Repetitive measurement with neuroimaging techniques could be useful instruments permitting to differentiate between Alzheimer disease (AD) and vascular dementia (VD). The major genetic risk factor for the development of late-onset AD is the allele epsilon4 of the apolipoprotein E (ApoE). Moreover nitric oxide (NO) and homocysteine (Hcy) seems to be correlated with the degree of cognitive impairment in demented subjects. The aim of this study was to investigate the association between serum NO and Hcy levels, global brain atrophy and brain vascular lesion in AD and VD patients. We report that high plasma levels of homocysteine resulted associated with AD and VD, suggesting that in AD elevated plasma Hcy might be a consequence of concomitant vascular dementia. Otherwise, plasma NO levels were not significantly different in any of the groups. Moreover, neuroimaging measures of vascular lesion level could be of usefulness to differentiate between AD and VD.