title: An event-based disease progression model and its application to familial Alzheimer's disease.
abstract: This study introduces a novel event-based model for disease progression. The model describes disease progression as a series of events. An event can consist of a significant change in symptoms or in tissue. We construct a forward model that relates heterogeneous measurements from a whole cohort of patients and controls to the event sequence and fit the model with a Bayesian estimation framework. The model does not rely on a priori classification of patients and therefore has the potential to describe disease progression in much greater detail than previous approaches. We demonstrate our model on serial T1 MRI data from a familial Alzheimer's disease cohort. We show progression of neuronal atrophy on a much finer level than previous studies, while confirming progression patterns from pathological studies, and integrate clinical events into the model.
authors.affiliation: Centre for Medical Image Computing, Department of Computer Science, University College London, UK. h.fonteijn@cs.ucl.ac.uk
authors.forename: Hubert M
authors.initials: HM
authors.lastname: Fonteijn
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Clarkson
authors.forename: Marc
authors.initials: M
authors.lastname: Modat
authors.forename: Josephine
authors.initials: J
authors.lastname: Barnes
authors.forename: Manja
authors.initials: M
authors.lastname: Lehmann
authors.forename: Sebastien
authors.initials: S
authors.lastname: Ourselin
authors.forename: Nick C
authors.initials: NC
authors.lastname: Fox
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Alexander
mesh_terms: D000465:Algorithms; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D003198:Computer Simulation; D018450:Disease Progression; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008954:Models, Biological; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013382:Subtraction Technique