Year: 2026
Type: preprint
Study design: Observational Study
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.
Source: medRxiv
Authors: Yu-Wen Cheng, Ta-Fu Chen, Lorinda Kwan-Chen Li-Ying, Raymond Y. Lo, Joshua Tsoh, Andrew Lung-Tat Chan, Adrian Wong, Vincent Chung Tong Mok, Connie TY Yan, Chien Jung Lu, Yu Sun, Pei-Ning Wang, YiChen Lee, Adeline Ng, FangDa Leng, Yu Chen, Cheng-Hsuan Li, Chin-Hsien Lin, Yu-Chen Chuang, Maria-Luisa Mandelli, Maria Luisa Gorno-Tempini, Boon Lead Tee
Institutions: National Taiwan University Hospital, Education University of Hong Kong, National Dong Hwa University, Chinese University of Hong Kong, Shatin Hospital, Prince of Wales Hospital, Queen Elizabeth Hospital, Mercy Hospital for Women, En Chu Kong Hospital, National Yang Ming Chiao Tung University, Taipei Veterans General Hospital, National Neuroscience Institute, University of California, San Francisco, UCSF Edward and Pearl Fein Memory and Aging Center
Language: English
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
Funders: Alzheimer's Association, Global Brain Health Institute, National Taiwan University Hospital, National Institutes of Health, University of California, San Francisco, National Institute on Aging, National Institute on Deafness and Other Communication Disorders, National Institute of Neurological Disorders and Stroke
Awards: G1099727449, Defining trajectories of dynamic biomarkers for C9ORF72 repeat expansion carriers, G3262109175, Dynamic Brain Imaging of Speech in Primary Progressive Aphasia, Primary Progressive Aphasia: Cognition, Anatomy and Progression, Chinese Language Assessment batteries for Primary Progressive Aphasia: Cantonese, Chinese Language Assessment in Primary Progressive Aphasia, Chinese Language Assessment batteries for Primary Progressive Aphasia(CLAP), G630354180, G6876577119, G7282017350, G7375618867, G898313041, G9000157136, Frontotemporal Dementia: Genes, Images, and Emotions, Training program in the neurology of language and neurodegenerative aphasias, The impact of bilingualism on cognitive reserve/resilience using socio-demographically and linguistically diverse populations, New Approaches to Dementia Heterogeneity, Asian Cohort for Alzheimer's Disease (ACAD), A Pragmatic Trial of the UCSF Brain Health Assessment for the Detection of Cognitive Impairment in Primary Care, Chinese language versions of the National Alzheimer's Coordinating Center's Uniform Data Set version 4: a linguistic and cultural adaptation study
OpenAlex ID: W7222945327