vitamin-b-12 and Cognition-Disorders

Dementia is a syndrome characterized by progressive cognitive impairment that interferes with independent function in daily activities. Symptoms of dementia depend on its cause and vary greatly between individuals. There is extensive evidence supporting a relationship between diet and cognitive functions. This systematic review studies the efficacy of using vitamin supplements in the diet as a solution to nutritional deficiencies and the prevention of dementia and mild cognitive impairment.. An intensive search of different databases (PubMed, Web of Science, and Cochrane CENTRAL) was performed. Articles that were published between 2011 and November 2021 were retrieved using the mentioned search strategy. This systematic review has been conducted according to the PRISMA statement.. Folic acid supplementation proved to have better outcomes on cognitive tests than their respective control groups. The combined supplementation of folic acid and vitamin B12 showed some discrepancies between studies. Thiamine as supplementation did not only prove to have a positive impact on cognitive performance when given alone but also when given in combination with folic acid. Regarding vitamin D supplementation, the results observed were not so encouraging. A concomitant supplementation of low-dose vitamin E and vitamin C was also not associated with an improvement of cognitive function.. The findings of this systematic review suggest that supplementation of B Complex vitamins, especially folic acid, may have a positive effect on delaying and preventing the risk of cognitive decline. Ascorbic acid and a high dose of vitamin E, when given separately, also showed positive effects on cognitive performance, but there is not sufficient evidence to support their use. The results of vitamin D supplementation trials are not conclusive in assessing the potential benefits that vitamin D might have on cognition.

Topics: Cognition Disorders; Dementia; Dietary Supplements; Humans; Vitamin B 12; Vitamins

Vitamin B deficiency and elevated total plasma homocysteine have been associated with cognitive impairment and dementia in later life, although it is unknown if treatment with these vitamins improves cognitive outcomes.. The objectives of this study were to examine the efficacy of treatment with vitamin B. We summarized findings from previous systematic reviews of clinical trials and performed a new systematic review and meta-analysis of 31 English-language, randomized placebo-controlled trials of B-vitamin supplementation of individuals with and without existing cognitive impairment.. Previous reviews have generally reported no effect of B vitamins on cognitive function in older adults with or without cognitive impairment at study entry, although these vitamins effectively lowered total plasma homocysteine levels in participants. Ten randomized placebo-controlled trials of 1925 participants with pre-existing cognitive impairment and 21 trials of 15,104 participants without cognitive impairment have been completed to date but these generally confirmed findings from previous reviews with the exception of two trials that showed a modest but clinically uncertain benefit for vitamins in people with elevated plasma homocysteine. B-vitamin supplementation did not show an improvement in Mini-Mental State Examination scores for individuals with (mean difference 0.16, 95% confidence interval - 0.18 to 0.51) and without (mean difference 0.04, 95% confidence interval - 0.10 to 0.18) cognitive impairment compared to placebo.. Raised total plasma homocysteine is associated with an increased risk of cognitive impairment and dementia, although available evidence from randomized controlled trials shows no obvious cognitive benefit of lowering homocysteine using B vitamins. Existing trials vary greatly in the type of supplementation, population sampled, study quality, and duration of treatment, thereby making it difficult to draw firm conclusions from existing data. Findings should therefore be viewed in the context of the limitations of the available data and the lack of evidence of effect should not necessarily be interpreted as evidence of no effect.

Topics: Aged; Cognition; Cognition Disorders; Dementia; Dietary Supplements; Female; Folic Acid; Homocysteine; Humans; Male; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Vitamin B12 and folic acid deficiencies are particularly frequent conditions in older people. Since these metabolic disorders represent relevant dyscognitive factors, the assessment of vitamin B12 and folic acid levels is essential in the diagnostic approach of cognitive disorders, such as mild cognitive impairment and dementia in an outpatient memory clinic. This article summarizes the relevant diagnostic and therapeutic aspects of vitamin B12 and folic acid deficiencies and their effects on cognition. The literature review is supplemented by a data analysis of a naturalistic cohort of 250 patients from this outpatient memory clinic.

Topics: Aged; Aged, 80 and over; Cognition; Cognition Disorders; Data Analysis; Folic Acid; Folic Acid Deficiency; Humans; Outpatients; Universities; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Acetylcholine; Cognition Disorders; Humans; Parkinson Disease; Severity of Illness Index; Vitamin B 12

Hyperhomocysteinemia has been associated with cognitive disorders such as mild cognitive impairment, Alzheimer's disease and vascular dementia. Previous studies showed that levodopa-treated Parkinson's disease (PD) patients were likely to have elevated homocysteine levels. In addition, epidemiological evidence found that cognitive impairment presented in the vast majority of PD patients. However, what role homocysteine played in cognitive function of PD patients remained debated. Therefore, we conducted this meta-analysis to investigate the possible correlations among cognitive function, homocysteine, folate and vitamin B12 levels in PD patients. A structured literature search was carried out on Pubmed, Springer, EMbase, Cochrane library, CNKI, VP and Wanfang database up to April 2016 using strict inclusion criteria. Data on demographic information, levodopa equivalent dosage, homocysteine, folate and vitamin B12 levels and Mini Mental Scale Examination scores were collected and pooled. The mean difference (MD) with 95% confidence intervals (CIs) was used as the effect size. Of 75 articles identified, 15 were eligible for inclusion. The results suggested that PD patients with cognitive dysfunction were likely to have higher homocysteine levels(MD=5.05, 95%CI [4.03, 6.07]), lower folate(MD=-0.21, 95%CI [-0.34, -0.08]) and vitamin B12 levels(MD=-47.58, 95%CI [-72.07, -23.09]). We again verified a close relationship between hyperhomocysteinemia and PD (MD=5.67, 95%CI [4.40, 6.94]). We concluded that hyperhomocysteinemia was related to cognitive impairment of PD patients, and further studies should focus on the intervention to lower homocysteine level, hopefully to provide useful advice for clinical practice.

Topics: Adult; Aged; Aged, 80 and over; Cognition; Cognition Disorders; Female; Folic Acid; Homocysteine; Humans; Levodopa; Male; Middle Aged; Parkinson Disease; Treatment Outcome; Vitamin B 12

Increase in serum homocysteine is shown to be a potential risk factor for cognitive impairment. Evidence suggests that vitamin B supplementation may reduce cognitive decline by lowering the homocysteine levels. The current meta-analysis evaluated the efficacy of folic acid along with vitamin B12 and/or B6 in lowering homocysteine, thereby attenuating cognitive decline in elderly patients with Alzheimer disease or dementia. Randomized controlled trials (RCTs) comparing the efficacy of folate and B vitamin supplementation in patients with cognitive decline secondary to Alzheimer disease or dementia were identified using the keywords, "homocysteine, hyper-homocysteinemia, B vitamin, vitamin B6, B12, folic acid, cognitive, Alzheimer's disease, and dementia." The outcome measures analyzed were the Mini-Mental State Examination (MMSE) score and serum homocysteine. Of the 77 studies identified, 4 RCTs were included in the current meta-analysis. The baseline characteristics, age, and gender distribution of patients among the 2 groups (supplement vs placebo) were comparable. The results reveal that the intervention group achieved significantly greater reduction in homocysteine levels than the control (pooled difference in means = -3.625, 95% confidence interval [CI] = -5.642 to -1.608, P < .001). However, no significant difference in MMSE (pooled difference in means = 0.027, 95% CI = -0.518 to 0.573, P = 0.921) was observed between the groups. Taken together, vitamin B supplementation was effective in reducing serum homocysteine levels. However, it did not translate into cognitive improvement, indicating that the existing data on vitamin B-induced improvement in cognition by lowering homocysteine levels are conflicting.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Cognition; Cognition Disorders; Dementia; Dietary Supplements; Drug Therapy, Combination; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Vitamin B 12; Vitamin B 6; Vitamin B Complex

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. Homocysteine may interact with both risk factors and protective factors, thereby identifying people at risk but also providing potential strategies for early intervention. Public health steps to slow cognitive decline should be promoted in individuals who are at risk of dementia, and more trials are needed to see if simple interventions with nutrients can prevent progression to dementia.

Topics: Aging; Animals; Biomarkers; Cerebrovascular Circulation; Cognition Disorders; Cognitive Dysfunction; Dietary Supplements; Evidence-Based Medicine; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Neurodegenerative Diseases; Nootropic Agents; Nutritional Status; Practice Guidelines as Topic; Risk Factors; Vitamin B 12; Vitamin B 6

Elevated plasma homocysteine ​​(Hcy) levels have been associated with cognitive dysfunction in a wide range of conditions. The aim of this review is to establish which cognitive domains and populations are the most affected.. We systematically review the literature and consider all articles that showed any relationship between plasma Hcy levels and scores achieved on cognitive performance tests in both, the general population and patients suffering from central nervous system disorders and other diseases. When effect sizes were available and combinable, several meta-analyses were performed.. We found 111 pertinent articles. There were 24 cohort studies, 18 randomized trials, 21 case-control studies, and 48 cross-sectional studies. This review reveals a positive trend between cognitive decline and increased plasma Hcy concentrations in general population and in patients with cognitive impairments. Results from the meta-analyses also confirm this trend. Treatment with vitamin supplementation fails to show a reduction in cognitive decline.. Further investigations are warranted to clarify this relationship. Earlier detection of the elevated Hcy levels may be an effective intervention to prevent cognitive impairment and dementia.

Topics: Cognition; Cognition Disorders; Cross-Sectional Studies; Folic Acid; Homocysteine; Humans; Vitamin B 12

Vitamin B-12 is essential for brain development, neural myelination, and cognitive function. Inadequate vitamin B-12 status during pregnancy and early childhood has been associated with adverse child health outcomes, including impaired cognitive development. However, the underlying mechanisms have not been elucidated. This review was conducted to examine the evidence that links vitamin B-12 and cognition in children. The search strategy resulted in 17 studies: 3 cross-sectional, 1 case-control, and 12 cohort studies, and 1 randomized trial. Cognitive processes assessed included attention, memory, and perception. Developmental outcomes, academic performance, and intelligence quotient were also considered. Despite the high prevalence of vitamin B-12 insufficiency and associated risk of adverse cognitive outcomes in children, to our knowledge, no studies to date have been conducted to examine the effects of vitamin B-12 supplementation on cognition in children. The role of vitamin B-12 in the etiology of child cognitive outcomes needs to be elucidated to inform public health interventions.

Topics: Attention; Child; Child Development; Child Nutritional Physiological Phenomena; Cognition; Cognition Disorders; Dietary Supplements; Humans; Memory; Nutritional Status; Vitamin B 12; Vitamin B 12 Deficiency

The objective of this review was to evaluate the evidence from human studies on the intake of vitamins, either as monotherapies or in combination with other vitamins, as neuroprotective agents that may delay the onset of cognitive decline in older adults.. Evidence-based methodologies were used to capture and evaluate the highest levels of evidence.. The current evidence available showed no association for cognitive benefits of vitamins B6 or B12 as a monotherapy, and recent systematic reviews provide no clear evidence that supplementation with vitamin B6, B12 and/or folic acid improves dementia outcomes or slows cognitive decline, even though it may normalise homocysteine levels. Meta-analyses from systematic reviews have shown an association between low vitamin D levels and diminished cognitive function, although causality cannot be confirmed from the available evidence. There is no convincing evidence for an association of vitamin A, vitamin C or vitamin E either as a monotherapy or in combination with other antioxidant vitamins such as β-carotene and the prevention of cognitive decline. The appraisal of nineteen systematic reviews and meta-analyses has highlighted the heterogeneity between studies, and the need for better consensus on definitions of cognitive decline, duration of testing and agreement on which specific endpoints are clinically relevant.. Evaluation of the totality of the currently available evidence indicates that intake of the above vitamins, either as a monotherapy, or in combination with other vitamins, has no clinically-relevant effect on delaying cognitive decline or delaying the onset of dementia in older adults.

Topics: Aged; Antioxidants; Ascorbic Acid; beta Carotene; Cognition; Cognition Disorders; Dementia; Dietary Supplements; Folic Acid; Homocysteine; Humans; Meta-Analysis as Topic; Vitamin A; Vitamin B 12; Vitamin B 6; Vitamin D; Vitamin D Deficiency; Vitamin E; Vitamins

To summarize existing evidence on the effect of serum folate and vitamin B12 levels on cognitive impairment among elders via a meta-analysis, also including unpublished data from a cross-sectional study of seniors ( > 65 years) residing in Velestino, Greece.. Serum measurements and Mini-Mental State Examination (MMSE) assessments were available for 593 Velestinians. In addition, 12 studies availing data on folate blood levels (N = 9,747) and 9 on B12 (N = 8,122) were identified following a search algorithm; pooled effect estimates were derived.. Cognitive impairment (MMSE < 24) among Velestenians was associated with lower education level in both genders; decreased social activity, depressive symptoms and low folate levels in males; older age in females. Meta-analyses showed an adverse effect of low-folate levels on cognition (OR: 1.66, 95% CI: 1.40-1.96); B12 was nonsignificantly associated (OR: 1.11, 95% CI: 0.88-1.40).. Low folate levels are associated with cognitive impairment of seniors; underlying pathophysiological mechanisms should be further explored.

Topics: Aged; Aged, 80 and over; Cognition Disorders; Cross-Sectional Studies; Female; Folic Acid; Greece; Humans; Male; Risk Factors; Socioeconomic Factors; Vitamin B 12

High plasma total homocysteine (tHcy) has been associated with cognitive impairment but lowering tHcy with B-vitamins has produced equivocal results. We aimed to determine whether B-vitamin supplementation would reduce tHcy and the incidence of new cognitive impairment among individuals with stroke or transient ischemic attack≥6 months previously.. A total of 8164 patients with stroke or transient ischemic attack were randomly allocated to double-blind treatment with one tablet daily of B-vitamins (folic acid, 2 mg; vitamin B6, 25 mg; vitamin B12, 500 μg) or placebo and followed up for 3.4 years (median) in the VITAmins TO Prevent Stroke (VITATOPS) trial. For this prespecified secondary analysis of VITATOPS, the primary outcome was a new diagnosis of cognitive impairment, defined as a Mini-Mental State Examination (MMSE) score<24 on ≥2 follow-up visits. Secondary outcomes were cognitive decline, and the mean tHcy and MMSE at final follow-up.. A total of 3089 participants (38%) voluntarily undertook the MMSE>6 months after the qualifying stroke; 2608 participants were cognitively unimpaired (MMSE≥24), of whom 2214 participants (1110 B-vitamins versus 1104 placebo) had follow-up MMSEs during 2.8 years (median). At final follow-up, allocation to B-vitamins, compared with placebo, was associated with a reduction in mean tHcy (10.2 μmol/L versus 14.2 μmol/L; P<0.001) but no change from baseline in the mean MMSE score (-0.22 points versus -0.25 points; difference, 0.03; 95% confidence interval, -0.13 to 0.19; P=0.726) and no difference in the incidence of cognitive impairment (5.51% versus 5.47%; risk ratio, 1.01; 95% confidence interval, 0.69-1.48; P=0.976), cognitive decline (9.1% versus 10.3%; risk ratio, 0.89; 0.67-1.18; P=0.414), or cognitive impairment or decline (11.0% versus 11.3%; risk ratio, 0.98; 0.75-1.27; P=0.855).. Daily supplementation with folic acid, vitamin B6, and vitamin B12 to a self-selected clinical trial cohort of cognitively unimpaired patients with previous stroke or transient ischemic attack lowered mean tHcy but had no effect on the incidence of cognitive impairment or cognitive decline, as measured by the MMSE, during a median of 2.8 years.. URL: http://www.controlled-trials.com. Unique identifier: ISRCTN74743444; URL: http://www.clinicaltrials.gov. Unique identifier: NCT00097669.

Topics: Aged; Cognition Disorders; Double-Blind Method; Female; Follow-Up Studies; Homocysteine; Humans; Ischemic Attack, Transient; Male; Middle Aged; Placebos; Recurrence; Stroke; Treatment Outcome; Vitamin B 12; Vitamin B Complex

Vitamin B12 deficiency causes a wide range of hematological, gastrointestinal, psychiatric and neurological disorders. Hematological presentation of cobalamin deficiency ranges from the incidental increase of mean corpuscular volume and neutrophil hypersegmentation to symptoms due to severe anemia, such as angor, dyspnea on exertion, fatigue or symptoms related to congestive heart failure, such as ankle edema, orthopnea and nocturia. Neuropsychiatric symptoms may precede hematologic signs and are represented by myelopathy, neuropathy, dementia and, less often, optic nerve atrophy. The spinal cord manifestation, subacute combined degeneration (SCD), is characterized by symmetric dysesthesia, disturbance of position sense and spastic paraparesis or tetraparesis. The most consistent MRI finding is a symmetrical abnormally increased T2 signal intensity confined to posterior or posterior and lateral columns in the cervical and thoracic spinal cord. Isolated peripheral neuropathy is less frequent, but likely overlooked. Vitamin B12 deficiency has been correlated negatively with cognitive functioning in healthy elderly subjects. Symptoms include slow mentation, memory impairment, attention deficits and dementia. Optic neuropathy occurs occasionally in adult patient. It is characterized by symmetric, painless and progressive visual loss. Parenteral replacement therapy should be started soon after the vitamin deficiency has been established.

Topics: Cognition Disorders; Humans; Nervous System; Optic Nerve Diseases; Peripheral Nervous System Diseases; Subacute Combined Degeneration; Vitamin B 12; Vitamin B 12 Deficiency

Hyperhomocysteinemia is a risk factor for neurological diseases, but the underlying pathophysiology has not been adequately explained. Mild hyperhomocysteinemia, which is sometimes associated with a low plasma level of vitamin B9, B12 and folic acid, is responsible in the toxicity in neural cell by activating NMDA receptor. Indeed, even if vitamin supplementation has clearly proven its efficiency on lowering plasma levels of homocysteine, recent studies do not show any positive effect of vitamin therapy on cognitive function. The hypothesis that this therapy is inefficient has been recently reinforced by two randomized trials on the effects of vitamin supplementation. Several hypotheses still need to be explored: Mechanisms of homocysteine toxicity and that of total uselessness of vitamin supplementation; the possible need to complete the actual data with further, more powerful studies in order to prove the role of homocysteine in the development of neurodegenerative diseases and a clinical effect of vitamin therapy.

Topics: Aged; Brain; Cognition Disorders; Dietary Supplements; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Neurodegenerative Diseases; Nutritional Physiological Phenomena; Receptors, N-Methyl-D-Aspartate; Risk Factors; Vitamin B 12

Current recommendations on vitamin B12 intake vary from 1.4 to 3.0 μg per day and are based on the amount needed for maintenance of hematologic status or on the amount needed to compensate obligatory losses. This systematic review evaluates whether the relation between vitamin B12 intake and cognitive function should be considered for underpinning vitamin B12 recommendations in the future. The authors summarized dose-response evidence from randomized controlled trials and prospective cohort studies on the relation of vitamin B12 intake and status with cognitive function in adults and elderly people. Two randomized controlled trials and 6 cohort studies showed no association or inconsistent associations between vitamin B12 intake and cognitive function. Random-effects meta-analysis showed that serum/plasma vitamin B12 (50 pmol/L) was not associated with risk of dementia (4 cohort studies), global cognition z scores (4 cohort studies), or memory z scores (4 cohort studies). Although dose-response evidence on sensitive markers of vitamin B12 status (methylmalonic acid and holotranscobalamin) was scarce, 4 of 5 cohort studies reported significant associations with risk of dementia, Alzheimer's disease, or global cognition. Current evidence on the relation between vitamin B12 intake or status and cognitive function is not sufficient for consideration in the development of vitamin B12 recommendations. Further studies should consider the selection of sensitive markers of vitamin B12 status.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Cognition; Cognition Disorders; Dementia; Diet; Humans; Methylmalonic Acid; Transcobalamins; Vitamin B 12

The objective of this review is to provide an overview of nutritional factors involved in cognitive aging and dementia with a focus on nutrients that are also important in neurocognitive development. Several dietary components were targeted, including antioxidant nutrients, dietary fats and B-vitamins. A critical review of the literature on each nutrient group is presented, beginning with laboratory and animal studies of the underlying biological mechanisms, followed by prospective epidemiological studies and randomised clinical trials. The evidence to date is fairly strong for protective associations of vitamin E from food sources, the n-3 fatty acid, DHA, found in fish, a high ratio of polyunsaturated to saturated fats, and vitamin B12 and folate. Attention to the level of nutrient intake is crucial for interpreting the literature and the inconsistencies across studies. Most of the epidemiological studies that observe associations have sufficient numbers of individuals who have both low and adequate nutrient status. Few of the randomised clinical trials are designed to target participants who have low baseline status before randomising to vitamin supplement treatments, and this may have resulted in negative findings. Post-hoc analyses by some of the trials reveal vitamin effects in individuals with low baseline intakes. The field of diet and dementia is a relatively young area of study. Much further work needs to be done to understand dietary determinants of cognitive aging and diseases. Further, these studies must be particularly focused on the levels of nutrient intake or status that confer optimum or suboptimal brain functioning.

Topics: Aging; Animals; Cognition Disorders; Dementia; Diet; Dietary Fats; Docosahexaenoic Acids; Folic Acid; Humans; Vitamin B 12; Vitamin E; Vitamins

This review examines the associations between low vitamin B12 levels, neurodegenerative disease, and cognitive impairment. The potential impact of comorbidities and medications associated with vitamin B12 derangements were also investigated. In addition, we reviewed the evidence as to whether vitamin B12 therapy is efficacious for cognitive impairment and dementia.. A systematic literature search identified 43 studies investigating the association of vitamin B12 and cognitive impairment or dementia. Seventeen studies reported on the efficacy of vitamin B12 therapy for these conditions.. Vitamin B12 levels in the subclinical low-normal range (<250 ρmol/L) are associated with Alzheimer's disease, vascular dementia, and Parkinson's disease. Vegetarianism and metformin use contribute to depressed vitamin B12 levels and may independently increase the risk for cognitive impairment. Vitamin B12 deficiency (<150 ρmol/L) is associated with cognitive impairment. Vitamin B12 supplements administered orally or parenterally at high dose (1 mg daily) were effective in correcting biochemical deficiency, but improved cognition only in patients with pre-existing vitamin B12 deficiency (serum vitamin B12 levels <150 ρmol/L or serum homocysteine levels >19.9 μmol/L).. Low serum vitamin B12 levels are associated with neurodegenerative disease and cognitive impairment. There is a small subset of dementias that are reversible with vitamin B12 therapy and this treatment is inexpensive and safe. Vitamin B12 therapy does not improve cognition in patients without pre-existing deficiency. There is a need for large, well-resourced clinical trials to close the gaps in our current understanding of the nature of the associations of vitamin B12 insufficiency and neurodegenerative disease.

Topics: Alzheimer Disease; Cognition Disorders; Dementia; Humans; Vitamin B 12; Vitamin B 12 Deficiency; Vitamins

Elevated total plasma homocysteine has been linked to the development of cognitive impairment and dementia in later life and this can be reliably lowered by the daily supplementation of vitamin B6, B12, and folic acid. We performed a systematic review and meta-analysis of 19 English language randomized, placebo-controlled trials of homocysteine lowering B-vitamin supplementation of individuals with and without cognitive impairment at the time of study entry. We standardized scores to facilitate comparison between studies and to enable us to complete a meta-analysis of randomized trials. In addition, we stratified our analyses according to the folate status of the country of origin. B-vitamin supplementation did not show an improvement in cognitive function for individuals with (SMD = 0.10, 95%CI -0.08 to 0.28) or without (SMD = -0.03, 95%CI -0.1 to 0.04) significant cognitive impairment. This was irrespective of study duration (SMD = 0.05, 95%CI -0.10 to 0.20 and SMD = 0, 95%CI -0.08 to 0.08), study size (SMD = 0.05, 95%CI -0.09 to 0.19 and SMD = -0.02, 95%CI -0.10 to 0.05), and whether participants came from countries with low folate status (SMD = 0.14, 95%CI -0.12 to 0.40 and SMD = -0.10, 95%CI -0.23 to 0.04). Supplementation of vitamins B12, B6, and folic acid alone or in combination does not appear to improve cognitive function in individuals with or without existing cognitive impairment. It remains to be established if prolonged treatment with B-vitamins can reduce the risk of dementia in later life.

Topics: Cognition Disorders; Dietary Supplements; Folic Acid; Homocysteine; Humans; Randomized Controlled Trials as Topic; Treatment Outcome; Vitamin B 12; Vitamin B 6

This review focuses on recent developments and controversies in the diagnosis, consequences, and management of subclinical cobalamin deficiency (SCCD), which affects many elderly persons.. Diagnosis of SCCD depends exclusively on biochemical tests whose individual limitations suggest that combinations of tests are needed, especially in epidemiologic research. The causes of SCCD are unknown in more than 60% of cases, which limits prognostic predictions and identification of health consequences. After years of varying, often inconclusive associations, new clinical trials suggest that homocysteine reduction by high doses of folic acid, cobalamin, and pyridoxine may reduce progression of structural brain changes and cognitive impairment, especially in predisposed individuals. The causative or contributory roles, if any, of SCCD itself in cognitive dysfunction require direct study. If the findings are confirmed, high-dose supplementation with three vitamins will probably be more effective than fortification of the diet.. The story of SCCD, which is severalfold times more common in the elderly than clinical cobalamin deficiency but also differs from it in arising only infrequently from severe malabsorption and thus being less likely to progress, continues to evolve. Preventive benefits need to be confirmed and expanded, and will require fuller understanding of SCCD pathophysiology, natural history, and health consequences.

