A method for inferring regional origins of neurodegeneration
View/ Open
Date
2018-02-02Author
Torok, Justin
Maia, Pedro D.
Powell, Fon
Pandya, Sneha
Raj, Ashish
Metadata
Show full item recordAbstract
**Please note that the full text is embargoed** ABSTRACT: Alzheimer’s disease, the most common form of dementia, is characterized by the emergence and spread of senile plaques and neurofibrillary tangles, causing widespread neurodegeneration. Though the progression of Alzheimer’s disease is considered to be stereotyped, the significant variability within clinical populations obscures this interpretation on the individual level. Of particular clinical importance is understanding where exactly pathology, e.g. tau, emerges in each patient and how the incipient atrophy pattern relates to future spread of disease. Here we demonstrate a newly developed graph theoretical method of inferring prior disease states in patients with Alzheimer’s disease and mild cognitive impairment using an established network diffusion model and an L1-penalized optimization algorithm. Although the ‘seeds’ of origin using our inference method successfully reproduce known trends in Alzheimer’s disease staging on a population level, we observed that the high degree of heterogeneity between patients at baseline is also reflected in their seeds. Additionally, the individualized seeds are significantly more predictive of future atrophy than a single seed placed at the hippocampus. Our findings illustrate that understanding where disease originates in individuals is critical to determining how it progresses and that our method allows us to infer early stages of disease from atrophy patterns observed at diagnosis. [© The Author(s) (2018). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. DOI: https://doi.org/10.1093/brain/awx371]