Four subgroups of Alzheimer's disease based on patterns of atrophy using VBM and a unique pattern for early onset disease

To clarify the involvement of the posterior cingulate cortex (PCC) in Alzheimer's disease (AD), we analyzed brain volume loss by voxel-based morphometry. Forty patients with non-familial AD and 20 patients with mild cognitive impairment (MCI) were recruited and compared to 88 elderly volunteers and 40 young volunteers. Local atrophy with aging was observed bilaterally in the perisylvian opercula, anterior cingulate cortex, caudate head, dorsomedial thalamus and parahippocampal cortex. In addition to those, atrophy in AD patients was observed in the amygdala, hippocampus, subcallosal region, posterior-associated cortices and PCC. We classified AD into four subgroups according to the atrophy pattern; atrophy in the amygdala/hippocampal formations (Hipp), in the Hipp and posterior cortices, in the Hipp and PCC and in the PCC and posterior cortices (PCC/-TOPa). As a result, the probability of PCC/-TOPa was 90% for ages <65 years, whereas that of the Hipp was 100% for disease duration >36 months. PCC atrophy was found in 16 of 40 AD patients and eight of 20 MCI patients. There seemed to be two subgroups with atrophy of the PCC, the one with disease progression and the other without. The latter had characteristic features of early onset and no significant atrophy in the amygdala/anterior hippocampus. There are at least four atrophy patterns that raise doubts about a single disease entity or progression in AD. This may reflect a different hierarchical pattern of progression in patients who have atrophy in PCC and posterior cortices when compared to the Braak staging scheme.