vitamin-b-12 and Memory-Disorders

Homocysteine, a sulfur-containing amino acid, is a metabolite of the essential amino acid methionine, and exists at a critical biochemical intersection in the methionine cycle - between S-adenosylmethionine, the indispensable ubiquitous methyl donor, and vitamins B12 and folic acid. High blood levels of homocysteine signal a breakdown in this vital process, resulting in far-reaching biochemical and life consequences. The link between homocysteine and cardiovascular disease is well established, and decreasing plasma total homocysteine by providing nutritional cofactors for its metabolism has been shown to reduce the risk of cardiovascular events. Information has been emerging regarding a connection between homocysteine metabolism and cognitive function, from mild cognitive decline (age-related memory loss) to vascular dementia and Alzheimer's disease. Significant deficiencies in the homocysteine re-methylation cofactors cobalamin (B12) and folate, as well as the trans-sulfuration cofactor vitamin B6, are commonly seen in the elderly population, with a resultant increase in homocysteine with advancing age. Hyperhomocysteinemia has been shown to be an independent risk factor for cognitive dysfunction. Indirect and direct vascular damage can be caused by homocysteine, which has been implicated in vascular dementia, with an increased risk of multiple brain infarcts and dementia as homocysteine levels rise. A significant correlation has been found between risk of Alzheimer's disease and high plasma levels of homocysteine, as well as low levels of folic acid, and vitamins B6 and B12. All of these disease associations are thought to be interrelated via increased homocysteine and S-adenosylhomocysteine and subsequent hypomethylation of numerous substances, including DNA and proteins, that render vascular structures and neurons more susceptible to damage and apoptosis. Providing the nutritional cofactors for proper functioning of the methionine cycle may improve methylation and protect the brain from damage. Further studies need to be performed to assess whether this will also reduce the risk of cognitive diseases and/or improve cognitive functioning.

Topics: Alzheimer Disease; Cardiovascular Diseases; Cognition Disorders; Dementia, Vascular; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Memory Disorders; Methionine; Methionine Adenosyltransferase; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B 6

A 69-year-old woman reported marked restriction of voluntary movements of the hands in the preceding 6 months. She had also experienced loss of motivation, memory and concentration. Her skin was pale yellow, and scratches on her skin indicated marked pruritus.. Neurological examination revealed decreased vibratory sense in both legs. Haemoglobin concentration was 8.3 g/dl, mean corpuscular volume 114 fl, vitamin B12 level < 100 ng/l, folic acid level normal. Antibody titre against parietal cells was increased, vitamin B12 resorption diminished. Gastroscopy revealed small raised lesions, made up of hyperplastic cells which stained with chromogranin, indicating a diagnosis of microcarcinoid of the gastric mucosa.. On administration of cobalamine (1,000 micrograms i.m. daily for 2 weeks, twice weekly for 6 weeks, then once per week for the last 7 months) the blood picture returned to normal, but the microcarcinoids, the psychological symptoms and the apraxia of the hands were unchanged.

Topics: Aged; Carcinoid Tumor; Chronic Disease; Female; Gastritis, Atrophic; Hematinics; Humans; Memory Disorders; Nervous System Diseases; Psychopathology; Stomach Neoplasms; Vitamin B 12; Vitamin B 12 Deficiency

There are growing evidence indicating that the adolescent brain is persistently affected by the use of psychostimulant agents. In this regard, alcohol drinking has become rather common among the adolescents in many societies during the last decade. It is currently well known that long-term ethanol exposure deteriorates various cognitive functions such as learning and memory. Mechanistically, these adverse effects have been shown to be mediated by oxidative damage to central nervous system. On the other hand, Vit-B12 is known to improve cognitive performance by suppression of oxidative parameters. Thus, in the present study we aimed to test whether treatment by Vit-B12 could prevent ethanol-induced complications in mice using behavioral and biochemical methods. Different groups of male Syrian mice received ethanol, ethanol+Vit-B12, Vit-B12 alone, or saline during adolescence and then learning and memory functions were assessed by Morris water maze (MWM) and Passive Avoidance (PA) tests. Finally, mice were sacrificed for measurement of biochemical factors. Results indicated that, adolescent ethanol intake impairs learning and memory function through exacerbation of oxidative stress and Vit-B12 treatment improves these complications by re-establishment of oxidant/anti-oxidant balance in CNS. Moreover, we found that Vit-B12 prevents ethanol-induced reduction of BDNF and enhancement of GFAP and acetylcholinesterase (AChE) activity. In conclusion, it seems that Vit-B12 supplementation could be used as an effective therapeutic strategy to prevent learning and memory defects induced by chronic alcohol intake during adolescence.

