The pathophysiology of Alzheimer's disease (AD) links amyloid plaques, neurofibrillary tangles, and neurodegeneration to neural network dysfunction, which ultimately manifests as symptoms of cognitive impairment. Patients with typical or atypical AD have dysfunction of brain networks that support cognitive functions that are impaired. Emerging evidence suggests that, in patients with the same degree of regional atrophy of these systems, hypometabolism or disrupted fcMRI connectivity may vary, offering the opportunity to intervene to improve network function and potentially symptoms, at least for a period of time. Preliminary evidence from studies with repetitive transcranial magnetic stimulation (rTMS) in humans demonstrate that these brain networks can be modulated in a manner that promotes improved behavioral task performance. However, most of this work has been done in cognitively normal young individuals, with many questions remaining regarding the potential application of rTMS to patients with prodromal AD. In this pilot project, we aim to investigate the selectivity of rTMS modulation of these two networks in patients with aMCI and lvPPA due to underlying AD based on amyloid and tau PET imaging collected as part of a separate project. We will examine the selectivity of rTMS modulation using simultaneous functional MRI and FDG-PET, and will investigate the effects on memory and language task performance The ultimate goal of this research is to begin to determine how TMS changes brain network function in patients with diseased brains and whether this could potentially support benefits in cognitive function in typical and atypical clinical forms of AD.

Public Health Relevance

The dysfunction of major brain networks is thought to be the basis of symptoms in patients with typical or atypical Alzheimer's disease (AD). Studies with repetitive transcranial magnetic stimulation (rTMS) in humans demonstrate that these brain networks can be modulated in a manner that promotes improved behavioral task performance. Here we seek to understand whether rTMS can improve the function of brain networks and symptoms in patients with very early typical and atypical AD.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AG056958-02
Application #
9551486
Study Section
Clinical Neuroscience and Neurodegeneration Study Section (CNN)
Program Officer
Wagster, Molly V
Project Start
2017-09-01
Project End
2019-04-30
Budget Start
2018-05-01
Budget End
2019-04-30
Support Year
2
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
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