Disturbances of one-carbon metabolism in neuropsychiatric disorders: a review.
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Carbon↗
Biomedical subjects
B Regland
Publications and source records attributed to B Regland.
Influence of vitamin B12 on brain methionine adenosyltransferase activity in senile dementia of the Alzheimer's type.
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 Vmax was significantly increased by 25% and 19%, respectively. MAT Vmax 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.
Age of Onset↗
Stepwise comparative status analysis (STEP): a tool for identification of regional brain syndromes in dementia.
A method for clinical examination of patients with dementia, stepwise comparative status analysis (STEP), is presented. It combines psychiatric and neurologic status examination methods to identify certain common dementia symptoms by which the patient's regional brain symptom profile can be determined. Fifty status variables (items) are estimated with respect to occurrence and severity. The analysis is performed in three steps. The scores on the 'primary' variables reflect observations of single dementia symptoms. These scores form the basis for the assessment of the 'compound' variables, which in turn form the basis for evaluation of the 'complex' variables, one of which describes the patient's regional (predominant) brain syndrome (subcortical, frontosubcortical, frontal, frontoparietal, parietal, or global). In 96 mildly and moderately demented inpatients, the global (42%) and frontosubcortical (31%) were the most common. Ninety-one percent of the patients with vascular dementia had a predominant frontal and/or subcortical symptomatology.
Aged↗
Homocysteinemia is a common feature of schizophrenia.
A significant proportion of patients with schizophrenia have increased homocysteine levels that are unrelated to psychopharmacological medication or nutrient deficiency in folate or cobalamin. This supports the hypothesis that inherent methylation deficiency is involved in the pathogenesis of schizophrenia.
Adolescent↗
Trypsin inhibition: a potential cause of cobalamin deficiency common to the pathogenesis of Alzheimer-type dementia and AIDS dementia complex?
There is increasing evidence for an association between Alzheimer-type dementia (AD) and nutritionally independent cobalamin deficiency. Furthermore, low serum cobalamin values occur in a kindred with familial Alzheimer's disease (FAD) and histopathological confirmation of AD neuropathology. The Cobalamin deficiency could be either a consequence or cause of amyloidogenesis. Cobalamin deficiency is also associated with the acquired immunodeficiency syndrome (AIDS). A common pathogenic mechanism may exist for AIDS dementia complex (ADC) and AD, but there is no explanation at present for these associations. This paper presents the hypothesis that protease inhibition is a common factor in AD and ADC resulting in protein-bound cobalamin malabsorption and disrupted cobalamin metabolism.
AIDS Dementia Complex↗
Decreased methionine adenosyltransferase activity in erythrocytes of patients with dementia disorders.
ATP:1-methionine S-adenosyltransferase (EC 2.5.1.6, MAT) activity was analyzed in erythrocytes from nine patients with a clinical diagnosis of probable Alzheimer's disease (Pro.AD), four with possible Alzheimer's disease (Pos.AD), three with mild cognitive dysfunction (MCD) and two with dementia of vascular origin (VD), and 10 age-matched control subjects. Significantly lower kinetic parameters (Vmax and Km towards methionine) for MAT were observed in all the dementia cases. In the subgroup of Pro.AD patients who also had low plasma levels of vitamin B12 (B12), the reduction in MAT Km was significantly correlated with an increase in the serum levels of homocysteine, while no such correlation was observed in all the other dementia groups. Treatment for 6 months of this subgroup of Pro.AD patients with B12 (1 mg x 7 days + 1 mg/week, i.m.), S-adenosylmethionine (SAM, 200 mg twice daily, p.o.) and folate (2.5 mg every 2 days, p.o.) caused a significant decrease in homocysteine in parallel with a significant increase in Km for MAT. These findings support the hypothesis that aberrations in the B12 dependent transmethylation reactions might be involved in the pathogenesis of dementia, and suggest that the evaluation of erythrocyte MAT activity may be a useful marker for the detection of such an aberration.
Age Distribution↗
Regulation of the hypothalamic-pituitary-adrenal axis in dementia disorders.
