This study aimed to analyze the characteristics of cognitive impairment in adult-onset neuronal intranuclear inclusion disease (NIID). Seven patients with adult-onset NIID were collected consecutively from the memory clinic of Xuanwu hospital from February to December 2019. These cases were diagnosed with skin biopsy triggered by DWI high-intensity signals in corticomedullary junction on brain MRI. We used a battery of neuropsychological scales to detect the patient's performance in each cognitive domain, and made a detailed analysis on the characteristics of cognitive impairment. All seven cases had cognitive impairment, and four of them had met the criteria for dementia. The scores of Montreal Cognitive Assessment and Frontal Assessment Battery were abnormal in all patients. The executive dysfunction was confirmed by the abnormal scores of Trail Making Test (5/7, 71%) and Clock Drawing Test (4/7, 57%). Bad performance in Auditory Verbal Learning Test (6/7, 86%) demonstrated that the memory was also a very commonly impaired cognitive domain. The low score on the animal fluency (4/7, 57%), Boston Naming Test (3/7, 43%), and Pentagon and Cube Copying Test (4/7, 57%) indicated that the language and visuospatial skills were also impaired. Fazekas scores were significantly correlated to the global cognition, executive and language functions (r = 0.788-0.906, P < 0.05). There is obvious impairment in multiple cognitive domains in adult-onset NIID, and both the executive dysfunction and memory deficit are very common. Leukoencephalopathy may be the main course of cognitive impairment in adult-onset NIID.