Watanabe Hiroyuki, Duffy Joseph R, Clark Heather, Machulda Mary M, Graff-Radford Jonathan, Thu Pham Nha Trang, Dickson Dennis W, Lowe Val J, Whitwell Jennifer L, Josephs Keith A
From the Departments of Neurology (H.W., J.R.D., H.C., J.G.-R., K.A.J.), Psychology (M.M.M.), and Radiology (N.T.T.P., V.J.L., J.L.W.), Mayo Clinic, Rochester, MN; and Department of Neuroscience (Neuropathology) (D.W.D.), Mayo Clinic, Jacksonville, FL.
Neurology. 2024 Nov 12;103(9):e209924. doi: 10.1212/WNL.0000000000209924. Epub 2024 Oct 8.
Evidence has accumulated that the 2011 consensus criteria for primary progressive aphasia (PPA) do not fully capture features of logopenic variant PPA (lvPPA/LPA). We aimed to examine clinical, neuroimaging, and neuropathologic features of PPA lacking features of nonfluent/semantic variants and to provide practical additions to the 2011 consensus criteria.
This was a retrospective examination of data from 2 observational cohort studies where patients with PPA were prospectively recruited at Mayo Clinic. Based on performance on 2 cardinal features (repetition and comprehension), patients were classified as: pure-LPA (poor repetition, acceptable comprehension), Wernicke-like (poor in both), anomic-like (acceptable in both), and transcortical sensory aphasia-like (TCSA-like) (acceptable repetition, poor comprehension).
The entire cohort consisted of 102 patients with PPA lacking features of nonfluent/semantic variants (median age at onset 63.5 years, 56% female). Thirty-one patients were followed up at 1 year. Twenty-three patients were included in a neuropathologic cohort. The proportion of repetition-preserved PPA (anomic-like and TCSA-like) was more than double that of repetition-impaired PPA (pure-LPA and Wernicke-like) (73% vs 27%). Regarding clinical course, the anomic-like subgroup was a prodromal state of the pure-LPA or TCSA-like subgroup, whereas the pure-LPA and TCSA-like subgroups were a prodromal state of the Wernicke-like subgroup. There was left temporoparietal atrophy on MRI and/or hypometabolism on F-fluorodeoxyglucose-PET in all groups. Furthermore, repetition-impaired PPA showed severe hypometabolism in the left superior temporal lobe associated with repetition ability. Regarding pathologic diagnoses, 70% had Alzheimer disease (AD). The pure-LPA, Wernicke-like, and TCSA-like subgroups all showed AD pathology. Only 53% of the anomic-like subgroup had AD. The remaining 47% showed Pick disease (7%), frontotemporal lobar degeneration with TDP-43-immunoreactive pathology (20%), and Lewy body disease (20%).
This observed clinical heterogeneity reflects different time points/severities of the same disease process and hence can be reconceptualized as an AD-related aphasia spectrum, incorporating lvPPA and the 4 subgroups (pure-LPA, Wernicke-like, anomic-like, and TCSA-like). Specifying moderate/severe repetition deficits as a core feature of lvPPA in the 2011 consensus criteria can enhance its pathologic correlations. Recognizing progressive anomic aphasia (anomic-like) as an additional PPA variant could lessen pathologic heterogeneity of lvPPA.
已有证据表明，2011年原发性进行性失语（PPA）的共识标准未能充分涵盖言语流畅性变异型PPA（lvPPA/LPA）的特征。我们旨在研究缺乏非流畅型/语义变异型特征的PPA的临床、神经影像学和神经病理学特征，并为2011年共识标准提供实用的补充内容。
这是一项对2项观察性队列研究数据的回顾性分析，研究中在梅奥诊所前瞻性招募了PPA患者。根据两项主要特征（复述和理解）的表现，患者被分为：纯LPA型（复述差，理解尚可）、韦尼克样型（两者均差）、命名性失语样型（两者均尚可）和经皮质感觉性失语样型（TCSA样型）（复述尚可，理解差）。
整个队列由102例缺乏非流畅型/语义变异型特征的PPA患者组成（发病年龄中位数为63.5岁，56%为女性）。31例患者进行了1年的随访。23例患者纳入神经病理学队列。复述保留的PPA（命名性失语样型和TCSA样型）的比例是复述受损的PPA（纯LPA型和韦尼克样型）的两倍多（73%对27%）。关于临床病程，命名性失语样型亚组是纯LPA型或TCSA样型亚组的前驱状态，而纯LPA型和TCSA样型亚组是韦尼克样型亚组的前驱状态。所有组在MRI上均有左侧颞顶叶萎缩和/或在F-氟脱氧葡萄糖-PET上有代谢减低。此外，复述受损的PPA在左侧颞上叶表现出与复述能力相关的严重代谢减低。关于病理诊断，70%患有阿尔茨海默病（AD）。纯LPA型、韦尼克样型和TCSA样型亚组均显示AD病理改变。命名性失语样型亚组只有53%患有AD。其余47%表现为皮克病（7%）、伴有TDP-43免疫反应性病理改变的额颞叶变性（20%）和路易体病（20%）。
观察到的这种临床异质性反映了同一疾病过程的不同时间点/严重程度，因此可以重新概念化为一种与AD相关的失语谱系，纳入lvPPA和4个亚组（纯LPA型、韦尼克样型、命名性失语样型和TCSA样型）。在2011年共识标准中将中度/重度复述缺陷指定为lvPPA的核心特征可以增强其与病理的相关性。将进行性命名性失语（命名性失语样型）识别为另一种PPA变异型可以减少lvPPA的病理异质性。
