title: Cerebellar integrity in the amyotrophic lateral sclerosis-frontotemporal dementia continuum.
abstract: Amyotrophic lateral sclerosis (ALS) and behavioural variant frontotemporal dementia (bvFTD) are multisystem neurodegenerative disorders that manifest overlapping cognitive, neuropsychiatric and motor features. The cerebellum has long been known to be crucial for intact motor function although emerging evidence over the past decade has attributed cognitive and neuropsychiatric processes to this structure. The current study set out i) to establish the integrity of cerebellar subregions in the amyotrophic lateral sclerosis-behavioural variant frontotemporal dementia spectrum (ALS-bvFTD) and ii) determine whether specific cerebellar atrophy regions are associated with cognitive, neuropsychiatric and motor symptoms in the patients. Seventy-eight patients diagnosed with ALS, ALS-bvFTD, behavioural variant frontotemporal dementia (bvFTD), most without C9ORF72 gene abnormalities, and healthy controls were investigated. Participants underwent cognitive, neuropsychiatric and functional evaluation as well as structural imaging using voxel-based morphometry (VBM) to examine the grey matter subregions of the cerebellar lobules, vermis and crus. VBM analyses revealed: i) significant grey matter atrophy in the cerebellum across the whole ALS-bvFTD continuum; ii) atrophy predominantly of the superior cerebellum and crus in bvFTD patients, atrophy of the inferior cerebellum and vermis in ALS patients, while ALS-bvFTD patients had both patterns of atrophy. Post-hoc covariance analyses revealed that cognitive and neuropsychiatric symptoms were particularly associated with atrophy of the crus and superior lobule, while motor symptoms were more associated with atrophy of the inferior lobules. Taken together, these findings indicate an important role of the cerebellum in the ALS-bvFTD disease spectrum, with all three clinical phenotypes demonstrating specific patterns of subregional atrophy that associated with different symptomology.
authors.affiliation: Neuroscience Research Australia, Randwick, New South Wales, Australia; School of Medical Sciences, University of New South Wales, Randwick, New South Wales, Australia.
authors.forename: Rachel H
authors.initials: RH
authors.lastname: Tan
authors.affiliation: Neuroscience Research Australia, Randwick, New South Wales, Australia; School of Medical Sciences, University of New South Wales, Randwick, New South Wales, Australia.
authors.forename: Emma
authors.initials: E
authors.lastname: Devenney
authors.affiliation: Neuroscience Research Australia, Randwick, New South Wales, Australia; School of Medical Sciences, University of New South Wales, Randwick, New South Wales, Australia.
authors.forename: Carol
authors.initials: C
authors.lastname: Dobson-Stone
authors.affiliation: Neuroscience Research Australia, Randwick, New South Wales, Australia; School of Medical Sciences, University of New South Wales, Randwick, New South Wales, Australia.
authors.forename: John B
authors.initials: JB
authors.lastname: Kwok
authors.affiliation: Neuroscience Research Australia, Randwick, New South Wales, Australia; School of Medical Sciences, University of New South Wales, Randwick, New South Wales, Australia; ARC Centre of Excellence in Cognition and its Disorders, Sydney, New South Wales, Australia.
authors.forename: John R
authors.initials: JR
authors.lastname: Hodges
authors.affiliation: Neuroscience Research Australia, Randwick, New South Wales, Australia; Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Kiernan
authors.affiliation: Neuroscience Research Australia, Randwick, New South Wales, Australia; School of Medical Sciences, University of New South Wales, Randwick, New South Wales, Australia.
authors.forename: Glenda M
authors.initials: GM
authors.lastname: Halliday
authors.affiliation: Neuroscience Research Australia, Randwick, New South Wales, Australia; ARC Centre of Excellence in Cognition and its Disorders, Sydney, New South Wales, Australia; University of Cambridge, Department of Clinical Neurosciences, Cambridge, United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: Hornberger
mesh_terms: D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D000073885:C9orf72 Protein; D002531:Cerebellum / Q000473:pathology / Q000503:physiopathology; D005260:Female; D057180:Frontotemporal Dementia / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011506:Proteins / Q000235:genetics*
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D011506:Proteins