Brain network efficiency is influenced by the pathologic source of corticobasal syndrome

OBJECTIVE: To apply network-based statistics to diffusion-weighted imaging tractography data and detect Alzheimer disease vs non-Alzheimer degeneration in the context of corticobasal syndrome. METHODS: In a cross-sectional design, pathology was confirmed by autopsy or a pathologically validated CSF total tau-to-β-amyloid ratio (T-tau/Aβ). Using structural MRI data, we identify association areas in fronto-temporo-parietal cortex with reduced gray matter density in corticobasal syndrome (n = 40) relative to age-matched controls (n = 40). Using these fronto-temporo-parietal regions of interest, we construct structural brain networks in clinically similar subgroups of individuals with Alzheimer disease (n = 21) or non-Alzheimer pathology (n = 19) by linking these regions by the number of white matter streamlines identified in a deterministic tractography analysis of diffusion tensor imaging data. We characterize these structural networks using 5 graph-based statistics, and assess their relative utility in classifying underlying pathology with leave-one-out cross-validation using a supervised support vector machine. RESULTS: Gray matter density poorly discriminates between Alzheimer disease and non-Alzheimer pathology subgroups with low sensitivity (57%) and specificity (52%). In contrast, a statistic of local network efficiency demonstrates very good discriminatory power, with 85% sensitivity and 84% specificity. CONCLUSIONS: Our results indicate that the underlying pathologic sources of corticobasal syndrome can be classified more accurately using graph theoretical statistics derived from patterns of white matter network organization in association cortex than by regional gray matter density alone. These results highlight the importance of a multimodal neuroimaging approach to diagnostic analyses of corticobasal syndrome.