阿尔茨海默病及血管性痴呆患者血清胆固醇、 Vit B12和叶酸变化的临床研究

目的探讨阿尔茨海默病(AD)和血管性痴呆(VaD)与血清胆固醇、血脂、Vit B12和叶酸的关系.方法对35例AD、35例VaD和16例健康对照组血清胆固醇、血脂、叶酸及Vit B12进行测定,并进行组间对比研究.结果AD组和VaD组血清胆固醇、甘油三酯明显高于对照组(P＜0.05),并且VaD组甘油三酯水平与对照组相比差异更明显(P＜0.01),而AD和VaD之间无显著性差异(P＞0.05),VaD组叶酸水平显著低于AD组和正常对照组(P＜0.05).Vit B12水平各组间相比无显著性差异(P＞0.05).结论血清叶酸水平降低可能与VaD发病有关,AD和VaD血清总胆固醇和甘油三酯明显增高,降低胆固醇及血脂可能对AD和VaD预防和治疗有益.     

A cross-sectional study on thyroid status in North Indian elderly outpatients with dementia

Background:

Several population based studies have demonstrated an association between hypo-or hyperthyroidism and dementia in last two decades. As a consequence, thyroid stimulating hormone has become part of the screening laboratory test for dementia.

Aim:

The aim of the present study was to evaluate the association between thyroid function and Alzheimer''s disease (AD) and vascular dementia (VaD) and to determine the risk of AD and VaD in clinically euthyroid patients.

Materials and Methods:

A cross-sectional hospital based study was carried out in subjects diagnosed with AD/VaD and were assessed for thyroid status as routine screening test.

Results:

Free T3, free T4 and TSH were studied in 114 AD patients (mean age: 65 years), 35 VaD patients (mean age: 62 years) and 105 control subjects (mean age: 62 years). In AD group, TSH levels were significantly lower than controls (P = 0.00) and for each unit increase in TSH level, the odds of having dementia decreased by 37.1%. No such relation was seen in VaD.

Conclusion:

The results suggest a consistent association of subclinical hyperthyroidism and AD.     

Dementia and subnormal levels of vitamin B12: Effects of replacement therapy on dementia

Routine determination of serum vitamin B₁₂ levels is generally recommended as part of the screening of demented patients, based on the notion that vitamin B₁₂ deficiency is one of the causes of reversible dementia. We studied the effects of vitamin B₁₂ replacement therapy in a prospective longitudinal study at a memory clinic, with special emphasis on assessment of severity of dementia: not only cognitive deterioration, but also disability in the activities of daily life, behavioural problems, and the burden experienced by the caregiver were examined using instruments of proven validity. In a series of 170 consecutive patients with dementia, subnormal serum vitamin B₁₂ levels were found in 26 cases (15%); all but one fulfilled diagnostic criteria for possible Alzheimer's disease. Cobalamin supplementation was given to all patients and the effect was evaluated after 6 months. When the size and pattern of individual change scores, and the mean change scores on all instruments were taken into account, functioning after replacement therapy was not improved. When change scores of treated patients were compared with those of patients with Alzheimer's disease (n = 69), vitamin B₁₂ replacement did not result in slowing of the progression of dementia. Contrary to widely accepted beliefs, subnormal serum vitamin B₁₂ levels are not a (quantitatively) important cause of reversible dementia.     

Peripheral neuropathy with vitamin B12 deficiency

Summary Seven patients with neuropathy associated with vitamin B₁₂ deficiency are reported. Four of them had other signs of malabsorption aside from the abnormal Schilling test. The neuropathy was diagnosed on the basis of the whole clinical picture and the neurophysiological findings. The pathogenesis of the peripheral nerve disease is discussed in the light of the evidence in the literature.

