R01NS123378

Stroke Connectome MRI Biomarkers for VCID Risk Assessment - Project Summary

Every year, more than 795,000 people in the United States have a stroke, with currently around 4.7 million survivors. Approximately 20% of survivors develop Vascular Contributions to Cognitive Impairments and Dementia (VCID), which is second only to Alzheimer's disease (AD). While several putative biomarkers are known, a considerable gap exists in stroke research in terms of validation and interaction of biomarkers of VCID.

There is a critical need to better understand the complex interactions of VCID risk factors, baseline cognitive and brain health, and incident stroke lesion burden on post-stroke brain changes and subsequent development of VCID. The specific aims of this project will address this need innovatively by:

1. Utilizing a novel Neighborhood Disadvantage Atlas to geo-spatially map and quantify socio-economic disadvantage.
2. Quantifying vascular risk burden.
3. Incorporating baseline brain and cognitive health.
4. Leveraging technical advances in state-of-the-art connectome MRI.
5. Applying network neuroscience and machine learning.

In addition, we will recruit participants from underrepresented minority groups (African Americans, Hispanics, Native Americans), rural/urban, low/high SES who might be at increased risk for VCID. Our central hypothesis is that VCID risk factors, baseline cognitive and brain health, incident stroke damage, and post-stroke brain changes will act in concert through brain perfusion, structure, and connectivity pathways in determining whether a stroke patient develops VCID.

We will collect longitudinal connectome MRI and neuropsychological data from a prospective cohort of patients 55-90 years old with incident ischemic stroke in the left (N=50) or right (N=50) middle cerebral artery territory. We will prospectively collect data on N=50 and retrospectively use N=100 from AD Connectome Project for matched healthy controls.

Aim 1 (Brain Changes): Characterize how the interaction of VCID risk factors (e.g., cardiovascular, demographics), baseline brain health, and the extent of incident stroke damage will affect post-stroke brain changes at 6 months.

Aim 2 (Brain-Cognition Relationships): Characterize specific relationships between VCID risk factors, baseline cognition, brain, incident stroke, post-stroke brain changes, and post-stroke cognitive function at 6 and 12 months across 5 cognitive domains including executive function, attention, language, memory, and visuospatial. We will use advanced machine learning to build predictive models that will identify contributory and deleterious brain changes associated with post-stroke cognitive outcomes.

Successful completion of the project will provide currently lacking scientific understanding of the intricate biological relationships between VCID risk factors, stroke MRI biomarkers, and their interactions that underlie the biology of cognitive outcomes after an ischemic stroke. The results will lay a strong foundation for building accurate diagnosis, prognosis, disease monitoring tools, and future clinical studies that can aid in positively altering disease progression and reducing illness burden on patients due to post-ischemic stroke VCID.

University Of Wisconsin System

(1) TO SUPPORT EXTRAMURAL RESEARCH FUNDED BY THE NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE (NINDS) INCLUDING: BASIC RESEARCH THAT EXPLORES THE FUNDAMENTAL STRUCTURE AND FUNCTION OF THE BRAIN AND THE NERVOUS SYSTEM; RESEARCH TO UNDERSTAND THE CAUSES AND ORIGINS OF PATHOLOGICAL CONDITIONS OF THE NERVOUS SYSTEM WITH THE GOAL OF PREVENTING THESE DISORDERS; RESEARCH ON THE NATURAL COURSE OF NEUROLOGICAL DISORDERS; IMPROVED METHODS OF DISEASE PREVENTION; NEW METHODS OF DIAGNOSIS AND TREATMENT; DRUG DEVELOPMENT; DEVELOPMENT OF NEURAL DEVICES; CLINICAL TRIALS; AND RESEARCH TRAINING IN BASIC, TRANSLATIONAL AND CLINICAL NEUROSCIENCE. THE INSTITUTE IS THE LARGEST FUNDER OF BASIC NEUROSCIENCE IN THE US AND SUPPORTS RESEARCH ON TOPICS INCLUDING BUT NOT LIMITED TO: DEVELOPMENT OF THE NERVOUS SYSTEM, INCLUDING NEUROGENESIS AND PROGENITOR CELL BIOLOGY, SIGNAL TRANSDUCTION IN DEVELOPMENT AND PLASTICITY, AND PROGRAMMED CELL DEATH; SYNAPSE FORMATION, FUNCTION, AND PLASTICITY; LEARNING AND MEMORY; CHANNELS, TRANSPORTERS, AND PUMPS; CIRCUIT FORMATION AND MODULATION; BEHAVIORAL AND COGNITIVE NEUROSCIENCE; SENSORIMOTOR LEARNING, INTEGRATION AND EXECUTIVE FUNCTION; NEUROENDOCRINE SYSTEMS; SLEEP AND CIRCADIAN RHYTHMS; AND SENSORY AND MOTOR SYSTEMS. IN ADDITION, THE INSTITUTE SUPPORTS BASIC, TRANSLATIONAL AND CLINICAL STUDIES ON A NUMBER OF DISORDERS OF THE NERVOUS SYSTEM INCLUDING (BUT NOT LIMITED TO): STROKE; TRAUMATIC INJURY TO THE BRAIN, SPINAL CORD AND PERIPHERAL NERVOUS SYSTEM; NEURODEGENERATIVE DISORDERS; MOVEMENT DISORDERS; BRAIN TUMORS; CONVULSIVE DISORDERS; INFECTIOUS DISORDERS OF THE BRAIN AND NERVOUS SYSTEM; IMMUNE DISORDERS OF THE BRAIN AND NERVOUS SYSTEM, INCLUDING MULTIPLE SCLEROSIS; DISORDERS RELATED TO SLEEP; AND PAIN. PROGRAMMATIC AREAS, WHICH ARE PRIMARILY SUPPORTED BY THE DIVISION OF NEUROSCIENCE, ARE ALSO SUPPORTED BY THE DIVISION OF EXTRAMURAL ACTIVITIES, THE DIVISION OF TRANSLATIONAL RESEARCH, THE DIVISION OF CLINICAL RESEARCH, THE OFFICE OF TRAINING AND WORKFORCE DEVELOPMENT, THE OFFICE OF PROGRAMS TO ENHANCE THE NEUROSCIENCE WORKFORCE, AND THE OFFICE OF INTERNATIONAL ACTIVITIES. (2) TO EXPAND AND IMPROVE THE SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM; TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT; TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT; AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. TO UTILIZE THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM; TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS; TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS; TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT; AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.866 - Aging Research

National Institute of Neurological Disorders and Stroke (NNDS) [HHS - NIH]

National Institute on Aging (NIA) [HHS - NIH]

Madison, Wisconsin 53715 United States

Single Zip Code

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the total obligations have increased 387% from $736,934 to $3,586,234.