Wednesday, July 2, 2025 7/2/2025

Understanding the structural, functional, and prognostic implications of cortical excitability in Alzheimer's disease

Award Number: K23AG068364
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 05/15/2021
PERIOD OF PERFORMANCE END DATE: 04/30/2026

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Understanding the structural, functional, and prognostic implications of cortical excitability in Alzheimer's disease - PROJECT SUMMARY/ABSTRACT Recent therapeutic drug trials in Alzheimer’s disease (AD) have failed to improve cognitive outcomes despite improvements on imaging-based targets (e.g., amyloid PET). One possible missing link is a failure to restore normal neuronal function. Measures of cortical excitability using transcranial magnetic stimulation with electroencephalography (TMS-EEG) have the potential to fill this gap by measuring the neuronal response to controlled perturbation. However, practical applications of TMS-EEG measures are currently limited by a dearth of data from brain regions involved in early-stage AD pathophysiology, and a lack of understanding of how cortical excitability is related to clinically useful metrics. The long-term goal of this project is to determine the extent to which cortical excitability is an important prognostic marker and/or treatment target in AD. This study assesses excitability in both motor cortex—a well-characterized TMS site—and parietal cortex—a brain involved in the early stages of AD pathogenesis. The objective of the present proposal is to understand how parietal cortical excitability is related to neuroimaging abnormalities and prognosis in a cohort of early-stage symptomatic AD participants (early AD). The hypothesis is that increased cortical excitability in parietal cortex is related to neurodegeneration, decreased network connectivity, and more rapid clinical decline. This will be tested with three independent Aims to assess how cortical excitability is related to 1) local cortical thickness, 2) resting state fMRI connectivity; and 3) disease progression. The proposed project is highly innovative, using TMS-EEG measures to capture local cortical excitability in AD, integrating neuroimaging and neurophysiologic measurements, and testing the extent to which cortical excitability predicts meaningful clinical outcomes. This contribution will be significant because it will inform our understanding of how measures of synaptic function are related to progression of AD pathology. Findings from this study will lay the groundwork for future clinical trials in AD seeking to measure restoration of neuronal function using novel biomarkers. The candidate has a strong commitment to a clinical research career in Alzheimer’s disease and related dementias. She is a practicing cognitive neurologist at Beth Israel Deaconess Medical Center and Instructor in Neurology at Harvard Medical School. Her training plan and research project are specifically designed to build her expertise in AD biomarkers, advanced neuroimaging techniques, and biostatistics for AD clinical trials. Her mentorship team, led by Dr. Daniel Press and Dr. Michael Fox, will provide critical guidance on the integration of TMS measures with neuroimaging. Additional mentorship will be provided by Dr. Mouhsin Shafi on TMS-EEG, Dr. Reisa Sperling on AD biomarkers, and Dr. Long Ngo on biostatistics. Completion of this five-year career development plan will allow the candidate to launch a career as an independent investigator using novel neurophysiologic tools to advance prognosis and treatment of AD.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $206,634 )
2025	2025	BETH ISRAEL DEACONESS MEDICAL CENTER, INC.	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Aging Research	002	5	5/20/2025	NON-COMPETING CONTINUATION	$165,021
2025	2025	BETH ISRAEL DEACONESS MEDICAL CENTER, INC.	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Aging Research	000	4	12/30/2024	SUPPLEMENT FOR EXPANSION	$75,352
2025	2024	BETH ISRAEL DEACONESS MEDICAL CENTER, INC.	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Aging Research	001	4	4/8/2025	NON-COMPETING CONTINUATION	-$33,739
														Subtotal = $206,634

Issue Date FY: 2024 ( Subtotal = $165,023 )
2024	2024	BETH ISRAEL DEACONESS MEDICAL CENTER, INC.	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Aging Research	000	4	5/6/2024	NON-COMPETING CONTINUATION	$165,023
														Subtotal = $165,023

Issue Date FY: 2023 ( Subtotal = $165,020 )
2023	2023	BETH ISRAEL DEACONESS MEDICAL CENTER, INC	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Aging Research	000	3	5/11/2023	NON-COMPETING CONTINUATION	$165,020
														Subtotal = $165,020

Issue Date FY: 2022 ( Subtotal = $219,020 )
2022	2022	BETH ISRAEL DEACONESS MEDICAL CENTER, INC	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Aging Research	001	2	9/7/2022	SUPPLEMENT FOR EXPANSION	$54,000
2022	2022	BETH ISRAEL DEACONESS MEDICAL CENTER, INC	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Aging Research	000	2	6/1/2022	NON-COMPETING CONTINUATION	$165,020
														Subtotal = $219,020

Issue Date FY: 2021 ( Subtotal = $165,021 )
2021	2021	BETH ISRAEL DEACONESS MEDICAL CENTER, INC	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Aging Research	001	1	7/20/2021	NEW	$0
2021	2021	BETH ISRAEL DEACONESS MEDICAL CENTER, INC	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Aging Research	000	1	5/11/2021	NEW	$165,021
														Subtotal = $165,021

Grand Total All Awards = $920,718

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Understanding the structural, functional, and prognostic implications of cortical excitability in Alzheimer's disease

Award Number: K23AG068364

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 05/15/2021

PERIOD OF PERFORMANCE END DATE: 04/30/2026

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