Topics: Acetylcholinesterase; Animals; Antioxidants; Brain; Brain-Derived Neurotrophic Factor; Ethanol; Glial Fibrillary Acidic Protein; Male; Maze Learning; Memory Disorders; Mice; Oxidants; Oxidative Stress; Vitamin B 12

The cholesterol-oxidized metabolite 27-hydroxycholesterol (27-OHC) is synthesized by CYP27A1, which is a key factor in vitamin D and oxysterol metabolism. Both vitamin D and 27-OHC are considered to play important roles in Alzheimer’s disease (AD). The study aims to research the effects of co-supplementation of vitamin D, folic acid, and vitamin B12 on learning and memory ability in vitamin D-deficient mice, and to explore the underlying mechanism. In this study, C57BL/6J mice were fed a vitamin D-deficient diet for 13 weeks to establish a vitamin D-deficient mice model. The vitamin D-deficient mice were then orally gavaged with vitamin D (VD), folic acid (FA), and vitamin B12 (VB12) alone or together for eight weeks. Following the gavage, the learning and memory ability of the mice were evaluated by Morris Water Maze and Novel object recognition test. The CYP27A1-related gene and protein expressions in the liver and brain were determined by qRT-PCR. The serum level of 27-OHC was detected by HPLC-MS. Serum levels of 25(OH)D, homocysteine (Hcy), and S-Adenosylmethionine (SAM) were measured by ELISA. After feeding with the vitamin D-deficient diet, the mice performed longer latency to a platform (p < 0.001), lower average speed (p = 0.026) in the Morris Water Maze, a lower time discrimination index (p = 0.009) in Novel object recognition, and performances were reversed after vitamin D, folic acid and vitamin B12 supplementation alone or together (p < 0.05). The gene expressions of CYP27A1 in the liver and brain were upregulated in the vitamin D-deficiency (VDD) group compared with the control (CON) group (p = 0.015), while it was downregulated in VDD + VD and VDD + VD-FA/VB12 groups compared with the VDD group (p < 0.05), with a similar trend in the protein expression of CYP27A1. The serum levels of 27-OHC were higher in the VDD group, compared with CON, VDD + VD, and VDD + VD-FA/VB12 group (p < 0.05), and a similar trend was found in the brain. The serum 25(OH)D levels were significantly decreased in the vitamin D-deficiency group (p = 0.008), and increased in the vitamin D-supplemented group (p < 0.001). The serum levels of SAM were higher in the B vitamins-supplemented group, compared with CON and VDD groups (p < 0.05). This study suggests that CYP27A1 expression may be involved in the mechanism of learning and memory impairment induced by vitamin D deficiency. Co-supplementation with vitamin D, folic acid, and vitamin B12 significantly reverses this eff

Topics: Animals; Folic Acid; Memory Disorders; Mice; Mice, Inbred C57BL; S-Adenosylmethionine; Vitamin B 12; Vitamin B Complex; Vitamin D; Vitamin D Deficiency

Topics: Adult; Anesthetics, Inhalation; Ataxia; Demyelinating Diseases; Female; Humans; Inhalant Abuse; Magnetic Resonance Imaging; Male; Medical Futility; Memory Disorders; Mental Disorders; Mood Disorders; Nitrous Oxide; Psychoses, Substance-Induced; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B Complex; Young Adult

Topics: Anemia, Pernicious; Diagnosis, Differential; Humans; Intrinsic Factor; Magnetic Resonance Imaging; Male; Memory Disorders; Middle Aged; Muscle Weakness; Spinal Cord; Vitamin B 12; Vitamin B 12 Deficiency

