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Investigating Resistance and Resilience Mechanisms in Alzheimer’s Disease

Award Number: R01AG056366
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/15/2017
PERIOD OF PERFORMANCE END DATE: 02/29/2028

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Investigating Resistance and Resilience Mechanisms in Alzheimer’s Disease - PROJECT SUMMARY / ABSTRACT Cognitive Aging and risk of Alzheimer's disease, and Alzheimer's related dementias (AD/ADRD) is due to multiple aging and pathological processes that are driven by several upstream brain mechanisms and risk factors. The success of recent multi-domain interventions and our preliminary data suggests that multiple mechanisms need to be targeted for effective dementia prevention. In 2018, we proposed a simplistic conceptual framework that builds on existing concepts using the nomenclature of resistance in the context of avoiding AD pathology and resilience in the context of coping with AD pathology for investigating these distinct mechanisms. This proposal addresses an important barrier for developing effective therapeutic or preventive strategies for AD dementia - the poor understanding of how upstream risk factors and brain mechanisms (resistance and resilience) that could contribute to or protect from protein accumulation and neurodegeneration. Our central hypothesis is that identifying upstream brain mechanisms of resistance and resilience and modeling the complex inter-relationships between protective factors, brain mechanisms, and longitudinal changes in amyloid, tau, and cognition will aid in effective design of dementia prevention strategies. To test this hypothesis, our primary aim is to identify mechanisms of resistance and resilience using the existing infrastructure of the population-based Mayo Clinic Study of Aging (MCSA) (individuals aged ≥50 years) and Rochester Epidemiology Project (REP) which maintains a comprehensive medical records-linkage system. We will collect the following variables for this proposal: Genetics, Social Determinants of Health (SDoH), and systemic health (up to 20 years prior to scan from REP), longitudinal PiB and tau PET, baseline cutting edge MRI (high resolution T1/T2/FLAIR and multi-shell diffusion MRI to assess perivascular spaces, microstructural integrity, and cortical thickness), and cognitive decline. Our secondary aim is to develop and validate MRI- based resilience markers that can be used in the NIA-AA research framework alongside with AT(N) biomarkers to adjust for individual variability in cognition. Considering brain health measures (other than those included in the evaluation of N) as resilience markers will improve the prediction of cognitive decline across all aging and dementia studies. These measures will be able to capture biological variability due to SDoH and systemic health and facilitate better comparison of biomarkers across populations.


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 = $779,639 )
2026	2026	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Aging Research	000	9	3/20/2026	NON-COMPETING CONTINUATION	$779,639
														Subtotal = $779,639

Issue Date FY: 2025 ( Subtotal = $764,047 )
2025	2025	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Aging Research	000	8	3/7/2025	NON-COMPETING CONTINUATION	$701,675
2025	2025	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Aging Research	001	8	6/9/2025	NON-COMPETING CONTINUATION	$62,372
														Subtotal = $764,047

Issue Date FY: 2024 ( Subtotal = $779,639 )
2024	2024	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Aging Research	002	7	2/28/2024	NON-COMPETING CONTINUATION	$701,675
2024	2024	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Aging Research	003	7	7/3/2024	NON-COMPETING CONTINUATION	$77,964
2024	2023	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Aging Research	001	6	2/9/2024	COMPETING CONTINUATION	$258,948
2024	2021	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Aging Research	000	5	2/9/2024	NON-COMPETING CONTINUATION	-$258,948
														Subtotal = $779,639

Issue Date FY: 2023 ( Subtotal = $810,339 )
2023	2023	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Aging Research	001	6	2/15/2023	COMPETING CONTINUATION	$799,314
2023	2023	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Aging Research	002	6	3/30/2023	COMPETING CONTINUATION	$11,025
2023	2021	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Aging Research	000	5	2/7/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $810,339

Issue Date FY: 2021 ( Subtotal = $777,951 )
2021	2021	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Aging Research	000	5	6/29/2021	NON-COMPETING CONTINUATION	$777,951
														Subtotal = $777,951

Issue Date FY: 2020 ( Subtotal = $777,951 )
2020	2020	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Aging Research	000	4	5/28/2020	NON-COMPETING CONTINUATION	$777,951
														Subtotal = $777,951

Issue Date FY: 2019 ( Subtotal = $774,901 )
2019	2019	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Aging Research	000	3	5/21/2019	NON-COMPETING CONTINUATION	$774,901
														Subtotal = $774,901

Issue Date FY: 2018 ( Subtotal = $781,451 )
2018	2018	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Aging Research	000	2	6/25/2018	NON-COMPETING CONTINUATION	$781,451
														Subtotal = $781,451

Issue Date FY: 2017 ( Subtotal = $791,656 )
2017	2017	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Aging Research	001	1	9/21/2017	NEW	$0
2017	2017	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Aging Research	000	1	9/5/2017	NEW	$791,656
														Subtotal = $791,656

Grand Total All Awards = $7,037,574

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Investigating Resistance and Resilience Mechanisms in Alzheimer’s Disease

Award Number: R01AG056366

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/15/2017

PERIOD OF PERFORMANCE END DATE: 02/29/2028

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