Objective: To explore the relationship between apolipoprotein E (ApoE) gene polymorphism and hydrogen proton magnetic resonance spectroscopy ((1)H-MRS) in patients with Alzheimer's disease (AD) and amnestic mild cognitive impairment(aMCI). Methods: The cognitive function of 35 AD patients (AD group), 35 aMCI patients (aMCI group) and 36 normal controls (NC group) were evaluated by neuropsychological scales, including Mini-mental State Examination (MMSE) and Cambridge Cognitive Examination-Chinese version (CAMCOG-C). The genotypes of ApoE were analyzed by high-resolution melting assay. Brain regional metabolites were measured via (1)H-MRS technique with the regions of interest (ROIs) located in the left frontal lobe and left hippocampus. Results: The CAMCOG-C (NC group 94.00 (8.50);aMCI group 86.00(8.00);AD group 61.00(18.0)) and MMSE (NC group 29.00 (2.00);aMCI group 26.00(2.00);AD group 13.00(9.5)) scores in AD and aMCI group were significantly lower in comparison with that in NC group (P<0.05). There was multi-domain cognitive impairment both in AD and aMCI. The CAMCOG-C (ε4 carriers 76.00(28.00);no-ε4 carriers 89.00 (17.00)) and MMSE (ε4 carriers 23.00(16.00);no-ε4 carriers (27.00 (6.00))scores in ε4 carriers were significantly lower than those in no-ε4 carriers (P<0.05). The AD and aMCI groups showed decreased NAA/Cr ratio in the left hippocampus as well as elevated Cho/Cr ratio and MI/Cr in the left frontal lobe compared to the NC group (P<0.05). This change was even more pronounced in AD group when compared to aMCI group. The NAA/Cr ratio and Cho/Cr ratio in the left hippocampus in ε4 carriers were lower, the MI/Cr ratio in left frontal lobe in ε4 carriers was higher (P<0.05). Conclusions: ApoE gene polymorphism affects the alteration of (1)H-MRS in AD and aMCI patients. The combination of ApoE gene polymorphism and (1)H-MRS may be more useful to differentiate and diagnose AD and aMCI early.
目的： 探讨载脂蛋白E（ApoE）基因型对遗忘型轻度认知障碍（aMCI）和阿尔茨海默病（AD）患者氢质子磁共振波谱（(1)H-MRS）的影响。 方法： 选取2016年1月至2018年1月就诊于安徽医科大学第一附属医院神经内科的35例AD患者（AD组），35例aMCI患者（aMCI组）和36名性别和年龄相匹配的认知正常者（对照组，NC组）为研究对象，采用简易智能状态量表（MMSE）、剑桥老年认知检查表中国修订版（CAMCOG-C）等多种神经心理学量表对所有受试对象进行认知功能评价；采用高分辨率熔解曲线法分析ApoE基因型；利用(1)H-MRS技术，计算左侧海马和左侧额叶的N-乙酰天冬氨酸/肌酸（NAA/Cr）、胆碱/肌酸（Cho/Cr）、肌醇/肌酸（MI/Cr）的比值。 结果： AD组和aMCI组MMSE评分[NC组29.00（2.00）分、aMCI组26.00（2.00）分、AD组13.00（9.50）分]、CAMCOG-C总分[NC组94.00 （8.50）分、aMCI组86.00（8.00）分、AD组61.00（18.0）分]及其亚分包括定向、语言、记忆、执行、计算、思维、知觉等子项目评分均显著低于对照组，差异均有统计学意义（均P<0.05）。AD和aMCI组中ε4等位基因携带率均显著高于对照组，且AD组中ApoE ε4等位基因携带率较aMCI组更高（均P<0.05）。ApoE ε4等位基因携带者MMSE评分[ApoE ε4等位基因携带者23.00（16.00）分、非携带者27.00 （6.00）分]及CAMCOG-C评分[ApoE ε4等位基因携带者76.00（28.00）分、非携带者89.00（17.00）分]均显著低于非携带者（均P<0.05）。MRS结果中，AD组和aMCI组左侧海马NAA/Cr比值均显著低于对照组，且AD组左侧海马NAA/Cr比值显著低于aMCI组；AD组和aMCI组左侧额叶Cho/Cr比值和MI/Cr比值显著高于对照组，且以AD组升高较aMCI更为明显（均P<0.05）；ApoE ε4等位基因携带者左侧海马NAA/Cr和Cho/Cr比值均显著低于非携带者组，左侧额叶MI/Cr比值显著高于非携带者组（均P<0.05）。 结论： ApoE等位基因影响aMCI和AD患者MRS改变，联合ApoE基因型和MRS检测对AD及aMCI早期诊断及评估具有一定的临床价值。.
Keywords: Alzheimer′s disease; Apolipoprotein E; Hydrogen proton magnetic resonance spectroscopy; Mild cognitive impairment.