To evaluate whether cerebral white matter integrity is related to cognitive function, and whether diffusion tensor imaging (DTI) could differentiate amnestic mild cognitive impairment (aMCI) from Alzheimer's disease (AD), 12 patients with AD, 12 with aMCI, and 12 controls were recruited for this study. Cognitive functions of all subjects were assessed using the Mini-Mental State Examination (MMSE) and AD Assessment Scale - Cognitive Subscale (ADAS-Cog). DTI studies were acquired, and fractional anisotropy (FA) and mean diffusivity (MD) values of normal-appearing white matter (NAWM) in multiple brain regions were obtained. Results showed that MMSE and ADAS-Cog subscores were significantly associated with white matter integrity of the temporal-parietal lobes. A decrease in FA values and an increase in MD values in multiple cortical regions were confirmed in patients with AD compared to controls. MD values in the posterior region of the corpus callosum in aMCI differed from those of early AD. Significant reductions of FA values in the NAWM of the parietal lobe was observed in aMCI compared to controls. Our data indicate that the microstructural white matter integrity in the temporal-parietal lobes is gradually impaired in the progressive process of AD, and that splenium MD values could be used as a biomarker differentiating aMCI from AD.