From the Dementia Research Centre (S.M., C.J.D.H., J.J., E.B., J.C.S.J., A.C., J.D.R., J.D.W.), Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, United Kingdom; Research and Innovation Centre for Dementia-CRIDEM (S.M., C.M., V.M., S.P., S.S., V.B.), Azienda Ospedaliero-Universitaria Careggi, Florence; Vita-Salute San Raffaele University (S.M.), Milan; IRCCS Policlinico San Donato (S.M.), San Donato Milanese, Italy; Division of Neurology (A.C.), Department of Internal Medicine, King Chulalongkorn Memorial Hospital, Thai Red Cross Society; Cognitive Clinical and Computational Neuroscience Research Unit (A.C.), Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; University of Florence (G.G.), Italy; Department of Psychology & Language Sciences (A.V.), University College London, United Kingdom; Department of Neuroscience, Psychology, Drug Research and Child Health (A.I., S.B., B.N., S.S.), University of Florence, Azienda Ospedaliera-Universitaria Careggi; and IRCCS Fondazione Don Carlo Gnocchi (B.N., S.S., V.B.), Florence, Italy.
Neurology. 2024 Dec 24;103(12):e210058. doi: 10.1212/WNL.0000000000210058. Epub 2024 Nov 21.
Current formulations of primary progressive aphasia (PPA) derive largely from English-speaking patients. We hypothesized that language-specific characteristics influence PPA phenotypes in 2 contrasting languages: Italian and English.
We undertook a retrospective, cross-sectional, observational comparison of 2 patient cohorts representing all major PPA syndromes, in London and Florence. Neuropsychological scores in a range of linguistic and general cognitive domains were normalized to native speaker controls and dichotomized as impaired/unimpaired. Proportions were compared using χ tests and adjusted for symptom duration and severity of cognitive impairment using logistic regression.
The cohorts comprised 106 (48.1% female) Italian speakers (14 nonfluent/agrammatic [nfvPPA], 20 semantic [svPPA], 41 logopenic variant [lvPPA], 31 mixed PPA [mPPA]) and 166 (45.2% female) English speakers (70 nfvPPA, 45 svPPA, 42 lvPPA, 9 mPPA). Comparing cohorts, the English cohort was younger (mean 62.7 [SD = 8.4] vs 65.9 [7.8] years; = 0.003, Cohen = 0.39), with longer symptom duration (4.6 [4.3] vs 3.1 [2.5] years; = 0.048, = 1.08), a higher proportion of nfvPPA cases (42% vs 13%, χ = 25.4, < 0.001), and lower proportions of lvPPA (25% vs 38%, χ = 5.46, = 0.019) and mPPA (5% vs 29%, χ = 29.3, < 0.001). English-speaking nfvPPA patients had less frequent expressive agrammatism (46% vs 93%, = 0.015, odds ratio [OR] 16.05, 95% CI 1.70-151.13) but more frequently impaired single-word comprehension (60% vs 8%, = 0.013, OR 0.06, 95% CI 0.00-0.56). English svPPA patients had more frequent surface dyslexia (68% vs 30%, = 0.046, OR 0.24, 95% CI 0.06-0.97) and dysgraphia (38% vs 10%, = 0.021, OR 0.09, 95% CI 0.01-0.70) while English lvPPA patients had more frequently impaired single-word comprehension (89% vs 29%, < 0.001, OR 0.05, 95% CI 0.01-0.28), word repetition (61% vs 26%, = 0.020, OR 0.24, 95% CI 0.07-0.80), nonword repetition (78% vs 30%, = 0.010, OR 0.18, 95% CI 0.05-0.06), nonverbal working memory (69% vs 36%, = 0.005, OR 0.10, 95% CI 0.02-0.51), and visuomotor function (89% vs 25%, < 0.001, OR 0.02, 95% CI 0.01-0.20).
Language-specific characteristics influenced PPA phenotypes, with more frequent expressive agrammatism in Italian (reflecting its morphologic complexity), more frequently impaired word processing in English (reflecting its articulatory, acoustic, and orthographic complexity), and increased prevalence of mPPA in Italian. These findings have implications for PPA diagnosis and management. Limitations of test heterogeneity and cohort size should be addressed in future, prospective, multicenter initiatives using cross-linguistic tools.
目前的原发性进行性失语症（PPA）分类主要来源于英语患者。我们假设语言特异性特征会影响两种截然不同语言中的 PPA 表型：意大利语和英语。
我们回顾性地比较了伦敦和佛罗伦萨的两个患者队列，这两个队列代表了所有主要的 PPA 综合征。在一系列语言和一般认知领域的神经心理学评分与母语对照者进行了标准化，并分为受损/未受损。使用 χ 检验比较比例，并使用逻辑回归根据症状持续时间和认知障碍严重程度进行调整。
队列包括 106 名（48.1%女性）意大利语患者（14 名非流利/语法障碍性 PPA [nfvPPA]，20 名语义性 PPA [svPPA]，41 名失读性变异型 PPA [lvPPA]，31 名混合型 PPA [mPPA]）和 166 名（45.2%女性）英语患者（70 名 nfvPPA，45 名 svPPA，42 名 lvPPA，9 名 mPPA）。比较两个队列，英语队列更年轻（平均 62.7 [SD=8.4] vs 65.9 [7.8] 岁； = 0.003，Cohen = 0.39），症状持续时间更长（4.6 [4.3] vs 3.1 [2.5] 年； = 0.048， = 1.08），nfvPPA 病例比例更高（42% vs 13%， χ = 25.4， < 0.001），lvPPA（25% vs 38%， χ = 5.46， = 0.019）和 mPPA（5% vs 29%， χ = 29.3， < 0.001）比例较低。英语 nfvPPA 患者更常出现表达性语法障碍（46% vs 93%， = 0.015，优势比 [OR] 16.05，95%置信区间 [CI] 1.70-151.13），但更常出现单词语义理解受损（60% vs 8%， = 0.013，OR 0.06，95%CI 0.00-0.56）。英语 svPPA 患者更常出现表面失读症（68% vs 30%， = 0.046，OR 0.24，95%CI 0.06-0.97）和书写障碍（38% vs 10%， = 0.021，OR 0.09，95%CI 0.01-0.70），而英语 lvPPA 患者则更常出现单词语义理解受损（89% vs 29%， < 0.001，OR 0.05，95%CI 0.01-0.28）、单词重复（61% vs 26%， = 0.020，OR 0.24，95%CI 0.07-0.80）、非单词重复（78% vs 30%， = 0.010，OR 0.18，95%CI 0.05-0.06）、非语言工作记忆（69% vs 36%， = 0.005，OR 0.10，95%CI 0.02-0.51）和视动功能（89% vs 25%， < 0.001，OR 0.02，95%CI 0.01-0.20）。
语言特异性特征影响了 PPA 表型，意大利语中更常出现表达性语法障碍（反映了其形态复杂性），英语中更常出现受损的单词处理（反映了其发音、声学和拼写复杂性），意大利语中 mPPA 的发病率更高。这些发现对 PPA 的诊断和管理具有启示意义。未来应使用跨语言工具，在更大规模的前瞻性多中心研究中解决测试异质性和队列规模的局限性。
