Homocysteine, folate, and vitamin B-12 in mild cognitive impairment, Alzheimer disease, and vascular dementia

BACKGROUND: Evidence supports an independent association between plasma total homocysteine concentrations and the risk of vascular disease. Recent epidemiologic studies reappraised the possibility that vascular risk factors might play a role in the pathogenesis not only of vascular dementia (VaD) but also of Alzheimer disease (AD). OBJECTIVE: The objective was to investigate the relations of mild cognitive impairment, AD, and VaD with blood homocysteine, folate, and vitamin B-12. DESIGN: The study population consisted of 314 consecutive subjects, 228 of whom were eligible for analyses. Plasma total homocysteine, serum folate, and serum vitamin B-12 concentrations were measured in 55 nondemented elderly control subjects, 81 mildly cognitively impaired subjects (Clinical Dementia Rating: 0.5), and 92 demented patients prevalently in a mild disease stage and with a clinical diagnosis of AD (n = 74) or VaD (n = 18). RESULTS: Subjects in the lowest folate tertile had significantly higher adjusted odds ratios (ORs) for mild cognitive impairment (OR: 3.1; 95% CI: 1.2, 8.1) and dementia (3.8; 1.3, 11.2). Hyperhomocysteinemia was significantly associated with dementia (adjusted OR: 4.3; 1.3, 14.7) and AD (adjusted OR: 3.7; 1.1, 13.1). In subjects with a Clinical Dementia Rating of 0.5, the mean (+/- SE) Mini-Mental State Examination score was significantly lower (P < 0.05) in the highest homocysteine tertile (24.5 +/- 0.5) than in the lowest tertile (26.6 +/- 0.5). No significant associations were found between minimum medial temporal lobe thickness or leukoaraiosis and any biochemical measure in the dementia and AD groups. CONCLUSIONS: These findings suggest that relative folate deficiency may precede AD and VaD onset. Hyperhomocysteinemia might also be an early risk factor for cognitive decline in the elderly, but its role in dementia development must be addressed in future longitudinal studies.     

Variability of epidemiological measures in mild cognitive impairment and dementia

Variability in occurrence estimates is one of the basic features of the epidemiology of dementia and mild cognitive impairment (MCI). This review will cover two levels of variability that affect epidemiological research on dementia and MCI: the conceptual and the operational level. More specifically, it is highlighted how the lack of a precise definition of MCI leads to a greater variability in the occurrence estimates of this condition, when compared to dementia. Variability will decrease only when more precise criteria and aims of the concept "MCI" will be specified.     

Folate and vitamin B-12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification

BACKGROUND: Historic reports on the treatment of pernicious anemia with folic acid suggest that high-level folic acid fortification delays the diagnosis of or exacerbates the effects of vitamin B-12 deficiency, which affects many seniors. This idea is controversial, however, because observational data are few and inconclusive. Furthermore, experimental investigation is unethical. OBJECTIVE: We examined the relations between serum folate and vitamin B-12 status relative to anemia, macrocytosis, and cognitive impairment (ie, Digit Symbol-Coding score < 34) in senior participants in the 1999-2002 US National Health and Nutrition Examination Survey. DESIGN: The subjects had normal serum creatinine concentrations and reported no history of stroke, alcoholism, recent anemia therapy, or diseases of the liver, thyroid, or coronary arteries (n = 1459). We defined low vitamin B-12 status as a serum vitamin B-12 concentration < 148 pmol/L or a serum methylmalonic acid concentration > 210 nmol/L-the maximum of the reference range for serum vitamin B-12-replete participants with normal creatinine. RESULTS: After control for demographic characteristics, cancer, smoking, alcohol intake, serum ferritin, and serum creatinine, low versus normal vitamin B-12 status was associated with anemia [odds ratio (OR): 2.7; 95% CI: 1.7, 4.2], macrocytosis (OR: 1.8; 95% CI: 1.01, 3.3), and cognitive impairment (OR: 2.5; 95% CI: 1.6, 3.8). In the group with a low vitamin B-12 status, serum folate > 59 nmol/L (80th percentile), as opposed to < or = 59 nmol/L, was associated with anemia (OR: 3.1; 95% CI: 1.5, 6.6) and cognitive impairment (OR: 2.6; 95% CI: 1.1, 6.1). In the normal vitamin B-12 group, ORs relating high versus normal serum folate to these outcomes were < 1.0 (P(interaction) < 0.05), but significantly < 1.0 only for cognitive impairment (0.4; 95% CI: 0.2, 0.9). CONCLUSION: In seniors with low vitamin B-12 status, high serum folate was associated with anemia and cognitive impairment. When vitamin B-12 status was normal, however, high serum folate was associated with protection against cognitive impairment.     

