Fig. 4.

Model of the direct effect of exercise on vascular function in Alzheimer’s disease. Exercise-induced effects may act directly on the peripheral and cerebral vascular function and consequently act indirectly on AD-related symptoms and comorbidities. Indeed, during exercise, blood flow and vascular shear stress greatly increase in tissue beds with high metabolic activity, leading to the activation of endothelial NO synthase, improving NO bioavailability. In addition, in response to the increased energy demand during exercise, VEGF is upregulated, which mediates mediating in morphology, number, and diameter of capillary and arteries. This angiogenic process is associated with functional changes and improvement in organ blood flow, including cerebral blood flow (CBF), which is significantly altered in the AD process