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Abstract

Primary progressive aphasia (PPA) encompasses the three subtypes nonfluent/agrammatic variant PPA, semantic
variant PPA, and the logopenic variant PPA, which are characterized by distinct patterns of language difficulties
and regional brain atrophy. To validate the potential of structural magnetic resonance imaging data for early in-
dividual diagnosis, we used support vector machine classification on grey matter density maps obtained by
voxel-based morphometry analysis to discriminate PPA subtypes (44 patients: 16 nonfluent/agrammatic variant
PPA, 17 semantic variant PPA, 11 logopenic variant PPA) from 20 healthy controls (matched for sample size, age,
and gender) in the cohort of the multi-center study of the German consortium for frontotemporal lobar degen-
eration. Here, we compared a whole-brain with a meta-analysis-based disease-specific regions-of-interest ap-
proach for support vector machine classification. We also used support vector machine classification to
discriminate the three PPA subtypes from each other. Whole brain support vector machine classification enabled
a very high accuracy between 91 and 97% for identifying specific PPA subtypes vs. healthy controls, and 78/95%
for the discrimination between semantic variant vs. nonfluent/agrammatic or logopenic PPA variants. Only for
the discrimination between nonfluent/agrammatic and logopenic PPA variants accuracy was low with 55%. Inter-
estingly, the regions that contributed the most to the support vector machine classification of patients
corresponded largely to the regions that were atrophic in these patients as revealed by group comparisons. Al-
though the whole brain approach took also into account regions that were not covered in the regions-of-interest
approach, both approaches showed similar accuracies due to the disease-specificity of the selected networks.
Conclusion, support vector machine classification of multi-center structural magnetic resonance imaging data
enables prediction of PPA subtypes with a very high accuracy paving the road for its application in clinical
settings.