In 163 patients with dementia disorders, subdivided into Alzheimer's disease with early onset (AD; n = 40), senile dementia of the Alzheimer type (SDAT; n = 56), vascular dementia (VAD; n = 45) and dementia of unspecified type (NUD; n = 22) the dexamethasone suppression test (DST) was performed. The patients were rated according to the DSM-III-R criteria as having mild, moderate or severe dementia and were also assessed using the GBS scale which gives a profile of the dementia syndrome. In the total group of dementia there were significant correlations between severity of dementia and post-DST levels. The frequency of pathological DST also correlated significantly with the severity of dementia. In the subgroups of dementia a strong correlation between severity of dementia and high post-DST cortisol levels was found only in the VAD group. Between the subgroups of dementia disorders there were no significant differences in basal cortisol levels. The percentage of pathological DST was lowest in the AD group (40%). It was somewhat higher in the VAD group (49%), still higher in the SDAT group (54%) and highest in the NUD group (59%). When the relationship between post-DST cortisol levels and GBS scores was analyzed, significant correlations were found mainly in the VAD group. There intellectual impairment, anxiety, fear-panic and restlessness correlated significantly with post-DST cortisol levels. The results indicate hypothalamic overactivity in a substantial number of demented patients. In VAD and to a certain extent also in SDAT a disconnection between cortical areas, including the hippocampus, and the hypothalamus is assumed. Overactivity in the hypothalamic-pituitary-adrenal (HPA) axis is due to stress, and an insufficient feedback system leads to chronic stress adaptation failure.
Aged↗
[B12 deficiency is more than pernicious!].
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Humans↗
Homocysteinemia and schizophrenia as a case of methylation deficiency.
A 27-year-old woman is described whose disorder meets the DSM-III-R criteria for a diagnosis of schizophrenia and who was found to have a significantly increased serum level of homocysteine. Repeatedly, she improved on frequent cobalamin injections and deteriorated in periods without treatment. The effects of prolonged weekly treatment appeared to diminish as time went on, suggesting that the abnormality was not wholly cobalamin-dependent. It was found that methylenetetrahydrofolate reductase (MR) activity in cultured skin fibroblasts was reduced to a magnitude that is found among people with heterozygous deficiency. A defect in MR activity indicates a deficiency in methyltetrahydrofolate (MTHF), with a consequent reduction of the remethylation of homocysteine to methionine. Thus, reduced methylation may explain the increased levels of homocysteine and the transient effects of cobalamin treatment in the patient. Theoretically, MTHF should be the optimal treatment for her. The case reported highlights the importance of assessing the serum homocysteine level in order to detect methylation deficiency in patients with schizophrenia.
Adult↗
Hypothalamic dysfunction in dementia.
In 40 patients with Alzheimer's disease (AD) 56 patients with senile dementia of Alzheimer type (SDAT) and 45 patients with vascular dementia (VAD) degree of dementia was rated into mild, moderate and severe according to DSM-III-R and on the GBS scale. Basal cortisol levels were determined and a dexamethasone test (DST) performed. Basal cortisol levels were high in all the dementia groups. Forty percent of AD patients, 54% of SDAT patients and 49% of VAD patients were non suppressors. Significant correlations between post DST cortisol levels and rated variables were seen mainly in the VAD group. The pathological DST could hardly be explained by presence of depression. In dementia, especially those with white matter disturbances, disconnections between cortical areas (hippocampus) and hypothalamus can be assumed explaining a reduced inhibitory tone on hypothalamus. When characterizing VAD patients with pathological DST these patients were significantly more intellectually impaired, showed higher degree of anxiety, restlessness and fear-panic than VAD patients with normal DST. Some behaviourial disturbances in dementia disorders may be a consequence of HPA over activity rather than a consequence of the dementia process itself.
Aged↗
[Vitamin B 12 deficiency--even a neuropsychiatric problem].
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Humans↗
The role of amyloid beta-protein in Alzheimer's disease.
Deposition of amyloid beta-protein in the brain has been regarded as the central event in Alzheimer's disease; however, amyloid beta-protein precursor is an endogenous protein, probably with neurotrophic functions. An alternative hypothesis is that amyloid beta-protein is involved in the disease process secondarily, as a protective reactant when brain cells are injured. Insufficiency of amyloid beta-protein precursor, whether because of a genetic defect or in relation to the action of environmental factors, then allows development of Alzheimer changes.
Alzheimer Disease↗
Dementia patients with low serum cobalamin concentration: relationship to atrophic gastritis.
Serum concentrations of group I pepsinogens (pepsinogen-I) and gastrin were determined in patients with dementia disorders in order to assess the relationship, if any, between these indices of gastric mucosal function and serum cobalamin (vitamin B12) levels. A significant positive correlation between pepsinogen-I and B12 and, as expected, an inverse relationship between gastrin and pepsinogen-I concentrations was found, indicating that vitamin B12 deficiency was mainly determined by gastric mucosal atrophy (atrophic gastritis) in this West-Swedish sample of patients with dementia disorders. Patients with low B12 but normal gastrin and pepsinogen-I concentrations should, therefore, be further evaluated for possible nutritional deficiency, as well as nongastric causes of poor B12 assimilation from the diet.
Aged↗
Slowed synthesis of DNA and methionine is a pathogenetic mechanism common to dementia in Down's syndrome, AIDS and Alzheimer's disease?
