A computational neurodegenerative disease progression score: Method and results with the Alzheimer's disease neuroimaging initiative cohort

Bruno M. Jedynak, Andrew Lang, Bo Liu, Elyse Katz, Yanwei Zhang, Bradley T. Wyman, David Raunig, C. Pierre Jedynak, Brian Caffo, Jerry L. Prince

Research output: Contribution to journalArticlepeer-review

Abstract

While neurodegenerative diseases are characterized by steady degeneration over relatively long timelines, it is widely believed that the early stages are the most promising for therapeutic intervention, before irreversible neuronal loss occurs. Developing a therapeutic response requires a precise measure of disease progression. However, since the early stages are for the most part asymptomatic, obtaining accurate measures of disease progression is difficult. Longitudinal databases of hundreds of subjects observed during several years with tens of validated biomarkers are becoming available, allowing the use of computational methods. We propose a widely applicable statistical methodology for creating a disease progression score (DPS), using multiple biomarkers, for subjects with a neurodegenerative disease. The proposed methodology was evaluated for Alzheimer's disease (AD) using the publicly available AD Neuroimaging Initiative (ADNI) database, yielding an Alzheimer's DPS or ADPS score for each subject and each time-point in the database. In addition, a common description of biomarker changes was produced allowing for an ordering of the biomarkers. The Rey Auditory Verbal Learning Test delayed recall was found to be the earliest biomarker to become abnormal. The group of biomarkers comprising the volume of the hippocampus and the protein concentration amyloid beta and Tau were next in the timeline, and these were followed by three cognitive biomarkers. The proposed methodology thus has potential to stage individuals according to their state of disease progression relative to a population and to deduce common behaviors of biomarkers in the disease itself.

Original languageEnglish (US)
Pages (from-to)1478-1486
Number of pages9
JournalNeuroImage
Volume63
Issue number3
DOIs
StatePublished - Nov 15 2012

Keywords

  • Alzheimer's disease
  • Biomarkers
  • Disease progression score
  • Neurodegenerative diseases

ASJC Scopus subject areas

  • Neurology
  • Cognitive Neuroscience

Fingerprint

Dive into the research topics of 'A computational neurodegenerative disease progression score: Method and results with the Alzheimer's disease neuroimaging initiative cohort'. Together they form a unique fingerprint.

Cite this