Abstract Body (Do not enter title and authors here): Introduction
Circulating progenitor cells (CPC’s) are mononuclear stem cells which originate in the bone marrow, and circulate in the blood, playing a role in promoting vascular regeneration and healing. Previous studies have shown associations between lower levels of CPC’s and increased all-cause mortality, MACE, and atherosclerosis. Additionally, those with cognitive disorders such as Alzheimer’s disease have been shown to have reduced levels of CPC’s, and some association between CPC’s and cognitive decline has been shown. Clinical surrogates for cognitive decline include a lower Montreal Cognitive Assessment (MoCA) score, and an increase in white matter hyperintensities (WMH) on MRI. We hypothesize that reduced circulating EPCs are associated with a lower MoCA score and an increased number of white matter hyperintensities (WMH) on MRI.

Methods
In 181 participants (40.3% male, 41.4% Black) with and without mild cognitive impairment, CPCs were enumerated by flow cytometry as CD45^med mononuclear cells expressing CD34 and co-expression with either CD133, chemokine CXC motif receptor 4 (CXCR4), or vascular endothelial growth factor receptor-2 (VEGF2R). Participants were followed for four years and underwent neuropsychiatric testing and MRI imaging. MoCA testing was used to evaluate multiple domain cognitive function. Diffusion weighted MRI was used to evaluate for WMH indicating microvascular damage. Linear regression modeling was used to determine the cross-sectional association between CPC’s and both the MoCA score and burden of WMH after adjusting for age, gender, race, body mass index, history of heart failure, and history of chronic kidney disease.

Results
Lower levels of CD34/VEGF2R were associated with lower MoCA scores (β=1.31, p=0.025) and more WMH (β= -2109.1, p=0.011) when comparing first and fourth quartile of CPC concentration. Additionally, decreased CD34/133 and CD34/CXCR4 were associated with an increased burden of WMH (β= -3491.1, p=0.029 and β= -2419.8, p=0.012) when first and fourth quartiles were compared.

Conclusions
Lower CPC counts of CD34 subsets were associated with worse performance on MoCA and more white matter hyperintensities on MRI, demonstrating that lower endothelial regenerative capacity may lead to decreased cognition and cognitive decline.