Topics: Asymptomatic Diseases; Cognition Disorders; Dietary Supplements; Folic Acid; Food, Fortified; Humans; Vitamin B 12; Vitamin B 12 Deficiency; Vitamins

It is now 30 years since the first publications stating that supplementation with folate could prevent neural tube defects appeared and 20 years since the definitive data, including prevention of other birth defects. Since then epidemiological studies and animal experiments have identified folate as a molecule at the crossroads of neural development. Fortification of food has greatly reduced the incidence of spina bifida. Much interest has focussed on long-term sequelae in children born to mothers severely deprived of folate (and other nutrients) such as during the Dutch Hunger Winter of 1944 and in poor parts of the world. In addition, deficiency in folate and B12 are increasingly discussed as a possible contributing factor in dementia and congenital orofacial and heart malformations. The year 2011 saw the publication of a study that implicated low folate intake in poorer school performance of adolescents as judged by school marks. This has enormous social implications but needs confirmation from other settings. This review assesses the current state of evidence and sets the data in context of whether folate has a role in the development and plasticity of the nervous system even after birth, with particular emphasis on childhood and adolescence.

Topics: Adolescent; Cardiovascular Diseases; Child; Child, Preschool; Cognition Disorders; Educational Status; Embryonic Development; Folic Acid; Folic Acid Deficiency; Humans; Nervous System; Neural Tube Defects; Socioeconomic Factors; Vitamin B 12

The objective of this review was to elucidate the relationship between VaD and various nutritional factors based on epidemiological studies.. 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. Nutrition is one of the main modifiable variables that may influence the development of VaD.. A systematic review of literature was conducted using the PubMed, Web of Science, and CINAHL Plus databases with search parameters inclusive of vascular dementia, nutrition, and vascular cognitive impairment (VCI).. Fourteen articles were found that proposed a potential role of specific nutritional components in VaD. These components included antioxidants, lipids, homocysteine, folate, vitamin B12, and fish consumption. Antioxidants, specifically Vitamin E and C, and fatty fish intake were found to be protective against VaD risk. Fried fish, elevated homocysteine, and lower levels of folate and vitamin B12 were associated with increased VaD. Evidence for dietary lipids was inconsistent, although elevated midlife serum cholesterol may increase risk, while late-life elevated serum cholesterol may be associated with decreased risk of VaD.. Currently, the most convincing evidence as to the relationship between VaD and nutrition exists for micronutrients, particularly Vitamin E and C. Exploration of nutrition at the macronutrient level and additional long term prospective cohort studies are warranted to better understand the role of nutrition in VaD disease development and progression. At present, challenges in this research include limitations in sample size, which was commonly cited. Also, a variety of diagnostic criteria for VaD were employed in the studies reviewed, indicating the need for constructing a correct nosological definition of VaD for consistency and conformity in future studies and accurate clinical diagnosis of VaD.

Topics: Animals; Antioxidants; Ascorbic Acid; Cholesterol; Cognition Disorders; Dementia, Vascular; Diet; Disease Progression; Fishes; Folic Acid; Humans; Meat; Nutritional Status; Prevalence; Risk Factors; Vitamin B 12; Vitamin E

Poor vitamin B₁₂ status may lead to the development of cognitive decline and dementia but there is a large variation in the quality, design of and results reported from these investigations. We have undertaken a systematic review of the evidence for the association between vitamin B₁₂ status and cognitive decline in older adults. A database search of the literature to 2011 was undertaken, using keywords related to vitamin B₁₂ and cognition. All prospective cohort studies assessing the association of serum vitamin B₁₂ or biomarkers were included. Quality assessment and extraction of the data were undertaken by two researchers. The quality assessment tool assigns a positive, neutral or negative rating. Of 3772 published articles, thirty-five cohort studies (n 14 325 subjects) were identified and evaluated. No association between serum vitamin B₁₂ concentrations and cognitive decline or dementia was found. However, four studies that used newer biomarkers of vitamin B₁₂ status (methylmalonic acid and holotranscobalamin (holoTC)) showed associations between poor vitamin B₁₂ status and the increased risk of cognitive decline or dementia diagnosis. In general, the studies were of reasonable quality (twenty-one positive, ten neutral and four negative quality) but of short duration and inadequate subject numbers to determine whether an effect exists. Future studies should be of adequate duration (at least 6 years), recruit subjects from the seventh decade, choose markers of vitamin B₁₂ status with adequate specificity such as holoTC and/or methylmalonic acid and employ standardised neurocognitive assessment tools and not screening tests in order to ascertain any relationship between vitamin B₁₂ status and cognitive decline.

Topics: Aged; Aged, 80 and over; Biomarkers; Cognition; Cognition Disorders; Cognitive Dysfunction; Dementia; Disease Progression; Female; Humans; Male; Methylmalonic Acid; Middle Aged; Nutritional Status; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

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. Folate and vitamin B-12 participate in Hcy remethylation and largely determine Hcy status. Consequently, much of the relevant research has focused on these 2 B vitamins. The many subtly different hypotheses that investigators have addressed by attempting to link several B-vitamin status indicators to diverse cognition-related outcomes have created a confusing body of conflicting studies that seems to defy summarization. Nevertheless, themes are discernible that aid interpretation, foster hypothesis generation, and inform future study design. For example, despite a shared metabolic pathway, Hcy, vitamin B-12, and folate are differently related to specific cognitive outcomes. Although consistency of findings across studies is often touted as essential to distinguishing causal from coincidental relationships, discrepancies among study findings can be even more informative.

Topics: Alzheimer Disease; Cognition; Cognition Disorders; Folic Acid; Homocysteine; Humans; Methylation; Vitamin B 12; Vitamin B Complex; Vitamin B Deficiency

Cobalamin (vitamin B12) deficiency in the elderly is an under recognized problem in daily clinical practice. It seems to be important because the deficiency of this vitamin can lead to irreversible neurological damage, anemia, osteoporosis, and cerebrovascular and cardiovascular diseases. Some clinical abnormalities that we thought were related to the normal aging changes may actually be caused by cobalamin deficiency, such as lack of ankle jerk reflex. The prevalence of cobalamin deficiency increases with age (ranges from 0.6% to 46% depending on the population studies and criteria for diagnosis). Other than clinical manifestations, there are some biomarkers for detection of cobalamin deficiency: the red blood cell mean corpuscular volume (MCV); serum cobalamin level; plasma holotranscobalamin; serum methylmalonic acid (MMA) levels and serum homocysteine levels. The interpretation and the application of these biomarkers are here presented.

Topics: Aging; Biomarkers; Cognition Disorders; Erythrocyte Indices; Female; Homocysteine; Humans; Male; Methylmalonic Acid; Vitamin B 12; Vitamin B 12 Deficiency

A roundtable to discuss the measurement of vitamin B-12 (cobalamin) status biomarkers in NHANES took place in July 2010. NHANES stopped measuring vitamin B-12-related biomarkers after 2006. The roundtable reviewed 3 biomarkers of vitamin B-12 status used in past NHANES--serum vitamin B-12, methylmalonic acid (MMA), and total homocysteine (tHcy)--and discussed the potential utility of measuring holotranscobalamin (holoTC) for future NHANES. The roundtable focused on public health considerations and the quality of the measurement procedures and reference methods and materials that past NHANES used or that are available for future NHANES. Roundtable members supported reinstating vitamin B-12 status measures in NHANES. They noted evolving concerns and uncertainties regarding whether subclinical (mild, asymptomatic) vitamin B-12 deficiency is a public health concern. They identified the need for evidence from clinical trials to address causal relations between subclinical vitamin B-12 deficiency and adverse health outcomes as well as appropriate cutoffs for interpreting vitamin B-12-related biomarkers. They agreed that problems with sensitivity and specificity of individual biomarkers underscore the need for including at least one biomarker of circulating vitamin B-12 (serum vitamin B-12 or holoTC) and one functional biomarker (MMA or tHcy) in NHANES. The inclusion of both serum vitamin B-12 and plasma MMA, which have been associated with cognitive dysfunction and anemia in NHANES and in other population-based studies, was preferable to provide continuity with past NHANES. Reliable measurement procedures are available, and National Institute of Standards and Technology reference materials are available or in development for serum vitamin B-12 and MMA.

Topics: Biomarkers; Cognition Disorders; Homocysteine; Humans; Methylmalonic Acid; Nutrition Surveys; Public Health; Vitamin B 12; Vitamin B 12 Deficiency

Vitamin B12 (cobalamin) is necessary for development of the fetus and child. Pregnant women who are vegetarian or vegan, have Crohn's or celiac disease, or have undergone gastric bypass surgery are at increased risk of B12 deficiency. Low serum levels of B12 have been linked to negative impacts in cognitive, motor, and growth outcomes. Low cobalamin levels also may be related to depression in adults. Some studies indicate that B12 supplementation may improve outcomes in children, although more research is needed in this area. Overall, the mechanisms of B12 action in development remain unclear. Further studies in this area to elucidate the pathways of cobalamin influence on development, as well as to prevent B12 deficiency in pregnant women and children are indicated.

Topics: Ataxia; Child; Coenzymes; Cognition Disorders; Depression, Postpartum; Developmental Biology; Diet; Embryo, Mammalian; Female; Fetal Development; Fetus; Humans; Infant, Newborn; Neural Tube Defects; Pregnancy; Vitamin B 12; Vitamin B 12 Deficiency

Neuroinflammatory oxidative stress occurs early in AD pathology. Elevated blood Hcy is a useful marker for such neuroinflammation. Hcy contributes to pathological cascades involving AP and NFTs. In AD, Hcy should be lowered by B-vitamin supplements and NAC.

Topics: Acetylcysteine; Alzheimer Disease; Cognition Disorders; Free Radical Scavengers; Homocysteine; Humans; Oxidative Stress; Plaque, Amyloid; Tetrahydrofolates; Vitamin B 12; Vitamin B Complex

Conducting long-term nutrition intervention studies on cognition can be challenging. The gaps in current methodology are addressed via a case study of the relationship between vitamin B(12) and cognition in people aged 60 and older. There is robust evidence from many observational studies, both cross-sectional and longitudinal, showing that a deficit of the vitamin is associated with poor or declining cognition in this age group, but supplementation of the vitamin in trials does not bring about improved cognition. The evidence from observational studies as well as clinical trials is reviewed here, and the potential difficulties in conducting long-term nutritional intervention studies in this area are highlighted.

Topics: Aged; Cognition; Cognition Disorders; Female; Humans; Male; Middle Aged; Vitamin B 12; Vitamin B 12 Deficiency

Deficiencies of the vitamins folate, B(12) , and B(6) are associated with neurological and psychological dysfunction and with congenital defects. In the elderly, cognitive impairment and incident dementia may be related to the high prevalence of inadequate B vitamin status and to elevations of plasma homocysteine. Plausible mechanisms include homocysteine neurotoxicity, vasotoxicity, and impaired S-adenosylmethionine-dependent methylation reactions vital to central nervous system function. In light of this, it is imperative to find safe ways of improving vitamin B status in the elderly without exposing some individuals to undue risk.

Topics: Aged; Aging; Brain; Cognition Disorders; Homocysteine; Humans; Nutritional Status; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B 6; Vitamin B 6 Deficiency; Vitamin B Complex

Vitamin B(12) is essential for DNA synthesis and for cellular energy production.This review aims to outline the metabolism of vitamin B(12), and to evaluate the causes and consequences of sub-clinical vitamin B(12) deficiency. Vitamin B(12) deficiency is common, mainly due to limited dietary intake of animal foods or malabsorption of the vitamin. Vegetarians are at risk of vitamin B(12) deficiency as are other groups with low intakes of animal foods or those with restrictive dietary patterns. Malabsorption of vitamin B(12) is most commonly seen in the elderly, secondary to gastric achlorhydria. The symptoms of sub-clinical deficiency are subtle and often not recognized. The long-term consequences of sub-clinical deficiency are not fully known but may include adverse effects on pregnancy outcomes, vascular, cognitive, bone and eye health.

Topics: Absorption; Biomarkers; Cardiovascular Diseases; Cognition Disorders; Female; Food; Humans; Male; Neural Tube Defects; Nutritional Requirements; Osteoporosis; Pregnancy; Pregnancy Complications; Vitamin B 12; Vitamin B 12 Deficiency

Vitamin B-12 deficiency is often associated with cognitive deficits. Here we review evidence that cognition in the elderly may also be adversely affected at concentrations of vitamin B-12 above the traditional cutoffs for deficiency. By using markers such as holotranscobalamin and methylmalonic acid, it has been found that cognition is associated with vitamin B-12 status across the normal range. Possible mediators of this relation include brain atrophy and white matter damage, both of which are associated with low vitamin B-12 status. Intervention trials have not been adequately designed to test whether these associations are causal. Pending the outcome of better trials, it is suggested that the elderly in particular should be encouraged to maintain a good, rather than just an adequate, vitamin B-12 status by dietary means.

Topics: Aged; Aging; Biomarkers; Cognition Disorders; Female; Humans; Male; Methylmalonic Acid; Nutritional Requirements; Nutritional Status; Risk Factors; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

Since the introduction of folic acid fortification of flour 10 y ago, an initiative to consider fortifying flour with vitamin B-12 has gained momentum in the United States. The impetus for this move stems from several considerations, including some evidence that a proportion of neural tube defect pregnancies may be the result of vitamin B-12 rather than folate deficiency. However, no interventional trials have taken place to show the efficacy of vitamin B-12 supplementation or fortification in the primary prevention or recurrence of neural tube defect pregnancies, as was the case with folic acid. Other reasons put forward for the institution of vitamin B-12 fortification include the high prevalence of vitamin B-12 deficiency in certain demographic groups, including the elderly and the young in some countries. Much of this deficiency, however, is subclinical and not associated with manifest morbidity. Moreover, individuals affected by the most severe cases of vitamin B-12 deficiency that are associated with morbidity would not benefit from the concentrations of vitamin B-12 fortification that are practical or that are being considered, because such individuals suffer from malabsorption of vitamin B-12 rather than from an inadequacy of intake of the vitamin. In addition to the well-recognized complications of vitamin B-12 deficiency, such as macrocytic anemia and neurological complications affecting sensory and motor function, more subtle effects have also been described, including osteopenia, neurocognitive impairment, and increased vascular disease risk associated with elevated homocysteine. This analysis focuses on the research questions that are pertinent to the consideration of whether or not to introduce mandatory vitamin B-12 fortification in the United States.

Topics: Age Factors; Aging; Cognition Disorders; Flour; Food, Fortified; Humans; Neural Tube Defects; Nutritional Requirements; Risk Factors; United States; Vitamin B 12; Vitamin B 12 Deficiency

Elevated serum homocysteine, decreased folate and low vitamin B(12) serum levels are associated with poor cognitive function, cognitive decline and dementia. Despite evidence of an epidemiological association, randomised controlled trials did not provide any clear evidence so far that supplementation with vitamin B(12) and/or folate improves dementia or slows cognitive decline, even though it might normalise homocysteine levels. In this report, we review the current knowledge on the relationship between homocysteine, folate and vitamin B(12) levels and the way their disruption influences cognitive function in adults.

Topics: Adult; Clinical Trials as Topic; Cognition Disorders; Cross-Sectional Studies; Dietary Supplements; Folic Acid; Homocysteine; Humans; Longitudinal Studies; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B Complex

There has been increasing research into the role of nutritional factors in mood and cognitive disorders in later life. This review evaluates findings from recent research for the role and effect of n-3 polyunsaturated fatty acids (PUFAs) and B vitamins in mood and cognitive disorders in later life.. Epidemiological studies, including genetic epidemiological ones, continue to provide support for the role of folate and/or vitamin B12 in mood disorders in later life. However, evidence from recent randomized controlled trials for the effect of these B vitamins and n-3 PUFAs is modest. There is little robust evidence for the effect of these nutrients on cognitive disorders in later life.. Larger randomized controlled trials allowing more appropriate meta-analyses are required to further evaluate current findings. Additionally, methods derived from research in geriatric medicine may assist in conceptualizing a role for these nutrients.

Topics: Aged; Animals; Cognition Disorders; Diet; Dietary Fats; Fatty Acids, Unsaturated; Fishes; Folic Acid; Folic Acid Deficiency; Geriatric Psychiatry; Humans; Mental Disorders; Mood Disorders; Nutritional Status; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B Complex

Topics: Aged; Aged, 80 and over; Aging; Cognition; Cognition Disorders; Female; Folic Acid; Folic Acid Deficiency; Humans; Male; Middle Aged; Nutritional Requirements; Nutritional Status; Vitamin B 12; Vitamin B 12 Deficiency

Folate deficiency can result in congenital neural tube defects and megaloblastic anaemia. Low folate levels may be due to insufficient dietary intake or inefficient absorption, but impaired metabolic utilization also occurs.Because B12 deficiency can produce a similar anaemia to folate deficiency, there is a risk that folate supplementation can delay the diagnosis of B12 deficiency, which can cause irreversible neurological damage. Folic acid supplements may sometimes therefore include vitamin B12 supplements with simultaneous administration of vitamin B12.Lesser degrees of folate inadequacy are associated with high blood levels of the amino acid homocysteine which has been linked with the risk of arterial disease, dementia and Alzheimer's disease. There is therefore interest in whether dietary supplementation can improve cognitive function in the elderly.However, any apparent benefit from folic acid which was given in combination with B12 needs to be "corrected" for any effect of vitamin B12 alone. A separate Cochrane review of vitamin B12 and cognitive function has therefore been published.. To examine the effects of folic acid supplementation, with or without vitamin B12, on elderly healthy or demented people, in preventing cognitive impairment or retarding its progress.. Trials were identified from a search of the Cochrane Dementia and Cognitive Improvement Group's Specialized Register on 10 October 2007 using the terms: folic acid, folate, vitamin B9, leucovorin, methyltetrahydrofolate, vitamin B12, cobalamin and cyanocobalamin. This Register contains references from all major health care databases and many ongoing trials databases. In addition MEDLINE, EMBASE, CINAHL, PsychINFO and LILACS were searched (years 2003-2007) for additional trials of folate with or without vitamin B12 on healthy elderly people.. All double-blind, placebo-controlled, randomized trials, in which supplements of folic acid with or without vitamin B12 were compared with placebo for elderly healthy people or people with any type of dementia or cognitive impairment.. The reviewers independently applied the selection criteria and assessed study quality. One reviewer extracted and analysed the data. In comparing intervention with placebo, weighted mean differences and standardized mean difference or odds ratios were estimated.. Eight randomized controlled trials fulfilled the inclusion criteria for this review. Four trials enrolled healthy older people, and four recruited participants with mild to moderate cognitive impairment or dementia with or without diagnosed folate deficiency. Pooling the data was not possible owing to heterogeneity in sample selections, outcomes, trial duration, and dosage. Two studies involved a combination of folic acid and vitamin B12.There is no adequate evidence of benefit from folic acid supplementation with or without vitamin B12 on cognitive function and mood of unselected healthy elderly people. However, in one trial enrolling a selected group of healthy elderly people with high homocysteine levels, 800 mcg/day folic acid supplementation over three years was associated with significant benefit in terms of global functioning (WMD 0.05, 95% CI 0.004 to 0.096, P = 0.033); memory storage (WMD 0.14, 95% CI 0.04 to 0.24, P = 0.006) and information-processing speed (WMD 0.09, 95% CI 0.02 to 0.16, P = 0.016).Four trials involved people with cognitive impairment. In one pilot trial enrolling people with Alzheimer's disease, the overall response to cholinesterase inhibitors significantly improved with folic acid at a dose of 1mg/day (odds ratio: 4.06, 95% CI 1.22 to 13.53; P = 0.02) and there was a significant improvement in scores on the Instrumental Activities of Daily Living and the Social Behaviour subscale of the Nurse's Observation Scale for Geriatric Patients (WMD 4.01, 95% CI 0.50 to 7.52, P = 0.02). Other trials involving people with cognitive impairment did not show any benefit in measures of cognitive function from folic acid, with or without vitamin B12.Folic acid plus vitamin B12 was effective in reducing serum homocysteine concentrations (WMD -5.90, 95% CI -8.43 to -3.37, P < 0.00001). Folic acid was well tolerated and no adverse effects were reported.. The small number of studies which have been done provide no consistent evidence either way that folic acid, with or without vitamin B12, has a beneficial effect on cognitive function of unselected healthy or cognitively impaired older people. In a preliminary study, folic acid was associated with improvement in the response of people with Alzheimer's disease to cholinesterase inhibitors. In another, long-term use appeared to improve the cognitive function of healthy older people with high homocysteine levels. More studies are needed on this important issue.

Topics: Cognition; Cognition Disorders; Dementia; Dietary Supplements; Drug Therapy, Combination; Folic Acid; Folic Acid Deficiency; Humans; Randomized Controlled Trials as Topic; Vitamin B 12

Despite their important role in cognitive function, the value of B vitamin supplementation is unknown. A systematic review of the effect of pyridoxine hydrochloride (hereinafter "vitamin B(6)"), cyanocobalamin or hydroxycobalamin (hereinafter "vitamin B(12)"), and folic acid supplementation on cognitive function was performed.. Literature search conducted in MEDLINE with supplemental articles from reviews and domain experts. We included English language randomized controlled trials of vitamins B(6) and/or B(12) and/or folic acid supplementation with cognitive function outcomes.. Fourteen trials met our criteria; most were of low quality and limited applicability. Approximately 50 different cognitive function tests were assessed. Three trials of vitamin B(6) and 6 of vitamin B(12) found no effect overall in a variety of doses, routes of administration, and populations. One of 3 trials of folic acid found a benefit in cognitive function in people with cognitive impairment and low baseline serum folate levels. Six trials of combinations of the B vitamins all concluded that the interventions had no effect on cognitive function. Among 3 trials, those in the placebo arm had greater improvements in a small number of cognitive tests than participants receiving either folic acid or combination B-vitamin supplements. The evidence was limited by a sparsity of studies, small sample size, heterogeneity in outcomes, and a lack of studies that evaluated symptoms or clinical outcomes.. The evidence does not yet provide adequate evidence of an effect of vitamin B(6) or B(12) or folic acid supplementation, alone or in combination, on cognitive function testing in people with either normal or impaired cognitive function.

Topics: Cognition; Cognition Disorders; Dietary Supplements; Folic Acid; Humans; Randomized Controlled Trials as Topic; Treatment Outcome; Vitamin B 12; Vitamin B 6; Vitamin B Complex

We conducted a systematic review to evaluate the association between folate, vitamin B-6, vitamin B-12, and cognitive function in the elderly. Our search was conducted in Medline for English-language publications of human subjects from 1966 through November 2006; we supplemented these results with information from article reviews and domain experts. We included longitudinal cohort and case-control studies of B vitamins and analyses of cognitive tests or Alzheimer's disease. We evaluated the quality and heterogeneity of study outcomes and assessed 30 different cognitive function tests. Of 24 studies that met eligibility criteria, 16 were determined to be of fair quality. A majority of the studies reviewed 2 or more B vitamins. Considerable heterogeneity was found among B-vitamin-level thresholds, comparisons, and data analyses. Six of 10 folate studies reported a significant association between low baseline blood folate concentrations and subsequent poor test performance in the global cognitive domain, and 4 of 9 folate studies found associations between low blood folate concentrations and increased prevalence of Alzheimer's disease. Studies did not reveal an association of vitamin B-6 and vitamin B-12 blood concentrations with cognitive-test performance or Alzheimer's disease, nor was B-vitamin dietary intake associated with cognitive function. Higher plasma homocysteine concentrations were associated with poorer cognitive function. Although the majority of studies indicated that low blood folate concentrations predicted poorer cognitive function, data supporting this association were limited because of the heterogeneity in cognition-assessment methodology, and scarcity of good quality studies and standardized threshold levels for categorizing low B-vitamin status.

Topics: Aged; Cognition Disorders; Folic Acid; Humans; Vitamin B 12; Vitamin B 6

The most common cause of vitamin B12 deficiency in older people is malabsorption of food-bound vitamin B12. Thus, it is suggested that the recommended daily allowance of 2.4 microg/d be met primarily with crystalline vitamin B12, which is believed to be well absorbed in individuals who have food-bound malabsorption. There is concern that high intakes of folic acid from fortified food and dietary supplements might mask the macrocytic anemia of vitamin B12 deficiency, thereby eliminating an important diagnostic sign. One recent study indicates that high serum folate levels during vitamin B12 deficiency exacerbate (rather than mask) anemia and worsen cognitive symptoms. Another study suggests that once vitamin B12 deficiency is established in subjects with food-bound malabsorption, 40 microg/d to 80 microg/d of oral crystalline vitamin B12 for 30 d does not reverse the biochemical signs of deficiency. Together, these studies provide further evidence that public health strategies are needed to improve vitamin B12 status in order to decrease the risk of deficiency and any potentially adverse interactions with folic acid.

