Elevated plasma homocysteine levels in patients treated with levodopa: association with vascular disease

BACKGROUND: Hyperhomocysteinemia is a risk factor for vascular disease and potentially for dementia and depression. The most common cause of elevated homocysteine levels is deficiency of folate or vitamin B(12). However, patients with Parkinson disease (PD) may have elevated homocysteine levels resulting from methylation of levodopa and dopamine by catechol O-methyltransferase, an enzyme that uses S-adenosylmethionine as a methyl donor and yields S-adenosylhomocysteine. Since S-adenosylhomocysteine is rapidly converted to homocysteine, levodopa therapy may put patients at increased risk for vascular disease by raising homocysteine levels. OBJECTIVES: To determine whether elevations in plasma homocysteine levels caused by levodopa use are associated with increased prevalence of coronary artery disease (CAD), and to determine what role folate and vitamin B(12) have in levodopa-induced hyperhomocysteinemia. DESIGN/METHODS: Subjects included 235 patients with PD followed up in a movement disorders clinic. Of these, 201 had been treated with levodopa, and 34 had not. Blood samples were collected for the measurement of homocysteine, folate, cobalamin, and methylmalonic acid levels. A history of CAD (prior myocardial infarctions, coronary artery bypass grafting, or coronary angioplasty procedures) was prospectively elicited. We analyzed parametric data by means of 1-way analysis of variance or the t test, and categorical data by means of the Fisher exact test or chi(2) test. RESULTS: Mean +/- SD plasma homocysteine levels were significantly higher in patients treated with levodopa (16.1 +/- 6.2 micro mol/L), compared with levodopa-na?ve patients (12.2 +/- 4.2 micro mol/L; P<.001). We found no difference in the plasma concentration of folate, cobalamin, or methylmalonic acid between the 2 groups. Patients whose homocysteine levels were in the higher quartile (>or=17.7 micro mol/L) had increased prevalence of CAD (relative risk, 1.75; 95% confidence interval, 1.08-2.70;P=.04). CONCLUSIONS: Levodopa therapy, rather than PD, is a cause of hyperhomocysteinemia in patients with PD. Deficiency of folate or vitamin B(12) levels does not explain the elevated homocysteine levels in these patients. To our knowledge, this is the first report that levodopa-related hyperhomocysteinemia is associated with increased risk for CAD. These findings have implications for the treatment of PD in patients at risk for vascular disease, and potentially for those at risk for dementia and depression.     

Behavioural and psychological symptoms of Alzheimer type dementia are not correlated with plasma homocysteine concentration

BACKGROUND/AIMS: Vitamin B12 and folate deficiencies have been associated with cognitive impairment and various psychiatric symptoms but not specifically with behavioural and psychological symptoms of dementia (BPSD). A limitation of previous studies in dementia was lack of concurrent homocysteine measurement especially as it may provide a better indicator of tissue activities of these vitamins. This study was designed to clarify whether a relationship exists between plasma homocysteine concentration and BPSD. METHODS: Plasma homocysteine, serum vitamin B12 and folate were measured in 23 Alzheimer's disease (AD) patients with BPSD and 27 AD patients without BPSD as determined through the use of the Neuropsychiatric Inventory (NPI). Blood levels of measured substances were also correlated with individual NPI scores and with cumulative NPI scores for different cluster of symptoms. RESULTS: There was no significant difference (p = 0.956) in the mean plasma homocysteine levels between AD patients with BPSD (17.48 micromol/l) and AD patients without BPSD (17.34 micromol/l). Similarly, there was no significant difference between the two groups in the mean serum B12 (382.61 and 391.60 pg/ml, respectively) and folate (7.95 and 10.02 ng/ml, respectively). Mean levels for both vitamins were well within the laboratory reference range. Neither individual nor cluster NPI scores correlated significantly with plasma homocysteine. CONCLUSION: This study shows for the first time that BPSD are not associated with hyperhomocysteinaemia in Alzheimer dementia. Although previous studies have identified homocysteine as an independent risk factor in AD, the results reported here do not lend weight to an aetiological role for homocysteine specifically in BPSD.     

