Novel Statistically-Derived Composite Measures for Assessing the Efficacy of Disease-Modifying Therapies in Prodromal Alzheimer's Disease Trials: An AIBL Study

Samantha C. Burnham*, Nandini Raghavan, William Wilson, David Baker, Michael T. Ropacki, Gerald Novak, David Ames, Kathryn Ellis, Ralph N. Martins, Paul Maruff, Colin L. Masters, Gary Romano, Christopher C. Rowe, Greg Savage, S. Lance Macaulay, Vaibhav A. Narayan, Alzheimer's Disease Neuroimaging Initiative, The AIBL Research Group

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    19 Citations (Scopus)

    Abstract

    Background: There is a growing consensus that disease-modifying therapies must be given at the prodromal or preclinical stages of Alzheimer's disease (AD) to be effective. A major unmet need is to develop and validate sensitive measures to track disease progression in these populations. Objective: To generate novel statistically-derived composites from standard scores, which have increased sensitivity in the assessment of change from baseline in prodromal AD. Methods: An empirically based method was employed to generate domain specific, global, and cognitive-functional novel composites. The novel composites were compared and contrasted with each other, as well as standard scores for their ability to track change from baseline. The longitudinal characteristics and power to detect decline of the measures were evaluated. Data from participants in the Australian Imaging, Biomarkers and Lifestyle (AIBL) Study characterized as mild cognitively impaired with high neocortical amyloid-β burden were utilized for the study. Results: The best performing standard scores were CDR Sum-of-Boxes and MMSE. The statistically-derived novel composites performed better than the standard scores from which they were derived. The domain-specific composites generally did not perform as well as the global composites or the cognitive-functional composites. Conclusion: A systematic method was employed to generate novel statistically-derived composite measures from standard scores. Composites comprised of measures including function and multiple cognitive domains appeared to best capture change from baseline. These composites may be useful to assess progression or lack thereof in prodromal AD. However, the results should be replicated and validated using an independent clinical sample before implementation in a clinical trial.

    Original languageEnglish
    Pages (from-to)1079-1089
    Number of pages11
    JournalJournal of Alzheimer's Disease
    Volume46
    Issue number4
    DOIs
    Publication statusPublished - 26 Jun 2015

    Fingerprint

    Dive into the research topics of 'Novel Statistically-Derived Composite Measures for Assessing the Efficacy of Disease-Modifying Therapies in Prodromal Alzheimer's Disease Trials: An AIBL Study'. Together they form a unique fingerprint.

    Cite this