Topics: Aging; Anemia; Cognition Disorders; Diagnosis, Differential; Dietary Supplements; Folic Acid; Food, Fortified; Humans; Intestinal Absorption; Nutritional Status; Public Health; Vitamin B 12; Vitamin B 12 Deficiency

Serum homocysteine increases with age and is also considered a marker for low serum vitamin B(12) and folate. Furthermore, raised serum total homocysteine has been associated with atrophic changes in the brain. An association between serum vitamin B(12)/folate and cognitive impairment would be of considerable public health importance in view of the increasing numbers of elderly people.. To systematically review published studies on the relationship between serum vitamin B(12), folate and total homocysteine and cognitive function in the elderly.. A systematic review was undertaken of published evidence in English, examining the association between low serum vitamin B(12)/folate and raised total homocysteine with cognitive impairment (as indicated by low scores on neuropsychological testing) in subjects aged over 60 years. Sixteen electronic databases and cited articles were searched. Of 383 potential articles, six fulfilled the eligibility criteria: three case control and three cohort studies were identified. 'The Cochrane Non-Randomized Studies Methods Group' guidelines were used for assessment and extraction of data from these studies.. All three case control studies found that serum total homocysteine was significantly higher in cases when compared with controls, and there was wide variation for both serum vitamin B(12) and folate in both groups of participants. The relationship of serum folate and vitamin B(12) status with cognitive impairment was heterogeneous and one case control study reported decreasing cognitive scores with increasing serum vitamin B(12). In the cohort studies, although serum total homocysteine could predict the rate of decline in neuropsychological testing, the overall odds ratio/relative risk (RR) of developing cognitive impairment in relation to levels of serum B(12) and serum folate were not significant. Although one study reported a significant RR of developing Alzheimer's disease when both serum folate and B(12) levels were low. One cohort study reported an increased prevalence of Alzheimer's type dementia in subjects who had normal serum vitamin B(12) at baseline.. Serum total homocysteine is negatively correlated with neuropsychological tests scores. But the evidence does not support a correlation between serum vitamin B(12) or folate and cognitive impairment in people aged over 60 years. Hence, there is little evidence to justify treating cognitive impairment with vitamin B(12) or folate supplementation. This is consistent with the findings from recent systematic reviews of randomized double-blind trials, which have not found any evidence of potential benefit of vitamin supplementation. Further research is required in order to establish whether raised serum total homocysteine is a cause or consequence of disease.

Topics: Aged; Aged, 80 and over; Case-Control Studies; Cognition Disorders; Cohort Studies; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Vitamin B 12

In cross-sectional studies, low levels of folate and B12 have been shown to be associated with cognitive decline and dementia Evidence for the putative role of folate, vitamin B12 in neurocognitive and other neurological functions comes from reported cases of severe vitamin deficiencies, particularly pernicious anemia, and homozygous defects in genes that encode for enzymes of one-carbon metabolism. The neurological alterations seen in these cases allow for a biological role of vitamins in neurophysiology. Results are quite controversial and there is an open debate in literature, considering that the potential and differential role of folate and B12 vitamin in memory acquisition and cognitive development is not completely understood or accepted. What is not clear is the fact that vitamin B12 and folate deficiency deteriorate a pre-existing not overt pathological situation or can be dangerous even in normal subjects. Even more intriguing is the interaction between B12 and folate, and their role in developing hyperhomocysteinemia. The approach to the rehabilitation of the deficiency with adequate vitamin supplementation is very confusing. Some authors suggest it, even in chronic situations, others deny any possible role. Starting from these quite confusing perspectives, the aim of this review is to report and categorize the data obtained from the literature. Despite the plausible biochemical mechanism, further studies, based on clinical, neuropsychological, laboratory and (lastly) pathological features will be necessary to better understand this fascinating biochemical riddle.

Topics: Cognition; Cognition Disorders; Dementia; Folic Acid; Folic Acid Deficiency; Homocysteine; Humans; Methylmalonic Acid; Vitamin B 12; Vitamin B 12 Deficiency

Inadequate folate status is associated with an increased risk for chronic diseases that may have a negative impact on the health of the aging population. Folate, a water-soluble vitamin, includes naturally occurring food folate and synthetic folic acid in supplements and fortified foods. Inadequate folate status may result in hyperhomocysteinemia, a significant risk factor for atherosclerotic vascular disease, changes in DNA that may result in pro-carcinogenic effects and increased risk for cognitive dysfunction. Folate status may be negatively influenced by inadequate intake, genetic polymorphisms and interactions with various drugs. In the US, folic acid is now added to enriched grain products and continues to be included in the majority of ready-to-eat breakfast cereals. Recent data indicate that the folate status in the US population has improved significantly, presumably due to the effects of fortification. Folic acid (not food folate) intake in excess of the Tolerable Upper Intake Level may mask the diagnosis of a vitamin B(12) deficiency, which is more prevalent in the elderly than younger individuals. When folic acid supplements are recommended, a multivitamin that includes vitamin B(12) should also be advised. To safely and effectively increase folate intake in the elderly, naturally occurring folate-rich food sources should be promoted. Folate-rich foods include orange juice, dark green leafy vegetables, asparagus, strawberries and legumes. These foods are also excellent sources of other health-promoting nutrients associated with chronic disease risk reduction.

Topics: Aged; Biological Availability; Cardiovascular Diseases; Cognition Disorders; Dietary Supplements; Female; Folic Acid; Folic Acid Deficiency; Food, Fortified; Humans; Male; Neoplasms; Nutrition Policy; Risk Factors; United States; Vegetables; Vitamin B 12; Vitamin B 12 Deficiency

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

An association between neuropsychiatric disorders and vitamin B12 deficiency has been recognized since 1849 when pernicious anaemia was first described. It has been suggested that deficiency of vitamin B12 might contribute to age-associated cognitive impairment. Low serum vitamin B12 concentrations are found in more than 10% of older people. A high prevalence of low serum vitamin B12 levels, and other indicators of vitamin B12 deficiency have been reported among people with Alzheimer's disease. A review is needed of trials assessing effects of vitamin B12 supplementation on cognitive function in later life.. To examine the effect of B12 supplementation on cognitive function of demented and elderly healthy people in terms of preventing the onset or progression of cognitive impairment or dementia.. The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 12 September 2002 using the terms listed in additional table 1. In addition MEDLINE 1966 to 2002/09 and EMBASE 1980-2002/08 were searched using the same terms and cognit* to pick up studies with healthy volunteers.. All randomized double-blind trials in which vitamin B12 at any dose was compared with placebo.. Both reviewers applied the selection criteria to assess the quality of the studies. One reviewer collated and analysed the data. For each outcome measure data were sought on every patient randomized.. From the two included studies (Seal 2002; Fourniere 1997) of people with dementia and low serum vitamin B12 levels, there was no statistically significant evidence of treatment effect, vitamin B12 supplementation compared with placebo, on cognitive function.. Evidence of any efficacy of vitamin B12 in improving the cognitive function of people with dementia and low serum B12 levels is insufficient. The two trials of acceptable methodology (Fourniere 1997; Seal 2002) were restricted to a small number of patients with Alzheimer's disease and other types of cognitive impairment. No trials involving people without dementia or using other definitions of vitamin B12 deficiency were found.

Topics: Aged; Cognition; Cognition Disorders; Dementia; Humans; Randomized Controlled Trials as Topic; Vitamin B 12; Vitamin B 12 Deficiency

Folates are vitamins essential to the development of the central nervous system. Insufficient folate activity at the time of conception and early pregnancy can result in congenital neural tube defects. In adult life folate deficiency has been known for decades to produce a characteristic form of anaemia ("megaloblastic"). More recently degrees of folate inadequacy, not severe enough to produce anaemia, have been found to be associated with high blood levels of the amino acid homocysteine. Such degrees of folate inadequacy can arise because of insufficient folates in the diet or because of inefficient absorption or metabolic utilisation of folates due to genetic variations. Conventional criteria for diagnosing folate deficiency may be inadequate for identifying people capable of benefiting from dietary supplementation. High blood levels of homocysteine have been linked with the risk of arterial disease, dementia and Alzheimer's disease. There is therefore interest in whether dietary supplements of folic acid (an artificial chemical analogue of naturally occurring folates) can improve cognitive function of people at risk of cognitive decline associated with ageing or dementia, whether by affecting homocysteine metabolism or through other mechanisms. There is a risk that if folic acid is given to people who have undiagnosed deficiency of vitamin B12 it may lead to neurological damage. Vitamin B12 deficiency produces both an anaemia identical to that of folate deficiency but also causes irreversible damage to the central and peripheral nervous systems. Folic acid will correct the anaemia of vitamin B12 deficiency and so delay diagnosis but will not prevent progression to neurological damage. For this reason trials of folic acid supplements may involve simultaneous administration of vitamin B12. Apparent benefit from folic acid given in the combination would therefore need to be "corrected" for any effect of vitamin B12 alone. A separate Cochrane review of vitamin B12 and cognitive function is being prepared.. To examine the effects of folic acid supplementation, with or without vitamin B12, on elderly healthy and demented people, in preventing cognitive impairment or retarding its progress.. Trials were identified from a search of the Cochrane Dementia and Cognitive Improvement Specialized Register Group on 9 April 2003 using the terms: folic acid, folate, vitamin B9, leucovorin, methyltetrahydrofolate, vitamin B12, cobalamin, cyanocobalamin, dementia, cognitive function, cognitive impairment, Alzheimer's disease, vascular dementia, mixed dementia and controlled trials. MEDLINE and EMBASE (both all years) were searched for additional trials on healthy people.. All double-blind placebo-controlled randomized trials, in which supplements of folic acid with or without vitamin B12 were compared with placebo for elderly healthy people or people with any type of dementia or cognitive impairment.. The reviewers independently applied the selection criteria and assessed study quality. One reviewer extracted and analysed the data. In comparing intervention with placebo, weighted mean differences, and standardized mean difference or odds ratios were estimated.. Four randomized controlled trials fulfilled the inclusion criteria for this review. One trial (Bryan 2002) enrolled healthy women, and three (Fioravanti 1997; Sommer 1998; VITAL 2003) recruited people with mild to moderate cognitive impairment or dementia with or without diagnosed folate deficiency. Fioravanti 1997 enrolled people with mild to moderate cognitive impairment or dementia as judged by scores on the Mini-Mental State Examination (MMSE) and Global Deterioration Scale and with serum folate level<3ng/l. One trial (VITAL 2003) studied the effects of a combination of vitamin B12 and folic acid on patients with mild to moderate cognitive impairment due to Alzheimer's disease or mixed dementia. The analysis from the included trials found no benefit from folic acid with or without vitamin B12 in comparison with placebo on any measures of cognition and mood for healthy or cognitively impaired or demented people: Folic acid effect and healthy participants: there was no benefit from of oral 750 mcg folic acid per day for five weeks compared with placebo on measures of cognition and mood of 19 healthy women aged 65 to 92. Folic acid effect and people with mild to moderate cognitive decline or dementia: there were no statistically significant results in favour of folic acid with or without vitamin B12 on any measures of cognitive function. Scores on the Mini-Mental State Examination (MMSE) revealed no statistically significant benefit from 2 mg per day folic acid plus 1mg vitamin B12 for 12 weeks when compared with placebo (WMD 0.39, 95% CI -0.43 to 1.21, P=0.35). Cognitive scores on the Alzheimer's Disease Scale (ADAS-Cog) showed no statistically significant benefit from 2 mg /day folic acid plus 1 mg /day vitamin B12 for 12 weeks compared with placebo (WMD 0.41, 95% -1.25 to 2.07, P=4.63). The Bristol Activities of Daily Living Scale (BADL) revealed no benefit from 2mg per day of folic acid plus 1 mg vitamin B12 for 12 weeks in comparison with placebo (WMD -0.57, 95%CI -1.95 to 0.81, P=0.42). None of the sub tests of the Randt Memory Test (RMT) showed statistically significant benefit from 15 mg of folic acid orally per day for 9 weeks when compared with placebo. One trial (Sommer 1998) reported a significant decline compared with placebo in two cognitive function tasks in demented patients who had received high doses of folic acid (10 mg /day) for unspecified periods. One trial (VITAL 2003) showed that 2 mg folic acid plus 1 mg vitamin B12 daily for 12. There was no beneficial effect of 750 mcg of folic acid per day on measures of cognition or mood in older healthy women. In patients with mild to moderate cognitive decline and different forms of dementia there was no benefit from folic acid on measures of cognition or mood. Folic acid plus vitamin B12 was effective in reducing the serum homocysteine concentrations. Folic acid was well tolerated and no adverse effects were reported. More studies are needed.

Topics: Cognition; Cognition Disorders; Dementia; Dietary Supplements; Drug Therapy, Combination; Folic Acid; Folic Acid Deficiency; Humans; Randomized Controlled Trials as Topic; Vitamin B 12

Topics: Aging; Cognition Disorders; Folic Acid; Homocysteine; Humans; Vitamin B 12

Topics: Aged; Aged, 80 and over; Cognition Disorders; Humans; Methylmalonic Acid; Vitamin B 12; Vitamin B 12 Deficiency

In moderately advanced Parkinson's disease (PD), low serum vitamin B12 levels are common and are associated with neuropathy and cognitive impairment. However, little is known about B12 in early PD.. To determine the prevalence of low vitamin B12 status in early PD and whether it is associated with clinical progression.. We measured vitamin B12 and other B12 status determinants (methylmalonic acid, homocysteine, and holotranscobalamin) in 680 baseline and 456 follow-up serum samples collected from DATATOP participants with early, untreated PD. Borderline low B12 status was defined as serum B12 <184 pmol/L (250 pg/mL), and elevated homocysteine was defined as >15 µmol/L. Outcomes included the UPDRS, ambulatory capacity score (sum of UPDRS items 13-15, 29&30), and MMSE, calculated as annualized rates of change.. At baseline, 13% had borderline low B12 levels, 7% had elevated homocysteine, whereas 2% had both. Elevated homocysteine at baseline was associated with worse scores on the baseline MMSE. Analysis of study outcomes showed that compared with the other tertiles, participants in the low B12 tertile (<234 pmol/L; 317 pg/mL) developed greater morbidity as assessed by greater annualized worsening of the ambulatory capacity score. Elevated homocysteine was associated with greater annualized decline in MMSE (-1.96 vs. 0.06; P = 0001). Blood count indices were not associated with B12 or homocysteine status.. In this study of early PD, low B12 status was common. Low B12 at baseline predicted greater worsening of mobility whereas elevated homocysteine predicted greater cognitive decline. Given that low B12 and elevated homocysteine can improve with vitamin supplementation, future studies should test whether prevention or early correction of these nutritionally modifiable conditions slows development of disability. © 2018 International Parkinson and Movement Disorder Society.

Topics: alpha-Tocopherol; Antioxidants; Antiparkinson Agents; Cognition Disorders; Double-Blind Method; Female; Follow-Up Studies; Homocysteine; Humans; Male; Mental Status Schedule; Middle Aged; Parkinson Disease; Predictive Value of Tests; Selegiline; Treatment Outcome; Vitamin B 12

The available evidence from randomised controlled trials suggests that vitamin B12 supplementation does not improve neurologic function in older people with marginal but not deficient Vitamin B12 status. This secondary analysis used data from the Older People and Enhanced Neurological function (OPEN) randomised controlled trial to assess whether baseline vitamin B12 status or change in vitamin B12 status over 12 months altered the effectiveness of dietary vitamin B12 supplementation on neurologic function in asymptomatic older people with depleted vitamin B12 status at study entry.. Vitamin B12 status was measured as serum concentrations of vitamin B12, holotranscobalamin, homocysteine and via a composite indicator (cB12). Neurological function outcomes included eleven electrophysiological measures of sensory and motor components of peripheral and central nerve function. Linear regression analyses were restricted to participants randomised into the intervention arm of the OPEN trial (n=91).. Analyses revealed an inconsistent pattern of moderate associations between some measures of baseline vitamin B12 status and some neurological responses to supplementation. The directions of effect varied and heterogeneity in effect across outcomes could not be explained according to type of neurological outcome. There was no evidence of differences in the neurological response to vitamin B12 supplementation according to change from baseline over 12 months in any indicator of B12 status.. This secondary analysis of high-quality data from the OPEN trial provides no evidence that baseline (or change from baseline) vitamin B12 status modifies the effect of vitamin B12 supplementation on peripheral or central nerve conduction among older people with marginal vitamin B12 status. There is currently insufficient evidence of efficacy for neurological function to support population-wide recommendations for vitamin B12 supplementation in healthy asymptomatic older people with marginal vitamin B12 status.

Topics: Aged; Cognition; Cognition Disorders; Dietary Supplements; Female; Health Services for the Aged; Humans; Male; Treatment Outcome; United Kingdom; Vitamin B 12; Vitamin B 12 Deficiency

Nutritional interventions have shown varied efficacy on cognitive performance during Alzheimer's disease (AD). Twenty-four individuals diagnosed with AD received a nutraceutical formulation (NF: folate, alpha-tocopherol, B12, S-adenosyl methioinine, N-acetyl cysteine, acetyl-L-carnitine) under open-label conditions (ClinicalTrials.gov NCT01320527). Primary outcome was cognitive performance. Secondary outcomes were behavioral and psychological symptoms of dementia (BPSD) and activities of daily living. Participants maintained their baseline cognitive performance and BPSD over 12 months. These findings are consistent with improvement in cognitive performance and BPSD in prior placebo-controlled studies with NF, and contrast with the routine decline for participants receiving placebo.

Topics: Aged; Aged, 80 and over; alpha-Tocopherol; Alzheimer Disease; Cognition Disorders; Dietary Supplements; Disease Progression; Female; Folic Acid; Follow-Up Studies; Humans; Male; Mood Disorders; Neuropsychological Tests; Psychiatric Status Rating Scales; Time Factors; Vitamin B 12

Increasing evidence points toward the efficacy of nutritional modifications in delaying cognitive decline and mood/behavioral difficulties in Alzheimer's disease (AD). Nutritional supplementation with individual agents has shown varied results suggesting the need for combinatorial intervention.. We set out to determine whether nutritional intervention could positively impact cognitive performance and behavioral difficulties for individuals diagnosed with AD.. A double-blind, multi-site, phase II study (ClinicalTrials.gov NCT01320527; Alzheimer's Association Trialmatch) was conducted in which 106 individuals with AD were randomized to a nutraceutical formulation (NF; folate, alpha-tocopherol, B12, S-adenosyl methioinine, N-acetyl cysteine, acetyl-L-carnitine) or placebo for 3 or 6 months, followed by an open-label extension where participants received NF for 6 additional months.. The NF cohort improved versus the placebo cohort within 3 months (Clox-1 p = 0.0083, 95%CI [0.4481, 2.9343]; Dementia Rating Scale p = 0.0266, 95%CI [0.1722, 2.7171]). Caregivers reported non-significant improvements in Neuropsychiatric Inventory. Both cohorts improved or maintained baseline performance during open-label extensions. Activities of Daily Living did not change for either cohort.. These findings extend phase I studies where NF maintained or improved cognitive performance and mood/behavior.

Topics: Aged; Aged, 80 and over; alpha-Tocopherol; Alzheimer Disease; Caregivers; Cognition Disorders; Cohort Studies; Dietary Supplements; Double-Blind Method; Female; Folic Acid; Humans; Male; Middle Aged; Mood Disorders; Time Factors; Vitamin B 12

Supplementation with vitamins, minerals and phytonutrients may be beneficial for cognition, especially in older adults. The aim of this study was to assess the effects of multivitamin supplementation in older adults on cognitive function and associated blood biomarkers. In a randomised, double blind, placebo-controlled trial, healthy women (n = 68) and men (n = 48) aged 55-65 years were supplemented daily for 16 weeks with women's and men's formula multivitamin supplements. Assessments at baseline and post-supplementation included computerised cognitive tasks and blood biomarkers relevant to cognitive aging. No cognitive improvements were observed after supplementation with either formula; however, several significant improvements were observed in blood biomarkers including increased levels of vitamins B6 and B12 in women and men; reduced C-reactive protein in women; reduced homocysteine and marginally reduced oxidative stress in men; as well as improvements to the lipid profile in men. In healthy older people, multivitamin supplementation improved a number of blood biomarkers that are relevant to cognition, but these biomarker changes were not accompanied by improved cognitive function.

Topics: Aged; Aging; Biomarkers; C-Reactive Protein; Cognition; Cognition Disorders; Dietary Supplements; Double-Blind Method; Female; Homocysteine; Humans; Lipids; Male; Middle Aged; Oxidative Stress; Reference Values; Sex Factors; Vitamin B 12; Vitamin B 6; Vitamins

We investigated the effects of 2-year folic acid and vitamin B12 supplementation on cognitive performance in elderly people with elevated homocysteine (Hcy) levels.. This multicenter, double-blind, randomized, placebo-controlled trial included 2,919 elderly participants (65 years and older) with Hcy levels between 12 and 50 µmol/L. Participants received daily either a tablet with 400 µg folic acid and 500 µg vitamin B12 (B-vitamin group) or a placebo tablet. Both tablets contained 15 µg vitamin D3. Data were available for global cognitive functioning assessed by Mini-Mental State Examination (n = 2,556), episodic memory (n = 2,467), attention and working memory (n = 759), information processing speed (n = 731), and executive function (n = 721).. Mean age was 74.1 (SD 6.5) years. Hcy concentrations decreased 5.0 (95% confidence interval -5.3 to -4.7) µmol/L in the B-vitamin group and 1.3 (-1.6 to -0.9) µmol/L in the placebo group. Cognitive domain scores did not differ over time between the 2 groups, as determined by analysis of covariance. Mini-Mental State Examination score decreased with 0.1 (-0.2 to 0.0) in the B-vitamin group and 0.3 (-0.4 to -0.2) in the placebo group (p = 0.05), as determined by an independent t test.. Two-year folic acid and vitamin B12 supplementation did not beneficially affect performance on 4 cognitive domains in elderly people with elevated Hcy levels. It may slightly slow the rate of decline of global cognition, but the reported small difference may be attributable to chance.. This study provides Class I evidence that 2-year supplementation with folic acid and vitamin B12 in hyperhomocysteinemic elderly people does not affect cognitive performance.

Topics: Aged; Aged, 80 and over; Cognition; Cognition Disorders; Dietary Supplements; Double-Blind Method; Executive Function; Female; Folic Acid; Humans; Male; Memory; Neuropsychological Tests; Vitamin B 12

High plasma total homocysteine (tHcy) has been associated with cognitive impairment but lowering tHcy with B-vitamins has produced equivocal results. We aimed to determine whether B-vitamin supplementation would reduce tHcy and the incidence of new cognitive impairment among individuals with stroke or transient ischemic attack≥6 months previously.. A total of 8164 patients with stroke or transient ischemic attack were randomly allocated to double-blind treatment with one tablet daily of B-vitamins (folic acid, 2 mg; vitamin B6, 25 mg; vitamin B12, 500 μg) or placebo and followed up for 3.4 years (median) in the VITAmins TO Prevent Stroke (VITATOPS) trial. For this prespecified secondary analysis of VITATOPS, the primary outcome was a new diagnosis of cognitive impairment, defined as a Mini-Mental State Examination (MMSE) score<24 on ≥2 follow-up visits. Secondary outcomes were cognitive decline, and the mean tHcy and MMSE at final follow-up.. A total of 3089 participants (38%) voluntarily undertook the MMSE>6 months after the qualifying stroke; 2608 participants were cognitively unimpaired (MMSE≥24), of whom 2214 participants (1110 B-vitamins versus 1104 placebo) had follow-up MMSEs during 2.8 years (median). At final follow-up, allocation to B-vitamins, compared with placebo, was associated with a reduction in mean tHcy (10.2 μmol/L versus 14.2 μmol/L; P<0.001) but no change from baseline in the mean MMSE score (-0.22 points versus -0.25 points; difference, 0.03; 95% confidence interval, -0.13 to 0.19; P=0.726) and no difference in the incidence of cognitive impairment (5.51% versus 5.47%; risk ratio, 1.01; 95% confidence interval, 0.69-1.48; P=0.976), cognitive decline (9.1% versus 10.3%; risk ratio, 0.89; 0.67-1.18; P=0.414), or cognitive impairment or decline (11.0% versus 11.3%; risk ratio, 0.98; 0.75-1.27; P=0.855).. Daily supplementation with folic acid, vitamin B6, and vitamin B12 to a self-selected clinical trial cohort of cognitively unimpaired patients with previous stroke or transient ischemic attack lowered mean tHcy but had no effect on the incidence of cognitive impairment or cognitive decline, as measured by the MMSE, during a median of 2.8 years.. URL: http://www.controlled-trials.com. Unique identifier: ISRCTN74743444; URL: http://www.clinicaltrials.gov. Unique identifier: NCT00097669.

