Instantiated mixed effects modeling of Alzheimer's disease markers
File(s)NeuroImage2016_v1(1).pdf (1.45 MB)
Accepted version
Author(s)
Type
Journal Article
Abstract
The assessment and prediction of a subject's current and future risk of developing neurodegenerative diseases like Alzheimer's disease are of great interest in both the design of clinical trials as well as in clinical decision making. Exploring the longitudinal trajectory of markers related to neurodegeneration is an important task when selecting subjects for treatment in trials and the clinic, in the evaluation of early disease indicators and the monitoring of disease progression. Given that there is substantial intersubject variability, models that attempt to describe marker trajectories for a whole population will likely lack specificity for the representation of individual patients. Therefore, we argue here that individualized models provide a more accurate alternative that can be used for tasks such as population stratification and a subject-specific prognosis. In the work presented here, mixed effects modeling is used to derive global and individual marker trajectories for a training population. Test subject (new patient) specific models are then instantiated using a stratified “marker signature” that defines a subpopulation of similar cases within the training database. From this subpopulation, personalized models of the expected trajectory of several markers are subsequently estimated for unseen patients. These patient specific models of markers are shown to provide better predictions of time-to-conversion to Alzheimer's disease than population based models.
Date Issued
2016-07-02
Date Acceptance
2016-06-24
Citation
NeuroImage, 2016, 142, pp.113-125
ISSN
1053-8119
Publisher
Elsevie
Start Page
113
End Page
125
Journal / Book Title
NeuroImage
Volume
142
Copyright Statement
© 2016 Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
Sponsor
Technology Strategy Board
Innovate UK
Grant Number
TSB - 101353
TSB Ref: 101685
Subjects
AD markers
Alzheimer's disease
Longitudinal modeling
Subject stratification
Alzheimer's Disease Neuroimaging Initiative (ADNI)
Neurology & Neurosurgery
11 Medical And Health Sciences
17 Psychology And Cognitive Sciences
Publication Status
Published