Cobalamin, folate, methylmalonic acid, homocysteine, and gastritis markers in dementia

The prevalence of dementia disorders, cobalamin and/or folate deficiency as well as gastritis increases with age. To investigate whether there is an association between these conditions, plasma homocysteine (Hcy), serum methylmalonic acid, serum cobalamin and blood folate concentrations were measured. Gastritis was indirectly diagnosed by measuring serum antibodies against H,K-ATPase, HELICOBACTER PYLORI and intrinsic factor, using enzyme-linked immunosorbent assays. The studied groups consisted of 47 patients with Alzheimer's disease (AD), 9 with AD pathology in combination with additive vascular lesions, 59 with vascular dementia, 8 who were cognitively impaired, and 101 control cases. Plasma Hcy concentrations were significantly elevated in the dementia groups, with the highest levels in patients with vascular pathology. We conclude that hyperhomocysteinemia is a common finding in patients with dementia disorders of different etiologies. The markers for gastritis did not contribute to an elucidation of a possible connection between this condition, dementia disorders, or cobalamin/folate deficiency.     

Optimal use of markers for cobalamin and folate status in a psychogeriatric population

BACKGROUND: Cobalamin/folate deficiency is common in elderly subjects and may lead to psychiatric symptoms, but even more often it increases the severity of other organic and non-organic mental diseases. It is therefore of importance to evaluate the optimal use of different markers of cobalamin/folate status in a psychogeriatric population. METHODS: We measured serum cobalamin, blood folate, plasma homocysteine (tHcy) and serum methylmalonic acid (MMA) in 475 well-defined psychogeriatric patients. RESULTS: The findings in the present study showed that many (41%) of the patients with normal levels of serum MMA (< 0.41 micromol/l) had pathological values of at least one of the other markers for cobalamin/folate status, whereas only 17% of patients with normal plasma tHcy (< 19.9 micromol/l) had pathological levels of other markers. If patients with decreased levels of serum cobalamin and/or blood folate were also excluded from these patients, only nine patients with slightly elevated levels of serum MMA remained. In the present study different upper reference limits were also tested for both serum MMA and plasma tHcy. However, the use of these limits did not cause any diagnostic improvement in the evaluation of cobalamin-folate status. Plasma tHcy was increased in almost all diagnosis groups of the psychogeriatric patients, whereas serum MMA was increased in only some groups. The distribution of the two common polymorphisms of the methylenetetrahydrofolate reductase gene (C677T and A1298C) was similar in patients with elevated and normal plasma tHcy. CONCLUSIONS: The findings in the present study suggest the use of plasma tHcy, serum cobalamin and blood folate to evaluate cobalamin-folate status in psychogeriatric patients and to omit the use of serum MMA.     

Increased plasma homocysteine levels without signs of vitamin B12 deficiency in patients with multiple sclerosis assessed by blood and cerebrospinal fluid homocysteine and methylmalonic acid

OBJECTIVE: The aim of this study was to evaluate if multiple sclerosis (MS) is associated with vitamin B12 (cobalamin) deficiency. METHODS: We measured serum vitamin B12, plasma folate, serum methylmalonic acid (MMA), plasma homocysteine (tHcy) and also cerebrospinal fluid (CSF) MMA and tHcy in 72 patients with MS and 23 controls. RESULTS: The mean plasma tHcy level was significantly increased in MS patients (11.6 micromol/L) compared with controls (7.4 micromol/L) (P = 0.002). Seven patients showed low serum vitamin B12 levels but only one of them had concomitant high plasma tHcy. None of them showed high serum MMA. Plasma or blood folate levels did not differ between MS patients and controls. We found no significant differences in mean values or frequency of pathological tests of serum B12, serum MMA, mean corpuscular volume (MCV), haemoglobin concentration, CSF tHcy or CSF MMA between patients and healthy subjects. There were no correlations between CSF and serum/plasma levels of MMA or tHcy. Serum vitamin B12, serum MMA, plasma tHcy, CSF Hcy or CSF MMA were not correlated to disability status, activity of disease, duration of disease or age. CONCLUSIONS: The relevance of the increased mean value of plasma tHcy thus seems uncertain and does not indicate functional vitamin B12 deficiency. We can not, however, exclude the possibility of a genetically induced dysfunction of the homocysteine metabolism relevant for the development of neuroinflammation/degeneration. Our findings indicate that, regardless of a significant increase in plasma tHcy in MS patients, the MS disease is not generally associated with vitamin B12 deficiency since we did not find any other factors indicating vitamin B12 deficiency. Analysis of CSF MMA and CSF tHcy, which probably reflects the brain vitamin B12 status better than serum, are not warranted in MS. We conclude that B12 deficiency, in general, is not associated with MS.     

