目的： 1型糖尿病(Type 1 diabetes mellitus， T1DM)是糖尿病的一种特殊类型，是特指因胰岛β细胞破坏而导致胰岛素绝对缺乏，具有酮症倾向的代谢性疾病。目前有研究对1型糖尿病患者认知功能进行了探讨，但研究结果存在不一致性，而认知功能损伤的神经机制也不清楚。本研究试图通过检测1型糖尿病儿童青少年患者和儿童期起病(＜18岁)的1型糖尿病成年患者的认知功能，以了解1型糖尿病患者是否存在认知损伤及其损伤的特征；通过检测儿童期起病的1型糖尿病成年患者的脑影像特征及其与患者认知功能受损的关系，来探讨1型糖尿病患者认知功能损伤的神经机制。 方法： (1)对181名1型糖尿病儿童青少年患者与140名健康对照进行了韦氏智力测验、韦氏记忆测验、威斯康辛卡片分类测验(WSCT)等神经心理测验。比较两组在智力、记忆功能、注意与执行功能等认知功能的差异，并进一步分析慢性高血糖和严重低血糖以及严重低血糖初次发作年龄对1型糖尿病患者认知功能的影响。(2)对56名儿童期起病的1型糖尿病成年患者与64名的健康对照进行了韦氏智力测验、韦氏记忆测验、威斯康辛卡片分类测验(WSCT)、持续注意反应任务(SART)等神经心理测验，比较了两组被试在在智力、记忆功能、执行功能与持续注意等认知功能的差异。(3)30名儿童期起病的1型糖尿病患者和28名健康对照接受了核磁共振扫描，采用基于体素的形态学测量方法(VBM-DARTEL)测量两组被试的全脑灰质体积，比较两组被试大脑灰质结构的差异，并进一步分析患者大脑灰质结构改变与其认知功能损伤的关系。(4)采用低频振幅的方法(ALFF)对30名儿童期起病的1型糖尿病患者和28名健康对照的静息态数据进行分析，探讨1型糖尿病患者在静息状态下大脑神经元自发活动特征，并进一步分析患者静息态脑功能改变与其认知功能损伤的关系。 结果： (1)1型糖尿病儿童青少年患者在智商、相似性测验得分、言语听觉记忆测验得分均显著低于健康对照(p＜0.05)。有过严重低血糖发作的1型糖尿病患儿在相似性测验得分显著低于没有经历过严重低血糖发作的1型糖尿病患儿(p＜0.05)；严重低血糖早发作患儿在智商、木块图测验得分、视觉图形记忆测验得分均显著低于比严重低血糖迟发作患儿(p＜0.05)。高血糖暴露指数会影响1型糖尿病患儿的木块图测验得分(t=-3.162，p＜0.05)和WSCT持续错误得分(t= -2.479，p＜0.05)。 (2)儿童期起病的1型糖尿病成年患者在智商、数字广度测验得分、填图测验得分、木块图测验得分、言语听觉记忆测验得分、视觉图形记忆测验得分、WSCT总错误和持续错误得分均显著低于健康对照组，SART误按数显著多于健康对照组(p＜0.05)。 (3)1型糖尿病患者存在灰质体积的异常，异常的脑区主要表现在中脑和小脑蚓部，其灰质体积显著低于健康对照者。通过相关分析发现1型糖尿病患者的中脑灰质体积与言语听觉记忆测验得分呈正相关(r=0.439，p=0.025)，小脑蚓部灰质体积与WSCT连续错误得分呈正相关(r=0.436，p=0.033)。 (4)1型糖尿病患者存在静息态脑功能的异常，主要表现为在左侧中央前回、左侧中央后回、左侧脑岛、左侧顶叶缘上回、1型糖尿病患者的ALFF值显著增高；在右侧基底核(壳核)、右侧脑岛、右侧颞上回、左右侧小脑后叶，1型糖尿病患者的ALFF值显著降低。通过相关分析发现1型糖尿病患者的右侧脑岛与颞上回这一区域ALFF值与言语听觉记忆-延时呈显著正相关(r=0.422，p=0.040)，左侧小脑ALFF值与SART测验反应时呈显著负相关(r=-0.473，p=0.020)。 结论： (1)1型糖尿病儿童青少年患者存在认知功能损伤，主要表现为智力和言语听觉记忆功能下降，慢性高血糖会影响患者的空间感知觉和执行能力，而严重低血糖，尤其是发作在儿童期的早期阶段，会影响患者的记忆尤其是视觉空间记忆。儿童期起病的1型糖尿病患者在成年后仍会出现认知功能的损伤，主要表现在智力、言语听觉记忆、视觉图形记忆、持续注意和执行功能等方面的损伤。 (2)儿童期起病的1型糖尿病成年患者的脑结构和功能发生改变，脑结构异常主要是中脑和小脑蚓部的灰质体积减小，脑功能异常主要表现为中央前回、中央后回、脑岛、左右侧小脑神经元自发活动的异常。这些脑区结构与功能的异常可能是患者认知功能损伤的神经病理学基础。 图27幅，表16个，参考文献276篇 关键词：认知发展；认知功能；1型糖尿病；血糖；基于体素的形态学测量；静息态功能磁共振成像；低频振幅 分类号：B849

 Objective: Type 1 diabetes mellitus (T1DM) is a chronic metabolic condition characterized by a lifelong dependence on exogenous insulin that occurs predominantly in children and adolescents. The central nervous system is a major organ system affected in type 1 diabetes. In this study, we used cognitive assessment and neuroimaging to examine brain function in patients with type 1 diabetes mellitus. Methods: (1) A total of 181 children and adolescents with type 1 diabetes mellitus, 140 healthy controls participated in the study. The study evaluated the differences between the two groups in terms of cognitive function, IQ, memory, attention, information processing speed and executive function. And we examined effects of specific diabetes-related variables including chronic hyperglycemia and severe hypoglycemia on cognitive outcomes. (2) A total of 56 adults with childhood onset type 1 diabetes mellitus, 64 healthy controls participated in the study. The study evaluated the differences between the two groups in terms of cognitive function, IQ, memory, attention, information processing speed and executive function. (3) A total of 30 adults with adults with childhood onset type 1 diabetes mellitus, 28 healthy controls participated in the study. We used 3.0T MRI and VBM_DARTEL approach on Statistical Parametrical Mapping (SPM) to analyze the data. The VBM gray matter volume of the two group were compared. And to analyze the relationship between the gray matter volume and cognitive impairment in patients with type 1 diabetes mellitus. (4) ALFF analysis was used to detect neural spontaneous activity and the between-group differences in ALFF values were compared. And to analyze the relationship between the ALFF values and cognitive impairment in patients with type 1 diabetes mellitus. Results: (1) The T1DM group