Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA.
Department of Quantitative Health Sciences (Biostatistics), Mayo Clinic, Rochester, MN 55905, USA.
Brain. 2024 May 3;147(5):1696-1709. doi: 10.1093/brain/awae016.
Progressive apraxia of speech (PAOS) is a neurodegenerative motor-speech disorder that most commonly arises from a four-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 PAOS that had been followed for many years. Ninety-one subjects with PAOS (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 analysed = 217). Volumes, metabolism and flortaucipir uptake were measured for subcortical and cortical regions, for all scans. Bayesian hierarchical models were used to model longitudinal change across imaging modalities with PAOS subtypes being compared at baseline, 4 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 4 years, and faster rates of change in these regions, compared with 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 4 years, as well as 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 supplementary motor area and precentral cortex, with no clear differences observed across phonetic and prosodic groups. These findings support different patterns of disease spread in PAOS 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 PAOS.
进行性失语症 (PAOS) 是一种神经退行性运动言语障碍，最常见于四重复tau 病。最近的研究已经确定，进行性失语症不是一种同质疾病，而是有不同的亚型：语音亚型的特征是声音扭曲替代，韵律亚型的特征是语速缓慢且分段，混合亚型的特征是两者兼有，但缺乏任何一种的主导地位。有一些证据表明，不同亚型的横断面神经退行性变模式不同，尽管尚不清楚纵向神经退行性变模式是否不同。我们检查了在一个经过多年随访的大量 PAOS 患者队列中，MRI 上的萎缩、18F-氟脱氧葡萄糖-PET 上的低代谢和 flortaucipir-PET 上的 tau 摄取的纵向模式。神经退行性研究小组招募了 91 名 PAOS 患者（51 名语音型，40 名韵律型）。其中，54 名（27 名语音型，27 名韵律型）返回进行年度随访，共进行了 7 次纵向随访（总共分析了 217 次随访）。在所有扫描中，均测量了皮质下和皮质区域的体积、代谢和 flortaucipir 摄取。使用贝叶斯层次模型对影像学模态的纵向变化进行建模，比较了 PAOS 亚型在基线、基线后 4 年以及在变化率方面的差异。与韵律组相比，语音组在基线和 4 年后的 Broca 区和纹状体中体积较小，代谢较差，这些区域的变化速度更快。在语音组中，还发现低代谢和 flortaucipir 摄取向颞叶和顶叶更快地扩散。相比之下，在基线和 4 年后，韵律组的小脑齿状核、中脑、黑质和丘脑体积较小，且萎缩速度比语音组快。在小脑齿状核和黑质中还观察到更大的低代谢和 flortaucipir 摄取。在辅助运动区和中央前回中观察到混合结果，在语音和韵律组之间没有观察到明显差异。这些发现支持 PAOS 亚型中不同的疾病传播模式，语音亚型为皮质纹状体模式，韵律亚型为脑干和丘脑模式，为 PAOS 的病理生理学和异质性提供了见解。
