Strategic white matter tracts for processing speed deficits in age-related small vessel disease

Objective: Cerebral small vessel disease is the most common cause of vascular cognitive impairment and typically manifests with slowed processing speed. We investigated the impact of lesion location on processing speed in age-related small vessel disease. Methods: A total of 584 community-dwelling elderly underwent brain MRI followed by segmentation of white matter hyperintensities. Processing speed was determined by the timed measure of the Trail Making Test part B. The impact of the location of white matter hyperintensities was assessed by voxel-based lesion-symptom mapping and graph-based statistical models on regional lesion volumes in major white matter tracts. Results: Voxel-based lesion-symptom mapping identified multiple voxel clusters where the presence of white matter hyperintensities was associated with slower performance on the Trail Making Test part B. Clusters were located bilaterally in the forceps minor and anterior thalamic radiation. Region of interest-based Bayesian network analyses on lesion volumes within major white matter tracts depicted the same tracts as direct predictors for an impaired Trail Making Test part B performance. Conclusions: Our findings highlight damage to frontal interhemispheric and thalamic projection fiber tracts harboring frontal-subcortical neuronal circuits as a predictor for processing speed performance in age-related small vessel disease.