Xia Wenqing, Yin Xiao, Zhang Yujie, Ge Shenghui, Chen Yuchen, Ma Jianhua
Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Department of Radiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Neuroendocrinology. 2025;115(1):48-59. doi: 10.1159/000542902. Epub 2024 Dec 2.
The glymphatic system is regarded as a key factor in the pathogenesis of neurodegenerative diseases. Given the heightened risk of cognitive impairment in patients with type 2 diabetes mellitus (T2DM), the possible alterations in the glymphatic system in T2DM patients remain to be explored. Diffusion tensor imaging (DTI) analysis along the perivascular space (ALPS) index can be utilized to model the glymphatic system in humans. Our aim was to explore the relationship between the ALPS index and cognitive function in patients with T2DM and whether this relationship is modulated by gray matter (GM) integrity anchored by the ALPS index.
All participants underwent evaluation using a comprehensive cognitive assessment scale to determine their neurocognitive status. The ALPS index was calculated based on DTI data, and the disparity in ALPS index values between patients with T2DM and healthy controls (HCs) was examined. Furthermore, multiple linear regression analysis was conducted in the T2DM group to identify the GM regions associated with the ALPS index, and the volumes of the GM partitions were extracted. The volume of GM partitions was used as the regulating variable, the ALPS index was used as the independent variable, and cognitive test scores were used as the dependent variable in our analysis.
The ALPS index differed significantly between the two groups, and the ALPS index in patients with T2DM was significantly lower than that in HCs. In addition, our analysis revealed a correlation between the ALPS index and GM volume in the insular region, consistent with the observed GM atrophy in the patient cohort. Moreover, a significant negative correlation was observed between the ALPS index in patients and performance on the Trail-Making Test-A (TMT-A), and this relationship was moderated by GM integrity. In patients with more severe GM atrophy, the ALPS index was more strongly correlated with cognitive function.
In this study, a decreased ALPS index was found in T2DM patients, indicating impaired glymphatic function in this population. Furthermore, a significant association was detected between the ALPS index and cognitive performance in T2DM patients, and this correlation was influenced by GM integrity. Therefore, the ALPS index has the potential to be used as a biomarker of cognitive impairment in diabetic patients. Further studies are needed to investigate the diagnostic and therapeutic implications of glymphatic dysfunction in T2DM patients with cognitive impairment.
类淋巴系统被认为是神经退行性疾病发病机制中的一个关键因素。鉴于2型糖尿病（T2DM）患者认知障碍风险增加，T2DM患者类淋巴系统可能存在的改变仍有待探索。沿血管周围间隙（ALPS）指数的扩散张量成像（DTI）分析可用于模拟人体类淋巴系统。我们的目的是探讨T2DM患者的ALPS指数与认知功能之间的关系，以及这种关系是否受由ALPS指数所锚定的灰质（GM）完整性的调节。
所有参与者均使用综合认知评估量表进行评估，以确定其神经认知状态。基于DTI数据计算ALPS指数，并检查T2DM患者与健康对照（HCs）之间ALPS指数值的差异。此外，在T2DM组中进行多元线性回归分析，以确定与ALPS指数相关的GM区域，并提取GM分区的体积。在我们的分析中，将GM分区的体积用作调节变量，将ALPS指数用作自变量，将认知测试分数用作因变量。
两组之间的ALPS指数存在显著差异，T2DM患者的ALPS指数显著低于HCs。此外，我们的分析显示，ALPS指数与岛叶区域的GM体积之间存在相关性，这与患者队列中观察到的GM萎缩一致。此外，观察到患者的ALPS指数与连线测验A（TMT-A）的表现之间存在显著负相关，并且这种关系受GM完整性的调节。在GM萎缩更严重的患者中，ALPS指数与认知功能的相关性更强。
在本研究中，发现T2DM患者的ALPS指数降低，表明该人群类淋巴功能受损。此外，在T2DM患者中检测到ALPS指数与认知表现之间存在显著关联，并且这种相关性受GM完整性的影响。因此，ALPS指数有可能用作糖尿病患者认知障碍的生物标志物。需要进一步研究以探讨类淋巴功能障碍对T2DM认知障碍患者的诊断和治疗意义。
