Alzheimer?s Disease (AD) affects millions of people in the US and worldwide, and is becoming an increased burden on individual and society. Individuals with amnestic mild cognitive impairment (aMCI) are at greater risk for development of AD. A reliable method of treatment for individuals with aMCI could help not only to improve the lives of elderly individuals with memory impairment, but also potentially prevent or delay the development of AD. Theta burst transcranial magnetic stimulation (TBS) is a non-invasive neuromodulation method that shows promise for improving memory and may be applied to brain areas that are functionally connected to the hippocampus in order to restore memory function. Because the ability to apply stimulation to modify memory functions depends on the application of stimulation at distinct and specific sites in the complex neuronal circuitry underlying these functions, neuroimaging guided targeting of TBS treatment will provide individualized tailoring of therapeutic intervention needed for maximum efficacy. The proposed project will therefore implement a novel high-resolution functional magnetic resonance imaging (fMRI) guided TBS method to improve hippocampal-cortical connectivity and consequent episodic memory in elderly aMCI individuals with and without genetic risk for AD. Functional MRI, scalp electroencephalography (EEG), and genetic testing will also be used to characterize brain network changes and genetic factors that are associated with TBS related memory restoration. The implications of TBS related memory restoration to patients affected with disorders of memory is of great significance and of urgent need. The proposed project will therefore develop a novel method for memory enhancement, characterize associated brain changes, contribute to the understanding of hippocampal-cortical networks and their role in memory, and ultimately provide a novel therapeutic approach to human memory disorders. The data from this project will demonstrate a proof-of-concept that TBS can be used to improve memory in aMCI, and will launch an emerging and pivotal area of research that will provide therapeutic interventions for patients afflicted with life debilitating cognitive disorders.

Public Health Relevance

Alzheimer?s disease (AD) is the most common form of dementia and affects as many as six million Americans, with incidence increasing with lifespan and healthcare costs astronomical. Because amnestic mild cognitive impairment (aMCI) can often precede conversion to full AD, with accelerated and debilitating memory deficits, it is increasingly important to develop therapies that can restore memory function in aMCI subjects prior to conversion and grant a multipronged understanding of the neural basis for aMCI as a precursor to AD. We will combine structural and functional magnetic resonance imaging, scalp electroencephalography, genetic testing, and image-guided theta-burst transcranial magnetic stimulation to improve memory function in elderly individuals with aMCI and elucidate individual differences and functional changes underlying clinical improvements, aiding the development of individually tailored noninvasive therapies for restoring memory function and contributing to our knowledge of the functional bases of memory in the coherence and dynamic evolution of brain networks.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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Mclinden, Kristina
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University of California Los Angeles
Schools of Arts and Sciences
Los Angeles
United States
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