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Early Life Cardiovascular Disease Risk Factors, Epigenetic Age Acceleration, and Alzheimer's Disease Related Brain Health

Award Number: R01AG077000
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Early Life Cardiovascular Disease Risk Factors, Epigenetic Age Acceleration, and Alzheimer's Disease Related Brain Health - ABSTRACT Dementia is a major global health challenge, and Alzheimer’s disease (AD) comprises 70% of dementia cases. Because AD has no effective treatment options, the Lancet Commission recently emphasized the critical need for effective, life-course prevention of AD. Epigenetic age acceleration (EAA), or increased DNA methylation (DNAm)-based age relative to chronological age, was identified as a powerful biomarker of AD-related neurobiological substrates and cognitive function in older adults. Likewise, our preliminary data demonstrated associations between EAA and cognitive function in midlife, a critical epoch in brain health when subclinical pathology first emerges, and dementia prevention may be most effective. Works by us and others have also identified associations between cardiovascular disease (CVD) risk factors and EAA, suggesting that EAA could help to explain the intricate link between early life heart and midlife brain health. Despite these intriguing data, prospective associations between childhood CVD risk factors and EAA in adulthood remain unknown and temporal associations are not established. In addition, there is a paucity of research examining the relationships of EAA with midlife cognitive function decline and AD-related neurobiological substrates. We hypothesize that EAA is associated with cognitive decline and neurobiological substrates in midlife and mediates the associations of early life CVD risk factors with these midlife brain health endpoints. To test this hypothesis, we will leverage the rich resources of the Bogalusa Heart Study (BHS), including life-long measures of CVD risk factors, three repeated measures of genome-wide DNAm in adulthood, and two midlife measures of cognitive function over 11-years follow-up in the full cohort of 1,298 BHS participants (850 whites and 448 African Americans). Furthermore, midlife AD-related neurobiological substrates from 3T magnetic resonance imaging (MRI) and amyloid photon emission tomography (PET) scans are also available in a random subsample of 350 BHS participants. As part of the on-going visit cycle (2020-2024), we propose MRI in another random subsample of 350 BHS participants, amyloid PET scans in another random subsample of 50 participants, along with an additional genome-wide DNAm measure in the full BHS cohort. With these data, we will assess prospective and temporal associations of early life CVD risk factors with EAA (Aim 1); examine the associations of EAA with 11-year changes in cognitive function (Aim 2) and neurobiological substrates in midlife (Aim 3); and analyze the mediating effects of EAA on associations of childhood CVD risk factors with midlife brain health endpoints (Aim 4). The molecular characterization of midlife brain health may have broad implications, ranging from the improvement of risk stratification and sub-phenotyping efforts to the pinpointing of molecular targets for drug development. Identifying CVD risk factor precursors to EAA might suggest optimal strategies to prevent EAA and its brain-related sequelae.


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 = $637,746 )
2025	2025	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Aging Research	000	4	1/28/2025	NON-COMPETING CONTINUATION	$637,746
														Subtotal = $637,746

Issue Date FY: 2024 ( Subtotal = $708,607 )
2024	2024	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Aging Research	003	3	6/10/2024	NON-COMPETING CONTINUATION	$70,861
2024	2024	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Aging Research	002	3	1/29/2024	NON-COMPETING CONTINUATION	$637,746
2024	2023	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Aging Research	001	2	12/5/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$723,442
2024	2022	ADMINISTRATORS OF THE TULANE EDUCATIONAL FUND, THE	6823 SAINT CHARLES AVE	NEW ORLEANS	LA	70118	ORLEANS	USA	Aging Research	000	1	12/5/2023	NEW	-$723,442
														Subtotal = $708,607

Issue Date FY: 2023 ( Subtotal = $708,607 )
2023	2023	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Aging Research	002	2	9/11/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2023	2023	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Aging Research	001	2	3/8/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$708,607
2023	2022	ADMINISTRATORS OF THE TULANE EDUCATIONAL FUND, THE	6823 SAINT CHARLES AVE	NEW ORLEANS	LA	70118	ORLEANS	USA	Aging Research	000	1	3/8/2023	NEW	$0
														Subtotal = $708,607

Issue Date FY: 2022 ( Subtotal = $751,377 )
2022	2022	ADMINISTRATORS OF THE TULANE EDUCATIONAL FUND, THE	6823 SAINT CHARLES AVE	NEW ORLEANS	LA	70118	ORLEANS	USA	Aging Research	000	1	4/1/2022	NEW	$751,377
														Subtotal = $751,377

Grand Total All Awards = $2,806,337

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Early Life Cardiovascular Disease Risk Factors, Epigenetic Age Acceleration, and Alzheimer's Disease Related Brain Health

Award Number: R01AG077000

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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