轻度认知障碍患者血浆同型半胱氨酸和血清维生素B12及叶酸水平变化研究

目的 探讨轻度认知障碍(MCI)患者血浆同型半胱氨酸(Hcy)、血清维生素B12及叶酸水平的变化及相互关系.方法 MCI组80例,正常对照组80例,检测所有观察对象的血浆同型半胱氨酸、血清VitB12及叶酸水平并分析相互关系.结果 MCI组血浆Hey水平较正常组显著增高为(18.9±8.8)μmol/L vs(14.35±5.7)μmol/L,而血清叶酸和VitB12水平在正常组和MCI组之间并没有显著差异;相对于血浆Hey正常组,MCI比值比(0R)在轻、中度高同型半胱氨酸血症组中增高(OR=1.85,95%CI=1.56～2.95;OR=3.32,95%CI=1.61～6.48;P=0.001);无论在MCI组还是在正常组中,血浆Hey与血清叶酸及Vit B12的水平均呈负相关.结论 血浆Hey水平升高与MCI相关,叶酸和VitB122缺乏可能导致血浆Hcy水平升高.     

Homocysteine, vitamin B12, and folic acid levels in Alzheimer's disease, mild cognitive impairment, and healthy elderly: baseline characteristics in subjects of the Australian Imaging Biomarker Lifestyle study

There is some debate regarding the differing levels of plasma homocysteine, vitamin B12 and serum folate between healthy controls (HC), mild cognitive impairment (MCI), and Alzheimer's disease (AD). As part of the Australian Imaging Biomarker Lifestyle (AIBL) study of aging cohort, consisting of 1,112 participants (768 HC, 133 MCI patients, and 211 AD patients), plasma homocysteine, vitamin B12, and serum and red cell folate were measured at baseline to investigate their levels, their inter-associations, and their relationships with cognition. The results of this cross-sectional study showed that homocysteine levels were increased in female AD patients compared to female HC subjects (+16%, p-value < 0.001), but not in males. Red cell folate, but not serum folate, was decreased in AD patients compared to HC (-10%, p-value = 0.004). Composite z-scores of short- and long-term episodic memory, total episodic memory, and global cognition all showed significant negative correlations with homocysteine, in all clinical categories. Increasing red cell folate had a U-shaped association with homocysteine, so that high red cell folate levels were associated with worse long-term episodic memory, total episodic memory, and global cognition. These findings underscore the association of plasma homocysteine with cognitive deterioration, although not unique to AD, and identified an unexpected abnormality of red cell folate.     

Plasma homocysteine levels in multiple sclerosis

BACKGROUND: There is evidence that homocysteine contributes to various neurodegenerative disorders, and elevated plasma homocysteine levels have been observed in patients with multiple sclerosis (MS). OBJECTIVE: To investigate if and why plasma homocysteine levels are increased in MS, and whether they play a role in the disease course. METHODS: We compared plasma levels of homocysteine in 88 patients with MS and 57 healthy controls. In the MS group, 28 had a benign course, 37 were secondary progressive, and 23 primary progressive. To explore the underlying mechanisms, we measured serum levels of vitamins B6 and B12, folate, interleukin (IL)-12, tumour necrosis factor (TNF)-alpha, leukocyte nitric oxide production, and plasma diene conjugate levels (measure of oxidative stress). RESULTS: Mean (SD) plasma homocysteine concentration was higher in patients (13.8 (4.9) micromol/l) than in controls (10.1 (2.5) micromol/l; p<0.0001). However, there were no significant differences in homocysteine levels between the three clinical subgroups of MS. Serum concentrations of vitamin B6, vitamin B12, and folate were not different between patients with MS and controls. In the MS group, there were no correlations between plasma homocysteine levels and the serum concentrations of IL-12 or TNF-alpha, leukocyte nitric oxide production, or plasma diene conjugate levels. CONCLUSIONS: Elevated plasma homocysteine occurs in both benign and progressive disease courses of MS, and seems unrelated to immune activation, oxidative stress, or a deficiency in vitamin B6, vitamin B12, or folate.     

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.     

