title: Distinct Subtypes of Behavioral Variant Frontotemporal Dementia Based on Patterns of Network Degeneration.
abstract: OBJECTIVE
  Clearer delineation of the phenotypic heterogeneity within behavioral variant frontotemporal dementia (bvFTD) will help uncover underlying biological mechanisms and improve clinicians' ability to predict disease course and to design targeted management strategies.
  
  
  OBJECTIVE
  To identify subtypes of bvFTD syndrome based on distinctive patterns of atrophy defined by selective vulnerability of specific functional networks targeted in bvFTD using statistical classification approaches.
  
  
  METHODS
  In this retrospective observational study, 90 patients meeting the Frontotemporal Dementia Consortium consensus criteria for bvFTD underwent evaluation at the Memory and Aging Center of the Department of Neurology at University of California, San Francisco. Patients underwent a multidisciplinary clinical evaluation, including clinical demographics, genetic testing, symptom evaluation, neurologic examination, neuropsychological bedside testing, and socioemotional assessments. All patients underwent structural magnetic resonance imaging at their earliest evaluation at the memory clinic. From each patient's structural imaging scans, the mean volumes of 18 regions of interest (ROI) constituting the functional networks specifically vulnerable in bvFTD, including the salience network (SN), with key nodes in the frontoinsula and pregenual anterior cingulate, and the semantic appraisal network (SAN), anchored in the anterior temporal lobe and subgenual cingulate, were estimated. Principal component and cluster analyses of ROI volumes were used to identify patient clusters with anatomically distinct atrophy patterns. Data were collected from from June 19, 2002, to January 13, 2015.
  
  
  METHODS
  Evaluation of brain morphology and other clinical features, including presenting symptoms, neurologic examination signs, neuropsychological performance, rate of dementia progression, and socioemotional function, in each patient cluster.
  
  
  RESULTS
  Ninety patients (54 men [60%]; 36 women [40%]; mean [SD] age at evaluation, 55.1 [9.7] years) were included in the analysis. Four subgroups of patients with bvFTD with distinct anatomic patterns of network degeneration were identified, including 2 salience network-predominant subgroups (frontal/temporal [SN-FT] and frontal [SN-F]), a semantic appraisal network-predominant group (SAN), and a subcortical-predominant group. Subgroups demonstrated distinct patterns of cognitive, socioemotional, and motor symptoms, as well as genetic compositions and estimated rates of disease progression.
  
  
  CONCLUSIONS
  Divergent patterns of vulnerability in specific functional network components make an important contribution to the clinical heterogeneity of bvFTD. The data-driven anatomic classification identifies biologically meaningful anatomic phenotypes and provides a replicable approach to disambiguate the bvFTD syndrome.
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco.
authors.forename: Kamalini G
authors.initials: KG
authors.lastname: Ranasinghe
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco.
authors.forename: Katherine P
authors.initials: KP
authors.lastname: Rankin
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Pressman
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco.
authors.forename: David C
authors.initials: DC
authors.lastname: Perry
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco2Department of Epidemiology and Biostatistics, University of California, San Francisco.
authors.forename: Iryna V
authors.initials: IV
authors.lastname: Lobach
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco3Department of Pathology, University of California, San Francisco.
authors.forename: William W
authors.initials: WW
authors.lastname: Seeley
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Coppola
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Karydas
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco3Department of Pathology, University of California, San Francisco.
authors.forename: Lea T
authors.initials: LT
authors.lastname: Grinberg
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco.
authors.forename: Tal
authors.initials: T
authors.lastname: Shany-Ur
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco.
authors.forename: Suzee E
authors.initials: SE
authors.lastname: Lee
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco.
authors.forename: Gil D
authors.initials: GD
authors.lastname: Rabinovici
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco.
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Rosen
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Gorno-Tempini
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco.
authors.forename: Adam L
authors.initials: AL
authors.lastname: Boxer
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco.
authors.forename: Zachary A
authors.initials: ZA
authors.lastname: Miller
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco.
authors.forename: Winston
authors.initials: W
authors.lastname: Chiong
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco.
authors.forename: Mary
authors.initials: M
authors.lastname: DeMay
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco.
authors.forename: Joel H
authors.initials: JH
authors.lastname: Kramer
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco.
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Possin
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco.
authors.forename: Virginia E
authors.initials: VE
authors.lastname: Sturm
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco5Departments of Neurosurgery and Neurology, University of Colorado Anschutz School of Medicine, Aurora.
authors.forename: Brianne M
authors.initials: BM
authors.lastname: Bettcher
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco.
authors.forename: Michael
authors.initials: M
authors.lastname: Neylan
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco.
authors.forename: Diana D
authors.initials: DD
authors.lastname: Zackey
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco.
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Nguyen
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco.
authors.forename: Robin
authors.initials: R
authors.lastname: Ketelle
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco.
authors.forename: Nikolas
authors.initials: N
authors.lastname: Block
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco.
authors.forename: Teresa Q
authors.initials: TQ
authors.lastname: Wu
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco.
authors.forename: Alison
authors.initials: A
authors.lastname: Dallich
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco.
authors.forename: Natanya
authors.initials: N
authors.lastname: Russek
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco.
authors.forename: Alyssa
authors.initials: A
authors.lastname: Caplan
authors.affiliation: Center for Autism Research and Treatment, University of California, Los Angeles.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Geschwind
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco7Gladstone Institute of Neurological Disease, San Francisco, California.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Vossel
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco.
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Miller
mesh_terms: D000368:Aged; D001921:Brain / Q000473:pathology*; D000073885:C9orf72 Protein; D003430:Cross-Sectional Studies; D005260:Female; D057180:Frontotemporal Dementia / Q000150:complications* / Q000235:genetics; D005820:Genetic Testing; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D001523:Mental Disorders / Q000145:classification* / Q000209:etiology*; D008609:Mental Status Schedule; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009483:Neuropsychological Tests; D011506:Proteins / Q000235:genetics; D012189:Retrospective Studies; D012720:Severity of Illness Index; D016875:tau Proteins / Q000235:genetics
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D011506:Proteins; D016875:tau Proteins