INS and obesity due to melanocortin 4 receptor deficiency: Overweight and obesity in midlife can increase the risk of AD in later life.22 One possible explanation of this relationship is that obesity is a risk factor for DM41 which is also a risk factor for AD by itself.1,18 Another explanation is that there is a relationship between obesity and resistance to insulin42 and insulin resistance could play a role in AD.43 With respect to PAF, and despite the importance of these two risk factors, reduction of them has lesser effects on AD prevention comparing to the others, both in Iran and the world.