title: Loss of functional connectivity is greater outside the default mode network in nonfamilial early-onset Alzheimer's disease variants.
abstract: The common and specific involvement of brain networks in clinical variants of Alzheimer's disease (AD) is not well understood. We performed task-free ("resting-state") functional imaging in 60 nonfamilial AD patients, including 20 early-onset AD (age at onset <65 years, amnestic/dysexecutive deficits), 24 logopenic aphasia (language deficits), and 16 posterior cortical atrophy patients (visual deficits), as well as 60 healthy controls. Seed-based connectivity analyses were conducted to assess differences between groups in 3 default mode network (DMN) components (anterior, posterior, and ventral) and 4 additional non-DMN networks: left and right executive-control, language, and higher visual networks. Significant decreases in connectivity were found across AD variants compared with controls in the non-DMN networks. Within the DMN components, patients showed higher connectivity in the anterior DMN, in particular in logopenic aphasia. No significant differences were found for the posterior and ventral DMN. Our findings suggest that loss of functional connectivity is greatest in networks outside the DMN in early-onset and nonamnestic AD variants and may thus be a better biomarker in these patients.
authors.affiliation: Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, USA; Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, CA, USA; Dementia Research Centre, Department of Neurodegenerative Disease, Institute of Neurology, University College London, London, UK. Electronic address: m.lehmann@ucl.ac.uk.
authors.forename: Manja
authors.initials: M
authors.lastname: Lehmann
authors.affiliation: Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, CA, USA.
authors.forename: Cindee
authors.initials: C
authors.lastname: Madison
authors.affiliation: Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, USA; Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, CA, USA.
authors.forename: Pia M
authors.initials: PM
authors.lastname: Ghosh
authors.affiliation: Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Zachary A
authors.initials: ZA
authors.lastname: Miller
authors.affiliation: Functional Imaging in Neuropsychiatric Disorders (FIND) Laboratory, Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Greicius
authors.affiliation: Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Joel H
authors.initials: JH
authors.lastname: Kramer
authors.affiliation: Department of Psychiatry, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, UC Los Angeles, Los Angeles, USA.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Coppola
authors.affiliation: Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Miller
authors.affiliation: Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, USA; Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, CA, USA; Lawrence Berkeley National Laboratory, Life Sciences Division, Berkeley, CA, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Jagust
authors.affiliation: Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Maria L
authors.initials: ML
authors.lastname: Gorno-Tempini
authors.affiliation: Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, USA.
authors.forename: William W
authors.initials: WW
authors.lastname: Seeley
authors.affiliation: Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, USA; Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, CA, USA; Lawrence Berkeley National Laboratory, Life Sciences Division, Berkeley, CA, USA.
authors.forename: Gil D
authors.initials: GD
authors.lastname: Rabinovici
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D001037:Aphasia; D001284:Atrophy; D001921:Brain / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000473:pathology; D056344:Executive Function / Q000502:physiology; D059907:Functional Neuroimaging; D014644:Genetic Variation; D006801:Humans; D007802:Language; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D009415:Nerve Net / Q000503:physiopathology*; D009434:Neural Pathways / Q000503:physiopathology*; D014796:Visual Perception
keywords: Alzheimer's disease; Functional magnetic resonance imaging; Intrinsic connectivity; Logopenic-variant primary progressive aphasia; Networks; Posterior cortical atrophy