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Systemic and dietary advanced glycation end products in type 2 diabetes-related cognitive decline and incident dementia: effects on Alzheimer's pathology and cerebrovascular disease

Award Number: R01AG061093
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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ABSTRACT Treatments for Alzheimer's disease (AD) and cognitive decline is a health priority in our aging population and especially in elderly with type 2 diabetes (T2D) who are at high risk of developing these conditions. Compelling small scale studies suggest that high dietary and serum levels of Advanced Glycation End products (AGEs), a group of glucose-derived compounds, chronically elevated in T2D, contribute to cognitive impairment and increased AD and vascular brain pathology in old age. However, there is scarcity of large scale longitudinal studies of well-characterized older adults with T2D making it difficult to obtain evidence linking dietary and serum AGEs with impaired cognition in T2D elderly and whether serum AGEs mediate the associations of dietary AGEs with cognition. These gaps in knowledge impede the development of treatments based on AGEs to decrease the growing burden of AD and cognitive decline. To fill these gaps, the overall goal of this proposal is to test the hypothesis that dietary and circulating AGEs are related to impaired cognition in T2D elderly through an association with AD-related and cerebrovascular neuropathologies. To achieve these aims, we will enroll 921 non-demented community-dwelling T2D older adults from the Israel Diabetes and Cognitive Decline Study (IDCD; R01 AG034087) who undergo annual cognitive testing. This study proposes a comprehensive assessment of dietary and serum AGEs levels. In 255 IDCD participants we will quantify blood brain barrier (BBB) dysfunction (using novel contrast-enhanced MRI), cerebral blood flow (CBF; via ASL-MRI), cerebrovascular reactivity (with Transcranial Doppler), carotid plaque volume burden (via 3D ultrasound), and amyloid (via PET). This comprehensive large-scale study will 1) provide evidence that dietary and serum AGEs levels are related to incident dementia and cognitive decline in older adults with T2D, 2) identify the key neuropathological indices linking dietary and serum AGEs with cognition and 3) test if serum AGEs mediate the association of dietary AGEs with cognition and neuropathology. These data are crucial for developing treatments targeting AGEs for late-life T2D-related cognitive impairment. Thus, these data have the potential to decrease the growing burden of cognitive impairment and affect the brain health of millions in our aging population.


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	2024	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	65 BERGEN ST	NEWARK	NJ	07107	ESSEX	USA	Aging Research	004	5	10/15/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$1,397,453
2025	2023	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Aging Research	003	4	10/15/2024	SUPPLEMENT FOR EXPANSION	-$32,609
2025	2023	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Aging Research	002	4	10/15/2024	NON-COMPETING CONTINUATION	-$731,702
2025	2022	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Aging Research	001	3	10/15/2024	SUPPLEMENT FOR EXPANSION	-$45,425
2025	2022	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Aging Research	000	3	10/15/2024	NON-COMPETING CONTINUATION	-$587,717
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $787,175 )
2024	2024	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	65 BERGEN ST	NEWARK	NJ	07107	ESSEX	USA	Aging Research	002	5	8/1/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$78,716
2024	2024	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	65 BERGEN ST	NEWARK	NJ	07107	ESSEX	USA	Aging Research	001	5	2/1/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$708,459
2024	2023	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Aging Research	000	4	2/1/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $787,175

Issue Date FY: 2023 ( Subtotal = $764,311 )
2023	2023	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Aging Research	000	4	1/18/2023	NON-COMPETING CONTINUATION	$731,702
2023	2023	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Aging Research	001	4	1/19/2023	SUPPLEMENT FOR EXPANSION	$32,609
														Subtotal = $764,311

Issue Date FY: 2022 ( Subtotal = $926,923 )
2022	2022	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Aging Research	003	3	4/21/2022	NON-COMPETING CONTINUATION	$86,041
2022	2022	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Aging Research	001	3	12/7/2021	SUPPLEMENT FOR EXPANSION	$59,852
2022	2022	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Aging Research	002	3	12/10/2021	SUPPLEMENT FOR EXPANSION	$6,650
2022	2022	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Aging Research	000	3	12/1/2021	NON-COMPETING CONTINUATION	$774,380
														Subtotal = $926,923

Issue Date FY: 2021 ( Subtotal = $10,902 )
2021	2021	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Aging Research	001	2	8/1/2021	SUPPLEMENT FOR EXPANSION	$10,902
2021	2020	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Aging Research	000	2	3/15/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $10,902

Issue Date FY: 2020 ( Subtotal = $854,145 )
2020	2020	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Aging Research	000	2	12/4/2019	NON-COMPETING CONTINUATION	$768,731
2020	2020	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Aging Research	001	2	1/30/2020	NON-COMPETING CONTINUATION	$85,414
														Subtotal = $854,145

Issue Date FY: 2019 ( Subtotal = $910,096 )
2019	2019	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Aging Research	001	1	1/30/2019	NEW	$0
2019	2019	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Aging Research	000	1	1/28/2019	NEW	$910,096
														Subtotal = $910,096

Grand Total All Awards = $4,253,552

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Systemic and dietary advanced glycation end products in type 2 diabetes-related cognitive decline and incident dementia: effects on Alzheimer's pathology and cerebrovascular disease

Award Number: R01AG061093

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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