UF1NS125488

The University of Kentucky MarkVCID Biomarker Validation Cohort: Development of a Toolbox to Advance VCID Interventional Studies - Abstract

The MarkVCID Consortium was established to discover and cross-site validate biomarkers of cerebral small vessel disease (CSVD) with an ultimate goal of developing a toolbox of biomarkers that will have diagnostic, disease stratification, and longitudinal tracking utility for future vascular contributions to cognitive impairment and dementia (VCID) clinical trials.

The University of Kentucky (UK) was selected as one of the seven MarkVCID sites in its initial funding period in 2016. Being in the heart of the Stroke Belt, Kentucky is a state with a high prevalence of cardiovascular and cerebrovascular disease, and the University of Kentucky is a center of excellence for stroke and dementia, with UK being a designated comprehensive stroke center and has an NIA Alzheimer's Disease Research Center (ADRC).

During our current funding period, we successfully recruited a cohort of 126 individuals (exceeding our originally proposed 120) with varying levels of cardiovascular risk factors and a large proportion of whom have defined subjective memory complaints (SMCs), with some defined as mild cognitive impairment (MCI). All participants underwent the MarkVCID MRI battery, blood collection, and neuropsychological and clinical assessment, while one quarter also contributed CSF. Importantly, all participants have consented to autopsy; a requirement we initiated at the beginning of our MarkVCID recruitment.

UK MarkVCID has fully participated in the validation of every biomarker kit except the OCT-A kit. We have also led two biomarker kits: the white matter growth and regression kit and the CSF PLGF kit.

In this renewal connected to UH3NS100606 under RFA-NS-16-020, we propose to expand our cohort to 200 individuals, with a particular focus on expanding recruitment of diverse populations and individuals with SMCs and MCI. Having participated in the harmonization, instrumental validation, and now biological validation of all MRI and fluid biomarker kits, we are poised to make significant contributions in the continuation of the consortium.

We have proposed three specific aims to achieve the goals laid out in RFA-NS-21-005:

Specific Aim 1: Retain and expand a diverse cohort enriched for individuals with subjective memory complaints and cognitive impairment at high risk for cerebral small vessel disease.

Specific Aim 2: Work with the consortium to facilitate data, imaging, and fluid sharing and accelerate our validation of the MarkVCID candidate biomarkers in our cohort.

Specific Aim 3: Fully engage in leadership roles within the consortium and serve in a consulting capacity for both internal and external researchers seeking to explore biomarkers and/or develop new clinical trials and interventional studies for the treatment of VCID.

University Of Kentucky Research Foundation

(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 NEUROSCIENCE WORKFORCE DEVELOPMENT, 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

93.866 - Aging Research

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

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

Lexington, Kentucky 40526 United States

Single Zip Code

Small Vessel VCID Biomarker Validation Consortium Sites (U01)(Clinical Trials Not Allowed) (RFA-NS-21-005)

Amendment Since initial award the End Date has been extended from 07/31/23 to 07/31/26 and the total obligations have increased 150% from $2,448,000 to $6,120,000.