However, a possible point of contention could regard the genuine efficacy of PDE5 inhibitors on improving cognitive aspects, since their effect could have been attributed to the increased blood flow and glucose metabolism (as mentioned above, the initial use of PDE5 inhibitors was for treating hypertension and erectile dysfunction, due to the effect of PDE5 inhibitors on vasodilatation) [80]. This evidence concerns the gene PDE5A and hypertensive disorder.