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Blood-Brain Barrier Disruption as a Biomarker for Perioperative Neurocognitive Disorder:Cognitive Recovery after Elective Surgery

Award Number: R01AG058648
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Blood-Brain Barrier Disruption as a Biomarker for Perioperative Neurocognitive Disorder:Cognitive Recovery after Elective Surgery - Despite decades of research, little is known about how to effectively prevent postoperative delirium or postoperative cognitive dysfunction; however, emerging perspectives on the role of the blood-brain barrier (BBB) in health and disease suggest that increased permeability (BBB dysfunction) may be associated with the development of postoperative delirium (POD) and postoperative cognitive dysfunction (POCD). Up to half of all older adults develop POD, and POCD is reported in 5-20% of surgical patients over 65 years; at present, neither condition can be effectively prevented nor treated and both are associated with decreased quality of life and survival, as well as numerous other negative outcomes. Our long-term goal is to advance knowledge of the effects of surgical stress on the aging brain, ultimately leading to effective strategies to improve the cognitive safety of surgery. The objective of this research is to investigate the extent to which an innovative brain imaging technique, water exchange index MRI (WEI-MRI) evidence of BBB dysfunction predicts the incidence of POD and POCD, in a longitudinal study of older adults undergoing major elective non-cardiac surgeries. Our central hypothesis is that in the aging brain, BBB dysfunction is a biomarker for brain vulnerability that predicts increased risk for POD, POCD, and progressive cognitive decline. We will test this hypothesis by accomplishing the following specific aims: 1) Evaluate associations between BBB permeability and the incidence of POD; 2) Evaluate associations between BBB permeability and the incidence of POCD; and 3) Identify changes in markers of endothelial injury and inflammation in peripheral blood that predict POD and POCD. This approach is innovative because it employs a noninvasive technology to precisely measure BBB permeability and pinpoint the area(s) of the brain in which it occurs. The proposed research is significant in that it will lay essential groundwork for development of future interventions to improve the cognitive safety of major elective surgeries in the aging population. Recognition of BBB dysfunction may be of critical prognostic importance in determining brain susceptibility to surgical stress.


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 = $0 )
2025	2024	RHODE ISLAND HOSPITAL	593 EDDY ST	PROVIDENCE	RI	02903	PROVIDENCE	USA	Aging Research	001	5	3/12/2025	SUPPLEMENT FOR EXPANSION	$0
2025	2023	RHODE ISLAND HOSPITAL	593 EDDY ST	PROVIDENCE	RI	02903	PROVIDENCE	USA	Aging Research	002	5	3/14/2025	NON-COMPETING CONTINUATION	$0
2025	2023	RHODE ISLAND HOSPITAL	593 EDDY ST	PROVIDENCE	RI	02903	PROVIDENCE	USA	Aging Research	000	5	3/11/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $398,715 )
2024	2024	RHODE ISLAND HOSPITAL	593 EDDY ST	PROVIDENCE	RI	02903	PROVIDENCE	USA	Aging Research	000	5	2/19/2024	SUPPLEMENT FOR EXPANSION	$398,715
														Subtotal = $398,715

Issue Date FY: 2023 ( Subtotal = $735,198 )
2023	2023	RHODE ISLAND HOSPITAL	593 EDDY ST	PROVIDENCE	RI	02903	PROVIDENCE	USA	Aging Research	000	5	1/31/2023	NON-COMPETING CONTINUATION	$735,198
														Subtotal = $735,198

Issue Date FY: 2022 ( Subtotal = $717,121 )
2022	2022	RHODE ISLAND HOSPITAL	593 EDDY ST	PROVIDENCE	RI	02903	PROVIDENCE	USA	Aging Research	000	4	2/3/2022	NON-COMPETING CONTINUATION	$645,407
2022	2022	RHODE ISLAND HOSPITAL	593 EDDY ST	PROVIDENCE	RI	02903	PROVIDENCE	USA	Aging Research	001	4	6/13/2022	NON-COMPETING CONTINUATION	$71,714
														Subtotal = $717,121

Issue Date FY: 2021 ( Subtotal = $741,596 )
2021	2021	RHODE ISLAND HOSPITAL	593 EDDY ST	PROVIDENCE	RI	02903	PROVIDENCE	USA	Aging Research	000	3	2/23/2021	NON-COMPETING CONTINUATION	$741,596
														Subtotal = $741,596

Issue Date FY: 2020 ( Subtotal = $741,596 )
2020	2020	RHODE ISLAND HOSPITAL	593 EDDY ST	PROVIDENCE	RI	02903	PROVIDENCE	USA	Aging Research	001	2	2/18/2020	NON-COMPETING CONTINUATION	$741,596
2020	2019	RHODE ISLAND HOSPITAL	593 EDDY ST	PROVIDENCE	RI	02903	PROVIDENCE	USA	Aging Research	000	1	2/12/2020	NEW	$0
														Subtotal = $741,596

Issue Date FY: 2019 ( Subtotal = $845,395 )
2019	2019	RHODE ISLAND HOSPITAL	593 EDDY ST	PROVIDENCE	RI	02903	PROVIDENCE	USA	Aging Research	000	1	4/24/2019	NEW	$845,395
														Subtotal = $845,395

Grand Total All Awards = $4,179,621

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Blood-Brain Barrier Disruption as a Biomarker for Perioperative Neurocognitive Disorder:Cognitive Recovery after Elective Surgery

Award Number: R01AG058648

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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