James R. Burrell

Background and purpose The heterogeneity of cognitive and behavioural disturbances in frontotemporal dementia–motor neuron disease (FTD‐MND), and clinical differences between FTD‐MND and FTD subtypes, have been illustrated cross‐sectionally. This study aimed to examine the FTD‐MND disease trajectory by comparing clinical features of FTD‐MND and the behavioural variant FTD (bvFTD) longitudinally. Methods Neuropsychological and disease severity assessments were conducted in a cohort of FTD‐MND (baseline, n = 42; follow‐up, n = 18) and bvFTD (baseline, n = 116; follow‐up, n = 111) using a longitudinal, case–control design. Age‐, sex‐, and education‐matched controls ( n = 52) were recruited. Predictors of clinical progression were analyzed. Voxel‐based morphometry analysis was undertaken to investigate the progression of brain atrophy. Results At baseline, FTD‐MND was characterized by semantic and general cognition deficits, whereas bvFTD had greater behavioural disturbances. General cognition and language deteriorated in FTD‐MND when followed longitudinally. Language deficits at baseline predicted cognitive deterioration and disease progression and correlated with progressive atrophy of language regions. Further deterioration in behaviour was evident in bvFTD over time. The rate of disease progression (i.e., general cognition, semantic association, and disease severity) was significantly faster in FTD‐MND than in bvFTD. Conclusions FTD‐MND and bvFTD appear to have distinct disease trajectories, with more rapid progression in FTD‐MND. Language impairments should be closely monitored in FTD‐MND as potential predictors of cognitive deterioration and disease progression.