Research Paper Volume 12, Issue 13 pp 12622—12647
Fully bayesian longitudinal unsupervised learning for the assessment and visualization of AD heterogeneity and progression
- 1 Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden
- 2 Department of Biomedical Engineering and Health Systems (MTH), KTH Royal Institute of Technology, Stockholm, Sweden
- 3 Department of Radiology, Mayo Clinic, Rochester, MN, USA
- 4 Department of Neuroimaging, Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
Received: March 22, 2020 Accepted: June 19, 2020https://doi.org/10.18632/aging.103623
How to Cite
Copyright © 2020 Poulakis et al. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Tau pathology and brain atrophy are the closest correlate of cognitive decline in Alzheimer’s disease (AD). Understanding heterogeneity and longitudinal progression of atrophy during the disease course will play a key role in understanding AD pathogenesis. We propose a framework for longitudinal clustering that simultaneously: 1) incorporates whole brain data, 2) leverages unequal visits per individual, 3) compares clusters with a control group, 4) allows for study confounding effects, 5) provides cluster visualization, 6) measures clustering uncertainty. We used amyloid-β positive AD and negative healthy subjects, three longitudinal structural magnetic resonance imaging scans (cortical thickness and subcortical volume) over two years. We found three distinct longitudinal AD brain atrophy patterns: one typical diffuse pattern (n=34, 47.2%), and two atypical patterns: minimal atrophy (n=23 31.9%) and hippocampal sparing (n=9, 12.5%). We also identified outliers (n=3, 4.2%) and observations with uncertain classification (n=3, 4.2%). The clusters differed not only in regional distributions of atrophy at baseline, but also longitudinal atrophy progression, age at AD onset, and cognitive decline. A framework for the longitudinal assessment of variability in cohorts with several neuroimaging measures was successfully developed. We believe this framework may aid in disentangling distinct subtypes of AD from disease staging.