Endothelial progenitor cells are depleted in older adults with cognitive impairment and white matter volume loss

Abstract

AbstractBackgroundDepletion of endothelial progenitor cells (EPCs) has been linked to vascular disease and both mild cognitive impairment (MCI) and Alzheimer’s disease (AD) dementia. EPCs have been shown to support oligodendrocyte precursor cell proliferation in the oligovascular niche, suggesting a potential role in protecting white matter (WM) integrity. We studied the relationship between in vitro EPC proliferation and both WM volume and cognitive function.MethodSixty‐three community dwelling older adults (Mage = 70.94; SDage = 7.39), free of dementia or clinical stroke, underwent venipuncture, neuropsychological testing, and brain MRI. Blood leukocyte fractions were cultured over one week in colony forming unit (CFU)‐Hill media to produce EPCs. On the 5th day, colonies were counted. Cognitive function was measured by a comprehensive neuropsychological battery and the Clinical Dementia Rating (CDR) Scale. WM volumes were measured by Region‐of‐interest (ROI) analysis on T1‐MPRAGE scans using FreeSurfer 5.3. Univariate Analysis of Covariance (ANCOVA) compared CFU‐Hill counts and CDR scores, and multiple linear regression analyses determined the relationship between CFU‐Hill counts, neuropsychological tests and WM ROIs, after controlling for age, sex and education.ResultCFU‐Hill counts were depleted in participants with CDR = 0.5 [F(1, 51) = 5.84, p = 0.02]. Lower CFU‐Hill counts were associated with worse performances on tests of executive functioning [(1) Animals: F(4, 60) = 4.10, p = 0.005; ΔR2 = 0.16; β= 0.41; ΔF = 12.51, p = 0.001; (2) Fruits and Vegetables: F(4, 60) = 4.00, p = 0.006; β=0.36; ΔR2 = 0.12; ΔF = 7.54, p = 0.009; (3) Trails B: F(4, 44)=9.43; p <0.001; β= 0.24; ΔR2 = 0.057; ΔF = 4.69, p = 0.036]. Posterior corpus callosum volume positively predicted CFU‐Hill counts [F(5, 42)=2.62; p =0.038; β= 0.41; ΔR2 = 0.14; ΔF = 7.69, p = 0.008].ConclusionFindings suggest EPCs may be linked to impaired cognition and WM volume loss in older adults, potentially implicating EPCs in protecting against vascular‐related WM injury and resulting executive dysfunction. Further studies of EPCs, WM integrity, and executive dysfunction are warranted to evaluate a potential protective role for EPCs in cerebrovascular disease with implications for dementia risk assessment and prevention.