Frontotemporal dementia is associated with considerable clinical, genetic and pathological heterogeneity. The objective of this study is to characterise the imaging signatures of the main FTD phenotypes along the ALS-FTD spectrum. A total of 100 participants underwent comprehensive multimodal neuroimaging, genetic testing and neuropsychological evaluation. Seven patients with behavioural variant FTD (bvFTD), 11 patients with non-fluent-variant primary progressive aphasia (nfvPPA), two patients with sematic-variant primary progressive aphasia(svPPA), 10 patients with amyotrophic lateral sclerosis and FTD carrying the C9orf72 hexanucleotide repeat (C9 + ALS-FTD), 10 patients with ALS-FTD without hexanucleotide repeats (C9-ALS-FTD), 20 ALS patients without behavioural or cognitive deficits (ALSnci) and 40 healthy controls (HC) were included in a prospective quantitative neuroimaging study. Phenotype-specific spatial patterns of pathology were identified along the ALS-FTD spectrum, highlighting a strikingly focal distribution of disease burden as opposed to global atrophy. Significant motor cortex and corticospinal tract degeneration was identified in both bvFTD and nfvPPA patients. C9-ALS-FTD patients exhibited widespread extramotor pathology and significant precentral gyrus atrophy compared to ALSnci patients. ROI analyses confirmed focal grey matter alterations in Broca's and Wernicke's area in language variant FTD cohorts. Our findings confirm that the clinical manifestations of FTD are underpinned by phenotype-specific patterns of white and grey matter degeneration.
Keywords: Magnetic resonance imaging; neurodegeneration; neuroimaging.