title: Quantitative validation of a visual rating scale for frontal atrophy: associations with clinical status, APOE e4, CSF biomarkers and cognition.
abstract: OBJECTIVE
  To validate a visual rating scale of frontal atrophy with quantitative imaging and study its association with clinical status, APOE ε4, CSF biomarkers, and cognition.
  
  
  METHODS
  The AddNeuroMed and ADNI cohorts were combined giving a total of 329 healthy controls, 421 mild cognitive impairment patients, and 286 Alzheimer's disease (AD) patients. Thirty-four patients with frontotemporal dementia (FTD) were also included. Frontal atrophy was assessed with the frontal sub-scale of the global cortical atrophy scale (GCA-F) on T1-weighted images. Automated imaging markers of cortical volume, thickness, and surface area were evaluated. Manual tracing was also performed.
  
  
  RESULTS
  The GCA-F scale reliably reflects frontal atrophy, with orbitofrontal, dorsolateral, and motor cortices being the regions contributing most to the GCA-F ratings. GCA-F primarily reflects reductions in cortical volume and thickness, although it was able to detect reductions in surface area too. The scale showed significant associations with clinical status and cognition.
  
  
  CONCLUSIONS
  The GCA-F scale may have implications for clinical practice as supportive diagnostic tool for disorders demonstrating predominant frontal atrophy such as FTD and the executive presentation of AD. We believe that GCA-F is feasible for use in clinical routine for the radiological assessment of dementia and other disorders.
  
  
  CONCLUSIONS
  • The GCA-F visual rating scale reliably reflects frontal brain atrophy. • Orbitofrontal, dorsolateral, and motor cortices are the most contributing regions. • GCA-F shows significant associations with clinical status and cognition. • GCA-F may be supportive diagnostic tool for disorders demonstrating predominant frontal atrophy. • GCA-F may be feasible for use in radiological routine.
authors.affiliation: Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Novum, 5th floor, SE-141 86, Stockholm, Sweden. daniel.ferreira.padilla@ki.se.
authors.forename: Daniel
authors.identifier: http://orcid.org/0000-0001-9522-4338
authors.initials: D
authors.lastname: Ferreira
authors.affiliation: Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.|Department of Radiology, Karolinska University Hospital in Huddinge, Huddinge, Sweden.
authors.forename: Lena
authors.initials: L
authors.lastname: Cavallin
authors.affiliation: Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.|Department of Radiology, Karolinska University Hospital in Huddinge, Huddinge, Sweden.
authors.forename: Tobias
authors.initials: T
authors.lastname: Granberg
authors.affiliation: Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Novum, 5th floor, SE-141 86, Stockholm, Sweden.
authors.forename: Olof
authors.initials: O
authors.lastname: Lindberg
authors.affiliation: Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Novum, 5th floor, SE-141 86, Stockholm, Sweden.
authors.forename: Carlos
authors.initials: C
authors.lastname: Aguilar
authors.affiliation: Institute of Gerontology and Geriatrics, University of Perugia, Perugia, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Mecocci
authors.affiliation: INSERM U 558, University of Toulouse, Toulouse, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Vellas
authors.affiliation: 3rd Department of Neurology, Aristoteleion Panepistimeion Thessalonikis, Thessaloniki, Greece.
authors.forename: Magda
authors.initials: M
authors.lastname: Tsolaki
authors.affiliation: Medical University of Lodz, Lodz, Poland.
authors.forename: Iwona
authors.initials: I
authors.lastname: Kłoszewska
authors.affiliation: University of Eastern Finland, University Hospital of Kuopio, Kuopio, Finland.
authors.forename: Hilkka
authors.initials: H
authors.lastname: Soininen
authors.affiliation: Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Lovestone
authors.affiliation: Department of Neuroimaging, Institute of Psychiatry, King's College London, London, UK.|NIHR Biomedical Research Centre for Mental Health, London, UK.|NIHR Biomedical Research Unit for Dementia, London, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Simmons
authors.affiliation: Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Novum, 5th floor, SE-141 86, Stockholm, Sweden.
authors.forename: Lars-Olof
authors.initials: LO
authors.lastname: Wahlund
authors.affiliation: Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Novum, 5th floor, SE-141 86, Stockholm, Sweden.
authors.forename: Eric
authors.initials: E
authors.lastname: Westman
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000503:physiopathology; D053327:Apolipoprotein E4 / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D003071:Cognition / Q000502:physiology*; D005260:Female; D005625:Frontal Lobe / Q000000981:diagnostic imaging*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged
chemical_list: D053327:Apolipoprotein E4; D015415:Biomarkers
keywords: Alzheimer’s disease; Frontal atrophy; Frontotemporal dementia; Mild cognitive impairment; Neuroimaging