Although leukoaraiosis can be considered as a part of the normal aging process, it is strongly associated with stroke, cognitive impairment and other disabilities. The pathogenesis of leukoaraiosis is poorly understood, even if chronic ischemia with consequent arteriolosclerosis probably due to endothelial dysfunction has been suggested. To date, treatment focuses only on prevention of lesion formation and progression by aggressive control of risk factors, beginning at an early age and continuing throughout life. L-Arginine, a semi-essential amino acid, is a precursor of NO in the reaction catalyzed by endothelial nitric oxide synthase and, it has been recently found to importantly influence endothelial function. Arginine supplementation has been demonstrated to be safe and effective therapy for many health conditions, particularly vascular diseases such as intermittent claudication, angina pectoris, erectile dysfunction and MELAS. Thus we hypothesize that, since a lack of endothelium-derived NO may be responsible for several features of LA, long-term administration of high oral doses of L-Arg may slow LA progression and the associated functional impairment.