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Folate vascular dementia

Mahavir Singh, Akash K George, Rubens Petit Homme, Avisek Majumder, Anwesha Laha, Harpal S Sandhu, Suresh C Tyagi
Cystathionine-β-synthase (CBS) gene encodes L-serine hydrolyase which catalyzes β-reaction to condense serine with homocysteine (Hcy) by pyridoxal-5'-phosphate helps to form cystathionine which in turn is converted to cysteine. CBS resides at the intersection of transmethylation, transsulfuration, and remethylation pathways, thus lack of CBS fundamentally blocks Hcy degradation; an essential step in glutathione synthesis. Redox homeostasis, free-radical detoxification and one-carbon metabolism (Methionine-Hcy-Folate cycle) require CBS and its deficiency leads to hyperhomocysteinemia (HHcy) causing retinovascular thromboembolism and eye-lens dislocation along with vascular cognitive impairment and dementia...
May 25, 2018: Experimental Eye Research
Rita Moretti, Paola Caruso, Matteo Dal Ben, Corrado Conti, Silvia Gazzin, Claudio Tiribelli
Dementia is a worldwide health problem which affects millions of patients; Alzheimer's disease (AD) and subcortical vascular dementia (sVAD) are the two most frequent forms of its presentation. As no definite therapeutic options have been discovered, different risk factors for cognitive impairment have been searched for potential therapies. This report focuses on the possible evidence that vitamin D deficiency and hyper-homocysteinemia can be considered as two important factors for the development or the progression of neurodegenerative or vascular pathologies...
2017: Frontiers in Aging Neuroscience
Kevin Dam, Martina Füchtemeier, Tracy D Farr, Philipp Boehm-Sturm, Marco Foddis, Ulrich Dirnagl, Olga Malysheva, Marie A Caudill, Nafisa M Jadavji
Folates are B-vitamins that are vital for normal brain function. Deficiencies in folates either genetic (methylenetetrahydrofolate reductase, MTHFR) or dietary intake of folic acid result in elevated levels of homocysteine. Clinical studies have shown that elevated levels of homocysteine (Hcy) may be associated with the development of dementia, however this link remains unclear. The purpose of this study was to evaluate the impact of increased Hcy levels on a mouse model of vascular cognitive impairment (VCI) produced by chronic hypoperfusion...
March 15, 2017: Behavioural Brain Research
A David Smith, Helga Refsum
Moderately elevated plasma total homocysteine (tHcy) is a strong modifiable risk factor for vascular dementia and Alzheimer's disease. Prospectively, elevated tHcy is associated with cognitive decline, white matter damage, brain atrophy, neurofibrillary tangles, and dementia. Most homocysteine-lowering trials with folate and vitamins B6 and/or B12 tested as protective agents against cognitive decline were poorly designed by including subjects unlikely to benefit during the trial period. In contrast, trials in high-risk subjects, which have taken into account the baseline B vitamin status, show a slowing of cognitive decline and of atrophy in critical brain regions, results that are consistent with modification of the Alzheimer's disease process...
July 17, 2016: Annual Review of Nutrition
Małgorzata Bednarska-Makaruk, Ałła Graban, Agata Sobczyńska-Malefora, Dominic J Harrington, Michael Mitchell, Kieran Voong, Letian Dai, Wanda Łojkowska, Anna Bochyńska, Danuta Ryglewicz, Anna Wiśniewska, Hanna Wehr
Epigenetics (particularly DNA methylation) together with environmental and genetic factors, are key to understanding the pathogenesis of many diseases including dementia. Disturbances in DNA methylation have already been implicated in dementia. Homocysteine metabolism, with folate and vitamin B12 as essential cofactors, is integral to methylation processes. We evaluated in a case-control study the association of global DNA methylation, homocysteine, folate and vitamin B12 status with dementia. Selected polymorphisms of genes previously associated with dementia development and the influence of various factors on DNA methylation were also investigated...
August 2016: Experimental Gerontology
Atticus H Hainsworth, Natalie E Yeo, Erica M Weekman, Donna M Wilcock
Homocysteine is produced physiologically in all cells, and is present in plasma of healthy individuals (plasma [HCy]: 3-10μM). While rare genetic mutations (CBS, MTHFR) cause severe hyperhomocysteinemia ([HCy]: 100-200μM), mild-moderate hyperhomocysteinemia ([HCy]: 10-100μM) is common in older people, and is an independent risk factor for stroke and cognitive impairment. As B-vitamin supplementation (B6, B12 and folate) has well-validated homocysteine-lowering efficacy, this may be a readily-modifiable risk factor in vascular contributions to cognitive impairment and dementia (VCID)...
