Composite grey matter fingerprints for genetic frontotemporal dementia.
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Bouzigues Arabella, Campana Giulia, Joulot Matthieu, Gensollen Nicolas, Russell Lucy L, Foster Phoebe H, Ferry-Bolder Eve, Van Swieten John Cornelis, Jiskoot Lize C, Seelaar Harro, Sánchez-Valle Raquel, Laforce Robert, Graff Caroline, Galimberti Daniela, Vandenberghe Rik, de Mendonca Alexandre, Tiraboschi Pietro, Santana Isabel, Gerhard Alexander, Levin Johannes, Sorbi Sandro, Otto Markus, Bertoux Maxime, Lebouvier Thibaud, Ducharme Simon, Butler Chris, Finger Elizabeth, Tartaglia Maria Carmela, Masellis Mario, Rowe James Benedict, Synofzik Matthis, Moreno Fermin, Borroni Barbara, Leber Isabelle, Zanusso Gianluigi, Rohrer Jonathan Daniel, Migliaccio Raffaella, GENetic Frontotemporal dementia Initiative (GENFI)
Аннотация
METHODS: Cortical and subcortical grey matter volume and thickness from structural MRI were assessed in a large cohort of 892 participants including presymptomatic and symptomatic carriers of mutations within the three main genetic causes of FTD (C9 open reading-frame 72 (C9orf72), progranulin (GRN) and microtubule-associated protein tau (MAPT)) compared with mutation-negative relatives (controls). We compared the distribution of grey matter changes of each metric at different stages of the disease cross sectionally. We aimed to identify grey matter composites for each genetic group which would show the earliest changes and which separated presymptomatic carriers from controls.
RESULTS: While C9orf72 mutation carriers showed widespread presymptomatic grey matter changes, MAPT and particularly GRN mutation carriers showed changes more proximally to symptom onset. Our composite grey matter signatures, which discriminate asymptomatic/prodromal carriers from controls with high to very high areas under the curve, involved bilateral thalami volumes, precuneus and postcentral thickness in C9orf72; left caudal middle frontal thickness, frontal pole and pars orbitalis volumes in GRN; right temporal pole volume and left insula thickness in MAPT mutation carriers.
CONCLUSION: We propose the use of cortical thickness and volume measurements combined from multiple regions into a composite region of interest for each FTD genetic group to identify the earliest changes and track disease progression. Our quasi-longitudinal design illustrates that these regions continue to evolve throughout the symptomatic stages. Investigating how our selected composites progress and validating these in longitudinal samples will be invaluable for future clinical trials.