Patterns of atrophy in pathologically confirmed dementias: a voxelwise analysis

Description: Imaging is recommended to support the clinical diagnoses of dementias, yet few imaging studies have pathological confirmation. This study aims to characterise patterns of brain volume loss in six primary pathologies compared to controls and to each other using a voxel-wise analysis. 186 patients with a diagnosis of dementia during life and histopathological confirmation of underlying pathology (107 Alzheimer’s disease [68 early-onset (before 65 years), 29 late-onset, 10 Presenilin-1 mutation carriers], 25 dementia with Lewy bodies, 11 3-repeat-tau, 17 4-repeat-tau, 12 TDP43A, 14 TDP43C), 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 grey and white matter volume. Early-onset and late-onset Alzheimer’s disease demonstrated distinct patterns of grey matter volume loss, with more extensive temporoparietal reduction in the early-onset group, and more focal medial temporal lobe loss in the late-onset group. The Presenilin-1 group had similar parietal extension to the early-onset group with more 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 pre-/post-central gyri volume was reduced in comparison to other pathological groups. Tau and TDP43A pathologies demonstrated similar patterns of frontotemporal volume loss, although less extensive in the right hemisphere in the 4-repeat-tau group, with greater parietal extension in the TDP43A group. The TDP43C group demonstrated greater left anterior-temporal involvement. Pathologically distinct dementias exhibit characteristic patterns of regional volume loss compared to controls and other dementias. Voxel-wise differences identified in these cohorts highlight imaging-signatures that may aid in the differentiation of dementia subtypes during life.

Related article: http://doi.org/10.1136/jnnp-2016-314978