title: Network-selective vulnerability of the human cerebellum to Alzheimer's disease and frontotemporal dementia.
abstract: SEE SCHMAHMANN DOI101093/BRAIN/AWW064 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Neurodegenerative diseases are associated with distinct and distributed patterns of atrophy in the cerebral cortex. Emerging evidence suggests that these atrophy patterns resemble intrinsic connectivity networks in the healthy brain, supporting the network-based degeneration framework where neuropathology spreads across connectivity networks. An intriguing yet untested possibility is that the cerebellar circuits, which share extensive connections with the cerebral cortex, could be selectively targeted by major neurodegenerative diseases. Here we examined the structural atrophy in the cerebellum across common types of neurodegenerative diseases, and characterized the functional connectivity patterns of these cerebellar atrophy regions. Our results showed that Alzheimer's disease and frontotemporal dementia are associated with distinct and circumscribed atrophy in the cerebellum. These cerebellar atrophied regions share robust and selective intrinsic connectivity with the atrophied regions in the cerebral cortex. These findings for the first time demonstrated the selective vulnerability of the cerebellum to common neurodegenerative disease, extending the network-based degeneration framework to the cerebellum. Our work also has direct implications on the cerebellar contribution to the cognitive and affective processes that are compromised in neurodegeneration as well as the practice of using the cerebellum as reference region for ligand neuroimaging studies.
authors.affiliation: 1 QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
authors.forename: Christine C
authors.initials: CC
authors.lastname: Guo
authors.affiliation: 2 Neuroscience Research Australia, Sydney, Australia 3 School of Medical Sciences, University of New South Wales, Sydney, Australia.
authors.forename: Rachel
authors.initials: R
authors.lastname: Tan
authors.affiliation: 2 Neuroscience Research Australia, Sydney, Australia 3 School of Medical Sciences, University of New South Wales, Sydney, Australia 4 ARC Centre of Excellence in Cognition and its Disorders, Sydney, Australia.
authors.forename: John R
authors.initials: JR
authors.lastname: Hodges
authors.affiliation: 5 School of Automation, Northwestern Polytechnical University, Xian, China.
authors.forename: Xintao
authors.initials: X
authors.lastname: Hu
authors.affiliation: 6 Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
authors.forename: Saber
authors.initials: S
authors.lastname: Sami
authors.affiliation: 2 Neuroscience Research Australia, Sydney, Australia 4 ARC Centre of Excellence in Cognition and its Disorders, Sydney, Australia 7 Norwich Medical School, University of East Anglia, Norwich, UK m.hornberger@uea.ac.uk.
authors.forename: Michael
authors.initials: M
authors.lastname: Hornberger
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000473:pathology*; D018888:Aphasia, Primary Progressive / Q000473:pathology*; D001284:Atrophy / Q000473:pathology; D016022:Case-Control Studies; D002531:Cerebellum / Q000473:pathology*; D002540:Cerebral Cortex / Q000473:pathology; D005260:Female; D057180:Frontotemporal Dementia / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000473:pathology; D059906:Neuroimaging
keywords: cerebellum; intrinsic connectivity; neurodegeneration; selective vulnerability