Moyamoya disease and cerebrovascular atherosclerotic disease are both chronic ischemic diseases with similar presentations of vascular cognitive impairment. The aim of the present study was to investigate the patts of microstructural damage associated with vascular cog-nitive impairment in the two diseases. The study recruited 34 patients with moyamoya disease (age 43.9 ± 9.2 years; 20 men and 14 women, 27 patients with cerebrovascular atherosclerotic disease (age: 44.6 ± 7.6 years; 17 men and 10 women), and 31 normal controls (age 43.6 ± 7.3 years; 18 men and 13 women) from Huashan Hospital of Fudan University in China. Cognitive function was assessed using the Mini-Mental State Examination, long-term delayed recall of Auditory Verbal Leing Test, Trail Making Test Part B, and the Symbol Digit Modalities Test. Single-photon emission-computed tomography was used to examine cerebral perfusion. Voxel-based morphometry and tract-based spatial statistics were performed to identify regions of gray matter atrophy and white matter deterioration in patients and normal controls. The results demonstrated that the severity of cognitive impairment was similar between the two diseases in all tested domains. Patients with moyamoya disease and those with cerebrovascular atherosclerotic disease suffered from disturbed supratentorial hemodynamics. Gray matter atrophy in bilateral middle cingulate cortex and parts of the frontal gyrus was prominent in both diseases, but in general, was more severe and more diffuse in those with moyamoya disease. White matter deterioration was significant for both diseases in the genu and body of corpus callosum, in the anterior and superior corona radiation, and in the posterior thalamic radiation, but in moyamoya disease, it was more diffuse and more severe. Vascular cognitive impairment was associated with regional microstructural damage, with a potential link between, gray and white matter damage. Overall, these results provide insight into the pathophysiological nature of vascular cognitive im-pairment. This study was approved by the Institutional Review Board in Huashan Hospital, China (approval No. 2014-278). This study was registered with ClinicalTrials.gov on December 2, 2014 with the identifier NCT02305407.