Clinical staging and disease progression in frontotemporal dementia.

OBJECTIVE: We aimed to develop a novel tool capable of staging disease severity in frontotemporal dementia (FTD) based upon functional dependence and behavioral changes, and to assess change over time in the 3 main FTD variants (behavioral variant FTD [bvFTD]; progressive nonfluent aphasia [PNFA]; and semantic dementia [SemD]).

METHODS: The Frontotemporal Dementia Rating Scale (FRS) was developed in a validation cohort of 77 consecutive clinic attendees (bvFTD = 29; PNFA = 20; SemD = 28) and applied to an independent sample of 75 patients (bvFTD = 28; PNFA = 21; SemD = 26) to establish intergroup differences. Assessments from 42 patients followed up after 12 months were used to determine annual progression. Finally, a combined sample (n = 152) was used to determine length of symptoms in each severity category.

RESULTS: Six severity stages were identified and operationalized based upon a 30-item questionnaire (very mild to profound). The cross-sectional study revealed much greater levels of impairment in bvFTD than in the language variants, with limited correlation with general cognitive measures. Patients with SemD showed the closest association between length of symptoms and stage, taking, on average, 10 years to reach the severe stage. Patients with bvFTD appear to move most quickly between stages and patients with PNFA were intermediate. The FRS was capable of detecting functional deterioration in all 3 variants over 12 months.

CONCLUSIONS: Disease progression differs across frontotemporal dementia (FTD) variants. Patients with behavioral variant FTD progress rapidly whereas those with semantic dementia progress more slowly. The Frontotemporal Dementia Rating Scale can aid in staging and determining disease progression. Length of symptoms and global cognitive assessments alone do not reflect disease severity and progression in FTD.