Original Research ARTICLE
Subtypes Of Alzheimer’s Disease Display Distinct Network Abnormalities Extending Beyond Their Pattern Of Brain Atrophy
- 1Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Sweden
- 2Department of Physics, University of Gothenburg, Sweden
Different subtypes of Alzheimer’s disease (AD) with characteristic distributions of neurofibrillary tangles and corresponding brain atrophy patterns have been identified using structural magnetic resonance imaging (MRI). However, the underlying biological mechanisms that determine this differential expression of neurofibrillary tangles are still unknown. Here, we applied graph theoretical analysis to structural MRI data to test the hypothesis that differential network disruption is at the basis of the emergence of these AD subtypes. We studied a total of 175 AD patients and 81 controls. Subtyping was done using the Scheltens’ scale for medial temporal lobe atrophy, the Koedam’s scale for posterior atrophy, and the Pasquier’s global cortical atrophy scale for frontal atrophy. A total of 89 AD patients showed a brain atrophy pattern consistent with typical AD; 30 patients showed a limbic-predominant pattern; 29 patients showed a hippocampal-sparing pattern; and 27 showed minimal atrophy. We built brain structural networks from 68 cortical regions and 14 subcortical gray matter structures for each AD subtype and for the controls, and we compared between-group measures of integration, segregation, and modular organization. At the global level, modularity was increased and differential modular reorganization was detected in the four subtypes. We also found a decrease of transitivity in the typical and hippocampal-sparing subtypes, as well as an increase of average local efficiency in the minimal atrophy and hippocampal-sparing subtypes. We conclude that the AD subtypes have a distinct signature of network disruption associated with their atrophy patterns and further extending to other brain regions, presumably reflecting the differential spread of neurofibrillary tangles. We discuss the hypothetical emergence of these subtypes and possible clinical implications.
Keywords: Alzheimer’s disease, graph theory, Neurofibrillary Tangles, structural MRI, subtypes, heterogeneity
Received: 05 Jan 2019;
Accepted: 01 May 2019.
Edited by:Carlos Gómez, University of Valladolid, Spain
Reviewed by:Yi Su, Banner Alzheimer’s Institute, United States
Alexandra Abos, Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Spain
Copyright: © 2019 Ferreira, Pereira, Volpe and Westman. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Dr. Daniel Ferreira, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden, firstname.lastname@example.org