Landau Susan M, Horng Andy, Fero Allison, Jagust William J
From Helen Wills Neuroscience Institute (S.M.L., A.H., W.J.J.), University of California, Berkeley; and Life Sciences Division (S.M.L., A.F., W.J.J.), Lawrence Berkeley National Laboratory, CA.
Neurology. 2016 Apr 12;86(15):1377-1385. doi: 10.1212/WNL.0000000000002576. Epub 2016 Mar 11.
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.
We first investigated the reliability of florbetapir- PET in patients with AD and patients with MCI using CSF-Aβ1-42 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.
Florbetapir and CSF-Aβ1-42 +/- 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.
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.
在一项前瞻性队列研究——阿尔茨海默病神经影像学计划（ADNI）中，研究淀粉样蛋白阴性的阿尔茨海默病（AD）和轻度认知障碍（MCI）患者的临床及生物标志物特征。
我们首先使用脑脊液Aβ1-42作为淀粉样蛋白测量的对照，研究氟代硼吡咯正电子发射断层扫描（florbetapir-PET）在AD患者和MCI患者中的可靠性。然后，我们比较了氟代硼吡咯阴性与阳性患者在几种AD特异性生物标志物、基线和纵向认知测量以及人口统计学和临床医生报告数据方面的差异。
氟代硼吡咯和脑脊液Aβ1-42的±状态在98%的AD患者（89%的MCI患者）中一致，这表明大多数氟代硼吡咯阴性扫描是淀粉样蛋白状态的可靠反映。与氟代硼吡咯阳性的AD患者（24%）和MCI患者（30%）相比，氟代硼吡咯阴性的AD患者（n = 27/177；15%）和MCI患者（n = 74/217，34%）更有可能是APOE4阴性（MCI为83%，AD为96%）。氟代硼吡咯阴性的患者还具有较少的AD特异性代谢减低、较低的脑脊液磷酸化tau蛋白（p-tau）和总tau蛋白（t-tau），以及更好的纵向认知表现，并且更有可能正在服用抗抑郁药物。仅在MCI患者中，与氟代硼吡咯阳性的参与者相比，氟代硼吡咯阴性的参与者海马萎缩和代谢减低较少，功能活动问卷得分较低。
总体而言，图像分析问题似乎不是淀粉样蛋白阴性的主要原因。ADNI中氟代硼吡咯阴性的患者具有多种与氟代硼吡咯阳性患者不同的临床和生物标志物特征，这表明一种或多种非AD病因（可能包括血管疾病和抑郁症）导致了他们类似AD的表型。
