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This study aimed to examine the FTD\u2010MND disease trajectory by comparing clinical features of FTD\u2010MND and the behavioural variant FTD (bvFTD) longitudinally.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Neuropsychological and disease severity assessments were conducted in a cohort of FTD\u2010MND (baseline, <jats:italic>n<\/jats:italic>\u00a0=\u200942; follow\u2010up, <jats:italic>n<\/jats:italic>\u00a0=\u200918) and bvFTD (baseline, <jats:italic>n<\/jats:italic>\u00a0=\u2009116; follow\u2010up, <jats:italic>n<\/jats:italic>\u00a0=\u2009111) using a longitudinal, case\u2013control design. Age\u2010, sex\u2010, and education\u2010matched controls (<jats:italic>n<\/jats:italic>\u00a0=\u200952) were recruited. Predictors of clinical progression were analyzed. Voxel\u2010based morphometry analysis was undertaken to investigate the progression of brain atrophy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>At baseline, FTD\u2010MND was characterized by semantic and general cognition deficits, whereas bvFTD had greater behavioural disturbances. General cognition and language deteriorated in FTD\u2010MND 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\u2010MND than in bvFTD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>FTD\u2010MND and bvFTD appear to have distinct disease trajectories, with more rapid progression in FTD\u2010MND. Language impairments should be closely monitored in FTD\u2010MND as potential predictors of cognitive deterioration and disease progression.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.15518","type":"journal-article","created":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T16:43:21Z","timestamp":1659545001000},"page":"3158-3169","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Distinct disease trajectories in frontotemporal dementia\u2013motor neuron disease and behavioural variant <scp>frontotemporal dementia<\/scp>: A longitudinal study"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4978-8201","authenticated-orcid":false,"given":"Zhe","family":"Long","sequence":"first","affiliation":[{"name":"Department of Neurology The Second Xiangya Hospital of Central South University  Changsha China"},{"name":"Faculty of Medicine and Health University of Sydney  Sydney New South Wales 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