Purpose: The goal of this project was to compare MRI measures of hippocampal, entorhinal cortex (ERC), and whole brain longitudinal change in cognitively normal elderly controls (C), non-demented subjects with cognitive impairment (CI), and demented (D) subjects. Methods: 16 C, 6 CI, and 7 D subjects of comparable age were studied with MRI twice, at least 1 year apart. Longitudinal change in total brain size was measured by several methods, including computerized segmentation, non-linear warping, and change in the fluid/tissue boundaries between cerebrospinal fluid (CSF) and brain. Change in hippocampal volume was measured by semi-automated methods, and ERC volumes were manually measured. Results: The annual rate of atrophy was greater in D versus C and D versus CI for cortical gray matter (cGM) (P = 0.009 and 0.002), hippocampus (P = 0.0001 and 0.002), and for the change in the fluid/tissue boundary (P = 0.03 and 0.03). The annual rate of atrophy of ERC was greater in both CI and D versus C (P = 0.01 and 0.0002). No significant differences between groups were found using non-linear warping. Conclusions: In CI, the greatest annual rates of atrophy were in ERC, while in D the greatest annual rates of atrophy were in hippocampus and cortex. Progressive ERC atrophy was observed with a greater degree of cognitive impairment, while hippocampal and cortical atrophy were only observed in demented subjects. (C) 2002 Elsevier Science Inc. All rights reserved.