'Alzheimer's Progression Score': Development of a Biomarker Summary Outcome for AD Prevention Trials.

Title'Alzheimer's Progression Score': Development of a Biomarker Summary Outcome for AD Prevention Trials.
Publication TypeJournal Article
Year of Publication2016
AuthorsLeoutsakos J-M, Gross AL, Jones RN, Albert MS, Breitner JCS
JournalJ Prev Alzheimers Dis
Date Published2016

BACKGROUND: Alzheimer's disease (AD) prevention research requires methods for measurement of disease progression not yet revealed by symptoms. Preferably, such measurement should encompass multiple disease markers.

OBJECTIVES: Evaluate an item response theory (IRT) model-based latent variable Alzheimer Progression Score (APS) that uses multi-modal disease markers to estimate pre-clinical disease progression.

DESIGN: Estimate APS scores in the BIOCARD observational study, and in the parallel PREVENT-AD Cohort and its sister INTREPAD placebo-controlled prevention trial. Use BIOCARD data to evaluate whether baseline and early APS trajectory predict later progression to MCI/dementia. Similarly, use longitudinal PREVENT-AD data to assess test measurement invariance over time. Further, assess portability of the PREVENT-AD IRT model to baseline INTREPAD data, and explore model changes when CSF markers are added or withdrawn.

SETTING: BIOCARD was established in 1995 and participants were followed up to 20 years in Baltimore, USA. The PREVENT-AD and INTREPAD trial cohorts were established between 2011-2015 in Montreal, Canada, using nearly identical entry criteria to enroll high-risk cognitively normal persons aged 60+ then followed for several years.

PARTICIPANTS: 349 cognitively normal, primarily middle-aged participants in BIOCARD, 125 high-risk participants aged 60+ in PREVENT-AD, and 217 similar subjects in INTREPAD. 106 INTREPAD participants donated up to four serial CSF samples.

MEASUREMENTS: Global cognitive assessment and multiple structural, functional, and diffusion MRI metrics, sensori-neural tests, and CSF concentrations of tau, Aβ42 and their ratio.

RESULTS: Both baseline values and early slope of APS scores in BIOCARD predicted later progression to MCI or AD. Presence of CSF variables strongly improved such prediction. A similarly derived APS in PREVENT-AD showed measurement invariance over time and portability to the parallel INTREPAD sample.

CONCLUSIONS: An IRT-based APS can summarize multimodal information to provide a longitudinal measure of pre-clinical AD progression, and holds promise as an outcome for AD prevention trials.

Alternate JournalJ Prev Alzheimers Dis
PubMed ID29034223
PubMed Central IDPMC5639716
Grant ListP50 AG005146 / AG / NIA NIH HHS / United States
U19 AG033655 / AG / NIA NIH HHS / United States

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