Methionine is an essential amino acid found in rich quantities in average American diet such as meats, fish and eggs. Excessive consumption of such food often exceeds the normal requirement of the methionine in our body; which found to be related to the development of neurodegenerative disorders. However, the mechanistic pathways of methionine's influence on the brain are unclear. The present study is focus on the effects of high methionine, low folate and low vitamin B6/B12 (HM-LF-LV) diet on the dysfunction of neuronal and vascular specific markers in the brain. C57BL6/J male mice (8-10 week old) were fed with HM-LF-LV diet for a 6 week period. Cognitive function of mice was determine by measuring short-term memory using a Novel Object Recognition test (NORT). Neuronal dysfunction were evaluate by measuring the levels of Neuronal nuclear antigen (NeuN), Neuron-specific-enolase (NSE) and Fluoro-jade C(FJC) fluorescence; while cerebrovascular disruption were evaluate by assessing levels of endothelial junction proteins Vascular Endothelial-Cadherin (VE-Cadherin) and Claudin-5 in harvested brain tissue. Cerebrovascular permeability was assess by evaluating microvascular leakage of fluorescently labeled albumin in vivo. Endothelial and Neuronal Nitric Oxide Synthase (eNOS, nNOS) regulation and vascular inflammation (ICAM: intercellular adhesion molecules) were also evaluate in brain tissue. All assessments were conduct at weekly intervals throughout the study duration. NORT showed a significant temporal decrease in short-term memory of mice fed on HM-LF-LV diet for 6 weeks compared to the wild-type control group. Our experimental data showed that neuronal dysfunction (decreased NeuN levels and increased FJC positive neurons in brain) was more prominent in HM-LF-LV diet fed mice compared to normal diet fed control mice. In experimental mice, cerebrovascular disruption was found to be elevated as evident from increased pial venular permeability (microvascular leakage) and decreased in VE-Cadherin expression compared to control. Slight decrease in nNOS and increase in eNOS in experimental mice suggest a trend towards the decrease in potential for neuronal development due to the long-term HM-LF-LV diet fed. Collectively, our results suggest that a diet containing high methionine, low folate and low vitamin B6/B12 results in increased neuronal degeneration and vascular dysfunction, leading to short-term memory loss. Interestingly, significant neuronal damage pre

Topics: Animals; Dose-Response Relationship, Drug; Folic Acid; Male; Memory Disorders; Memory, Short-Term; Methionine; Mice; Mice, Inbred C57BL; Neurodegenerative Diseases; Vitamin B 12; Vitamin B 6; Vitamin B Complex

In the present study, we investigated the effects of microinjection of vitamin B

Topics: Analgesics; Animals; CA1 Region, Hippocampal; Catheters, Indwelling; Disease Models, Animal; Dose-Response Relationship, Drug; Exploratory Behavior; Facial Pain; Formaldehyde; Male; Maze Learning; Memory Disorders; Microinjections; Motor Activity; Naloxone; Narcotic Antagonists; Nootropic Agents; Rats, Wistar; Scopolamine; Vibrissae; Vitamin B 12

Hypobaric hypoxia (HH) leads to reduced oxygen delivery to brain. It could trigger cognitive dysfunction and increase the risk of dementia including Alzheimer's disease (AD). The present study was undertaken in order to examine whether B vitamins (B6, B12, folate, and choline) could exert protective effects on hypoxia-induced memory deficit and AD related molecular events in mice. Adult male Kunming mice were assigned to five groups: normoxic control, hypoxic model (HH), hypoxia+vitamin B6/B12/folate (HB), hypoxia+choline (HC), hypoxia+vitamin B6/B12/folate+choline (HBC). Mice in the hypoxia, HB, HC, and HBC groups were exposed to hypobaric hypoxia for 8 h/day for 28 days in a decompression chamber mimicking 5500 meters of high altitude. Spatial and passive memories were assessed by radial arm and step-through passive test, respectively. Levels of tau and glycogen synthase kinase (GSK)-3β phosphorylation were detected by western blot. Homocysteine (Hcy) concentrations were determined using enzymatic cycling assay. Mice in the HH group exhibited significant spatial working and passive memory impairment, increased tau phosphorylation at Thr181, Ser262, Ser202/Thr205, and Ser396 in the cortex and hippocampus, and elevated Hcy levels compared with controls. Concomitantly, the levels of Ser9-phosphorylated GSK-3β were significantly decreased in brain after hypoxic treatment. Supplementations of vitamin B6/B12/folate+choline could significantly ameliorate the hypoxia-induced memory deficits, observably decreased Hcy concentrations in serum, and markedly attenuated tau hyperphosphorylation at multiple AD-related sites through upregulating inhibitory Ser9-phosphorylated GSK-3β. Our finding give further insight into combined neuroprotective effects of vitamin B6, B12, folate, and choline on brain against hypoxia.

Topics: Animals; Avoidance Learning; Cerebral Cortex; Choline; Dietary Supplements; Disease Models, Animal; Folic Acid; Glycogen Synthase Kinase 3 beta; Hippocampus; Homocysteine; Hypoxia; Male; Maze Learning; Memory; Memory Disorders; Mice; Phosphorylation; tau Proteins; Vitamin B 12; Vitamin B 6; Vitamin B Complex

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 82.93 ± 3.561 μmol). After 11 weeks on the diet, the hyperhomocysteinemic mice showed a spatial memory deficit as assessed by the 2-day radial-arm water maze. Also, magnetic resonance imaging and subsequent histology revealed significant microhemorrhage occurrence. We found neuroinflammation induced in the hyperhomocysteinemic mice as determined by elevated interleukin (IL)-1β, tumor necrosis factor (TNF)α, and IL-6 in brain tissue. Finally, we found increased expression and increased activity of the matrix metalloproteinase 2 (MMP2) and MMP9 systems that are heavily implicated in the pathogenesis of cerebral hemorrhage. Overall, we have developed a dietary model of VaD that will be valuable for studying the pathophysiology of VaD and also for studying the comorbidity of VaD with other dementias and other neurodegenerative disorders.

