Alzheimer disease (AD) and vascular dementia (VaD) together represent the majority of dementia cases. Since their neuropsychological profiles often overlap and white matter lesions are observed in elderly subjects including AD, differentiating between VaD and AD can be difficult. Characterization of these different forms of dementia would benefit by identification of quantitative imaging biomarkers specifically sensitive to AD or VaD. Parameters of microstructural abnormalities derived from diffusion tensor imaging (DTI) have been reported to be helpful in differentiating between dementias, but only few studies have used them to compare AD and VaD with a voxelwise approach. Therefore, in this study a whole brain statistical analysis was performed on DTI data of 93 subjects (31 AD, 27 VaD, and 35 healthy controls-HC) to identify specific white matter patterns of alteration in patients affected by VaD and AD with respect to HC. Parahippocampal tracts were found to be mainly affected in AD, while VaD showed more spread white matter damages associated with thalamic radiations involvement. The genu of the corpus callosum was predominantly affected in VaD, while the splenium was predominantly affected in AD revealing the existence of specific patterns of alteration useful in distinguishing between VaD and AD. Therefore, DTI parameters of these regions could be informative to understand the pathogenesis and support the etiological diagnosis of dementia. Further studies on larger cohorts of subjects, characterized for brain amyloidosis, will allow to confirm and to integrate the present findings and, furthermore, to elucidate the mechanisms of mixed dementia. These steps will be essential to translate these advances to clinical practice. © 2018 Palesi, De Rinaldis, Vitali, Castellazzi, Casiraghi, Germani, Bernini, Anzalone, Ramusino, Denaro, Sinforiani, Costa, Magenes, D'Angelo, Gandini Wheeler-Kingshott and Micieli.