Background.
Region of interest (ROI)-based measurements of atrophy of medial temporal lobe (MTL) structures are sensitive markers of Alzheimer's disease (AD), but some overlap may exist with non-demented controls.

Objective.
To test whether voxel-based morphometry (VBM) with Statistical Parametric Mapping (SPM99) can detect atrophy in AD patients and controls overlapping on MTL ROI-based volumetric measures.

Methods.
Overlapping cases were taken from 27 probable AD and 25 non-demented controls who had undergone high resolution 3D brain magnetic resonance and ROI-based measurements of hippocampal volumes. When the distribution of normalized hippocampal volumes was plotted against age, 7 AD patients (age 73 ± 11, 5 women, mini-mental state exam, MMSE 20 ± 5) and 11 controls (age 70 ± 6, 6 women, MMSE 30 ± 1) were overlapping by ROI-based hippocampal measure (1.34 ± 0.21 vs. 1.39 ± 0.12, p = 0.62). Two separate VBM comparisons were carried out to detect regions more atrophic in AD than in controls and vice versa using SPM99. Analyses were carried out with p < 0.001, and age and intracranial volume were included as covariates.

Results.
When compared to controls, AD patients showed bilateral atrophy in the the temporoparietal, cingulate, precuneus, and medial temporal regions. In the opposite comparison, controls showed a restricted area of apparent gray matter reduction centered in the straight sinus but no neocortical atrophy.

Conclusion.
VBM might be more sensitive than ROI-based measures to detect atrophy in AD.