Comparison of subtyping methods for neuroimaging studies in Alzheimer’s disease: a call for harmonization

Author:

Mohanty Rosaleena1,Mårtensson Gustav1,Poulakis Konstantinos1,Muehlboeck J-Sebastian1,Rodriguez-Vieitez Elena1,Chiotis Konstantinos1,Grothe Michel J23,Nordberg Agneta14,Ferreira Daniel1,Westman Eric15,

Affiliation:

1. Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden

2. Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain

3. Clinical Dementia Research Section, German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany

4. Theme Aging, Karolinska University Hospital, Stockholm, Sweden

5. Department of Neuroimaging, Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK

Abstract

Abstract Biological subtypes in Alzheimer’s disease, originally identified on neuropathological data, have been translated to in vivo biomarkers such as structural magnetic resonance imaging (sMRI) and positron emission tomography (PET), to disentangle the heterogeneity within Alzheimer’s disease. Although there is methodological variability across studies, comparable characteristics of subtypes are reported at the group level. In this study, we investigated whether group-level similarities translate to individual-level agreement across subtyping methods, in a head-to-head context. We compared five previously published subtyping methods. Firstly, we validated the subtyping methods in 89 amyloid-beta positive Alzheimer’s disease dementia patients (reference group: 70 amyloid-beta negative healthy individuals) using sMRI. Secondly, we extended and applied the subtyping methods to 53 amyloid-beta positive prodromal Alzheimer’s disease and 30 amyloid-beta positive Alzheimer’s disease dementia patients (reference group: 200 amyloid-beta negative healthy individuals) using sMRI and tau PET. Subtyping methods were implemented as outlined in each original study. Group-level and individual-level comparisons across methods were performed. Each individual subtyping method was replicated, and the proof-of-concept was established. At the group level, all methods captured subtypes with similar patterns of demographic and clinical characteristics, and with similar cortical thinning and tau PET uptake patterns. However, at the individual level large disagreements were found in subtype assignments. Although characteristics of subtypes are comparable at the group level, there is a large disagreement at the individual level across subtyping methods. Therefore, there is an urgent need for consensus and harmonization across subtyping methods. We call for establishment of an open benchmarking framework to overcome this problem.

Publisher

Oxford University Press (OUP)

Subject

General Earth and Planetary Sciences,General Environmental Science

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