Background and purpose The role of intracranial steno-occlusive disease in cognitive impairment and dementia is unclear and has not been well studied. Methods A total of 32 consecutive patients (13 males, aged 54 +/- 12 years) with asymptomatic steno-occlusive middle cerebral artery (MCA) disease, defined as >70% stenosis on maximum intensity projection images or a complete signal loss of MCA trunk on magnetic resonance angiography, and 20 age- and education-matched normal controls (12 males, 60 +/- 8 years old) were compared for neuropsychological performance, gray matter volume and neural network analysis. Results The patient group did not show a significant decrease in gray matter volume or cognitive tests except for their performance on the grooved pegboard test. However, graph analysis of resting-state functional magnetic resonance imaging showed significant decreases in network strength, global efficiency and the clustering coefficient, as well as a longer characteristic path length (P < 0.05). The diffusive decrease pattern was particularly located in interhemispheric connectivity and there was no compensatory hyperconnectivity in any brain regions. Conclusion In asymptomatic steno-occlusive MCA disease, cognition and neural network changes are mismatched and have underlying pathophysiological mechanisms that are different from those of neurodegenerative disease.