Non-invasive brain stimulation plus computer-based memory training for mild cognitive impairment

Combining Brain Stimulation With Computerized Cognitive Training for MCI

This trial will test whether a short course of non-invasive brain stimulation combined with one of two computer-based brain-training programs helps people aged 60–85 with mild cognitive impairment improve memory, thinking, mood, and daily function.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 60 Years to 85 Years
• Sex: All
• Sponsor: Medical University of South Carolina (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Charleston, South Carolina)
• Trial ID: NCT07526740 on ClinicalTrials.gov

What this trial studies

This randomized, controlled trial gives all participants accelerated intermittent theta burst stimulation (iTBS) over three days while randomly assigning them to active computerized cognitive training (CCT) or a sham CCT. The primary goals are to determine feasibility, acceptability, and preliminary effect sizes for combined iTBS+CCT on memory, other cognitive domains, mood, and daily function in people with MCI. Outcomes are measured with standardized neurocognitive tests, psychosocial measures, and collateral reports from a co-participant. Participants must be English-speaking adults aged 60–85 on stable medications and able to attend in-person visits at the study site.

Who should consider this trial

Good fit: Ideal participants are English-speaking adults aged 60–85 with mild cognitive impairment who have adequate sensorimotor and verbal abilities, a nearby co-participant for collateral information, and stable medications.

Not a fit: People with more advanced dementia, unstable medical or psychiatric conditions, inability to tolerate brain stimulation, non-English speakers, or those without a willing co-participant are less likely to benefit or be eligible.

Why it matters

Potential benefit: If successful, the combined treatment could produce measurable improvements in memory, thinking, mood, and everyday functioning for people with MCI.

How similar studies have performed: Prior small studies pairing transcranial magnetic stimulation with cognitive training have reported modest cognitive benefits, but accelerated 3-day iTBS combined with brief CCT is relatively novel and unproven.

Eligibility criteria

Inclusion Criteria:

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:

1. 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.
2. 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.
3. 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).

Exclusion Criteria:

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.

Where this trial is running

Charleston, South Carolina

• Medical University of South Carolina — Charleston, South Carolina, United States (Recruiting)

Study contacts

• Principal investigator: Stephanie Aghamoosa — Medical University of South Carolina
• Study coordinator: Kaitlin Cox

Conditions Mild Cognitive Impairment; Mild Neurocognitive Disorder; Neurocognitive Disorders; Cognitive Dysfunction; Cognition Disorders; Aging; Alzheimers; Memory Loss