Neuropsychological Decline Improves Prediction of Dementia Beyond Alzheimer's Disease Biomarker and Mild Cognitive Impairment Diagnoses
Neuropsychological Decline Improves Prediction of Dementia Beyond Alzheimer's Disease Biomarker and Mild Cognitive Impairment Diagnoses
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DOI：
10.3233/jad-180525
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发表时间：
2019-01-01
影响因子：
4
通讯作者：
Lai, Mark H. C.
中科院分区：
文献类型：
--
作者：
Nation, Daniel A.;Ho, Jean K.;Lai, Mark H. C.
背景资料：认知功能障碍的临床诊断传统上是基于一个单一的认知考试，但串行认知测试可以敏感的微妙的认知变化，在无症状的individuals和通知cognitive trackless.Objective：我们评估的预后效用确定纵向神经心理学下降沿着与单一的认知考试和阿尔茨海默病（AD）脑脊液（CSF）生物标志物预测痴呆。我们还研究了基于下降trajectors.Method的脑容量差异：回归模型量化了12个月的神经心理学下降相对于非痴呆老年人（N = 1,074）的规范性预期。随访期间进展为痴呆（18-120个月）使用独立评估模式进行诊断。在控制年龄、性别、教育、载脂蛋白E4和基线认知诊断的考克斯回归模型中，神经心理学下降预测痴呆风险增加，chi（2）= 69.861，p < 0.001，比值比= 2.841，即使在校正CSF生物标志物（淀粉样蛋白-β、磷酸化tau、总tau）后，chi（2）= 26.365，p < 0.001，比值比= 2.283。基于体素的形态学分析表明，较小的海马和内侧颞叶体积参与者neuropsychological decline.Conclusions：神经心理学下降的纵向诊断提高了预后的准确性超越单一的认知检查诊断和AD CSF生物标志物，即使在无症状的老年人。具有神经心理学衰退轨迹的老年人表现出较小的内侧颞叶和海马脑体积。纵向诊断方法可能有利于在无症状个体中进行AD临床试验的选择和随机化程序。
Background: A clinical diagnosis of cognitive impairment is traditionally based on a single cognitive exam, but serial cognitive testing can be sensitive to subtle cognitive changes in asymptomatic individuals and inform cognitive trajectory.Objective: We evaluated the prognostic utility of identifying longitudinal neuropsychological decline along with single cognitive exam and Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers in predicting dementia. We also examined brain volumetric differences based on decline trajectories.Method: Regression models quantified 12-month neuropsychological decline relative to normative expectations among nondemented older adults (N = 1,074). Progression to dementia over follow-up (18-120 months) was diagnosed using independent modes of assessment.Results: In Cox regression models controlling for age, sex, education, apolipoprotein E4, and baseline cognitive diagnosis, neuropsychological decline predicted increased dementia risk, chi(2) = 69.861, p < 0.001, odds ratio = 2.841, even after correction for CSF biomarkers (amyloid-beta, phosphorylated tau, total tau), chi(2) = 26.365, p < 0.001, odds ratio = 2.283. Voxel-based morphometry analysis indicated smaller hippocampal and medial temporal volume in participants with neuropsychological decline.Conclusions: Longitudinal diagnosis of neuropsychological decline improved prognostic accuracy beyond single cognitive exam diagnoses and AD CSF biomarkers, even in asymptomatic older adults. Older adults with a trajectory of neuropsychological decline exhibit smaller medial temporal and hippocampal brain volume. Longitudinal diagnostic approaches may benefit selection and randomization procedures for AD clinical trials in asymptomatic individuals.