Mapping Alzheimer’s Disease Pseudo-Progression With Multimodal Biomarker Trajectory Embeddings

Alzheimer’s Disease (AD) is a neurodegenerative disorder characterized by progressive cognitive degeneration and motor impairment, affecting millions worldwide. Mapping the progression of AD is crucial for early detection of loss of brain function, timely intervention, and development of effective treatments. However, accurate measurements of disease progression are still challenging at present. This study presents a novel approach to understanding the heterogeneous pathways of AD through longitudinal biomarker data from medical imaging and other modalities. We propose an analytical pipeline adopting two popular machine learning methods from the single-cell transcriptomics domain, PHATE and Slingshot, to project multimodal biomarker trajectories to a low-dimensional space. These embeddings serve as our pseudotime estimates. We applied this pipeline to the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset to align longitudinal data across individuals at various disease stages. Our approach mirrors the technique used to cluster single-cell data into cell types based on developmental timelines. Our pseudotime estimates revealed distinct patterns of disease evolution and biomarker changes over time, providing a deeper understanding of the temporal dynamics of AD. The results show the potential of the approach in the clinical domain of neurodegenerative diseases, enabling more precise disease modeling and early diagnosis.