iTBS rTMS in Mild Cognitive Impairment

The purposes of this research are to test whether it is feasible to administer a treatment protocol called intermittent theta burst stimulation (iTBS) repetitive transcranial magnetic stimulation (rTMS) in adults with mild cognitive impairment (MCI), and to test whether iTBS rTMS treatments can improve memory in mild cognitive impairment (MCI).

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.

Eligibility Criteria:
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