Hyperhomocysteinemia in l-dopa treated Parkinson''s disease patients: effect of cobalamin and folate administration

Homocysteine (Hcy) is a risk factor for vascular diseases, cognitive impairment and dementia. L-dopa treatment may represent an acquired cause of hyperhomocysteinemia (HHcy), as evidenced by studies in rats as well as in Parkinson's disease (PD) patients. Folate and cobalamin status also seems to influence the effects of L-dopa on plasma Hcy levels; therefore B-vitamins supplementation has been proposed to reduce the HHcy in L-dopa treated PD patients. Plasma Hcy, folate, and cobalamin levels were evaluated in 20 PD patients treated with L-dopa in the baseline condition and following a 5-week period of treatment with cobalamin and folate; results were compared with 35 controls. Analysis of data revealed that Hcy levels were higher in L-dopa treated PD patients when compared with age- and sex-matched controls and that supplementation of the diet with cobalamin and folate is effective in reducing Hcy concentrations; these findings may have important implications in the treatment of PD patients who are potentially at risk for vascular diseases and cognitive impairment or dementia.     

Homocysteine,apolipoproteine E and methylenetetrahydrofolate reductase in Alzheimer's disease and mild cognitive impairment

BACKGROUND: Alzheimer's disease (AD) is the most common dementia disorder in elderly people. Currently, the only known genetic factor associated with the development of sporadic AD is the apolipoprotein E (ApoE) 4 allele. There is a need to identify other environmental and genetic risk factors that could modulate the risk of developing sporadic AD. OBJECTIVE: To analyse the correlation between the ApoE and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and plasma homocysteine levels and vitamins (B(12) and folic acid) concentrations in serum from patients with AD and mild cognitive impairment (MCI) as compared with control group. METHODS: The study was carried out in 99 AD patients, 98 subjects with MCI and 100 healthy subjects. Diagnosis of probable AD was made according to the NINCDS-ADRDA and DSM-IV criteria. The following factors were analysed: age, gender, duration of disease, concentration of plasma total homocysteine, folic acid and vitamin B(12) in the serum and the polymorphism of MTHRF and ApoE genes. The results obtained were analysed by multivariate analysis of regression. RESULTS: We found that plasma total homocysteine is increased in AD patients (p < 0.0001) and depended on the MTHFR T/T genotype in the presence of low folate levels (p < 0.05). The increased frequency of ApoE4 allele in the AD population was independent of homocysteine, folic acid and vitamin B(12) levels and MTHFR status. CONCLUSIONS: We conclude that the concentration of plasma total homocysteine is increased in AD patients. This may be associated with the T/T genotype in the MTHFR gene; however, the distribution of the MTHRF C677T polymorphism in the Polish population does not differ in AD and controls.     

MTHFR基因多态性及同型半胱氨酸与青年脑血管病的关系

目的:研究Ns,N10-亚甲基四氢叶酸还原酶(MTHFR)基因多态性及血浆同型半胱氨酸(Hcy)水平与青年脑血管病的关系。方法:研究对比40例青年脑血管病患者(首次发病年龄≤50岁)及32例健康青年人的MTHFR基因多态性及血浆Hcy水平。结果:(1)对照组及病例组T/T纯合子率分别为37.5％和22.5％;T等位基因频率分别为60.9％和51.3％,差异均无显著统计意义(均P>0.05)。(2)病例组血浆Hcy几何均值(11.0±2.3μmol/L)显著高于对照组(8.0±1.4μmol/L,P<0.05)。(3)所有受试者中T/T组Hcy值高于C/C组(10.4μmol/L和7.6μmol/L),但差异无显著性(P>0.05)。结合叶酸考虑,进一步将所有受试者按叶酸中位数水平分组。叶酸中位数以下组中,T/T组Hcy值显著高于C/C组(P<0.05);而叶酸中位数以上组中,T/T组Hcy值与C/C组无显著差异。(4)血浆Hcy与叶酸、维生素B12呈显著负相关,与肌酐呈显著正相关。吸烟者血浆Hcy水平显著高于不吸烟者(P<0.05)。结论:(1)本组人群MTHFR基因C677T突变的纯合子在低叶酸状态下可引起血浆Hcy水平显著增高,但与青年脑血管病无显著关系。MTHFR基因677TT纯合突变可能为健康青年人脑血管的保护因素。(2)血浆Hcy水平与青年脑血管病的发生密切相关。(3)叶酸、维生素B12肌酐、吸烟是Hcy的非遗传影响因素。     