Topics: Aged; Cognition Disorders; Double-Blind Method; Female; Follow-Up Studies; Homocysteine; Humans; Ischemic Attack, Transient; Male; Middle Aged; Placebos; Recurrence; Stroke; Treatment Outcome; Vitamin B 12; Vitamin B Complex

Micronutrient deficiencies can affect cognitive function. Many young children in low- and middle-income countries have inadequate cobalamin (vitamin B-12) status.. The objective was to measure the association of plasma concentrations of folate, cobalamin, total homocysteine, and methylmalonic acid with cognitive performance at 2 occasions, 4 mo apart, in North Indian children aged 12-18 mo.. Bayley Scales of Infant Development II were used to assess cognition. In multiple regression models adjusted for several potential confounders, we measured the association between biomarkers for folate and cobalamin status and psychomotor or mental development scores on the day of blood sampling and 4 mo thereafter.. Each 2-fold increment in plasma cobalamin concentration was associated with a significant increment in the mental development index score of 1.3 (95% CI: 0.2, 2.4; P = 0.021). Furthermore, each 2-fold increment in homocysteine or methylmalonic acid concentration was associated with a decrement in mental development index score of 2.0 (95% CI: 0.5, 3.4; P = 0.007) or 1.1 (95% CI: 0.3, 1.8; P = 0.004) points, respectively. Plasma folate concentration was significantly and independently associated with mental development index scores only when children with poor cobalamin status were excluded, ie, in those who had cobalamin concentrations below the 25th percentile. None of these markers was associated with psychomotor scores in the multiple regression models.. Cobalamin and folate status showed a statistically significant association with cognitive performance. Given the high prevalence of deficiencies in these nutrients, folate and cobalamin supplementation trials are required to measure any beneficial effect on cognition.

Topics: Biomarkers; Child Development; Cognition Disorders; Cohort Studies; Developmental Disabilities; Female; Folic Acid; Folic Acid Deficiency; Homocysteine; Humans; India; Infant; Male; Methylmalonic Acid; Neurogenesis; Nutritional Status; Prevalence; Psychomotor Performance; Vitamin B 12; Vitamin B 12 Deficiency

Homocysteine is a risk factor for Alzheimer's disease. In the first report on the VITACOG trial, we showed that homocysteine-lowering treatment with B vitamins slows the rate of brain atrophy in mild cognitive impairment (MCI). Here we report the effect of B vitamins on cognitive and clinical decline (secondary outcomes) in the same study.. This was a double-blind, single-centre study, which included participants with MCI, aged ≥ 70 y, randomly assigned to receive a daily dose of 0.8 mg folic acid, 0.5 mg vitamin B(12) and 20 mg vitamin B(6) (133 participants) or placebo (133 participants) for 2 y. Changes in cognitive or clinical function were analysed by generalized linear models or mixed-effects models.. The mean plasma total homocysteine was 30% lower in those treated with B vitamins relative to placebo. B vitamins stabilized executive function (CLOX) relative to placebo (P = 0.015). There was significant benefit of B-vitamin treatment among participants with baseline homocysteine above the median (11.3 µmol/L) in global cognition (Mini Mental State Examination, P < 0.001), episodic memory (Hopkins Verbal Learning Test-delayed recall, P = 0.001) and semantic memory (category fluency, P = 0.037). Clinical benefit occurred in the B-vitamin group for those in the upper quartile of homocysteine at baseline in global clinical dementia rating score (P = 0.02) and IQCODE score (P = 0.01).. In this small intervention trial, B vitamins appear to slow cognitive and clinical decline in people with MCI, in particular in those with elevated homocysteine. Further trials are needed to see if this treatment will slow or prevent conversion from MCI to dementia.

Topics: Aged; Aged, 80 and over; Cognition; Cognition Disorders; Double-Blind Method; Executive Function; Female; Folic Acid; Homocysteine; Humans; Linear Models; Male; Memory; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Evidence remains unclear as to whether folic acid (FA) and vitamin B-12 supplementation is effective in reducing depressive symptoms.. The objective was to determine whether oral FA + vitamin B-12 supplementation prevented cognitive decline in a cohort of community-dwelling older adults with elevated psychological distress.. A randomized controlled trial (RCT) with a completely crossed 2 × 2 × 2 factorial design comprising daily oral 400 μg FA + 100 μg vitamin B-12 supplementation (compared with placebo), physical activity promotion, and depression literacy with comparator control interventions for reducing depressive symptoms was conducted in 900 adults aged 60-74 y with elevated psychological distress (Kessler Distress 10-Scale; scores >15). The 2-y intervention was delivered in 10 modules via mail with concurrent telephone tracking calls. Main outcome measures examined change in cognitive functioning at 12 and 24 mo by using the Telephone Interview for Cognitive Status-Modified (TICS-M) and the Brief Test of Adult Cognition by Telephone (processing speed); the Informant Questionnaire on Cognitive Decline in the Elderly was administered at 24 mo.. FA + vitamin B-12 improved the TICS-M total (P = 0.032; effect size d = 0.17), TICS-M immediate (P = 0.046; d = 0.15), and TICS-M delayed recall (P = 0.013; effect size d = 0.18) scores at 24 mo in comparison with placebo. No significant changes were evident in orientation, attention, semantic memory, processing speed, or informant reports.. Long-term supplementation of daily oral 400 μg FA + 100 μg vitamin B-12 promotes improvement in cognitive functioning after 24 mo, particularly in immediate and delayed memory performance. This trial was registered at clinicaltrials.gov as NCT00214682.

Topics: Administration, Oral; Aged; Cognition Disorders; Depression; Dietary Supplements; Female; Folic Acid; Geriatric Assessment; Humans; Interviews as Topic; Male; Mental Recall; Middle Aged; Stress, Psychological; Surveys and Questionnaires; Vitamin B 12; Vitamin B Complex

Although patients harboring confluent white matter hyperintensities (WMH) are at high risk of cognitive decline, this risk varies among individuals. We investigated the predictors for cognitive decline in stroke patients with confluent WMH.. We followed up 100 stroke patients with confluent WMH who were participants of the VITAmins TO Prevent Stroke study for 2 years. We investigated the association between clinical features, apolipoprotein E status, imaging measures (infarcts, microbleeds, volumes of WMH, cortical gray matter [cGM], lateral ventricles, and hippocampi), and B vitamins with changes in cognitive measures (clinical dementia rating scale, Mini-Mental State Examination, Mattis dementia rating scale--initiation/perseveration subscale). We performed Pittsburgh compound B imaging among dementia converters.. Multivariate regression analysis showed that increase in clinical dementia rating scale grade was associated with cGM atrophy, absence of hyperlipidemia, and lower diastolic blood pressure at baseline. cGM atrophy and absence of hyperlipidemia were also associated with deterioration in Mini-Mental State Examination and Mattis dementia rating scale--initiation/perseveration subscale scores. Pittsburgh compound B retention typical of Alzheimer's disease was found only in 10% of dementia converters. Incident stroke and B vitamins were not associated with cognitive decline.. Among stroke patients with confluent WMH, cGM atrophy and absence of hyperlipidemia are important predictors for cognitive decline. Significant cognitive decline can occur in the absence of incident stroke or Alzheimer's pathology.

Topics: Aged; Atrophy; Brain; Cognition Disorders; Double-Blind Method; Female; Folic Acid; Humans; Magnetic Resonance Imaging; Male; Nerve Fibers, Myelinated; Secondary Prevention; Stroke; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Whether homocysteine lowering by B vitamins can reduce cognitive decline in Alzheimer disease and vascular dementia patients is unclear.. 140 subjects with mild to moderate Alzheimer disease or vascular dementia were randomly assigned to take 1 mg of methylcobalamin and 5 mg of folic acid, or placebo once daily for 24 months. The primary outcome was Mattis dementia rating scale (MDRS). Secondary outcomes were MDRS domain scores, neuropsychiatric inventory and Cornell scale for depression in dementia. Measurements were performed at baseline and every six months during the study. Fasting plasma tHCY concentrations were measured at baseline and month 18.. Trial groups were well matched in baseline characteristics. The average plasma tHCY concentration of subjects was 14.1 ± 3.8 μmol/L. 80% of subjects completed the trial. The supplement group had average plasma tHCY reduced to 9.3 ± 2.7 μmol/L. There was no significant group difference in changes in any of the neuropsychological scores, but among those with elevated plasma tHCY (>13 μmol/L), the decline in MDRS (construction domain) was significantly smaller in the supplement group (median 0 versus 2 points in placebo group, P = 0.003).. Homocysteine lowering in dementia patients did not significantly reduce global cognitive decline.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Cognition Disorders; Dementia, Vascular; Depression; Double-Blind Method; Drug Therapy, Combination; Female; Folic Acid; Homocysteine; Hong Kong; Humans; Hyperhomocysteinemia; Male; Neuropsychological Tests; Patient Dropouts; Vitamin B 12; Vitamin B Complex

Older people have a high risk of vitamin B12 deficiency; this can lead to varying degrees of cognitive and neurological impairment. CBL deficiency may present as macrocytic anemia, subacute combined degeneration of the spinal cord, or as neuropathy, but is often asymptomatic in older people. Less is known about subclinical vitamin B12 deficiency and concurrent neuroconduction and cognitive impairment. A Programme of Complementary Feeding for the Older Population (PACAM) in Chile delivers 2 complementary fortified foods that provide approximately 1.4 μg/day of vitamin B12 (2.4 μg/day elderly RDA). The aim of the present study is to assess whether supplementation with vitamin B12 will improve neuroconduction and cognitive function in older people who have biochemical evidence of vitamin B12 insufficiency in the absence of clinical deficiency.. We designed a cluster double-blind placebo-controlled trial involving community dwelling people aged 70-79 living in Santiago, Chile. We randomized 15 clusters (health centers) involving 300 people (20 per cluster). Each cluster will be randomly assigned to one of three arms: a) a 1 mg vitamin B12 pill taken daily and a routine PACAM food; b) a placebo pill and the milk-PACAM food fortified to provide 1 mg of vitamin B12; c) the routine PACAM food and a placebo pill.The study has been designed as an 18 month follow up period. The primary outcomes assessed at baseline, 4, 9 and 18 months will be: serum levels of vitamin B12, neuroconduction and cognitive function.. In view of the high prevalence of vitamin B12 deficiency in later life, the present study has potential public health interest because since it will measure the impact of the existing program of complementary feeding as compared to two options that provide higher vitamin B12 intakes that might potentially may contribute in preserving neurophysiologic and cognitive function and thus improve quality of life for older people in Chile.. ISRCTN: ISRCTN02694183.

Topics: Aged; Chile; Clinical Protocols; Cognition; Cognition Disorders; Dietary Supplements; Double-Blind Method; Food, Fortified; Humans; Neural Conduction; Public Health; Vitamin B 12; Vitamin B 12 Deficiency

To investigate whether supplementing older men with vitamins B(12), B(6), and folic acid improves cognitive function.. The investigators recruited 299 community-representative hypertensive men 75 years and older to a randomized, double-blind controlled clinical trial of folic acid, vitamin B(6), and B(12) supplementation vs placebo over 2 years. The primary outcome of interest was the change in the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog). A secondary aim of the study was to determine if supplementation with vitamins decreased the risk of cognitive impairment and dementia over 8 years.. The groups were well-balanced for demographic and biochemical parameters. There was no difference in the ADAS-cog change from baseline to 24 months between the placebo (0.8, SD 4.0) and vitamins group (0.7, SD 3.4). The adjusted scores in the treatment groups did not differ over time (placebo 0.2 lower, z = 0.71, p = 0.478). There was a nonsignificant 28% decrease in the risk of cognitive impairment (odds ratio 0.72, 95% confidence interval 0.25-2.09) and dementia (hazard ratio 0.72, 95% confidence interval 0.29-1.78) over 8 years of follow-up.. The daily supplementation of vitamins B(12), B(6), and folic acid does not benefit cognitive function in older men, nor does it reduce the risk of cognitive impairment or dementia.. This study provides Class I evidence that vitamin supplementation with daily doses of 500 μg [DOSAGE ERROR CORRECTED] of B(12), 2 mg of folic acid, and 25 mg of B(6) over 2 years does not improve cognitive function in hypertensive men aged 75 and older.

Topics: Aged; Aged, 80 and over; Cognition; Cognition Disorders; Community Health Planning; Dementia; Dietary Supplements; Double-Blind Method; Folic Acid; Follow-Up Studies; Geriatrics; Homocysteine; Humans; Male; Neuropsychological Tests; Patient Compliance; Time Factors; Vitamin B 12; Vitamin B 6; Vitamin B Complex

The aim of this study is to determine whether B12 replacement would ameliorate cognitive and psychiatric symptoms in elderly subjects with dementia and low serum B12 levels.. A test group (n = 28) of nursing home residents with low serum B12 levels (<250 pg/mL) and a matched comparison group (n = 28) with normal serum B12 levels (>300 pg/mL) were evaluated by blinded raters while the test group received intramuscular (IM) B12 replacement therapy. All subjects were assessed at baseline, 8 weeks, and 16 weeks with the Dementia Rating Scale, Brief Psychiatric Rating Scale, and Geriatric Depression Scale.. Although B12 replacement produced significant improvement in hematologic and metabolic parameters, it yielded no significant effect on cognitive or psychiatric variables. A few subjects evidenced notable individual treatment responses; however, these were not statistically more frequent than in the normal B12 group.. These results suggest that B12 replacement is unlikely to benefit cognitive or psychiatric symptoms in the vast majority of elderly dementia patients with low serum B12 levels.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Brief Psychiatric Rating Scale; Cognition Disorders; Dementia, Multi-Infarct; Female; Follow-Up Studies; Homes for the Aged; Humans; Injections, Intramuscular; Male; Mental Status Schedule; Nursing Homes; Psychometrics; Single-Blind Method; Vitamin B 12; Vitamin B 12 Deficiency

To examine whether use of vitamins B(12), B(6), and folate was associated with reduced severity of depressive symptoms and 2-year incidence of clinically significant depression.. The investigators recruited 299 men aged 75 years and older free of clinically significant depression (Beck Depression Inventory [BDI] score < 18). They were randomly assigned to treatment with 400 microg B(12) + 2 mg folic acid + 25 mg B(6) per day (N = 150) or placebo (N = 149). The BDI was the primary outcome measure of the study. Follow-up assessments took place 6, 12, 18, and 24 months after baseline. Analyses were intention-to-treat. The study was conducted from June 2001 to June 2004.. 118 and 123 men treated with vitamins and placebo, respectively, completed this 2-year trial (19.4% dropout rate). Analysis of variance for repeated measures showed that there was no difference between the groups (F = 0.76, df = 1, p = .384) nor was there a significant change of BDI scores over time (F = 1.26, df = 4, p = .284). Cox regression revealed that participants treated with vitamins were 24% more likely to remain free of depression during the trial, although the difference between groups was not significant (95% CI = 0.68 to 2.28). At the end of the study, 84.3% of men treated with vitamins and 79.1% of those treated with placebo remained free of clinically significant depressive symptoms. The number of people needed to treat to show benefit was 21.. The results of this study showed that treatment with B(12), folic acid, and B(6) is no better than placebo at reducing the severity of depressive symptoms or the incidence of clinically significant depression over a period of 2 years in older men.. www.anzctr.org.au Identifier: ACTRN012605000045617.

Topics: Aged; Cognition Disorders; Depression; Diagnostic and Statistical Manual of Mental Disorders; Folic Acid; Humans; Male; Neuropsychological Tests; Prevalence; Severity of Illness Index; Surveys and Questionnaires; Time Factors; Vitamin B 12; Vitamin B 6

Blood levels of homocysteine may be increased in Alzheimer disease (AD) and hyperhomocysteinemia may contribute to disease pathophysiology by vascular and direct neurotoxic mechanisms. Even in the absence of vitamin deficiency, homocysteine levels can be reduced by administration of high-dose supplements of folic acid and vitamins B(6) and B(12). Prior studies of B vitamins to reduce homocysteine in AD have not had sufficient size or duration to assess their effect on cognitive decline.. To determine the efficacy and safety of B vitamin supplementation in the treatment of AD.. A multicenter, randomized, double-blind controlled clinical trial of high-dose folate, vitamin B(6), and vitamin B(12) supplementation in 409 (of 601 screened) individuals with mild to moderate AD (Mini-Mental State Examination scores between 14 and 26, inclusive) and normal folic acid, vitamin B(12), and homocysteine levels. The study was conducted between February 20, 2003, and December 15, 2006, at clinical research sites of the Alzheimer Disease Cooperative Study located throughout the United States.. Participants were randomly assigned to 2 groups of unequal size to increase enrollment (60% treated with high-dose supplements [5 mg/d of folate, 25 mg/d of vitamin B(6), 1 mg/d of vitamin B(12)] and 40% treated with identical placebo); duration of treatment was 18 months.. Change in the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-cog).. A total of 340 participants (202 in active treatment group and 138 in placebo group) completed the trial while taking study medication. Although the vitamin supplement regimen was effective in reducing homocysteine levels (mean [SD], -2.42 [3.35] in active treatment group vs -0.86 [2.59] in placebo group; P < .001), it had no beneficial effect on the primary cognitive measure, rate of change in ADAS-cog score during 18 months (0.372 points per month for placebo group vs 0.401 points per month for active treatment group, P = .52; 95% confidence interval of rate difference, -0.06 to 0.12; based on the intention-to-treat generalized estimating equations model), or on any secondary measures. A higher quantity of adverse events involving depression was observed in the group treated with vitamin supplements.. This regimen of high-dose B vitamin supplements does not slow cognitive decline in individuals with mild to moderate AD.. clinicaltrials.gov Identifier: NCT00056225.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Cognition; Cognition Disorders; Dietary Supplements; Female; Folic Acid; Homocysteine; Humans; Male; Methylenetetrahydrofolate Reductase (NADPH2); Psychiatric Status Rating Scales; Vitamin B 12; Vitamin B 6; Vitamin B Complex

High homocysteine concentrations may be neurotoxic and contribute to cognitive decline in older persons.. The objective was to examine the effect of supplementation with folic acid, vitamin B-12, and vitamin B-6 on cognitive change in women with cardiovascular disease (CVD) or CVD risk factors.. The Women's Antioxidant and Folic Acid Cardiovascular Study is a randomized placebo-controlled trial designed to test the effect of a combination of B vitamins (2.5 mg folic acid/d, 50 mg vitamin B-6/d, and 1 mg vitamin B-12/d) on secondary prevention of CVD. Female health professionals aged >or=40 y (n = 5442) with CVD or >or=3 coronary risk factors in 1998 (after folic acid fortification began in the United States) were randomly assigned to treatment. Shortly after randomization (mean: 1.2 y), a substudy of cognitive function was initiated among 2009 participants aged >or=65 y. Telephone cognitive function testing was administered up to 4 times over 5.4 y with 5 tests of general cognition, verbal memory, and category fluency. Repeated-measures analyses were conducted, and the primary outcome was a global composite score averaging all test results.. Mean cognitive change from baseline did not differ between the B vitamin and placebo groups (difference in change in global score: 0.03; 95% CI: -0.03, 0.08; P = 0.30). However, supplementation appeared to preserve cognition among women with a low baseline dietary intake of B vitamins.. Combined B vitamin supplementation did not delay cognitive decline among women with CVD or CVD risk factors. The possible cognitive benefits of supplementation among women with a low dietary intake of B vitamins warrant further study.

Topics: Aged; Aged, 80 and over; Cardiovascular Diseases; Chi-Square Distribution; Cognition; Cognition Disorders; Dietary Supplements; Double-Blind Method; Female; Folic Acid; Follow-Up Studies; Homocysteine; Humans; Hyperhomocysteinemia; Psychometrics; Risk Factors; Statistics, Nonparametric; Vitamin B 12; Vitamin B 6; Vitamin B Complex

To examine the effects of aerobic exercise or vitamin B supplementation on cognitive function in older adults with mild cognitive impairment (MCI).. Randomised placebo-controlled trial.. General community.. Community-dwelling adults aged 70-80 with MCI. Interventions : The 152 participants were randomly assigned to two. (1) a twice-weekly, group-based, moderate-intensity walking programme (WP, n = 77) or a low-intensity placebo activity programme (n = 75) for one year; and (2) daily vitamin pill containing 5 mg folic acid, 0.4 mg vitamin B-12, 50 mg vitamin B-6 (FA/B12/B6, n = 78) or placebo pill (n = 74) for one year.. Cognitive function, measured with neuropsychological tests at baseline and after six and 12 months.. Median session attendance at the exercise programmes (25th-75th percentile) was 63% (2%-81%) and median compliance with taking pills (25th-75th percentile) was 100% (99%-100%). Gender was an effect modifier. Intention-to-treat analysis revealed no main intervention effect for either intervention. In women in the WP, attention (Stroop combination task) improved by 0.3 seconds (p = 0.04) and memory (auditory verbal learning test) by 0.04 words (p = 0.06) with each percentage increase in session attendance. In men attending at least 75% of the sessions, the WP improved memory (beta 1.5 (95% CI: 0.1 to 3.0) words).. The walking programme and/or FA/B12/B6 supplementation were not effective in improving cognition within one year. The walking programme, however, was efficacious in improving memory in men and memory and attention in women with better adherence.. International Standard Randomised Controlled Trial Number Register, 19227688, http://www.controlled-trials.com/isrctn/

Topics: Aged; Aged, 80 and over; Cognition Disorders; Double-Blind Method; Exercise Therapy; Female; Folic Acid; Humans; Male; Memory; Netherlands; Neuropsychological Tests; Patient Compliance; Treatment Outcome; Vitamin B 12; Vitamin B 6; Walking

The results of observational studies suggest that plasma homocysteine concentrations are inversely related to cognitive function in older people. Our objective was to test the hypothesis that lowering the plasma homocysteine concentration improves cognitive function in healthy older people.. We conducted a two-year, double-blind, placebo-controlled, randomized clinical trial involving 276 healthy participants, 65 years of age or older, with plasma homocysteine concentrations of at least 13 micromol per liter. Homocysteine-lowering treatment was a daily supplement containing folate (1000 microg) and vitamins B12 (500 microg) and B6 (10 mg). Tests of cognition were conducted at baseline and after one and two years of treatment. Treatment effects were adjusted for baseline values, sex, and education.. On average, during the course of the study, the plasma homocysteine concentration was 4.36 micromol per liter (95 percent confidence interval, 3.81 to 4.91 micromol per liter) lower in the vitamin group than in the placebo group (P<0.001). Overall, there were no significant differences between the vitamin and placebo groups in the scores on tests of cognition.. The results of this trial do not support the hypothesis that homocysteine lowering with B vitamins improves cognitive performance. (Australian Clinical Trials registry number, ACTR NO 12605000030673.).

Topics: Aged; Cognition; Cognition Disorders; Dementia; Dietary Supplements; Double-Blind Method; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Male; Mental Status Schedule; Psychological Tests; Vitamin B 12; Vitamin B Complex

Vitamin B-12 deficiency is associated with cognitive impairment in older people. However, evidence from randomized trials of the effects of vitamin B-12 supplementation on cognitive function is limited and inconclusive.. The objective was to investigate whether daily supplementation with high doses of oral vitamin B-12 alone or in combination with folic acid has any beneficial effects on cognitive function in persons aged >/=70 y with mild vitamin B-12 deficiency.. In a double-blind, placebo-controlled trial, 195 subjects were randomly assigned to receive 1000 microg vitamin B-12, 1000 microg vitamin B-12 + 400 microg folic acid, or placebo for 24 wk. Vitamin B-12 status was assessed on the basis of methylmalonic acid, total homocysteine (tHcy), and holotranscobalamin (holoTC) concentrations before and after 12 and 24 wk of treatment. Cognitive function was assessed before and after 24 wk of treatment with the use of an extensive neuropsychologic test battery that included the domains of attention, construction, sensomotor speed, memory, and executive function.. Vitamin B-12 status did not change significantly after treatment in the placebo group; however, oral vitamin B-12 supplementation corrected mild vitamin B-12 deficiency. Vitamin B-12 + folic acid supplementation increased red blood cell folate concentrations and decreased tHcy concentrations by 36%. Improvement in memory function was greater in the placebo group than in the group who received vitamin B-12 alone (P = 0.0036). Neither supplementation with vitamin B-12 alone nor that in combination with folic acid was accompanied by any improvement in other cognitive domains.. Oral supplementation with vitamin B-12 alone or in combination with folic acid for 24 wk does not improve cognitive function.

