Patterns of atrophy in pathologically confirmed dementias: a voxelwise analysis

J Neurol Neurosurg Psychiatry. 2017 Nov;88(11):908-916. doi: 10.1136/jnnp-2016-314978. Epub 2017 May 4.


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 (

Keywords: Alzheimer’s disease; MRI; brain atrophy; dementia; neuropathology.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / pathology
  • Atrophy
  • Brain / diagnostic imaging
  • Brain / pathology*
  • Brain Mapping
  • Case-Control Studies
  • Dementia / diagnostic imaging
  • Dementia / pathology*
  • Female
  • Frontotemporal Dementia / diagnostic imaging
  • Frontotemporal Dementia / pathology
  • Gray Matter / diagnostic imaging
  • Gray Matter / pathology
  • Humans
  • Image Interpretation, Computer-Assisted
  • Lewy Body Disease / diagnostic imaging
  • Lewy Body Disease / pathology
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Organ Size / physiology
  • Presenilin-1 / analysis
  • Retrospective Studies
  • TDP-43 Proteinopathies / diagnostic imaging
  • TDP-43 Proteinopathies / pathology
  • White Matter / diagnostic imaging
  • White Matter / pathology
  • tau Proteins / analysis


  • MAPT protein, human
  • Presenilin-1
  • tau Proteins