Biomarker progressions explain higher variability in stage-specific cognitive decline than baseline values in Alzheimer disease

Hiroko H. Dodge, Jian Zhu, Danielle Harvey, Naomi Saito, Lisa C. Silbert, Jeffrey A. Kaye, Robert A. Koeppe, Roger L. Albin

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


Background It is unknown which commonly used Alzheimer disease (AD) biomarker values - baseline or progression - best predict longitudinal cognitive decline. Methods 526 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI). ADNI composite memory and executive scores were the primary outcomes. Individual-specific slope of the longitudinal trajectory of each biomarker was first estimated. These estimates and observed baseline biomarker values were used as predictors of cognitive declines. Variability in cognitive declines explained by baseline biomarker values was compared with variability explained by biomarker progression values. Results About 40% of variability in memory and executive function declines was explained by ventricular volume progression among mild cognitive impairment patients. A total of 84% of memory and 65% of executive function declines were explained by fluorodeoxyglucose positron emission tomography (FDG-PET) score progression and ventricular volume progression, respectively, among AD patients. Conclusions For most biomarkers, biomarker progressions explained higher variability in cognitive decline than biomarker baseline values. This has important implications for clinical trials targeted to modify AD biomarkers.

Original languageEnglish (US)
Pages (from-to)690-703
Number of pages14
JournalAlzheimer's and Dementia
Issue number6
StatePublished - Nov 1 2014


  • ADNI
  • ADNI-exe
  • ADNI-mem
  • Biomarker
  • Biomarker progressions
  • Cognitive declines
  • MCI
  • MRI volume

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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