Noninvasive Brain Stimulation for Mild Cognitive Impairment
Condition: Mild Cognitive Impairment; Mild Neurocognitive Disorder; Cognitive Decline; Mental Deterioration; Cognitive Dysfunction; Memory Decline; Memory Loss; Memory Impairment
MeSH terms: Memory Disorders; Cognitive Dysfunction; Neurocognitive Disorders
Study type: Interventional

Summary: 
      The goal of this study is to test the efficacy of repetitive Transcranial Magnetic
      Stimulation (rTMS) as a treatment for Mild Cognitive Impairment (MCI). Participants will be
      randomly assigned to one of three treatment groups: Group 1: Active Dorsolateral Prefrontal
      Cortex (DLPFC) rTMS; Group 2: Active Lateral Parietal Cortex (LPC) rTMS; and Group 3:
      Inactive rTMS (Placebo) control (evenly split between each coil location). Participation in
      the study takes approximately 7 ½ months-including a 2-to 4-week treatment phase (20 rTMS
      sessions) and a 6-month follow-up phase.
    

Detailed description: 
      This study aims to test the efficacy of a non-pharmacological treatment for MCI that involves
      noninvasive brain stimulation (NIBS). Early studies in Alzheimer's disease (AD) dementia
      patients have found that repetitive transcranial magnetic stimulation (rTMS, a form of NIBS)
      improved global cognitive function and activities of daily living. Given that in AD, neuronal
      loss and synaptic dysfunction progress along brain networks, the results of these early
      studies of brain stimulation suggest there is sufficient neuroplasticity in AD for
      efficacious effects of brain stimulation. Of the very few rTMS studies in MCI that have been
      published, the effect size appears to be moderately large. However, it is not clear whether
      the dorsolateral prefrontal cortex (DLPFC), the stimulation site used in the most of the
      prior MCI/AD rTMS trials, is the optimal site for achieving the most efficacious effects
      including effects on episodic memory. Importantly, when other investigators used rTMS to
      stimulate a lateral parietal cortical (LPC) site in healthy young adults, significant effects
      of rTMS on memory were measureable weeks later. Moreover, functional connectivity of brain
      regions was selectively increased, including the posterior cingulate cortex (PCC), a "hub" of
      brain networks that is affected in amnestic MCI.

      Because stimulation of the DLPFC and the LPC may each have distinct effects, we designed this
      pilot trial to have two active rTMS treatment groups: DLPFC and LPC. A third group will
      receive inactive (placebo) rTMS to achieve a controlled, randomized, double-blind trial. For
      each of the three groups, stimulation will be bilateral, based on effects achieved in the AD
      studies. The primary hypothesis is that active rTMS (to either site of stimulation) will be
      superior to inactive (placebo) rTMS in improving memory. Measures of change in functional
      connectivity will be computed to examine whether there is evidence that rTMS changes
      connectivity of the PCC with other regions of the brain. In addition to looking at effects of
      rTMS on functional connectivity and cognition in relation to the cortical site stimulated,
      genetic markers will be collected toward addressing heterogeneity of response. To track the
      durability of rTMS effects on memory, participants will be followed longer than in any prior
      study (up to 6 months after the intervention). If this study finds rTMS improves memory in
      older adults with MCI, further clinical development of this non-pharmacological treatment
      could ultimately improve the lives of millions of older adults who have MCI and are at an
      increased risk of developing dementia.
    

Intervention name(s): Active rTMS (Bilateral DLPFC); Active rTMS (Bilateral LPC); Placebo rTMS (Inactive)
Intervention type(s): Device; Device; Device
Intervention description(s): TMS Stimulation Parameters for the active DLPFC rTMS intervention group will be: 10 Hz, 4-second train duration and 11-second inter-train interval. During each session, 2,000 pulses will be applied for each hemisphere (for a total of 4,000 pulses per session). Participants will receive 20 sessions (1 or 2 sessions per day, M-F).; TMS Stimulation Parameters for the active LPC rTMS intervention group will be: 10 Hz, 4-second train duration and 11-second inter-train interval. During each session, 2,000 pulses will be applied for each hemisphere (for a total of 4,000 pulses per session). Participants will receive 20 sessions (1 or 2 sessions per day, M-F).; For the Placebo rTMS (Inactive) group, the participant will wear scalp electrodes through which a low voltage, low electric current (2-20mA at no more than 100V) is passed to mimic the sensation of receiving actual rTMS. Participants will receive 20 sessions (1 or 2 sessions per day, M-F).
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: mild cognitive impairment; tms; rtms; transcranial magnetic stimulation; noninvasive brain stimulation; non-pharmacological