PDF(Pubmed)
Abstract：
UNASSIGNED: Our previous multicenter case-control study showed that aging, up-regulation of platelet glycogen synthase kinase-3β (GSK-3β), impaired olfactory function, and ApoE ϵ4 genotype were associated with cognitive decline in type 2 diabetes mellitus (T2DM) patients. However, the causal relationship between these biomarkers and the development of cognitive decline in T2DM patients remains unclear.
UNASSIGNED: To further investigate this potential relationship, we designed a 6-year follow-up study in 273 T2DM patients with normal cognitive in our previous study. Baseline characteristics of the study population were compared between T2DM patients with and without incident mild cognitive impairment (MCI). We utilized Cox proportional hazard regression models to assess the risk of cognitive impairment associated with various baseline biomarkers. Receiver operating characteristic curves (ROC) were performed to evaluate the diagnostic accuracy of these biomarkers in predicting cognitive impairment.
UNASSIGNED: During a median follow-up time of 6 years (with a range of 4 to 9 years), 40 patients (16.13%) with T2DM developed MCI. Participants who developed incident MCI were more likely to be older, have a lower education level, have more diabetic complications, a higher percentage of ApoE ϵ4 allele and a higher level of platelet GSK-3β activity (rGSK-3β) at baseline (P<0.05). In the longitudinal follow-up, individuals with higher levels of rGSK-3β were more likely to develop incident MCI, with an adjusted hazard ratio (HR) of 1.60 (95% confidence interval [CI] 1.05, 2.46), even after controlling for potential confounders. The AUC of the combination of age, rGSK-3β and ApoEϵ4 allele predicted for incident MCI was 0.71.
UNASSIGNED: Platelet GSK-3β activity could be a useful biomarker to predict cognitive decline, suggesting the feasibility of identifying vulnerable population and implementing early prevention for dementia.
UNASSIGNED: To further investigate this potential relationship, we designed a 6-year follow-up study in 273 T2DM patients with normal cognitive in our previous study. Baseline characteristics of the study population were compared between T2DM patients with and without incident mild cognitive impairment (MCI). We utilized Cox proportional hazard regression models to assess the risk of cognitive impairment associated with various baseline biomarkers. Receiver operating characteristic curves (ROC) were performed to evaluate the diagnostic accuracy of these biomarkers in predicting cognitive impairment.
UNASSIGNED: During a median follow-up time of 6 years (with a range of 4 to 9 years), 40 patients (16.13%) with T2DM developed MCI. Participants who developed incident MCI were more likely to be older, have a lower education level, have more diabetic complications, a higher percentage of ApoE ϵ4 allele and a higher level of platelet GSK-3β activity (rGSK-3β) at baseline (P<0.05). In the longitudinal follow-up, individuals with higher levels of rGSK-3β were more likely to develop incident MCI, with an adjusted hazard ratio (HR) of 1.60 (95% confidence interval [CI] 1.05, 2.46), even after controlling for potential confounders. The AUC of the combination of age, rGSK-3β and ApoEϵ4 allele predicted for incident MCI was 0.71.
UNASSIGNED: Platelet GSK-3β activity could be a useful biomarker to predict cognitive decline, suggesting the feasibility of identifying vulnerable population and implementing early prevention for dementia.
摘要：
■我们之前的多中心病例对照研究表明，血小板糖原合成酶激酶-3β(GSK-3β)上调,嗅觉功能受损，ApoEε4基因型与2型糖尿病（T2DM）患者认知功能下降有关。然而,这些生物标志物与T2DM患者认知功能减退之间的因果关系尚不清楚.
■为了进一步研究这种潜在的关系，我们设计了一项为期6年的随访研究,纳入了我们之前研究的273例认知正常的T2DM患者.比较了有和没有轻度认知障碍（MCI）的T2DM患者的研究人群的基线特征。我们利用Cox比例风险回归模型来评估与各种基线生物标志物相关的认知障碍的风险。进行受试者工作特征曲线（ROC）以评估这些生物标志物在预测认知障碍中的诊断准确性。
■在6年的中位随访时间内（范围为4至9年），40例（16.13%）T2DM患者发生MCI。发生MCI事件的参与者更有可能年龄较大，教育水平较低，有更多的糖尿病并发症，较高的ApoEε4等位基因百分比和较高水平的血小板GSK-3β活性（rGSK-3β）在基线（P<0.05）。在纵向随访中，rGSK-3β水平较高的个体更有可能发生事件MCI，调整后的风险比（HR）为1.60（95％置信区间[CI]1.05，2.46），即使在控制了潜在的混杂因素之后。年龄组合的AUC，预测事件MCI的rGSK-3β和ApoEε4等位基因为0.71。
■血小板GSK-3β活性可能是预测认知衰退的有用生物标志物，提示识别脆弱人群和实施早期预防痴呆的可行性。
■为了进一步研究这种潜在的关系，我们设计了一项为期6年的随访研究,纳入了我们之前研究的273例认知正常的T2DM患者.比较了有和没有轻度认知障碍（MCI）的T2DM患者的研究人群的基线特征。我们利用Cox比例风险回归模型来评估与各种基线生物标志物相关的认知障碍的风险。进行受试者工作特征曲线（ROC）以评估这些生物标志物在预测认知障碍中的诊断准确性。
■在6年的中位随访时间内（范围为4至9年），40例（16.13%）T2DM患者发生MCI。发生MCI事件的参与者更有可能年龄较大，教育水平较低，有更多的糖尿病并发症，较高的ApoEε4等位基因百分比和较高水平的血小板GSK-3β活性（rGSK-3β）在基线（P<0.05）。在纵向随访中，rGSK-3β水平较高的个体更有可能发生事件MCI，调整后的风险比（HR）为1.60（95％置信区间[CI]1.05，2.46），即使在控制了潜在的混杂因素之后。年龄组合的AUC，预测事件MCI的rGSK-3β和ApoEε4等位基因为0.71。
■血小板GSK-3β活性可能是预测认知衰退的有用生物标志物，提示识别脆弱人群和实施早期预防痴呆的可行性。
