Abstract #0153

Latent Atrophy Factors in Alzheimer's Disease

Xiuming Zhang¹, Elizabeth C. Mormino², Reisa A. Sperling², Mert R. Sabuncu^3,4, and B.T. Thomas Yeo^1,3,5

¹ASTAR-NUS Clinical Imaging Research Centre, Department of Electrical and Computer Engineering, Singapore Institute for Neurotechnology and Memory Networks Program, National University of Singapore, Singapore, Singapore, ²Department of Neurology, Massachusetts General Hospital/Harvard Medical School, Charlestown, MA, United States, ³Martinos Center for Biomedical Imaging, Massachusetts General Hospital/Harvard Medical School, Charlestown, MA, United States, ⁴Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, United States, ⁵Centre for Cognitive Neuroscience, Duke-NUS Graduate Medical School, Singapore, Singapore

Alzheimer's disease (AD) is the most common form of dementia and greatly heterogeneous. Here we develop a model of the heterogeneity of AD-related atrophy, demonstrating that most AD dementia patients and at-risk nondemented participants express multiple latent atrophy factors to varying degrees. Our study also demonstrates that these atrophy factors are associated with distinct cognitive decline trajectories across the preclinical and clinical stages. Our results provide a framework by which biomarker readouts could potentially predict disease progression at the individual level. Our analytic strategy is general and might be utilized to discover subtypes within and across other heterogeneous brain disorders.

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