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Zusammenfassung Es wird über 7 Patienten mit einer Neuropathie bei gesicherter Vitamin B₁₂ Resorptionsstörung berichtet. Bei 4 Patienten wurden andere Anzeichen einer Malabsorption neben dem pathologischen Schilling Test festgestellt. Die Neuropathie wird aus dem gesamten klinischen Bild und den neurophysiologischen Befunden diagnostiziert. Die Pathogenese der peripheren Nervenschädigung wird anhand der Literatur diskutiert.

     

Correlations between cognitive, behavioural and psychological findings and levels of vitamin B12 and folate in patients with dementia

BACKGROUND: Associations between low levels of folate and vitamin B12 and cognitive impairment in patients with dementia have been reported. Some studies revealed correlations between low levels of vitamin B12 and behavioural and psychological signs and symptoms of dementia (BPSD) in Alzheimer's disease (AD) patients. Given the lack of studies in frontotemporal dementia (FTD) and on folate and given the methodological shortcomings of former publications, we set up a prospective study. METHODS: At inclusion, AD (n=152) and FTD (n=28) patients underwent a neuropsychological examination. Behaviour was assessed using a battery of behavioural assessment scales. Determination of serum vitamin B12 and red cell folate levels were performed within a time frame of two weeks of inclusion. RESULTS: In both patient groups, significantly negative correlations between levels of serum vitamin B12 and red cell folate and the degree of cognitive deterioration were found. No correlations with BPSD were found in the AD patient group. In FTD patients, levels of vitamin B12 were negatively correlated with both hallucinations (p=0.022) and diurnal rhythm disturbances (p=0.036). CONCLUSIONS: The observed negative correlations between levels of vitamin B12 and folate and cognitive impairment in both AD and FTD patients, raise the possibility of a non-specific etiological role. Although levels of vitamin B12 and folate did not correlate with BPSD in AD patients, negative correlations between serum vitamin B12 levels and BPSD in FTD patients were revealed. Decreased serum vitamin B12 levels may predispose FTD patients to develop hallucinations and diurnal rhythm disturbances.     

Decreased vitamin B12 and folate levels in cerebrospinal fluid and serum of multiple sclerosis patients after high-dose intravenous methylprednisolone

Twenty-one patients (15 women, 6 men) with definite multiple sclerosis (MS) were treated with 1000 mg intravenous methylprednisolone-succinate (MP) daily for 10 days. Before MP treatment there was a negative correlation (r = 0.59,P = 0.0084) between serum vitamin B₁₂ and progression rate, defined as the ratio of the score on Kurtzke's Expanded Disability Status Scale and disease duration. A significant decrease was demonstrated in the cerebrospinal fluid (CSF) and serum levels of folate and in the CSF level of Viamin B12 after MP treatment. The decrease in serum B12 was not statistically significant. After MP treatment all median levels of vitamin B₁₂ and folate were below the reference medians. We hypothesize that low or reduced vitamin B₁₂/folate levels found in MS patients may be related to previous corticosteroid treatments. Otherwise a more causal relationship between low Viamin B₁₂/folate and MS cannot be excluded. Further studies may be required to clarify the vitamin B₁₂ and folate metabolism in patients with MS.     

Sensory peripheral neuropathy of vitamin B12 deficiency: A primary demyelinating disease?

Summary In five patients with peripheral neuropathy due to vitamin B₁₂ deficiency, electrodiagnostic studies demonstrated severe reduction in sensory nerve conduction velocities compatible with a demyelinating disorder affecting sensory nerve fibres. It is suggested that in some patients lack of vitamin B₁₂ may cause primary sensory demyelinating neuropathy.     

