Abstract
BACKGROUND: Cognitive impairment is a complication of type 2 diabetes with high prevalence and serious harm. This study aims to identify serum and imaging biomarkers of type 2 diabetes with mild cognitive impairment (MCI) and to study whether spontaneous brain activities evaluated by functional MRI mediate the relationships between these serum neuroprotein biomarkers and cognitive ability. METHODS: According to Montreal Cognitive Assessment (MoCA) scores, 38 patients with MCI and 32 patients with normal cognition in type 2 diabetes were recruited. Serum neuroproteins were determined with Olink Proteomics. Brain activities were evaluated by functional MRI. Logistic regression were performed to determine the biomarkers of type 2 diabetes with MCI. Mediation analysis were performed to examine the potential causal chain between the neuroproteins and cognitive ability. RESULTS: The levels of Epiregulin (EREG), Abhydrolase domain containing 14B (ABHD14B) and Inositol monophosphatase 1 (IMPA1) decreased, while the level of Cysteine-rich intestinal protein 2 (CRIP2) increased in type 2 diabetic patients with MCI (FDR p < 0.05). Combination of EREG and CRIP2, a ROC curve was generated with an AUC of 0.85 and an accuracy of 70.0%, and a sensitivity of 86.7% for diagnosing type 2 diabetes with MCI. Brain activities in bilateral superior parietal gyrus, bilateral postcentral gyrus, left inferior frontal gyrus, right cerebellum 6, left cerebellum crus1 decreased, while increased in right hippocampus and left middle frontal gyrus in type 2 diabetic patients with MCI (FDR p < 0.05). The mALFF values in the left cerebellum crus-1 mediated 29.1% of the association between the EREG and MoCA scores (p < 0.001). The mALFF values in the right cerebellum-6, left cerebellum crus-1, right hippocampus, right superior parietal gyrus and right postcentral gyrus all significantly and partially mediated the association between ABHD14B levels and MoCA scores, with mediating effects of 21.7%, 27.1%, 25.8%, 20.7% and 19.2%, respectively (all p values < 0.001). CONCLUSIONS: Type 2 diabetic patients with MCI exhibit specific serum neuroprotein and functional MRI characteristics. The relationships between these neuroproteins and cognitive ability were mediated by spontaneous brain activities.