White matter lesions are frequently observed in the elderly, and have been postulated to be responsible for dementia and parkinsonism. At first, we revealed that cholinergic pathways are damaged in the external capsule due to white matter lesions in Binswanger's disease. In addition, a flumazenil (FMZ)-PET study, a marker of benzodiazepine/GABAA receptors, revealed that FMZ-binding was decreased in the prefrontal cortex and the insular cortex in demented patients with extensive white matter lesions. In contrast, FMZ-binding was decreased in the premotor cortex and the striatum in the patients with extensive white matter lesions and parkinsonism, as compared to those with white matter lesions but without parkinsonism. These results indicate that subcortical nerve fiber damages may impair neural networks and hence, the neural function in the corresponding gray matter.