Lyu Wenjiao, Chen Yuna, Zhao Kui, Tan Xin, Wu Ye, Qiu Shijun
Department of Radiology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
Department of Endocrinology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
Front Neurosci. 2023 Apr 11;17:1141261. doi: 10.3389/fnins.2023.1141261. eCollection 2023.
This study aimed to investigate potential biological mechanisms underlying cognitive function alterations in Type 2 diabetes mellitus (T2DM) patients by integrating cortical morphology with peripheral cytokine levels and brain-derived neurotrophic factor (BDNF) levels, and to offer potential insights for the early detection of T2DM-related cognitive impairment.
This study included 16 T2DM patients with a Montreal Cognitive Assessment (MoCA) score of at least 26 points, as well as 16 healthy controls with normal cognitive function. The participants also completed the digit span test and digit symbol substitution test. Participants' serum levels of Interleukin 4 (IL-4), IL-6, IL-10, tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and BDNF were also examined. Each subject underwent a high-resolution 3T structural brain MRI scan. Based on the aparc. a2009s atlas, we calculated the cortical thickness, sulcus depth, gyrification index, and fractal dimension for each participant using surface-based morphometry (SBM). Correlation analysis between cognitive measures, serum levels of cytokines and BDNF, and SBM indices were further performed.
The levels of IL-4 and BDNF showed significant group differences. In the T2DM group, the sulcus depth exhibited a significant decrease in the left transverse frontopolar gyri and sulci, as well as in the right pole-occipital; the fractal dimension showed a significant increase in the right posterior-dorsal part of the cingulate gyrus; and the gyrification index significantly increased in the left inferior part of the precentral sulcus and right triangular part of the inferior frontal gyrus. Correlation analysis revealed a significant positive correlation between IL-10 levels and the sulcus depth of left transverse frontopolar gyri and sulci; a significant positive correlation between the sulcus depth of the right pole-occipital and the digit span test-forward scores, and a significant negative correlation between the gyrification index of the left inferior part of the precentral sulcus and the digit span test-backward scores among T2DM participants.
T2DM patients without cognitive impairment displayed reductions in IL 4 and BDNF levels, as well as significant alterations in their SBM indices, indicating that prior to the emergence of cognitive impairment, the SBM indices, peripheral cytokines, and BDNF may have altered in T2DM patients. IL-10 may lessen inflammation-related brain edema and preserve sulcus depth in T2DM patients through its anti-inflammatory activity.
本研究旨在通过整合皮质形态学与外周细胞因子水平及脑源性神经营养因子（BDNF）水平，探究2型糖尿病（T2DM）患者认知功能改变的潜在生物学机制，并为T2DM相关认知障碍的早期检测提供潜在见解。
本研究纳入了16名蒙特利尔认知评估（MoCA）得分至少为26分的T2DM患者，以及16名认知功能正常的健康对照者。参与者还完成了数字广度测试和数字符号替换测试。还检测了参与者血清白细胞介素4（IL-4）、IL-6、IL-10、肿瘤坏死因子-α（TNF-α）、干扰素-γ（IFN-γ）和BDNF的水平。每位受试者均接受了高分辨率3T脑部结构MRI扫描。基于aparc.a2009s图谱，我们使用基于表面的形态测量法（SBM）计算了每位参与者的皮质厚度、脑沟深度、脑回指数和分形维数。进一步进行了认知测量、细胞因子和BDNF血清水平与SBM指数之间的相关性分析。
IL-4和BDNF水平存在显著的组间差异。在T2DM组中，左侧额极横回和脑沟以及右侧枕极的脑沟深度显著降低；扣带回右侧后背部的分形维数显著增加；中央前沟左侧下部和额下回右侧三角部的脑回指数显著增加。相关性分析显示，IL-10水平与左侧额极横回和脑沟的脑沟深度之间存在显著正相关；右侧枕极的脑沟深度与数字广度测试顺向得分之间存在显著正相关，而T2DM参与者中中央前沟左侧下部的脑回指数与数字广度测试逆向得分之间存在显著负相关。
无认知障碍的T2DM患者表现出IL-4和BDNF水平降低，以及其SBM指数的显著改变，表明在认知障碍出现之前，T2DM患者的SBM指数、外周细胞因子和BDNF可能已经发生改变。IL-10可能通过其抗炎活性减轻T2DM患者炎症相关的脑水肿并维持脑沟深度。