Effect of oral vitamin B-12 with or without folic acid on cognitive function in older people with mild vitamin B-12 deficiency: a randomized, placebo-controlled trial

BACKGROUND: Vitamin B-12 deficiency is associated with cognitive impairment in older people. However, evidence from randomized trials of the effects of vitamin B-12 supplementation on cognitive function is limited and inconclusive. OBJECTIVE: The objective was to investigate whether daily supplementation with high doses of oral vitamin B-12 alone or in combination with folic acid has any beneficial effects on cognitive function in persons aged >/=70 y with mild vitamin B-12 deficiency. DESIGN: In a double-blind, placebo-controlled trial, 195 subjects were randomly assigned to receive 1000 microg vitamin B-12, 1000 microg vitamin B-12 + 400 microg folic acid, or placebo for 24 wk. Vitamin B-12 status was assessed on the basis of methylmalonic acid, total homocysteine (tHcy), and holotranscobalamin (holoTC) concentrations before and after 12 and 24 wk of treatment. Cognitive function was assessed before and after 24 wk of treatment with the use of an extensive neuropsychologic test battery that included the domains of attention, construction, sensomotor speed, memory, and executive function. RESULTS: Vitamin B-12 status did not change significantly after treatment in the placebo group; however, oral vitamin B-12 supplementation corrected mild vitamin B-12 deficiency. Vitamin B-12 + folic acid supplementation increased red blood cell folate concentrations and decreased tHcy concentrations by 36%. Improvement in memory function was greater in the placebo group than in the group who received vitamin B-12 alone (P = 0.0036). Neither supplementation with vitamin B-12 alone nor that in combination with folic acid was accompanied by any improvement in other cognitive domains. CONCLUSION: Oral supplementation with vitamin B-12 alone or in combination with folic acid for 24 wk does not improve cognitive function.     

血清叶酸和维生素B12水平与抑郁症的关系

目的通过观察抑郁症患者血清叶酸和维生素B12浓度,探讨营养因素与抑郁症的相关性。方法选择Hamilton抑郁量表17项中得分大于17分和／或Hamilton焦虑量表14项中得分超过14分的30例患者组成抑郁症组,Hamilton抑郁量表得分低于17分、Hamilton焦虑量表得分低于14分的30例患者作为对照组。检测血红蛋白、血清叶酸和维生素B12水平以及进行Zung抑郁自评量表（SDS,20项）和焦虑自评量表（SAS,20项）测查。采用t检验比较两组以上指标的差异。结果抑郁症组血清叶酸[（4．06±1．61）vs．（6．48±2．36）ng／ml,P〈0．05]和维生素B12水平[（427．96±126．20）vs．（498．46±119．08）pg／ml,P〈0．05]均显著低于对照组。血清叶酸和维生素B12水平与Hamilton抑郁分值均无相关性。结论抑郁症患者的血清叶酸和维生素B12水平低于正常人。     

叶酸联合维生素B6/B12心对脑缺血半暗带区影响

目的 研究叶酸(FA)、维生素B6(VB6)和维生素B12(VB12)对局灶性脑缺血-中脑动脉闭塞(MCAO)大鼠缺血半暗带区(ischemie penumbra,IP)的影响.方法 将SD大鼠随机分为中脑动脉闭塞模型组(MCAO)、MCAO+叶酸组(MCAO+FA)和MCAO+复合维生素(叶酸+VB6+VB12)组(MCAO+CV);预防性给药28 d后,手术制备各组大鼠大脑中动脉闭塞(MCAO)模型,造成局灶性脑缺血,对脑部进行磁共振(MRI)扫描,观察预防性给予叶酸及其联合VB6及VB12,对缺血半暗带区的改善效果.结果 缺血后6 h,半暗带区表观弥散系数(ADC):MCAO+FA组为0.61±0.04,MCAO+CV组为0.63±0.04,均高于MCAO组的0.50±0.05(P<0.05),2组平均弥散系数(DCavg)依次为0.74±0.04,0.77±0.06,均高于MCAO组的0.67±0.04(P<0.05),MCAO组部分各向异性值(FA)为0.80±0.06,高于MCAO组的0.62±0.04(P<0.05).结论 补充叶酸能使脑缺血半暗带区向正常灌注区发展,抑制缺血核心区的扩大,联合补充VB6和VB12效果更佳.     

Sparing effect of folic acid deficiency on the development of vitamin B12 deficiency in baboons fed a vitamin B12 deficient diet.

