Objective: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
Keywords: Frontotemporal dementia; Frontotemporal dementia–motor neuron disease.
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