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Lancet Neurol:唐氏综合征成人血浆神经丝轻链浓度的诊断和预后表现及纵向变化

2021-10-24 Naomii MedSci原创

血浆 NfL 浓度对唐氏综合症中的症状性阿尔茨海默病具有出色的诊断和预后性能。血浆 NfL 的纵向轨迹支持其在临床试验中用作治疗诊断标志物。

      患有唐氏综合症的成年人患阿尔茨海默病的风险极高,但在这一人群中诊断阿尔茨海默病具有挑战性。近日,有研究人员验证血浆神经丝轻链 (NfL) 在诊断唐氏综合征症状性阿尔茨海默病中的临床效用,评估其预后价值,并确定成人唐氏综合征的纵向变化

      进行了一项多中心队列研究,包括从法国、德国、西班牙、英国和美国的 6 家医院和大学医疗中心招募的唐氏综合征成人(≥18 岁),他们已经接受评估、随访并提供至少两个血浆样本。参与者被当地临床医生分类为无症状(即没有临床怀疑阿尔茨海默病)、前驱阿尔茨海默病或阿尔茨海默病痴呆。研究将随访期间沿阿尔茨海默病连续体进展的个体分类为进展者。

      血浆样本进行了回顾性分析;使用用于生物标志物检测的商业试剂盒集中测量 NfL 浓度。使用方差分析来评估基线 NfL 浓度的差异,Cox 回归来研究它们的预后价值,以及线性混合模型来估计纵向变化。为了解释潜在的混杂因素,我们将年龄、性别和智力障碍作为分析中的协变量。

  • 2010 年 8 月 2 日至 2019 年 7 月 16 日期间,共分析了来自 236 名唐氏综合症患者的 608 份样本:165 人(70%)无症状,32 人(14%)患有前驱阿尔茨海默病,29 人(12%)患有阿尔茨海默病痴呆; 10 [4%] 名参与者被排除在外,因为他们的分类不确定。
  • 平均随访时间为 3·6 年(SD 1·6,范围 0·6-9·2)。
  • 基线血浆 NfL 浓度显示前驱组的受试者操作特征曲线下面积为 0·83 (95% CI 0·76–0·91),痴呆组为 0·94 (0·90-0·97)以区别于无症状的参与者。基线 NfL 浓度增加 1 pg/mL 与 1·04 倍的临床进展风险相关(95% CI 1·01–1·07;p=0·0034)。
  • 无症状非进展组的血浆 NfL 浓度显示每年增加 3·0% (95% CI 0·4–5·8),在无症状组中每年增加 11·5% (4·9-18·5)无症状进展者组,前驱阿尔茨海默病进展者组每年 16·0% (8·4–24·0)。在患有阿尔茨海默病痴呆的参与者中,NfL 浓度平均增加了 24·3% (15·3–34·1)。

      血浆 NfL 浓度对唐氏综合症中的症状性阿尔茨海默病具有出色的诊断和预后性能。血浆 NfL 的纵向轨迹支持其在临床试验中用作治疗诊断标志物。

文献来源:Carmona-Iragui M, Alcolea D, Barroeta I, et al. Diagnostic and prognostic performance and longitudinal changes in plasma neurofilament light chain concentrations in adults with Down syndrome: a cohort study. Lancet Neurol. 2021;20(8):605-614. doi:10.1016/S1474-4422(21)00129-0

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    2022-05-08 yinhl1978
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    2021-11-15 howi
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