Topics: Animals; Brain; Cerebral Hemorrhage; Dementia, Vascular; Diet; Disease Models, Animal; Folic Acid; Humans; Hyperhomocysteinemia; Inflammation; Interleukin-1beta; Interleukin-6; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Memory Disorders; Methionine; Mice; Mice, Inbred C57BL; Vitamin B 12; Vitamin B 6

Topics: Aged; Carcinoid Tumor; Female; Humans; Memory Disorders; Stomach Neoplasms; Vitamin B 12; Vitamin B 12 Deficiency

Hyperhomocysteinemia is associated with an increased risk of Alzheimer's disease (AD). Our previous work has demonstrated that combined folate and vitamin B12 (vit-B12) supplementation prevents tau hyperphosphorylation and memory deficits induced by acute administration of homocysteine in young rats. Here, we further investigated whether folate/vit-B12 supplementation is also effective in aged rats with a chronically high level of homocysteine. 18-month-old rats were injected with homocysteine via the vena caudalis with or without a concurrent folate/vit-B12 supplementation for 28 weeks. We found that hyperhomocysteinemia induced tau hyperphosphorylation and accumulation in hippocampus and cortex. Concurrent signaling changes included the activation of glycogen synthase kinases-3β, cyclin-dependent kinase-5, c-Jun N-terminal kinase, extracellular signal-regulated kinase, and p38MAPK, and inhibition of protein phosphatase 2A. Although the ability to learn was not affected, the aged rats exhibited significant memory deficits. Folate/vit-B12 supplementation attenuated these biochemical and behavioral correlates. These data demonstrate that folate/vit-B12 supplementation is also effective in a chronic hyperhomocysteinemia model in reversing the AD-like tau pathologies and memory deficits.

Topics: Aging; Animals; Chronic Disease; Dietary Supplements; Disease Models, Animal; Drug Therapy, Combination; Folic Acid; Hyperhomocysteinemia; Male; Memory Disorders; Phosphorylation; Rats; Rats, Sprague-Dawley; tau Proteins; Vitamin B 12

Hyperhomocysteinemia and beta-amyloid (Abeta) overproduction are critical etiological and pathological factors in Alzheimer disease, respectively; however, the intrinsic link between them is still missing. Here, we found that Abeta levels increased and amyloid precursor protein (APP) levels simultaneously decreased in hyperhomocysteinemic rats after a 2-week induction by vena caudalis injection of homocysteine. Concurrently, both the mRNA and protein levels of presenilin-1, a component of gamma-secretase, were elevated, whereas the expression levels of beta-secretase and presenilin-2 were not altered. We also observed that levels of phosphorylated APP at threonine-668, a crucial site facilitating the amyloidogenic cleavage of APP, increased in rats with hyperhomocysteinemia, although the phosphorylation per se did not increase the binding capacity of pT668-APP to the secretases. The enhanced phosphorylation of APP in these rats was not relevant to either c-Jun N-terminal kinase or cyclin-dependent kinase-5. A prominent spatial memory deficit was detected in rats with hyperhomocysteinemia. Simultaneous supplementation of folate and vitamin-B12 attenuated the hyperhomocysteinemia-induced abnormal processing of APP and improved memory. Our data revealed that hyperhomocysteinemia could increase Abeta production through the enhanced expression of gamma-secretase and APP phosphorylation, causing memory deficits that could be rescued by folate and vitamin-B12 treatment in these rats. It is suggested that hyperhomocysteinemia may serve as an upstream factor for increased Abeta production as seen in patients with Alzheimer disease.

Topics: Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Amyloid Precursor Protein Secretases; Animals; Blotting, Western; Brain; Enzyme-Linked Immunosorbent Assay; Folic Acid; Gene Expression; Hyperhomocysteinemia; Immunohistochemistry; Immunoprecipitation; Memory Disorders; Phosphorylation; Presenilin-1; Presenilin-2; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Vitamin B 12; Vitamin B Complex

An elevated blood level of homocysteine is a risk factor for cognitive impairment and dementia. Homocysteine can be lowered by folate and/or vitamin B12 supplementation; antioxidants might also be required for optimal reduction in neurovascular tissue. This report presents clinical and radiological findings from administering the antioxidant N-acetylcysteine together with B vitamins to cognitively impaired patients with hyperhomocysteinaemia.. A case series (n = 7) performed in a semi-rural General Practice setting. Formal cognitive assessments were performed in five patients, and radiological assessments in one patient, before and after supplementation.. The addition of N-acetylcysteine resulted in subjective clinical improvement in all patients, and an objective improvement in cognitive scores in five patients. One patient had radiological evidence of halted disease progression over a twelve month period.. N-acetylcysteine, together with B vitamin supplements, improves cognitive status in hyperhomocysteinaemic patients. Randomized controlled clinical trials are required to formally evaluate this treatment approach.

