Botha Hugo, Duffy Joseph R, Whitwell Jennifer L, Strand Edythe A, Machulda Mary M, Schwarz Christopher G, Reid Robert I, Spychalla Anthony J, Senjem Matthew L, Jones David T, Lowe Val, Jack Clifford R, Josephs Keith A
Department of Neurology (Behavioural Neurology), Mayo Clinic, Rochester, MN, USA.
Department of Neurology (Speech Pathology), Mayo Clinic, Rochester, MN, USA.
Cortex. 2015 Aug;69:220-36. doi: 10.1016/j.cortex.2015.05.013. Epub 2015 May 27.
The consensus criteria for the diagnosis and classification of primary progressive aphasia (PPA) have served as an important tool in studying this group of disorders. However, a large proportion of patients remain unclassifiable whilst others simultaneously meet criteria for multiple subtypes. We prospectively evaluated a large cohort of patients with degenerative aphasia and/or apraxia of speech using multidisciplinary clinical assessments and multimodal imaging. Blinded diagnoses were made using operational definitions with important differences compared to the consensus criteria. Of the 130 included patients, 40 were diagnosed with progressive apraxia of speech (PAOS), 12 with progressive agrammatic aphasia, 9 with semantic dementia, 52 with logopenic progressive aphasia, and 4 with progressive fluent aphasia, while 13 were unclassified. The PAOS and progressive fluent aphasia groups were least impaired. Performance on repetition and sentence comprehension was especially poor in the logopenic group. The semantic and progressive fluent aphasia groups had prominent anomia, but only semantic subjects had loss of word meaning and object knowledge. Distinct patterns of grey matter loss and white matter changes were found in all groups compared to controls. PAOS subjects had bilateral frontal grey matter loss, including the premotor and supplementary motor areas, and bilateral frontal white matter involvement. The agrammatic group had more widespread, predominantly left sided grey matter loss and white matter abnormalities. Semantic subjects had bitemporal grey matter loss and white matter changes, including the uncinate and inferior occipitofrontal fasciculi, whereas progressive fluent subjects only had left sided temporal involvement. Logopenic subjects had diffuse and bilateral grey matter loss and diffusion tensor abnormalities, maximal in the posterior temporal region. A diagnosis of logopenic aphasia was strongly associated with being amyloid positive (46/52 positive). Our findings support consideration of an alternative way of identifying and categorizing subtypes of degenerative speech and language disorders.
原发性进行性失语症(PPA)的诊断和分类共识标准一直是研究这类疾病的重要工具。然而,很大一部分患者仍无法分类,而其他患者则同时符合多种亚型的标准。我们使用多学科临床评估和多模态成像对一大群患有退行性失语症和/或言语失用症的患者进行了前瞻性评估。采用与共识标准有重要差异的操作定义进行盲法诊断。在纳入的130例患者中,40例被诊断为进行性言语失用症(PAOS),12例为进行性语法缺失性失语症,9例为语义性痴呆,52例为音韵性进行性失语症,4例为进行性流利性失语症,13例未分类。PAOS组和进行性流利性失语症组受损最轻。音韵性组在复述和句子理解方面的表现尤其差。语义性组和进行性流利性失语症组有明显的命名障碍,但只有语义性组患者存在词义和物体知识丧失。与对照组相比,所有组均发现了不同的灰质丢失和白质变化模式。PAOS患者双侧额叶灰质丢失,包括运动前区和辅助运动区,双侧额叶白质受累。语法缺失组的灰质丢失和白质异常更广泛,主要位于左侧。语义性组患者双侧颞叶灰质丢失和白质变化,包括钩束和枕颞下束,而进行性流利性组仅左侧颞叶受累。音韵性组患者存在弥漫性双侧灰质丢失和弥散张量异常,在颞叶后部最为明显。音韵性失语症的诊断与淀粉样蛋白阳性密切相关(52例中有46例阳性)。我们的研究结果支持考虑采用另一种方法来识别和分类退行性言语和语言障碍的亚型。