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Background and Objective: D-dimer prompts fibrinolysis system, which is involved in Alzheimer’s disease and the complications of type 2 diabetic patients, especially among those with carotid artery plaques. Hence, this study aims to investigate the role of D-dimer in early cognitive impairment among type 2 diabetic patients with carotid artery plaques. Methods: A total of 175 Chinese patients with type 2 diabetes were recruited and divided into two groups according to the Montreal Cognitive Assessment score. Demographic data were collected, plasma D-dimer was tested through VIDAS D-dimer New, neuropsychological tests were examined, and carotid artery plaques were detected by ultrasound and further stratified by vulnerability and level. Results: A total of 67 types 2 diabetic patients with Mild Cognitive Impairment (MCI) displayed significantly increased plasma D-dimer levels compared with their health-cognition controls (p = 0.011). Plasma D-dimer concentration was negatively related with Digit Span Test scores in diabetic patients with vulnerable plaques (r=-0.471, p=0.023) and Stroop Color Word Test C (number) in diabetic patients with stable plaques (r=-0.482, p<0.001). Multivariable regression analysis further showed that D-dimer concentration was an independent factor of diabetic MCI with carotid artery plaque (p=0.005), and D-dimer concentration especially contributed to the high risk of MCI with vulnerable plaques (p=0.028) or high levels of carotid plaque (p=0.023). Conclusion: Elevated D-dimer level predicts the high risk of early cognitive impairment in type 2 diabetic patients with carotid artery plaques, especially vulnerable plaques or high levels of carotid plaques.