采用多模态MRI研究海马损伤介导的血管危险因素相关性认知损害

Cerebrovascular disease is the most common cause of cognitive impairment and dementia. Epidemiological data and our previous study indicated that combined vascular risk factors (VRFs), independent of stroke or detectable cerebral lesions, significantly increase the risk of dementia and cognitive impairment，including vascular cognitive impairment and Alzheimer disease. However, the principal pathophysiological basis of this increase has not been fully elucidated. Our preliminary study suggested that abnormal hippocampal glutamate neurotransmitter may play an important role in the pathophysiology of VRF-associated cognitive impairment. However, it is remain unknown whether hippocampal glutamate neurotransmitter stimulate or contribute to the cognitive impairment-associated pathological changes (such as medial temporal lobe and hippocampus atrophy). Based on our previous research results, we hypothesized that the abnormal hippocampal glutamate neurotransmitter metobolites impaired by combined VRFs can promote hippocampus volume shrinking and then lead to a cognitive impairment. In the present study, we will conduct the second follow-up for our previous subjects (Clinical research registration number: ChiCTR-RNC-12002205). VRFs burden will be quantified by Framingham Stroke Risk Profile (FSRP) score, and the cognitive function will be reviewed using a series of neuropsychological scale. Multi modal resonance method, including magnetic resonance spectrum (H-MRS) and voxel-based morphometry (VBM), will be used to explore whether the abnormal hippocampal glutamate neurotransmitter metobolites impaired by combined VRFs can promote hippocampus volume shrinking and then lead to a cognitive impairment.

脑血管病是导致痴呆与认知损害最常见的病因之一。血管危险因素（VRF）如高血压、糖尿病等可以不依赖卒中及明显的脑结构损害而增加认知损害的风险，包括血管性痴呆（VaD）和阿尔兹海默尔病（AD），但是其中的病理生理机制尚未完全阐明。我们的初步研究提示，海马谷氨酸递质代谢紊乱参与了VRF相关的认知损害。但是这种早期神经递质的改变是否启动或促进了与认知损害相关的主要病理改变（如海马萎缩），目前尚不清楚。基于前期的研究，我们提出假设，VRF可能会通过损害海马谷氨酸代谢而促进海马体积缩小从而导致认知损害。本项目将在既往研究的基础上继续随访研究，采用弗明汉卒中风险量表评估VRF负担，采用完整的认知量表复查受试者的认知功能。采用包括磁共振波谱和基于体素的形态测量法在内的多模态MRI探讨海马谷氨酸递质代谢是否影响了海马体积改变从而介导了VRF相关的认知损害。为VaD和AD等痴呆的研究和防治提供新的思路。

一、研究背景.痴呆是影响我国老年人群生存质量的重大疾病，近年来针对痴呆阶段的临床药物试验均告失败，提示早期干预可能是防治痴呆发生发展的关键。流行病学研究显示血管危险因素（VRF）如高血压、糖尿病等可以不依赖卒中及明显的脑结构损害而增加认知损害的风险，包括血管性痴呆（VaD）和阿尔兹海默尔病（AD），但是其中的病理生理机制尚未完全阐明。.二、主要研究内容.本项目的目的是探索痴呆更早期阶段（血管危险因素相关性认知损害）的病理生理基础，为早期防治提供理论依据。本项目纳入了93例具有不同VRF负荷，但非痴呆和非卒中的受试者；所有受试者接受了完整的神经心理评估、完整的临床及血管危险因素评估及多模态磁共振扫描，通过FreesurferV6.0准确计算了海马总体积和各海马亚区的体积。继而探索了海马亚区体积、认知功能及血管危险因素负担之间的关系。.三、主要结果及关键数据.（1）左侧海马沟体积扩大是血管危险因素相关性认知损害最早期的海马损害表现。.（2）在糖尿病亚组分析中，左侧海马尾体积缩小是糖尿病导致认知损害最早期的海马结构改变。.四、科学意义.本项目的实施为血管危险因素相关性认知损害这一新概念提供了理论依据，揭示了血管危险因素导致早期认知下降的物质基础，即海马亚区结构的改变。