Background: Quantitative MRI assessment methods have limited utility due to a lack of standardized methods and measures for Alzheimer disease (AD) and amnestic mild cognitive impairment (aMCI). Objective: To employ a relatively new and easy-to-use quantitative assessment method to reveal volumetric changes in subcortical gray matter (GM) regions, hippocampus, and global intracranial structures as well as the diagnostic performance and best thresholds of total hippocampal volumetry in individuals with AD and those with aMCI. Method: A total of 74 individuals-37 with mild to moderate AD, 19 with aMCI, and 18 with normal cognition (NC)-underwent a 3T MRI. Fully automated segmentation and volumetric measurements were performed. Results: The AD and aMCI groups had smaller volumes of amygdala, nucleus accumbens, and hippocampus compared with the NC group. These same two groups had significantly smaller total white matter volume than the NC group. The AD group had smaller total GM volume compared with the aMCI and NC groups. The thalamus in the AD group showed a subtle atrophy. There were no significant volumetric differences in the caudate nucleus, putamen, or globus pallidus between the groups. Conclusion: The amygdala and nucleus accumbens showed atrophy comparable to the hippocampal atrophy in both the AD and aMCI groups, which may contribute to cognitive impairment. Hippocampal volumetry is a reliable tool for differentiating between AD and NC groups but has substantially less power in differentiating between AD and aMCI groups. The loss of total GM volume differentiates AD from aMCI and NC.