Tuesday, September 16, 2025 9/16/2025

Identifying Associations between Brain Iron, Neurocognitive Networks and Protective Factors

Award Number: R01AG068055
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2021
PERIOD OF PERFORMANCE END DATE: 02/28/2026

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Identifying Associations between Brain Iron, Neurocognitive Networks and Protective Factors - Identifying Associations between Brain Iron, Neurocognitive Networks and Protective Factors Alzheimer’s disease (AD) involves accumulation of pathological levels of amyloid-beta (Aβ) and phospho-tau proteins. However, a significant proportion of individuals with AD pathology do not have clinical AD, indicating contributions of other factors. Novel in-vivo measures are required to track other factors contributing to AD-related cognitive declines. Increasing evidence suggests that age-related accumulation of brain iron and its correlates contribute to the manifestation of memory declines. Our recent neuroimaging results suggest that high brain iron concentration, measured with in vivo quantitative susceptibility mapping (QSM), is associated poor connectivity within brain memory networks. This proposal seeks to identify associations between QSM-based iron concentration and neurocognitive changes toward a goal of improving AD biomarkers. We will also define the interplay between QSM-based iron signal, AD pathology, inflammatory markers on cognitive declines. Finally, we will test the possibility that brain iron accumulation may be slowed by an antioxidant rich diet. We propose to study 140 healthy older adults using neuroimaging measures including fMRI and QSM, measures of CSF and plasma Aβ, p-tau and t-tau and inflammatory markers. Additional structural neuroimaging measures will include regional volumes, FLAIR imaging for quantification of WMH volumes and diffusion tensor imaging for quantification of regionally distributed white matter connectivity. A subset of participants will be complete the same CSF and imaging measures approximately 3 years later. We aim to identify (1) effects of QSM-based iron signal on functional and structural brain networks supporting cognition; (2) associations between brain iron, inflammatory markers, AD pathology and cognitive declines and; (3) modifiers of brain iron or its effects on cognition. We will test hypotheses that high QSM-based brain iron is associated with low connectivity in memory circuits independently of AD pathology but may and synergistically interacts with AD over time. We will also test the hypothesis that reserve factors will offset the effects of brain iron on cognitive functions via mechanisms of brain maintenance or plastic functional brain reorganization of large-scale brain functional networks in some older adults.


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 = $531,018 )
2025	2025	UNIVERSITY OF KENTUCKY RESEARCH FOUNDATION, THE	500 S LIMESTONE	LEXINGTON	KY	40526	FAYETTE	USA	Aging Research	001	5	6/10/2025	NON-COMPETING CONTINUATION	$43,348
2025	2025	UNIVERSITY OF KENTUCKY RESEARCH FOUNDATION, THE	500 S LIMESTONE	LEXINGTON	KY	40526	FAYETTE	USA	Aging Research	000	5	3/18/2025	NON-COMPETING CONTINUATION	$487,670
														Subtotal = $531,018

Issue Date FY: 2024 ( Subtotal = $633,811 )
2024	2024	UNIVERSITY OF KENTUCKY RESEARCH FOUNDATION, THE	500 S LIMESTONE	LEXINGTON	KY	40526	FAYETTE	USA	Aging Research	000	4	3/19/2024	NON-COMPETING CONTINUATION	$570,430
2024	2024	UNIVERSITY OF KENTUCKY RESEARCH FOUNDATION, THE	500 S LIMESTONE	LEXINGTON	KY	40526	FAYETTE	USA	Aging Research	001	4	6/28/2024	NON-COMPETING CONTINUATION	$63,381
														Subtotal = $633,811

Issue Date FY: 2023 ( Subtotal = $532,675 )
2023	2023	UNIVERSITY OF KENTUCKY RESEARCH FOUNDATION, THE	500 S LIMESTONE 109 KINKEAD HALL	LEXINGTON	KY	40526	FAYETTE	USA	Aging Research	000	3	3/9/2023	NON-COMPETING CONTINUATION	$532,675
														Subtotal = $532,675

Issue Date FY: 2022 ( Subtotal = $552,874 )
2022	2022	UNIVERSITY OF KENTUCKY RESEARCH FOUNDATION, THE	500 S LIMESTONE 109 KINKEAD HALL	LEXINGTON	KY	40526	FAYETTE	USA	Aging Research	001	2	6/13/2022	NON-COMPETING CONTINUATION	$55,287
2022	2022	UNIVERSITY OF KENTUCKY RESEARCH FOUNDATION, THE	500 S LIMESTONE 109 KINKEAD HALL	LEXINGTON	KY	40526	FAYETTE	USA	Aging Research	000	2	2/25/2022	NON-COMPETING CONTINUATION	$497,587
														Subtotal = $552,874

Issue Date FY: 2021 ( Subtotal = $567,868 )
2021	2021	UNIVERSITY OF KENTUCKY	500 S LIMESTONE 109 KINKEAD HALL	LEXINGTON	KY	40526	FAYETTE	USA	Aging Research	000	1	4/20/2021	NEW	$567,868
														Subtotal = $567,868

Grand Total All Awards = $2,818,246

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Identifying Associations between Brain Iron, Neurocognitive Networks and Protective Factors

Award Number: R01AG068055

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/01/2021

PERIOD OF PERFORMANCE END DATE: 02/28/2026

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