Enlarged perivascular spaces (ePVS) are difficult to quantify, and their etiologies and consequences are poorly understood. Vanderbilt Memory and Aging Project participants (n = 327, 73 ± 7 years) completed 3T brain MRI to quantify ePVS volume and count, longitudinal neuropsychological assessment, and cardiac MRI to quantify aortic stiffness. Linear regressions related (1) PWV to ePVS burden and (2) ePVS burden to cross-sectional and longitudinal neuropsychological performance adjusting for key demographic and medical factors. Higher aortic stiffness related to greater basal ganglia ePVS volume (β = 7.0×10−5, p = 0.04). Higher baseline ePVS volume was associated with worse baseline information processing (β = -974, p = 0.003), executive function (β = -81.9, p < 0.001), and visuospatial performances (β = -192, p = 0.02) and worse longitudinal language (β = -54.9, p = 0.05), information processing (β = -147, p = 0.03), executive function (β = -10.9, p = 0.03), and episodic memory performances (β = -10.6, p = 0.02). Results were similar for ePVS count. Greater arterial stiffness relates to worse basal ganglia ePVS burden, suggesting cardiovascular aging as an etiology. ePVS burden is associated with adverse cognitive trajectory, emphasizing the clinical relevance of ePVS.