Higher atrophy rate of entorhinal cortex than hippocampus in AD

Abstract

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.

Figure 1

Relationship between atrophy rates of entorhinal cortex (ERC) and hippocampus (HP) in patients with Alzheimer disease (AD) and cognitively normal (CN) subjects. The dashed line is the line of identity. Subjects below the line of identity have higher atrophy rates in the ERC than in the hippocampus.

Figure 2

Atrophy rates of entorhinal cortex (ERC: ● and solid line) and hippocampus (HP: ● and dashed line) in patients with Alzheimer disease as a function of memory impairment, measured using the Delayed List Recall (DLR) test. DLR scores represent percentage of correctly remembered words, normalized to the maximum number of words on the list. To account for floor effects of DLR when patients were moderately to severely demented, only mildly impaired patients with DLR score greater than zero were included in regression analyses.