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The Striatum and Hippocampus: "Hubs" of White Matter Connections in Parkinson's Disease Cognitive Decline

Award Number: F30AG067651
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 01/01/2021
PERIOD OF PERFORMANCE END DATE: 05/31/2024

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The Striatum and Hippocampus: "Hubs" of White Matter Connections in Parkinson's Disease Cognitive Decline - Due to an aging population and increased lifespan, dementia is an increasing clinical and public health issue. The most common and well-known cause is Alzheimer’s disease (AD), but other important disorders are involved in the development of AD-related dementias (ADRD). What is less appreciated is that Parkinson’s disease (PD), the second most common neurodegenerative disease, while often associated with motor dysfunction, contributes to ADRD with an incidence of dementia as high as 80% in late stages in which most have AD co-pathology. Therefore, this population exhibits a range of cognitive deficits that enables insight into mechanisms involved in ADRD. There seem to be two distinct cognitive profiles in these patients. One is a benign frontal profile characterized by executive and attention deficits, whereas the other is a posterior profile characterized by memory and visuospatial deficits that is associated with faster progression to dementia, often with AD co-pathology. The premise of this application is that identifying the neural circuitry underlying frontal and posterior function may provide insight into structural alterations occurring in ADRD. Dopaminergic therapies are known to improve frontal circuitry function, but not posterior circuitry, leading to the hypothesis that posterior circuit alterations are due to non-dopaminergic pathology, such as AD co-pathology. If true, the pattern of frontal-vs-posterior involvement may lead to differential responses to current treatments in ADRD. I plan to apply diffusion tensor tractography, a sensitive and widely available MRI technique, to measure microstructural integrity of white matter (WM) connections between brain regions. My central hypothesis is that WM alterations in frontal and posterior circuitry occurs in PD (Aim 1); that these alterations are associated with specific cognitive deficits and relate to differing rates of progression to dementia (Aim 2); and the ratio of frontal to posterior damage (F/P ratio) modulates the cognitive response to treatment (e.g., levodopa, deep brain stimulation, Aim 3). These aims will be implemented by leveraging existing datasets allowing a cost-effective and impactful investigation. This study immediately will impact knowledge of WM circuits related to dementia with insight into underlying mechanisms and therapeutic strategies, as well as provide the foundational line of research for future study of microstructural signatures of AD/ADRD. I have assembled a world-class mentoring team with expertise in areas related to my research and a history of highly-successful mentoring. The environment and institutional resources available to me for this project are excellent with a well-developed training plan and access to required equipment and research datasets. The proposed project and training plan will position me at the intersection of neuroscience and engineering, and enable me to tackle important clinical problems with the latest technological advancements. My new skills in neuroimaging analysis and neuropsychological testing to probe neurocognitive circuitry will provide a foundation for my career as an independent physician-engineer focused on alleviating the burden of AD/ADRD.


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 = -$24,941 )
2025	2024	PENNSYLVANIA STATE UNIVERSITY	500 UNIVERSITY DRIVE	HERSHEY	PA	17033	DAUPHIN	USA	Aging Research	002	4	3/25/2025	NON-COMPETING CONTINUATION	-$6,832
2025	2024	PENNSYLVANIA STATE UNIVERSITY	500 UNIVERSITY DRIVE	HERSHEY	PA	17033	DAUPHIN	USA	Aging Research	001	4	1/28/2025	NON-COMPETING CONTINUATION	$0
2025	2024	PENNSYLVANIA STATE UNIVERSITY	500 UNIVERSITY DRIVE	HERSHEY	PA	17033	DAUPHIN	USA	Aging Research	000	4	11/21/2024	NON-COMPETING CONTINUATION	-$18,109
														Subtotal = -$24,941

Issue Date FY: 2024 ( Subtotal = $52,694 )
2024	2024	PENNSYLVANIA STATE UNIVERSITY	500 UNIVERSITY DRIVE	HERSHEY	PA	17033	DAUPHIN	USA	Aging Research	000	4	12/5/2023	NON-COMPETING CONTINUATION	$52,694
														Subtotal = $52,694

Issue Date FY: 2023 ( Subtotal = $52,694 )
2023	2023	PENNSYLVANIA STATE UNIVERSITY, THE	500 UNIVERSITY AVE RM C1607	HERSHEY	PA	17033	DAUPHIN	USA	Aging Research	000	3	11/10/2022	NON-COMPETING CONTINUATION	$51,752
2023	2023	PENNSYLVANIA STATE UNIVERSITY	500 UNIVERSITY DRIVE	HERSHEY	PA	17033	DAUPHIN	USA	Aging Research	001	3	2/23/2023	NON-COMPETING CONTINUATION	$942
														Subtotal = $52,694

Issue Date FY: 2022 ( Subtotal = $33,549 )
2022	2022	PENNSYLVANIA STATE UNIVERSITY, THE	500 UNIVERSITY AVE RM C1607	HERSHEY	PA	17033	DAUPHIN	USA	Aging Research	001	2	5/2/2022	NON-COMPETING CONTINUATION	$717
2022	2022	PENNSYLVANIA STATE UNIVERSITY, THE	500 UNIVERSITY AVE RM C1607	HERSHEY	PA	17033	DAUPHIN	USA	Aging Research	002	2	7/26/2022	NON-COMPETING CONTINUATION	-$1
2022	2022	PENNSYLVANIA STATE UNIVERSITY, THE	500 UNIVERSITY AVE RM C1607	HERSHEY	PA	17033	DAUPHIN	USA	Aging Research	000	2	11/19/2021	NON-COMPETING CONTINUATION	$32,833
														Subtotal = $33,549

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2020	PENNSYLVANIA STATE UNIVERSITY, THE	500 UNIVERSITY AVE RM C1607	HERSHEY	PA	17033	DAUPHIN	USA	Aging Research	001	1	12/22/2020	NEW	$0
2021	2020	PENNSYLVANIA STATE UNIVERSITY, THE	500 UNIVERSITY AVE RM C1607	HERSHEY	PA	17033	DAUPHIN	USA	Aging Research	002	1	5/27/2021	NEW	$0
2021	2020	PENNSYLVANIA STATE UNIVERSITY, THE	500 UNIVERSITY AVE RM C1607	HERSHEY	PA	17033	DAUPHIN	USA	Aging Research	000	1	10/21/2020	NEW	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $32,209 )
2020	2020	PENNSYLVANIA STATE UNIVERSITY, THE	500 UNIVERSITY DR C1607	HERSHEY	PA	17033	DAUPHIN	USA	Aging Research	000	1	9/17/2020	NEW	$32,209
														Subtotal = $32,209

Grand Total All Awards = $146,205

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The Striatum and Hippocampus: "Hubs" of White Matter Connections in Parkinson's Disease Cognitive Decline

Award Number: F30AG067651

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 01/01/2021

PERIOD OF PERFORMANCE END DATE: 05/31/2024

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