Longitudinal changes in functional capacity, cognition, and behaviour in the frontotemporal dementias and Alzheimer’s disease

Objective: This study aimed to investigate the changes in functional capacity, cognition, and behavioural disturbances with disease progression in a well-characterised cohort of frontotemporal dementia (FTD), and typical and atypical presentations of Alzheimer's disease (AD).Methods: We recruited 126 behavioural variant FTD (bvFTD), 40 progressive nonfluent aphasia (PNFA), 64 semantic dementia (SD), 45 logopenic progressive aphasia (LPA), and 115 typical AD patients. Functional capacity, cognition, and behavioural disturbances were measured annually over ~7 years using the Disability Assessment for Dementia, Addenbrooke’s Cognitive Examination-III, and the Cambridge Behavioural Inventory-Revised carer questionnaire, respectively.Results: Linear mixed effects models revealed disproportionate functional impairment in bvFTD at baseline and throughout the study period, relative to the other dementia syndromes. In contrast, functional capacity among the other syndromes showed a more uniform pattern of decline, with less severe functional impairment at baseline and ~7-10% mean annual decline. Early functional impairments in bvFTD coincided with pronounced behavioural, eating, and motivational disturbances, which remained relatively stable over the study period. In contrast, SD patients demonstrated an escalation of florid behavioural changes including stereotypical and eating changes. While florid behavioural problems remained relatively indolent in PNFA, LPA, and AD, motivational disturbances emerged across all groups with disease progression. Finally, all groups demonstrated cognitive decline, most severe in the LPA group.Conclusion: Our findings provide a comprehensive overview of distinct functional, cognitive, and behavioural profiles across dementia syndromes with disease progression. Identifying pivotal progression milestones across syndromes has the potential to improve clinical management and reduce carer burden.