Topics: Administration, Oral; Aged; Aged, 80 and over; Cognition; Cognition Disorders; Dietary Supplements; Double-Blind Method; Drug Therapy, Combination; Female; Folic Acid; Homocysteine; Humans; Male; Memory; Methylmalonic Acid; Psychomotor Performance; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

Associations between vitamin B-12 deficiency and impaired cognitive function and depression have been reported.. A randomized placebo controlled study including 140 individuals with an increased plasma methylmalonic acid (0.40-2.00 micromol/l) not previously treated with vitamin B-12. Cognitive function was assessed by the Cambridge Cognitive Examination (CAMCOG), Mini-Mental State Examination (MMSE), and a 12-words learning test. Symptoms of depression were evaluated by the Major Depression Inventory. The main outcome measure was change in cognitive function and depression score from baseline to follow-up 3 months later.. At baseline 78 (56%) individuals had cognitive impairment judged from the CAMCOG score and 40 (29%) according to the MMSE; 18 (13%) individuals had symptoms of depression. No improvement was found in cognitive function comparing the treatment and placebo group (total CAMCOG score: P = 0.43), nor among individuals with only slightly impaired cognitive function (n = 44, total CAMCOG score: P = 0.42). The treatment group did not improve in depression score as compared to the placebo group (P = 0.18).. The duration of impaired cognitive function was unknown.. A high proportion of individuals with an increased plasma methylmalonic acid had impaired cognitive function, and a rather high prevalence of depression was observed. However, vitamin B-12 treatment did not improve cognitive function or symptoms of depression within the 3-months study period.

Topics: Aged; Cognition Disorders; Depressive Disorder; Female; Humans; Male; Placebos; Severity of Illness Index; Treatment Outcome; Vitamin B 12

To examine the association of cognitive impairment with platelet activation and reactive oxygen species and total homocysteine levels; and to assess the biochemical efficacy of treatment with aspirin and vitamin supplements in people at high risk of dementia.. People with dementia or mild cognitive impairment.. In a 2 x 2 x 2 factorial design trial, 149 people at high-risk of dementia were randomized to receive either low-dose aspirin (81 mg) or placebo; and folic acid (2 mg) plus vitamin B12 (1 mg) or placebo; and vitamins E (500 mg) plus C (200 mg) or placebo. Participants were seen twice before and once after 12 weeks of treatment.. At each visit, participants had their cognitive function assessed and had blood collected for homocysteine, folate and vitamin B12 determination and urine collected for markers of platelet activation (11-dehydro-thromboxane B2) and reactive oxygen species (8-epi-PGF2 alpha).. Prior to treatment, cognitive function was inversely related with homocysteine and with urinary thromboxane and isoprostane, and these associations were independent of age. Aspirin was associated with a median reduction in 11-dehydrothromboxane B2 of 73% (P < 0.001). B-vitamins lowered plasma homocysteine concentration by 30% (P < 0.0001) and antioxidant vitamins lowered isoprostane excretion by 26% (P < 0.1). No effect of treatment on cognitive function was detected.. Aspirin and B-vitamins were effective in reducing biochemical factors associated with cognitive impairment in people at risk of dementia. Large-scale trials are now required to assess the relevance of aspirin and B-vitamins for the maintenance of cognitive function in people at risk of dementia.

Topics: Aged; Aged, 80 and over; Aspirin; Cognition Disorders; Dementia; Female; Folic Acid; Follow-Up Studies; Homocysteine; Humans; Isoprostanes; Male; Middle Aged; Oxidative Stress; Platelet Activation; Platelet Aggregation Inhibitors; Riboflavin; Thromboxanes; Vitamin B 12; Vitamins

To investigate the effect of cobalamin/folate supplementation on cognitive function in elderly patients with dementia.. The cobalamin/folate status of the patients was evaluated by measuring plasma homocysteine, serum methylmalonic acid, serum cobalamin and blood folate. Thirty-three patients were studied and repeatedly assessed with the Mini-Mental State Examination (MMSE) and 'A short cognitive performance test for assessing memory and attention' (SKT) during vitamin substitution.. Patients with mild-moderate dementia and elevated plasma homocysteine levels improved clinically with increased test scores after vitamin substitution, while severely demented patients and patients with normal plasma homocysteine levels did not improve clinically.. Plasma homocysteine may be the best marker for detecting treatable cobalamin/folate deficiency in patients with dementia.

Topics: Aged; Attention; Biomarkers; Cognition Disorders; Dementia; Female; Folic Acid; Homocysteine; Humans; Male; Memory; Mental Status Schedule; Vitamin B 12

This was a 4-week randomized placebo-controlled double-blind study to assess augmentation of open tricyclic antidepressant treatment with 10 mg each of vitamins B1, B2, and B6 in 14 geriatric inpatients with depression. The active vitamin group demonstrated significantly better B2 and B6 status on enzyme activity coefficients and trends toward greater improvement in scores on ratings of depression and congnitive function, as well as in serum nortriptyline levels compared with placebo-treated subjects (Ss). Without specific supplementation, B12 levels increased in Ss receiving B1/B2/B6 and decreased in placebo Ss. These findings offer preliminary support for further investigation of B complex vitamin augmentation in the treatment of geriatric depression.

Topics: Aged; Cognition Disorders; Depressive Disorder; Drug Therapy, Combination; Female; Folic Acid; Humans; Male; Nortriptyline; Nutritional Status; Psychological Tests; Pyridoxine; Riboflavin; Thiamine; Vitamin B 12; Vitamin B Complex

To examine the effects of cobalamin repletion on cognition in elderly subjects with low serum cobalamin and evidence of cognitive dysfunction.. Time series data collected in an open trial of parenteral cobalamin therapy.. Outpatient geriatric assessment centers, inpatient geropsychiatry unit, and tertiary care university hospital.. Twenty-two subjects with low serum cobalamin (less than 150 pmol/L) and evidence of cognitive dysfunction were entered consecutively over an 8-month period of time. Eighteen subjects completed the study.. Subjects received 1000 micrograms of cyanocobalamin intramuscularly daily for 1 week, then weekly for 1 month, then monthly thereafter for a minimum of six months. OUTPATIENT MEASURE: The Mattis Dementia Rating Scale (DRS) was administered both before and at least 6 months after full cobalamin replacement therapy. The hypothesis that cognitive improvement was dependent on the duration of cognitive symptoms was formulated a posteriori.. After a minimum of 6 months of cobalamin therapy, 11 of 18 patients showed cognitive improvement. There was a striking correlation between duration of cognitive symptoms and response to therapy. Patients symptomatic for less than 12 months gained an average of twenty points on the DRS (paired t test P = 0.0076), whereas patients symptomatic greater than 12 months lost an average of three points (paired t test P = .34). Two patients symptomatic for only 3 months normalized their DRS scores, gaining 31 and 28 points, respectively.. There may be a time-limited window of opportunity for effective intervention in patients with cognitive dysfunction and low serum cobalamin.

Topics: Aged; Aged, 80 and over; Cognition; Cognition Disorders; Female; Humans; Male; Pilot Projects; Psychological Tests; Time Factors; Vitamin B 12

Vitamin B. Дефицит витамина B

Topics: Aged; Cognition; Cognition Disorders; Humans; Risk Factors; Vitamin B 12; Vitamin B 12 Deficiency

The uncertainty surrounding high intakes of folic acid and associations with cognitive decline in older adults with low vitamin B12 status has been an obstacle to mandatory folic acid fortification for many years. We estimated the prevalence of combinations of low/normal/high vitamin B12 and folate status and compared associations with global cognitive function using two approaches, of individuals in a population-based study of those aged ≥50 years in the Republic of Ireland. Cross-sectional data from 3781 men and women from Wave 1 of The Irish Longitudinal Study on Ageing were analysed. Global cognitive function was assessed by the Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Prevalence estimates for combinations of vitamin B12 (plasma vitamin B12 < or ≥258 pmol/l) and folate (plasma folate ≤ or >45·3 nmol/l) concentrations were generated. Negative binomial regression models were used to investigate the associations of vitamin B12 and folate status with global cognitive function. Of the participants, 1·5 % (n 51) had low vitamin B12 (<258 pmol/l) and high folate (>45·3 nmol/l) status. Global cognitive performance was not significantly reduced in these individuals when compared with those with normal status for both B-vitamins (n 2433). Those with normal vitamin B12/high folate status (7·6 %) had better cognitive performance (MMSE: incidence rate ratio (IRR) 0·82, 95 % CI 0·68, 0·99; P = 0·043, MoCA: IRR 0·89, 95 % CI 0·80, 0·99; P = 0·025). We demonstrated that high folate status was not associated with lower cognitive scores in older adults with low vitamin B12 status. These findings provide important safety information that could guide fortification policy recommendations in Europe.

Topics: Aged; Aging; Cognition; Cognition Disorders; Cross-Sectional Studies; Female; Folic Acid; Humans; Ireland; Longitudinal Studies; Male; Middle Aged; Vitamin B 12

Previous studies have suggested that prenatal maternal folate deficiency is associated with reduced prenatal brain growth and psychological problems in offspring. However, little is known about the longer-term impact. The aims of this study were to investigate whether prenatal maternal folate insufficiency, high total homocysteine levels and low vitamin B12 levels are associated with altered brain morphology, cognitive and/or psychological problems in school-aged children. This study was embedded in Generation R, a prospective population-based cohort study. The study sample consisted of 256 Dutch children aged between 6 and 8 years from whom structural brain scans were collected using MRI. The mothers of sixty-two children had insufficient (<8 nmol/l) plasma folate concentrations in early pregnancy. Cognitive development was assessed by the Snijders-Oomen Niet-verbale intelligentietest - Revisie and the NEPSY-II-NL. Psychological problems were assessed at age 6 years using the parent report of the Child Behavior Checklist. Low prenatal folate levels were associated with a smaller total brain volume (B -33·34; 95 % CI -66·7, 0·02; P=050) and predicted poorer performance on the language (B -0·28; 95 % CI -0·52, -0·04; P=0·020) and visuo-spatial domains (B -0·27; 95 % CI -0·50, -0·04; P=0·021). High homocysteine levels (>9·1 µmol/l) predicted poorer performance on the language (B -0·31; 95 % CI -0·56, -0·06; P=0·014) and visuo-spatial domains (B -0·36; 95 % CI -0·60, -0·11; P=0·004). No associations with psychological problems were found. Our findings suggest that folate insufficiency in early pregnancy has a long-lasting, global effect on brain development and is, together with homocysteine levels, associated with poorer cognitive performance.

Topics: Brain; Child; Child Behavior Disorders; Cognition Disorders; Cohort Studies; Female; Folic Acid; Folic Acid Deficiency; Homocysteine; Humans; Language Development Disorders; Magnetic Resonance Imaging; Male; Netherlands; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Prospective Studies; Vitamin B 12; Vitamin B 12 Deficiency

The correlation among high levels of total homocysteine, low levels of B. In this study serum homocysteine, B

Topics: Adult; Cognition; Cognition Disorders; Cross-Sectional Studies; Female; HIV; HIV Seropositivity; Homocysteine; Humans; Male; Middle Aged; Vitamin B 12; Vitamin D; Vitamin D Deficiency; Vitamins

Hyperhomocysteinemia, vitamin B12 and folate deficiency have been linked to cognitive dysfunction in multiple sclerosis (MS) patients.. This study aimed to investigate the relation of serum homocysteine (Hcy), vitamin B12 and folate to cognitive functions in MS patients.. Forty-five MS patients and twenty matched healthy controls were included. Subjects were submitted to cognitive assessment using a selected psychometric battery and measurement of serum levels of homocysteine, B12 and folic acid.. MS patients showed significant worse performance in cognitive scales compared to controls (P  ≤ 0.05). Serum homocysteine, vitamin B12 and folate showed no significant difference between patients and controls (P  > 0.05). Serum homocysteine was negatively correlated with total score of Addenbrooke's Cognitive Examination (ACE), paced auditory serial addition test and controlled oral word association test scores. Serum vitamin B12 was positively correlated with ACE language, visuospatial and total scores and negatively correlated with trail making B score. Serum folate was significantly positively correlated with ACE language and total scores. Homocysteine was the only significant predictor for cognitive impairment in MS patients.. Serum homocysteine may play a role in cognitive dysfunction in MS patients.

Topics: Adult; Brain; Case-Control Studies; Cognition Disorders; Female; Folic Acid; Homocysteine; Humans; Linear Models; Magnetic Resonance Imaging; Male; Multiple Sclerosis; Psychometrics; Statistics, Nonparametric; Vitamin B 12

To report five cases of subacute combined degeneration (SCD) with brain involvement and explore its clinical and imaging characteristics.. A retrospective study was performed on the clinical data and brain MRI of five patients with subacute combined degeneration with brain involvement (out of 107 cases with SCD in total). White matter lesions (WML) assessment was performed qualitatively using Fazekas scale score.. The main symptoms in four patients were weakness in both lower extremities and unstable walking (limb weakness in three patients, dizziness in three patients, and blurred vision in one patient). One patient had memory loss and cognitive dysfunction. The MMSE scale indicated mild dementia in one patient. On head MRI (Magnetic Resonance Imaging), multifocal and symmetrical high signals of T2WI and FLAIR were observed in the frontal lobe and periventricular white matter in four patients, while another patient showed preferential atrophy in frontal regions. Fazekas scale scores ranged from 1-6.. Adult subacute combined degeneration seldom involves the brain. Multifocal and symmetrical high signal white matter lesions can be found on FLAIR and T2WI, as well as frontal atrophy on head MRI.

Topics: Aged; Atrophy; Cognition Disorders; Female; Homocysteine; Humans; Leukoencephalopathies; Magnetic Resonance Imaging; Male; Mental Status Schedule; Middle Aged; Retrospective Studies; Subacute Combined Degeneration; Vitamin B 12

Topics: Adult; Age Factors; Alzheimer Disease; Cognition; Cognition Disorders; Cohort Studies; Diet; Dietary Supplements; Executive Function; Female; Folic Acid; Humans; Longitudinal Studies; Male; Memory; Middle Aged; Niacin; Psychomotor Performance; Verbal Learning; Vitamin B 12; Vitamin B 6; Vitamin B Complex; Vitamin B Deficiency; Young Adult

The concept of combinatorial biomarkers was conceived when it was noticed that simple biomarkers are often inadequate for recognizing and characterizing complex diseases. Here we present an algorithmic search method for complex biomarkers which may predict or indicate Alzheimer's disease (AD) and other kinds of dementia. We show that our method is universal since it can describe any Boolean function for biomarker discovery. We applied data mining techniques that are capable to uncover implication-like logical schemes with detailed quality scoring. The new SCARF program was applied for the Tucson, Arizona based Critical Path Institute's CAMD database, containing laboratory and cognitive test data for 5821 patients from the placebo arm of clinical trials of large pharmaceutical companies, and consequently, the data is much more reliable than numerous other databases for dementia. The results of our study on this larger than 5800-patient cohort suggest beneficial effects of high B12 vitamin level, negative effects of high sodium levels or high AST (aspartate aminotransferase) liver enzyme levels to cognition. As an example for a more complex and quite surprising rule: Low or normal blood glucose level with either low cholesterol or high serum sodium would also increase the probability of bad cognition with a 3.7 multiplier. The source code of the new SCARF program is publicly available at http://pitgroup.org/static/scarf.zip.

Topics: Aged; Alzheimer Disease; Arizona; Biomarkers; Cognition; Cognition Disorders; Cohort Studies; Data Mining; Dementia; Humans; Male; Vitamin B 12

Vitamin B12 is essential for the integrity of the central nervous system. However, performances in different cognitive domains relevant to vitamin B12 deficiency remain to be detailed. To date, there have been limited studies that examined the relationships between cognitions and structural neuroimaging in a single cohort of low-vitamin B12 status. The present study aimed to depict psychometrics and magnetic resonance imaging (MRI) morphometrics among patients with vitamin B12 deficiency, and to examine their inter-relations.. We compared 34 consecutive patients with vitamin B12 deficiency (serum level ≤ 250 pg/ml) to 34 demographically matched controls by their cognitive performances and morphometric indices of brain MRI. The correlations between psychometrics and morphometrics were analyzed.. The vitamin B12 deficiency group had lower scores than the controls on total scores of Mini-Mental Status Examination (MMSE) and Cognitive Abilities Screening Instrument (CASI) (both P < 0.05), language (P < 0.01), orientation (P < 0.01), and mental manipulation (P < 0.05). The patients also showed a greater frontal horn ratio than the controls (P < 0.05). Bicaudate ratio, fronto-occipital ratio, uncotemporal index, and normalized interuncal distance all showed a strong correlation with the total score of MMSE and CASI (all P < 0.01). Among these psychometric and morphometric indices, pronounced correlations between bicaudate ratio and long-term memory, mental manipulation, orientation, language, and verbal fluency were noted (all P < 0.01).. Vitamin B12 deficiency is associated with a global cognition decline with language, orientation, and mental manipulation selectively impaired. Preferential atrophy in frontal regions is the main neuroimaging feature. Although the frontal ratio highlights the relevant atrophy among patients, the bicaudate ratio might be the best index on the basis of its strong association with global cognition and related cognitive domains, implying dysfunction of fronto-subcortical circuits as the fundamental pathogenesis related to vitamin B12 deficiency.

Topics: Aged; Brain; Case-Control Studies; Cognition; Cognition Disorders; Female; Humans; Magnetic Resonance Imaging; Male; Memory, Long-Term; Middle Aged; Neuropsychological Tests; Psychometrics; Vitamin B 12; Vitamin B 12 Deficiency

Undernutrition as well as low levels of vitamin B12 and folic acid are common problems among older adults. However, recommended routine nutritional status assessment tools may result in inadequate vitamin serum levels to go unnoticed. Therefore, the aim of this study is to evaluate the inadequacy of serum levels of vitamin B12 and folic acid within Mini Nutritional Assessment (MNA) classification categories among older adults. A cross-sectional study was conducted with 97 older adults residing in care homes in Portugal. Undernutrition was identified through the MNA, and serum levels of vitamin B12 and folic acid were measured using chemiluminescence. Cognitive function, depressive symptoms and functional characteristics were also assessed using the Abbreviated Mental Test Score, the Epidemiologic Studies Depression Scale and the Barthel Index, respectively. The mean age of older adults was 82.2 (6.3) years; 3.1% were undernourished and 26.8% were at undernutrition risk. In the MNA normal nutritional status group, 11.8% presented vitamin B12 deficiency (<200 pg/ml), 32.4% had low serum levels (200-400 pg/ml) and 4.4% had folic acid deficiency (<3 ng/ml). A high proportion of older adults with low serum levels of vitamin B12 presenting normal nutritional status by MNA was identified. This finding emphasizes the need to evaluate serum vitamin B12 levels, independently of the MNA results.

Topics: Aged; Aged, 80 and over; Cognition; Cognition Disorders; Cross-Sectional Studies; Depression; Female; Folic Acid; Folic Acid Deficiency; Geriatric Assessment; Hematinics; Humans; Luminescence; Male; Malnutrition; Nutrition Assessment; Nutritional Status; Portugal; Reference Values; Vitamin B 12; Vitamin B 12 Deficiency

Cobalamin (Cbl) is an essential vitamin for human health. While an increasing body of evidence supports the negative impact of Cbl deficiency on cognition, the causality has yet to be determined, and the reported therapeutic responses after Cbl supplement therapy have been inconsistent. Besides, few reports have described neuroimaging characteristics associated with the therapeutic response.. To describe and compare technetium-99m ethyl cysteinate dimer single-photon emission computed tomography (Tc-99m-ECD SPECT) findings in 2 patients with Cbl deficiency with distinct therapeutic responses.. Case 1 scored 12/30 in the mini-mental state examination (MMSE) and 34/100 in the cognitive abilities screening instrument (CASI). Profound deficits in mental manipulation, drawing, short-term/long-term memory, and verbal fluency were noted. Case 2 scored 24/30 in the MMSE and 78/100 in the CASI, mainly due to impaired mental manipulation, abstract thinking, and borderline performance in short-term memory and verbal fluency. While both cases showed widespread hypoperfusion within bilateral frontotemporal regions and thalamus on Tc-99m-ECD SPECT, Case 2 demonstrated relatively preserved radio-uptake in the frontal regions, especially the anterior cingulate cortex (ACC) and prefrontal cortex (PFC), consistent with the better therapeutic response (Case 1: 12/30 to 11/30 in the MMSE; Case 2: 24/30 to 28/30 in the MMSE).. Given that the ACC integrates the limbic system and frontosubcortical circuits and the PFC governs executive function, the extent and severity of hypofrontality may be responsible for the worse prognosis. Our Tc-99m-ECD SPECT observations revealed that the negative impact on cerebral metabolic tone is relevant to the severity of Cbl deficiency, and the functional integrity of the ACC and PFC is highly associated with the preservation of global cognitive function in our cases with Cbl deficiency.

Topics: Aged; Cognition Disorders; Cysteine; Female; Gyrus Cinguli; Humans; Middle Aged; Organotechnetium Compounds; Prefrontal Cortex; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency; Vitamins

There is a growing focus on nutritional therapy for Alzheimer's disease (AD), and controversy exists regarding the association between AD and homocysteine (Hcy), vitamin B12, and folate levels.. The present study evaluated the association between AD and the combined levels of Hcy, vitamin B12, and folate.. This case-control study consisted of 115 patients with AD and 115 matched controls. Serum folate and vitamin B12 were measured using an automated immunoassay analyzer. Plasma Hcy was measured using high-performance liquid chromatography. The association between AD and Hcy, vitamin B12, and folate was analyzed using binary logistic regression, adjusted for age and sex.. With the combination of normal blood Hcy, vitamin B12, and folate levels as the reference category, low vitamin B12 in subjects with normal Hcy and folate was associated with AD (adjusted odds ratio [OR], 4.6; 95% confidence interval [CI]: 1.6-13.2). The combination of low vitamin B12 and folate in subjects with normal Hcy was associated with AD (adjusted OR, 4.3; 95% CI: 1.3-14.6). The combination of high Hcy and low folate levels in patients with normal vitamin B12 was associated with AD (adjusted OR, 17.0; 95% CI: 5.4- 53.4). The combination of high Hcy, low vitamin B12, and any folate level was associated with AD (adjusted OR, 30.5; 95% CI: 9.7-95.9).. Vitamin B12 was directly associated with AD. The combination of high Hcy, low vitamin B12, and any folate level represented the poorest association with AD.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Case-Control Studies; Chromatography, High Pressure Liquid; Cognition Disorders; Confidence Intervals; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Odds Ratio; Psychiatric Status Rating Scales; Retrospective Studies; Surveys and Questionnaires; Vitamin B 12

To analyse the relationship between serum folate (SF), vitamin B12 and impaired cognitive function in the Chilean elderly.. We analysed the relationships between impaired cognitive function and age, SF (µg/l) and vitamin B12 (pg/ml) with Student's t test, as well as between impaired cognitive function and gender, educational level, residence area, diabetes and hypertension with the χ 2 test. Multiple logistic regressions with interactions were estimated to assess the impact of SF on impaired cognitive function according to these methods.. Chile.. Older adults (>65 years, n 1051), drawn from representative households of a national prevalence study, assessed using the Modified Mini Mental Status Examination (MMMSE). Individuals with altered MMMSE scores (≤13 points) were sequentially assessed using the Pfeffer Functional Activities Questionnaire (PFAQ).. Multivariate models using the MMMSE demonstrated an increased risk of impaired cognitive function for seniors who had hypertension, diabetes and higher vitamin B12 levels. SF and its square (SF2) were statistically significant, indicating that this predictor of impaired cognitive function displays a U-shaped distribution. The interaction between SF and vitamin B12 was not statistically significant. Models using the MMMSE plus PFAQ suggested that urban residence decreased the risk of impaired cognitive function, whereas male gender, older age, vitamin B12 levels and hypertension increased this risk. The variables SF and SF2 and the SF × vitamin B12 interaction were statistically significant (P<0.05). The risk of impaired cognitive function depended on different combinations of SF and vitamin B12 levels. When SF was low, a one-unit increase in SF (1 µg/l) diminished the risk. When SF was elevated, a further increase in SF raised the risk, especially at low vitamin B12 levels.. The relationship between folate, vitamin B12 and impaired cognitive function warrants further study.

Topics: Activities of Daily Living; Age Factors; Aged; Chile; Cognition; Cognition Disorders; Cross-Sectional Studies; Female; Folic Acid; Folic Acid Deficiency; Geriatric Assessment; Humans; Hypertension; Male; Nutrition Assessment; Nutritional Status; Sex Factors; Surveys and Questionnaires; Urban Population; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B Complex

To determine the association between hyperhomocysteinemia and cognitive function, taking into account the effect of B group vitamin (BGV) deficiency.. Cross-sectional.. Memory Clinic, S. Anna University Hospital, Ferrara, Italy.. Elderly individuals (≥65) (N = 318; 44 normal cognition, 127 with cognitive impairment, 147 with dementia) divided into four groups according to plasma homocysteine (high vs normal) and BGV (normal vs deficit) levels.. Cognitive, clinical, biochemical, functional, and neuroimaging parameters were evaluated.. Hyperhomocysteinemia (>15 μmol/L) was associated with a higher prevalence of cognitive and functional impairment and dementia (odds ratio (OR) = 1.98, 95% confidence interval (CI) = 1.13-3.48), independent of BGV status and other confounders. Participants with hyperhomocysteinemia with normal BGV status had the worst functional status and the highest prevalence of dementia (high homocysteine/normal BGV vs normal homocysteine/normal BGV: OR = 3.20, 95% CI = 1.65-6.21). Homocysteine levels were correlated negatively with folate and vitamin B12 levels and glomerular filtration rate and positively with free thyroxine and uric acid levels (model coefficient of determination = 0.43).. Hyperhomocysteinemia was associated with worse cognitive and functional status and dementia independently of BGV levels. Approximately half of participants with hyperhomocysteinemia had normal BGV levels, suggesting that other unmeasured factors might be associated with high homocysteine levels.