Meta-analysis of the relationship between homocysteine, vitamin B12, folate, and multiple sclerosis

A meta-analysis was conducted to assess the relationship between serum homocysteine, vitamin B₁₂, and folate levels in patients with multiple sclerosis (MS). The DerSimonian and Laird Q test was used to evaluate the degree of heterogeneity between studies and a funnel plot was used to assess publication bias. The pooled effect size (standardized mean difference [SMD]) between patients with MS and control patients) from a random effects model was 0.84 (95% confidence interval: 0.18, 1.49) for homocysteine and -0.25 (-0.45, -0.04) for vitamin B₁₂, and from a fixed effects model was 0.98 (0.80, 1.16) for homocysteine and -0.25 (-0.41, -0.09) for vitamin B₁₂. Both nutrients were statistically significant, but the SMD for folate was not. Patients with MS were found to have raised homocysteine levels but low B₁₂ levels, which might contribute to the pathogenesis of MS.     

Vitamin B12 and folate levels in progression of Alzheimer’s disease – a short report

Abstract

Background: The status of vitamin B12 and folate has been implicated in the development and progression of Alzheimer’s disease.

Methods: The study explored this issue through a retrospective case-control study design, with follow up of the case group for 18?months. The case group (n?=?136) comprised patients 65?years or older diagnosed with Alzheimer’s disease and having a Mini-mental State Examination score (MMSE) of ≤ 27. The control group comprised healthy adults 65?years or older (n?=?338) with a MMSE score of >27.

Results: Vitamin B12 and folate levels were not found to differ between case and control groups. B12 and folate status at baseline was not predictive of disease progression in the case group.

Discussion: This lack of association differs from other studies which have shown a protective effect of vitamin B12 and folate on cognitive decline.

• KEY POINTS

• The findings of this study do not confirm evidence suggesting an effect of vitamin B12 and folate levels on development and progression of Alzheimer’s disease.

• Folate and B12 levels were similar in the Alzheimer’s group to those of healthy controls.

• Folate and B12 levels at initial assessment were not predictive of disease progression.

     

Reversal of severe neurological abnormalities after vitamin B12 replacement in the Imerslund-Grasbeck syndrome

Summary Vitamin B₁₂ malabsorption in the ileum has been postulated as the underlying cause of the Imerslund-Grasbeck syndrome comprising megaloblastic anemia, proteinuria, and multiple neurological abnormalities. A young Saudi child with spasticity, truncal ataxia, cerebral atrophy, megaloblastic anaemia and proteinuria is described. Replacement therapy with parenteral vitamin B₁₂ resulted in the complete resolution of his neurological findings and brain atrophy.     

Giant axonal neuropathy: Possibly secondary to vitamin B12 malabsorption

Summary A giant axonal neuropathy is described in an adult with no evidence of a childhood onset of his disease and no history of exposure to toxic hydrocarbons. A causal relation to vitamin B₁₂ malabsorption is proposed. This case suggests the need to expand the spectrum of diagnoses that must be considered when giant axons are encountered in peripheral nerve biopsy specimens.     

叶酸和维生素B12对老年大鼠海马中tau蛋白磷酸化的影响

目的研究叶酸和维生素B12与tau蛋白磷酸化的关系，及叶酸和维生素B12在阿尔茨海默病（Alzheimer disease’s，AD）的发病机制中的可能作用。方法用免疫印迹和免疫组织化学的方法观察和比较2个月龄和40个月龄大鼠海马中tau蛋白的磷酸化情况，以及用叶酸和维生素B12处理后的40个月龄大鼠海马中tau蛋白的磷酸化水平。结果发现40个月龄老年大鼠脑中tau蛋白Ser396／404位点磷酸化水平比2个月龄大鼠高97％。同时发现用叶酸和维生素B12处理后，40个月龄大鼠海马中tau蛋白Ser396／404位点的过度磷酸化水平降低了27％。结论叶酸和维生素B12对神经骨架蛋白tau有一定的保护作用。     

Folate, Vitamin B12, and Homocysteine as Risk Factors for Cognitive Decline in the Elderly

Objective

Cross-sectional studies have shown that the dysregulation of one-carbon metabolism is associated with cognitive impairment. However, the findings of longitudinal studies investigating this association have been inconsistent. This study investigated the prospective associations between cognitive decline and the levels of folate, vitamin B₁₂ and homocysteine both at baseline and over course of the study period.

