iTBS rTMS in Mild Cognitive Impairment

To test the feasibility of conducting a 10-day Intermittent Theta Burst Stimulation (iTBS) repetitive Transcranial Magnetic Stimulation (rTMS) protocol twice using a cross-over design in individuals with Mild Cognitive Impairment (MCI), pilot test the study protocol to assess study design, and collect pilot data on the effect of stimulations over 3 different brain regions (left dorsolateral prefrontal cortex (DLPFC), lateral parietal cortex (LPC), vertex) on working memory, new-learning and executive function in MCI. Neuropsychological and sleep measures, functional brain magnetic resonance imaging (fMRI), high density EEG and questionnaires will be performed at 5 timepoints - baseline, post-treatment after first period of 10 daily iTBS rTMS sessions, post-washout period of 4 weeks, post-treatment after cross-over to second period of 10 daily iTBS rTMS sessions, and 4 weeks follow-up post-treatment.

Inclusion criteria

• Must speak English fluently
• Diagnosis of MCI as defined by:

• Clinical diagnosis by a neurologist
• Neuropsychological testing support of MCI
• Meet criteria for MCI
• Subjective cognitive decline reported by participant and/or an informant
• Objective memory impairment in one or more cognitive domains for age
• Essentially preserved general cognitive function
• Largely intact functional activities
• Does not meet criteria for dementia as judged by a clinician
• Eligible for transcranial magnetic stimulation (TMS) based on safety criteria
• Clinical Dementia Rating=0.5
• Geriatric Depression Scale score less than 6
• Medically stable and in good general health
• Not pregnant, lactating, or of childbearing potential
• Stable medication regimen for at least 4 weeks prior to baseline visit
• Adequate visual and auditory abilities to complete neuropsychological testing
• Ability to provide informed consent
• Have a care partner who is available to accompany the participant to study visits for the duration of the protocol.

Exclusion criteria

• Inability to communicate in the English language
• Meet criteria for dementia
• Contraindications to TMS or MRI, including patients who have

• conductive, ferromagnetic or other magnetic-sensitive metals implanted in their head or within 30 cm of the treatment coil (e.g., cochlear implants, implanted electrodes/stimulators, aneurysm clips or coils, stents, bullet fragments or jewelry)
• active or inactive implants, including deep brain stimulators, cochlear implants, vagus nerve stimulators or implanted device leads
• Any true positive findings on the TMS safety screening form
• Prior exposure to TMS, electroconvulsive therapy (ECT), or any neurostimulation within the past 12 months
• History of epilepsy or seizures
• Medical conditions that increase risk of seizures

• History of traumatic brain injury
• History of intracranial mass or lesion
• History of stroke, including hemorrhagic stroke and ischemic stroke
• Psychiatric disorders

• Primary psychotic disorder (schizophrenia, schizoaffective, or schizophreniform disorder), any history
• Primary mood disorder (major depressive disorder, bipolar disorder) within the past 12 months
• Substance use disorder (except caffeine and nicotine) within the past 12 months
• Active symptoms of depression, anxiety, mania, psychosis, or substance use (except caffeine and nicotine) within the past year

• Active symptoms of depression will be identified based on geriatric depression scale ≥ 6
• Other active symptoms of psychiatric conditions to be determined by study investigators
• Sleep disorders that are considered clinically significant and not sufficiently treated by the investigative team, including untreated obstructive sleep apnea (apnea-hypopnea index >15), untreated/suboptimally treated REM sleep behavior disorder, untreated/suboptimally treated restless legs syndrome
• Pregnancy or suspected pregnancy
• Participation in another concurrent interventional clinical trial
• Any unstable medical condition
• Inability to provide informed consent
• Inability to adhere to the protocol