Background.
Atrophy of medial temporal lobe is a sensitive marker of Alzheimer's disease (AD). The state-of-the-art technique to measure atrophy is manual outlining of the structure contour slice by slice on digital images by an expert tracer. The availability of automated methods would significantly improve the clinical feasibility of atrophy measurements.

Objective.
To test the validity of an automated method of MR-based image analysis (voxel-based morphometry with Statistical Parametric Mapping, SPM99) to detect regional atrophy in very mild AD.

Methods.
Twenty-nine probable AD patients (mini mental state exam, MMSE 21+4) and 26 non-demented controls (MMSE 29+1) underwent high resolution 3D brain MR. Three patients (aged 66, 79, 81) had very mild dementia severity (MMSE 26 and 27). The following procedures were carried out based on SPM99 algorithms: spatial normalization of the whole brain to a stereotactic template, segmentation into gray matter, white matter and cerebro-spinal fluid, and smoothing of the gray matter. Three separate experiments were carried out: comparison of all patients with all controls (p<.05 for multiple comparisons correction); comparison of three very mild AD patients with all controls (p<.0001 uncorrected); correlation of the gray matter density with MMSE score.

Results.
In the whole group, the regions with the greatest atrophy corresponded to the left and right hippocampal/amygdalar complex. Other smaller and less significantly atrophic regions were located in the temporal and cingulate gyri, precuneus, insular cortex, caudate nucleus, and frontal cortex. In the 3 very mild AD patients, atrophic regions were detected in the hippocampal/amygdalar complex bilaterally. The MMSE score corralated with gray matter density reduction in the temporal and posterior cingulate gyri, and precuneus, mainly to the right.

Conclusions.
The technique is a valid tool to detect regional atrophy in mild AD.