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Updated: Jun 29, 2026

DeepOmicsAE: Representing Signaling Modules in Alzheimer's Disease with Deep Learning Analysis of Proteomics, Metabolomics, and Clinical Data
Published on: December 15, 2023
Machine learning classification and regional differentiation of neuropathologically-confirmed Alzheimer's disease and
David K Park1, Allison B Constant2, Lawrence S Honig2,3,4
1Department of Biomedical Engineering, Columbia University, New York, NY, USA.
Background:
Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) co-occur frequently, and growing evidence, including neuropathology, supports synergistic interplay between the diseases. We tested whether a single T1-weighted MRI scan may differentiate neuropathologically confirmed comorbid AD/DLB and AD controls using heterogeneously acquired neuroimaging.
Methods:
We obtained structural neuroimaging, on two groups, AD with and without DLB pathology. Convolutional neural networks are trained across dimensions. We introduce a triple-ensemble strategy consisting of majority voting schemes within a variety of plane permutations. In addition, we conduct voxel-wise statistical analyses.
Results:
Here we show convolutional neural networks record a classification accuracy of 0.820 and an f1 score of 0.79 in identifying comorbid DLB/AD from AD patients. Prediction accuracy is higher proximal to date of death, while the trained model largely outperforms clinical baseline diagnosis. The slice-level performance varies depending on the sampled brain location, with sensitivity highest in the temporal lobe and specificity highest in the occipital lobe. In DLB/AD, gray matter is relatively preserved though atrophy is observed in the occipital lobe, suggesting that the comorbidity differentially affects brain loss and may accelerate it in the occipital lobe.
Conclusions:
This study demonstrates how machine learning approaches can address diverse neuroimaging data from clinical sources to differentiate neurodegenerative diseases using a true gold standard of neuropathological confirmation. The frameworks utilized here can be extended to other diseases that are frequently co-occurring and feasibly extend to single scan diagnostic clinical utility of scans already being acquired.
Insights
Machine learning accurately differentiates Alzheimer's disease (AD) with dementia with Lewy bodies (DLB) comorbidity from AD using MRI scans. This approach offers improved diagnostic potential for overlapping neurodegenerative diseases.
Area of Science:
- Neuroimaging
- Machine Learning
- Neuropathology
Background:
- Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) frequently co-occur, suggesting synergistic interactions.
- Neuropathological evidence supports a combined interplay between AD and DLB pathologies.
- Differentiating comorbid AD/DLB from AD alone is clinically significant.
Purpose of the Study:
- To determine if a single T1-weighted MRI scan can differentiate neuropathologically confirmed comorbid AD/DLB from AD controls.
- To evaluate the efficacy of machine learning models in analyzing heterogeneously acquired neuroimaging data.
- To assess the potential of neuroimaging biomarkers for diagnosing co-occurring neurodegenerative diseases.
Main Methods:
- Structural neuroimaging data from two groups (AD with and without DLB pathology) were analyzed.
- Convolutional neural networks (CNNs) were trained across different dimensions using a triple-ensemble strategy.
- Voxel-wise statistical analyses were conducted alongside CNN-based classification.
Main Results:
- CNNs achieved 0.820 classification accuracy and 0.79 f1 score in identifying comorbid DLB/AD from AD patients.
- Prediction accuracy improved closer to the date of death and outperformed clinical baseline diagnosis.
- Differential patterns of gray matter preservation and occipital lobe atrophy were observed in DLB/AD compared to AD.
Conclusions:
- Machine learning effectively utilizes diverse neuroimaging data for differentiating neurodegenerative diseases with neuropathological confirmation.
- The developed frameworks can be extended to other co-occurring diseases.
- This approach shows potential for single-scan diagnostic utility in clinical settings for already acquired scans.
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