Subtypes of progressive aphasia: application of the international consensus criteria and validation using β-amyloid imaging
Subtypes of progressive aphasia: application of the international consensus criteria and validation using β-amyloid imaging
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DOI：
10.1093/brain/awr216
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发表时间：
2011-10-01
期刊：
影响因子：
14.5
通讯作者：
Hodges, John R.
中科院分区：
文献类型：
--
作者：
Leyton, Cristian E.;Villemagne, Victor L.;Hodges, John R.
原发性进行性失语包括一组不同的神经退行性疾病，具有不同的临床特征和潜在的病理基础。一项重大进展是最近公布了三个主要变体的国际共识标准，即：语义性、非流畅性/语法和对数性。对数变异被认为代表了阿尔茨海默病的非典型表现，尽管目前这方面的证据有限。语义和非流利/无语法的变体分别与TDP-43和tau病理的额颞叶变性有很大关联。国际共识标准对未选定的临床样本的适用性尚不清楚，也不存在用于得出诊断的商定的临床评估标准。我们使用新开发的进行性失语症语言量表，评估了在专家中心连续3年期间看到的47例原发性进行性失语。其中30名患者接受了C-11标记的匹兹堡化合物B正电子发射断层扫描成像，这是一种被认为是阿尔茨海默病的生物标志物，可以检测β-淀粉样蛋白的堆积，并与年龄匹配的以遗忘型阿尔茨海默病为主的典型阿尔茨海默病患者组(n=10)进行比较。应用基于四个关键语音和语言变量(运动性言语障碍、语法错误、单字理解和句子重复)的算法对47例患者中的45例(96%)进行分类，并显示出与基于国际共识标准的金标准专家临床诊断的高度一致性。新皮质β-淀粉样蛋白负荷水平在不同的失语症变种之间差别很大。在13名对数减少症患者中，12名(92%)有阳性的β-淀粉样蛋白摄取。相比之下，9个语义变体中有1个(11%)和8个不流利/不语法的案例中有2个(25%)是阳性的。尽管失语症患者的总负荷较低，但在对数变异的病例中，β-淀粉样蛋白在感兴趣皮质区域的分布与典型阿尔茨海默病患者相同。句子重复和句子理解障碍与β-淀粉样蛋白的新皮质负荷呈正相关，而单词理解障碍则呈负相关。使用基于四个关键变量的简单言语和语言评估表，可以将国际共识标准应用于大多数原发性进行性失语症患者。β-淀粉样蛋白成像证实了对数变异体的阿尔茨海默病病理发生率较高，而其他两种变异体的阿尔茨海默病发病率较低。这项研究为阿尔茨海默病临床表现的生物学基础提供了洞察，阿尔茨海默病的临床表现似乎与β-淀粉样蛋白负荷无关。
Primary progressive aphasia comprises a heterogeneous group of neurodegenerative conditions with diverse clinical profiles and underlying pathological substrates. A major development has been the publication of the recent International Consensus Criteria for the three major variants namely: semantic, non-fluent/agrammatic and logopenic. The logopenic variant is assumed to represent an atypical presentation of Alzheimer pathology although evidence for this is, at present, limited. The semantic and non-fluent/agrammatic variants are largely associated with frontotemporal lobar degeneration with TDP-43 and tau pathology, respectively. The applicability of the International Consensus Criteria to an unselected clinical sample is unknown and no agreed clinical evaluation scale on which to derive the diagnosis exists. We assessed 47 consecutive cases of primary progressive aphasic seen over a 3-year period in a specialist centre, using a newly developed progressive aphasia language scale. A subgroup of 30 cases underwent C-11-labelled Pittsburgh Compound B positron emission tomography imaging, a putative biomarker of Alzheimer's disease that detects beta-amyloid accumulation, and they were compared with an age-matched group (n = 10) with typical, predominately amnestic Alzheimer's disease. The application of an algorithm based on four key speech and language variables (motor speech disorders, agrammatism, single-word comprehension and sentence repetition) classified 45 of 47 (96%) of patients and showed high concordance with the gold standard expert clinical diagnosis based on the International Consensus Criteria. The level of neocortical beta-amyloid burden varied considerably across aphasic variants. Of 13 logopenic patients, 12 (92%) had positive beta-amyloid uptake. In contrast, one of nine (11%) semantic variant and two of eight (25%) non-fluent/agrammatic cases were positive. The distribution of beta-amyloid across cortical regions of interest was identical in cases with the logopenic variant to that of patients with typical Alzheimer's disease although the total load was lower in the aphasic cases. Impairments of sentence repetition and sentence comprehension were positively correlated with neocortical burden of beta-amyloid, whereas impaired single-word comprehension showed a negative correlation. The International Consensus Criteria can be applied to the majority of cases with primary progressive aphasic using a simple speech and language assessment scale based upon four key variables. beta-amyloid imaging confirms the higher rate of Alzheimer pathology in the logopenic variant and, in turn, the low rates in the other two variants. The study offers insight into the biological basis of clinical manifestations of Alzheimer's disease, which appear topographically independent of beta-amyloid load.