Original Investigation
December 2015

Progression in Behavioral Variant Frontotemporal DementiaA Longitudinal Study

Author Affiliations
  • 1Neuroscience Research Australia, Sydney, Australia
  • 2Prince of Wales Clinical School, University of New South Wales, Sydney, Australia
  • 3Brain and Mind Research Institute, Sydney, Australia
  • 4School of Medical Sciences, University of New South Wales, Sydney, Australia
  • 5ARC Centre of Excellence in Cognition and Its Disorders, Sydney, Australia
  • 6Department of Clinical Neurosciences, University of Cambridge, Cambridge, England

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JAMA Neurol. 2015;72(12):1501-1509. doi:10.1001/jamaneurol.2015.2061

Importance  A gap in the literature exists regarding progression in behavioral variant frontotemporal dementia (BVFTD). Guidance is needed concerning markers that will enable clinicians to discriminate FTD more effectively from phenocopies and to identify factors that determine progression and thereby prognosis.

Objectives  To observe longitudinal outcomes and progression in probable and possible BVFTD in accordance with international diagnostic criteria and to identify features that may aid clinicians to prognosticate better in cases of possible BVFTD.

Design, Setting, and Participants  Longitudinal cohort study performed in a specialist tertiary FTD research clinic. Fifty-eight consecutive patients were followed up longitudinally from January 1, 2008, through December 31, 2013, and classified as having possible, probable, or definite BVFTD at presentation and latest review. Final follow-up was completed on December 31, 2013, and data were analyzed from January 1 to August 1, 2014.

Main Outcomes and Measures  Clinical, pathological, genetic, neuropsychological, and neuroimaging data were analyzed to categorize patients, to compare differences between groups with changed and unchanged diagnoses, to determine rates of progression in BVFTD, and to identify prognostic features in possible BVFTD.

Results  At presentation, 38 of the 58 patients fulfilled criteria for probable BVFTD; of these, 36 continued to satisfy probable criteria or underwent conversion to definite criteria over time. The remaining 20 patients satisfied possible criteria only, and 11 of these patients changed categories over time to probable or definite BVFTD and showed progression on cognitive and functional measures (termed changed status). Of these 11 patients, 8 (73%) carried the C9orf72 expansion. A positive family history, memory impairment, and clinical abnormalities at presentation were key features of progression (P < .05). A continuum of neuropsychological scores, progression rates, and atrophy severity emerged across patients in probable, possible, changed status, and nonchanged status groups; patients with probable BVFTD exhibited the most severe abnormalities.

Conclusions and Relevance  Behavioral variant FTD shows variable progression over time. Clinicians can use a detailed neurologic and cognitive assessment to identify key predictive features of progression when faced with possible BVFTD, whereas a diagnosis of probable BVFTD is accurate in a clinical setting.