The accumulation of AGEs also affects various cellular constituents of the BBB, resulting in increased BBB permeability and cognitive impairment.97–99 Vascular endothelial dysfunction further promotes the production of inflammatory mediators that disrupt the BBB,59,63,64,100 which exposes the brain parenchyma to potentially neurotoxic proteins.101 Classical inflammatory mediators such as IL-1β, IL-6, IL-10, TNF-α, vascular cell adhesion protein-1 (VCAM-1), and matrix metalloproteinases (MMP)-2 and -9 suggest vascular neuroinflammation. Here, VCAM1 is linked to Cognitive impairment.