Topics: Acetylcysteine; Aged; Aged, 80 and over; Antioxidants; Cognition Disorders; Family Practice; Female; Folic Acid; Humans; Hyperhomocysteinemia; Male; Memory Disorders; Memory, Short-Term; Radiography; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B Complex

Topics: Aged; Humans; Intestinal Absorption; Intrinsic Factor; Memory Disorders; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Acetylcysteine; Administration, Oral; Aged; Aged, 80 and over; Antioxidants; Dietary Supplements; Drug Therapy, Combination; Female; Folic Acid; Humans; Hyperhomocysteinemia; Male; Memory Disorders; Memory, Short-Term; Treatment Outcome; Vitamin B 12

We examined the relation between plasma total homocysteine (tHcy), folate, vitamin B12, and episodic memory in elderly community-dwelling subjects. A population-based study was conducted in 1992 and 1993, and subjects were re-investigated after 6 years. Plasma analytes were determined on both occasions. At follow-up, memory performance, using the Kendrick Object Learning Test, was investigated in 2,189 subjects (age, 65-67 years at baseline). Subjects with memory deficit (test score, < 25) had higher tHcy and lower folate at follow-up compared with those without memory deficit: 12.6 (95% confidence interval [CI], 12.1, 13.1) versus 11.5 (95% CI, 11.3, 11.6) micromol/L (p < 0.001) for tHcy, and 6.7 (95% CI, 6.2, 7.1) versus 7.6 (95% CI, 7.5, 7.8) nmol/L (p < 0.001) for folate. The risk of memory deficit increased according to quintiles of tHcy both at baseline and at follow-up. A decline in tHcy, or an increase in folate, over a 6-year period was associated with a higher memory test score; and vice versa. These findings indicate that increased plasma tHcy is an independent risk factor for memory deficit both cross-sectionally and prospectively, and that a "favorable" change in folate or tHcy concentrations over time is associated with better memory performance.

Topics: Aged; Biomarkers; Cross-Sectional Studies; Female; Folic Acid; Follow-Up Studies; Homocysteine; Humans; Male; Memory; Memory Disorders; Prospective Studies; Risk Factors; Vitamin B 12

Elevated plasma total homocysteine (tHcy) is a risk factor for cardiovascular disease and is reported to be an independent risk factor for Alzheimer disease (AD) and cognitive decline. tHcy may potentiate neurotoxic and vasculopathic processes, including amyloid beta protein (Abeta) metabolism, implicated in neurodegenerative diseases.. To examine the relationship of plasma total tHcy levels with clinical, demographic, biochemical, and genetic factors in aging, mild cognitive impairment (MCI), AD, cerebral amyloid angiopathy (CAA), and Parkinson disease (PD).. Plasma tHcy, folate, vitamin B(12), creatinine, and Abeta levels were assessed in individuals evaluated in the Memory, Stroke, and Movement Disorders Units of Massachusetts General Hospital with diagnoses of AD (n = 145), MCI (n = 47), PD (n = 93), CAA (67), hypertensive intracerebral hemorrhage (hICH) (n = 25), and no dementia (n = 88).. The tHcy levels did not differ across AD, MCI, CAA, hICH, and nondemented control subjects but were increased in the PD group (p < 0.01). The elevated levels within the PD group were due to high tHcy in individuals taking levodopa (p < 0.0001). Increasing tHcy was associated with worse cognition in the PD cases, but not the other diagnostic groups. tHcy levels positively correlated with plasma Abeta levels even after adjustments for age and creatinine (p < 0.0001).. Mean tHcy levels increased with age but did not discriminate diagnostic groups aside from significant elevation in patients with PD taking levodopa. The positive association between tHcy and plasma Abeta levels raises the possibility that these circulating factors could interact to affect AD risk and cognition in PD.

