ORIGINAL RESEARCH article
Front. Aging Neurosci.
Sec. Neurocognitive Aging and Behavior
Volume 17 - 2025 | doi: 10.3389/fnagi.2025.1629870
Mediating role of brain aging in the effect of white matter hyperintensities on post-stroke aphasia severity
Provisionally accepted
- 1Department of Radiology, Qilu Hospital of Shandong University and Qilu Medical Imaging Institute of Shandong University, Jinan, China
- 2MR Research Collaboration, Siemens Healthineers Ltd., Shanghai, China
- 3Shandong Key Laboratory for Magnetic Field-free Medicine and Functional Imaging, Institute of Magnetic Field-free Medicine and Functional Imaging, Shandong University, Jinan 250014, China
- 4National Innovation Platform for Industry-Education Integration in Medicine-Engineering Interdisciplinary, Shandong University, Jinan 250014, China
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Objectives: White matter hyperintensities (WMH) have been associated with the severity of post-stroke aphasia (PSA), but the contribution of overall brain health remains unclear. Brain age is a neurobiological indicator of aging that is based on whole-brain structural neuroimaging. This study investigated the impact of brain age on language function after stroke. Methods: Fifty-seven patients with PSA and left-hemisphere lesions were included. The Fazekas scale was used to evaluate WMH burden, including periventricular WMH (PWMH) and deep WMH (DWMH). Brain age was estimated using structural 3D T1-weighted imaging, and the Brain-Predicted Age Difference (brain-PAD) was calculated. Multivariate linear regression and mediation analysis were conducted to examine associations among WMH burden, brain-PAD, and aphasia severity. The interaction between WMH burden and brain-PAD was also assessed. Results: Higher levels of PWMH and DWMH were associated with increased brain-PAD in PSA patients (PWMH: p = 0.024; DWMH: p < 0.001). Mediation analysis indicated that WMH had an indirect effect on auditory comprehension via brain-PAD (PWMH: β = -9.360, p = 0.028, q = 0.042) and a direct effect on naming impairment (PWMH: β = -15.812, p = 0.030, q = 0.042; DWMH: β = -19.217, p = 0.030, q = 0.042) . A significant interactive effect of PWMH burden and brain-PAD on auditory comprehension was also observed (β = -4.040, p = 0.004, q = 0.033). Conclusions: Our findings highlight the influence of neuroanatomical aging and WMH burden on post-stroke language deficits, supporting the consideration of both brain-PAD and WMH severity when assessing aphasia severity to inform clinical assessment and treatment planning.
Keywords: Post-stroke aphasia, white matter hyperintensities, Brain age, Interaction Analysis, Mediation analysis
Received: 16 May 2025; Accepted: 03 Oct 2025.
Copyright: © 2025 Xu, Wu, Zhu, Qu, Xu, Xin and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Dawei Wang, 202335941@mail.sdu.edu.cn
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