Grey And White Matter Mri Signatures Of The Frontotemporal Lobar Degeneration Continuum (S49.006)

Objective. To identify overlapping and unique grey (GM) and white matter (WM) signatures within the frontotemporal lobar degeneration (FTLD) continuum, and discriminate likely FTLD-TAU and FTLD-TDP patients using structural and diffusion tensor (DT) MRI. Background. Our understanding of brain networks’ alterations in each FTLD syndrome has been fruitfully expanded in the past few years through the use of MRI. Despite the clinical, genetic and pathological overlap, patterns of brain damage across the whole continuum are still largely unexplored. Methods. T1-weighted and DT MRI were collected from 35 motor neuron disease (MND), 14 behavioral variant of frontotemporal dementia, 12 semantic and 11 nonfluent primary progressive aphasia, 21 progressive supranuclear palsy syndrome patients and 28 controls. Patterns of GM atrophy and WM tract damage were established. Results. All patient groups, with the exception of MND cases with a pure motor syndrome, shared a focal GM atrophy centered around the dorsolateral and medial frontal cortex and a largely overlapping pattern of WM damage involving the genu and body of the corpus callosum and ventral frontotemporal and dorsal frontoparietal WM pathways. Surrounding this common area, phenotype (symptom)-specific GM and WM regions of damage were found in each group. Patients with a high likelihood of an underlying FTLD-TAU had more severe WM damage relative to patients who are likely to harbor FTLD-TDP pathology, despite a similar pattern of GM atrophy. Conclusions. In the FTLD spectrum, WM damage is more severe than GM atrophy. Frontal cortex and WM pathways represent the common target of neurodegeneration in these conditions. The topographic pattern of damage supports a “prion-like” protein propagation through WM connections as underlying mechanism of the stereotyped progression of FTLD. Funding. This study was partially supported by the following grants: Italian Ministry of Healthy (#RF-2010-2313220, and #GR-2010-2303035); CurePSP Foundation (#MD505-12_001).