Topics: Aged; Aged, 80 and over; Aging; Alzheimer Disease; Amyloid beta-Peptides; Brain; Causality; Cerebral Amyloid Angiopathy; Cognition Disorders; Creatinine; Female; Folic Acid; Homocysteine; Humans; Levodopa; Male; Memory Disorders; Middle Aged; Neurodegenerative Diseases; Parkinson Disease; Predictive Value of Tests; Vitamin B 12

The unknown biochemical basis for neurologic dysfunction in cobalamin deficiency and the frequent divergence between neurologic and hematologic manifestations led us to study homocysteine metabolism in 22 patients with pernicious anemia. Serum levels of total homocysteine (tHcy), methionine, S-adenosylmethionine (AdoMet), cysteine, cysteinylglycine (cys-gly), and glutathione (GSH) were measured. Only levels of tHcy and cysteine were increased and only GSH was decreased in cobalamin deficiency as a whole, compared with 17 control subjects. AdoMet correlated only with methionine levels (P =.015) and cysteine only with cys-gly (P =.007) in healthy subjects, but in cobalamin-deficient patients AdoMet correlated instead with cysteine, cys-gly, and folate levels only (P =.008, P =.03, and P =.03, respectively). Significant differences appeared in clinically subgrouped cobalamin-deficient patients. The 11 patients with neurologic defects had higher mean levels of folate (27.9 versus 15.4 nM), AdoMet (117.2 versus 78.6 nM), cysteine (462 versus 325 microM), and cys-gly (85.0 versus 54.7 microM) than the 11 neurologically unaffected patients. Cobalamin therapy restored all metabolic changes to normal. The results indicate that changes in several metabolic pathways differ in patients with and without neurologic dysfunction. Cysteine levels were the most significant predictors of neurologic dysfunction, but it is unclear if they are direct or indirect indicators of neurotoxicity. The higher AdoMet levels in neurologically affected patients may result from inhibition of glycine N-methyltransferase by those patients' higher folate levels. The origin of the folate differences is unclear and possibly varied. Low AdoMet and GSH levels were independent predictors of anemia.

Topics: Anemia; Anemia, Pernicious; Cysteine; Dipeptides; Folic Acid; Glutathione; Homocysteine; Humans; Memory Disorders; Methionine; Movement Disorders; Nervous System Diseases; Retrospective Studies; S-Adenosylmethionine; Sensation Disorders; Vitamin B 12; Vitamin B 12 Deficiency

Our objective was to determine whether dietary supplementation with phosphatidylcholine (PC) plus vitamin B12 could afford beneficial effects on biochemical and biophysical events in the brain of senescence-accelerated mouse (SAM) substrain SAMP8. We measured learning behaviour, hippocampal protein kinase C (PKC) activity, cerebral antioxidant status, phospholipid composition and fatty acid composition in 6-month-old SAMP8 and in age-matched controls (SAM substrain SAMR1). In comparison with SAMR1, SAMP8 showed a significant elevation in total grading score of senescence and a significant decline in acquisition SAMP8 had a lower hippocampal PKC activity and cerebral PKC-beta mRNA abundance than SAMR1. SAMP8 had increased cerebral lipid peroxide levels and proportion of sphingomyelin, and a lower proportion of 20 : 4n-6 and 22 : 6n-3 in cerebral phosphtidylethanolamine than SAMR1. SAMP8 fed the PC combined with vitamin B12 diet had an increased PKC activity and a higher proportion of 22 : 6n-3 than SAMP8 fed the control diet. These results indicate the potential benefit of PC combined with vitamin B12 as a dietary supplement.

Topics: Aging; Animals; Antioxidants; Cerebral Cortex; Diet; Fatty Acids, Omega-3; Hippocampus; Isoenzymes; Lipids; Memory Disorders; Mice; Mice, Inbred Strains; Models, Animal; Phosphatidylcholines; Phosphatidylethanolamines; Protein Kinase C; Protein Kinase C beta; Vitamin B 12

We studied the effect of low levels of vitamin B12 and folic acid, alone or combined, on cognitive performance in a population-based sample of 698 older adults (mean age = 68.7 years). No evidence was found for a vitamin-related memory deficit, but research participants with low levels of vitamin B12 exhibited reduced information processing speed relative to participants with normal vitamin B12 levels.

Topics: Aged; Aging; Cognition Disorders; Female; Folic Acid; Humans; Male; Memory Disorders; Middle Aged; Netherlands; Neuropsychological Tests; Vitamin B 12

The relationship between vitamin status and cognitive functioning has been addressed in several recent studies with inconclusive results. The purpose of this study was to examine separate and combined effects of serum vitamin B12 and folic acid on episodic memory functioning in very old age.. Four study groups were selected from a population-based sample of healthy very old adults (90-101 years of age): normal B12/normal folic acid, low B12/normal folic acid, normal B12/low folic acid, and low B12/low folic acid. Cutoff levels were set at 180 pmol/L for vitamin B12 and at 13 nmol/L for folic acid. Subjects completed two episodic recall tasks (objects and words) and two episodic recognition tasks (faces and words).. Neither vitamin affected recognition or primary memory. Most interesting, although B12 was unrelated to recall performance, subjects with low folic acid levels showed impairment in both word recall and object recall.. These results replicate and extend previous findings that folic acid may be more critical than B12 to memory functioning in late life. The selective effects of folic acid on episodic recall were discussed in terms of encoding and retrieval mechanisms, as well as in relation to brain protein synthesis.

