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White Matter Structural Integrity and Cognition in Children with Sickle Cell Disease

Award Number: F32HL143915
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 03/31/2019
PERIOD OF PERFORMANCE END DATE: 11/01/2021

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White Matter Structural Integrity and Cognition in Children with Sickle Cell Disease - Children with sickle cell disease (SCD) experience widespread cognitive deficits along with numerous other medical consequences including stroke, silent cerebral infarction (SCI), acute chest syndrome, pulmonary hypertension, chronic kidney disease, and premature death. Molecular changes within the sickled cell greatly reduces the oxygen-carrying capacity of the blood, but understanding of the pathophysiology of cerebrovascular disease such as stroke and SCI is inadequate. Therefore, the specific mechanisms by which cognitive deficits occur are not yet fully understood. The cognitive deficits experienced by children with SCD are associated with impairments in daily functioning and reduced education attainment, making cognition a critical target for treatment and intervention. Thus, understanding how cognitive deficits are related to poor white matter in children with SCD with and without SCI is a critical next step in efforts to intervene and remediate cognitive deficits. Because children with SCD experience widespread white matter abnormalities, we suggest that characterizing their brain organization as a structural connectome may help to explain why changes in axon fiber microstructure (e.g., demyelination or loss of axons) in diffuse locations along a fiber pathway may lead to the same cognitive deficits in different children. As this is the first study to assess structural connectomes using diffusion MRI in children with SCD, we begin with the broad aim to determine whether children with SCD have impaired global structural connectivity efficiency in comparison to controls. We will next determine whether children with SCD and SCI and children with SCD without SCI have differences in network efficiency calculated using graph theory analyses. Additionally, we will investigate rich club organization, which is a set of highly connected and interconnected regions and determine whether there are differences between children with SCD and controls and investigate whether there is preferential rich club disruption in children with SCD and SCI. We will examine whether these graph metrics correlate with cognition in SCD with and without SCI. Finally, we will assess Montelukast, a targeted intervention, and whether Montelukast provides improvements in oxygen availability and thus improves global structural connectivity efficiency and rich club organization in children with sleep-disordered breathing, a common medical complication associated with SCD. The goal of this proposal is to gain a more complex understanding of the global efficiency and rich club organization of the structural connectome, determine associations with cognitive deficits, and whether efficiency can be improved and cognitive deficits be ameliorated by intervention. The findings will have important implications for functional outcomes for children with SCD and will provide information that could influence the development of future treatment options tailored to the specific cognitive and clinical needs of this population.


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: 2023 ( Subtotal = $0 )
2023	2021	UNIVERSITY COLLEGE LONDON	GOWER STREET	LONDON				GBR	Blood Diseases and Resources Research	005	3	1/19/2023	NON-COMPETING CONTINUATION	$0
2023	2020	UNIVERSITY COLLEGE LONDON	GOWER STREET	LONDON				GBR	Blood Diseases and Resources Research	004	2	1/19/2023	NON-COMPETING CONTINUATION	$0
2023	2018	UNIVERSITY COLLEGE LONDON	GOWER STREET	LONDON				GBR	Blood Diseases and Resources Research	001	1	1/19/2023	NEW	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = -$22,422 )
2022	2021	UNIVERSITY COLLEGE LONDON	GOWER STREET	LONDON				GBR	Blood Diseases and Resources Research	000	3	4/28/2022	NON-COMPETING CONTINUATION	$0
2022	2021	REDACTED DUE TO PII		LONDON				GBR	Blood Diseases and Resources Research	001	3	5/10/2022	NON-COMPETING CONTINUATION	-$22,422
														Subtotal = -$22,422

Issue Date FY: 2021 ( Subtotal = $66,762 )
2021	2021	UNIVERSITY COLLEGE LONDON	GOWER STREET	LONDON				GBR	Blood Diseases and Resources Research	002	3	8/3/2021	NON-COMPETING CONTINUATION	$11,850
2021	2021	REDACTED DUE TO PII		LONDON				GBR	Blood Diseases and Resources Research	001	3	4/5/2021	NON-COMPETING CONTINUATION	$54,540
2021	2020	REDACTED DUE TO PII		LONDON				GBR	Blood Diseases and Resources Research	000	2	3/9/2021	NON-COMPETING CONTINUATION	$372
														Subtotal = $66,762

Issue Date FY: 2020 ( Subtotal = $64,554 )
2020	2020	REDACTED DUE TO PII		LONDON		WC1E 6BT		GBR	Blood Diseases and Resources Research	000	2	3/27/2020	NON-COMPETING CONTINUATION	$52,704
2020	2020	UNIVERSITY COLLEGE LONDON	GOWER STREET	LONDON		WC1E 6BT		GBR	Blood Diseases and Resources Research	001	2	4/23/2020	NON-COMPETING CONTINUATION	$11,850
														Subtotal = $64,554

Issue Date FY: 2019 ( Subtotal = $0 )
2019	2018	REDACTED DUE TO PII		LONDON		WC1E 6BT		GBR	Blood Diseases and Resources Research	000	1	12/20/2018	NEW	$0
2019	2018	REDACTED DUE TO PII		LONDON		WC1E 6BT		GBR	Blood Diseases and Resources Research	001	1	12/20/2018	NEW	$0
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $58,282 )
2018	2018	UNIVERSITY COLLEGE LONDON	GOWER STREET	LONDON		WC1E 6BT		GBR	Blood Diseases and Resources Research	000	1	9/24/2018	NEW	$48,432
2018	2018	UNIVERSITY COLLEGE LONDON	GOWER STREET	LONDON		WC1E 6BT		GBR	Blood Diseases and Resources Research	001	1	9/25/2018	NEW	$9,850
														Subtotal = $58,282

Grand Total All Awards = $167,176

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White Matter Structural Integrity and Cognition in Children with Sickle Cell Disease

Award Number: F32HL143915

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 03/31/2019

PERIOD OF PERFORMANCE END DATE: 11/01/2021

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