IC‐P‐026: White matter damage in frontotemporal lobar degeneration spectrum

The clinical and pathological heterogeneity of frontotemporal lobar degeneration (FTLD)-related disorders poses a significant diagnostic challenge, and in vivo prediction of underlying histopathology can be significantly improved by supplementing the clinical evaluation with imaging biomarkers. Structural MRI showed that each syndrome is associated with a specific pattern of focal atrophy. White matter (WM) alterations are also a major pathological characteristic in FTLD. By measuring directional changes in water diffusivity, diffusion tensor (DT) MRI allows to investigate brain WM microstructure. In this study, we assessed WM damage in patients with a clinical diagnosis of the behavioural variant frontotemporal dementia (bvFTD) and the three primary progressive aphasia (PPA) variants, and compared these results with the corresponding brain atrophy patterns. DT and T1-weighted MR images were obtained from 13 bvFTD and 20 PPA (9 nonfluent/agrammatic, 7 semantic, and 4 logopenic) patients. Tract-based spatial statistics was applied to investigate brain WM damage in a voxel-by-voxel analysis. DT MRI metrics were also measured in “critical” WM tracts. Grey matter (GM) and WM atrophy was assessed using voxel-based morphometry. Patients with bvFTD showed a widespread pattern of DT MRI abnormalities affecting most of the WM, bilaterally. In PPA patients, WM damage was more focal and varied across the three syndromes: a predominant left fronto-temporo-parietal damage was seen in nonfluent, a predominant left frontotemporal injury in semantic, and a selective left frontoparietal involvement in logopenic patients. In each syndrome, DT MRI changes extended beyond the topography of GM loss. Left uncinate damage was the best predictor of patient diagnosis in each group, followed by the involvement of anterior corpus callosum in bvFTD, left superior longitudinal fasciculus in nonfluent, and left inferior longitudinal fasciculus in semantic patients. This study provides insight into the similarities and differences of WM damage in bvFTD and PPA variants. DT MRI metrics hold promise to serve as early markers of WM integrity loss that only at a later stage may be detectable by volumetric measures, and contribute to the diagnostic work-up of frontotemporal lobar degeneration syndromes.