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- Homocysteine and neuropsychiatric disorders
Several studies have demonstrated that folate supplementation is the most effective means of intervention.
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- [Homocysteine and neuropsychiatric disorders]. - PubMed - NCBI.
The Homocysteine Lowering Trialists' Collaboration 70 published a meta-analysis of 12 studies involving subjects, and concluded that folic acid at doses between 0. A study comparing doses of 0. The benefits of vitamins B12 and B6 are more modest. Meta-analysis of the effect of vitamin B12 suggested that a dose of 0. After two months almost all of the patients with elevated tHcy pre-treatment were cognitively and behaviourally improved, while the majority of patients with normal pre-treatment tHcy did not improve. Treatment with folic acid carries the risk of precipitating subacute combined degeneration of the spinal cord in individuals with subclinical vitamin B12 deficiency.
How should this information influence current clinical practice? We recommend that patients with stroke, symptoms of cerebrovascular disease, AD or mild cognitive impairment should be screened for hyperhomocysteinemia, and high Hcy treated with folic acid. Conditions known to be associated with high Hcy levels e. While the focus of folic acid fortification of cereals has so far been neural tube defects, the potential of reducing Hcy levels in the population 76 should also be a factor in the determination of governmental policy.
Dr S Reutens helped with the literature search and Angie Russell with manuscript preparation. Impaired homocysteine metabolism and atherothrombotic disease. The metabolism of homocysteine: Eur J Pediatr ; Homocysteine and its disulfide derivatives: Arterioscler Thromb Vasc Biol ; Measurement and use of total plasma homocysteine. Am J Hum Genet ; Hyperhomocysteinemia and atherosclerotic vascular disease: Arch Intern Med ; Methylenetetrahydrofolate reductase polymorphism, plasma folate, homocysteine, and risk of myocardial infarction in US physicians.see
[Homocysteine and neuropsychiatric disorders].
Reutens S, Sachdev P. Homocysteine in neuropsychiatric disorders of the elderly. Int J Geriatr Psychiatry ; Vascular pathology of homocysteinemia: Am J Pathol ; The pathogenesis of coronary artery disease. A possible role for methionine metabolism. J Clin Invest ; A quantitative assessment of plasma homocysteine as a risk factor for vascular disease: Probable benefits of increasing folic acid intakes.
Hyperhomocyst e inemia is associated with impaired endothelium-dependent vasodilation in humans. Promotion of vascular smooth muscle cell growth by homocysteine: A link to atherosclerosis. Potential role for adenosine in the pathogenesis of the vascular complications of hyperhomocysteinemia. Homocysteine and other sulfhydryl compounds enhance the binding of lipoprotein a to fibrin: Homocysteine elicits a DNA damage response in neurons that promotes apoptosis and hypersensitivity to excitotoxicity.
Involvement of N-methyl-D-aspartate receptor and free radical in homocysteine-mediated toxicity on rat cerebellar granule cells. A meta-analysis of cerebrovascular disease and hyperhomocysteinemia. Scand J Clin Lab Invest ; Relation of serum homocysteine and lipoprotein a concentrations to atherosclerotic disease in a prospective Finnish population based study. A prospective study of plasma homocyst e ine and risk of ischemic stroke. Homocysteine and ischaemic stroke in men: J Epidemiol Community Health ; Prospective study of serum total homocysteine concentration and risk of stroke in middle-aged British men.
Homocysteine and risk of cardiovascular disease among postmenopausal women.
Nonfasting plasma total homocysteine levels and stroke incidence in elderly persons: Ann Intern Med ; Homocysteine and short-term risk of myocardial infarction and stroke in the elderly: A common polymorphism in the methylenetetrahydrofolate reductase gene, homocysteine, and ischemic cerebrovascular disease.
Elevated plasma homocysteine levels and risk of silent brain infarction in elderly people. Homocysteine in cerebral macroangiography and microangiopathy. Identification of cognitive impairment in the elderly: Homocysteine is an early marker.
Dement Geriatr Cogn Disord ; J Neural Transm ; J Am Geriatr Soc ; Pathogenicity of thermolabile methylenetetrahydrofolate reductase for vascular dementia. Homocysteine as a risk factor for cognitive impairment in stroke patients. The topograhy and determinants of white matter hyperintensities in a middle-aged community sample Abstract S Plasma homocysteine levels, cerebrovascular risk factors, and cerebral white matter changes leukoaraiosis in patients with Alzheimer disease.
Abnormal amino acid metabolism in patients with early stage Alzheimer dementia. Is metabolic evidence for vitamin B12 and folate deficiency more frequent in elderly patients with Alzheimer disease? Folate, vitamin B12, serum total homocysteine levels in confirmed Alzheimer's disease.
Total serum homocysteine in senile dementia of Alzheimer type. The plasma homocysteine concentration is better than that of serum methylmalonic acid as a marker for sociopsychological performance in a psychogeriatric population. Homocysteine and cognitive function in the Sacramento area Latino study on aging. Am J Clin Nutr ; Plasma folate, vitamin B 12 , and total homocysteine and homozygosity for CT mutation of the 5,methylene tetrahydrofolate reductase gene in patients with Alzheimer's dementia.
Homocysteine, vitamin B6, and vascular disease in AD patients. Elevated plasma homocysteine levels in centenarians are not associated with cognitive impairment. Mech Ageing Dev ; Relationship between plasma homocysteine levels and brain atrophy in healthy elderly individuals. Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. N Engl J Med ; Hyperhomocysteinemia associated with poor recall in the third National Health and Nutrition Examination Survey.
Relations of vitamin B12, vitamin B6, folate, and homocysteine to cognitive performance the Normative Aging Study. Plasma total homocysteine and cognitive performance in a volunteer elderly population. Ann NY Acad Sci ; Homocysteine, B vitamin status, and cognitive function in the elderly. Total homocysteine and cognitive decline in a community-based sample of elderly subjects: Am J Epidemiol ; Plasma total homocysteine levels and cognitive function in older high functioning adults: Macarthur Studies of Successful Aging.
Folate, vitamin B12, and homocysteine in major depressive disorder. Am J Psychiatry ; Vitamin B 12 deficiency and depression in physically disabled older women: Homocysteine, folate, methylation, and monoamine metabolism in depression. J Neurol Neurosurg Psychiatry ; Coppen A, Bailey J. Enhancement of the antidepressant action of fluoxetine by folic acid: A randomised, placebo controlled trial.
J Affect Disord ; The author presents an overview of the current literature on homocysteine as a risk factor for neuropsychiatric disorders.
Individual articles were hand searched for relevant cross-references. It is biologically plausible that high homocysteine levels may cause brain injury and neuropsychiatric disorders. Homocysteine is proatherogenic and prothrombotic, thereby increasing the risk of cerebrovascular disease, and may have a direct neurotoxic effect.
Homocysteine and neuropsychiatric disorders
Evidence for homocysteine as a risk factor for cerebral microvascular disease is conflicting but warrants further study. Cross-sectional and some longitudinal studies support increased prevalence of stroke and vascular dementia in hyperhomocysteinemic individuals.
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The evidence of increased neurodegeneration is accumulating. The relationship with depression is still tentative, as it is with epilepsy. Currently, treatment studies are necessary to place the evidence on a stronger footing, and maybe high-risk patients should be screened for hyperhomocysteinemia and this should be treated with folic acid.