Research Paper Volume 12, Issue 19 pp 19701—19710

Voxel-based morphometry focusing on medial temporal lobe structures has a limited capability to detect amyloid β, an Alzheimer’s disease pathology

Masashi Kameyama1, *, , Kenji Ishibashi2, *, , Jun Toyohara2, , Kei Wagatsuma2, , Yumi, Umeda-Kameyama3, , Keigo Shimoji1, , Kazutomi Kanemaru4, , Shigeo Murayama4, , Sumito Ogawa3, , Aya M. Tokumaru1, , Kenji Ishii2, ,

  • 1 Department of Diagnostic Radiology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo 173-0015, Japan
  • 2 Research Team for Neuroimaging, Tokyo Metropolitan Institute of Gerontology, Tokyo 173-0015, Japan
  • 3 Department of Geriatric Medicine, The University of Tokyo School of Medicine, Tokyo 113-8655, Japan
  • 4 Department of Neurology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, 113-0015, Japan
* Equal contribution

Received: March 22, 2019       Accepted: July 30, 2020       Published: October 5, 2020
How to Cite

Copyright: © 2020 Kameyama et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Voxel-based morphometry (VBM) analysis of nuclear Magnetic Resonance Imaging (MRI) data allows the identification of medial temporal lobe (MTL) atrophy and is widely used to assist the diagnosis of Alzheimer’s disease (AD). However, its reliability in the clinical environment has not yet been confirmed. To determine the credibility of VBM, amyloid positron emission tomography (PET) and VBM studies were compared retrospectively. Patients who underwent Pittsburgh Compound B (PiB) PET were retrospectively recruited. Ninety-seven patients were found to be amyloid negative and 116 were amyloid positive. MTL atrophy in the PiB positive group, as quantified by thin sliced 3D MRI and VBM software, was significantly more severe (p =0.0039) than in the PiB negative group. However, data histogram showed a vast overlap between the two groups. The area under the ROC curve (AUC) was 0.646. MMSE scores of patients in the amyloid negative and positive groups were also significantly different (p = 0.0028), and the AUC was 0.672. Thus, MTL atrophy could not reliably differentiate between amyloid positive and negative patients in a clinical setting, possibly due to the wide array of dementia-type diseases that exist other than AD.


AD: Alzheimer’s disease; AGD: argyrophilic grain dementia; DARTEL: diffeomorphic anatomical registration through exponentiated lie algebra; FTLD: fronto-temporal lobe dementia; DLB: dementia with Lewy bodies; MCI: mild cognitive impairment; MMSE: Mini-Mental State Examination; MRI: nuclear magnetic resonance imaging; PET: positron emission tomography; PiB: Pittsburgh Compound B; PSP: progressive supranuclear palsy; ROC: receiver operating characteristic analysis; SPM: statistical parametric mapping; VBM: voxel-based morphometry.