PREVALENCE AND SPECTRUM OF B12 DEFICIENCY IN THE AGED

老年人维生素B12的患病率很高(10%-20%) (钴胺)缺乏，但这种情况的临床后果 不足之处仍不得而知。血清甲基丙二酸升高和 总同型半胱氨酸是最敏感和特异的指标 临床不足。高同型半胱氨酸血症被发现是一种 年轻人群中血管疾病的独立危险因素 人口。这项提案的一个主要目标是确定 钴胺缺乏是否导致高同型半胱氨酸血症 与心血管疾病相关的一个大的种族 从女性健康与老龄化看多元化女性老年人口 学习。还将确定钴胺缺乏症是否与 甲基丙二酸和/或总同型半胱氨酸水平升高导致 巨幼细胞性贫血和/或振动感觉障碍和 平衡。标准复合维生素的使用效果将会被确定。 钴胺或叶酸缺乏或升高的患病率 代谢物。钴胺状态与常见病的相互作用 不耐热亚甲基四氢叶酸还原酶基因的多态性 将在老年门诊人群中进行钴胺研究 有神经系统疾病的有缺陷的受试者或有极端 高同型半胱氨酸和巨幼细胞性贫血。它还将 确定纯合子不耐热突变是否会导致 甲硫氨酸负荷后同型半胱氨酸水平异常。聚合酶 将使用基于链式反应的方法对受试者进行基因分型和 稳定同位素稀释气相色谱-质谱法 将用来定量甲基丙二酸和总 同型半胱氨酸。在食物叶酸强化计划完全完成后 1998年实施，数百万美国老年人以前 未经治疗的钴胺缺乏症将暴露于强化的叶酸 食物。这项建议旨在调查临床后果 以改善老年人钴胺缺乏症 对这些患者进行诊断和替代治疗。

The elderly have a high prevalence (10-20%) of vitamin B12 (cobalamin) deficiency, but the clinical consequences of this deficiency are still unknown. Elevated serum methylmalonic acid and total homocysteine are the most sensitive and specific measures of clinical deficiency. Hyperhomocysteinemia has been found to be an independent risk factor for vascular disease in younger populations. A major objective of this proposal is to determine whether hyperhomocysteinemia due to cobalamin deficiency is correlated with cardiovascular disease in a large ethnically diverse female elderly population from the Women's Health and Aging Study. It will also be determined whether cobalamin deficiency with elevated methylmalonic acid and/or total homocysteine levels causes megaloblastic anemia and/or disorders of vibration sense and balance. The effect of standard multivitamin use will be determined on the prevalence of cobalamin or folate deficiency or elevated metabolites. The interaction between cobalamin status and a common polymorphism for thermolabile methylenetetrahydrofolate reductase will be studied in an elderly outpatient population, in cobalamin deficient subjects with neurologic disease or those with extremely high levels of homocysteine and megaloblastic anemia. It will also be determined whether the homozygous thermolabile mutations cause an abnormal post methionine load homocysteine level. Polymerase chain reaction based methods will be used to genotype subjects and stable isotope dilution gas chromatography-mass spectrometry assays will be used to quantitate methylmalonic acid and total homocysteine. After the food folate fortification program is fully implemented in 1998, millions of elderly Americans with previously untreated cobalamin deficiency will be exposed to folate fortified food. This proposal seeks to investigate the clinical consequences of cobalamin deficiency in the elderly in order to improve diagnosis and replacement therapy for these individuals.