title: Predicting Development of Amyotrophic Lateral Sclerosis in Frontotemporal Dementia.
abstract: A proportion of patients with frontotemporal dementia (FTD) also develop amyotrophic lateral sclerosis (ALS).
  
  
  
  We aimed to establish the risk of developing ALS in patients presenting with FTD and to identify the relevant clinical variables associated with progression from FTD to FTD-ALS.
  
  
  
  Of 218 consecutive patients with FTD, 10.1% had a dual FTD-ALS diagnosis at presentation. The remaining 152 FTD patients with follow-up of at least 12 months were included in the present study. We calculated the rate of progression to FTD-ALS and compared the baseline characteristics of FTD patients who developed ALS to those who did not develop ALS.
  
  
  
  Five percent of FTD patients developed ALS. The incidence rate of ALS was 6.7/100 patient-years in patients with FTD symptoms since 1 year, which declined with duration of FTD symptoms. No FTD patients developed ALS after 5 years. Five out of 8 FTD patients who developed ALS had presented with a mixed behavioral variant FTD and progressive non-fluent aphasia (bvFTD+PNFA) phenotype, 2 with bvFTD, and 1 with PNFA. Progression to FTD-ALS was significantly more frequent in patients with bvFTD+PNFA compared to those without this phenotype (p < 0.0001, OR 38.3, 95% CI: 7.3 to 199.2), and in FTD patients who carried the C9orf72 repeat expansion compared to those without the repeat expansion (p = 0.02, OR 8.0, 95% CI: 1.7 to 38.6).
  
  
  
  FTD patients with a mixed bvFTD+PNFA phenotype and with a C9orf72 repeat expansion should be closely monitored for the possible development of ALS. The risk of developing ALS in FTD appears to decline with the duration of FTD symptoms.
authors.affiliation: Neuroscience Research Australia, Sydney, Australia.|ARC Centre of Excellence in Cognition and its Disorders, Sydney, Australia.|School of Medical Sciences, The University of New South Wales, Sydney, Australia.|Department of Molecular Genetics, VIB, Antwerp, Belgium.|Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
authors.forename: Tim
authors.initials: T
authors.lastname: Van Langenhove
authors.affiliation: Neuroscience Research Australia, Sydney, Australia.|ARC Centre of Excellence in Cognition and its Disorders, Sydney, Australia.|School of Medical Sciences, The University of New South Wales, Sydney, Australia.
authors.forename: Olivier
authors.initials: O
authors.lastname: Piguet
authors.affiliation: Neuroscience Research Australia, Sydney, Australia.|ARC Centre of Excellence in Cognition and its Disorders, Sydney, Australia.|School of Medical Sciences, The University of New South Wales, Sydney, Australia.
authors.forename: James R
authors.initials: JR
authors.lastname: Burrell
authors.affiliation: Neuroscience Research Australia, Sydney, Australia.|ARC Centre of Excellence in Cognition and its Disorders, Sydney, Australia.|Faculty of Health Sciences, The University of Sydney, Sydney, Australia.|Department of Neurology, Massachusetts General Hospital, Charlestown, USA.
authors.forename: Cristian
authors.initials: C
authors.lastname: Leyton
authors.affiliation: Neuroscience Research Australia, Sydney, Australia.|ARC Centre of Excellence in Cognition and its Disorders, Sydney, Australia.|School of Medical Sciences, The University of New South Wales, Sydney, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Foxe
authors.affiliation: Neuroscience Research Australia, Sydney, Australia.|ARC Centre of Excellence in Cognition and its Disorders, Sydney, Australia.
authors.forename: Melissa
authors.initials: M
authors.lastname: Abela
authors.affiliation: Neuroscience Research Australia, Sydney, Australia.|ARC Centre of Excellence in Cognition and its Disorders, Sydney, Australia.|School of Medical Sciences, The University of New South Wales, Sydney, Australia.
authors.forename: Lauren
authors.initials: L
authors.lastname: Bartley
authors.affiliation: Neuroscience Research Australia, Sydney, Australia.|School of Medical Sciences, The University of New South Wales, Sydney, Australia.
authors.forename: Woojin S
authors.initials: WS
authors.lastname: Kim
authors.affiliation: Neuroscience Research Australia, Sydney, Australia.|School of Medical Sciences, The University of New South Wales, Sydney, Australia.
authors.forename: Eve
authors.initials: E
authors.lastname: Jary
authors.affiliation: Neuroscience Research Australia, Sydney, Australia.|School of Medical Sciences, The University of New South Wales, Sydney, Australia.
authors.forename: Yue
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Neuroscience Research Australia, Sydney, Australia.|School of Medical Sciences, The University of New South Wales, Sydney, Australia.
authors.forename: Carol
authors.initials: C
authors.lastname: Dobson-Stone
authors.affiliation: Neuroscience Research Australia, Sydney, Australia.|School of Medical Sciences, The University of New South Wales, Sydney, Australia.
authors.forename: John B
authors.initials: JB
authors.lastname: Kwok
authors.affiliation: Neuroscience Research Australia, Sydney, Australia.|School of Medical Sciences, The University of New South Wales, Sydney, Australia.
authors.forename: Glenda M
authors.initials: GM
authors.lastname: Halliday
authors.affiliation: Neuroscience Research Australia, Sydney, Australia.|ARC Centre of Excellence in Cognition and its Disorders, Sydney, Australia.|School of Medical Sciences, The University of New South Wales, Sydney, Australia.
authors.forename: John R
authors.initials: JR
authors.lastname: Hodges
mesh_terms: D017668:Age of Onset; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis* / Q000209:etiology*; D000073885:C9orf72 Protein / Q000235:genetics; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D057180:Frontotemporal Dementia / Q000150:complications* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011237:Predictive Value of Tests; D011569:Psychiatric Status Rating Scales
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human
keywords: Amyotrophic lateral sclerosis; disease progression; frontotemporal dementia; incidence; primary progressive aphasia; prognosis