Association between Subcortical Vascular Lesion Location and Cognition: A Voxel-Based and Tract-Based Lesion-Symptom Mapping Study. The SMART-MR Study

Introduction: Lacunar lesions (LLs) and white matter lesions (WMLs) affect cognition. We assessed whether lesions located in specific white matter tracts were associated with cognitive performance taking into account total lesion burden. Methods: Within the Second Manifestations of ARTerial disease Magnetic Resonance (SMART-MR) study, cross-sectional analyses were performed on 516 patients with manifest arterial disease. We applied an assumption-free voxel-based lesion-symptom mapping approach to investigate the relation between LL and WML locations on 1.5 Tesla brain MRI and compound scores of executive functioning, memory and processing speed. Secondly, a multivariable linear regression model was used to relate the regional volume of LLs and WMLs within specific white matter tracts to cognitive functioning. Results: Voxel-based lesion-symptom mapping identified several clusters of voxels with a significant correlation between WMLs and executive functioning, mostly located within the superior longitudinal fasciculus and anterior thalamic radiation. In the multivariable linear regression model, a statistically significant association was found between regional LL volume within the superior longitudinal fasciculus and anterior thalamic radiation and executive functioning after adjustment for total LL and WML burden. Conclusion: These findings identify the superior longitudinal fasciculus and anterior thalamic radiation as key anatomical structures in executive functioning and emphasize the role of strategically located vascular lesions in vascular cognitive impairment.