2型糖尿病工作记忆功能代偿机制的多模态MRI研究

The cognitive impairment of type 2 diabetes mellitus (T2DM) is mainly featured as working memory impairment with unrevealed mechanism. Previous studies suggest that the impairment and compensation of working memory both occur in the patients at the early stage of T2DM. Preventing the impairment while reserving the compensation of working memory is the key point to maintain working memory in the early T2DM patients. We previously observed a significant decrease in working memory in some T2DM patients, which was accompanied with axonal density decrease in the genu of corpus callosum and anterior limb of internal capsule. While in the T2DM patients with normal working memory, axonal density decrease in the genu of corpus callosum and increase in the superior longitudinal fasciculus were observed. Taking together, these findings suggest that the compensation of working memory was accompanied with white matter remodeling. We thus raised the hypothesis that the white matter remodeling in the genu of corpus callosum, superior longitudinal fasciculus and anterior limb of internal capsule within the frontal lobe is the underlying mechanism for the compensation of working memory impairment in the early T2DM patients. We plan to integrate the neurobehavioral assessment, multi-modal MRI and digital modeling techniques to evaluate the white matter remodeling within the prefrontal cortex and working memory of T2DM patients, so as to establish the interactive causal model of white matter remodeling and brain compensation, and to elucidate the white matter remodeling mechanism for working memory compensation in T2DM patients. This project will provide new insight for the therapeutic strategy for the cognitive impairment in T2DM patients.

2型糖尿病（T2DM）认知功能损伤主要表现为工作记忆损伤，但其机制不明。既往研究发现，T2DM早期工作记忆功能损伤与代偿共存，维持代偿，减少损伤是保证T2DM患者工作记忆功能的关键。我们在预实验中通过神经行为学及多模态MRI技术观察到:部分T2DM患者工作记忆显著降低，且胼胝体膝部和内囊前肢轴索密度降低，而工作记忆正常的T2DM患者内囊前肢轴索密度降低的同时上纵束的轴索密度升高，提示工作记忆功能代偿时出现白质重塑。于是，我们提出科学假说：T2DM早期前额叶内胼胝体膝部、上纵束、内囊前肢的白质重塑是工作记忆功能的重要代偿机制。本课题拟综合运用神经行为学、多模态MRI和数字建模等技术，评估T2DM前额叶白质重塑特征以及工作记忆能力，建立白质重塑与脑区代偿的交互因果作用模型，阐明T2DM患者工作记忆功能代偿的白质重塑机制，为T2DM患者认知功能损伤的临床防治策略提供新思路。

2型糖尿病（T2DM）认知功能损伤主要表现为执行能力和记忆力的损伤，但其机制不明。既往研究发现，T2DM早期认知功能损伤与代偿共存，维持代偿，减少损伤是保证T2DM患者执行能力和记忆力的关键。本课题综合运用神经行为学、多模态MRI和数字建模等技术，发现2型糖尿病(T2DM)认知损伤早期起到代偿作用的功能网络为以视觉-运动通路为核心的网络。在中年T2DM患者中，由于脑损伤较轻且存在认知储备，故未发现白质重塑现象，而在70岁左右的老年T2DM患者中即存在功能网络的代偿现象也存在白质重塑，且随着认知表现的下降，白质重塑的程度会不断加大。正式由于白质重塑和功能网络的代偿，白质网络的拓扑学全局及局部效率都能够保持在正常老年人的水平。上述的代偿相关的功能网络及白质重塑网络都与T2DM患者的执行能力和记忆力显著相关。综合评估了T2DM代偿网络相关的白质重塑特征以及其执行能力和记忆力，建立白质重塑与脑区代偿的交互因果作用模型，探索了T2DM患者执行能力和记忆力代偿的白质重塑机制，为T2DM患者认知功能损伤的临床防治策略提供新思路。