轻度认知障碍患者海马和皮质下核团形状特征预测AD病理改变的研究

Morphological characteristics of hippocampus and subcortical nuclei in mild cognitive impairment patients and its prediction of pathological changes in Alzheimer’s disease

目的:探索皮质下核团的形状在轻度认知障碍(MCI)中的改变特征,及其在无创性预测AD源性MCI上的临床意义。方法:搜集AD神经影像学项目(ADNI)数据库中MCI组112例及正常对照组(NC)140例,采用顶点分析法比较组间海马,丘脑、杏仁核等皮质下核团的形状,并与简明精神状态量表(MMSE)评分、脑脊液β淀粉样蛋白42(Aβ42)、总Tau蛋白(t-Tau)及磷酸化Tau蛋白(p-Tau)水平作相关性分析。进一步根据脑脊液Aβ42及p-Tau的水平,将MCI患者分为A+T+(Aβ42及p-Tau均阳性)、A+T-(Aβ42阳性,p-Tau阴性)与A-T-(Aβ42及p-Tau均阴性)3个亚组,比较组间皮质下核团的形状差异。结果:MCI组相比于NC组的左侧海马背外侧、右侧海马腹内侧、左侧丘脑前背侧、右侧丘脑背内侧、双侧杏仁核前背侧及左侧尾状核前内侧出现显著萎缩(P<0.01)。双侧海马、丘脑及杏仁核的形变量与MMSE及Aβ42呈显著正相关(P<0.05);左侧尾状核形变量与MMSE呈显著正相关,与Aβ42无显著相关;左侧杏仁核形变量与t-Tau及p-Tau呈显著负相关,其余核团与t-Tau及p-Tau未见显著相关。MCI患者中A+T+组比A-T-组的左侧杏仁核前背侧显著萎缩(P<0.05),而A+T+与A+T-及A+T-与A-T-的组间比较未见统计学差异。结论:MCI患者的皮质下核团表面形状存在特异性改变,且伴随不同AD病理改变的MCI亚组间,核团的损伤机制存在差异。表明皮质下核团形状分析有助于早期诊断MCI并预测AD源性MCI,从而实现针对性干预和治疗,延缓AD病情进展。

Objective To explore the shape change of subcortical nuclei in mild cognitive impairment(MCI)patients and it’s clinical significance in noninvasive prediction of MCI of AD origin.Methods 112MCI patients and 140 normal controls(NC)from Alzheimer’s disease Neuroimaging Initiative(ADNI)were enrolled.The shape of hippocampus and subcortical nuclei,such as thalamus and amygdala were compared between groups by vertex analysis and the correlations between shape change and Mini-Mental State Examination(MMSE),cerebrospinal fluid Amyloidβ-protein 42(Aβ42),total Tau(t-Tau)and phosphorylated Tau(p-Tau)were analyzed.According to the level of cerebrospinal fluid Aβ42 and p-Tau,MCI patients were further divided into 3 subgroups as A+T+(both positive for Aβ42 and p-Tau),A+T-(positive for Aβ42 while negative for p-Tau)and A-T-(both negative for Aβ42 and p-Tau),and the shape of subcortical nuclei were also compared between groups.Results Compared with the NC group,MCI group showed significant atrophy in left dorsolateral hippocampus,right ventromedial hippocampus,left anterodorsal thalamus,right dorsomedial thalamus,bilateral anterodorsal amygdala and left anteromedial caudate(P<0.01).The surface deformation degree of bilateral hippocampus,thalamus and amygdala were significantly positively correlated with MMSE and Aβ42,while that of the left caudate was significantly positively correlated with MMSE but not with Aβ42;the deformation degree of the left amygdala was negatively correlated with t-Tau and p-Tau,while other nuclei showed no correlation(P<0.05).Among MCI patients,the left anterodorsal amygdala of A+T+group showed significantly atrophy than A-T-group,while the comparison between A+T+and A+T-and the comparison between A+T-and A-T-showed no significant difference(P<0.05).Conclusion There are specific changes in the shape of subcortical nuclei in MCI patients,and the damage mechanism of nuclei showed significant difference in MCI subgroups with various pathological processes of AD.It is suggested that shape analysis of the subcortical nuclei is helpful for early diagnosis of MCI and prediction of MCI of AD origin,so as to achieve targeted intervention and treatment and to delay the progression of AD.