
These are self-report questionnaires to which respondents rate their perceived (i.e., subjective) cognitive abilities and symptoms (i.e., depression, anxiety, fatigue, sleep disturbance) on a 5-point scale (from 1-"Not at all"; "Never" to 5-"Very much"; "Always", respectively) during the specified timeframe. It is a computer adaptive test given as a REDCap survey that yields normed T-scores (range T=0-100; Mean T=50, SD=10). Higher scores indicate more of the respective symptom.
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Medical University of South Carolina
Lead sponsor
National Institutes of Health (NIH)
Collaborator
National Institute on Aging (NIA)
Collaborator
