Differential early subcortical involvement in genetic FTD within the GENFI cohort.
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Bocchetta Martina, Todd Emily G, Peakman Georgia, Cash David M, Convery Rhian S, Russell Lucy L, Thomas David L, Eugenio Iglesias Juan, van Swieten John C, Jiskoot Lize C, Seelaar Harro, Borroni Barbara, Galimberti Daniela, Sanchez-Valle Raquel, Laforce Robert, Moreno Fermin, Synofzik Matthis, Graff Caroline, Masellis Mario, Carmela Tartaglia Maria, Rowe James B, Vandenberghe Rik, Finger Elizabeth, Tagliavini Fabrizio, de Mendonça Alexandre, Santana Isabel, Butler Chris R, Ducharme Simon, Gerhard Alexander, Danek Adrian, Levin Johannes, Otto Markus, Sorbi Sandro, Le Ber Isabelle, Pasquier Florence, Rohrer Jonathan D, Genetic Frontotemporal dementia Initiative (GENFI)
Аннотация
METHODS: 480 mutation carriers from the Genetic FTD Initiative (GENFI) were included (198 GRN, 202 C9orf72, 80 MAPT), together with 298 non-carrier cognitively normal controls. Cortical and subcortical volumes of interest were generated using automated parcellation methods on volumetric 3 T T1-weighted MRI scans. Mutation carriers were divided into three disease stages based on their global CDR® plus NACC FTLD score: asymptomatic (0), possibly or mildly symptomatic (0.5) and fully symptomatic (1 or more).
RESULTS: In all three groups, subcortical involvement was seen at the CDR 0.5 stage prior to phenoconversion, whereas in the C9orf72 and MAPT mutation carriers there was also involvement at the CDR 0 stage. In the C9orf72 expansion carriers the earliest volume changes were in thalamic subnuclei (particularly pulvinar and lateral geniculate, 9-10%) cerebellum (lobules VIIa-Crus II and VIIIb, 2-3%), hippocampus (particularly presubiculum and CA1, 2-3%), amygdala (all subregions, 2-6%) and hypothalamus (superior tuberal region, 1%). In MAPT mutation carriers changes were seen at CDR 0 in the hippocampus (subiculum, presubiculum and tail, 3-4%) and amygdala (accessory basal and superficial nuclei, 2-4%). GRN mutation carriers showed subcortical differences at CDR 0.5 in the presubiculum of the hippocampus (8%).
CONCLUSIONS: C9orf72 expansion carriers show the earliest and most widespread changes including the thalamus, basal ganglia and medial temporal lobe. By investigating individual subregions, changes can also be seen at CDR 0 in MAPT mutation carriers within the limbic system. Our results suggest that subcortical brain volumes may be used as markers of neurodegeneration even prior to the onset of prodromal symptoms.