title: Disease-specific patterns of cortical and subcortical degeneration in a longitudinal study of Alzheimer's disease and behavioural-variant frontotemporal dementia.
abstract: Clinical differentiation between Alzheimer's disease (AD) and behavioural-variant frontotemporal dementia (bvFTD) is challenging due to overlapping clinical features at presentation. Whilst diagnostic criteria for both disorders incorporate evidence of frontal and temporal cortical atrophy, understanding of the progression of atrophy in these disorders is limited. This study aimed to elucidate common and disease-specific progressive changes in cortical and subcortical brain structures in AD and bvFTD.
  
  
  
  Forty-one AD, 37 bvFTD and 33 healthy controls underwent baseline MRI and of these longitudinal follow-up was obtained for 20AD and 20 bvFTD (1 to 4years). A total of 87 AD and 70 bvFTD consecutive scans were included in the study. The trajectories of progression in cortical and subcortical structures were identified with FreeSurfer and linear mixed effect modelling.
  
  
  
  The results uncovered cortical and subcortical disease-specific trajectories of neurodegeneration in AD and bvFTD. Specifically, direct comparisons between patient groups revealed that over time AD showed greater cortical atrophy in the inferior parietal and posterior cingulate cortex than bvFTD. Conversely, bvFTD patients showed greater atrophy in the striatum than AD over time.
  
  
  
  These results indicate that atrophy in the posterior cingulate and the striatum diverges with disease progression in these dementia syndromes and may represent a potential diagnostic biomarker for tracking rates of progression of AD and bvFTD. These findings may help inform future drug trials by identifying appropriate outcome measures to quantify drug efficacy and their ability to modulate disease progression over time.
authors.affiliation: Neuroscience Research Australia, Sydney, Australia; Australia Research Council Centre of Excellence in Cognition and its Disorders, Sydney, Australia; School of Medical Sciences, the University of New South Wales, Sydney, Australia. Electronic address: r.landin-romero@neura.edu.au.
authors.forename: Ramon
authors.initials: R
authors.lastname: Landin-Romero
authors.affiliation: Neuroscience Research Australia, Sydney, Australia; Australia Research Council Centre of Excellence in Cognition and its Disorders, Sydney, Australia; School of Medical Sciences, the University of New South Wales, Sydney, Australia.
authors.forename: Fiona
authors.initials: F
authors.lastname: Kumfor
authors.affiliation: Neuroscience Research Australia, Sydney, Australia; Australia Research Council Centre of Excellence in Cognition and its Disorders, Sydney, Australia; Faculty of Health Sciences, the University of Sydney, Lidcombe, NSW, Australia.
authors.forename: Cristian E
authors.initials: CE
authors.lastname: Leyton
authors.affiliation: Neuroscience Research Australia, Sydney, Australia; Australia Research Council Centre of Excellence in Cognition and its Disorders, Sydney, Australia; School of Psychology, the University of New South Wales, Sydney, Australia.
authors.forename: Muireann
authors.initials: M
authors.lastname: Irish
authors.affiliation: Neuroscience Research Australia, Sydney, Australia; Australia Research Council 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
authors.affiliation: Neuroscience Research Australia, Sydney, Australia; Australia Research Council 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
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000473:pathology*; D001284:Atrophy; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D057180:Frontotemporal Dementia / Q000000981:diagnostic imaging / Q000473:pathology*; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged
keywords: Atrophy patterns; Cortical surface; Dementia; FreeSurfer; Longitudinal; Mixed models; Neuroimaging; Progression; Subcortical volume