Ischemic damage of large-scale networks between cortical regions leading to disconnection may cause cognitive impairment associated with widespread functional disturbance. However, it remains unclear to what extent this mechanism contributes to the development of cognitive impairment or dementia, because there is no way to evaluate quantitatively and precisely the amount of the disconnection in each patient. We investigated atrophy of the corpus callosum as a surrogate marker for damage of large-scale networks. In ca-rotid artery disease without cortical infarction, callosal atrophy was associated with cognitive impairment and widespread cerebral cortical hypometabolism. Ischemic loss of the pyramidal cells in layer 3 originating long association and commissural fibers, which may result in calllosal atrophy, may lead to the disconnection be-tween cortical regions. In patients with lacunar infarction and white matter lesions, callosal atrophy was a predictor of global cognitive impairment, whereas the extent of white matter lesions per se was related to impairment of frontal lobe function independent of callosal atrophy. Callosal atrophy may parallel the total loss of fibers in the white matter, the degree of which may determine the severity of disconnection. Damage of largescale networks is important for the development of cognitive impairment in ischemic stroke.
