title: An event-based model for disease progression and its application in familial Alzheimer's disease and Huntington's disease.
abstract: Understanding the progression of neurological diseases is vital for accurate and early diagnosis and treatment planning. We introduce a new characterization of disease progression, which describes the disease as a series of events, each comprising a significant change in patient state. We provide novel algorithms to learn the event ordering from heterogeneous measurements over a whole patient cohort and demonstrate using combined imaging and clinical data from familial Alzheimer's and Huntington's disease cohorts. Results provide new detail in the progression pattern of these diseases, while confirming known features, and give unique insight into the variability of progression over the cohort. The key advantage of the new model and algorithms over previous progression models is that they do not require a priori division of the patients into clinical stages. The model and its formulation extend naturally to a wide range of other diseases and developmental processes and accommodate cross-sectional and longitudinal input data.
authors.affiliation: Centre for Medical Image Computing, University College London, Gower Street, WC1E 6BT, London, UK. hubert.fonteijn@fcdonders.ru.nl
authors.forename: Hubert M
authors.initials: HM
authors.lastname: Fonteijn
authors.forename: Marc
authors.initials: M
authors.lastname: Modat
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Clarkson
authors.forename: Josephine
authors.initials: J
authors.lastname: Barnes
authors.forename: Manja
authors.initials: M
authors.lastname: Lehmann
authors.forename: Nicola Z
authors.initials: NZ
authors.lastname: Hobbs
authors.forename: Rachael I
authors.initials: RI
authors.lastname: Scahill
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Tabrizi
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 / Q000175:diagnosis* / Q000235:genetics*; D001921:Brain / Q000473:pathology*; D003198:Computer Simulation; D018450:Disease Progression; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D006816:Huntington Disease / Q000175:diagnosis* / Q000235:genetics*; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008954:Models, Biological; D010363:Pattern Recognition, Automated / Q000379:methods; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013382:Subtraction Technique