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Sci Rep. 2019 Aug 29;9(1):12506. doi: 10.1038/s41598-019-48446-0.

Network analysis of canine brain morphometry links tumour risk to oestrogen deficiency and accelerated brain ageing.

Author information

1
Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Easter Bush Campus, Roslin, Midlothian, EH25 9RG, UK. ninar@mrc-lmb.cam.ac.uk.
2
Centre for Clinical Brain Sciences, University of Edinburgh, Chancellor's Building, Edinburgh, Midlothian, EH16 4SB, UK. ninar@mrc-lmb.cam.ac.uk.
3
Medical Research Council Laboratory of Molecular Biology, Cambridge Biomedical Campus, Francis Crick Avenue, Cambridge, CB2 0QH, UK. ninar@mrc-lmb.cam.ac.uk.
4
Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Easter Bush Campus, Roslin, Midlothian, EH25 9RG, UK.
5
Alzheimer Scotland Dementia Research Centre, University of Edinburgh, 7 George Square, Edinburgh, Scotland, EH8 9JZ, UK.
6
Department of Biomedical Engineering, University of Delaware, Newark, DE, 19716, USA.

Abstract

Structural 'brain age' is a valuable but complex biomarker for several brain disorders. The dog is an unrivalled comparator for neurological disease modeling, however canine brain morphometric diversity creates computational and statistical challenges. Using a data-driven approach, we explored complex interactions between patient metadata, brain morphometry, and neurological disease. Twenty-four morphometric parameters measured from 286 canine brain magnetic resonance imaging scans were combined with clinical parameters to generate 9,438 data points. Network analysis was used to cluster patients according to their brain morphometry profiles. An 'aged-brain' profile, defined by a small brain width and volume combined with ventriculomegaly, was revealed in the Boxer breed. Key features of this profile were paralleled in neutered female dogs which, relative to un-neutered females, had an 11-fold greater risk of developing brain tumours. Boxer dog and geriatric dog groups were both enriched for brain tumour diagnoses, despite a lack of geriatric Boxers within the cohort. Our findings suggest that advanced brain ageing enhances brain tumour risk in dogs and may be influenced by oestrogen deficiency-a risk factor for dementia and brain tumours in humans. Morphometric features of brain ageing in dogs, like humans, might better predict neurological disease risk than patient chronological age.

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