Methods

A total of 607 (83%) elderly individuals were selected from a group of 732 elderly individuals without dementia at baseline and followed over a 2.4-year study period. The Mini-Mental State Examination (MMSE) was administered to the subjects, and the serum levels of folate, vitamin B₁₂ and homocysteine were assayed both at baseline and at follow-up examinations. Covariates included demographic data, disability, depression, alcohol consumption, physical activity, vascular risk factors, serum creatinine level, vitamin intake, and apolipoprotein E genotype.

Results

Cognitive decline was associated with decreasing quintiles of folate at baseline, a relative decline in folate and an increase in homocysteine across the two examinations after adjustment for relevant covariates.

Conclusion

These results suggest that folate and homocysteine are involved in the etiology of cognitive decline in the elderly.     

Downbeat nystagmus indicates cerebellar or brain-stem lesions in vitamin B12 deficiency

Summary Two cases of vitamin B₁₂ deficiency caused by gastric atrophy are described. Together with the neuropsychiatric features usually associated with this condition, a downbeat nystagmus syndrome was observed. It is concluded that vitamin B₁₂ deficiency may also result in lesions to those cerebellar or brain-stem structures that are generally assumed to cause downbeat nystagmus.     

Influence of vitamin B12 on brain methionine adenosyltransferase activity in senile dementia of the Alzheimer's type

Summary The influence of vitamin B₁₂ on the activity of methionine adenosyltransferase (MAT) in postmortem brains of patients with senile dementia of the Alzheimer's type (SDAT) was investigated. In samples of cortex gyrus frontalis from SDAT patients with normal and low levels of serum B₁₂, MAT V_max was significantly increased by 25% and 19%, respectively. MAT V_max from a SDAT group chronically treated with B₁₂ was similar to controls. In contrast to cortex gyrus frontalis, no significant alterations were seen in MAT activity in nucleus caudatus. This study provides evidence that SDAT is associated with significant alterations in transmethylation mechanisms in specific regions of the brain. The relationship between blood levels of B₁₂ and the actual status of this vitamin in the brain influencing the rates of synthesis of both methionine and SAM may, however, be far more complex and cannot be directly clarified on the basis of the present human brain results.     

Intergenotypic variation of Vitamin B12 and Folate in AD: In north indian population

Objectives:

Changes in lifestyle habits such as diet modification or supplementation have been indicated as probable protective factors for a number of chronic conditions including Alzheimer''s disease (AD). With this background, we aim to hypothesize that whether C677T polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene contributes towards the risk of developing AD and its association with vitamin B12 and folate levels.

Materials and Methods:

A case-control study comprising of total 200 subjects, within the age group of 50-85 years. Their blood samples were analyzed for serum folate, vitamin B12 levels, and MTHFR C677T polymorphism by restriction fragment length polymorphism (RFLP).

Results:

The mean plasma levels of vitamin B12 and folate were significantly lower in study group when compared to the control group (P < 0.001). Genotypic and allelic frequency of MTHFR gene in both groups was found to be significant (P < 0.05). The intergenotypic variations of vitamin B12 and folate were found to be significant (P < 0.001).

Conclusion:

We concluded that the subjects with homozygous mutated alleles are more prone to AD and also pointed out the influence of presence/absence of MTHFR T allelic variants on serum folate and vitamin B12 levels.     

