Brain Stimulation and Cognitive Training for MCI

NCT07526740 | Recruiting DMC FDA Device

• 2 other identifiers: Pro001383521K23AG090691-01
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Mild Cognitive Impairment (MCI); Mild Neurocognitive Disorder; Neurocognitive Disorders; Cognitive Dysfunction; Cognition Disorders

Keywords

Aging; Alzheimers; Memory Loss; Mild Cognitive Impairment; Transcranial Magnetic Stimulation; cognitive training

Outcome Measures

Primary Outcomes (5)

• 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.

  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.

  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.

  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).

  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).

  Week 0 (1 week pre-treatment), Week 2 (1 week post-treatment), and Week 6 (4 weeks post-treatment)

Secondary Outcomes (2)

• Change in Quick Dementia Rating System (QDRS) Total Score

  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

  Week 0 (1 week pre-treatment), Week 2 (1 week post-treatment), and Week 6 (4 weeks post-treatment)

Other Outcomes (1)

• Change in PROMIS Cognitive Function, Depression, Anxiety, Sleep Disturbance, and Fatigue T-scores

  Week 0 (1 week pre-treatment), Week 2 (1 week post-treatment), and Week 6 (4 weeks post-treatment)

Study Arms (2)

iTBS+CCT

EXPERIMENTAL

Participants will receive 12 sessions of accelerated iTBS and 11 sessions of active CCT on each of 3 treatment days.

Device: Accelerated iTBS; Device: Computerized Cognitive Training

iTBS+shamCCT

SHAM COMPARATOR

Participants will receive 12 sessions of accelerated iTBS and 11 sessions of sham CCT on each of 3 treatment days.

Device: Accelerated iTBS; Device: Sham Computerized Cognitive Training

Interventions

Accelerated iTBS DEVICE

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.

iTBS+CCT; iTBS+shamCCT

Sham Computerized Cognitive Training DEVICE

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).

iTBS+shamCCT

Computerized Cognitive Training DEVICE

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).

iTBS+CCT

Eligibility Criteria

• Age: 60 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• i. Age 60-85 (inclusive). ii. English as a first/primary language. iii. Adequate sensorimotor function and verbal expressive abilities to complete all assessments.
• iv. 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.
• v. Meets the following requirements for current and prior medications and treatments:
• Is on fixed pharmacotherapy (i.e. stable dose of medication/s) for ≥ 4 weeks before enrollment. This includes, but is not limited to, cholinesterase inhibitors, NMDA receptor antagonists, and antidepressants.
• Anti-amyloid monoclonal antibody therapy for AD/MCI:
• Prior treatment is permitted if last infusion occurred ≥ 8 weeks before enrollment.
• Current treatment is permitted if the dose has been stable for ≥ 12 weeks before enrollment, with no planned dose change during study participation.
• Prior TMS treatment is permitted if the last stimulation session was ≥ 24 weeks before enrollment.
• vi. Documented diagnosis of MCI per NIA-AA criteria or Mild Neurocognitive Disorder per DSM-5 criteria by a healthcare provider within the past year, with a presumed etiology of possible or probable AD42 vii. Met actuarial neuropsychological criteria for MCI43 within the past year (i.e. ≥2 impaired scores within one cognitive domain, or ≥1 impaired scores in ≥3 domains, where an impaired score is defined as ≤16th percentile using appropriate demographically-corrected norms).

You may not qualify if:

• i. Telephone Interview for Cognitive Status (TICS) score of ≤ 22 suggestive of dementia.
• ii. Prior diagnosis of Dementia (NIA-AA) or Major Neurocognitive Disorder (DSM-5).
• iii. Daily/weekly anticholinergic or sedative use. Stimulants may be allowed pending investigator review.
• iv. 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).
• v. Plan to initiate treatment for AD/MCI with monoclonal antibody therapy during study participation.
• vi. For those currently receiving monoclonal antibody therapy, documented history of clinically significant amyloid-related imaging abnormalities (ARIA) in their medical record.
• vii. Current use of any implanted brain stimulation device. viii. Enrolled in a clinical trial or has received an investigational medication or device in the last 30 days that may impact cognition or mood.
• ix. MRI contraindications (e.g., ferromagnetic implants, claustrophobia). x. Unable or unwilling to engage in BrainHQ activities. xi. TMS contraindications (e.g., ferromagnetic implants, conditions or treatments that lower seizure threshold, taking medications that have short half-lives) or no identifiable motor threshold.

Sponsors & Collaborators

• Medical University of South Carolina: lead
• National Institutes of Health (NIH): collaborator
• National Institute on Aging (NIA): collaborator

Study Sites (1)

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

RECRUITING

MeSH Terms

Conditions

Cognitive Dysfunction; Neurocognitive Disorders; Cognition Disorders; Memory Disorders

Condition Hierarchy (Ancestors)

Mental Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Stephanie Aghamoosa

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kaitlin Cox

CONTACT

843-608-1674; coxkai@musc.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor-Faculty

Model Details: Each participant will be randomized after W0 (pre-treatment assessments) to either active or sham CCT. We will use a random permuted block design (block sizes of 2 and 4) to ensure equal sample sizes of the two groups, with an allocation ratio of 1:1 and stratification by monoclonal antibody (mAB) treatment (i.e., naïve vs. treated, where "treated" refers to either prior or current treatment) to ensure balance across groups in this covariate. All participants will receive the same number of CCT and iTBS sessions per day irrespective of group they are assigned.

Study Record Dates

• First Submitted: April 2, 2026
• First Posted: April 13, 2026
• Study Start: March 16, 2026
• Primary Completion (Estimated): May 31, 2030
• Study Completion (Estimated): May 31, 2030
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (1)