Nevertheless, endothelial mechanisms leading to cognitive impairment and dementia are still primarily underestimated.43,59 Stroke and chronic hypoperfusion lead to endothelial oxidative damage,60,61 while Nox2 activity has been implicated in brain endothelial dysfunction following ischaemia.62 We found that mediators of endothelial activation angiopoietin-2 (Angpt2) and VEGF were significantly increased in the vasculature at 6-12weeks hypoperfusion, while Nox2 deletion reduced their expression. This evidence concerns the gene CYBB and dementia.