Logopenic and Nonfluent Variants of Primary Progressive Aphasia Are Differentiated by Acoustic Measures of Speech Production

Differentiation of logopenic (lvPPA) and nonfluent/agrammatic (nfvPPA) variants of Primary Progressive Aphasia is important yet remains challenging since it hinges on expert based evaluation of speech and language production. In this study acoustic measures of speech in conjunction with voxel-based morphometry were used to determine the success of the measures as an adjunct to diagnosis and to explore the neural basis of apraxia of speech in nfvPPA. Forty-one patients (21 lvPPA, 20 nfvPPA) were recruited from a consecutive sample with suspected frontotemporal dementia. Patients were diagnosed using the current gold-standard of expert perceptual judgment, based on presence/absence of particular speech features during speaking tasks. Seventeen healthy age-matched adults served as controls. MRI scans were available for 11 control and 37 PPA cases; 23 of the PPA cases underwent amyloid ligand PET imaging. Measures, corresponding to perceptual features of apraxia of speech, were periods of silence during reading and relative vowel duration and intensity in polysyllable word repetition. Discriminant function analyses revealed that a measure of relative vowel duration differentiated nfvPPA cases from both control and lvPPA cases (r2 = 0.47) with 88% agreement with expert judgment of presence of apraxia of speech in nfvPPA cases. VBM analysis showed that relative vowel duration covaried with grey matter intensity in areas critical for speech motor planning and programming: precentral gyrus, supplementary motor area and inferior frontal gyrus bilaterally, only affected in the nfvPPA group. This bilateral involvement of frontal speech networks in nfvPPA potentially affects access to compensatory mechanisms involving right hemisphere homologues. Measures of silences during reading also discriminated the PPA and control groups, but did not increase predictive accuracy. Findings suggest that a measure of relative vowel duration from of a polysyllable word repetition task may be sufficient for detecting most cases of apraxia of speech and distinguishing between nfvPPA and lvPPA.

原发性进行性失语（Primary Progressive Aphasia, PPA）的语义流畅性受损型（logopenic variant, lvPPA）与非流利/语法缺失型（nonfluent/agrammatic variant, nfvPPA）亚型的鉴别诊断具有重要临床价值，但始终颇具挑战——其核心依赖专家对言语及语言产出的主观评估。本研究结合言语声学测量与基于体素的形态测量学（voxel-based morphometry, VBM），旨在评估此类测量作为诊断辅助手段的有效性，并探索非流利/语法缺失型PPA患者言语失用症（apraxia of speech）的神经机制。本研究从疑似额颞叶痴呆的连续入组样本中纳入41例患者（21例lvPPA、20例nfvPPA），所有患者均基于说话任务中特定言语特征的有无，通过当前金标准的专家感知判断完成确诊；同时纳入17名年龄匹配的健康成人作为对照。11名对照与37例PPA患者完成了磁共振成像（MRI）扫描，其中23例PPA患者额外接受了淀粉样配体PET成像。本研究选取与言语失用症（apraxia of speech）感知特征相关的测量指标：朗读过程中的沉默时段，以及多音节单词重复任务中的相对元音时长与相对元音强度。判别函数分析结果显示，相对元音时长这一指标可将nfvPPA患者与对照及lvPPA患者区分开来（决定系数$r^2=0.47$），且与nfvPPA患者言语失用症的专家判断结果一致性达88%。基于体素的形态测量学（VBM）分析显示，相对元音时长与言语运动规划及编程关键脑区的灰质强度呈正相关，这些脑区包括双侧中央前回（precentral gyrus）、补充运动区（supplementary motor area）及额下回（inferior frontal gyrus），且仅在nfvPPA组中出现受累。nfvPPA患者的额叶言语网络出现双侧受累，这可能会干扰涉及右侧半球同源脑区的代偿机制的激活。朗读沉默时段测量同样可区分PPA患者与对照人群，但未能提升预测准确率。本研究结果表明，通过多音节单词重复任务获取的相对元音时长测量指标，足以检出绝大多数言语失用症病例，并有效区分nfvPPA与lvPPA亚型。