Vogiatzoglou A, Refsum H, Johnston C, Smith S M, Bradley K M, de Jager C, Budge M M, Smith A D
Department of Physiology, Anatomy and Genetics, University of Oxford, Le Gros Clark Building, South Parks Rd., Oxford OX1 3QX, UK.
Neurology. 2008 Sep 9;71(11):826-32. doi: 10.1212/01.wnl.0000325581.26991.f2.
To investigate the relationship between markers of vitamin B(12) status and brain volume loss per year over a 5-year period in an elderly population.
A prospective study of 107 community-dwelling volunteers aged 61 to 87 years without cognitive impairment at enrollment. Volunteers were assessed yearly by clinical examination, MRI scans, and cognitive tests. Blood was collected at baseline for measurement of plasma vitamin B(12), transcobalamin (TC), holotranscobalamin (holoTC), methylmalonic acid (MMA), total homocysteine (tHcy), and serum folate.
The decrease in brain volume was greater among those with lower vitamin B(12) and holoTC levels and higher plasma tHcy and MMA levels at baseline. Linear regression analysis showed that associations with vitamin B(12) and holoTC remained significant after adjustment for age, sex, creatinine, education, initial brain volume, cognitive test scores, systolic blood pressure, ApoE epsilon4 status, tHcy, and folate. Using the upper (for the vitamins) or lower tertile (for the metabolites) as reference in logistic regression analysis and adjusting for the above covariates, vitamin B(12) in the bottom tertile (<308 pmol/L) was associated with increased rate of brain volume loss (odds ratio 6.17, 95% CI 1.25-30.47). The association was similar for low levels of holoTC (<54 pmol/L) (odds ratio 5.99, 95% CI 1.21-29.81) and for low TC saturation. High levels of MMA or tHcy or low levels of folate were not associated with brain volume loss.
Low vitamin B(12) status should be further investigated as a modifiable cause of brain atrophy and of likely subsequent cognitive impairment in the elderly.
研究老年人群中维生素B12状态标志物与5年内每年脑容量损失之间的关系。
对107名年龄在61至87岁、入组时无认知障碍的社区志愿者进行前瞻性研究。每年通过临床检查、MRI扫描和认知测试对志愿者进行评估。在基线时采集血液,用于测量血浆维生素B12、转钴胺素(TC)、全转钴胺素(holoTC)、甲基丙二酸(MMA)、总同型半胱氨酸(tHcy)和血清叶酸。
基线时维生素B12和holoTC水平较低、血浆tHcy和MMA水平较高的人群脑容量下降幅度更大。线性回归分析表明,在调整年龄、性别、肌酐、教育程度、初始脑容量、认知测试分数、收缩压、载脂蛋白E ε4状态、tHcy和叶酸后,与维生素B12和holoTC的关联仍然显著。在逻辑回归分析中,以上三分位数的上限(针对维生素)或下限(针对代谢物)作为参考,并对上述协变量进行调整,最低三分位数(<308 pmol/L)的维生素B12与脑容量损失率增加相关(比值比6.17,95%可信区间1.25 - 30.47)。低水平的holoTC(<54 pmol/L)(比值比5.99,95%可信区间1.21 - 29.81)和低TC饱和度的关联相似。高水平的MMA或tHcy或低水平的叶酸与脑容量损失无关。
低维生素B12状态应作为老年人脑萎缩及可能随后出现认知障碍的一个可改变原因进行进一步研究。