Cheng Zhenyu, Yang Linfeng, Li Meng, Zhang Qihao, Li Jing, Zhang Nan, Che Yena, Chen Yiwen, Liang Pengcheng, Wang Yuanyuan, Wang Na, Zhang Xinyue, Liang Changhu, Guo Lingfei
School of Medical Imaging, Binzhou Medical University, Yantai, Shandong, China.
Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education, Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Hum Brain Mapp. 2025 Jun 15;46(9):e70263. doi: 10.1002/hbm.70263.
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder that significantly impacts cognitive health. Although the vascular complications of T2DM have been extensively studied, research on brain iron deposition in T2DM remains scarce, and few studies have directly linked iron accumulation in cognition-related subcortical nuclei to cognitive dysfunction. This study aims to evaluate brain iron deposition using quantitative susceptibility mapping (QSM) and identify key subcortical nuclei associated with T2DM-related cognitive decline. A total of 224 participants were recruited, including 112 T2DM patients and 112 healthy controls. QSM was used to assess iron deposition in subcortical nuclei. Structural equation modeling was employed to construct interaction models between metabolic changes, susceptibility values, and cognitive function. Additionally, polynomial regression analysis was performed to evaluate the association between glycemic variability and the QSM values of subcortical nuclei. Our findings confirmed that T2DM patients exhibited pronounced iron deposition in the caudate and putamen compared to healthy controls. Correlation analyses showed that higher QSM values in the anterior putamen, posterior putamen, and posterior caudate were associated with slower processing speed (SDMT), reduced memory performance (AVLT) and poorer executive function (TMT, SCWT), indicating that greater iron accumulation in these nuclei is associated with poorer cognitive performance. In our SEM, metabolic dysregulation was significantly associated with higher subcortical susceptibility (β = 0.224, p = 0.010). The model further demonstrated that susceptibility values partially mediated the effect of metabolic factors on cognition (indirect effect β = -0.056, p = 0.018) and that the overall impact of metabolic dysregulation on cognition remained significant (β = -0.142, p = 0.037). Polynomial regression found that HbA1c was the strongest predictor of anterior putamen susceptibility, and a similar pattern was observed in the posterior caudate. The study demonstrates that the role of brain iron deposition in T2DM-related cognitive dysfunction. These findings reveal an important underlying mechanism of T2DM-induced cognitive impairment and provide evidence for early intervention strategies to mitigate cognitive decline in T2DM patients.
2型糖尿病（T2DM）是一种严重影响认知健康的慢性代谢紊乱疾病。尽管T2DM的血管并发症已得到广泛研究，但关于T2DM患者脑铁沉积的研究仍然很少，而且几乎没有研究直接将与认知相关的皮质下核中铁的积累与认知功能障碍联系起来。本研究旨在使用定量磁化率成像（QSM）评估脑铁沉积，并确定与T2DM相关认知衰退相关的关键皮质下核。共招募了224名参与者，包括112名T2DM患者和112名健康对照者。使用QSM评估皮质下核中的铁沉积。采用结构方程模型构建代谢变化、磁化率值和认知功能之间的相互作用模型。此外，进行多项式回归分析以评估血糖变异性与皮质下核QSM值之间的关联。我们的研究结果证实，与健康对照者相比，T2DM患者在尾状核和壳核中表现出明显的铁沉积。相关性分析表明，壳核前部、壳核后部和尾状核后部较高的QSM值与较慢的处理速度（SDMT）、降低的记忆表现（AVLT）和较差的执行功能（TMT、SCWT）相关，这表明这些核中更多的铁积累与较差的认知表现相关。在我们的结构方程模型中，代谢失调与较高的皮质下磁化率显著相关（β = 0.224，p = 0.010）。该模型进一步表明，磁化率值部分介导了代谢因素对认知的影响（间接效应β = -0.056，p = 0.018），并且代谢失调对认知的总体影响仍然显著（β = -0.142，p = 0.037）。多项式回归发现，糖化血红蛋白（HbA1c）是壳核前部磁化率的最强预测因子，在尾状核后部也观察到类似模式。该研究证明了脑铁沉积在T2DM相关认知功能障碍中的作用。这些发现揭示了T2DM诱发认知障碍的一个重要潜在机制，并为减轻T2DM患者认知衰退的早期干预策略提供了证据。
