Registration accuracy for VBM studies varies according to region and degenerative disease grouping.

Voxel-based morphometry studies are frequently cited as having the advantage of being objective compared to region-of-interest methods. This statement assumes, however, that all regions are treated equally both in controls and diseased cohorts. This study aimed to test whether this statement is correct by analyzing fiducial landmarks in controls, Alzheimer's disease (as a model of mild generalized atrophy model); Frontotemporal Dementia (focal atrophy model) and Semantic Dementia (extreme focal atrophy model). Standard SPM5 and DARTEL were evaluated using either raw or skull-stripped/bias corrected scans. The results indicated that with all methods there was variability in the degree of misregistration across regions and that there was a disease grouping interaction-most severely in the extreme focal atrophy model (Semantic Dementia). Preprocessing improved VBM outputs both with standard SPM and DARTEL. In the latter case, this occurred to an extreme degree-DARTEL using raw data was grossly insensitive to a ground truth (manually verified hippocampal atrophy in AD) whereas DARTEL after preprocessing yielded excellent results with respect to this yardstick.

Atrophy patterns in histologic vs clinical groupings of frontotemporal lobar degeneration.

OBJECTIVE: Predictable patterns of atrophy are associated with the clinical subtypes of frontotemporal dementia (FTD): behavioral variant (bvFTD), semantic dementia (SEMD), and progressive nonfluent aphasia (PNFA). Some studies of pathologic subtypes have also suggested specific atrophy patterns; however, results are inconsistent. Our aim was to test the hypothesis that clinical, but not pathologic, classification (FTD with ubiquitin inclusions [FTD-U] and FTD with tau inclusions [FTD-T]) is associated with predictable patterns of regional atrophy. METHODS: Magnetic resonance scans of nine FTD-U and six FTD-T patients (histologically confirmed) were compared with 25 controls using voxel-based morphometry (VBM). Analyses were conducted with the patient group classified according to histologic or clinical variant. Additionally, three Alzheimer pathology patients who had the syndrome of SEMD in life (FTD-A) were analyzed. RESULTS: The VBM studies in clinical variants confirmed established patterns of atrophy (SEMD, rostral temporal; bvFTD, mesial frontal; PNFA, left insula). FTD-U and FTD-T VBM results were very similar, showing severe atrophy in the temporal poles, mesial frontal lobe, and insulae. A conjunction analysis confirmed this similarity. Subgroup analysis found that SEMD associated with either FTD-T or FTD-U was associated with similar rostral temporal atrophy; however, FTD-A had a qualitatively different pattern of left hippocampal atrophy. CONCLUSIONS: While there is predictable atrophy for clinical variants of frontotemporal dementia (FTD), histologic FTD variants show no noticeable differences. Reports of specific atrophy profiles are likely the result of idiosyncrasies in small groups. Semantic dementia associated with Alzheimer pathology, however, presented a distinct atrophy pattern.