MRI-guided clustering of patients with mild dementia due to Alzheimer's disease using self-organizing maps

Introduction: Alzheimer's disease (AD) is a phenotypically and pathologically heterogenous neurodegenerative disorder. This heterogeneity can be studied and disentangled using data-driven clustering techniques. Methods: We implemented a self-organizing map clustering algorithm on baseline volum...

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Main Authors: Kellen K. Petersen, Bhargav T. Nallapu, Richard B. Lipton, Ellen Grober, Ali Ezzati
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:NeuroImage: Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2666956024000333
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author Kellen K. Petersen
Bhargav T. Nallapu
Richard B. Lipton
Ellen Grober
Ali Ezzati
author_facet Kellen K. Petersen
Bhargav T. Nallapu
Richard B. Lipton
Ellen Grober
Ali Ezzati
author_sort Kellen K. Petersen
collection DOAJ
description Introduction: Alzheimer's disease (AD) is a phenotypically and pathologically heterogenous neurodegenerative disorder. This heterogeneity can be studied and disentangled using data-driven clustering techniques. Methods: We implemented a self-organizing map clustering algorithm on baseline volumetric MRI measures from nine brain regions of interest (ROIs) to cluster 1041 individuals enrolled in the placebo arm of the EXPEDITION3 trial. Volumetric MRI differences were compared among clusters. Demographics as well as baseline and longitudinal cognitive performance metrics were used to evaluate cluster characteristics. Results: Three distinct clusters, with an overall silhouette coefficient of 0.491, were identified based on MRI volumetrics. Cluster 1 (N = 400) had the largest baseline volumetric measures across all ROIs and the best cognitive performance at baseline. Cluster 2 (N = 269) had larger hippocampal and medial temporal lobe volumes, but smaller parietal lobe volumes in comparison with the third cluster (N = 372). Significant between-group mean differences were observed between Clusters 1 and 2 (difference, 2.38; 95% CI, 1.85 to 2.91; P < 0.001), Clusters 1 and 3 (difference, 1.93; 95% CI, 1.41 to 2.44; P < 0.001), but not between Clusters 2 and 3 (difference, 0.45; 95% CI, −0.11 to 1.02; P = 0.146) in ADAS-14. Conclusions: Volumetric MRI can be used to identify homogenous clusters of amyloid positive individuals with mild dementia. The groups identified differ in baseline and longitudinal characteristics. Cluster 1 shows little ADAS-14 change over the first 40 weeks of study on placebo treatment and may be unsuitable for identifying early benefits of treatment.
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spelling doaj-art-6c544ce44de2425788dfecc50d6f8bc72025-08-20T01:57:11ZengElsevierNeuroImage: Reports2666-95602024-12-014410022710.1016/j.ynirp.2024.100227MRI-guided clustering of patients with mild dementia due to Alzheimer's disease using self-organizing mapsKellen K. Petersen0Bhargav T. Nallapu1Richard B. Lipton2Ellen Grober3Ali Ezzati4Department of Neurology, Washington University in St. Louis, St. Louis, MO, USA; Corresponding author.The Saul R. Korey Department of Neurology, Albert Einstein College of Medicine, New York City, NY, USAThe Saul R. Korey Department of Neurology, Albert Einstein College of Medicine, New York City, NY, USAThe Saul R. Korey Department of Neurology, Albert Einstein College of Medicine, New York City, NY, USAThe Saul R. Korey Department of Neurology, Albert Einstein College of Medicine, New York City, NY, USA; Department of Neurology, University of California-Irvine, Irvine, CA, USAIntroduction: Alzheimer's disease (AD) is a phenotypically and pathologically heterogenous neurodegenerative disorder. This heterogeneity can be studied and disentangled using data-driven clustering techniques. Methods: We implemented a self-organizing map clustering algorithm on baseline volumetric MRI measures from nine brain regions of interest (ROIs) to cluster 1041 individuals enrolled in the placebo arm of the EXPEDITION3 trial. Volumetric MRI differences were compared among clusters. Demographics as well as baseline and longitudinal cognitive performance metrics were used to evaluate cluster characteristics. Results: Three distinct clusters, with an overall silhouette coefficient of 0.491, were identified based on MRI volumetrics. Cluster 1 (N = 400) had the largest baseline volumetric measures across all ROIs and the best cognitive performance at baseline. Cluster 2 (N = 269) had larger hippocampal and medial temporal lobe volumes, but smaller parietal lobe volumes in comparison with the third cluster (N = 372). Significant between-group mean differences were observed between Clusters 1 and 2 (difference, 2.38; 95% CI, 1.85 to 2.91; P < 0.001), Clusters 1 and 3 (difference, 1.93; 95% CI, 1.41 to 2.44; P < 0.001), but not between Clusters 2 and 3 (difference, 0.45; 95% CI, −0.11 to 1.02; P = 0.146) in ADAS-14. Conclusions: Volumetric MRI can be used to identify homogenous clusters of amyloid positive individuals with mild dementia. The groups identified differ in baseline and longitudinal characteristics. Cluster 1 shows little ADAS-14 change over the first 40 weeks of study on placebo treatment and may be unsuitable for identifying early benefits of treatment.http://www.sciencedirect.com/science/article/pii/S2666956024000333Alzheimer's diseaseStructural MRIUnsupervised learningMachine learningSubtypesMild dementia
spellingShingle Kellen K. Petersen
Bhargav T. Nallapu
Richard B. Lipton
Ellen Grober
Ali Ezzati
MRI-guided clustering of patients with mild dementia due to Alzheimer's disease using self-organizing maps
NeuroImage: Reports
Alzheimer's disease
Structural MRI
Unsupervised learning
Machine learning
Subtypes
Mild dementia
title MRI-guided clustering of patients with mild dementia due to Alzheimer's disease using self-organizing maps
title_full MRI-guided clustering of patients with mild dementia due to Alzheimer's disease using self-organizing maps
title_fullStr MRI-guided clustering of patients with mild dementia due to Alzheimer's disease using self-organizing maps
title_full_unstemmed MRI-guided clustering of patients with mild dementia due to Alzheimer's disease using self-organizing maps
title_short MRI-guided clustering of patients with mild dementia due to Alzheimer's disease using self-organizing maps
title_sort mri guided clustering of patients with mild dementia due to alzheimer s disease using self organizing maps
topic Alzheimer's disease
Structural MRI
Unsupervised learning
Machine learning
Subtypes
Mild dementia
url http://www.sciencedirect.com/science/article/pii/S2666956024000333
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