【摘要】 目的 探讨不同阿尔茨海默病（AD）相关病理负荷及认知状态下脑血流量（CBF）及脑血流网络的改变，深化对AD疾病谱系中神经生物学机制的理解。方法 从阿尔茨海默病神经影像学倡议（ADNI）数据库确定29例淀粉样蛋白β(Aβ)阴性的认知正常者（Aβ-CN组）、34例Aβ阳性的认知正常者（Aβ+CN组）和39例Aβ阳性的认知障碍者（Aβ+CI组）。搜集受试者的人口学资料、神经心理学测试结果及影像学数据。从动脉自旋标记（ASL）成像中获取CBF信息，使用基于体素的形态学分析（VBM）方法比较得到三组受试者CBF存在差异的脑区，并将这些脑区的CBF与神经心理学测试量表得分进行偏相关分析。构建基于CBF值的脑血流网络并利用图论分析方法分析网络全局属性及节点属性的变化特征。结果 三组间在额叶、颞叶、顶叶等脑区的CBF存在显著差异（GRF校正，体素水平均P<0.001，团簇水平均P<0.05）。其中Aβ+CN组较Aβ-CN组在双侧前扣带和旁扣带脑回、左侧顶下缘角回、左侧颞中回及左侧颞下回区域的CBF显著降低。Aβ+CI组较Aβ+CN组在右侧眶部额中回及左侧颞中回区域的CBF显著降低，较Aβ-CN组在所有差异脑区的CBF显著降低（P均<0.05）。相关性分析提示右侧眶部额中回CBF与阿尔茨海默病认知评估量表（ADAS）得分呈负相关（r=-0.338,P=0.011,FDR校正），左侧颞下回CBF与蒙特利尔认知评估量表（MoCA）得分呈正相关（r=0.329,P=0.011,FDR校正），右侧前扣带和旁扣带脑回CBF与MoCA得分呈正相关（r=0.280,P=0.044,FDR校正）。图论分析结果显示Aβ+CI组较Aβ+CN组全局效率显著降低（P=0.039）,Aβ+CI组较Aβ-CN组小世界属性和局部效率显著增加（P分别为0.034和0.032），全局效率显著降低（P=0.005）。结论 随着Aβ病理进展及认知功能下降，额叶、颞叶和顶叶等区域的CBF及脑血流网络模式发生显著改变，这些发现从CBF角度为AD疾病谱系的病理及神经生物学机制的探索提供了一定的理论研究基础。更多还原

【Abstract】 Objective To investigate alterations in cerebral blood flow(CBF) and cerebral blood flow network under different Alzheimer’s disease(AD)-related pathological burdens and cognitive states, and to deepen the understanding of neurobiological mechanisms in the AD disease spectrum. Methods Data were obtained from the Alzheimer’s Disease Neuroimaging Initiative(ADNI) database, including 29 Aβ-negative cognitively normal subjects(Aβ-CN), 34 Aβ-positive cognitively normal subjects(Aβ+ CN), and 39 Aβ-positive cognitively impaired subjects(Aβ+ CI). Demographic data, neuropsychological test results, and imaging data of the subjects were collected. CBF information was obtained from arterial spin labeling(ASL) imaging. Voxel-based morphometry was used to compare and identify brain regions with CBF differences among the three groups, and partial correlation analysis was conducted between CBF in these regions and scores of neuropsychological assessment scales. A cerebral blood flow network based on CBF values was constructed, and graph theory analysis was applied to explore the changing characteristics of global network properties and nodal properties. Results Significant differences in CBF among the three groups were observed in brain regions including the frontal lobe, temporal lobe, and parietal lobe(GRF correction, voxel-level P < 0.001, cluster-level P< 0.05). Compared with the Aβ-CN group, the Aβ+ CN group showed significantly decreased CBF in the bilateral anterior cingulate and paracingulate gyri, left inferior parietal angular gyrus, left middle temporal gyrus, and left inferior temporal gyrus. Compared with the Aβ+ CN group, the Aβ+ CI group had significantly decreased CBF in the right orbital part of the middle frontal gyrus and left middle temporal gyrus; compared with the Aβ-CN group, the Aβ+ CI group showed significantly decreased CBF in all the above-mentioned brain regions with differences(all P<0.05). Correlation analysis indicated that CBF in the right orbital part of the middle frontal gyrus was negatively correlated with the score of Alzheimer’s Disease Assessment Scale-Cognitive Subscale(ADAS-13)(r =-0.338, P= 0.011, FDR correction); CBF in the left inferior temporal gyrus was positively correlated with the score of Montreal Cognitive Assessment(MoCA)(r = 0.329, P = 0.011, FDR correction); CBF in the right anterior cingulate and paracingulate gyri was positively correlated with the MoCA score(r = 0.280, P= 0.044, FDR correction). Graph theory analysis results showed that compared with the Aβ+ CN group, the Aβ+ CI group had a significantly decreased global efficiency(P= 0.039); compared with the Aβ-CN group, the Aβ+ CI group had significantly increased small-worldness(P= 0.034) and local efficiency(P= 0.032), global efficiency was significantly decreased(P=0.005). Conclusion With the progression of Aβ pathology and the decline of cognitive function, CBF and cerebral blood flow network patterns in regions such as the frontal lobe, temporal lobe, and parietal lobe undergo significant changes. These findings provide a certain theoretical basis for exploring the pathological and neurobiological mechanisms of the AD disease spectrum from the perspective of cerebral blood flow.更多还原