Topics: Aged; Aged, 80 and over; Analysis of Variance; Cross-Sectional Studies; Female; Folic Acid; Folic Acid Deficiency; Humans; Male; Memory; Memory Disorders; Mental Recall; Reference Values; Sampling Studies; Vitamin B 12; Vitamin B 12 Deficiency

We investigated the effects of egg phosphatidylcholine (PC) combined with vitamin B12 on memory in the Morris water maze task, and on choline and acetylcholine (ACh) concentrations in the brain of rats. Animals with nucleus basalis Magnocellularis (NBM) lesion received intragastric administration of egg PC or vitamin B12, or both for 18 days. Memory acquisition and retention were remarkably impaired in NBM lesioned rats compared with in sham-operated control. NBM lesioned group had lower choline and ACh concentrations than control group in the frontal cortex. High dose of egg PC alone significantly increased choline concentration, but did not change ACh concentration in the frontal cortex. High dose of vitamin B12 alone did not change choline and ACh concentrations in the brain. Either egg PC or vitamin B12 did not improve memory acquisition and retention. However, low dose of egg PC combined with vitamin B12 significantly increased ACh concentration and improved memory acquisition and retention in the NBM lesioned rats. We concluded that egg PC combined with vitamin B12 improved the memory impairment of NBM lesioned rats through the action on the cholinergic neurons.

Topics: Acetylcholine; Animals; Behavior, Animal; Choline; Eggs; Male; Memory Disorders; Phosphatidylcholines; Rats; Rats, Wistar; Substantia Innominata; Vitamin B 12

Recent studies suggest that vascular disease may contribute to the cause of Alzheimer disease (AD). Since elevated plasma total homocysteine (tHcy) level is a risk factor for vascular disease, it may also be relevant to AD.. To examine the association of AD with blood levels of tHcy, and its biological determinants folate and vitamin B12.. Case-control study of 164 patients, aged 55 years or older, with a clinical diagnosis of dementia of Alzheimer type (DAT), including 76 patients with histologically confirmed AD and 108 control subjects.. Referral population to a hospital clinic between July 1988 and April 1996.. Serum tHcy, folate, and vitamin B12 levels in patients and controls at entry; the odds ratio of DAT or confirmed AD with elevated tHcy or low vitamin levels; and the rate of disease progression in relation to tHcy levels at entry.. Serum tHcy levels were significantly higher and serum folate and vitamin B12 levels were lower in patients with DAT and patients with histologically confirmed AD than in controls. The odds ratio of confirmed AD associated with a tHcy level in the top third (> or = 14 micromol/L) compared with the bottom third (< or = 11 micromol/L) of the control distribution was 4.5 (95% confidence interval, 2.2-9.2), after adjustment for age, sex, social class, cigarette smoking, and apolipoprotein E epsilon4. The corresponding odds ratio for the lower third compared with the upper third of serum folate distribution was 3.3 (95% confidence interval, 1.8-6.3) and of vitamin B12 distribution was 4.3 (95% confidence interval, 2.1-8.8). The mean tHcy levels were unaltered by duration of symptoms before enrollment and were stable for several years afterward. In a 3-year follow-up of patients with DAT, radiological evidence of disease progression was greater among those with higher tHcy levels at entry.. Low blood levels of folate and vitamin B12, and elevated tHcy levels were associated with AD. The stability of tHcy levels over time and lack of relationship with duration of symptoms argue against these findings being a consequence of disease and warrant further studies to assess the clinical relevance of these associations for AD.

Topics: Aged; Aged, 80 and over; Aging; Alzheimer Disease; Case-Control Studies; Disease Progression; Female; Folic Acid; Homocysteine; Humans; Male; Memory Disorders; Middle Aged; Polymorphism, Genetic; Predictive Value of Tests; Risk Factors; Vascular Diseases; Vitamin B 12

Topics: Aged; Female; Folic Acid; Folic Acid Deficiency; Geriatric Psychiatry; Humans; Male; Memory Disorders; Vitamin B 12; Vitamin B 12 Deficiency

We examined the relationship between low levels of serum vitamin B12 (< 200 pmol/L) and folic acid (< 11 nmol/L), separately or combined, and episodic memory performance in very old age. Participants with low serum vitamin values were compared with a control group matched for age and educational level. Participants (N = 250) were selected from a group of nondemented, community-dwelling persons ages 75-96. Episodic memory was tested by means of free recall and recognition of slowly and rapidly presented words. Results indicated a deterioration in both free recall and recognition as a function of serum vitamin status. However, no linear effects of vitamin levels on memory were observed, indicating that vitamin B12 and folic acid status may effect memory only among individuals at the low end of the distribution. We speculate that the vitamin-related memory deficit may reflect encoding problems, possibly due to alterations in brain metabolism.

