轻度认知损伤（mild cognitive impairment, MCI）被认为是健康老化向阿尔茨海默病（Alzheimer’s disease, AD）转化的阶段。MCI病人在不该出现认知损伤的年纪却出现并不影响其日常生活的不同的认知损伤。前人研究报告了在MCI病人中，局部或长程的功能连接模式出现异常，但是很少有研究同时考察MCI病人局部至长程功能连接的异常模式，更少有研究探讨载脂蛋白E（Apolipoprotein E, ApoE）ε4等位基因对MCI距离相关功能连接的影响。本研究对以上问题进行了研究。研究一使用基于二维皮层表面的局部功能一致性及种子点功能连接的方法，对轻度认知损伤病人与健康对照组的静息态脑功能活动进行了考察，并且对病人组局部损伤相关的全脑长程功能连接异常模式进行了研究。结果显示，与健康对照组相比，MCI病人默认网络局部功能一致性显著降低，而与局部功能连接相关的长程功能连接改变主要位于默认网络（下降）、注意网络和感知运动网络（上升），且上升的功能连接与MCI患者情景记忆能力的提升显著相关。我们进一步地使用同样的方法，在研究二中考察ApoE ε4基因对不同病程的MCI病人距离相关的功能连接变化的影响。结果显示，携带ApoE ε4等位基因的晚期MCI病人，其额上回局部功能连接上升；结果还表明ApoE ε4基因携带者，默认网络和感知运动网络，与其他大尺度功能网络脑区，如感知运动网络和背侧注意网络/额顶控制网络长程功能连接的下降，以及感知运动网络与背侧注意网络/视觉网络关键脑区长程功能连接的上升。这些受基因和病程影响的距离相关的大脑功能连接异常模式的发现，对我们深入了解病理老化的发病机制具有重要意义。

Mild cognitive impairment (MCI) is considered as a transitional stage between normal aging and Alzheimer’s disease (AD). MCI patients suffer cognitive declines, which are unexpected based on the individual age but do not significantly interfere with their daily life. Alterations in both local and remote connectivity were reported inMCIpatients but rarely in the same group of patients; moreover, few studies investigated the effect of the distance-related functional connectivity by the high risk genotype-apolipoprotein E(ApoE) ε4allele-for Alzheimer’s disease. In the studyI, we first employed a novel resting-state functional magnetic resonance imaging (rfMRI)connectome index, regional functional homogeneity on the two-dimensional cortical surface, to detect full-cortex vertex-wise changes of the local rfMRI connectivity in 32 aMCI patients compared with 40 healthy controls, we thenused the seed-based functional connectivity to explore the remote rfMRI connectivity in aMCIpatients.The results revealed significantly lower local connectivity in the default network and higher local connectivity in the somatomotor network in aMCI patients. Abnormal remote connectivity relevant to local connectivity was primarily detectable within the default network (decrease)and in the attention and somatomotor networks (increase), which significantly associated with episodic memory performance in aMCI patients. In the study II, we used the same approachto investigatethe altered distance-related functional connectivity patternin early and late ApoEε4allele genotypecarriers and non-carriers. The results showed that the strengthened regional functional connectivity of superior frontal gyrus in lateMCIApoE ε4carriers, and detected the disrupted remote functional connectivity between default modeand somatomotor network anddorsalattention/frontoparietal controland somatomotor network regionsand enhanced remote functional connectivity between somatomotor network and ventral attention/visual network in MCI ApoE ε4carriers. These distance-related connectivity profiles illustrated a dysfunctional pattern that moderated by diagnosis and genemay help us revealthe underlying mechanisms of this pathological aging process.