Department of Endocrinology, Affiliated Zhongda Hospital of Southeast University, Nanjing, PR China.
Medical School of Southeast University, Nanjing, PR China.
J Alzheimers Dis. 2017;58(4):1163-1173. doi: 10.3233/JAD-170162.
Homocysteine (Hcy) is involved in the pathogenesis of type 2 diabetes mellitus (T2DM) and Alzheimer's disease.
We aimed to investigate the role of Hcy in T2DM patients with mild cognitive impairment (MCI), and to determine whether methylene tetrahydrofolate reductase (MTHFR) C677T or cystathionine beta-synthase (CBS) 844ins68 polymorphism is related to T2DM-associated MCI.
We recruited 285 T2DM patients and divided them into two groups, 140 patients with MCI, and 145 healthy-cognition controls, on the basis of Montreal Cognitive Assessment (MoCA) scores. Demographic characteristics, clinical parameters, and neuropsychological tests were assessed. MTHFR C677T and CBS 844ins68 polymorphisms were analyzed.
The MCI group exhibited significantly higher plasma total Hcy (tHcy) levels than control group (p < 0.001). Plasma tHcy level was negatively correlated with MoCA scores (p = 0.002), but positively associated with Trail Making Test A and B scores (p = 0.044; p = 0.005, respectively). Multivariable logistic regression model showed that high tHcy level was an independent factor for MCI in T2DM patients. No significant difference was observed in the genotype or allele distributions of MTHFR and CBS between MCI and control groups. We did not find significant MCI risks in MTHFR T allele compared with C allele, and in CBS I allele compared with D allele (OR = 1.361, p = 0.067; OR = 1.048, p = 0.909, respectively).
Increased plasma tHcy level was significantly related to T2DM-associated MCI, especially executive dysfunction. Further investigation with a large population size should be conducted to confirm these findings.
同型半胱氨酸（Hcy）参与 2 型糖尿病（T2DM）和阿尔茨海默病的发病机制。
我们旨在研究 Hcy 在伴有轻度认知障碍（MCI）的 T2DM 患者中的作用，并确定亚甲基四氢叶酸还原酶（MTHFR）C677T 或胱硫醚β-合酶（CBS）844ins68 多态性是否与 T2DM 相关的 MCI 有关。
我们招募了 285 名 T2DM 患者，并根据蒙特利尔认知评估（MoCA）评分将他们分为两组，140 名 MCI 患者和 145 名认知正常对照组。评估了人口统计学特征、临床参数和神经心理学测试。分析了 MTHFR C677T 和 CBS 844ins68 多态性。
MCI 组的血浆总同型半胱氨酸（tHcy）水平明显高于对照组（p<0.001）。血浆 tHcy 水平与 MoCA 评分呈负相关（p=0.002），但与 Trail Making Test A 和 B 评分呈正相关（p=0.044；p=0.005）。多变量 logistic 回归模型显示，高 tHcy 水平是 T2DM 患者 MCI 的独立因素。MCI 组和对照组在 MTHFR 和 CBS 的基因型或等位基因分布上无显著差异。与 C 等位基因相比，MTHFR T 等位基因与 MCI 无显著相关性，与 D 等位基因相比，CBS I 等位基因与 MCI 也无显著相关性（OR=1.361，p=0.067；OR=1.048，p=0.909）。
血浆 tHcy 水平升高与 T2DM 相关的 MCI 显著相关，特别是执行功能障碍。应进行更大规模的人群研究来证实这些发现。