Involuntary movements due to vitamin B12 deficiency

Abstract

Deficiency of vitamin B₁₂ produces protean effects on the nervous system, most commonly neuropathy, myelopathy, cognitive and behavioural symptoms, and optic atrophy. Involuntary movements comprise a relatively rare manifestation of this readily treatable disorder. Both adults and infants deficient in vitamin B₁₂ may present with chorea, tremor, myoclonus, Parkinsonism, dystonia, or a combination of these, which may precede diagnosis or become apparent only a few days after parenteral replacement therapy has begun. The pathogenesis of these movement disorders shows interesting parallels to certain neurodegenerative conditions. The clinical syndrome responds well to vitamin B₁₂ supplementation in most cases, and an early diagnosis is essential to reverse the haematological and neurological dysfunction characteristic of this disorder. In this article, we elucidate the association of vitamin B₁₂ deficiency with movement disorders in adults and in infants, discuss the pathogenesis of this association, review previously reported cases, and present a young adult male with severe generalized chorea that showed a salutary response to vitamin B₁₂ supplementation.     

Recovery of VEP delay in patients with vitamin B12 deficiency

Two patients with a neurologic syndrome of vitamin B₁₂ deficiency and delayed Visual Evoked Potentials are reported. VEP latencies returned to normal values from 90 to 110 days following parenteral treatment with cyanocobalamin.

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Sommario Sono descritti due pazienti che presentavano una sindrome neurologica da carenza di vitamina B-12 ed un allungamento della latenza del potenziale evocato visivo (VEP). Dopo rispettivamente 90 e 110 giorni dalla istituzione della terapia parenterale con cianocobalamina si è assistito alla rinormalizzazione delle latenze del VEP.

     

Homocysteine,vitamin B12 and folate levels in Iranian patients with Multiple Sclerosis: A case control study

Background

Recently, homocysteine (Hcy), folate, and vitamin B12 have been proposed to have several roles on MS pathogenesis.

Objective

We performed this study to determine the role of serum levels of Hcy, vitamin B12, and folate in patients with relapsing remitting MS (RRMS) and compared them with healthy controls.

Methods

We recruited 75 RRMS patients and 75 subjects as controls with the same age and sex. Homocysteine was measured using fluorimetric high-performance liquid chromatography. Plasma folate and vitamin B12 levels were measured through ion-capture method.

Results

Mean plasma levels of vitamin B12, folate, and Hcy in cases were 342.64 ± 210.66 pg/ml, 9.74 ± 4.77 ng/ml, and 22.73 ± 11.63 μM/L, respectively, which showed significant difference in comparison with the controls. In addition, there were significant correlations between mean serum Hcy levels and duration of disease (r = 0.2, p = 0.05) and treatment with interferon (r = 0.21, p = 0.01). In cases, Hcy level was higher among those on β interferon (24.56 ± 11.87 vs. 19.71 ± 10.75, p = 0.01).

Conclusions

We concluded that serum levels of vitamin B12 and folate decreased in RRMS patients, but Hcy levels increased significantly. It seems necessary to conduct prospective trials to determine whether the treatment with supplements and correct biomarker levels in the early stage of the disease can change the course of the disease. We recommend regular checking of the serum level of Hcy in patients who use disease-modifying drugs.     

阿尔茨海默病及血管性痴呆患者血清胆固醇及甲状腺激素变化的临床研究

目的探讨阿尔茨海默病(AD)和血管性痴呆(VaD)与血清胆固醇、甘油三脂、甲状腺激素的关系。方法对35例AD、35例VaD和16例健康对照组血清胆固醇、甘油三脂、甲状腺激素进行测定,并进行组间对比研究。结果 AD组和VaD组血清胆固醇、甘油三脂明显高于对照组(P<0．05),并且Va[)组甘油三脂水平与对照组相比差异更明显(P<0．01),而AD和VaD之间无显著性差异(P>0．05);AD组和VaD组血清总T4(TT4)水平明显高于健康对照组(P<0．01),而总T3(TT3)及TSH 3组之间无显著性差异。结论甲状腺激素代谢异常可能与 AD及VaD发病有关;血清胆固醇和甘油三脂增高与AD和VaD有明显的关系,降低胆固醇及血脂可能对AD和 VaD预防和治疗有益。