Possible biological mechanism underlying physical exercise in SVD The development of SVD is hypothesized to be related to endothelial dysfunction that results from chronic hypertension impairs cerebral vasomotor reactivity (CVR), a marker of cerebral autoregulation. Changes in CVR may reflect impairment in the homeostasis of blood pressure in the brain, hence cerebral perfusion becomes more dependent on the systemic blood pressure. Ischemia occurs in response to drop of systemic blood pressure and lead to hypoperfusion and subsequently the development of SVD. Using Transcranial Doppler (TCD) ultrasonography, our group previously showed that decreased CVR is associated with SVD. Reduced CVR is linked to cognitive decline, depression and poor physical functions in elderly persons. Physical exercise may lead to significant improvement in CVR. These data suggest that physical exercise is likely to benefit cognition, mood and physical functions in persons with SVD due to its positive effects on CVR.