神经血管耦联受损是2型糖尿病合并认知功能障碍的可能机制

Neurovascular uncoupling as a possible mechanism of cognitive impairment in patients with type 2 diabetes mellitus

目的探讨2型糖尿病(type 2 diabetes mellitus,T2DM)患者神经血管耦联(neurovascular coupling,NVC)功能与认知损害的关系。方法连续纳入2022年2月1日―2023年2月28日在海南医学院第二附属医院内分泌科住院的192例2型糖尿病患者和30例性别、年龄、受教育年限相匹配的健康对照(healthy control,HC),收集一般临床资料。所有受试者均进行蒙特利尔认知评估(Montreal Cognitive Assessment,MoCA)量表测试。应用功能经颅多普勒(fTCD)监测主动屈肘任务时脑血流速度曲线(cerebral blood flow velocity,CBFV)的动态变化来评估神经血管耦联功能。根据MoCA评分将T2DM患者分为T2DM认知正常(normal cognition,T2DM-NC)组和T2DM认知受损(impaired cognition,T2DM-IC)组。比较HC组、T2DM-NC组、T2DM-IC组3组间fTCD参数差异,分析fTCD参数与认MoCA评分的相关性。结果共纳入T2DM患者81例,HC组21例。T2DM组患者中包括T2DM-NC组52例,T2DM-IC组29例。T2DM-IC组糖化血红蛋白高于T2DM-NC组及HC组,差异有统计学意义(均P<0.05)。T2DM组患者运动平均脑血流速度(mean velocity,Vm)较基线增加百分比(ΔVm)、归一化运动Vm曲线下面积(normalized area under the curve,nAUC)和Vm斜率均低于HC组(均P<0.05)。3组归一化处理后,T2DM-IC组的nAUC显著低于HC组和T2DM-NC组,HC组Vm上升斜率显著高于T2DM-NC组和T2DM-IC组,差异有统计学意义(均P<0.01)。相关性分析示:ΔVm(r=0.343,P=0.001)及nAUC(r=0.356,P=0.001)与MoCA评分均呈正相关。基线搏动指数(pulsatility index,PI)(r=-0.496,P<0.001)、基线阻力指数(resistance index,RI)(r=-0.475,P<0.001)、运动PI(r=-0.542,P<0.001)、运动RI(r=-0.523,P<0.001)与MoCA评分均呈负相关。结论神经血管耦联功能受损是T2DM患者出现认知功能障碍的可能原因。

Objective To investigate the relationship between neurovascular coupling and cognitive impairment in patients with type 2 diabetes mellitus(T2DM).Methods We consecutively enrolled 192 patients with T2DM admitted to the Department of Endocrinology in The Second Affiliated Hospital of Hainan Medical University as well as 30 healthy con⁃trols matched for sex,age,and years of education from February 1,2022 to February 28,2023.General clinical data were collected.All the participants were tested with the Montreal Cognitive Assessment(MoCA).Neurovascular coupling function was assessed through the dynamic changes in cerebral blood flow velocity(CBFV)induced by active elbow flexion monitored using functional transcranial Doppler sonography(fTCD).Patients with T2DM were divided into normal cogni⁃tion(T2DM-NC)group and impaired cognition(T2DM-IC)group according to the MoCA score.The fTCD parameters were compared between the HC group,T2DM-NC group,and T2DM-IC group.The correlation between fTCD parameters and MoCA score was analyzed.Results A total of 81 patients with T2DM(52 with T2DM-NC and 29 with T2DM-IC)and 21 healthy volunteers were enrolled in this study.The glycated hemoglobin level was significantly higher in the T2DMIC group than in the T2DM-NC and HC groups.Compared with the HC group,the T2DM group showed a significantly smaller percentage change from baseline in mean CBFV(Vm)during motor(ΔVm),a significantly smaller normalized area under the curve of Vm during motor(nAUC),and a significantly lower Vm slope(all P<0.05).After normaliza⁃tion,the nAUC was significantly lower in the T2DM-IC group than in the T2DM-NC and HC groups,and the upward slope of Vm was significantly higher in the HC group than in the T2DM-NC and T2DM-IC groups(all P<0.01).TheΔVm(r=0.343,P=0.001)and nAUC(r=0.356,P=0.001)were positively correlated with MoCA score.Baseline pulsatility index(PI,r=−0.496,P<0.001),baseline resistance index(RI,r=−0.475,P<0.001),PI during motor(r=−0.542,P<0.001),and RI during motor(r=−0.523,P<0.001)were negatively correlated with MoCA score.Conclusion Neurovascular uncoupling is a possible cause of cognitive impairment in patients with T2DM.