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Alzheimer’s disease (AD) is a degenerative brain disease that affects millions of people around the world. As populations in the United States and worldwide age, the prevalence of Alzheimer’s disease will only increase. In turn, the social and financial costs of AD will create a difficult environment for many families and caregivers across the globe.By combining genetic information, brain scans, and clinical data, gathered over time through the Alzheimer’s Disease Neuroimaging Initiative(ADNI), we propose a newJoint High-Order Multi-Modal Multi-Task Feature Learning method to predict the cognitive performance and diagnosis of patients with and without AD.
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Unsupervised Machine Learning to Identify Separable Clinical Alzheimer’s Disease Sub-Populations
Heterogeneity among Alzheimer’s disease (AD) patients confounds clinical trial patient selection and therapeutic efficacy evaluation. This work defines separable AD clinical sub-populations using unsupervised machine learning. Clustering (t-SNE followed by k-means) of patient features and association rule mining (ARM) was performed on the ADNIMERGE dataset from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Patient sociodemographics, brain imaging, biomarkers, cognitive tests, and medication usage were included for analysis. Four AD clinical sub-populations were identified using between-cluster mean fold changes [cognitive performance, brain volume]: cluster-1 represented least severe disease [+17.3, +13.3]; cluster-0 [−4.6, +3.8] and cluster-3 [+10.8, −4.9] represented mid-severity sub-populations; cluster-2 represented most severe disease [−18.4, −8.4]. ARM assessed frequently occurring pharmacologic substances within the 4 sub-populations. No drug class was associated with the least severe AD (cluster-1), likely due to lesser antecedent disease. Anti-hyperlipidemia drugs associated with cluster-0 (mid-severity, higher volume). Interestingly, antioxidants vitamin C and E associated with cluster-3 (mid-severity, higher cognition). Anti-depressants like Zoloft associated with most severe disease (cluster-2). Vitamin D is protective for AD, but ARM identified significant underutilization across all AD sub-populations. Identification and feature characterization of four distinct AD sub-population “clusters” using standard clinical features enhances future clinical trial selection criteria and cross-study comparative analysis.
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- Award ID(s):
- 1944247
- PAR ID:
- 10330421
- Date Published:
- Journal Name:
- Brain Sciences
- Volume:
- 11
- Issue:
- 8
- ISSN:
- 2076-3425
- Page Range / eLocation ID:
- 977
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.3390/brainsci11080977
