The impact of strategic white matter hyperintensity lesion location on language

ABSTRACT Objective The impact of white matter hyperintensities (WMH) on language possibly depends on lesion location through disturbance of strategic white matter tracts. We examined the impact of WMH location on language in elderly Asians. Design Cross-sectional Setting Population-based Participants 819 residents of Singapore, ages (≥65 years) Measurements Clinical, cognitive and 3T MRI assessments were performed on all participants. Language was assessed using the Modified Boston Naming Test (MBNT) and Verbal Fluency (VF). Hypothesis-free region-of-interest-based (ROI) analyses based on major white matter tracts were used to determine the association between WMH location and language. Conditional dependencies between the regional WMH volumes and language were examined using Bayesian-network analysis. Results ROI-based analyses showed that WMH located within the anterior thalamic radiation (mean difference: -0.12, 95%CI: -0.22; -0.02, p=0.019) and uncinate fasciculus (mean difference: -0.09, 95%CI: -0.18; -0.01, p=0.022) in the left hemisphere were significantly associated with worse VF but did not survive multiple testing. Conversely, WMH volume in the left cingulum of cingulate gyrus was significantly associated with MBNT performance (mean difference:-0.09, 95%CI:-0.17;-0.02, p=0.016). Bayesian-network analyses confirmed the left cingulum of cingulate gyrus as a direct determinant of MBNT performance. Conclusions Our findings identify the left cingulum of cingulate gyrus as a strategic white matter tract for MBNT, suggesting that language- is sensitive to subcortical ischemic damage. Future studies on the role of sporadic ischemic lesions and vascular cognitive impairment should not only focus on total WMH volume but should also take WMH lesion location into account when addressing language.