Topics: Aged; Aged, 80 and over; Cognition; Cognition Disorders; Comorbidity; Confidence Intervals; Cross-Sectional Studies; Female; Folic Acid; Folic Acid Deficiency; Homocysteine; Humans; Hyperhomocysteinemia; Italy; Male; Odds Ratio; Prevalence; Risk Factors; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B 6; Vitamin B 6 Deficiency

Hyperhomocysteinemia is a recognized risk factor for cognitive decline and incident dementia in older adults. Two recent reports addressed the cumulative epidemiological evidence for this association but expressed conflicting opinions. Here, the evidence is reviewed in relation to Sir Austin Bradford Hill's criteria for assessing "causality," and the latest meta-analysis of the effects of homocysteine-lowering on cognitive function is critically examined. The meta-analysis included 11 trials, collectively assessing 22,000 individuals, that examined the effects of B vitamin supplements (folic acid, vitamin B12, vitamin B6) on global or domain-specific cognitive decline. It concluded that homocysteine-lowering with B vitamin supplements has no significant effect on cognitive function. However, careful examination of the trials in the meta-analysis indicates that no conclusion can be made regarding the effects of homocysteine-lowering on cognitive decline, since the trials typically did not include individuals who were experiencing such decline. Further definitive trials in older adults experiencing cognitive decline are still urgently needed.

Topics: Cognition; Cognition Disorders; Dementia; Dietary Supplements; Folic Acid; Homocysteine; Humans; Meta-Analysis as Topic; Risk Factors; Vitamin B 12; Vitamin B 6; Vitamin B Complex

A combination of high folate with low vitamin B12 plasma status has been associated with cognitive impairment in a population exposed to mandatory folic acid fortification. The objective of the present study was to examine the interactions between plasma concentrations of folate and vitamin B12 markers in relation to cognitive performance in Norwegian elderly who were unexposed to mandatory or voluntary folic acid fortification. Cognitive performance was assessed by six cognitive tests in 2203 individuals aged 72-74 years. A combined score was calculated using principal component analysis. The associations of folate concentrations, vitamin B12 markers (total vitamin B12, holotranscobalamin (holoTC) and methylmalonic acid (MMA)) and their interactions in relation to cognitive performance were evaluated by quantile regression and least-squares regression, adjusted for sex, education, apo-ɛ4 genotype, history of CVD/hypertension and creatinine. Cross-sectional analyses revealed an interaction (P= 0·009) between plasma concentrations of folate and vitamin B12 in relation to cognitive performance. Plasma vitamin B12 concentrations in the lowest quartile ( < 274 pmol/l) combined with plasma folate concentrations in the highest quartile (>18·5 nmol/l) were associated with a reduced risk of cognitive impairment compared with plasma concentrations in the middle quartiles of both vitamins (OR 0·22, 95 % CI 0·05, 0·92). The interaction between folate and holoTC or MMA in relation to cognitive performance was not significant. In conclusion, this large study population unexposed to mandatory folic acid fortification showed that plasma folate, but not plasma vitamin B12, was associated with cognitive performance. Among the elderly participants with vitamin B12 concentrations in the lower range, the association between plasma folate and cognitive performance was strongest.

Topics: Aged; Biomarkers; Cognition Disorders; Cross-Sectional Studies; Diet; Female; Folic Acid; Food, Fortified; Homocysteine; Humans; Male; Methylmalonic Acid; Norway; Nutritional Status; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

Cerebral white matter hyperintensities (WMH) are a consequence of cerebral small vessel disease. Statins have been shown to reduce recurrent stroke among patients with various stroke subtypes, including lacunar stroke, which also arises from small vessel disease. In this study, we investigated the hypothesis that prestroke statin use would reduce the progression of WMH and/or cognitive decline among stroke patients with confluent WMH. Patients (n = 100) were participants of the VITAmins To Prevent Stroke magnetic resonance imaging substudy. All patients had confluent WMH on magnetic resonance imaging at baseline. Eighty-one patients completed the 2-year follow-up. We assessed general cognition and executive function using the mini-mental state examination and Mattis dementia rating scale-initiation/perseveration subscale, respectively. We compared the change in volume of WMH and cognition between prestroke statin use and prestroke nonstatin use groups. We also evaluated the effects of prestroke statin use on incident lacunes and microbleeds. The prestroke statin use group (n = 51) had less WMH volume progression (1.54 ± 4.52 cm(3) vs 5.01 ± 6.00 cm(3), p = 0.02) compared with the prestroke nonstatin use group (n = 30). Multivariate linear regression modeling identified prestroke statin use as an independent predictor of WMH progression (β = -0.31, p = 0.008). Prestroke statin use was also associated with less decline (Mattis dementia rating scale-initiation/perseveration subscale; β = 0.47, p = 0.001). No association was observed with changes in mini-mental state examination scores. There were no between group differences on incident lacunes or incident microbleeds. Prestroke statin use may reduce WMH progression and decline in executive function in stroke patients with confluent WMH.

Topics: Aged; Cerebral Cortex; Cerebral Small Vessel Diseases; Cognition Disorders; Disease Progression; Female; Folic Acid; Humans; Magnetic Resonance Imaging; Male; Stroke; Vitamin B 12; Vitamin B 6; White Matter

To explore the correlation between serum levels of homocysteine (Hcy) and folate and cognitive function in first-episode drug-naїve schizophrenics.. A total of 60 first-episode schizophrenics (schizophrenia group) from our hospital and 60 healthy individuals (control group) were enrolled.Serum levels of folate and Hcy were measured with electrochemical luminescence method and enzymatic cycling assay respectively. Positive and Negative Syndrome Scale (PANSS) was used to evaluate the mental symptoms and Matrics Consensus Cognitive Battery (MCCB) was used to evaluate the cognitive function.. Serum level of folate in schizophrenia group (4.1 ± 1.9 ng/ml) was lower than that in control group (7.5 ± 1.9 ng/ml) (P < 0.001). And serum level of Hcy in schizophrenia group (27 ± 9 µmol/L) was significantly higher than that in control group (18 ± 6 µmol/L) (P = 0.006). Serum level of folate in schizophrenia group had negative correlations with Hcy level (r = -0.38, P = 0.002) and negative symptoms (r = -0.25, P < 0.05) while Hcy level was negatively correlated with cognitive function scores (r = -0.38, r = -0.33, r = -0.30, r = -0.30, P < 0.05).. Serum level of folate decreases while serum level of Hcy increases in first-episode schizophrenics. Both have some relevance with mental symptom and cognitive dysfunction.

Topics: Adolescent; Adult; Case-Control Studies; Cognition Disorders; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Schizophrenia; Vitamin B 12; Young Adult

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.. The tHcy, folate, and vitamin B12 levels in 82 patients with VCIND were reviewed retrospectively and compared with those of 80 stroke patients without cognitive impairment and 69 healthy controls by using the Montreal Cognitive Assessment (MoCA) scale and the event-related potential P300 to evaluate cognitive function.. The tHcy levels in the VCIND group were higher than those in the other two groups, whereas the folate and Vitamin B12 levels in the VCIND group were lower than those of the other two groups. The tHcy levels in the stroke group were higher than those in the control group, and the folate and vitamin B12 levels in the stroke group were lower than those in the control group. The patients in the VCIND group with high tHcy exhibited lower MoCA scores and prolonged P300 latency than those in with normal tHcy. Correlation analysis showed that tHcy level is positively correlated with P300 latency period and negatively correlated with MoCA score.. The tHcy levels were significantly higher and the vitamin B12 and folate levels were significantly lower in the patients with VCIND than those in the other groups. The high tHcy levels in the VCIND patients may be correlated with impaired cognitive function.

Topics: Adult; Aged; Brain; Case-Control Studies; Cognition; Cognition Disorders; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Risk Factors; Stroke; Vitamin B 12

It is possible that blood B vitamins level and cognitive function may be affected by dietary intake of these vitamins, no study however has yet been conducted on relationships between B vitamins intake and cognitive function among elderly population in Korea. This study examined the relationship between B vitamins intake and cognitive function among elderly in South Korea.. Participants consisted of 100 adults with mild cognitive impairment (MCI), 100 with Alzheimer's disease (AD), and 121 normal subjects. Dietary intake data that included the use of dietary supplements were obtained using a 24-hour recall method by well-trained interviewers. Plasma folate and vitamin B12 concentrations were analyzed by radioimmunoassay, and homocysteine (Hcy) was assessed by a high performance liquid chromatography-fluorescence method.. Plasma levels of folate and vitamin B12 were positively correlated with B vitamins intake; and plasma Hcy was negatively correlated with total intake of vitamin B2, vitamin B6, vitamin B12 and folate. In the AD group, a multiple regression analysis after adjusting for covariates revealed positive relationships between vitamin B2 intake and test scores for the MMSE-KC, Boston Naming, Word Fluency, Word List Memory and Constructional Recall Tests; and between vitamin B6 intake and the MMSE-KC, Boston Naming, Word Fluency, Word List Memory, Word List Recognition, Constructional Recall and Constructional Praxis Tests. Positive associations were observed between vitamin B12 intake and the MMSE-KC, Boston Naming, Constructional Recall and Constructional Praxis Tests, and between folate intake and the Constructional Recall Test. In the MCI group, vitamin B2 intake was positively associated with the MMSE-KC and Boston Naming Test, vitamin B6 intake was positively associated with the Boston Naming Test, and folate intake was positively associated with the MMSE-KC and Word List Memory test. No associations were observed in the normal group.. These results suggested that total B vitamins intake is associated with cognitive function in cognitively impaired AD and MCI elderly, and the association is stronger in AD patients.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Cognition; Cognition Disorders; Diet; Dietary Supplements; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Republic of Korea; Vitamin B 12; Vitamin B Complex

To determine whether high serum folate levels contribute to metabolite changes in elderly subjects with normal cobalamin levels.. Case series.. Outpatient clinic at a university-based staff model health maintenance organization.. Two hundred thirty-three ambulatory individuals without diabetes mellitus with normal renal function and normal cobalamin levels evaluated for cobalamin deficiency.. Cobalamin, serum folate, methylmalonic acid (MMA), and homocysteine.. Older individuals (≥60) with low-normal cobalamin levels (201-300 pg/mL) had higher MMA and lower homocysteine levels when serum folate levels were high (>20 ng/mL) than when serum folate levels were normal (P < .02), but serum folate levels within the normal range were not a determinant of either metabolite. In younger subjects with low-normal cobalamin levels, high serum folate levels were not associated with significant differences in either metabolite. At mid-normal cobalamin levels (301-600 pg/mL), high serum folate levels were associated with lower homocysteine levels in older adults (P < .001) but not with differences in MMA in either age group. Cobalamin therapy decreased or normalized MMA and homocysteine in 89% or more of participants even at pretherapy cobalamin levels greater than 600 pg/mL.. High serum folate levels are associated with higher MMA levels when cobalamin levels are low-normal, and this effect is age dependent, not progressive within the normal serum folate range (suggesting a threshold effect), and reversed by cobalamin therapy. Because MMA may be neurotoxic, these findings suggest caution in the use of folic acid supplements in elderly adults.

Topics: Aged; Aged, 80 and over; Causality; Cognition Disorders; Comorbidity; Female; Folic Acid; Geriatric Assessment; Homocysteine; Humans; Male; Methylmalonic Acid; Risk Factors; Severity of Illness Index; Vitamin B 12; Vitamin B 12 Deficiency

Cobalamin (Cb) blood levels are frequently measured among inpatients, but the relevance of Cb determination has not been correctly assessed in this clinical setting.. We aimed to prospectively evaluate current indications compared to traditional guidelines for assessing Cb blood levels among inpatients from internal medicine departments.. This study was conducted in French departments of internal medicine between 2008 and 2009. Inpatients who underwent Cb blood level determination during a 6-week study period were eligible.. 380 consecutive adult patients were included. The three most common indications for Cb assessment were anaemia (62.6%), cognitive impairment (20.2%) and undernutrition (17.4%). Traditional indications (ie, macrocytic non-regenerative anaemia, isolated macrocytosis, dementia and proprioceptive disorders) accounted for only 33.9% of all tests. Cb deficiency was identified in 40 (10.5%) of the 380 patients tested. Overall, traditional indications were not associated with a significantly higher prevalence of patients with low Cb levels than current guidelines (14% vs 8.8%; p=0.119). Non-regenerative macrocytic anaemia was the only indication with a significantly better performance compared to all other indications (11 of 62 patients (17.7%) vs 29 of 318 patients (9.1%); OR 2.15 (1.01-4.57), p=0.047). The main aetiological causes of Cb deficiency were intake deficiency, pernicious anaemia and food-Cb malabsorption. Homocysteine or methylmalonic acid dosage testing was very rarely performed.. Traditional indications did not perform better than other indications observed in current practice for identifying low Cb levels among inpatients from internal medicine departments. Future studies are needed to establish robust guidelines for inpatient screening.

Topics: Aged; Aged, 80 and over; Anemia; Cognition Disorders; Data Collection; Female; France; Humans; Inpatients; Internal Medicine; Male; Malnutrition; Mass Screening; Middle Aged; Prospective Studies; Vitamin B 12; Vitamin B 12 Deficiency

To investigate the associations of metformin, serum vitamin B12, calcium supplements, and cognitive impairment in patients with diabetes.. Participants were recruited from the Primary Research in Memory (PRIME) clinics study, the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging, and the Barwon region of southeastern Australia. Patients with Alzheimer disease (AD) (n=480) or mild cognitive impairment (n=187) and those who were cognitively intact (n=687) were included; patients with stroke or with neurodegenerative diseases other than AD were excluded. Subgroup analyses were performed for participants who had either type 2 diabetes (n=104) or impaired glucose tolerance (n=22).. Participants with diabetes (n=126) had worse cognitive performance than participants who did not have diabetes (n=1,228; adjusted odds ratio 1.51 [95% CI 1.03-2.21]). Among participants with diabetes, worse cognitive performance was associated with metformin use (2.23 [1.05-4.75]). After adjusting for age, sex, level of education, history of depression, serum vitamin B12, and metformin use, participants with diabetes who were taking calcium supplements had better cognitive performance (0.41 [0.19-0.92]).. Metformin use was associated with impaired cognitive performance. Vitamin B12 and calcium supplements may alleviate metformin-induced vitamin B12 deficiency and were associated with better cognitive outcomes. Prospective trials are warranted to assess the beneficial effects of vitamin B12 and calcium use on cognition in older people with diabetes who are taking metformin.

Topics: Aged; Aged, 80 and over; Calcium; Cognition Disorders; Diabetes Mellitus; Female; Humans; Logistic Models; Male; Metformin; Middle Aged; Prospective Studies; Vitamin B 12; Vitamin B 12 Deficiency

Homocysteine (Hcy) is a sulfur-containing amino acid involved in methionine metabolism. High plasma total Hcy (tHcy) has been quite frequently reported in patients with epilepsy treated with antiepileptic drugs (AEDs) mainly related to plasma folate reduction induced by AEDs themselves. The role of C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase gene (MTHFR) on the increase of plasma tHcy in patients with epilepsy taking AEDs is still controversial. Cognitive impairment may be associated with epilepsy either as the result of the epileptic syndrome per se or as a side effect induced by the AEDs. High plasma tHcy levels were associated with lower cognitive performances in patients affected by Alzheimer's disease and mild cognitive impairment and in healthy elderly. We searched for a correlation between plasma tHcy levels with the intelligence quotient (IQ) scores in a population of children and young adults with epilepsy treated with old and/or newer AEDs. The study group encompassed 179 patients (92 M, 51.5%) followed at our Unit of Child Neuropsychiatry and aged between 4 and 25years (mean+SD: 14.03±4.25). The inclusion criteria included the following: 1) diagnosis of epilepsy of "unknown cause" (cryptogenic) according to the ILAE classification, 2) age older than 3years, 3) stabilized antiepileptic treatment for at least 6months, and 4) clinical records of cognitive tests, plasma tHcy value, and results of MTHFR polymorphisms. Patients' mean tHcy value was 9.71±3.13μM/L (tHcy<9μM/L as our laboratory cutoff in nonepileptic controls). The mean TIQ score was 85.22 (SD±24.12); the mean VIQ score was 86.32 (SD±20.86); and the mean PIQ score was 86.94 (SD±21.51). C677T and A1298C MTHFR polymorphisms were detected in 74/92 (80%) examined patients and distributed into the following: CT (22.3%), TT (14.9%), CC (10.3%) for C677T, AC (16%), CC (1.1%), and AA (30.3%) for A1298C. Plasma tHcy levels were not significantly related to the IQ scores (TIQ, VIQ, or PIQ). Two significant findings came out. First, patients on AED polytherapy showed significantly lower TIQ, VIQ, and PIQ scores compared with the ones with AED monotherapy (p=0.032; p=0.008; p=0.005, respectively). However, this significant difference was not observed with the plasma tHcy levels compared with AED treatment. Second, patients with the 677TT genotype showed significantly higher tHcy levels versus those with the wt ones (p=0.049). In the latter group of patients, although the m

Topics: Adolescent; Adult; Anticonvulsants; Child; Cognition Disorders; Epilepsy; Female; Folic Acid; Homocysteine; Humans; Intelligence Tests; Male; Methylenetetrahydrofolate Reductase (NADPH2); Neuropsychological Tests; Polymorphism, Genetic; Statistics, Nonparametric; Vitamin B 12; Young Adult

To assess the magnitude of elderly (aged 60-85 years) persons with cognitive impairment and its relation with their dietary and anthropometric status.. Cross-sectional study. The cognitive status of the subjects was screened using the Mini Mental Score Examination (MMSE). The binary logistic regression coefficients were ascertained for determining the association of predictors like MMSE score, body mass index (BMI) and waist-to-hip ratio (WHR) with the age of the subjects.. Government hospitals, Vadodara, India.. Geriatric subjects (n = 50) aged 60-85 years.. The mean age of the elderly subjects was around 68 years old. The majority of subjects fell into the mild cognitive impairment (MCI) category, with Grade I obesity. We noted significant correlations (p < 0.05; p < 0.01) with energy, protein, vitamin B12, WHR and BMI.. Cognitive abnormalities doubly elevate with advancing age, with decreased intake of dietary nutrients. The cognitive assessment undertaken focused on this rampant under-diagnosed cognition. The burgeoning prodromal insidious stage of cognitive impairment demands rapid diagnosis for preserving mental health, or else severe deterioration takes over, leading to compromised mental abilities in the elderly.

Topics: Aged; Aged, 80 and over; Body Mass Index; Cognition Disorders; Cross-Sectional Studies; Dietary Proteins; Energy Intake; Female; Geriatric Assessment; Humans; India; Logistic Models; Male; Middle Aged; Nutritional Status; Pilot Projects; Prospective Studies; Socioeconomic Factors; Vitamin B 12; Waist-Hip Ratio

To evaluate cognitive functions and behavioral changes in the patients with vitamin B12 deficiency neurological syndromes (VBDNS) using detailed clinical psychometric and P3 studies and their response to treatment.. The patients with VBDNS were included and their detailed medical history was recorded. Neurobehavioral and cognitive functions were evaluated by neuropsychiatry inventory (NPI), forward and backward digit span, mini mental state examination (MMSE), Luria's three-step test, trail making test (TMT), motor speed and precision test (MSPT), Benton's visual retention test (BVRT), clock drawing (CD), category fluency, hospital anxiety and depression (HAD) scale, and cognitive evoked potential using oddball paradigm at baseline and 3 and 6 months following treatment. Complete hemogram, serum chemistry, vitamin B12, homocysteine, and craniospinal magnetic resonance imaging (MRI) were done.. Thirty-three patients with VBDNS, whose median age was 43 (12-68) years, five (15.2%) of whom were females were included. Twenty-one patients had neurobehavioral/cognitive decline, 26 myelopathy, and 17 neuropathy. MSPT, TMT, CD, and HAD scores improved significantly at 3 months and category naming and MMSE improved at 6 months compared to baseline. The P3 latency also improved significantly at 3 months. The baseline P3 changes correlated with MMSE, Luria's three-step test, and MSPT. Hemoglobin and mean corpuscular volume also correlated with some of the cognitive tests.. VBDNS results in frontal-subcortical neurobehavioral and cognitive abnormalities which may be due to cortical and subcortical dysfunction. The reversibility of these changes is suggestive of metabolic alteration in neuronal or myelin function.

Topics: Adolescent; Adult; Aged; Child; Cognition; Cognition Disorders; Event-Related Potentials, P300; Female; Follow-Up Studies; Homocysteine; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neuropsychological Tests; Psychometrics; Surveys and Questionnaires; Vitamin B 12; Vitamin B 12 Deficiency; Young Adult

Elevated homocysteine (Hcy) levels have been associated with an increased risk of cognitive impairment and Alzheimer's disease (AD). Tissue factor pathway inhibitor (TFPI) has recently emerged as a candidate marker of endothelial damage in AD. We investigated the relationship between plasma levels of folate, vitamin B12, Hcy, and TFPI, as well as cognitive function in 321 [100 each with mild cognitive impairment (MCI) and AD, 121 normal subjects] Korean elderly (mean age 74.8 ± 7.2 years). Plasma folate and vitamin B12 concentrations were analyzed by radioimmunoassay, Hcy by the HPLC-fluorescence method, and TFPI by enzyme-linked immunosorbent assay. Plasma Hcy levels were higher in patients with AD and MCI than those in normal subjects (p < 0.001). The AD group had higher proportions of hyperhomocysteinemic (>15 μM) and folate deficient (<3.0 ng/mL) (p = 0.026) subjects. A multiple regression analysis after adjusting for covariates revealed positive relationships between plasma folate and the MMSE-KC and Boston Naming Test, and between plasma vitamin B12 and the Word List Memory Test in the AD group, but negative associations between plasma Hcy and the Word List Memory and Constructional Recall Tests and between plasma TFPI and the Boston Naming, Word List Recall, and Constructional Recall Tests. In contrast, only plasma folate level was positively associated with the MMSE-KC and Boston Naming Test in the MCI group. No associations were observed in the normal group. These results suggest that plasma folate, vitamin B12, Hcy, and TFPI are associated with cognitive function in cognitively impaired (AD and MCI) elderly and that the association was stronger in patients with AD.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Cognition Disorders; Cross-Sectional Studies; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Lipoproteins; Male; Mental Status Schedule; Neuropsychological Tests; Vitamin B 12; Vitamin B 12 Deficiency

To investigate the cross-sectional relation between metabolic markers of vitamin B(12) status and cognitive performance, and possible effect modification by the presence of depression and apolipoprotein E (ApoE) ε4.. This is a population-based study of 1935 participants, aged 71 to 74 years, from Norway. Participants were administered a cognitive test battery, and vitamin B(12) status was assessed by measurements of plasma vitamin B(12), holotranscobalamin (holoTC), methylmalonic acid (MMA), and total homocysteine.. The geometric mean (95% confidence interval) for vitamin B(12) was 348 pM (341-354), whereas 5.9% of participants had vitamin B(12) levels lower than 200 pM. In linear regression analyses, holoTC (p = .039) and the holoTC/vitamin B(12) ratio (p = .013) were positively related, whereas MMA (p = .010) was inversely related, to global cognition, after adjustment for sex, education, ApoE status, plasma creatinine, and history of diabetes, cardiovascular disease, hypertension, and depression. Among those positive for ApoE ε4, but not among those without the ε4 allele, plasma vitamin B(12) was positively associated with global cognition (p = .015), whereas MMA was inversely related to global cognition (p = .036) and executive function (p = .014). In participants with depression, MMA was inversely associated with global cognition (p < .001) and episodic memory (p = .001).. Among the well-nourished elderly, low vitamin B(12) status is associated with cognitive deficit, particularly in those with the ApoE ε4 allele or with depression.

