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Higher atrophy rate of entorhinal cortex than hippocampus in AD

From the Magnetic Resonance Unit (Drs. Du, Schuff, Ganzer, Zhu, and Weiner), Department of Veterans Affairs Medical Center, San Francisco; Departments of Radiology (Drs. Schuff and Weiner), Psychiatry (Drs. Kramer, Yaffe, and Weiner), Neurology (Drs. Miller, Yaffe, and Weiner), Epidemiology (Dr. Yaffe), and Medicine (Dr. Weiner), University of California San Francisco; Department of Neurology (Drs. Jagust, Reed, and Mungas), University of California, Davis; and Department of Neurology (Dr. Chui), University of Southern California, Los Angeles.

Address correspondence and reprint requests to Dr. Michael W. Weiner, MR Unit, VA Medical Center (114M), University of California, San Francisco, 4150, Clement Street, San Francisco, CA 94121; e-mail: mweiner{at}itsa.ucsf.edu

Objectives: To determine if atrophy rates were higher for entorhinal cortex (ERC) than for hippocampus in Alzheimer disease (AD), to determine the relationship between hippocampal atrophy rate and memory impairment, and to compare atrophy rates of ERC and hippocampus in differentiating between patients with AD and cognitively normal (CN) controls.

Methods: Twenty patients with AD and 25 CN subjects had MRI scans and clinical evaluations twice approximately 1.9 years apart. ERC volumes were measured manually and hippocampal volumes were measured semiautomatically on volumetric T1-weighted MR images.

Results: In AD, the atrophy rate of ERC (7.1 ± 3.2%/year) was higher (p < 0.02) than that of hippocampus (5.9 ± 2.4%/year). Furthermore, memory deficit in mild AD, measured with the Delayed List Verbal Recall test, correlated significantly with atrophy rates of both ERC (r = -0.61) and hippocampus (r = -0.59). Atrophy rates of ERC and hippocampus were comparable in differentiating between AD and CN. Using atrophy rates of ERC or hippocampus to detect a 20% treatment effect with 90% power (p < 0.05) would require about 100 completed patients per arm in a 2-year study.

Conclusion: The finding in AD that the atrophy rate in the entorhinal cortex is higher than in the hippocampus is consistent with the view that AD pathology begins in the entorhinal cortex.

Received April 18, 2003. Accepted in final form October 14, 2003.

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