Periphery Biomarkers for Objective Diagnosis of Cognitive Decline in Type 2 Diabetes Patients

用于客观诊断 2 型糖尿病患者认知能力下降的外周生物标志物

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作者:Yanchao Liu, Shujuan Zhang, Benrong He, Liangkai Chen, Dan Ke, Shi Zhao, Yao Zhang, Wei Wei, Zhipeng Xu, Zihui Xu, Ying Yin, Wen Mo, Yanni Li, Yang Gao, Shihong Li, Weijin Wang, Huiling Yu, Dongqin Wu, Guilin Pi, Tao Jiang, Mingmin Deng, Rui Xiong, Huiyang Lei, Na Tian, Ting He, Fei Sun, Qiuzhi Zhou

Conclusion

A combination of the elevated plasma Aβ1-42/Aβ1-40 with activated platelet GSK-3β, ApoE ε4 genotype, olfactory decline, and aging could efficiently diagnose MCI in T2DM patients. Further longitudinal studies may consummate the model for early prediction of AD.

Methods

Eight hundred fifty-two T2DM patients collected from five medical centers were assigned randomly to training and validation cohorts. Plasma Aβ, platelet glycogen synthase kinase-3β (GSK-3β), apolipoprotein E (ApoE) genotypes, and olfactory and cognitive functions were measured by ELISA, dot blot, RT-PCR, Connecticut Chemosensory Clinical Research Center (CCCRC) olfactory test based on the diluted butanol, and Minimum Mental State Examination (MMSE) test, respectively, and multivariate logistic regression analyses were applied.

Results

Elevation of plasma Aβ1-42/Aβ1-40 is an independent risk factor of MCI in T2DM patients. Although using Aβ1-42/Aβ1-40 alone only reached an AUC of 0.631 for MCI diagnosis, addition of the elevated Aβ1-42/Aβ1-40 to our previous model (i.e., activated platelet GSK-3β, ApoE ε4 genotype, olfactory decline, and aging) significantly increased the discriminating efficiency of T2DM-MCI from T2DM-nMCI, with an AUC of 0.846 (95% CI: 0.794-0.897) to 0.869 (95% CI: 0.822-0.916) in the training cohort and an AUC of 0.848 (95% CI: 0.815-0.882) to 0.867 (95% CI: 0.835-0.899) in the validation cohort, respectively.

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