Amyloid negativity in patients with clinically diagnosed Alzheimer disease and MCI
Amyloid negativity in patients with clinically diagnosed Alzheimer disease and MCI
复制标题
DOI：
10.1212/wnl.0000000000002576
复制
发表时间：
2016-04-12
期刊：
影响因子：
9.9
通讯作者：
Jagust, William J.
中科院分区：
文献类型：
--
作者：
Landau, Susan M.;Horng, Andy;Jagust, William J.
目的：从阿尔茨海默病神经影像学倡议（ADNI）（一项前瞻性队列研究）中检查淀粉样蛋白阴性阿尔茨海默病（AD）和轻度认知障碍（MCI）患者的临床和生物标志物特征。方法：我们首先使用CSF-A（1 - 42）作为比较淀粉样蛋白测量值，研究了florbetapir-PET在AD患者和MCI患者中的可靠性。然后，我们比较了florbetapir-vs florbetapir+患者的几个AD特异性生物标志物，基线和纵向认知测量，人口统计学和临床医生报告data.Results：Florbetapir和CSF-A（1 - 42）+/-状态同意98%的AD（89%的MCI），表明大多数florbetapir-扫描是淀粉样蛋白状态的可靠代表。Florbetapir-AD（n = 27/177; 15%）和MCI（n = 74/217，34%）的APOE 4阴性（MCI 83%，AD 96%）的可能性高于其florbetapir+对应物（MCI 30%，AD 24%）。Florbetapir患者也有较少的AD特异性低代谢，较低的CSF p-tau和t-tau，以及更好的纵向认知表现，并且更有可能服用抑郁症药物。在MCI只有，florbetapir-参与者有较少的海马萎缩和代谢低下和较低的功能活动问卷分数相比，florbetapir + participator.Conclusions：总体而言，图像分析问题似乎不是淀粉样蛋白阴性的主要解释。Florbetapir-ADNI患者具有与其florbetapir+对应物不同的多种临床和生物标志物特征，表明一种或多种非AD病因（其可能包括血管疾病和抑郁症）解释了其AD样表型。
Objective:To examine the clinical and biomarker characteristics of patients with amyloid-negative Alzheimer disease (AD) and mild cognitive impairment (MCI) from the Alzheimer's Disease Neuroimaging Initiative (ADNI), a prospective cohort study.Methods:We first investigated the reliability of florbetapir- PET in patients with AD and patients with MCI using CSF-A(1-42) as a comparison amyloid measurement. We then compared florbetapir- vs florbetapir+ patients with respect to several AD-specific biomarkers, baseline and longitudinal cognitive measurements, and demographic and clinician report data.Results:Florbetapir and CSF-A(1-42) +/- status agreed for 98% of ADs (89% of MCIs), indicating that most florbetapir- scans were a reliable representation of amyloid status. Florbetapir- AD (n = 27/177; 15%) and MCI (n = 74/217, 34%) were more likely to be APOE4-negative (MCI 83%, AD 96%) than their florbetapir+ counterparts (MCI 30%, AD 24%). Florbetapir- patients also had less AD-specific hypometabolism, lower CSF p-tau and t-tau, and better longitudinal cognitive performance, and were more likely to be taking medication for depression. In MCI only, florbetapir- participants had less hippocampal atrophy and hypometabolism and lower functional activity questionnaire scores compared to florbetapir+ participants.Conclusions:Overall, image analysis problems do not appear to be a primary explanation of amyloid negativity. Florbetapir- ADNI patients have a variety of clinical and biomarker features that differ from their florbetapir+ counterparts, suggesting that one or more non-AD etiologies (which may include vascular disease and depression) account for their AD-like phenotype.