University of Kentucky
Small vessel disease biomarkers in a longitudinally-followed "stroke-belt" cohort
Summary
The University of Kentucky Sanders-Brown Center on Aging lies in the heart of the “stroke belt” in the southeastern US. Our work over the last 35 years, researching aging and dementia in our community-based population, has demonstrated that small vessel disease (SVD) is one of the most prevalent brain pathologies contributing to cognitive impairment and dementia, rivaling the contributions of Alzheimer’s disease. SVD can be seen in isolation or more commonly as a contributing pathology in cases of mixed dementia. Our primary focus is on the early detection and slowing of SVD progression in order to significantly reduce the risk for individuals to develop vascular cognitive impairment and dementia (VCID).
As such we have leveraged our strong community-based ties and outreach in order to explore SVD and its relationship to VCID in subjects who remain cognitively normal with or without significant cardiovascular risk factors and in those with early memory decline likely attributed to by their cardiovascular risk factor burden. Legacy work at our center involving several past large NIH-funded grants has allowed us to develop a historical database of several hundred individuals meeting the above criteria with full clinical and cognitive characterization that have donated blood, spinal fluid, and brain imaging in an effort to propel research forward. Access to this information and bio samples is provided based on availability to a wide range of researchers that span the globe. In addition, as part of our current efforts in the MarkVCID program, we have enrolled 130 individuals, including approximately 45 who are cognitively normal without evidence for SVD or poorly controlled cardiovascular risk factors, 45 who are cognitively normal but demonstrate early signs of SVD on brain imaging and have at least one poorly controlled cardiovascular risk factor, and another 40 subjects with early vascular cognitive impairment that have not yet met the criteria for functional deficits that would warrant a diagnosis of dementia. These subjects have undergone extensive clinical and cognitive characterization and have also donated blood, spinal fluid, and advanced state-of-the-art MRI brain imaging that is part of the MarkVCID protocol. Again, this information in the biospecimens are available for sharing with interested researchers across the globe.
In addition to our contributions to the widespread MarkVCID consortium efforts, the University of Kentucky site includes researchers with specific expertise that are driving the development of several novel biomarkers for VCID within the consortium currently. Led by Dr. Donna Wilcock, who also serves as chair of the MarkVCID Fluid-based Biomarkers subcommittee, and Dr. Gregory Jicha, University of Kentucky site is moving forward a novel biomarker assay investigating angiogenic dysregulation in cerebrospinal fluid. In addition, the University of Kentucky site has developed a unique MRI protocol that allows us to measure dynamic change in SVD over time. This novel protocol allows the detection of regression (healing) versus progression (further brain injury) of SVD. These novel biomarkers will provide novel insights into the biological mechanisms of SVD, and more importantly are expected to prove useful in our understanding of future interventions to slow or stop SVD in its tracks before one develops VCID.
Investigators Information
University of Kentucky Research Foundation
University of Kentucky Research Foundation
