Utility of Combinations of Biomarkers, Cognitive Markers, and Risk Factors to Predict Conversion From Mild Cognitive Impairment to Alzheimer Disease in Patients in the Alzheimer's Disease Neuroimaging Initiative
Utility of Combinations of Biomarkers, Cognitive Markers, and Risk Factors to Predict Conversion From Mild Cognitive Impairment to Alzheimer Disease in Patients in the Alzheimer's Disease Neuroimaging Initiative
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DOI：
10.1001/archgenpsychiatry.2011.96
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发表时间：
2011-09-01
影响因子：
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通讯作者：
Goldberg, Terry E.
中科院分区：
文献类型：
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作者：
Gomar, Jesus J.;Bobes-Bascaran, Maria T.;Goldberg, Terry E.
背景：生物标志物在理解与阿尔茨海默病相关的神经退行性过程中变得越来越重要。标记物包括局部脑体积、病理性A β 1-42和总tau的脑脊液测量、认知测量和个体风险factors.Objective：通过检查不同类别的生物标记物和认知标记物预测从轻度认知障碍到阿尔茨海默病的诊断状态变化的能力来确定它们的区分效用。设计：纵向研究。参与者：我们分析了阿尔茨海默病神经影像学倡议数据库，以研究在2年内转换为阿尔茨海默病的轻度认知障碍患者（n=116）和未转换的患者（n=204）。我们在一系列逻辑回归模型和效应量分析中确定了来自所有类别的标记物、生物标记物和风险因素的25个变量的预测效用。设置：阿尔茨海默病神经影像学倡议公共数据库。结果测量：主要结果测量是比值比、伪R2和效应量。结果：在综合逐步logistic回归模型中，因此包括来自所有标记物类别的变量，以下基线变量预测2年内的转换：延迟言语记忆和中颞叶皮质厚度的2个测量值。在检查下降率的效应量分析中，生物标志物的变化评分在2年内是适度的，但日常功能活动测量（功能评估问卷）的变化要大得多。功能评估问卷和连线测试的分数下降，部分B，占约50%的预测方差从轻度认知功能障碍的转换到阿尔茨海默病diseases.Conclusions：认知标记物在基线更强大的预测转换比大多数生物标志物。纵向分析表明，转换似乎不是由疾病的神经生物学轨迹的变化驱动的，而是由功能能力的急剧下降驱动的，在较小程度上，由执行功能的下降驱动的。
Context: Biomarkers have become increasingly important in understanding neurodegenerative processes associated with Alzheimer disease. Markers include regional brain volumes, cerebrospinal fluid measures of pathological A beta 1-42 and total tau, cognitive measures, and individual risk factors.Objective: To determine the discriminative utility of different classes of biomarkers and cognitive markers by examining their ability to predict a change in diagnostic status from mild cognitive impairment to Alzheimer disease.Design: Longitudinal study.Participants: We analyzed the Alzheimer's Disease Neuroimaging Initiative database to study patients with mild cognitive impairment who converted to Alzheimer disease (n=116) and those who did not convert (n=204) within a 2-year period. We determined the predictive utility of 25 variables from all classes of markers, biomarkers, and risk factors in a series of logistic regression models and effect size analyses.Setting: The Alzheimer's Disease Neuroimaging Initiative public database.Outcome Measures: Primary outcome measures were odds ratios, pseudo-R2s, and effect sizes.Results: In comprehensive stepwise logistic regression models that thus included variables from all classes of markers, the following baseline variables predicted conversion within a 2-year period: 2 measures of delayed verbal memory and middle temporal lobe cortical thickness. In an effect size analysis that examined rates of decline, change scores for biomarkers were modest for 2 years, but a change in an everyday functional activities measure (Functional Assessment Questionnaire) was considerably larger. Decline in scores on the Functional Assessment Questionnaire and Trail Making Test, part B, accounted for approximately 50% of the predictive variance in conversion from mild cognitive impairment to Alzheimer disease.Conclusions: Cognitive markers at baseline were more robust predictors of conversion than most biomarkers. Longitudinal analyses suggested that conversion appeared to be driven less by changes in the neurobiologic trajectory of the disease than by a sharp decline in functional ability and, to a lesser extent, by declines in executive function.