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Assessing the role of cerebrovascular brain injury and dysfunction in Alzheimer’s disease pathogenesis in the BEACoN Cohort

Award Number: R01AG053555
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY A critical gap in understanding the etiology of sporadic Alzheimer's disease (AD) is identifying the upstream factors that lead to the development of both Alzheimer’s pathology and related neural dysfunction. Vascular disease is found in approximately 80% of patients with concomitant AD pathology and thus may be an important contributor to the development of AD, however relationships between vascular health and the emergence of AD pathophysiology has not yet been comprehensively investigated in cognitively normal samples. While large vascular adverse events such as stroke are known to confer risk for developing vascular dementia, growing evidence suggests that subtle vascular damage accrued through a lifetime of injury could predispose neural structure and function to become more susceptible to AD-related pathophysiology. Critically, chronic and subtle forms of vascular disease are more commonly found in Black and Hispanic populations with reduced access to healthcare and could help explain the increased prevalence of AD in these populations. The goal of this renewal project is to establish the role of cerebrovascular injury and dysfunction (CVID) in the pathophysiology of preclinical AD and develop individualized imaging-based cerebrovascular profiles that predict memory decline across racially and ethnically diverse populations. We will conduct follow-up assessments in 100 nondemented older adults (over 60 years of age) in our current award (BEACoN Cohort: R01AG053555), which includes amyloid-PET (florbetapir), serial high-resolution MRI and tau-PET (MK-6240), our innovative digital cognitive biomarkers which assess pattern separation, and a full UDS-3 neuropsychological testing battery. We will complement this with targeted new recruitment (n = 100) to increase the representation of Hispanic/Latino and Black participants in our cohort. We have built an infrastructure to radically transform recruitment and retention in our study including innovative partnerships with clinical research organizations with a demonstrable track record in minority recruitment. Given focus on subtle vascular damage, we will exclude based on history of stroke or severe cardiovascular disease. Our aims are (1) Assess the novel biomarker framework in which CVID predicts tau accumulation, which predicts structural and functional deterioration of the medial temporal lobes (MTL), subsequently predicting decline in hippocampal pattern separation. (2) Construct individualized brain imaging based CVID profiles that differentially predict decline in hippocampal memory across racially and ethnically diverse populations. (3) Aim 3: Associate CVID profiles with modifiable lifestyle risk factors and structural and social determinants of health that are differentially distributed across racial and ethnic groups. In summary, we will develop a novel mechanistic framework for how CVID contributes to AD pathophysiology and memory/cognitive decline that directly addresses racial and ethnic disparities in AD risk. Cerebrovascular profiles, and their associated modifiable risk factors that confer the greatest risk of AD, will be identified as targets for future intervention.


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 = $2,372,389 )
2025	2025	UNIVERSITY OF CALIFORNIA IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Aging Research	000	8	12/19/2024	NON-COMPETING CONTINUATION	$2,290,197
2025	2025	UNIVERSITY OF CALIFORNIA IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Aging Research	001	8	1/23/2025	SUPPLEMENT FOR EXPANSION	$82,192
														Subtotal = $2,372,389

Issue Date FY: 2024 ( Subtotal = $2,615,119 )
2024	2024	UNIVERSITY OF CALIFORNIA IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Aging Research	004	7	7/1/2024	NON-COMPETING CONTINUATION	$254,466
2024	2024	UNIVERSITY OF CALIFORNIA IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Aging Research	000	7	2/1/2024	NON-COMPETING CONTINUATION	$2,290,197
2024	2024	UNIVERSITY OF CALIFORNIA IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Aging Research	001	7	2/29/2024	SUPPLEMENT FOR EXPANSION	$70,456
2024	2023	UNIVERSITY OF CALIFORNIA IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Aging Research	003	6	3/18/2024	COMPETING CONTINUATION	$399,891
2024	2021	UNIVERSITY OF CALIFORNIA IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Aging Research	002	5	3/18/2024	NON-COMPETING CONTINUATION	-$399,891
														Subtotal = $2,615,119

Issue Date FY: 2023 ( Subtotal = $2,561,798 )
2023	2023	UNIVERSITY OF CALIFORNIA, IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Aging Research	001	6	12/15/2022	COMPETING CONTINUATION	$2,561,798
2023	2021	UNIVERSITY OF CALIFORNIA, IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Aging Research	000	5	12/8/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,561,798

Issue Date FY: 2021 ( Subtotal = $1,487,182 )
2021	2021	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Aging Research	000	5	4/27/2021	NON-COMPETING CONTINUATION	$1,487,182
														Subtotal = $1,487,182

Issue Date FY: 2020 ( Subtotal = $1,487,182 )
2020	2020	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Aging Research	000	4	5/7/2020	NON-COMPETING CONTINUATION	$1,487,182
														Subtotal = $1,487,182

Issue Date FY: 2019 ( Subtotal = $1,487,182 )
2019	2019	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Aging Research	000	3	5/3/2019	NON-COMPETING CONTINUATION	$1,487,182
														Subtotal = $1,487,182

Issue Date FY: 2018 ( Subtotal = $1,452,335 )
2018	2018	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Aging Research	001	2	7/14/2018	SUPPLEMENT FOR EXPANSION	$720,278
2018	2018	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Aging Research	000	2	4/27/2018	NON-COMPETING CONTINUATION	$732,057
														Subtotal = $1,452,335

Issue Date FY: 2017 ( Subtotal = $756,327 )
2017	2017	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Aging Research	000	1	7/3/2017	NEW	$756,327
														Subtotal = $756,327

Grand Total All Awards = $14,219,514

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Assessing the role of cerebrovascular brain injury and dysfunction in Alzheimer’s disease pathogenesis in the BEACoN Cohort

Award Number: R01AG053555

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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