Progressive apraxia of speech is a neurodegenerative motor-speech disorder that most commonly arises from a 4-repeat tauopathy. Recent studies have established that progressive apraxia of speech is not a homogenous disease, but rather there are distinct subtypes: the phonetic subtype is characterized by distorted sound substitutions, the prosodic subtype by slow and segmented speech, and the mixed subtype by a combination of both but lack of predominance of either. There is some evidence that cross-sectional patterns of neurodegeneration differ across subtypes, although it is unknown whether longitudinal patterns of neurodegeneration differ. We examined longitudinal patterns of atrophy on MRI, hypometabolism on 18F-fluorodeoxyglucose-PET, and tau uptake on flortaucipir-PET in a large cohort of subjects with progressive apraxia of speech that had been followed for many years. Ninety-one subjects with progressive apraxia of speech (51 phonetic, 40 prosodic) were recruited by the Neurodegenerative Research Group. Of these, 54 (27 phonetic, 27 prosodic) returned for annual follow-up, with up to seven longitudinal visits (total visits analyzed = 217). Volumes, metabolism, and flortaucipir uptake was measured for subcortical and cortical regions, for all scans. Bayesian hierarchical models were used to model longitudinal change across imaging modalities with progressive apraxia of speech subtypes being compared at baseline, four years from baseline, and in terms of rates of change. The phonetic group showed smaller volumes and worse metabolism in Broca’s area and the striatum at baseline and after four years, and faster rates of change in these regions, compared to the prosodic group. There was also evidence of faster spread of hypometabolism and flortaucipir uptake into the temporal and parietal lobes in the phonetic group. In contrast, the prosodic group showed smaller cerebellar dentate, midbrain, substantia nigra, and thalamus volumes at baseline and after four years, and faster rates of atrophy, than the phonetic group. Greater hypometabolism and flortaucipir uptake were also observed in the cerebellar dentate and substantia nigra in the prosodic group. Mixed findings were observed in the SMA and precentral cortex, with no clear differences observed across phonetic and prosodic groups. These findings support different patterns of disease spread in progressive apraxia of speech subtypes, with corticostriatal patterns in the phonetic subtype and brainstem and thalamic patterns in the prosodic subtype, providing insight into the pathophysiology and heterogeneity of progressive apraxia of speech.

中文翻译：

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纵向弗洛托西皮尔、新陈代谢和音量在语音和韵律言语失用症之间存在差异

进行性言语失用症是一种神经退行性运动言语障碍，最常见的是由 4 次重复 tau 蛋白病引起。最近的研究表明，进行性言语失用症不是一种同质疾病，而是有不同的亚型：语音亚型的特点是声音替换失真，韵律亚型的特点是缓慢和分段的言语，混合亚型的特点是两者的结合但两者均不具备优势。有一些证据表明，不同亚型的神经退行性变的横截面模式有所不同，尽管尚不清楚神经退行性变的纵向模式是否有所不同。我们对一大群患有进行性言语失用症的受试者进行了多年跟踪，检查了 MRI 上的纵向萎缩模式、18F-氟脱氧葡萄糖-PET 上的代谢低下以及 flaucipir-PET 上的 tau 摄取。神经退行性研究小组招募了 91 名患有进行性言语失用症的受试者（51 名语音性失用症，40 名韵律性失用症患者）。其中，54 例（27 例语音，27 例韵律）返回进行年度随访，最多进行 7 次纵向访问（分析的总访问次数 = 217 次）。对于所有扫描，测量皮质下和皮质区域的体积、代谢和弗洛托西吡摄取。贝叶斯分层模型用于模拟跨成像模式的纵向变化，并在基线、基线四年后以及变化率方面比较言语亚型的进行性失用症。与韵律组相比，语音组在基线和四年后的布罗卡区和纹状体的体积更小，新陈代谢更差，并且这些区域的变化速度更快。还有证据表明，语音组代谢减退和弗洛托西吡吸收更快地扩散到颞叶和顶叶。相比之下，与语音组相比，韵律组在基线和四年后显示出较小的小脑齿状、中脑、黑质和丘脑体积，并且萎缩速度更快。在韵律组的小脑齿状核和黑质中也观察到更大的代谢减退和弗洛托西吡吸收。在 SMA 和中央前皮层中观察到了不同的结果，在语音和韵律组之间没有观察到明显的差异。这些发现支持进行性言语失用症的不同疾病传播模式，其中语音亚型中的皮质纹状体模式和韵律亚型中的脑干和丘脑模式，提供了对进行性言语失用症的病理生理学和异质性的见解。