Beyond Agrammatism: Syntax Processing in Chinese Primary Progressive Aphasia
- 1University of California, San Francisco
Abstract
Syntax processing impairment is a defining feature of primary progressive aphasia (PPA), particularly in the nonfluent/agrammatic variant. However, current models are derived largely from Indo-European languages, and it remains unclear whether the cognitive and neuroanatomical mechanisms of syntax processing generalize to Chinese, an analytic, pro-drop language that encodes grammatical relationships primarily through word order and function words rather than inflectional morphology.
Participants were recruited from the international Chinese Language Assessment in PPA cohort and included 64 individuals with PPA (19 logopenic, 15 nonfluent/agrammatic, 15 semantic, and 15 unclassifiable/mixed) and 60 cognitively healthy controls. Participants completed sentence comprehension and production tasks with systematically manipulated syntactic features. Item-level linguistic determinants were examined using ridge regression, diagnostic performance using receiver operating characteristic analyses, and neuroanatomical correlates using voxel-based morphometry of structural MRI.
Performance on sentence comprehension and production was influenced by grammatical and lexical features. Subject-relative clauses, passive constructions, a higher proportion of function words, longer character length, and greater lexical content were associated with poorer performance among participants with PPA. Sentence comprehension was impaired in the logopenic, nonfluent/agrammatic, and semantic variants, even when isolated to the syntactic component of the sentence comprehension task. Similarly, sentence production was impaired across all PPA variants (all P < 0.01 versus controls). No significant differences were observed among PPA variants. Adjusted receiver operating characteristic analyses demonstrated high discrimination between each PPA variant and controls, with areas under the curve ranging from 0.87 to 0.97 for sentence comprehension-syntax and from 0.91 to 0.97 for sentence production. However, pairwise comparisons showed no significant differences in discriminative performance among PPA variants after correction for multiple comparisons. Both sentence comprehension-syntax and sentence production showed associations with semantic and repetition measures in addition to motor speech measures. Voxel-based morphometry showed that higher sentence comprehension-syntax scores were associated with greater grey matter volume in left frontotemporal and cingulate regions, whereas higher sentence production scores were additionally associated with greater gray matter volume in frontostriatal structures, including the caudate, putamen, and thalamus.
Syntactic processing impairment in Chinese-speaking individuals with PPA extends beyond the nonfluent/agrammatic variant and is associated with distributed frontotemporal and frontostriatal regions, as well as lexical-semantic and auditory verbal short term memory mechanisms. These findings suggest that the cognitive and neural manifestations of syntactic impairment may be shaped by language-specific typological properties, underscoring the need for linguistically informed approaches to the assessment and interpretation of PPA.
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BibTeX
@misc{cheng2026beyond,
title = {{Beyond Agrammatism: Syntax Processing in Chinese Primary Progressive Aphasia}},
author = {Y.-W. Cheng and T.-F. Chen and L. K.-C. Li-Ying and R. Y. Lo and J. Tsoh and A. L.-T. Chan and A. Wong and V. C. T. Mok and C. T. Yan and C. J. Lu and Y. Sun and P.-N. Wang and Y. Lee and A. Ng and F. Leng and Y. Chen and C.-H. Li and C.-H. Lin and Y.-C. Chuang and M.-L. Mandelli and M. L. Gorno-Tempini and B. L. Tee},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.16.26365322},
url = {https://www.medrxiv.org/content/10.64898/2026.10.16.26365322v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Beyond Agrammatism: Syntax Processing in Chinese Primary Progressive Aphasia
AU - Y.-W. Cheng
AU - T.-F. Chen
AU - L. K.-C. Li-Ying
AU - R. Y. Lo
AU - J. Tsoh
AU - A. L.-T. Chan
AU - A. Wong
AU - V. C. T. Mok
AU - C. T. Yan
AU - C. J. Lu
AU - Y. Sun
AU - P.-N. Wang
AU - Y. Lee
AU - A. Ng
AU - F. Leng
AU - Y. Chen
AU - C.-H. Li
AU - C.-H. Lin
AU - Y.-C. Chuang
AU - M.-L. Mandelli
AU - M. L. Gorno-Tempini
AU - B. L. Tee
PY - 2026
DA - 2026/10/16
PB - medRxiv
DO - 10.64898/2026.10.16.26365322
UR - https://www.medrxiv.org/content/10.64898/2026.10.16.26365322v1
AB - Syntax processing impairment is a defining feature of primary progressive aphasia (PPA), particularly in the nonfluent/agrammatic variant. However, current models are derived largely from Indo-European languages, and it remains unclear whether the cognitive and neuroanatomical mechanisms of syntax processing generalize to Chinese, an analytic, pro-drop language that encodes grammatical relationships primarily through word order and function words rather than inflectional morphology. Participants were recruited from the international Chinese Language Assessment in PPA cohort and included 64 individuals with PPA (19 logopenic, 15 nonfluent/agrammatic, 15 semantic, and 15 unclassifiable/mixed) and 60 cognitively healthy controls. Participants completed sentence comprehension and production tasks with systematically manipulated syntactic features. Item-level linguistic determinants were examined using ridge regression, diagnostic performance using receiver operating characteristic analyses, and neuroanatomical correlates using voxel-based morphometry of structural MRI. Performance on sentence comprehension and production was influenced by grammatical and lexical features. Subject-relative clauses, passive constructions, a higher proportion of function words, longer character length, and greater lexical content were associated with poorer performance among participants with PPA. Sentence comprehension was impaired in the logopenic, nonfluent/agrammatic, and semantic variants, even when isolated to the syntactic component of the sentence comprehension task. Similarly, sentence production was impaired across all PPA variants (all P < 0.01 versus controls). No significant differences were observed among PPA variants. Adjusted receiver operating characteristic analyses demonstrated high discrimination between each PPA variant and controls, with areas under the curve ranging from 0.87 to 0.97 for sentence comprehension-syntax and from 0.91 to 0.97 for sentence production. However, pairwise comparisons showed no significant differences in discriminative performance among PPA variants after correction for multiple comparisons. Both sentence comprehension-syntax and sentence production showed associations with semantic and repetition measures in addition to motor speech measures. Voxel-based morphometry showed that higher sentence comprehension-syntax scores were associated with greater grey matter volume in left frontotemporal and cingulate regions, whereas higher sentence production scores were additionally associated with greater gray matter volume in frontostriatal structures, including the caudate, putamen, and thalamus. Syntactic processing impairment in Chinese-speaking individuals with PPA extends beyond the nonfluent/agrammatic variant and is associated with distributed frontotemporal and frontostriatal regions, as well as lexical-semantic and auditory verbal short term memory mechanisms. These findings suggest that the cognitive and neural manifestations of syntactic impairment may be shaped by language-specific typological properties, underscoring the need for linguistically informed approaches to the assessment and interpretation of PPA.
ER -