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Research paper
Patterns of atrophy in pathologically confirmed dementias: a voxelwise analysis
  1. Lorna Harper1,
  2. Femke Bouwman2,
  3. Emma J Burton3,
  4. Frederik Barkhof4,5,6,
  5. Philip Scheltens2,
  6. John T O’Brien7,
  7. Nick C Fox1,
  8. Gerard R Ridgway8,9,
  9. Jonathan M Schott1
  1. 1 Dementia Research Centre, University College London Institute of Neurology, London, UK
  2. 2 Alzheimer Centre, VU University Medical Centre, Amsterdam, The Netherlands
  3. 3 Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK
  4. 4 Department of Radiology and Nuclear Medicine, VU Medical Center, MS Center, Amsterdam, The Netherlands
  5. 5 Department of Brain Repair and Rehabilitation, University College London Institute of Neurology, London, UK
  6. 6 Department of Medical Physics & Biomedical Engineering, University College London Faculty of Engineering Sciences, London, UK
  7. 7 Department of Psychiatry, University of Cambridge, Cambridge, UK
  8. 8 FMRIB Centre, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
  9. 9 Wellcome Trust Centre for Neuroimaging, UCL Institute of Neurology, London, UK
  1. Correspondence to Lorna Harper, Dementia Research Centre, ION UCL, 8-11 Queen Square, London WC1N 3BG, UK; lornaharper01{at}


Objective Imaging is recommended to support the clinical diagnoses of dementias, yet imaging research studies rarely have pathological confirmation of disease. This study aims to characterise patterns of brain volume loss in six primary pathologies compared with controls and to each other.

Methods One hundred and eighty-six patients with a clinical diagnosis of dementia and histopathological confirmation of underlying pathology, and 73 healthy controls were included in this study. Voxel-based morphometry, based on ante-mortem T1-weighted MRI, was used to identify cross-sectional group differences in brain volume.

Results Early-onset and late-onset Alzheimer’s disease exhibited different patterns of grey matter volume loss, with more extensive temporoparietal involvement in the early-onset group, and more focal medial temporal lobe loss in the late-onset group. The Presenilin-1 group had similar parietal involvement to the early-onset group with localised volume loss in the thalamus, medial temporal lobe and temporal neocortex. Lewy body pathology was associated with less extensive volume loss than the other pathologies, although precentral/postcentral gyri volume was reduced in comparison with other pathological groups. Tau and TDP43A pathologies demonstrated similar patterns of frontotemporal volume loss, although less extensive on the right in the 4-repeat-tau group, with greater parietal involvement in the TDP43A group. The TDP43C group demonstrated greater left anterior-temporal involvement.

Conclusions Pathologically distinct dementias exhibit characteristic patterns of regional volume loss compared with controls and other dementias. Voxelwise differences identified in these cohorts highlight imaging signatures that may aid in the differentiation of dementia subtypes during life. The results of this study are available for further examination via NeuroVault (

  • dementia
  • Alzheimer’s disease
  • brain atrophy
  • neuropathology
  • MRI

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See:

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  • Contributors LH, GRR and JMS designed the study and wrote the manuscript. LH performed the analysis.

    FB, EJB, FB, PS, JTOB and NCF collected data and revised the manuscript.

  • Competing interests None declared.

  • Ethics approval National Research Ethics Service Committee London South East.

  • Provenance and peer review Commissioned; externally peer reviewed.

  • Data sharing statement To request access to the underlying research materials, please contact the corresponding author.

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