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.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 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 136 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 third 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, which is due to a lack of convenient equipment access. 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.