This study was designed to examine the roles of the characteristic cognitive indicators and specific MRI-based measurements in the differential diagnoses of Alzheimer disease (AD), vascular dementia (VaD), and normal aging. Fifty-two probable AD patients were recruited for the study. Twenty-seven VaD patients and 35 age-matched normal older adults (NC) were included as controls. All subjects underwent a battery of standardized neuropsychological tests. The MRI-based quantification technique was used to measure the volumes and T2 relaxation time (T2) of medial temporal lobe structures. Stepwise discriminant analyses showed cognitive indicators had a sensitivity ranging from 82% to 100% and specificity from 82% to 97% for differentiating AD from non-AD cases (VaD and normal controls), and the quantitative MRI-based measurements of medial temporal lobe structures correctly classified AD cases from non-AD cases with sensitivity from 80% to 96% and specificity from 83% to 97%. ROC curve analyses showed that the combination of cognitive and MRI measurements slightly increased the diagnostic accuracy of AD. The results suggest that both cognitive indicators and MRI-based medial temporal lobe measurements may be useful in differentiating AD from VaD and normal older adults. The combination of these possible indicators is promising in the early diagnosis of AD.