The effect of a vitamin B12 and folic acid deficient diet on juvenile and adolescent baboons (Papio cynocephalus anubis) was studied. The baboons developed clinical and hematological signs characteristics of folacin deficiency, although they were less severe in juvenile baboons. The signs disappeared when folic acid was replaced in the diet. The serum vitamin B12 levels increased in all baboons fed the vitamin B12 and folic acid deficient diet. When folic acid was added to the diet, the levels gradually decreased in adolescent baboons, liver vitamin B12 levels decreased to a lesser extent when fed a vitamin B12 and folic acid deficient diet than when fed a vitamin B12 deficient diet. In juvenile baboons fed a vitamin B12 and folic acid deficient diet, for 7 months and a vitamin B12 deficient diet for a further 11 months, liver vitamin B12 levels did not decrease at any time but were similar to those in baboons fed a vitamin B12 and folic acid supplemented diet.     

孤独症谱系障碍患儿血清叶酸及其代谢产物与维生素B12水平状况

探讨孤独症谱系障碍(autism spectrum disorder,ASD)患儿是否存在叶酸代谢异常,为建立ASD的早期预警信号和开展ASD儿童的靶向营养干预提供依据.方法 收集2015年10月-2016年9月期间在哈尔滨医科大学儿童发育行为研究中心就诊和接受康复训练,以及在本地某特教学校上学的典型ASD患者110名作为病例组,另选110名性别、年龄匹配的正常儿童青少年作为对照组.采用化学发光微粒子免疫技术(CMIA)检测2组儿童青少年血清中叶酸、维生素B12及同型半胱氨酸(Hcy)的浓度;应用酶联免疫吸附试验技术(ELISA)测定2组儿童青少年血清中叶酸代谢产物四氢叶酸(THFA)、5-甲基四氢叶酸(5-MTHF)、叶酸受体α(FRα)、叶酸受体自身抗体(FRAA)的含量,进行统计学分析.结果 ASD组血清叶酸和维生素B12的水平低于对照组,Hcy的水平高于对照组,差异均有统计学意义(t值分别为-3.12,-4.63,2.86,P值均<0.05);ASD组血清叶酸代谢产物5-MTHF的含量低于对照组,FRAA的含量高于对照组,差异均有统计学意义(t值分别为-2.28,2.88,P值均<0.05);而THFA,FRα 2组间差异均无统计学意义(P值均>0.05).结论 ASD患者体内存在明显的叶酸代谢异常,叶酸、维生素B12、5-MTHF水平降低,而Hcy、FRAA含量升高.ASD患者叶酸代谢异常可能成为ASD的预警信号,应及时开展靶向营养干预.     

Hyperhomocysteinemia,and low intakes of folic acid and vitamin B12 in urban North India

Summary Background and Aim An adverse coronary risk profile has been reported amongst rural-to-urban migrant population living in urban slums undergoing stressful socio-economic transition. These individuals are likely to have low intakes of folic acid and vitamin B12, which may have an adverse impact on serum levels of homocysteine (Hcy). To test this hypothesis, we studied serum levels of Hcy in subjects living in an urban slum of North India and healthy subjects from urban non-slum area. Methods Group I consisted of 46 subjects (22 males and 24 females) living in an urban slum, while group II consisted of healthy subjects (n = 26, 13 males and 13 females) living in the adjacent non-slum area. Anthropometric measurements, biochemical profile (fasting blood glucose, total cholesterol, serum triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol) and fasting serum levels of Hcy were measured. Dietary intakes of folic acid, vitamin B12, vitamin B1, and iron were calculated by the 24-hour dietary recall method. Serum levels of Hcy were correlated with dietary intakes of nutrients, anthropometry, and metabolic variables. Results Sex-adjusted serum levels of Hcy in mmol/L (Mean ± SD) were high, though statistically comparable, in both the groups (group I: 20.8 ± 5.9 and group II: 23.2 ± 5.9). Overall, higher than normal serum levels of Hcy (> 15 μmol/L) were recorded in 84 % of the subjects. A substantial proportion of subjects in both groups had daily nutrient intakes below that recommended for the Asian Indian population (folic acid: 93.4 % in group I and 96.7 % in group II, vitamin B12: 76.1 % in group I and 88.4 % in group II). However, between the two groups, average daily dietary intakes of both the nutrients were statistically comparable. As compared to non-vegetarians, vegetarians showed lower intakes of folic acid (p < 0.01) and vitamin B12 (p < 0.01) in both groups. On multivariate linear regression analysis with serum Hcy as the response variable and vegetarian/non-vegetarian status and sex (male/female) as predictor variables, higher serum levels of Hcy were observed in vegetarians vs non-vegetarians (β = 4.6, p < 0.05) and males vs females (β = 5.3, p < 0.01). Conclusions Low intakes of folic acid and vitamin B12, and hyperhomocysteinemia, in both the healthy population living in urban slums and adjacent urban non-slum areas, are important observations for the prevention of nutritional and cardiovascular diseases in the Indian subcontinent. Received: 30 October 2001, Accepted: 14 January 2002     