Topics: Aged; Apolipoprotein E4; Cognition; Cognition Disorders; Cross-Sectional Studies; Depression; Female; Homocysteine; Humans; Linear Models; Male; Methylmalonic Acid; Neuropsychological Tests; Norway; Regression Analysis; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

Elevated homocysteine has emerged as a risk factor for cognitive impairment even in healthy elderly persons. Reduced brain volume and white matter hyperintensities also occur in healthy elderly as well, but the interrelationships between these have not been well studied. We report these interrelationships in non demented, relatively healthy, community-dwelling older adults from a single East Asian population.. Two hundred twenty-eight right-handed participants age 55 years and above were evaluated. Persons with medical conditions or neurological diseases other than well-controlled diabetes mellitus and hypertension were excluded. Participants underwent quantitative magnetic resonance imaging of the brain using a standardized protocol and neuropsychological evaluation. Plasma homocysteine, folate, vitamin B(12), and markers for cardiovascular risk: blood pressure, body mass index, fasting blood glucose, and lipid profile were measured.. Elevated homocysteine was associated with reduced global cerebral volume, larger ventricles, reduced cerebral white matter volume, and lower cognitive performance in several domains. Elevated homocysteine was associated with reduced white matter volume (β = -20.80, t = -2.9, df = 223, p = 0.004) and lower speed of processing (β = -0.38, t = -2.1, df = 223, p = 0.03), even after controlling for age, gender, and education. However, the association between homocysteine and lower speed of processing disappeared after controlling for white matter volume. Elevated homocysteine was not associated with white matter hyperintensity volume or with hippocampal volume. Although homocysteine and folate levels were correlated, their effects on white matter volume were dissociated.. In non demented, relatively healthy adults, elevated homocysteine is associated with lower cognitive scores and reduced cerebral white matter volume. These effects can be dissociated from those related to white matter hyperintensities or reduced folate level.

Topics: Age Factors; Aged; Asian People; Brain; Cardiovascular Diseases; Cognition Disorders; Female; Folic Acid; Homocysteine; Humans; Linear Models; Magnetic Resonance Imaging; Male; Middle Aged; Nerve Fibers, Myelinated; Neuropsychological Tests; Organ Size; Singapore; Vitamin B 12

The importance of the B vitamins folate and vitamin B12 for healthy neurological development and function is unquestioned. Folate and vitamin B12 are required for biological methylation and DNA synthesis. Vitamin B12 also participates in the mitochondrial catabolism of odd-chain fatty acids and some amino acids. Inborn errors of their metabolism and severe nutritional deficiencies cause serious neurological and hematological pathology. Poor folate and vitamin B12 status short of clinical deficiency is associated with increased risk of cognitive impairment, depression, Alzheimer's disease and stroke among older adults and increased risk of neural tube defects among children born to mothers with low folate status. Folate supplementation and food fortification are known to reduce incident neural tube defects, and B vitamin supplementation may have cognitive benefit in older adults. Less is known about folate and vitamin B12 requirements for optimal brain development and long-term cognitive health in newborns, children and adolescents. While increasing suboptimal nutritional status has observed benefits, the long-term effects of high folate intake are uncertain. Several observations of unfavorable health indicators in children and adults exposed to high folic acid intake make it imperative to achieve a more precise definition of folate and B12 requirements for brain development and function.

Topics: Aging; Central Nervous System; Cognition; Cognition Disorders; Dietary Supplements; Epigenesis, Genetic; Folic Acid; Folic Acid Deficiency; Food, Fortified; Humans; Neural Tube Defects; Nutritional Status; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Cognition Disorders; Depression; Female; Folic Acid; Humans; Male; Mental Recall; Stress, Psychological; Vitamin B 12; Vitamin B Complex

The body mass index (BMI) is commonly used to assess nutritional status and the Mini Mental State Examination (MMSE) is a validated tool for assessing cognitive status in elderly people. Nutritional and cognitive aspects are closely related in dementia.. To establish whether BMI predicts cognitive decline in demented patients and whether an "alarm" BMI cut-off exists for declining MMSE scores.. 82 elderly demented patients underwent clinical, bio-chemical and functional assessment.. Transversal study.. The mean BMI was 26.08±4.48 kg/m² and the mean MMSE 18.68±5.38. Patients with BMI<25 kg/m² had significantly lower MMSE scores (16.5±5.53 vs 20.38±4.64; p 0.001), fat-free mass (FFM; 27.76±8.99 vs 37.38±10.58 kg; p<0.001), fat-free mass index (FFMI; 11.52±3.03 vs 14.67±2.89 kg/m²; p<0.001), and fat mass (FM; 24.90±6.89 vs 36.86±6.77 kg; p<0.001), as well as lower Mini Nutritional Assessment (MNA) scores (23.80±2.50 vs 25.00±2.29; p=0.03) and higher vitamin B12 levels (460.95±289.80 vs 332.43±82.07 pg/ml; p=0.01). In the sample as a whole, MMSE scores significantly correlated with scores for MNA (r=0.27, p=0.01), FFM (r=0.27, p=0.01), BMI (r=0.19, p=0.05), ADL (r=0.28, p=0.01) and instrumental activities of daily living (IADL; r=0.34, p=0.002). On multiple logistic regression, BMI<25 kg/m² was independently associated with the risk of moderate-severe cognitive impairment (OR=2.96; 95% CI; 1.16-7.55) and female gender was independently associated with severity of dementia (OR=3.14; 95% CI; 1.09-9.03).. BMI seems to indicate global health status in elderly demented people and a BMI of 25 kg/m² can be considered an "alarm" cut-off, lower values coinciding with a worse cognitive status based on MMSE scores.

Topics: Activities of Daily Living; Aged; Aged, 80 and over; Body Mass Index; Cognition Disorders; Dementia; Diet; Disease Progression; Female; Geriatric Assessment; Humans; Italy; Logistic Models; Male; Nutrition Assessment; Nutritional Status; Psychiatric Status Rating Scales; Severity of Illness Index; Sex Characteristics; Vitamin B 12

The C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene differs in frequency in various ethnic groups that have differing prevalence of age-related cognitive impairments. We used a series of neuro-psychological tests to examine the association of the MTHFR C677T polymorphism with cognition and depression and also to assess whether genotype modifies the association of folate and homocysteine with these outcomes. This study analyzed pooled cross-sectional data from 2 ethnically diverse cohorts of community-living adults: the Boston Puerto Rican Health Study (n = 939) and the Nutrition, Aging, and Memory in Elders study (n = 1017). Individuals in both cohorts underwent anthropometric and laboratory measurements and dietary and health assessments using validated questionnaires between the years 2003 and 2007. Cognitive outcomes included measures of global cognition [Mini-Mental Status Exam (MMSE)], depression (Center for Epidemiological Studies Depression Scale), and 3 factor scores for the domains of attention, executive function, and memory that were derived from a detailed set of neuropsychological tests. Low plasma vitamin B-12 concentrations were associated with poorer MMSE scores and higher depression scores, and low vitamin B-6 concentrations were associated with lower MMSE and worse attention and executive function in the multivariate analysis. In contrast, MTHFR genotype, folate, and homocysteine were not associated with cognition or depression in either ethnicity-pooled or stratified analysis. The current study did not find evidence of an association between the MTHFR C677T TT genotype and impaired cognition or depression in a population with adequate folate status and a high prevalence of cognitive impairment and depression.

Topics: Adult; Aged; Cognition Disorders; Cohort Studies; Cross-Sectional Studies; Depression; Female; Folic Acid; Gene Expression Regulation, Enzymologic; Homocysteine; Humans; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Polymorphism, Genetic; Vitamin B 12; Vitamin B 6

To investigate the cognitive significance of low to low-normal plasma vitamin B-12 concentrations and to shed light on the role that folate status plays in the association between vitamin B-12 status and cognitive decline.. Associations between plasma vitamin B-12 and folate and 8-year cognitive decline were evaluated, and the effects of interactions between vitamin B-12 status and folate status and supplemental folate use on cognitive decline were assessed.. The Framingham Heart Study - a prospective epidemiological study.. Five hundred forty-nine community-dwelling individuals aged 74.8 ± 4.6.. Mini-Mental State Examination (MMSE), plasma folate, vitamin B-12, methylmalonic acid, homocysteine, demographic factors, and body mass index.. MMSE scores declined by 0.24 points per year over the 8-year follow-up period. Decline was significantly faster in cohort members in the bottom two plasma vitamin B-12 quintile categories, and no apparent cognitive advantage was associated with plasma vitamin B-12 from 187 to 256.8 pmol/L over less than 186 pmol/L. In cohort members with plasma vitamin B-12 less than 258 pmol/L, having a plasma folate concentration greater than 20.2 nmol/L was associated with an approximate 1-point per year decline, as was use of supplemental folate.. Plasma vitamin B-12 levels from 187 to 256.8 pmol/L predict cognitive decline. Furthermore, having plasma vitamin B-12 levels in this range or below in conjunction with high plasma folate or supplemental folate use predicts especially rapid cognitive decline.

Topics: Aged; Cognition Disorders; Female; Folic Acid; Humans; Male; Neuropsychological Tests; Prospective Studies; Vitamin B 12

Elevated plasma homocysteine (Hcy) concentration is an independent risk factor for cardiovascular disease, and its involvement in endothelial cell dysfunction is well established. However, the role of Hcy and folate in the pathogenesis of Parkinson's disease (PD) remains controversial.. The study was aimed at evaluating the relationships between Hcy, vitamin B12, and folic acid levels in the blood and cognitive status in PD patients with the genetic polymorphisms of MTHFR (rs1801133: C>T-677C>T, rs1801131: A>C-1298A>C), COMT (rs4680: A>G-Val158Met, rs6269: A>G, rs4633: C>T, rs4818: C>G), or SLC19A1 (rs1051266: G>A-80G>A).. A total of 502 participants (248 with PD and 254 age-matched and sex-matched controls) were included in the study. The Unified Parkinson's Disease Rating Scale score, Hoehn-Yahr staging, and the Schwab-England scale were used to assess motor abilities and activity during daily life. Complex psychological examination with a battery of tests was used to classify patients into groups with (PDD) and without (nPDD) dementia. Blood samples were examined for Hcy, vitamin B12, and folic acid levels, as well as polymorphisms in genes related to Hcy metabolism, such as COMT, MTHFR, and SLC19A1(RFC-1).. The frequency of homozygous COMT rs4680G and rs4633C allele carriers was significantly decreased in PD patients in comparison with the controls (P=0.015; odds ratio=0.60; 95% confidence interval 0.41-0.90 and P=0.020; odds ratio=0.619; 95% confidence interval 0.42-0.92, respectively). No significant differences in the distribution of MTHFR 677C>T, 1298A>C, and SLC19A1 80G>A alleles and genotypes between PD patients and the controls were found. Hcy levels were significantly increased in PD patients (18±7.8 μmol/l) as compared with the controls (14.0±9.6 μmol/l, P=10(-8)) and were significantly associated with the MTHFR 677C>T polymorphism both in PD patients and controls, in which T allele carriers were characterized by markedly elevated Hcy plasma concentrations. No association was observed between Hcy plasma level and COMT and SLC19A polymorphisms. The results of multivariate logistic regression analysis revealed age (P=0.0003) and Hcy plasma levels (P=0.07) as independent risk factors predisposing individuals to PD dementia. The studied polymorphisms were not associated with cognitive status in PD patients.. The genetic factors studied were not associated with cognitive status in PD patients. Only age and Hcy plasma levels were found to be independent risk factors predisposing individuals to PD dementia. However, COMT: rs4680: A>G and rs4633: C>T polymorphisms were found to significantly affect PD risk, and the MTHFR 677C>T polymorphism helped determine plasma Hcy concentrations.

Topics: Catechol O-Methyltransferase; Cognition Disorders; Female; Folic Acid; Genetic Association Studies; Genetic Predisposition to Disease; Homocysteine; Humans; Male; Methylenetetrahydrofolate Reductase (NADPH2); Parkinson Disease; Polymorphism, Genetic; Reduced Folate Carrier Protein; Vitamin B 12

Thirty-three inpatients (22 females, 11 males, aged 79.4 ± 9.5 years) were investigated in this prospective cohort study to study the prevalence of polyneuropathy (PNP) and dementia in geriatric inpatients. Clinical and electrodiagnostic investigations, routine laboratory, including thyroid parameters, folic acid, vitamin B(12), homocysteine, neopterin, fibrinogen and glycosylated hemoglobin were measured in serum, the mini-mental state examination and computed tomographic scanning were performed in each patient. PNP was found clinically and electrodiagnostically in 96% of patients. Age was the most precipitating factor for PNP, and was significantly correlated to electrodiagnostic changes in the nerves investigated in both, upper and lower extremities, while clinical symptoms were confined only to the feet. Correlation was seen between homocysteine and the amplitude of the sural nerve (surAmpl) (rs = -0.406, p = 0.029) as well as the sural nerve conduction velocity (surNCV) (rs = -0.389, p = 0.037), and between neopterin and the grade of denervation (rs = 0.445, p = 0.014) in our patients. Neopterin and fibrinogen did not correlate significantly, but there was a trend to higher fibrinogen concentrations in patients with higher neopterin levels (rs = 0.344, p = 0.062). A trend of a correlation was seen between higher homocysteine concentrations and the number of changes in electrodiagnostic measurements (rs = 0.354, p = 0.055). Twenty-one of the 33 patients (64%) were demented, 9 (27%) presented clinically as mild cognitive impairment, 3 (9%) were not demented. Vascular risk factors were found in 83%: hypertension in 58%, hypercholesterinemia in 39%, cardiac disease in 36%, diabetes mellitus (DM) in 21%, peripheral arterial disease (PAD) in 9%. A significant correlation was found between homocysteine and folic acid concentrations (rs = -0.401, p = 0.028). Falls were reported in 48% of cases, indicating PNP as a risk factor in this group of patients. In conclusion, PNP was found very common with a high coincidence with dementia and a female preponderance, suggesting an influence on daily life (falls) in our subjects studied. PNP correlated significantly with markers for vascular disease as well as immune activation (homocysteine and neopterin) similar to earlier findings in patients with neurodegenerative disorders, suggesting common therapeutic options in patients with PNP and dementia.

Topics: Aged; Aged, 80 and over; Aging; Cognition Disorders; Cohort Studies; Dementia; Female; Folic Acid; Geriatrics; Homocysteine; Humans; Inflammation; Male; Mental Status Schedule; Neopterin; Neural Conduction; Polyneuropathies; Sural Nerve; Vascular Diseases; Vitamin B 12

Topics: Autistic Disorder; Biological Transport; Brain; Cognition Disorders; District of Columbia; Folic Acid; Genomic Instability; Humans; Methotrexate; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Receptors, N-Methyl-D-Aspartate; Vitamin B 12

Elevated plasma homocysteine concentrations have been associated with both cognitive impairment and dementia. However, it is unclear whether some cognitive domains are more affected than others, or if this relationship is independent of B12 and folate levels, which can also affect cognition. We examined the relationship between plasma homocysteine and cognitive decline in an older hypertensive population.. 182 older people (mean age 80 years) with hypertension and without dementia, were studied at one center participating in the Study on COgnition and Prognosis in the Elderly (SCOPE). Annual cognitive assessments were performed using a computerized assessment battery and executive function tests, over a 3-5 year period (mean 44 months). Individual rates of decline on five cognitive domains were calculated for each patient. End of study plasma homocysteine, folate and B12 concentrations were measured. The relationship between homocysteine levels and cognitive decline was studied using multivariate regression models, and by comparing high versus low homocysteine quartile groups.. Higher homocysteine showed an independent association with greater cognitive decline in three domains: speed of cognition (β = -27.33, p = 0.001), episodic memory (β = -1.25, p = 0.02) and executive function (β = -0.05, p = 0.04). The association with executive function was no longer significant after inclusion of folate in the regression model (β = -0.032, p = 0.22). Change in working memory and attention were not associated with plasma homocysteine, folate or B12. High homocysteine was associated with greater decline with a Cohen's d effect size of approximately 0.7 compared to low homocysteine.. In a population of older hypertensive patients, higher plasma homocysteine was associated with cognitive decline.

Topics: Aged; Aged, 80 and over; Aging; Biomarkers; Cognition; Cognition Disorders; Executive Function; Female; Folic Acid; Follow-Up Studies; Homocysteine; Humans; Hypertension; Male; Neuropsychological Tests; Risk Factors; Vitamin B 12

Various definitions, criteria, tests, and cutoffs have been used to define vitamin B-12 status; however, a need exists for the systematic study of vitamin B-12 status in the United States because of concerns about high folic acid intakes and the potential for associated adverse effects.. The objective was to determine the effect of different cutoff choices on outcomes and of the different degrees of serum vitamin B-12 status, definable by the concurrent use of a functional and circulating marker as the first steps to developing a data-based consensus on the biochemical diagnosis of vitamin B-12 deficiency.. Data from NHANES, a nationally representative cross-sectional survey, were examined for adults aged >19 y (mean ± SD age: 45 ± 1 y) from 1999 to 2004 (n = 12,612).. Commonly used cutoffs had a greater effect on prevalence estimates of low vitamin B-12 status with the use of vitamin B-12 than with the use of methylmalonic acid (MMA; 3-26% and 2-6%, respectively). A cutoff of >148 pmol/L for vitamin B-12 and of ≤210 nmol/L for MMA resulted in significant misclassifications. Approximately 1% of adults had a clear vitamin B-12 deficiency (low vitamin B-12 and elevated MMA); 92% of adults had adequate vitamin B-12 status. A high percentage of younger women characterized the group with low vitamin B-12 and normal MMA (2% of adults) and may have falsely reflected low vitamin B-12. Adults with elevated MMA (5%) only were demographically similar (ie, by age and race) to the deficient group and may have included some individuals with early vitamin B-12 deficiency.. These analyses indicate the challenges of assessing vitamin B-12 status when uncertainties exist about the appropriate cutoffs. Future studies should determine definable endpoints to achieve this goal.

Topics: Adult; Biomarkers; Cognition Disorders; Cross-Sectional Studies; Female; Humans; Male; Methylmalonic Acid; Middle Aged; Nutritional Status; United States; Vitamin B 12

Low vitamin B₁₂ concentrations have been associated with higher risks of cognitive impairment, but whether these associations are causal is uncertain. The associations of cognitive impairment with combinations of vitamin B₁₂, holotranscobalamin, methylmalonic acid, and total homocysteine, and with the vitamin B₁₂ transport proteins transcobalamin and haptocorrin, have not been previously studied.. We performed a population-based cross-sectional study of 839 people 75 years old or older. We examined the association of cognitive function as measured by mini-mental state examination scores, with markers of vitamin B₁₂ status. Spearman correlations as well as multivariate-adjusted odds ratios and 95% CIs for cognitive impairment were calculated for extreme thirds of serum concentrations of vitamin B₁₂, holotranscobalamin, methylmalonic acid, total homocysteine, combination of these markers in a wellness score, heaptocorrin, and transcobalamin for all data and with B₁₂ analogs in a nested case-control study.. Cognitive impairment was significantly associated with low vitamin B₁₂ [odds ratio 2.3 (95% CI 1.2-4.5)]; low holotranscobalamin [4.1 (2.0-8.7)], high methylmalonic acid [3.5 (1.8-7.1)], high homocysteine [4.8 (2.3-10.0)] and low wellness score [5.1 (2.61-10.46)]. After correction for relevant covariates, cognitive impairment remained significantly associated with high homocysteine [4.85 (2.24-10.53)] and with a low wellness score [5.60 (2.61-12.01)] but not with transcobalamin, haptocorrin, or analogs on haptocorrin.. Cognitive impairment was associated with the combined effects of the 4 biomarkers of vitamin B₁₂ deficiency when included in a wellness score but was not associated with binding proteins or analogs on haptocorrin.

Topics: Aged; Biomarkers; Case-Control Studies; Cognition Disorders; Cross-Sectional Studies; Homocysteine; Humans; Methylmalonic Acid; Risk Assessment; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

Fahr's syndrome is characterized by symmetrical and bilateral intracerebral calcifications, located in the basal ganglia and mostly associated with a phosphorus calcium metabolism disorder. It must be distinguished from genetic or sporadic Fahr's disease.. We report two cases of this syndrome, the first was revealed by psychotic and cognitive disorders and the other by epilepsy. In both cases, brain imaging and biology resulted in the diagnosis of Fahr's syndrome. The outcome was favorable after treatment in both cases.. These two observations illustrate various clinical signs of Fahr's syndrome.

Topics: Adult; Aged; Basal Ganglia Diseases; Calcinosis; Calcium; Calcium Metabolism Disorders; Cognition Disorders; Female; Humans; Male; Psychotic Disorders; Syndrome; Tomography, X-Ray Computed; Treatment Outcome; Vitamin B 12; Vitamin D

Elevated homocysteine concentrations are associated with an increased risk of cardiovascular disease and a decline in cognitive function. Intakes of choline and betaine, as methyl donors, may affect homocysteine concentrations.. The objective was to examine whether choline and betaine intakes, assessed from food-frequency questionnaires, are associated with total plasma homocysteine concentrations under both fasting and post-methionine-load conditions in both pre- and post-folic acid fortification periods in the United States.. We assessed the association between choline and betaine intakes and fasting and post-methionine-load homocysteine concentrations using the US Department of Agriculture revised food-composition tables and evaluated whether the associations varied by folic acid fortification periods in 1325 male and 1407 female participants in the sixth examination (1995-1998) of the Framingham Offspring Study.. A higher choline-plus-betaine intake was associated with lower concentrations of post-methionine-load homocysteine; the multivariate geometric means were 24.1 micromol/L (95% CI: 23.4, 24.9 micromol/L) in the top quintile of intake and 25.0 micromol/L (95% CI: 24.2, 25.7 micromol/L) in the bottom quintile (P for trend = 0.01). We found an inverse association between choline-plus-betaine intake and fasting homocysteine concentrations; the multivariate geometric mean fasting homocysteine concentrations were 9.6 micromol/L (95% CI: 9.3, 9.9 micromol/L) in the top quintile and 10.1 micromol/L (95% CI: 9.8, 10.4 micromol/L) in the bottom quintile (P for trend < 0.001). When we stratified by plasma folate and vitamin B-12 concentrations, the inverse association was limited to participants with low plasma folate or vitamin B-12 concentrations. In the postfortification period, the inverse association between choline-plus-betaine intake and either fasting or post-methionine-load homocysteine was no longer present.. Choline and betaine intakes were associated with both fasting and post-methionine-load total homocysteine concentrations, especially in participants with low folate and vitamin B-12 status. The inverse association between choline and betaine intakes and homocysteine concentrations was no longer present in the postfortification period.

Topics: Betaine; Cardiovascular Diseases; Choline; Cognition Disorders; Diet; Female; Folic Acid; Homocysteine; Humans; Male; Methionine; Vitamin B 12; Vitamin B 6

Topics: Acetylcysteine; Alzheimer Disease; Cognition Disorders; Free Radical Scavengers; Humans; Tetrahydrofolates; Vitamin B 12

Leukoencephalopathy and autonomic dysfunction have been described in individuals with very low serum B(12) levels (<200 pg/ml), in addition to psychiatric changes, neuropathy, dementia and subacute combined degeneration. Elevated homocysteine and methylmalonic acid levels are considered more sensitive and specific for evaluating truly functional B(12) deficiency. A previously healthy 62-year-old woman developed depression and cognitive deficits with autonomic dysfunction that progressed over the course of 5 years. The patient had progressive, severe leukoencephalopathy on multiple MRI scans over 5 years. Serum B(12) levels ranged from 267 to 447 pg/ml. Homocysteine and methylmalonic acid levels were normal. Testing for antibody to intrinsic factor was positive, consistent with pernicious anaemia. After treatment with intramuscular B(12) injections (1000 μg daily for 1 week, weekly for 6 weeks, then monthly), she made a remarkable clinical recovery but remained amnesic for major events of the last 5 years. Repeat MRI showed partial resolution of white matter changes. Serum B(12), homocysteine and methylmalonic acid levels are unreliable predictors of B(12)-responsive neurologic disorders, and should be thoroughly investigated and presumptively treated in patients with unexplained leukoencephalopathy because even long-standing deficits may be reversible.

Topics: Autoantibodies; Autonomic Nervous System Diseases; Brain; Cognition Disorders; Depressive Disorder; Drug Therapy, Combination; Female; Homocysteine; Humans; Intrinsic Factor; Leukoencephalopathies; Magnetic Resonance Imaging; Mental Status Schedule; Methylmalonic Acid; Middle Aged; Neurologic Examination; Psychometrics; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin D

Relationships between hyperhomocysteinemia (HHE) and neurodegenerative diseases have been widely studied. However, the impact of serum total homocysteine (tHcy) levels on cognitive function has not been confirmed. C677T polymorphisms in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene have impacts on tHcy level; it is suspected to influence cognitive function, but only few investigations have assessed its effects on non-dementia adults and the results have been controversial. Moreover, there is no report about Chinese subjects. In the present study, we determined C677T/MTHFR genotype, serum tHcy concentration and cognition in 182 nondemented subjects aged 55-88 years to probe the associations between MTHFRC677T mutation, increased tHcy levels and decreased cognitive function in a northern city in China. A serum tHcy level > or = 16 micromol/l was deemed HHE. Cognitive function was assessed by the Mini Mental State Examination (MMSE) and Basic Cognitive Aptitude Tests (BCAT). Results showed that: (i) subjects with the T allele had higher serum tHcy levels than those without, especially in lower folate status; (ii) T allele and CT/TT genotype frequencies in subjects with HHE were higher than in non-HHE subjects (P < 0.05); and (iii) serum tHcy level was inversely related to total BCAT score (P < 0.05) but MTHFR677 C to T polymorphism had no association with it. Our results confirmed that the MTHFR 677 C to T mutation, especially in lower serum folate concentration status, results in the increase of serum tHcy levels which is bad for cognitive function and indicates that higher serum folate level is of benefit in keeping lower serum tHcy level and better cognitive function. The results provide some valuable clues for individualized nutrition intervention of HHE and cognition decline in the middle-aged and the elderly.

