title: Functional connectivity in autosomal dominant and late-onset Alzheimer disease.
abstract: OBJECTIVE
  Autosomal dominant Alzheimer disease (ADAD) is caused by rare genetic mutations in 3 specific genes in contrast to late-onset Alzheimer disease (LOAD), which has a more polygenetic risk profile.
  
  
  OBJECTIVE
  To assess the similarities and differences in functional connectivity changes owing to ADAD and LOAD.
  
  
  METHODS
  We analyzed functional connectivity in multiple brain resting state networks (RSNs) in a cross-sectional cohort of participants with ADAD (n = 79) and LOAD (n = 444), using resting-state functional connectivity magnetic resonance imaging at multiple international academic sites.
  
  
  METHODS
  For both types of AD, we quantified and compared functional connectivity changes in RSNs as a function of dementia severity measured by the Clinical Dementia Rating Scale. In ADAD, we qualitatively investigated functional connectivity changes with respect to estimated years from onset of symptoms within 5 RSNs.
  
  
  RESULTS
  A decrease in functional connectivity with increasing Clinical Dementia Rating scores were similar for both LOAD and ADAD in multiple RSNs. Ordinal logistic regression models constructed in one type of Alzheimer disease accurately predicted clinical dementia rating scores in the other, further demonstrating the similarity of functional connectivity loss in each disease type. Among participants with ADAD, functional connectivity in multiple RSNs appeared qualitatively lower in asymptomatic mutation carriers near their anticipated age of symptom onset compared with asymptomatic mutation noncarriers.
  
  
  CONCLUSIONS
  Resting-state functional connectivity magnetic resonance imaging changes with progressing AD severity are similar between ADAD and LOAD. Resting-state functional connectivity magnetic resonance imaging may be a useful end point for LOAD and ADAD therapy trials. Moreover, the disease process of ADAD may be an effective model for the LOAD disease process.
authors: Department of Neurology, Washington University in St Louis, St Louis, Missouri.
authors: Jewell B
authors: JB
authors: Thomas
authors: Department of Neurology, Washington University in St Louis, St Louis, Missouri.
authors: Matthew R
authors: MR
authors: Brier
authors: Department of Neurology, Washington University in St Louis, St Louis, Missouri.
authors: Randall J
authors: RJ
authors: Bateman
authors: Department of Radiology, Washington University in St Louis, St Louis, Missouri.
authors: Abraham Z
authors: AZ
authors: Snyder
authors: Department of Radiology, Washington University in St Louis, St Louis, Missouri.
authors: Tammie L
authors: TL
authors: Benzinger
authors: Division of Biostatistics, Washington University in St Louis, St Louis, Missouri.
authors: Chengjie
authors: C
authors: Xiong
authors: Department of Neurology, Washington University in St Louis, St Louis, Missouri2Department of Radiology, Washington University in St Louis, St Louis, Missouri4Department of Anatomy and Neurobiology, Washington University in St Louis, St Louis, Missouri.
authors: Marcus
authors: M
authors: Raichle
authors: Department of Neurology, Washington University in St Louis, St Louis, Missouri.
authors: David M
authors: DM
authors: Holtzman
authors: Department of Neurology, Brigham and Women's Hospital, Massachusetts General Hospital, Harvard Medical School, Boston.
authors: Reisa A
authors: RA
authors: Sperling
authors: Department of Neurology, Columbia University Medical Center, New York, New York.
authors: Richard
authors: R
authors: Mayeux
authors: Department of Pathology and Laboratory Medicine, Indiana University, Bloomington.
authors: Bernardino
authors: B
authors: Ghetti
authors: Department of Neurology, Easton Center for Alzheimer's Disease Research, David Geffen School of Medicine, University of California, Los Angeles.
authors: John M
authors: JM
authors: Ringman
authors: Departments of Neurology and Psychiatry, Warren Alpert Medical School, Brown University, Providence, Rhode Island.
authors: Stephen
authors: S
authors: Salloway
authors: Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors: Eric
authors: E
authors: McDade
authors: Dementia Research Centre, Institute of Neurology, University College London, London, England.
authors: Martin N
authors: MN
authors: Rossor
authors: Dementia Research Centre, Institute of Neurology, University College London, London, England.
authors: Sebastien
authors: S
authors: Ourselin
authors: Neuroscience Research Australia, Sydney, Australia13School of Medical Sciences, University of New South Wales, Sydney, Australia.
authors: Peter R
authors: PR
authors: Schofield
authors: Mental Health Research Institute, University of Melbourne, Melbourne, Australia.
authors: Colin L
authors: CL
authors: Masters
authors: School of Medical Sciences, Edith Cowan University, Joondalup, Australia.
authors: Ralph N
authors: RN
authors: Martins
authors: Department of Medicine, University of California, San Francisco17Department of Radiology, University of California, San Francisco18Department of Psychiatry, University of California, San Francisco.
authors: Michael W
authors: MW
authors: Weiner
authors: Departments of Neurology and Psychiatry, Imaging Genetics Center, Laboratory of Neuroimaging, David Geffen School of Medicine at University of California, Los Angeles.
authors: Paul M
authors: PM
authors: Thompson
authors: Dementia Research Centre, Department of Neurodegeneration, Institute of Neurology, University College of London, London, England.
authors: Nick C
authors: NC
authors: Fox
authors: Department of Radiology, University of Michigan, Ann Arbor.
authors: Robert A
authors: RA
authors: Koeppe
authors: Department of Radiology, Mayo Clinic, Rochester, Minnesota.
authors: Clifford R
authors: CR
authors: Jack
authors: Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors: Chester A
authors: CA
authors: Mathis
authors: Department of Neurology, Washington University in St Louis, St Louis, Missouri.
authors: Angela
authors: A
authors: Oliver
authors: Department of Radiology, Washington University in St Louis, St Louis, Missouri.
authors: Tyler M
authors: TM
authors: Blazey
authors: Department of Psychiatry, Washington University in St Louis, St Louis, Missouri.
authors: Krista
authors: K
authors: Moulder
authors: Department of Neurology, Washington University in St Louis, St Louis, Missouri.
authors: Virginia
authors: V
authors: Buckles
authors: Department of Radiology, Washington University in St Louis, St Louis, Missouri.
authors: Russ
authors: R
authors: Hornbeck
authors: Department of Neurology, Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston.
authors: Jasmeer
authors: J
authors: Chhatwal
authors: Department of Neurology, Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston.
authors: Aaron P
authors: AP
authors: Schultz
authors: Department of Psychiatry, University of California, San Francisco.
authors: Alison M
authors: AM
authors: Goate
authors: Department of Neurology, Washington University in St Louis, St Louis, Missouri.
authors: Anne M
authors: AM
authors: Fagan
authors: Department of Neurology, Washington University in St Louis, St Louis, Missouri.
authors: Nigel J
authors: NJ
authors: Cairns
authors: Department of Radiology, Washington University in St Louis, St Louis, Missouri.
authors: Daniel S
authors: DS
authors: Marcus
authors: Department of Neurology, Washington University in St Louis, St Louis, Missouri.
authors: John C
authors: JC
authors: Morris
authors: Department of Neurology, Washington University in St Louis, St Louis, Missouri.
authors: Beau M
authors: BM
authors: Ances
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000145:classification / Q000235:genetics / Q000503:physiopathology*; D015331:Cohort Studies; D063132:Connectome / Q000379:methods*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000503:physiopathology*; D012720:Severity of Illness Index