Format

Send to

Choose Destination
J Prev Alzheimers Dis. 2016;3(4):229-235. doi: 10.14283/jpad.2016.120.

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

Author information

1
Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA.
2
Departments of Epidemiology and Mental Health, Johns Hopkins Center on Aging and Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
3
Department of Neurology and Psychiatry & Human Behavior, Warren Alpert Medical School, Brown University, Providence, RI, USA.
4
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
5
Centre for Studies on Prevention of Alzheimer's Disease (StoP-AD), Douglas Mental Health University Institute Research Centre, McGill University Faculty of Medicine. Montreal, Canada.

Abstract

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of the PREVENT-AD IRT model to baseline INTREPAD data, and explore model changes when CSF markers are added or withdrawn.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.

KEYWORDS:

Alzheimer’s disease; Pre-clinical; disease progression; multiple outcome modalities; prevention trials; summary outcome measures

Supplemental Content

Full text links

Icon for PubMed Central
Loading ...
Support Center