Johnson & Johnson Pharmaceutical Research & Development, Clinical Pharmacology Department, Raritan, New Jersey 08869, USA.
Br J Clin Pharmacol. 2013 Jan;75(1):146-61. doi: 10.1111/j.1365-2125.2012.04308.x.
The objective is to develop a semi-mechanistic disease progression model for mild cognitive impairment (MCI) subjects. The model aims to describe the longitudinal progression of ADAS-cog scores from the Alzheimer's disease neuroimaging initiative trial that had data from 198 MCI subjects with cerebrospinal fluid (CSF) information who were followed for 3 years.
Various covariates were tested on disease progression parameters and these variables fell into six categories: imaging volumetrics, biochemical, genetic, demographic, cognitive tests and CSF biomarkers.
CSF biomarkers were associated with both baseline disease score and disease progression rate in subjects with MCI. Baseline disease score was also correlated with atrophy measured using hippocampal volume. Progression rate was also predicted by executive functioning as measured by the Trail B-test.
CSF biomarkers have the ability to discriminate MCI subjects into sub-populations that exhibit markedly different rates of disease progression on the ADAS-cog scale. These biomarkers can therefore be utilized for designing clinical trials enriched with subjects that carry the underlying disease pathology.
旨在为轻度认知障碍（MCI）患者建立一种半机械性疾病进展模型。该模型旨在描述来自阿尔茨海默病神经影像学倡议（Alzheimer's disease neuroimaging initiative，ADNI）试验中 ADAS-cog 评分的纵向变化，该试验有 198 名 MCI 患者的脑脊液（CSF）信息，随访时间为 3 年。
在疾病进展参数上测试了各种协变量，这些变量分为六类：影像体积、生化、遗传、人口统计学、认知测试和 CSF 生物标志物。
CSF 生物标志物与 MCI 患者的基线疾病评分和疾病进展率相关。基线疾病评分也与海马体积测量的萎缩相关。进展率还可以通过 Trail B 测试测量的执行功能来预测。
CSF 生物标志物能够将 MCI 患者分为亚组，这些亚组在 ADAS-cog 量表上表现出明显不同的疾病进展速度。因此，这些生物标志物可用于设计临床试验，富集具有潜在疾病病理的患者。
