The Effects of Intermittent Theta Burst Stimulation in MCI and Early AD
Condition: Mild Cognitive Impairment; Alzheimer Disease; Cognitive Decline
MeSH terms: Alzheimer Disease; Cognitive Dysfunction
Study type: Interventional
Phase: Phase 2

Summary: 
      Transcranial magnetic stimulation (TMS) is a noninvasive brain stimulation technique that is
      increasingly used for a growing number of research and clinical applications.Typically, this
      transient magnetic field is focally applied with a figure-of-eight coil that is carefully
      placed on the surface of the scalp over a targeted stimulation site. Patterned repetitive TMS
      (rTMS), such as theta burst stimulation (TBS) can produce long-lasting effects on neural
      activity and behavior beyond the stimulation period (Chou et al., 2015a; Fitzgerald et al.,
      2006). In general, high frequency (> 5 Hz) rTMS and its newer version, intermittent theta
      burst stimulation (iTBS), facilitate cortical excitability, whereas low frequency (about 1
      Hz) rTMS and continuous theta burst stimulation contribute to opposite effects (Pascual-Leone
      et al., 2000; Huang et al., 2005; Wassermann and Zimmermann, 2012).Careful manipulation of
      the parameters comprising these patterned rTMS pulse trains can induce neuroplastic changes
      that resemble either long-term potentiation (LTP) or depression (Chen et al., 1997;
      Pascual-Leone et al., 1994). Early studies targeting the motor cortex helped elucidate which
      rTMS parameters promote particular responses and their neurophysiological underpinnings
      (Klomjai et al., 2015).

      In recent years, rTMS has been closely investigated to evaluate its potential to modulate
      cognitive functions in Alzheimer'sdisease (AD) and mild cognitive impairment (MCI). As
      compared to conventional excitatory rTMS protocols, iTBS leads to comparable effects with
      similar number of pulses but considerable shorter duration and lower intensity of stimulation
      (Bakker et al., 2015; Rossi, Hallett, Rossini, Pascual-Leone, & Safety, 2009). Recent
      literature also suggest that TBS has lower rates of reported adverse event (AE) compared to
      rTMS (Najib & Horvath, 2014). Therefore, iTBS is assumed to modulate cognitive function in
      people with cognitive impairments.
    

Detailed description: 
      Visit 1: Informed Consent, Brain MRI/Neuropsychological Battery

      Visit 2-11: (up to a week after visit 1) iTBS - or Sham-Treatment (10 sessions, 80% Resting
      Motor Threshold, 2s stimulation 8s inter-stimulus interval per train, 20 trains per block, 3
      blocks per session with a 5-min break, 1 session per day)

      Visit 12: (1 day or same day after visit 11) Functional Brain MRI/Neuropsychological Battery

      Visit 13: (4 weeks after visit 11) Functional Brain MRI/Neuropsychological Battery
    

Intervention name(s): intermittent theta burst stimulation
Intervention type(s): Device
Intervention description(s): active or Sham iTBS will be given to the AD/MCI patient
Other intervention name(s): Magstim rapid 2
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Transcranial magnetic stimulation; non-invasive brain stimulation