Vitamin B12-B6-folate treatment improves blood-brain barrier function in patients with hyperhomocysteinaemia and mild cognitive impairment

Thirty patients had mild cognitive impairment and increased homocysteine levels in serum. On average, they were supplemented orally with a high dose of a vitamin B12-B6-folate combination for 270 days. All patients had normal serum B12 and folate levels at baseline. Cerebrospinal fluid levels of the tau protein (CSF-tau) and the albumin ratio were measured before and after treatment. The serum homocysteine levels were normalised after treatment. The albumin ratio significantly correlated with vascular risk factors. At baseline, the ratio was higher in the patients in comparison with age-matched controls. After treatment, the ratio was significantly reduced, which may indicate a tightening of the blood-brain barrier. The CSF-tau levels did not change significantly although there was a numeric decline. None of the patients progressed into dementia during the treatment period. When treated with a vitamin B12-B6-folate combination, patients with mild cognitive impairment and hyperhomocysteinaemia appear to improve their blood-brain barrier function. They may also stabilise their cognitive status. Further investigations are warranted on the role of blood-brain barrier dysfunction in the pathogenesis of dementia.     

Reduced plasma homocysteine levels in levodopa/entacapone treated Parkinson patients

Hyperhomocysteinemia is not only a major risk factor for atherothrombotic disease, but is also strongly associated with an increased risk of dementia and cognitive impairment, both of which are common in the course of Parkinson's disease (PD). Previous work has found that levodopa increases plasma homocysteine concentrations. Animal studies have indicated that the catechol-O-methyltransferase (COMT) inhibitors can prevent levodopa-induced elevation of homocysteine concentrations by reducing the O-methylation of levodopa. The objective of our study was to assess the impact of entacapone, a COMT inhibitor, on plasma levels of homocysteine, serum folate, and vitamin B12 in levodopa-treated PD patients. Nineteen PD patients receiving only levodopa and 21 PD patients on a combination of levodopa and entacapone participated in the cross-sectional study. The control group consisted of 17 subjects on dopamine agonists. The mean plasma homocysteine concentration in the subjects on only levodopa was higher than that in the subjects on a combination of levodopa and entacapone (P=0.001) or in the control group (P=0.0001). Concentrations of serum vitamin B12 and serum folate were on average normal in all groups, but levodopa-treated subjects (with or without entacapone therapy) were more prone to have hypovitaminosis B12 (45%) than controls on dopamine agonists (6%). We suggest that the COMT inhibition may play a promising role in successfully controlling levodopa-induced hyperhomocysteinemia and in reducing the risk of pathologies probably linked to it. These preliminary findings and postulated hypotheses must now be confirmed in prospective studies.     

Homocysteine, folate, methylation, and monoamine metabolism in depression

OBJECTIVES: Previous studies suggest that folate deficiency may occur in up to one third of patients with severe depression, and that treatment with the vitamin may enhance recovery of the mental state. There are, however, difficulties in interpreting serum and red cell folate assays in some patients, and it has been suggested that total plasma homocysteine is a more sensitive measure of functional folate (and vitamin B12) deficiency. Other studies suggest a link between folate deficiency and impaired metabolism of serotonin, dopamine, and noradrenaline (norepinephrine), which have been implicated in mood disorders. A study of homocysteine, folate, and monoamine metabolism has, therefore, been undertaken in patients with severe depression. METHODS: In 46 inpatients with severe DSM III depression, blood counts, serum and red cell folate, serum vitamin B12, total plasma homocysteine, and, in 28 patients, CSF folate, S-adenosylmethionine, and the monoamine neurotransmitter metabolites 5HIAA, HVA, and MHPG were examined. Two control groups comprised 18 healthy volunteers and 20 patients with neurological disorders, the second group undergoing CSF examination for diagnostic purposes. RESULTS: Twenty four depressed patients (52%) had raised total plasma homocysteine. Depressed patients with raised total plasma homocysteine had significant lowering of serum, red cell, and CSF folate, CSF S-adenosylmethionine and all three CSF monoamine metabolites. Total plasma homocysteine was significantly negatively correlated with red cell folate in depressed patients, but not controls. CONCLUSIONS: Utilising total plasma homocysteine as a sensitive measure of functional folate deficiency, a biological subgroup of depression with folate deficiency, impaired methylation, and monoamine neurotransmitter metabolism has been identified. Detection of this subgroup, which will not be achieved by routine blood counts, is important in view of the potential benefit of vitamin replacement.     