May 2016: Biochimica et Biophysica Acta
Thomas Gregor Issac, Soundararajan Soundarya, Rita Christopher, Sadanandavalli Retnaswami Chandra
BACKGROUND: Vitamin B12 deficiency is a common condition causing neurologic, cognitive, psychiatric, and mood symptoms. With varied religious, ethnic, and socioeconomic heterogeneity among the people in India greatly influencing their dietary habits and with the high prevalence of Helicobacter pylori infection, Vitamin B12 deficiency is not uncommon, but is often under recognized due to the lack of classical symptomatic presentation. MATERIALS AND METHODS: Retrospective study on Vitamin B12 deficiency with neuropsychiatric symptoms in patients who attended neurology, psychiatry, and geriatric OPDs for a period of 1 year in a specialized neuropsychiatric institute in South India...
January 2015: Indian Journal of Psychological Medicine
Bo Jiang, Yumei Chen, Guoen Yao, Cunshan Yao, Hongmei Zhao, Xiangdong Jia, Yunyan Zhang, Junling Ge, Enchao Qiu, Chengyun Ding
BACKGROUND: Vascular cognitive impairment-no dementia (VCIND) refers to the early or mild cognitive impairment induced by cerebral vascular injury. Research shows that serum total homocysteine (tHcy) level is an independent risk factor for cerebral vascular disease and may be closely related to cognitive function.Current studies on the tHcy level in VCIND patients are limited, and the relationship of tHcy with cognitive function remains unclear. This study aims to investigate the tHcy levels in patients with VCIND and to determine their correlation with cognitive function, as well as to provide useful clues for preventing and treating VCIND...
2014: BMC Neurology
Ramin Ansari, Ali Mahta, Eric Mallack, Jin Jun Luo
Homocysteine (Hcy) is a sulfur-containing amino acid that is generated during methionine metabolism. It has a physiologic role in DNA metabolism via methylation, a process governed by the presentation of folate, and vitamins B6 and B12. Physiologic Hcy levels are determined primarily by dietary intake and vitamin status. Elevated plasma levels of Hcy (eHcy) can be caused by deficiency of either vitamin B12 or folate, or a combination thereof. Certain genetic factors also cause eHcy, such as C667T substitution of the gene encoding methylenetetrahydrofolate reductase...
October 2014: Journal of Clinical Neurology
Charlotte E Allan, Vyara Valkanova, Klaus P Ebmeier
Depression is more common in old age than dementia yet is underdiagnosed and undertreated. It is important to recognise that patients may not always present in a typical way, features that may indicate depression include anxiety, a preoccupation with somatic symptoms, and a change in function. The presence of understandable triggers and causes should not deter GPs from offering treatment, as long as symptoms are pervasive and continuously persist beyond two weeks. Age-related disabilities and changes to physical health are major risk factors for depression in older people...
May 2014: Practitioner
Nasim Mansoori, Manjari Tripathi, Rizwan Alam, Kalpana Luthra, Sumit Sharma, Ramakrishnan Lakshmy, Mani Kalaivani, Asok K Mukhopadhyay
Low level of vitamin B12 and folic acid has been reported to play an important role in the pathogenesis of Alzheimer's disease (AD) and vascular dementia (VaD). Serum folic acid and vitamin B12 were assayed in 80 AD and 50 VaD cases and in 120 healthy controls. The reduced folate carrier (RFC1) gene, rs1051266, which encodes the RFC 1, protein was analyzed for polymorphism by polymerase chain reaction-restriction fragment length polymorphism. It was observed that the patients having folic acid <8.45 ng/mL had 2...
February 2014: American Journal of Alzheimer's Disease and Other Dementias
Zboch Marzena, Leszek Jerzy
UNLABELLED: Alzheimer's disease (AD), vascular dementia (VaD) and mixed dementia (MD) are the most common dementia diseases among the elderly. Currently, there is no effective treatment of these diseases and, therefore, it seems justified to develop the principles of prevention, taking into account the elimination of risk factors. Among them folic acid deficiency may play an important role. THE AIM OF THE STUDY: To evaluate possible relationship of folate deficiency with the development of selected dementia diseases: vascular dementia (VaD), Alzheimer's disease (AD), mixed dementia (MD)...
October 2013: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
Undine E Lang, Stefan Borgwardt
Depression is a multicausal disorder and has been associated with the risk to develop cancer, dementia, diabetes, epilepsy and stroke. As a metabolic disorder depression has been associated with obesity, diabetes, insulin sensitivity, neuropeptide Y, glucose regulation, poor glycemic control, glucagone-like peptide-1, cholezystokinin, ghrelin, leptin, the endocannabinoid system, insulin-like growth factor and gastrin-releasing peptide. As a cardiovascular disease a close relationship exists between depression and blood pressure, heart rate, norepinephrine, sympathetic tone, vascular resistance, blood viscosity, plasma volume, intima thickness and atherosclerosis...
