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Metals and Developmental Origins of Late Life Cognitive Function

Award Number: R01ES031943
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/08/2020
PERIOD OF PERFORMANCE END DATE: 06/30/2025

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Metals and Developmental Origins of Late Life Cognitive Function - We propose to study the relation between prenatal, early postnatal, and adult exposure to metals and cognitive function in older age, and whether early life exposures modify effects of adult exposures. We will also explore whether those exposures and cognitive outcomes are associated with changes in blood-derived extracellular vesicle (EV) micro RNA expression (miRNA), which could represent epigenetic mechanisms underlying associations. We will conduct a cohort study among a subset of participants in the original St. Louis Baby Tooth (SLBT) study who donated their baby teeth in the 1950s and 1960s. Based on our pilot work, we anticipate easily being able to enroll 1,000 former SLBT participants (500 men and 500 women) who will have completed questionnaires and cognitive function testing, and from whom we will collect blood for miRNA analyses and repeated toenail samples for adult metal analyses. Prenatal and early postnatal exposure to several metals will be assessed by measuring metals in baby tooth enamel (using laser-ablation inductively coupled plasma mass spectrometry). Adult metal exposures will be assessed using X-Ray Fluorescence to measure metals in the toenail samples. EVs will be isolated from the blood samples and analyzed for EV miRNA expression levels. The SLBT provides a unique setting that will allow us to have individual-level biomarkers of early life and adult metal exposures in older adults on whom we can conduct cognitive function testing. This study setting allows us to have an unprecedented ability to examine whether early life exposures are related to late life cognitive health—a hypothesis suggested for metals exposure from animal research, but extremely hard to test in humans without the biomarker of such early exposure that the already collected baby teeth in the SLBT can provide.


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: 2026 ( Subtotal = $0 )
2026	2024	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE STE 3	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Environmental Health	000	5	11/20/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2024	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE STE 3	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Environmental Health	001	5	9/10/2025	NON-COMPETING CONTINUATION	$0
2025	2024	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE STE 3	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Environmental Health	000	5	5/19/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $448,111 )
2024	2024	HARVARD COLLEGE PRESIDENT & FELLOWS OF	677 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Environmental Health	000	5	6/14/2024	NON-COMPETING CONTINUATION	$448,111
														Subtotal = $448,111

Issue Date FY: 2023 ( Subtotal = $534,685 )
2023	2023	HARVARD COLLEGE PRESIDENT & FELLOWS OF	677 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Environmental Health	000	4	6/6/2023	NON-COMPETING CONTINUATION	$534,685
														Subtotal = $534,685

Issue Date FY: 2022 ( Subtotal = $546,209 )
2022	2022	HARVARD COLLEGE PRESIDENT & FELLOWS OF	677 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Environmental Health	000	3	6/24/2022	NON-COMPETING CONTINUATION	$546,209
														Subtotal = $546,209

Issue Date FY: 2021 ( Subtotal = $568,070 )
2021	2021	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	677 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Environmental Health	000	2	6/18/2021	NON-COMPETING CONTINUATION	$568,070
														Subtotal = $568,070

Issue Date FY: 2020 ( Subtotal = $545,360 )
2020	2020	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	677 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Environmental Health	000	1	9/8/2020	NEW	$545,360
														Subtotal = $545,360

Grand Total All Awards = $2,642,435

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Metals and Developmental Origins of Late Life Cognitive Function

Award Number: R01ES031943

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/08/2020

PERIOD OF PERFORMANCE END DATE: 06/30/2025

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