had lower scores on IQ, similarities test and verbal memory test than HC group (p < 0.05). Severe hypoglycemia had negative effect on perceptual reasoning score (p < 0.05). Compared with the late severe hypoglycemia subgroup, the early severe hypoglycemia subgroup (< 7 years old) performed worse on IQ, spatial perception and visual memory scores (p < 0.05). Greater exposure to hyperglycemia overtime had effect on spatial perception (t= -3.162, p < 0.05) and executive function (t = -2.479, p < 0.05) in children with type 1 diabetes. (2) Adult patients with childhood onset type 1 diabetes mellitus were significantly lower scores than the healthy controls in terms of IQ, the digit span test, picture completion test, block design test, verbal memory, visual memory, SART, and WCST (p < 0.05). (3) Adults with childhood onset type 1 diabetes mellitus have abnormal gray matter volume in the midbrain and cerebellar culmen, which were significantly lower than that of healthy controls. It was found that the gray matter volume reduction in the midbrain and cerebellum culmen were correlated with the cognitive deficits. And through correlation analysis, it is found that the volume abnormality of the midbrain was positively related to the verbal memory scores (r = 0.439, p = 0.025), and cerebellar culmen was positively related to the WSCT perseverative errors. (4) Adults with childhood onset type 1 diabetes mellitus have the abnormality of ALFF values. The ALFF values in the left precentral gyrus, the left postcentral gyrus, the left insula, and the left supramarginal gyrus were significantly higher than those in the healthy control group, and the ALFF values of the basal ganglia (putman nucleus), the right insula, the right superior temporal gyrus, and the cerebellar posterior lobe were significantly lower than those in the healthy control group. And through correlation analysis, it was found that the abnormality of ALFF values in these brain regions were associated with impaired cognitive function in patients with type 1 diabetes mellitus.The ALFF values in the the right insula and the right superior temporal gyrus was positively related to the verbal memory scores (r = 0.422, p = 0.040), the left cerebellar posterior lobe was negatively related to the response time of SART (r = -0.473, p = 0.020). Conclusions: (1) Children and adolescents with type 1 diabetes mellitus showed deficits in IQ, spatial perception and verbal memory. Severe hypoglycemia and chronic hyperglycemia had affected particular cognitive domains. Early exposure to severe hypoglycemia had negative impacts on IQ, spatial perception and visual memory. Adult patients with childhood onset type 1 diabetes mellitus were significantly lower than the healthy controls in terms of IQ, visuospatial perception ability, verbal memory, visual memory, sustained attention, and executive function. (2)Compared with healthy controls, adult patients with type 1 diabetes mellitus in childhood have reduced gray matter volume in the brain regions of the midbrain and the cerebellum, and have abnormalities of ALFF value, mainly manifested as abnormalities in spontaneous activity of left precentral gyrus, the left postcentral gyrus, the insula, and the left supramarginal gyrus, the basal ganglia (putman nucleus), the right superior temporal gyrus, and the cerebellum. The structural and functional abnormalities in these brain regions may be the neuropathology of cognitive deficits in patients with type 1 diabetes mellitus. Key words : Cognitive development, Cognitive functions, Type 1 diabetes mellitus, Glycemia, Voxel based morphometry (VBM), Resting-state functional MRI (rs-fMRI), Amplitude of low frequency fluctuation (ALFF) Classfication: B849