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Contribution of child development, biological aging, and beta-amyloid to cognitive function of the Louisville twins at midlife

Award Number: R01AG063949
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2019
PERIOD OF PERFORMANCE END DATE: 04/30/2026

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Contribution of child development, biological aging, and beta-amyloid to cognitive function of the Louisville twins at midlife - Project Summary/Abstract The proposed study will test whether accelerated biological aging at midlife predicts higher levels of preclinical AD biomarkers, as measured with a highly reliable plasma beta-amyloid (Aβ) marker, and whether the Aβ accumulation contributes to cognitive decline in midlife. The causal basis of the associations will be established by studying 750 individual twins age 40-64 from the Louisville Twin Study (LTS), who were studied extensively in childhood. We will relocate and recruit the twins, conduct in person cognitive functioning and physical assessments, collect 50cc of blood to quantify biological age, plasma-Aβ, and genotype. Our ability to recruit twins to the new phase of study is demonstrated by our 2018 Midlife Pilot Study, in which we collected cognitive ability, physical measurements, and blood to construct a biological aging measure for 40 participants, with a consent rate of 100%. Preliminary results suggest that accelerated biological age is a better predictor of episodic memory than global functioning, consistent with prior research. The LTS is the only twin study capable of linking biological aging, Aβ accumulation, and cognitive functioning at midlife to cognitive functioning in childhood, as other comparable longitudinal twin study samples are currently too young. Our study will address two research questions that can only be answered by longitudinal twin studies with intensive childhood measurements: 1) Do people with genetic and environmental predispositions for accelerated biological aging have greater Aβ accumulation and perform worse cognitively in midlife?; and 2) Do early life developmental characteristics cause accelerated biological aging, Aβ, and midlife cognitive functioning? We will complete the following specific aims: Quantify several markers of biological aging to test whether accelerated biological aging predicts Aβ accumulation and lower cognitive functioning at midlife by collecting biological, cognitive, memory, and functional ability data from LTS twins age 40-64 (Aim 1); Determine whether Aβ accumulation mediates effects of accelerated biological aging on declining cognitive functioning, adjusting for confounding genetic and environmental factors (Aim 2); Evaluate effects of early life characteristics on accelerated biological aging, Aβ accumulation, and cognitive functioning in midlife, adjusting for confounding genetic and environmental factors (Aim 3). The significance of the proposed research is specifying causal effects of biological aging in midlife on Aβ accumulation and cognitive functioning, using blood-based aging measures to predict Aβ accumulation, and specifying causal effects of early life developmental mechanisms on accelerated biological aging, Aβ accumulation, and cognitive functioning at midlife. The innovation of the proposed work is the application of a longitudinal twin design, affording us the capability to establish causal effects of biological aging on preclinical AD outcomes in humans for whom experimental randomization is not possible; and establishing new standards for plasma-Aβ data collection in longitudinal twin studies. Consistent with NIA's aims, this project will test the clinical utility of biological aging measures as early indicators of ADRD risk.


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	2023	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	Aging Research	000	5	5/13/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $68,001 )
2024	2024	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST	LOS ANGELES	CA	90089	LOS ANGELES	USA	Aging Research	001	5	12/4/2023	SUPPLEMENT FOR EXPANSION	$28,130
2024	2024	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST	LOS ANGELES	CA	90089	LOS ANGELES	USA	Aging Research	000	5	11/30/2023	SUPPLEMENT FOR EXPANSION	$39,871
														Subtotal = $68,001

Issue Date FY: 2023 ( Subtotal = $976,313 )
2023	2023	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST	LOS ANGELES	CA	90089	LOS ANGELES	USA	Aging Research	002	5	5/24/2023	SUPPLEMENT FOR EXPANSION	$23,344
2023	2023	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST	LOS ANGELES	CA	90089	LOS ANGELES	USA	Aging Research	000	4	11/26/2022	SUPPLEMENT FOR EXPANSION	$47,058
2023	2023	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST	LOS ANGELES	CA	90089	LOS ANGELES	USA	Aging Research	003	5	5/25/2023	SUPPLEMENT FOR EXPANSION	$47,058
2023	2023	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST	LOS ANGELES	CA	90089	LOS ANGELES	USA	Aging Research	001	5	5/23/2023	NON-COMPETING CONTINUATION	$858,853
														Subtotal = $976,313

Issue Date FY: 2022 ( Subtotal = $1,066,427 )
2022	2022	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Aging Research	001	4	7/26/2022	SUPPLEMENT FOR EXPANSION	$70,029
2022	2022	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Aging Research	000	4	5/23/2022	NON-COMPETING CONTINUATION	$996,398
														Subtotal = $1,066,427

Issue Date FY: 2021 ( Subtotal = $1,370,234 )
2021	2021	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Aging Research	000	2	2/25/2021	SUPPLEMENT FOR EXPANSION	$67,839
2021	2021	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Aging Research	001	2	5/10/2021	SUPPLEMENT FOR EXPANSION	$44,095
2021	2021	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Aging Research	003	3	6/30/2021	NON-COMPETING CONTINUATION	$44,095
2021	2021	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Aging Research	002	3	5/24/2021	NON-COMPETING CONTINUATION	$1,214,205
														Subtotal = $1,370,234

Issue Date FY: 2020 ( Subtotal = $1,095,034 )
2020	2020	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Aging Research	000	2	6/10/2020	NON-COMPETING CONTINUATION	$1,095,034
														Subtotal = $1,095,034

Issue Date FY: 2019 ( Subtotal = $1,138,735 )
2019	2019	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Aging Research	001	1	9/12/2019	NEW	$0
2019	2019	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Aging Research	002	1	9/14/2019	NEW	$0
2019	2019	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Aging Research	000	1	8/28/2019	NEW	$1,138,735
														Subtotal = $1,138,735

Grand Total All Awards = $5,714,744

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Contribution of child development, biological aging, and beta-amyloid to cognitive function of the Louisville twins at midlife

Award Number: R01AG063949

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2019

PERIOD OF PERFORMANCE END DATE: 04/30/2026

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