Mediating role of brain aging in the effect of white matter hyperintensities on post-stroke aphasia severity

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.

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.

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).

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.