Objective To investigate the changes of amyloid β-protein（Aβ）42，bilirubin and Mn-superoxide dismutase（Mn‑ SOD）in patients with Alzheimer's disease（AD），and their correlation with cognitive impairment. Methods A total of 106 patients with AD who were treated in the First Affiliated Hospital of Henan University from August 2020 to August 2022 were selected as the observation group. Meanwhile，110 age and gender-matched healthy elderly controls were selected as the control group. The general data of all subjects were analyzed，and cognitive function was evaluated with the Montreal Cognitive Assessment（MoCA）Scale. Serum Aβ 42，bilirubin and MnSOD levels were determined by enzyme-linked immunosorbent assay（ELISA）. Serum Aβ42，bilirubin and Mn‑ SOD under different electroencephalogram（EEG）monitoring results were comparatively analyzed. The relationship of serum indexes with EEG abnormalities and MoCA scores in patients with AD was analyzed. Results Serum Aβ42，bilirubin and MnSOD in the observation group were significantly lower than those in the control group（P < 0.05）. Univariate analysis results showed that MoCA scores of patients with Aβ42 ≤ 2.33 mg/L，bilirubin ≤ 20 umol/L，MnSOD ≤ 104.20 NU/mL and severe EEG abnormalities were significantly lower（P < 0.05）. Multiple linear regression analysis results showed that Aβ42 ≤ 2.33 mg/L，bilirubin ≤ 20 umol/L，MnSOD ≤ 104.20 NU/mL and severe EEG abnormalities were risk factors for cognitive impairment in patients with AD（P < 0.05）. Serum Aβ42，bilirubin and MnSOD in patients with different severity of EEG abnormalities were significantly different（P < 0.05）. Correlation analysis results showed that serum Aβ42，bilirubin and MnSOD were closely related to MoCA score and EEG abnormality（P < 0.05）. Conclusion Serum Aβ42，bilirubin and MnSOD in patients with AD were significantly lower than those in the normal elderly group. Besides， these indexes were closely related to cognitive impairment and the severity of EEG abnormality，which indicated that they could be used for early prediction of cognitive dysfunction，and help to take targeted measures for patients with AD as soon as possible.