Lack of association between plasma homocysteine and inflammation in psychogeriatric patients

Background/Objectives: In previous studies we observed a high incidence of elevated plasma homocysteine (tHcy) concentrations in psychogeriatric patients. Plasma tHcy is increased in folate deficiency. Folates are sensitive to oxidative stress. Oxidative stress, caused by inflammatory processes, could represent an endogenous reason for folate deficiency, even when the dietary intake of the vitamin is within the recommended range. It has been suggested that oxidative stress rather than insufficient folate intake causes hyperhomocysteinemia in different forms of psychogeriatric diseases. In the present study we investigated the association between plasma tHcy and C-reactive protein (CRP), a sensitive marker for inflammation, in psychogeriatric patients. Methods: Plasma tHcy, its main determinants, and CRP were measured in plasma and serum of 132 psychogeriatric patients (53 males and 79 females, mean age 75 +/- 12 years). Results: In the psychogeriatric patients, plasma tHcy was elevated and blood folate and serum creatinine were lower than in control subjects, whereas serum CRP concentrations did not differ significantly. We also subdivided the psychogeriatric patients into different diagnosis groups, yet there were no differences in serum CRP concentrations in these groups compared with age-matched control groups. There was a significant correlation between plasma tHcy and serum CRP (rho = 0.19, p < 0.05). A stepwise multiple regression analysis including serum CRP, age, blood folate, serum cobalamin, serum methylmalonic acid and serum creatinine showed that only blood folate (p < 0.001), age (p < 0.001), serum creatinine (p < 0.001), serum cobalamin (p < 0.001), and serum methylmalonic acid (p < 0.001) independently predicted plasma tHcy concentration. Thus CRP concentration was not an independent predictor of plasma tHcy. Conclusion: The present study did not show any association between inflammatory status and plasma tHcy concentration in psychogeriatric patients.     

Elevated plasma homocysteine concentration in elderly patients with mental illness is mainly related to the presence of vascular disease and not the diagnosis

BACKGROUND: Plasma total homocysteine (tHcy) is often elevated in patients with mental illness. Since patients with mental illness and vascular disease exhibit a higher plasma tHcy concentration than patients without vascular disease, it is possible that elevated plasma tHcy in mental illness is mainly due to concomitant vascular disease. METHODS: We have investigated plasma tHcy, cobalamin/folate status, renal function and the presence of vascular disease in patients with vascular dementia (VaD, n = 501), Alzheimer's disease (AD, n = 300), depression (n = 259) and in healthy subjects (n = 144) stratified according to age (below and above 75 years). RESULTS: Plasma tHcy concentration showed the highest increase in patients with VaD compared to patients with AD or depression. After the exclusion of patients with cobalamin/folate deficiencies and increased serum creatinine, patients with AD or depression above 75 years with vascular disease showed a similar elevation of plasma tHcy concentration as patients with VaD. Furthermore, patients with AD and depression without vascular disease showed a similar plasma tHcy concentration to healthy subjects. CONCLUSION: The findings imply that elevated plasma tHcy concentration in elderly patients with mental illness is mainly associated with the presence of vascular disease and is not related to the specific psychogeriatric diagnosis.     

