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    Chronic ischemia alters brain microstructural integrity and cognitive performance in adult moyamoya disease. Kazumata Ken,Tha Khin Khin,Narita Hisashi,Kusumi Ichiro,Shichinohe Hideo,Ito Masaki,Nakayama Naoki,Houkin Kiyohiro Stroke BACKGROUND AND PURPOSE:The mechanisms underlying frontal lobe dysfunction in moyamoya disease (MMD) are unknown. We aimed to determine whether chronic ischemia induces subtle microstructural brain changes in adult MMD and evaluated the association of changes with neuropsychological performance. METHODS:MRI, including 3-dimensional T1-weighted imaging and diffusion tensor imaging, was performed in 23 adult patients with MMD and 23 age-matched controls and gray matter density and major diffusion tensor imaging indices were compared between them; any alterations in the patients were tested for associations with age, ischemic symptoms, hemodynamic compromise, and neuropsychological performance. RESULTS:Decrease in gray matter density, associated with hemodynamic compromise (P<0.05), was observed in the posterior cingulate cortex of patients with MMD. Widespread reduction in fractional anisotropy and increases in radial diffusivity and mean diffusivity in some areas were also observed in bilateral cerebral white matter. The fractional anisotropy (r=0.54; P<0.0001) and radial diffusivity (r=-0.41; P<0.01) of white matter significantly associated with gray matter density of the cingulate cortex. The mean fractional anisotropy of the white matter tracts of the lateral prefrontal, cingulate, and inferior parietal regions were significantly associated with processing speed, executive function/attention, and working memory. CONCLUSIONS:In adult MMD, there were more white matter abnormalities than gray matter changes. Disruption of white matter may play a pivotal role in the development of cognitive dysfunction. 10.1161/STROKEAHA.114.007407