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Background and aims: Recent studies demonstrated that a signal change of functional magnetic resonance imaging (fMRI) in certain brain areas during the resting state is a significant marker in patients with mild cognitive impairment (MCI). However, the research of resting-state fMRI (rs-fMRI) on leukoaraiosis (LA) associated MCI is scarce. The aim of this study was to investigate differences of the rs-fMRI default network between patients with LA-associated MCI and normal subjects, and provide functional imaging evidence of LA-associated MCI during early stages of the disease.Method: All subjects were outpatients or thier residents of the Department of Neurology of the Beijing Tiantan Hospital. They were divided into MCI group and control group according to their cognitive function assessing by the Hamilton Depression Scale, Clinical Dementia Rating (CDR), Mini Mental State Exam and Montreal Cognitive Assessment. Demographic information was recorded. Brain MRI characteristics were assessed using the Fazekas scale. The independent components of fMRI data were analyzed by fMRI tool box. The experimental data and confounding factors were analyzed by General Liner Model.Results: A total of 31 right-handed patients with LA-associated MCI and 27 right-handed healthy control subjects were included. The active areas participating in the resting state for LA-associated MCI group were mostly consistent with those of the control group. Compared with controls, the LA-associated MCI patients exhibited significantly lower blood oxygen level-dependent (BOLD) signals in the left anterior cingulate cortex (P=0.021) and right parahippocampal gyrus (P=0.032). Whereas higher BOLD signals during the resting state in LA-associated MCI patients were observed in the left caudate nucleus (P=0.015), right frontal lobe (P=0.004), superior temporal gyrus and inferior parietal gyrus (P=0.001), No significant difference was shown in the posterior cingulate cortex and precuneus (P=0.138).Conclusion: Our findings demonstrated that the discriminating functional activation in specific brain areas could be identified in patients with LA-associated MCI, which might be used as an useful neuroimaging evidence for the early recognition of these patients.