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Cerebellar atrophy in neurodegeneration—a meta-analysis
  1. Helena M Gellersen1,
  2. Christine C Guo2,
  3. Claire O’Callaghan3,4,
  4. Rachel H Tan4,5,
  5. Saber Sami6,
  6. Michael Hornberger7,8
  1. 1 Department of Cognitive Neuroscience, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, The Netherlands
  2. 2 Mental Health Program, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia
  3. 3 Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Cambridge, UK
  4. 4 Brain and Mind Centre, Sydney Medical School, The University of Sydney, Sydney, Australia
  5. 5 Neuroscience Research Australia, Sydney, Australia
  6. 6 Department of Clinical Neuroscience, University of Cambridge, Cambridge, UK
  7. 7 Norwich Medical School, University of East Anglia, Norwich, UK
  8. 8 Dementia and Complexity in Later Life, NHS Norfolk and Suffolk Foundation Trust, UK
  1. Correspondence to Professor Michael Hornberger, Norwich Medical School, University of East Anglia, Norwich, UK; m.hornberger{at}uea.ac.uk

Abstract

Introduction The cerebellum has strong cortical and subcortical connectivity, but is rarely taken into account for clinical diagnosis in many neurodegenerative conditions, particularly in the absence of clinical ataxia. The current meta-analysis aims to assess patterns of cerebellar grey matter atrophy in seven neurodegenerative conditions (Alzheimer’s disease (AD), Parkinson’s disease (PD) and Huntington’s disease (HD), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), multiple system atrophy (MSA), progressive supranuclear palsy (MSP)).

Methods We carried out a systematic search in PubMed (any date: 14 July 2016) and a hand search of references from pertinent articles according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The authors were contacted to provide missing coordinate data. Peer-reviewed studies with direct comparison of patient and control groups, and availability of coordinate data of grey matter cerebellar atrophy in patients were included. These coordinates were used in an anatomical likelihood estimation meta-analysis.

Results Across 54 studies, clusters of cerebellar atrophy were found for AD, ALS, FTD, MSA, and PSP. Atrophy patterns were largely disease-specific, with overlap in certain areas of the cerebellar hemisphere, which showed marked atrophy in AD, ALS, FTD and PSP (Crus I/II), and MSA and PSP (lobules I–IV), respectively. Atrophy colocated with cerebellar areas implicated for motor (PSP, MSA) or cognitive symptoms (FTD, ALS, PSP) in the diseases.

Discussion Our findings suggest that cerebellar changes are largely disease-specific and correspond to cortical or subcortical changes in neurodegenerative conditions. High clinical variability in PD and HD samples may explain the absence of findings for consistent grey matter loss across studies. Our results have clinical implications for diagnosis and cerebellar neuroimaging referencing approaches.

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Footnotes

  • Contributor HMG, SS, MH: contributed to systematic literature search, statistical analysis and writing and revising of the manuscript.

    CCG: contributed to writing and revising of the manuscript; created cerebellar flatmaps.

    CO, RT: contributed to writing and revising of the manuscript.

  • Funding CO is supported by a National Health and Medical Research Council Neil Hamilton FairleyFellowship (GNT1091310). MH is funded by Alzheimer’s Research UK and Wellcome Trust. RT is supported by a National Health and Medical Research Council—Australian Research Council Dementia Research Development Fellowship (APP1110369). SSwould like to acknowledge funding from the James S. McDonnell Foundation.

  • Competing interests The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement All data used in this meta-analysis are available either in the main article or in the supplementary materials. All authors have full access to the raw data files used in this meta-analysis.

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