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Computing and deploying normative models for early detection of cerebrovascular deviations predictive of Alzheimer's Disease onset

Award Number: K01AG098047
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 09/11/2026
PERIOD OF PERFORMANCE END DATE: 05/31/2029

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Computing and deploying normative models for early detection of cerebrovascular deviations predictive of Alzheimer's Disease onset - PROJECT SUMMARY The objective of this K01 proposal is to provide Dr. Cole Korponay with the subject-matter expertise and methodological toolkit necessary to launch his career as an independent investigator, focused on identifying multi-modal predictive biomarkers of and treatment targets for brain-based illnesses. Recently, in a high-profile manuscript in Nature Human Behaviour, Dr. Korponay discovered a previously unknown hemodynamic phenomenon in fMRI data that has been conflated with neuronal activity. Though trained as a systems neuroscientist, he has since taken great interest in the ability to measure properties of the brain’s vascular system with non-invasive imaging, and in the potential of cerebrovascular data to complement neurocircuit data in assessments of brain pathology. In the process, Alzheimer’s Disease and Related Dementias (ADRD) have become of immense interest to Dr. Korponay, as they involve a complex interaction of both neuronal and vascular pathologies. As he has learned, cerebrovascular dysfunction is among the earliest pathologies to emerge in AD, and yet it remains an underused input to presymptomatic AD risk assessments due to a sparsity of normative hemodynamics reference data during aging. This K01 will provide Dr. Korponay with the necessary training to leverage newly available large-scale arterial spin labeling (ASL) datasets and a specialized method, Regressor Interpolation at Progressive Time Delays (RIPTiDe), to extract hemodynamics information from large-scale functional magnetic resonance imaging (fMRI) datasets. Training in normative modeling will then allow Dr. Korponay to construct the first large-scale normative models of brain hemodynamics (e.g., cerebral perfusion, blood transit times, etc.) during aging. Finally, training in predictive modeling and in the neurobiological and clinical features of aging and Alzheimer’s Disease and Related Dementias will allow Dr. Korponay to identify deviations from normative brain hemodynamics in the high-risk Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset that are predictive of later ADRD onset. A multidisciplinary team of experts will lead Dr. Korponay’s training: Dr. Lisa Nickerson (Mentor), Dr. Blaise Frederick (Co-Mentor), Dr. David Harper (Co-Mentor) and Dr. Saeed Hashem (Other Significant Contributor). Dr. Korponay’s training in cerebral hemodynamics, normative and predictive modeling, and neurobiological and clinical features of aging and ADRD will be applied and reinforced via the proposed research aims. Overall, this unique project benefits from a multidisciplinary research team and will culminate in an R01 submission leveraging the insights gained from this proposal. This project will equip Dr. Korponay with the skills necessary to lead a unique independent research program that synergizes neurocircuit and cerebrovascular neuroimaging data for individual-focused disease risk assessment, especially as it pertains to ADRD.


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 = $126,900 )
2026	2026	THE MCLEAN HOSPITAL CORPORATION	115 MILL ST	BELMONT	MA	02478	MIDDLESEX	USA	Aging Research	000	1	9/11/2026	NEW	$126,900
														Subtotal = $126,900

Grand Total All Awards = $126,900

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Computing and deploying normative models for early detection of cerebrovascular deviations predictive of Alzheimer's Disease onset

Award Number: K01AG098047

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 09/11/2026

PERIOD OF PERFORMANCE END DATE: 05/31/2029

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