Topics: Age Factors; Aged; Aging; Brain; Female; Folic Acid; Humans; Male; Memory Disorders; Mental Recall; Vitamin B 12

Topics: Humans; Memory Disorders; Memory, Short-Term; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Cognition Disorders; Female; Humans; Memory Disorders; Middle Aged; Neuropsychological Tests; Vitamin B 12; Vitamin B 12 Deficiency

We reviewed 153 episodes of cobalamin deficiency involving the nervous system that occurred in 143 patients seen over a recent 17-year period at 2 New York City hospitals. Pernicious anemia was the most common underlying cause of the deficiency. Neurologic complaints, most commonly paresthesias or ataxia, were the first symptoms of Cbl deficiency in most episodes. The median duration of symptoms before diagnosis and treatment with vitamin B12 was 4 months, although long delays in diagnosis occurred in some patients. Diminished vibratory sensation and proprioception in the lower extremities were the most common objective findings. A wide variety of neurologic symptoms and signs were encountered, however, including ataxia, loss of cutaneous sensation, muscle weakness, diminished or hyperactive reflexes, spasticity, urinary or fecal incontinence, orthostatic hypotension, loss of vision, dementia, psychoses, and disturbances of mood. Multiple neurologic syndromes were often seen in a single patient. In 42 (27.4%) of the 153 episodes, the hematocrit was normal, and in 31 (23.0%), the mean corpuscular volume was normal. Neutropenia and thrombocytopenia were unusual even in anemic patients. In nonanemic patients in whom diagnosis was delayed, neurologic progression frequently occurred although the hematocrit remained normal. In 27 episodes, the serum cobalamin concentration was only moderately decreased (in the range of 100-200 pg/ml) and in 2 the serum level was normal. Neurologic impairment, as assessed by a quantitative severity score, was judged to be mild in 99 episodes, moderate in 39 and severe in 15. Severity of neurologic dysfunction before treatment was clearly related to the duration of symptoms prior to diagnosis. In addition, the hematocrit correlated significantly with severity, independent of the longer duration of symptoms in nonanemic patients. Four patients experienced transient neurologic exacerbations soon after beginning treatment with cyanocobalamin, with subsequent recovery. Followup evaluation was adequate to assess the neurologic response to vitamin B12 therapy in 121 episodes. All patients responded, and in 57 (47.1%), recovery was complete, with no remaining symptoms or findings on examination. The severity score was reduced by 50% or greater after treatment in 91% of the episodes. Residual long-term moderate or severe neurologic disability was noted following only 7 (6.3%) episodes. The extent of neurologic involvement after treatment

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia, Pernicious; Ataxia; Evoked Potentials, Somatosensory; Humans; Memory Disorders; Mental Disorders; Middle Aged; Nervous System Diseases; Paresthesia; Peripheral Nervous System Diseases; Reflex, Abnormal; Regression Analysis; Sensation; Spinal Cord Diseases; Time Factors; Vitamin B 12; Vitamin B 12 Deficiency

Neurologic complications associated with vitamin B12 deficiency include spinal cord degeneration, peripheral neuropathy and alteration of mental status. The possibility of vitamin B12 deficiency must be considered in all patients with these nervous system disorders, even in those who do not have anemia. If treatment is started early, most of the neurologic deficits will resolve. Delayed therapy usually halts the progression of the disease, but permanent sequelae may occur.

Topics: Adult; Aged; Anemia, Pernicious; Central Nervous System Diseases; Confusion; Female; Humans; Male; Memory Disorders; Mental Disorders; Schilling Test; Spinal Cord Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Age Factors; Aged; Female; Folic Acid; Humans; Male; Memory Disorders; Middle Aged; Vitamin B 12

Topics: Child; Electroencephalography; Folic Acid; Galvanic Skin Response; Humans; Intellectual Disability; Memory Disorders; Orotic Acid; Personality Disorders; Vitamin B 12

Topics: Aged; Amino Acids; Asthenia; Dementia; Depression; Female; Humans; Male; Memory Disorders; Protein Deficiency; Vitamin B 12