2013: Cellular Physiology and Biochemistry
Karin Nilsson, Lars Gustafson, Björn Hultberg
BACKGROUND: Patients with vascular dementia (VaD) exhibit particularly elevated levels of plasma total homocysteine (tHcy) compared to patients with other psychogeriatric diseases. METHODS: We investigated the main determinants (age, renal impairment, cobalamin/folate status and presence of extracerebral vascular disease) of plasma tHcy in 525 patients with VaD. Furthermore, 270 patients with depression were used as a reference group to reveal the potential specificity of elevated plasma tHcy in patients with VaD...
January 2013: Dementia and Geriatric Cognitive Disorders Extra
Xuedong Liu, Ming Shi, Feng Xia, Junliang Han, Zhirong Liu, Bo Wang, Fang Yang, Li Li, Songdi Wu, Ling Wang, Nan Liu, Yali Lv, Gang Zhao
RATIONALE: Epidemiological studies suggest that elevated homocysteine is linked to stroke and heart disease. However, the results of lowering homocysteine levels in reducing the risk of stroke recurrence are controversial. AIMS: The study aims to evaluate whether homocysteine-lowering therapy with folic acid and vitamins B6 and B12 reduces recurrent stroke events and other combined incidence of recurrent vascular events and vascular death in ischemic stroke patients of low folate regions...
February 2015: International Journal of Stroke: Official Journal of the International Stroke Society
Tiffany L Sudduth, David K Powell, Charles D Smith, Abigail Greenstein, Donna M Wilcock
Vascular dementia (VaD) is the second leading cause of dementia behind Alzheimer's disease (AD) and is a frequent comorbidity with AD, estimated to occur in as many as 40% of AD patients. The causes of VaD are varied and include chronic cerebral hypoperfusion, microhemorrhages, hemorrhagic infarcts, or ischemic infarcts. We have developed a model of VaD by inducing hyperhomocysteinemia (HHcy) in wild-type mice. By placing wild-type mice on a diet deficient in folate, B6, and B12 and supplemented with excess methionine, we induced a moderate HHcy (plasma level homocysteine 82...
May 2013: Journal of Cerebral Blood Flow and Metabolism
Federico Cacciapuoti
Inheired or acquired hyperhomocysteinemia (HHcy) is associated with several impairments, as certain tumors, deep venous thrombosis, tube neural defects, osteoporosis, early atherosclerosis and vascular acute events (IMA, stroke, PVD), mild cognitive impairments till Alzheimer's disease (AD). But, vascular and neuronal derangements are the most frequent HHcy-manifestations. As far as early atherosclerosis, some clinical trials demonstrated that folates and B6-12 vitamins supplementation is unable to reduce atherosclerotic lesions and cardiovascular events, even if it lowers HHcy levels...
October 2013: Journal of Thrombosis and Thrombolysis
Martha Savaria Morris
Many epidemiologic studies have considered whether markers of B-vitamin status are associated with cognitive function and cognitive decline. This avenue of research was sparked by the homocysteine (Hcy) theory of cardiovascular disease, which was extended to Alzheimer's disease when a link between vascular dementia and Alzheimer's disease was discovered. Hcy could cause cognitive impairment via direct neurotoxicity. However, decreased remethylation of Hcy to methionine might also compromise cognitive function by means other than mere Hcy lowering...
November 1, 2012: Advances in Nutrition
Jarosław Sławek, Anna Roszmann, Piotr Robowski, Mirosława Dubaniewicz, Emilia J Sitek, Krystyna Honczarenko, Agnieszka Gorzkowska, Sławomir Budrewicz, Monika Mak, Monika Gołąb-Janowska, Ewa Koziorowska-Gawron, Marek Droździk, Mateusz Kurzawski, Tomasz Bandurski, Monika Białecka
BACKGROUND: The role of white matter hyperintensities (WMH) and homocysteine (Hcy) and other vascular risk factors in the pathogenesis of Parkinson's disease (PD) dementia (PDD) remains unclear. OBJECTIVE: The aim of the study was to assess the impact of WMH, Hcy and other biochemical and vascular risk factors on PDD. METHODS: A total of 192 patients with PD and 184 age- and sex-matched healthy controls were included. A semistructured interview was used to assess demographic and clinical variables with respect to vascular risk factors (arterial hypertension, diabetes mellitus, atrial fibrillation, ischemic heart disease, obliterative atherosclerosis, hypercholesterolemia, smoking, alcohol intake)...
2013: Neuro-degenerative Diseases
L Perez, L Heim, A Sherzai, K Jaceldo-Siegl, A Sherzai
OBJECTIVE: The objective of this review was to elucidate the relationship between VaD and various nutritional factors based on epidemiological studies. BACKGROUND: Vascular dementia (VaD) is the second most common type of dementia. The prevalence of VaD continues to increase as the US population continues to grow and age. Currently, control of potential risk factors is believed to be the most effective means of preventing VaD. Thus, identification of modifiable risk factors for VaD is crucial for development of effective treatment modalities...
April 2012: Journal of Nutrition, Health & Aging
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