This is a presentation of the hypothesis of a pathogenetic mechanism common to the dementia seen in Alzheimer's disease (AD), Down's Syndrome (DS) and the acquired immunodeficiency syndrome (AIDS). As there is experimental evidence of defective DNA repair capacity in AD and DS, unrepaired damage to DNA occurs in these diseases and may lead to complete breakdown of cellular function and ultimate cell death. Cobalamin and folate are coordinated in a vulnerable key position in the synthesis of DNA and S-adenosylmethionine (SAM). Cobalamin/folate deficiency, a significant feature in senile dementia of Alzheimer type and in AIDS-related dementia complex, will result in concomitant slowed synthesis of DNA and SAM. The enzyme cystathionine-beta-synthetase (CBS) has been localized to the chromosome band 21q22.3. Owing to gene dosage, CBS activity is increased in trisomy 21. As a consequence, cobalamin/folate metabolism is inhibited, which leads to slowing of DNA and SAM synthesis in DS patients. Amyloidosis is a hallmark of AD and DS brain neuropathology and recent experimental findings support the view that amyloid or amyloid precursors stimulate DNA synthesis, which is in agreement with the hypothesis presented in this paper. In summary, demented patients with cobalamin/folate deficiency, trisomy 21 and human immunodeficiency virus (HIV) infection display a simultaneous downregulation of DNA and SAM synthesis, which may indicate a pathway common to the dementia seen in AD, DS and AIDS.
AIDS Dementia Complex↗
Vitamin B12 in CSF: reduced CSF/serum B12 ratio in demented men.
Vitamin B12 concentrations were determined in serum and cerebrospinal fluid (CSF) of 32 controls and 102 patients with dementia. The dementias were classified as Alzheimer's disease (AD), senile dementia of Alzheimer type (SDAT) and multi-infarct dementia (MID). A substantial number of patients (n = 42) could not be assigned to any of these diagnostic groups, as their dementias were of non-AD/SDAT and non-MID types. They were instead assigned to a group called non ultra descriptum (NUD). CSF B12 correlated significantly with serum B12. There were no statistically significant differences in serum B12 levels between the groups. Although with considerable overlap, CSF B12 concentrations and CSF/serum B12 ratios were significantly lower in the NUD group than in the control group. The NUD group had significantly lower CSF/serum B12 ratios than the group of patients with AD/SDAT. There was significant male predominance in the group of demented patients that had low CSF/serum B12 ratios outside the bivariate reference region. CSF and serum B12 levels appear insufficient as measures of the true brain vitamin B12 status. It may be a more dynamic approach to use the CSF/serum B12 ratio as an indication of transport function across the blood brain barrier, and possibly also across the CSF brain cell barrier.
Aged↗
Vitamin B12-induced reduction of platelet monoamine oxidase activity in patients with dementia and pernicious anaemia.
Platelet monoamine oxidase (MAO) activity has previously been shown to be increased in patients with senile dementia of Alzheimer type (SDAT) and in patients with megaloblastic anaemia. Moreover, low serum B12 levels were found to be 4-5 times more frequent in SDAT compared with an unselected population of similar age. In the present investigation, platelet MAO activity was estimated in 14 SDAT patients with relatively low serum B12 levels and in 4 patients with pernicious anaemia. Before B12 therapy, platelet MAO activity was significantly increased in both patient groups compared with a control group. After B12 therapy, platelet MAO activity was significantly reduced in both patient groups to apparently normal levels. The present results show that B12 status is a controlling factor of platelet MAO activity and confirm that a significant connection exists between vitamin B12 deficiency and primary degenerative dementia disorders, such as SDAT.
Aged↗
Low B12 levels related to high activity of platelet MAO in patients with dementia disorders. A retrospective study.
In 35 patients with Alzheimer's presenile disease (AD), 56 patients with senile dementia of the Alzheimer type (SDAT), 54 patients with vascular dementia (VD) and 10 patients with confusional states, age, vitamin B12 in serum, P-folate, B-folate and B-Hb were investigated. Platelet monoamine oxidase (MAO) and cerebrospinal fluid (CSF) levels of homovanillic acid (HVA), 5-hydroxyin-doleacetic acid and 3-methoxy-4-hydroxyphenylglycol were measured. Group differences showed that vitamin B12 levels were reduced in the group of patients with confusional states and SDAT. Five out of ten and 13 out of 56 (respectively) had vitamin B12 concentrations below the lower limit of the reference value (130 pmol/l). A negative correlation was found between B12 levels and platelet MAO activity. The findings indicate that there is a subgroup of patients with late-onset dementia that has low vitamin B12 blood concentrations. HVA levels in CSF, usually found to be reduced in AD patients, were normal in this subgroup.
Aged↗
[Scanning electron microscopy studies of bronchial epithelium in pulmonary diseases].
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Adult↗