Estimating long-term multivariate progression from short-term data

Michael C. Donohue, Hélène Jacqmin-Gadda, Mélanie Le Goff, Ronald G. Thomas, Rema Raman, Anthony C. Gamst, Laurel A. Beckett, Clifford R. Jack, Michael W. Weiner, Jean François Dartigues, Paul S. Aisen

Research output: Contribution to journalArticlepeer-review

83 Scopus citations


Motivation Diseases that progress slowly are often studied by observing cohorts at different stages of disease for short periods of time. The Alzheimer's Disease Neuroimaging Initiative (ADNI) follows elders with various degrees of cognitive impairment, from normal to impaired. The study includes a rich panel of novel cognitive tests, biomarkers, and brain images collected every 6 months for as long as 6 years. The relative timing of the observations with respect to disease pathology is unknown. We propose a general semiparametric model and iterative estimation procedure to estimate simultaneously the pathological timing and long-term growth curves. The resulting estimates of long-term progression are fine-tuned using cognitive trajectories derived from the long-term "Personnes Agées Quid" study.

Results We demonstrate with simulations that the method can recover long-term disease trends from short-term observations. The method also estimates temporal ordering of individuals with respect to disease pathology, providing subject-specific prognostic estimates of the time until onset of symptoms. When the method is applied to ADNI data, the estimated growth curves are in general agreement with prevailing theories of the Alzheimer's disease cascade. Other data sets with common outcome measures can be combined using the proposed algorithm.

Availability Software to fit the model and reproduce results with the statistical software R is available as the grace package. ADNI data can be downloaded from the Laboratory of NeuroImaging.

Original languageEnglish (US)
Pages (from-to)S400-S410
JournalAlzheimer's and Dementia
Issue number5
StatePublished - Oct 1 2014


  • Growth curves
  • Multiple outcomes
  • Progression curves
  • Self-modeling regression
  • Semiparametric regression

ASJC Scopus subject areas

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Clinical Neurology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience


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