Alzheimer's disease assessment scale-cognitive 11-item progression model in mild-to-moderate Alzheimer's disease trials of bapineuzumab
Autor: | Omoniyi J. Adedokun, Alberto Russu, Kaori Ito, Scot Styren, Chuanpu Hu, Steven Xu, Mahesh N. Samtani, H. Robert Brashear, Ming Lu, Brian Corrigan, Sangeeta Raje |
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Rok vydání: | 2015 |
Předmět: |
Gerontology
medicine.medical_specialty education.field_of_study Population Regression analysis Cognition Disease Featured Article Alzheimer's disease Placebo Psychiatry and Mental health Bapineuzumab Concomitant Internal medicine medicine Disease progression model Neurology (clinical) Cognitive decline education Psychology ADAS-cog/11 medicine.drug |
Zdroj: | Alzheimer's & Dementia : Translational Research & Clinical Interventions |
ISSN: | 2352-8737 |
DOI: | 10.1016/j.trci.2015.09.001 |
Popis: | Introduction The objective of this study was to estimate longitudinal changes in disease progression (measured by Alzheimer's disease assessment scale-cognitive 11-item [ADAS-cog/11] scale) after bapineuzumab treatment and to identify covariates (demographics or baseline characteristics) contributing to the variability in disease progression rate and baseline disease status. Methods A population-based disease progression model was developed using pooled placebo and bapineuzumab data from two phase-3 studies in APOE e4 noncarrier and carrier Alzheimer's disease (AD) patients. Results A beta regression model with the Richard's function as the structural component best described ADAS-cog/11 disease progression for mild-to-moderate AD population. This analysis confirmed no effect of bapineuzumab exposure on ADAS-cog/11 progression rate, consistent with the lack of clinical efficacy observed in the statistical analysis of ADAS-cog/11 data in both studies. Assessment of covariates affecting baseline severity revealed that men had a 6% lower baseline ADAS-cog/11 score than women; patients who took two AD concomitant medications had a 19% higher (worse) baseline score; APOE e4 noncarriers had a 5% lower baseline score; and patients who had AD for a longer duration had a higher baseline score. Furthermore, shorter AD duration, younger age, APOE e4 carrier status, and use of two AD concomitant medications were associated with faster disease progression rates. Patients who had an ADAS-cog/11 score progression rate that was not statistically significantly different from 0 typically took no AD concomitant medications. Discussion The beta regression model is a sensible modeling approach to characterize cognitive decline in AD patients. The influence of bapineuzumab exposure on disease progression measured by ADAS-cog/11 was not significant. Trial Registration ClinicalTrials.gov identifier: NCT00575055 and NCT00574132 . |
Databáze: | OpenAIRE |
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