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Statistical method for neural mechanism mediating and moderating cognitive system in Alzheimer's disease and aging research.

Award Number: R01AG062578
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By Issue Date FY or Funding FY:

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Alzheimer's disease (AD), as well as normal aging, are associated with a wide range of brain and cognitive changes. In investigating cognitive changes, it has been observed that some people can sustain more brain changes or pathology than others, and this differential susceptibility is related to measures such as IQ, education, vocational experiences etc. This observation is the basis for the cognitive reserve (CR) hypothesis, where CR moderates the effects of brain changes on cognition. Recent developments in medical imaging, particularly multimodal neuroimaging, can provide better understanding of neural mechanisms that underlie both cognitive changes and the role of CR. However, existing statistical methods were not designed to accommodate large-scale multi-dimensional data, particularly for incorporating high-dimensional moderators and mediators. To address these issues, we propose to develop, validate, and apply software tools for the cross-sectional and longitudinal analysis of multimodal MR brain images and cognitive data acquired from individuals with normal cognitive aging, preclinical AD and AD from two independent studies of aging and Alzheimer's disease: the Reference Ability Neural Networks (RANN) (Yaakov Stern, PI) and the Alzheimer's Disease Neuroimaging Initiative (ADNI). We will demonstrate that the developed statistical methods offer improved accuracy and robustness over current tools. First, we will develop tools for identifying robust relationships between neurodegeneration or pathology markers and brain function (network expression measured by task fMRI) in the presence of CR as a moderator. Second, we will derive neural substrate of CR using resting-state functional MRI and task fMRI and then develop statistical tools to test the moderation effect of the imaging CR proxies. Third, we will develop the sparse moderated mediation methods for high-dimensional predictors and mediators accounting for moderation. to test whether network expression during cognitive tasks mediates the effect of brain changes (measured via multimodal structural MRI) on cognitive performance, cognitive decline and dementia transition, and whether the derived neural substrate of CR moderates the mediation.


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: 2024 ( Subtotal = $368,715 )
2024	2024	RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC.	1051 RIVERSIDE DR	NEW YORK	NY	10032	NEW YORK	USA	Aging Research	001	5	2/8/2024	NON-COMPETING CONTINUATION	$0
2024	2024	RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC.	1051 RIVERSIDE DR	NEW YORK	NY	10032	NEW YORK	USA	Aging Research	000	5	1/10/2024	NON-COMPETING CONTINUATION	$368,715
														Subtotal = $368,715

Issue Date FY: 2023 ( Subtotal = $409,683 )
2023	2023	RESEARCH FOUNDATION FOR MENTAL HYGIENE INC	1051 RIVERSIDE DR	NEW YORK	NY	10032	NEW YORK	USA	Aging Research	000	4	1/23/2023	NON-COMPETING CONTINUATION	$409,683
2023	2023	RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC.	1051 RIVERSIDE DR	NEW YORK	NY	10032	NEW YORK	USA	Aging Research	001	4	8/18/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $409,683

Issue Date FY: 2022 ( Subtotal = $409,683 )
2022	2022	RESEARCH FOUNDATION FOR MENTAL HYGIENE INC	1051 RIVERSIDE DR	NEW YORK	NY	10032	NEW YORK	USA	Aging Research	001	3	4/29/2022	NON-COMPETING CONTINUATION	$40,969
2022	2022	RESEARCH FOUNDATION FOR MENTAL HYGIENE INC	1051 RIVERSIDE DR	NEW YORK	NY	10032	NEW YORK	USA	Aging Research	000	3	12/15/2021	NON-COMPETING CONTINUATION	$368,714
														Subtotal = $409,683

Issue Date FY: 2021 ( Subtotal = $409,683 )
2021	2021	RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC.	1051 RIVERSIDE DR	NEW YORK	NY	10032	NEW YORK	USA	Aging Research	000	2	12/17/2020	NON-COMPETING CONTINUATION	$368,714
2021	2021	RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC.	1051 RIVERSIDE DR	NEW YORK	NY	10032	NEW YORK	USA	Aging Research	001	2	2/11/2021	NON-COMPETING CONTINUATION	$40,969
														Subtotal = $409,683

Issue Date FY: 2020 ( Subtotal = $448,099 )
2020	2020	RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC.	1051 RIVERSIDE DR	NEW YORK	NY	10032	NEW YORK	USA	Aging Research	000	1	1/9/2020	NEW	$448,099
														Subtotal = $448,099

Grand Total All Awards = $2,045,863

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Statistical method for neural mechanism mediating and moderating cognitive system in Alzheimer's disease and aging research.

Award Number: R01AG062578

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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