In vivo mapping of gray matter loss with voxel-based morphometry in mild Alzheimer's disease

Up till now, the study of regional gray matter atrophy in Alzheimer's disea se (AD) has been assessed with regions of interest, but this method is time -consuming, observer dependent, and poorly reproducible (especially in term s of cortical regions boundaries) and in addition is not suited to provide a comprehensive assessment of the brain. In this study, we have mapped gray matter density by means of voxel-based morphometry on Tl-weighted MRI volu me sets in 19 patients with mild AD and 16 healthy subjects of similar age and gender ratio and report highly significant clusters of gray matter loss with almost symmetrical distribution, affecting mainly and in decreasing o rder of significance the medial temporal structures, the posterior cingulat e gyrus and adjacent precuneus, and the temporoparietal association and per isylvian neocortex, with only little atrophy in the frontal lobe. The findi ngs are discussed in light of previous studies of gray matter atrophy in AD based either on postmortem or neuroimaging data and in relation to PET stu dies of resting glucose consumption. The limitations of the method are also discussed in some detail, especially with respect to the segmentation and spatial normalization procedures as they apply to pathological brains. Some potential applications of voxel-based morphometry in the study of AD are a lso mentioned. (C) 2001 Academic Press.