Empathy in primary progressive aphasia: Neural signatures and longitudinal trajectories

INTRODUCTION: Empathy is increasingly recognised as compromised in neurodegenerative disorders. However, its profile and neural bases in the nonfluent (nfvPPA) and logopenic (lvPPA) variants of primary progressive aphasia remain unclear. We aimed to characterize empathy at onset, examine its longitudinal course, and identify neural correlates in nfvPPA and lvPPA. METHODS: Thirty-four nfvPPA, 38 lvPPA, and 45 control subjects completed neuropsychological and MRI assessment, with follow-up up to 9 years. Empathy was measured using the Interpersonal Reactivity Index (Perspective Taking, Empathic Concern). RESULTS: At baseline, both PPA groups showed reduced cognitive empathy but preserved affective empathy. Lower empathy correlated with broader cognitive deficits in nfvPPA and predicted greater caregiver burden. Longitudinally, empathy remained stable in nfvPPA but declined in lvPPA. Brain-behavior analyses implicated temporo-parietal and frontal-insular regions, with progressive frontal atrophy predicting cognitive empathy decline in lvPPA. DISCUSSION: Findings demonstrate early empathy deficits in both variants, distinct trajectories, and syndrome-specific neural substrates, with important clinical implications.