A joint model for multiple dynamic processes and clinical endpoints: Application to Alzheimer's disease

Statistics in Medicine
Cécile Proust-LimaJean-François Dartigues

Abstract

As other neurodegenerative diseases, Alzheimer's disease, the most frequent dementia in the elderly, is characterized by multiple progressive impairments in the brain structure and in clinical functions such as cognitive functioning and functional disability. Until recently, these components were mostly studied independently because no joint model for multivariate longitudinal data and time to event was available in the statistical community. Yet, these components are fundamentally interrelated in the degradation process toward dementia and should be analyzed together. We thus propose a joint model to simultaneously describe the dynamics of multiple correlated components. Each component, defined as a latent process, is measured by one or several continuous markers (not necessarily Gaussian). Rather than considering the associated time to diagnosis as in standard joint models, we assume diagnosis corresponds to the passing above a covariate-specific threshold (to be estimated) of a pathological process that is modeled as a combination of the component-specific latent processes. This definition captures the clinical complexity of diagnoses such as dementia diagnosis but also benefits from simplifications for the computation of ma...Continue Reading

References

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Sep 18, 2007·Lifetime Data Analysis·Julien GaniayreLuc Letenneur
Dec 11, 2008·Annals of Neurology·Hélène AmievaJean François Dartigues
Sep 23, 2011·The Annals of Applied Statistics·Paul S Albert, Joanna H Shih
Oct 4, 2011·American Journal of Epidemiology·Cécile Proust-LimaHélène Jacqmin-Gadda
Oct 23, 2012·The British Journal of Mathematical and Statistical Psychology·Cécile Proust-LimaHélène Jacqmin-Gadda
Mar 29, 2014·Statistics in Medicine·Eleni-Rosalina AndrinopoulouEmmanuel Lesaffre
Apr 8, 2015·The International Journal of Biostatistics·Daniel CommengesBenoit Liquet
Apr 14, 2015·Journal of the Royal Statistical Society. Series B, Statistical Methodology·Jessica BarrettDavid Taylor-Robinson
Sep 9, 2016·BMC Medical Research Methodology·Graeme L HickeyRuwanthi Kolamunnage-Dona

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Citations

Sep 4, 2020·Computational and Mathematical Methods in Medicine·Jun ZhangKanghuai Liu

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