To comprehensively examine the clinical presentation of patients diagnosed with frontotemporal dementia-motor neuron disease (FTD-MND) compared to FTD subtypes. To clarify the heterogeneity of behavioural and language deficits in FTD-MND using a data-driven approach.Patients with FTD-MND (n = 31), behavioural variant FTD (n = 119), non-fluent variant primary progressive aphasia (n = 47), semantic variant primary progressive aphasia (n = 42), and controls (n = 127) underwent comprehensive clinical, cognitive and behavioural assessments. Two-step cluster analysis examined patterns of behavioural and language impairment. Voxel-based morphometry and tract-based spatial statistics were used to investigate differences across the subgroups that emerged from cluster analysis.More than half of FTD-MND patients initially presented with variable combinations of deficits (e.g., mixed behaviour/cognitive, mixed behaviour/cognitive/motor deficits), with 74% of them meeting criteria for FTD-MND within 24 months with a median of 12 months. The frequency and severity of behavioural and language abnormalities in FTD-MND lie between that seen in the three FTD phenotypes. Cluster analysis identified three patterns of behavioural and language impairment in FTD-MND. The three FTD-MND subgroups demonstrated different profiles of white matter tract disruption, but did not differ in age at onset, disease duration or patterns of cortical atrophy.While highly heterogeneous, in terms of behavioural and language deficits, and disease severity, the presentation of FTD-MND may be distinct to that of FTD. Distinct white matter degeneration patterns may underpin heterogeneous clinical profiles in FTD-MND. FTD presenting with mixed behavioural-language disturbances should be monitored closely for at least 12-24 months for the emergence of MND symptoms/signs.
Zhe Long, Muireann Irish, David Foxe, John R Hodges, Olivier Piguet, James R Burrell