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Functional network resilience to pathology in presymptomatic genetic frontotemp...

Rittman, Timothy; Borchert, Robin; Jones, Simon; van Swieten, John; Borroni, Barbara; Galimberti, Daniela; Masellis, Mario; Tartaglia, Maria Carmela

The presymptomatic phase of neurodegenerative diseases are characterized by structural brain changes without significant clinical features. We set out to investigate the contribution of functional network resilience to preserved cognition in presymptomatic genetic frontotemporal dementia. We studied 172 people from families carrying genetic abnormalities in C9orf72, MAPT, or PGRN. Networks were extracted from f...


The inner fluctuations of the brain in presymptomatic frontotemporal dementia: ...

Premi, Enrico; Calhoun, Vince D.; Diano, Matteo; Gazzina, Stefano; Cosseddu, Maura; Alberici, Antonella; Archetti, Silvana; Paternicò, Donata

Frontotemporal Dementia (FTD) is preceded by a long period of subtle brain changes, occurring in the absence of overt cognitive symptoms, that need to be still fully characterized. Dynamic network analysis based on resting-state magnetic resonance imaging (rs-fMRI) is a potentially powerful tool for the study of preclinical FTD. In the present study, we employed a "chronnectome" approach (recurring, time-varyin...


Uncovering the heterogeneity and temporal complexity of neurodegenerative disea...

Young, Alexandra L.; Marinescu, Razvan V.; Oxtoby, Neil P.; Bocchetta, Martina; Yong, Keir; Firth, Nicholas C.; Cash, David M.; Thomas, David L.

The heterogeneity of neurodegenerative diseases is a key confound to disease understanding and treatment development, as study cohorts typically include multiple phenotypes on distinct disease trajectories. Here we introduce a machine-learning technique-Subtype and Stage Inference (SuStaIn)-able to uncover data-driven disease phenotypes with distinct temporal progression patterns, from widely available cross-se...


White matter hyperintensities are seen only in GRN mutation carriers in the GEN...

Sudre, Carole H.; Bocchetta, Martina; Cash, David; Thomas, David L.; Woollacott, Ione; Dick, Katrina M.; van Swieten, John; Borroni, Barbara

Genetic frontotemporal dementia is most commonly caused by mutations in the progranulin (GRN), microtubule-associated protein tau (MAPT) and chromosome 9 open reading frame 72 (C9orf72) genes. Previous small studies have reported the presence of cerebral white matter hyperintensities (WMH) in genetic FTD but this has not been systematically studied across the different mutations. In this study WMH were assessed...


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