Longitudinal cerebral diffusion changes reflect progressive decline of language and cognition

Language deficits are regularly found in cortical neurodegenerative diseases. The progression of language deficits shows a considerable inter-individual variability even within one diagnostic group. We aimed at detecting patterns of altered diffusion as well as atrophy of cerebral gray and white matter which underlie ongoing language-related deterioration in patients with cortical neurodegenerative diseases. Diffusion tensor imaging and T1-weighted MRI data of 26 patients with clinically diagnosed neurodegenerative disorders were acquired at baseline and 14 months later in this prospective study. Language functions were assessed with a confrontation naming test and the Token Test. Diffusion and voxel-based morphometric measures were calculated and correlates of language performance were evaluated. Across all patients, the naming impairment was related to diffusion (false discovery rate-corrected P<0.05 at baseline) and atrophy abnormalities (family-wise error (FWE)-corrected P<0.05 at follow-up) primarily in the left temporal lobe. Deficits in the Token Test were correlated with predominantly left frontal MRI abnormalities (FWE-corrected P<0.05). The Token Test performance decline over 14 months was accompanied by further increasing abnormalities in the frontal cortex, left caudate, parietal cortex (all FWE-corrected P<0.05), and posterior callosal body (FWE-corrected P=0.055). Both diffusion and structural MRI were apt to elucidate the underpinnings of inter-individual differences in language-related deficits and to detect longitudinal changes that accompanied ongoing cognition and language decline, with mean diffusivity appearing most sensitive. This might indicate the usefulness of diffusion measures as markers for successful intervention in therapy studies.