Objectives: To test the applicability of an automated method of magnetic resonance image analysis (voxel based morphometry) to detect presence and severity of regional grey matter density reduction-a proxy of atrophy-in Alzheimer's disease.

Methods: Twenty nine probable Alzheimer's patients and 26 non-demented controls (mini-mental state examinations mean (SD) 21 (4) and 29 (1)) underwent high resolution 3D brain magnetic resonance imaging. Spatial normalisation to a stereotactic template, segmentation into grey matter, white matter, and cerebrospinal fluid, and smoothing of the grey matter were carried out based on statistical parametric mapping (SPM99) algorithms. Analyses were carried out: (a) contrasting all Alzheimer's patients with all controls (p<0.05 corrected for multiple comparisons); (b) contrasting the three Alzheimer's patients with mini-mental state of 26 and higher with all controls (p<0.0001 uncorrected); and (c) correlating grey matter density with mini-mental state score within the Alzheimer's group (p<0.0001 uncorrected).

Results: When all Alzheimer's patients were compared with controls, the largest atrophic regions corresponded to the right and left hippocampal/amygdalar complex. All parts of the hippocampus (head, body, and tail) were affected. More localised atrophic regions were in the temporal and cingulate gyri, precuneus, insular cortex, caudate nucleus, and frontal cortex. When the mildest Alzheimer's patients were contrasted with controls, the hippocampal/amygdalar complex were again found significantly atrophic bilaterally. The mini-mental state score correlated with grey matter density reduction in the temporal and posterior cingulate gyri, and precuneus, mainly to the right.

Conclusions: Voxel based morphometry with statistical parametric mapping is sensitive to regional grey matter density reduction in mild Alzheimer's disease.