Cognitive enhancement effect of piracetam in patients with mild cognitive impairment and dementia

Effectiveness and tolerability of two piracetam-containing drugs were compared in the frame of an open, multicentre, Phase-IV, prospective study with group and self control carried out in 9 Hungarian centres in 1998. Patients with cognitive decline from Alzheimer's disease and/or cerebrovascular origin have received the drug, in the first 4 weeks in 4800, later 2400 mg daily doses. One hundred four patients finished the study. No relevant difference with statistically significant degree was registered between the two groups. Based on this fact in this study data of the 104 patients were examined together. Authors examined two problems. The first: on which cognitive function is more effective the drug. Five factors of the modified Mini-Mental State Examination were separated and compared. Nearly all of them significantly increased especially the factors of memory, and concentration-psychomotor speed. The second examined field: are there certain subgroups with prognostic value about the effectiveness of piracetam treatment. Neither the duration of the illness, nor etiologic diagnosis, severity of cognitive decline, or former treatment with piracetam did influence significantly the efficacy. In case of depressive symptoms such connection was established: the more pronounced the severity of these symptoms the higher improvement can be expected in cognitive functions. This was also stressed by the logistic regression analysis. Authors described an original evaluation method of the trail-making test, which could widen the application of this popular test in psychopharmacologic studies. Final conclusions: the cognitive enhancer effect of piracetam appeared in a few weeks. This treatment could be effective even in Alzheimer's disease, in case of more pronounced cognitive decline, longer duration of the illness, and in case of former piracetam treatment as well. The degree of cognitive improvement was most pronounced in patients with comorbid depressive symptoms.     

叶酸、维生素B_(12)对糖尿病肾病大鼠肾脏保护作用的研究

目的研究叶酸、维生素B12与糖尿病大鼠肾脏病变之间的关系并探讨糖尿病肾脏病变的发生机制。方法选用SD大鼠80只,随机分为正常组(10只)和造模组(70只)。用高脂高糖高能量饲料喂养造模大鼠,10周后进行小剂量腹腔注射链脲佐菌素以诱导糖尿病大鼠模型,并将之分为糖尿病空白组、叶酸干预组、维生素B12干预组以及叶酸联合维生素B12干预组,继续喂养8周。实验期间测定血糖、总胆固醇、甘油三酯及胰岛素等并做肾脏PAS染色。结果①高脂饲料喂养较长时间后,再空腹注射低剂量链脲佐菌素(STZ)能成功诱导稳定的糖尿病大鼠模型。糖尿病模型大鼠的甘油三酯、总胆固醇水平及随机血糖分别为(1.07±0.27)、(2.29±0.42)和(21.12±4.21)mmol/L均较正常组的(0.68±0.11)、(1.11±0.20)和(5.73±0.26)mmol/L高,差异均有统计学意义(P<0.05)。②叶酸、维生素B12以及叶酸联合维生素B12均能减少糖尿病大鼠的24小时尿微量蛋白的增幅,其中联合干预组减少24小时尿蛋白增幅的作用最明显;各干预组大鼠的肾病理PAS染色显示肾脏病变程度均轻于糖尿病空白组大鼠,并且谷胱甘肽过氧化物酶(GSH-Px)水平高于糖尿病空白组大鼠,而丙二醛(MDA)水平明显低于糖尿病空白组大鼠(P<0.05)。结论对成年SD大鼠进行较长时间的高脂高糖高能量饲料喂养后,注射小剂量STZ能够诱导出糖尿病SD大鼠模型,补充叶酸、维生素B12能起到延缓肾脏病变的作用,其保护机制可能与抗氧化应激机制有关。     

肝病患者血清叶酸与维生素B12含量的临床意义

目的 探讨肝病患者血清叶酸(FA)与维生素B12(VitB12)含量的变化及其临床意义.方法 应用微粒子化学发光免疫分析技术(CLIA)检测315例肝病患者及84例健康对照者的血清FA和VitB12含量,并对检测数据进行统计学分析.结果 急性肝炎组血清FA含量与对照组比较,差异无统计学意义(P>0.05),但其VitB12含量明显高于对照组(P<0.05).慢性肝炎轻度组血清FA、VitB12含量与对照组相比,差异无统计学意义(P>0.05).慢性肝炎中度组血清FA、VitB12含量与对照组相比,差异有统计学意义(P<0.05).慢性肝炎重度组、肝炎后肝硬化组、原发性肝癌组的FA含量均低于对照组(P<0.01),VitB12含量均高于对照组(P<0.01).结论 血清FA、VitB12含量变化与肝细胞病损程度密切相关,其检测结果对肝脏疾病的诊断、治疗及预后判断具有重要的临床价值.