2型糖尿病记忆损害机制的影像遗传学研究

2型糖尿病（T2DM）可引起记忆下降并增加痴呆风险。利用横断面研究，我们发现T2DM患者存在陈述性记忆相关脑区萎缩，既往也发现这些脑区的结构和功能连接降低。但纵向上T2DM患者记忆和脑影像学改变的特征和机制仍不清楚。根据以往研究，本课题假设载脂蛋白E和结合珠蛋白基因在T2DM记忆下降和脑影像学改变过程中起重要作用。研究拟招募400名T2DM病人和200名正常对照组并检测候选基因多态性，评价陈述性记忆能力和多模态磁共振影像学指标，包括灰质形态、纤维连接、静息态功能连接及脑网络拓扑属性，随访两年后再次检测。横断面组间对照检测T2DM组记忆和影像学测量的差异；相关分析检测认知下降率和基线状态影像指标的关系；利用影像遗传学方法分析基因多态性与记忆下降相关影像学指标及影像学纵向改变程度之间是否存在关联。本研究可揭示T2DM记忆损害的神经生物学机制，为临床预测和治疗T2DM患者记忆下降提供影像学标记。

Type 2 diabetes mellitus (T2DM) is associated with memory decline and increases the risk of dementia. Based on cross-sectional analysis, our preliminary studies have revealed modest gray matter atrophy in the brain regions responsible for declarative memory. Previous studies also found decreased structural and functional connectivity involved in these key brain regions in T2DM. However, the characteristics and biological mechanisms for longitudinal memory decline and brain imaging changes in T2DM remains unclear. We hypothesize that the dynamic changes in memory function and brain structure/function may be related to the Apolipoprotein E (APOE) and Haptoglobin (Hp) genes. In the current design, 400 elder T2DM patients and 200 matched normal controls will be recruited and followed up after 2 years. The single nucleotide polymorphism (SNP) for candidate genes will be tested. Two-year changes in components of declarative memory performance and brain multi-modal magnetic resonance imaging parameters, including the gray matter morphology, white matter fiber connectivity, resting-state brain functional connectivity and topological properties of brain structural/functional networks, will be assessed. After cross-sectional comparisons between groups, we can reveal the alternations of memory and imaging measures in T2DM patients. In addition, correlation analyses between the brain imaging measures at baseline and memory decline rate in T2DM patients will be performed. Finally, the relationships between individual genotypes and brain imaging parameters related to memory impairment as well as the change rate of imaging measures during two years will be explored based on imaging genetics approach. Taking together, our findings is likely to yield more precise information about underlying biological mechanisms on memory impairment in T2DM, and may provide the imaging markers for predicting and treating memory decline in patients with T2DM .