认知意识受损对遗忘型轻度认知功能障碍患者的自我参照网络及病理标志物的影响

Effect of impaired cognitive awareness on the characteristics of self-referential network and pathological markers in amnestic mild cognitive impairment patients

目的:对伴有认知意识受损的遗忘型轻度认知功能障碍(amnestic mild cognitive impairment,aMCI)患者的自我参照网络(self-referential network,SRN)和脑脊液病理标志物β-淀粉样蛋白(amyloidβ-protein,Aβ),总Tau蛋白(total Tau,t-Tau)和磷酸化Tau蛋白(phosphorylated Tau,p-Tau)改变特征进行研究。方法:共纳入51例aMCI患者,根据认知意识指数将其分为认知意识受损aMCI组(n=20)与认知意识保留aMCI组(n=31)。两组患者均行静息态功能磁共振、腰椎穿刺、认知评估检查,采用独立成分分析方法提取SRN;用双样本t检验比较两组间SRN功能连接和脑脊液(Aβ,t-tau和p-tau)改变;用Pearson相关分析探讨认知意识指数与功能连接改变和脑脊液Aβ,t-tau和p-tau水平的关系。结果:认知意识受损aMCI组较认知意识保留aMCI组在双侧内侧眶额叶皮层、左侧前扣带回和右侧直回显示出功能连接增强(AlphaSim校正,P<0.001,体素数>17),两组间脑功能连接差异脑区信号值与认知意识指数呈负相关(r=-0.457,P<0.001)。认知意识受损aMCI组较认知意识保留aMCI组脑脊液Aβ水平明显降低(P<0.01),脑脊液t-tau水平(P<0.001)和p-tau水平(P<0.001)显著升高,Aβ水平与认知意识指数呈正相关(r=0.331,P=0.025),t-tau、p-tau水平与认知意识指数呈负相关(r=-0.534,-0.508,P均<0.001)。结论:SRN是认知意识的神经影像基础;伴有认知意识受损的aMCI患者存在SRN的功能连接受损和更严重的阿尔茨海默病病理标志物的沉积。

Objective:To analyse the changes of self-referential network(SRN)and cerebrospinal fluid pathological markers amyloidβ-protein(Aβ),total tau(t-tau)and phosphorylated tau(p-tau)for patients with amnestic mild cognitive impairment(aMCI).Methods:A total of 51 aMCI patients were enrolled in the study.According to the cognitive awareness index,they were divided into the aMCI group with impaired cognitive awareness(n=20)and the aMCI group(n=31)with cognitive awareness preserved.All patients underwent resting functional magnetic resonance(rsfMRI),lumbar puncture,and cognitive assessment.Independent component analysis was used to extract SRN;two-sample t test was used to explore the functional connectivity of SRN and cerebrospinal fluid(Aβ,t-tau and p-tau)changes;Pearson correlation analysis was used to explore the relationship between cognitive awareness index and functional connectivity changes and the levels of cerebrospinal fluid Aβ,t-tau and p-tau.Results:The aMCI group with impaired cognitive awareness showed hyperconnectivity in the bilateral medial orbitofrontal cortex,left anterior cingulate gyrus and right rectus gyrus(AlphaSim correction,P<0.001,voxel number>17).The difference in brain function connectivity between the two groups was negatively correlated with the cognitive awareness index(r=-0.457,P<0.000).The level of Aβin cerebrospinal fluid in the aMCI group with impaired cognitive awareness was significantly lower than that of the aMCI group with cognitive awareness preserved(P<0.01),p-tau and t-tau in cerebrospinal fluid were significantly increased than those of the aMCI group with cognitive awareness preserved(P<0.001).The cerebrospinal fluid Aβlevel was positively correlated with cognitive awareness index(r=0.331,P=0.025),and cerebrospinal fluid t-tau and p-tau levels were negatively correlated with cognitive consciousness index(r=-0.534,-0.508,both P<0.001).Conclusion:SRN is the neuroimaging basis of cognitive awareness;aMCI patients with impaired cognitive awareness have impaired functional connectivity of SRN and more severe deposition of Alzheimer′s disease pathological markers.