Multi-study validation of data-driven disease progression models to characterize evolution of biomarkers in Alzheimer's disease.

NeuroImage. Clinical
Damiano Archettifor EuroPOND Consortium

Abstract

Understanding the sequence of biological and clinical events along the course of Alzheimer's disease provides insights into dementia pathophysiology and can help participant selection in clinical trials. Our objective is to train two data-driven computational models for sequencing these events, the Event Based Model (EBM) and discriminative-EBM (DEBM), on the basis of well-characterized research data, then validate the trained models on subjects from clinical cohorts characterized by less-structured data-acquisition protocols. Seven independent data cohorts were considered totalling 2389 cognitively normal (CN), 1424 mild cognitive impairment (MCI) and 743 Alzheimer's disease (AD) patients. The Alzheimer's Disease Neuroimaging Initiative (ADNI) data set was used as training set for the constriction of disease models while a collection of multi-centric data cohorts was used as test set for validation. Cross-sectional information related to clinical, cognitive, imaging and cerebrospinal fluid (CSF) biomarkers was used. Event sequences obtained with EBM and DEBM showed differences in the ordering of single biomarkers but according to both the first biomarkers to become abnormal were those related to CSF, followed by cognitive scor...Continue Reading

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Citations

Jun 30, 2019·Brain Informatics·Samuel IddiUNKNOWN Alzheimer’s Disease Neuroimaging Initiative
Jul 9, 2020·Journal of Neurology·Timothy Rittman
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Oct 12, 2021·Global Spine Journal·GuanRui RenXiaoTao Wu

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Methods Mentioned

BETA
Enzyme Linked Immunosorbent Assay

Software Mentioned

EuroPOND
ARWiBo
FreeSurfer
SuStaIn ( Subtype and Stage Inference )
ViTA
DEBM
EBM
OASIS
PharmaCog
ADNI

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