Anatomical MRI staging of frontotemporal dementia variants.

INTRODUCTION:The three clinical variants of frontotemporal dementia (behavioral variant [bvFTD], semantic dementia, and progressive non-fluent aphasia [PNFA]) are likely to develop over decades, from the preclinical stage to death. METHODS:To describe the long-term chronological anatomical progression of FTD variants, we built lifespan brain charts of normal aging and FTD variants by combining 8022 quality-controlled MRIs from multiple large-scale data-bases, including 107 bvFTD, 44 semantic dementia, and 38 PNFA. RESULTS:We report in this manuscript the anatomical MRI staging schemes of the three FTD variants by describing the sequential divergence of volumetric trajectories between normal aging and FTD variants. Subcortical atrophy precedes focal cortical atrophy in specific behavioral and/or language networks, with a "radiological" prodromal phase lasting 8-10 years (time elapsed between the first structural alteration and canonical cortical atrophy). DISCUSSION:Amygdalar and striatal atrophy can be candidate biomarkers for future preclinical/prodromal FTD variants definitions. HIGHLIGHTS:We describe the chronological MRI staging of the most affected structures in the three frontotemporal dementia (FTD) syndromic variants. In behavioral variant of FTD (bvFTD): bilateral amygdalar, striatal, and insular atrophy precedes fronto-temporal atrophy. In semantic dementia: bilateral amygdalar atrophy precedes left temporal and hippocampal atrophy. In progressive non-fluent aphasia (PNFA): left striatal, insular, and thalamic atrophy precedes opercular atrophy.