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Network Modulation in Alzheimer's Disease


This study will assess the effects of noninvasive brain stimulation on memory and language in people with amnestic mild cognitive impairment (aMCI) or the logopenic variant of primary progressive aphasia (lvPPA). Repetitive transcranial magnetic stimulation (rTMS) will be used to stimulate nodes of brain networks that are thought to be affected in these two conditions. Researchers will compare the effects on cognitive-test performance after up to 2 weeks of treatment.

Minimum Age Maximum Age Gender Healthy Volunteers
18 Years 90 Years All No
September 1, 2018
December 2021

  • Diagnosis of either lvPPA or aMCI
  • Presence of underlying Alzheimer's pathology must be verified by positron emission tomography scan or cerebrospinal fluid biomarkers
  • Participants with lvPPA must have at least mild to moderate language impairment
  • Participants with MCI must have at least mild to moderate episodic memory impairment
  • Native English speaker
  • Study partner who can accompany participant to all study visits

  • Any history of seizures, unexplained loss of consciousness, or a first-degree family member with epilepsy (to ensure safety to receive rTMS)
  • Any history of significant co-occurring neurological illness unrelated to the neurodegenerative disease in question (e.g., multiple sclerosis) or significant medical problems (e.g., poorly controlled diabetes, hypertension, or cancer within 5 years)
  • Active symptoms of major depressive disorder, bipolar disorder, schizophrenia, substance use disorder, or significant intellectual disability
  • Magnetic resonance imaging (MRI) evidence of significant cerebrovascular disease, hydrocephalus, or space-occupying intracranial mass
  • Inability to undergo MRI or rTMS, including: cardiac pacemaker or pacemaker wires, neurostimulators, implanted pumps, metal in the body (rods, plates, screws, shrapnel, dentures, IUD), surgical aneurysm clips in the head, previous neurosurgery, or cochlear implants
  • Pregnant or breastfeeding

Repetitive TMS is a method to stimulate a specific part of the brain using electromagnetic induction. In this study, researchers will target a node of the default mode network, the angular gyrus, in MCI participants and a node of the language network, the posterior inferior frontal gyrus, in lvPPA participants. They will use functional connectivity MRI before and after rTMS to look for language-test and memory-test improvements in participants with lvPPA and MCI, respectively. Participants will receive rTMS for 5 consecutive days for up to 2 weeks. Some participants will receive active rTMS; some will receive a sham treatment.

Researchers will assess the reliability of their approach to brain-network modulation by studying the same subjects over repeated sessions, with the same methodology. They predict that changes in network functional connectivity following rTMS to the targeted brain regions will improve cognition and last for at least 2 weeks after treatment. They hypothesize that changes in network functional connectivity will be selective, in that stimulation to the angular gyrus will not modulate connectivity within the language network, while stimulation to the posterior inferior frontal gyrus will not modulate default mode network connectivity.

Name City State Zip Status Primary Contact
Massachusetts General Hospital
Charlestown Massachusetts 02129 Recruiting Courtney Sullivan

Brigham and Women's Hospital

Name Phone Email
Mark C Eldaief, M.D. (617) 726-1728


Neuromodulation of Language and Memory Networks in Alzheimer's Disease