Elevated plasma concentrations of homocysteine in antiepileptic drug treatment

PURPOSE: Homocysteine is an experimental convulsant and an established risk factor in atherosclerosis. A nutritional deficiency of vitamin B6, vitamin B12, or folate leads to increased homocysteine plasma concentrations. During treatment with carbamazepine (CBZ), phenytoin, or phenobarbital, a deficiency in these vitamins is common. The objective of the study was to test the hypothesis that antiepileptic drug (AED) treatment is associated with increased homocysteine plasma concentrations. METHODS: A total of 51 consecutive outpatients of our epilepsy clinic receiving stable, individually adjusted AED treatment and 51 sex- and age-matched controls were enrolled in the study. Concentrations of total homocysteine and vitamin B6 were measured in plasma; vitamin B12 and folate were measured in the serum of fasted subjects. RESULTS: Patients and controls differed significantly in concentrations of folate ( 13.5+/-1.0 vs. 17.4+/-0.8 nM and vitamin B6 (39.7+/-3.4 vs. 66.2+/-7.5 nM), whereas serum concentrations of vitamin B12 were similar. The homocysteine plasma concentration was significantly increased to 14.7+/-3.0 microM in patients compared with controls (9.5+/-0.5 microM; p < 0.05, Wilcoxon rank-sum test). The number of patients with concentrations of >15 microM was significantly higher in the patient group than among controls. The same result was obtained if only patients with CBZ monotherapy were included. Patients with increased homocysteine plasma concentrations had lower folate concentrations. CONCLUSIONS: These data support the hypothesis that prolonged AED treatment may increase plasma concentrations of homocysteine, although the alternative explanation that increased homocysteine plasma concentrations are associated with the disease and not the treatment cannot be completely excluded at the moment.     

Plasma homocysteine levels in patients treated with levodopa: motor and cognitive associations

OBJECTIVE: The aim of this study was to determine whether hyperhomocysteinemia caused by levodopa used in idiopathic Parkinson's disease (IPD) is associated with cognitive or physical impairments. The role of folate and vitamin B12 levels in this context was also ascertained. METHODS: Thirty-nine patients who had been followed with the diagnosis of IPD in our clinic for > 2 years and 28 healthy control subjects with similar demographic features were included in the study. The homocysteine, folic acid and vitamin B12 levels and the results of the short test of mental status (STMS) and the clock drawing test of IPD patients were compared with those of the controls. Subsequently, the patients with a homocysteine level of >14 micromol/l were compared with those having a homocysteine level of <14 micromol/l by means of detailed neuropsychometric test batteries. RESULTS: Homocysteine levels were significantly higher in the patient group in comparison with the controls. There was a negative correlation between hyperhomocysteinemia and the levels of vitamin B12 and folate. On the other hand, a positive correlation between hyperhomocysteinemia and the levodopa dose was detected. There was a positive correlation between hyperhomocysteinemia and unified Parkinson's disease rating scale (UPDRS) motor section. The critical dose of levodopa was observed to be 300 mg/d. In terms of cognitive and frontal functions, no significant difference was detected between the patients and control group. The subgroup with a homocysteine level of >14 micromol/l had a significantly poorer performance in frontal and memory tests. DISCUSSION: In patients with IPD who are detected to have hyperhomocysteinemia, the assessment of the cognitive performance, folic acid and vitamin B12 levels and the supplementation of folic acid and vitamin B12 to the treatment regimen might be appropriate.     

Plasma homocysteine concentration and its relation to symptoms of vascular disease in psychogeriatric patients

BACKGROUND: There is a high frequency of elevated plasma total homocysteine (tHcy) concentrations in elderly patients with mental disorders. Psychogeriatric patients with a history of vascular disease exhibit a significantly higher plasma tHcy concentration than patients without vascular disease. METHOD: The main reason for the present study is to further investigate the association between plasma tHcy concentration and vascular disease in psychogeriatric patients. We therefore investigated 152 psychogeriatric patients and determined plasma tHcy and its most important determinants (serum folate and serum cobalamin, serum cystatin C and serum creatinine). The patients were divided into two groups according to the presence of vascular disease. Eighty-seven patients had concomitant vascular disease. We also analysed the natriuretic peptide N-terminal pro brain natriuretic peptide (NT-proBNP) and protein S-100B in serum. NT-proBNP is a marker for congestive heart failure, whereas protein S-100B is a marker for brain damage. RESULTS: The plasma tHcy concentration is elevated in the presence of dementia or vascular disease in psychogeriatric patients. The presence of dementia or vascular disease is also associated with higher age, renal impairment and lower serum folate concentration than in patients without dementia or vascular disease. Furthermore, we observed elevated serum concentrations of NT-proBNP in patients with dementia or vascular disease as a sign of poorer cardiovascular status. Likewise, protein S-100B concentrations were elevated in patients with dementia or vascular disease, possibly indicating brain damage in these groups of patients. CONCLUSION: The high frequency of comorbidity of vascular disease and mental illness indicates a possibility to prevent and treat psychogeriatric disease by actively counteracting vascular disease in patients with psychogeriatric symptoms. Routine determination of NT-proBNP is valuable for obtaining information about cardiovascular status.