期刊
JOURNAL OF CLINICAL PHARMACOLOGY
卷 52, 期 5, 页码 629-644出版社
WILEY
DOI: 10.1177/0091270011405497
关键词
ADAS-cog; disease progression; Alzheimer disease; NONMEM; population modeling
资金
- Alzheimer's Disease Neuroimaging Initiative (ADNI
- National Institutes of Health [U01 AG024904]
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- Abbott
- AstraZeneca AB
- Bayer Schering Pharma AG
- Bristol-Myers Squibb
- Eisai Global Clinical Development
- Elan Corporation
- Genentech
- GE Healthcare
- GlaxoSmith Kline
- Innogenetics
- Johnson and Johnson
- Eli Lilly and Co
- Medpace
- Merck and Co
- Novartis AG
- Pfizer
- F. Hoffman La Roche
- Schering-Plough
- Synarc
- National Institutes of Health [P30 AG010129, K01 AG030514]
- Dana Foundation
The objective of this analysis was to develop a semi-mechanistic nonlinear disease progression model using an expanded set of covariates that captures the longitudinal change of Alzheimer's Disease Assessment Scale (ADAS-cog) scores from the Alzheimer's Disease Neuroimaging Initiative study that consisted of 191 Alzheimer disease patients who were followed for 2 years. The model describes the rate of progression and baseline disease severity as a function of influential covariates. The covariates that were tested fell into 4 categories: (1) imaging volumetric measures, (2) serum biomarkers, (3) demographic and genetic factors, and (4) baseline cognitive tests. Covariates found to affect baseline disease status were years since disease onset, hippocam pal volume, and ventricular volume. Disease progression rate in the model was influenced by age, total cholesterol, APOE epsilon 4 genotype, Trail Making Test (part B) score, and current levels of impairment as measured by ADAS-cog. Rote of progression was slower for mild and severe Alzheimer patients compared with moderate Alzheimer patients who exhibited faster rates of deterioration. In conclusion, this model describes disease progression in Alzheimer patients using novel covariates that are important for understanding the worsening of ADAS-cog scores over time and may be useful in the future for optimizing study designs through clinical trial simulations.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据