Progression in Behavioral Variant Frontotemporal Dementia: A Longitudinal Study.
OBJECTIVE
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.


OBJECTIVE
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.


METHODS
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.


METHODS
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
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.
Neuroscience Research Australia, Sydney, Australia2Prince of Wales Clinical School, University of New South Wales, Sydney, Australia3Brain and Mind Research Institute, Sydney, Australia.
Emma
E
Devenney
Neuroscience Research Australia, Sydney, Australia.
Lauren
L
Bartley
Neuroscience Research Australia, Sydney, Australia.
Chris
C
Hoon
Neuroscience Research Australia, Sydney, Australia3Brain and Mind Research Institute, Sydney, Australia.
Claire
C
O'Callaghan
Neuroscience Research Australia, Sydney, Australia4School of Medical Sciences, University of New South Wales, Sydney, Australia5ARC Centre of Excellence in Cognition and Its Disorders, Sydney, Australia.
Fiona
F
Kumfor
Neuroscience Research Australia, Sydney, Australia6Department of Clinical Neurosciences, University of Cambridge, Cambridge, England.
Michael
M
Hornberger
Neuroscience Research Australia, Sydney, Australia4School of Medical Sciences, University of New South Wales, Sydney, Australia.
John B
JB
Kwok
Neuroscience Research Australia, Sydney, Australia4School of Medical Sciences, University of New South Wales, Sydney, Australia.
Glenda M
GM
Halliday
ARC Centre of Excellence in Cognition and Its Disorders, Sydney, Australia.
Matthew C
MC
Kiernan
Neuroscience Research Australia, Sydney, Australia4School of Medical Sciences, University of New South Wales, Sydney, Australia5ARC Centre of Excellence in Cognition and Its Disorders, Sydney, Australia.
Olivier
O
Piguet
Neuroscience Research Australia, Sydney, Australia4School of Medical Sciences, University of New South Wales, Sydney, Australia.
John R
JR
Hodges
D000328:Adult; D000368:Aged; D001921:Brain / Q000473:pathology; D000073885:C9orf72 Protein; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D057180:Frontotemporal Dementia / Q000150:complications* / Q000235:genetics / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D001523:Mental Disorders / Q000175:diagnosis* / Q000209:etiology*; D008875:Middle Aged; D009483:Neuropsychological Tests; D011506:Proteins / Q000235:genetics; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric
D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D011506:Proteins