Topics: Aged; Aged, 80 and over; Aging; Cognition; Cognition Disorders; Female; Folic Acid; Genotype; Homocysteine; Humans; Hyperhomocysteinemia; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Polymorphism, Genetic; Vitamin B 12; Vitamin B 6; Vitamins

Total plasma homocysteine (tHcy) concentration is elevated in elderly patients with mental illness, and patients with vascular disease have higher plasma tHcy concentrations than patients without vascular disease. Increasing evidence indicates that vascular risk factors play a role in the development of cognitive impairment.. We have investigated the relation between plasma tHcy, its determinants and cognition, measured as MMSE, in 448 consecutively enrolled patients with dementia or other psychogeriatric diseases.. Multiple regression analyses showed that plasma tHcy was related to cognitive function in all patients as well as in demented and non-demented patients. The apparent close relationship between plasma tHcy and cognition was mainly dependent on its determinant age, whereas the other determinants of plasma tHcy exhibited a limited influence on the relation between plasma tHcy and cognition. Plasma tHcy has its own, albeit modest, relationship to cognitive function (predictive value about 5%).. Plasma tHcy itself seems to play a minor role in cognitive impairment in patients with dementia or other psychogeriatric diseases. When investigating the relation between plasma tHcy and cognition, it is important to consider the distribution of the main determinants of plasma tHcy and to correct plasma tHcy for these variables.

Topics: Aged; Aged, 80 and over; Cognition; Cognition Disorders; Creatinine; Dementia; Diagnostic and Statistical Manual of Mental Disorders; Female; Folic Acid; Homocysteine; Humans; Male; Mental Disorders; Middle Aged; Neuropsychological Tests; Regression Analysis; Tomography, X-Ray Computed; Vascular Diseases; Vitamin B 12

The question arises whether oxidative stress is connected with systemic immune activation in Alzheimer's disease (AD) and mild cognitive impairment (MCI). During immune response interferon-gamma stimulates the kynurenine (Kyn) pathway, a major route of L-tryptophan (Trp) degradation.. Plasma Kyn, Trp and the Kyn to Trp ratio (Kyn/Trp), carbonyl proteins (CP) as oxidative stress parameter and homocysteine, neopterin, folate and vitamin B12 were measured from patients with AD and MCI (n = 16: 6 females and 4 males with AD, 3 females and 3 males with MCI; 63.3 +/- 13.7 years), and an age matched healthy control group (n = 15: 11 females and 4 males; 62.8 +/- 3.6 years). We correlated the oxidative stress parameter CP with the degradation of Trp creating a new quotient CP/Trp and calculated the sensitivity, specificity, and cut-off values for CP, Trp, CP/Trp, and Kyn/Trp using discriminate analysis.. CP was significantly higher in AD/MCI (930 +/- 265 pmol/mg; p < 0.001) compared to controls (300 +/- 120 pmol/mg), Trp was significantly lower in AD/MCI (48.9 +/- 9.0 micromol/L; p < 0.001) than controls (65.2 +/- 10.7 micromol/L). While Kyn showed no significant difference between AD/MCI (1.72 +/- 0.56 micromol/L) and controls (1.53 +/- 0.29 micromol/L), Kyn/Trp was significantly higher in AD/MCI (35.2 +/- 8.8 micromol/mmol; p < 0.001) than in controls (23.7 +/- 4.2 micromol/mmol). CP/Trp ratio was more than 4 fold higher in the AD/MCI group (19.8 +/- 7.76 [(pmol/mg)/(micromol/L)]; p < 0.001) compared to controls (4.79 +/- 2.26 [(pmol/mg)/(micromol/L)]). Homocysteine, folate, vitamin B12, and neopterin showed no significant difference. Discriminant analysis provided CP alone as the best clinical marker with highest sensitivity and highest specificity for AD/MCI followed by the ratio of CP/Trp. ROC curve analysis provided the best result for CP/Trp.. These preliminary results support the hypothesis that oxidative damage to proteins is directly connected with Trp degradation and Kyn pathway in the systemic immune activation.

Topics: Aged; Alzheimer Disease; Biomarkers; Cognition Disorders; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Neopterin; Oxidative Stress; Protein Carbonylation; Reference Values; Tryptophan; Vitamin B 12

Studies have found elevated plasma homocysteine (Hcy) levels in bipolar disorder (BD). We investigated serum Hcy levels in euthymic BD patients, and its relationship with cognitive and psychosocial functioning.. Sixty-five BD type I euthymic patients and 49 healthy controls were assessed using a neuropsychological test battery. Hcy levels were measured using an HPLC method with fluorescence detection.. The mean Hcy levels were 1.37 mg/L for BD patients and 1.30 mg/L for healthy controls (P=0.342), male patients showing higher Hcy levels as compared to females (P=0.009). Older patients, those with later illness onset, and patients taking more medications showed higher Hcy levels, but no significant correlation was found with psychosocial functioning. Patients with "elevated" Hcy levels performed significantly worse on all neurocognitive tests, and in patients we found significant associations between Hcy levels and number of perseverations on the SCT (r=0.248, P=0.047), and number of moves on the ToH (r=0.265, P=0.033); however, a linear regression model revealed that Hcy was not a significant predictor of neurocognitive test performance.. Our findings suggest that increased homocysteinemia may play a role in the pathophysiology of neurocognitive deficits in BD, with a higher impact among older patients, or who had a delayed onset of illness.

Topics: Adult; Age Factors; Bipolar Disorder; Cognition Disorders; Demography; Diagnostic and Statistical Manual of Mental Disorders; Dysthymic Disorder; Female; Folic Acid; Homocysteine; Humans; Male; Neuropsychological Tests; Severity of Illness Index; Sex Factors; Vitamin B 12

Elevated homocysteine has been associated with a higher prevalence of cerebral white-matter lesions and infarcts, and worse cognitive performance. This raises the question whether factors involved in homocysteine metabolism, such as vitamin B(12), are also related to these outcomes. This study examined the association of several markers of vitamin B(12) status with cerebral white-matter lesions, infarcts and cognition.. The study evaluated the association of plasma concentrations of vitamin B(12), methylmalonic acid, holotranscobalamin and transcobalamin saturation with cerebral white-matter lesions and infarcts at baseline and cognition at baseline and during follow-up among 1019 non-demented elderly participants of the population-based Rotterdam Scan Study. Analyses were adjusted for several potential confounders, including homocysteine and folate concentration.. Poorer vitamin B(12) status was significantly associated with greater severity of white-matter lesions, in particular periventricular white-matter lesions, in a concentration-related manner. Adjustment for common vascular risk factors (including blood pressure, smoking, diabetes and intima media thickness) did not alter the associations. Adjustment for homocysteine and folate modestly weakened the associations. No association was observed for any of the studied markers of vitamin B(12) status with presence of brain infarcts and baseline cognition or cognitive decline during follow-up.. These results indicate that vitamin B(12) status in the normal range is associated with severity of white-matter lesions, especially periventricular lesions. Given the absence of an association with cerebral infarcts, it is hypothesised that this association is explained by effects on myelin integrity in the brain rather than through vascular mechanisms.

Topics: Aged; Biomarkers; Brain; Cerebral Infarction; Cerebrovascular Circulation; Cognition Disorders; Female; Folic Acid; Homocysteine; Humans; Magnetic Resonance Imaging; Male; Myelin Sheath; Neuropsychological Tests; Population Surveillance; Prevalence; Risk Factors; Severity of Illness Index; Vitamin B 12

Previous reports on pernicious anemia treatment suggested that high folic acid intake adversely influences the natural history of vitamin B-12 deficiency, which affects many elderly individuals. However, experimental investigation of this hypothesis is unethical, and the few existing observational data are inconclusive. With the use of data from the 1999-2002 National Health and Nutrition Examination Survey (NHANES), we evaluated the interaction between high serum folate and low vitamin B-12 status [ie, plasma vitamin B-12 < 148 pmol/L or methylmalonic acid (MMA) > 210 nmol/L] with respect to anemia and cognitive impairment. With subjects having both plasma folate < or = 59 nmol/L and normal vitamin B-12 status as the referent category, odds ratios for the prevalence of anemia compared with normal hemoglobin concentration and impaired compared with unimpaired cognitive function were 2.1 (95% CI: 1.1, 3.7) and 1.7 (95% CI: 1.01, 2.9), respectively, for those with low vitamin B-12 status but normal serum folate and 4.9 (95% CI: 2.3, 10.6) and 5.0 (95% CI: 2.7, 9.5), respectively, for those with low vitamin B-12 status and plasma folate >59 nmol/L. Among subjects with low vitamin B-12 status, mean circulating vitamin B-12 was 228 pmol/L for the normal-folate subgroup and 354 pmol/L for the high-folate subgroup. We subsequently showed increases in circulating homocysteine and MMA concentrations with increasing serum folate among NHANES participants with serum vitamin B-12 < 148 pmol/L, whereas the opposite trends occurred among subjects with serum vitamin B-12 > or = 148 pmol/L. These interactions, which were not seen in NHANES III before fortification, imply that, in vitamin B-12 deficiency, high folate status is associated with impaired activity of the 2 vitamin B-12-dependent enzymes, methionine synthase and MMA-coenzyme A mutase.

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Aging; Anemia, Pernicious; Cognition Disorders; Drug Interactions; Female; Folic Acid; Homocysteine; Humans; Male; Methylmalonic Acid; Methylmalonyl-CoA Mutase; Middle Aged; Nutrition Surveys; Nutritional Status; Odds Ratio; Prevalence; Vitamin B 12; Vitamin B 12 Deficiency

In some prospective studies, associations of serum vitamin B(12) and homocysteine concentrations with cognitive decline have been reported but few have examined the role of methylmalonic acid, a more specific marker of vitamin B(12) deficiency than homocysteine.. The aim of the study was to determine whether serum concentrations of vitamin B(12) or selected metabolites are related to cognitive decline.. A total of 516 subjects were selected in a stratified random sampling design from among Chicago Health and Aging Project participants for clinical evaluation. We used linear mixed models to examine the association of blood markers of vitamin B(12) status to change in cognitive scores over 6 years. Cognitive function was assessed every 3 years and measured as the sum of standardized scores on four tests.. Probable vitamin B(12) deficiency was observed in 14.2% of the sample. Elevated serum concentrations of homocysteine were present in 19.2% of subjects, and of methylmalonic acid, in 36.4%. Higher serum methylmalonic acid concentrations were predictive of faster rates of cognitive decline (beta = -0.00016, SE = 0.0001, p = 0.004) and higher serum vitamin B(12) concentrations were associated with slower rates of cognitive decline (beta = +0.00013, SE < 0.0001, p = 0.005) in multivariable adjusted mixed models. Serum concentrations of homocysteine had no relationship to cognitive decline.. Serum methylmalonic acid and vitamin B(12) concentrations may be the more important risk factors for cognitive decline when compared to serum homocysteine concentrations, particularly in older populations exposed to food fortification and possible supplements containing folic acid.

Topics: Aged; Aged, 80 and over; Biomarkers; Cognition Disorders; Cohort Studies; Female; Folic Acid; Folic Acid Deficiency; Humans; Indicators and Reagents; Male; Methylmalonic Acid; Risk Factors; Vitamin B 12; Vitamin B 12 Deficiency

The role of the plasma level of homocysteine (Hcy), as a primary outcome, and the effect of silent cerebrovascular lesions and genetic variants related to Hcy metabolism, as secondary outcomes, in the cognitive decline and dementia in Parkinson's disease (PD) were studied. This case-control study focused on 89 PD patients of minimum 10 years of evolution and older than 60 years, who were neuropsychologically classified either as cognitively normal (n = 37), having mild cognitive impairment (Petersen criteria) (n = 22), or suffering from dementia (DSM-IV) (n = 30), compared with cognitively normal age-matched control subjects (n = 30). Plasma levels of Hcy, vitamins B12 and B6, folic acid, polymorphisms in genes related to Hcy metabolism (MTHFR, MTR, MTRR, and CBS) and silent cerebrovascular events were analyzed. Plasma levels of Hcy were increased in PD patients (P = 0.0001). There were no differences between the groups of patients. The brain vascular burden was similar among PD groups. There was no association between polymorphisms in the studied genes and the Hcy plasma levels or cognitive status in PD patients. We found no evidence for a direct relationship between Hcy plasma levels and cognitive impairment and dementia in PD. No indirect effect through cerebrovascular disease or genetic background was found either.

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Aged; Aged, 80 and over; Brain; Carbon-Nitrogen Ligases; Case-Control Studies; Cognition Disorders; Cystathionine beta-Synthase; Depression; Female; Folic Acid; Homocysteine; Humans; Immunoassay; Logistic Models; Magnetic Resonance Imaging; Male; Mental Status Schedule; Middle Aged; Neuropsychological Tests; Parkinson Disease; Polymorphism, Genetic; Severity of Illness Index; Vitamin B 12; Vitamin B 6

Cobalamin C (cblC) disease, an inborn error of vitamin B(12) metabolism, results in neurometabolic, neurochemical and neuroanatomical changes. Little is known of the long-term effects of the disorder on cognition and behaviour in children. Here, the complete neuropsychological profiles of two 12-year-old girls with cblC disease are presented. The two girls were tested longitudinally with standardized neuropsychological tests including intellectual ability, attention and memory, as well as executive, adaptive and behavioural function. The results indicate the presence of intellectual dysfunction, attention problems, and concerns with behavioural aspects of executive function. Both patients demonstrated a pattern of decreasing intellectual function over time, which may reflect a growing developmental gap in comparison with their same age peers. These impairments are in contrast to the relatively spared verbal expression and comprehension abilities, as well as strengths in sociability. The findings highlight a pattern of neuropsychological strengths and weaknesses that may distinguish cblC disease from other inborn errors of metabolism. Overt sociability such as observed in these two patients may actually mask underlying cognitive deficits because the patients appear to function at a more advanced level than that reflected by quantitative assessment of intellectual and cognitive functioning. This is of clinical and functional importance and suggests that accurate determination of cognitive, adaptive and social abilities necessitates an in-depth and broad evaluation. The presence of significant intellectual and cognitive deficits also underscores the need to document and monitor cognitive development in children with cblC disease and to consider remediative and adaptive learning strategies.

Topics: Adaptation, Psychological; Child; Child Behavior; Child Behavior Disorders; Child, Preschool; Cognition; Cognition Disorders; Female; Humans; Infant; Metabolism, Inborn Errors; Neuropsychological Tests; Social Behavior; Vitamin B 12

The question arises as to whether oxidative stress has a primary role in neurodegeneration or is a secondary end-stage epiphenomenon. The aim of the present study was to determine oxidative stress parameters like malondialdehyde (MDA), carbonyl proteins (CP) and Albumin-disulphide (Alb-SSR) and relate these parameters to the immune parameter neopterin, folic acid and vitamin B12 as vitamins and homocysteine in patients with neuro-degenerative diseases (NDD), namely mild cognitive impairment (MCI) and Alzheimer's disease (AD) compared to an aged matched control group. MDA, CP and Alb-SSR were significantly increased in the NDD group compared to controls, but not vitamin B12, folic acid and neopterin. Significant correlations were found between CP and Alb-SSR, CP and MDA and between MDA and Alb-SSR including patients with NDD and the control group. These results support the hypothesis that oxidative damage to lipids and proteins is an important early event in the pathogenesis of neurodegenerative diseases.

Topics: Aged; Alzheimer Disease; Biomarkers; Case-Control Studies; Cognition Disorders; Disulfides; Female; Folic Acid; Homocysteine; Humans; Male; Malondialdehyde; Middle Aged; Neopterin; Nerve Degeneration; Oxidative Stress; Protein Carbonylation; Serum Albumin; Severity of Illness Index; Vitamin B 12

Recently, poor cognition and dementia have been associated with elevated homocysteine and low B vitamin concentrations. The aim of this study is to examine the association in community-dwelling older Japanese adults.. Ninety-nine subjects (71 women and 28 men; mean age 75 years) were eligible for analysis after exclusion of subjects with high serum creatinine concentrations (1.3mg/dl and over) and those taking vitamin supplements. Fasting blood samples were analyzed for plasma total homocysteine, serum folate, and serum vitamin B-12. Global cognitive function was assessed using the Mini-Mental State Examination (MMSE).. Multiple regression analysis revealed that homocysteine concentrations were predicted by concentrations of vitamin B-12 (p<0.001), folate (p<0.005), and creatinine (p<0.001) and age (p<0.005). Scores on the MMSE were associated with concentrations of homocysteine, vitamin B-12, and folate. The association between folate or vitamin B-12 concentrations and MMSE scores remained significant after adjusting for homocysteine concentrations. Folate concentrations, but neither homocysteine nor vitamin B-12 concentrations, were significantly associated with serum albumin concentrations.. Reduced folate and vitamin B-12 concentrations were independently associated with cognitive decline. The correlation between folate and albumin concentrations may imply that the reduction of folate in the Japanese older population is due to nutritional deficiency.

Topics: Age Factors; Aged; Aged, 80 and over; Albumins; Cholesterol; Cognition Disorders; Creatinine; Female; Folic Acid; Hemoglobins; Homocysteine; Humans; Japan; Male; Middle Aged; Regression Analysis; Vitamin B 12

The changes of plasma amyloid beta (Abeta42) protein, homocysteine and medial temporal lobe atrophy (MTA) were studied by the transition from cognitive health to mild cognitive impairment (MCI) and to Alzheimer's disease (AD) in a prospective cohort of individuals aged 75 years. MTA but not plasma Abeta42 measured at baseline predicted which persons remained cognitively healthy (CH) and who developed AD 2.5 years later. The increase of plasma Abeta42 over time significantly distinguished between persons who remained CH on the one hand and MCI converters and AD converters out of cognitive health on the other (CH-to-MCI and CH-to-AD converters). Although both groups showed similar increase of Abeta42 levels, CH-to-AD converters had a higher increase of homocysteine compared to CH-to-MCI converters or to persons remaining CH. In comparison to all cognitive subgroups, the AD converters from MCI at baseline showed the smallest increase of Abeta42 levels and rather no increase of homocysteine. In logistic regression analysis, the increase of plasma Abeta42 but not change of MTA significantly predicted the conversion from CH to MCI, and changes of MTA and homocysteine but not of plasma Abeta42 predicted the conversion from CH to AD. The increase of plasma Abeta42 correctly allocated CH-to-MCI and CH-to-AD converters with low (63%) specificity (for both) and low (60%) sensitivity (54% for AD group). These results indicate that (1) plasma Abeta42 alone is not suitable as a biomarker for AD, (2) in the course of cognitive deterioration of the AD-type the increase of plasma Abeta42 seems to be an initial event, (3) similar to cerebrospinal fluid, changes of plasma Abeta42 may reflect the transition from cognitive health to AD, and (4) whether persons with MCI develop AD may depend on an accumulation of further toxic metabolites such as homocysteine.

Topics: Aged; Alzheimer Disease; Amyloid beta-Peptides; Apolipoproteins E; Atrophy; Cognition Disorders; Cohort Studies; Disease Progression; Female; Folic Acid; Homocystine; Humans; Logistic Models; Magnetic Resonance Imaging; Male; Neuropsychological Tests; Peptide Fragments; Predictive Value of Tests; Psychometrics; Retrospective Studies; Temporal Lobe; Vitamin B 12

We have previously reported that homocysteine levels are elevated in euthymic bipolar patients with functional deterioration. The current study was designed to extend this finding by examining the relationship between neuropsychological functioning and homocysteine levels in euthymic bipolar patients.. Fifty-seven euthymic bipolar outpatients were assessed for serum levels of homocysteine, folic acid, and vitamin B-12 and administered a battery of neuropsychological tests.. We found that male bipolar subjects showed higher average homocysteine levels than a comparison group of normal subjects, that poorer functioning on a task of executive function (Wisconsin Card Sort) was related to higher homocysteine levels, and that folic acid or vitamin B-12 levels did not significantly affect neuropsychological functioning.. These results, while suggesting some relationship between higher homocysteine levels, bipolar illness, and impairment in cognitive function do not establish any causative effects.. The findings of this study confirm that in euthymic bipolar patients, higher homocysteine levels are associated with poorer performance in some neuropsychological tests. Treatment trials will be required before it will be known if the putative decrements in the executive function of bipolar patients can be reversed, or at least retarded, if homocysteine levels are reduced (as, for example, by dietary addition of B vitamin supplements).

Topics: Adolescent; Adult; Bipolar Disorder; Cognition; Cognition Disorders; Dysthymic Disorder; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Neuropsychological Tests; Severity of Illness Index; Vitamin B 12

Concerns about risks for older people with vitamin B12 deficiency have delayed the introduction of mandatory folic acid fortification in the UK. We examined the risks of anaemia and cognitive impairment in older people with low B12 and high folate status in the setting of voluntary fortification in the UK. Data were obtained from two cross-sectional studies (n 2403) conducted in Oxford city and Banbury in 1995 and 2003, respectively. Associations (OR and 95 % CI) of cognitive impairment and of anaemia with low B12 status (holotranscobalamin < 45 pmol/l) with or without high folate status (defined either as serum folate >30 nmol/l or >60 nmol/l) were estimated after adjustment for age, sex, smoking and study. Mean serum folate levels increased from 15.8 (sd 14.7) nmol/l in 1995 to 31.1 (sd 26.2) nmol/l in 2003. Serum folate levels were greater than 30 nmol/l in 9 % and greater than 60 nmol/l in 5 %. The association of cognitive impairment with low B12 status was unaffected by high v. low folate status (>30 nmol/l) (OR 1.50 (95 % CI 0.91, 2.46) v. 1.45 (95 % CI 1.19, 1.76)), respectively. The associations of cognitive impairment with low B12 status were also similar using the higher cut-off point of 60 nmol/l for folate status ((OR 2.46; 95 % CI 0.90, 6.71) v. (1.56; 95 % CI 1.30, 1.88)). There was no evidence of modification by high folate status of the associations of low B12 with anaemia or cognitive impairment in the setting of voluntary fortification, but periodic surveys are needed to monitor fortification.

Topics: Aged; Anemia, Pernicious; Cognition Disorders; Cross-Sectional Studies; Female; Folic Acid; Food, Fortified; Humans; Longitudinal Studies; Male; Nutritional Status; Odds Ratio; Risk; United Kingdom; Vitamin B 12; Vitamin B 12 Deficiency; Vitamins

Topics: Age Factors; Cognition Disorders; Folic Acid; Food, Fortified; Humans; Neural Tube Defects; Nutrition Surveys; Risk Assessment; Vitamin B 12

Topics: Cognition Disorders; Dose-Response Relationship, Drug; Folic Acid; Food, Fortified; Homocysteine; Humans; Immune System; Neoplasms; Nutrition Policy; Vitamin B 12; Vitamin B Complex

Historic reports on the treatment of pernicious anemia with folic acid suggest that high-level folic acid fortification delays the diagnosis of or exacerbates the effects of vitamin B-12 deficiency, which affects many seniors. This idea is controversial, however, because observational data are few and inconclusive. Furthermore, experimental investigation is unethical.. We examined the relations between serum folate and vitamin B-12 status relative to anemia, macrocytosis, and cognitive impairment (ie, Digit Symbol-Coding score < 34) in senior participants in the 1999-2002 US National Health and Nutrition Examination Survey.. The subjects had normal serum creatinine concentrations and reported no history of stroke, alcoholism, recent anemia therapy, or diseases of the liver, thyroid, or coronary arteries (n = 1459). We defined low vitamin B-12 status as a serum vitamin B-12 concentration < 148 pmol/L or a serum methylmalonic acid concentration > 210 nmol/L-the maximum of the reference range for serum vitamin B-12-replete participants with normal creatinine.. After control for demographic characteristics, cancer, smoking, alcohol intake, serum ferritin, and serum creatinine, low versus normal vitamin B-12 status was associated with anemia [odds ratio (OR): 2.7; 95% CI: 1.7, 4.2], macrocytosis (OR: 1.8; 95% CI: 1.01, 3.3), and cognitive impairment (OR: 2.5; 95% CI: 1.6, 3.8). In the group with a low vitamin B-12 status, serum folate > 59 nmol/L (80th percentile), as opposed to < or = 59 nmol/L, was associated with anemia (OR: 3.1; 95% CI: 1.5, 6.6) and cognitive impairment (OR: 2.6; 95% CI: 1.1, 6.1). In the normal vitamin B-12 group, ORs relating high versus normal serum folate to these outcomes were < 1.0 (P(interaction) < 0.05), but significantly < 1.0 only for cognitive impairment (0.4; 95% CI: 0.2, 0.9).. In seniors with low vitamin B-12 status, high serum folate was associated with anemia and cognitive impairment. When vitamin B-12 status was normal, however, high serum folate was associated with protection against cognitive impairment.

Topics: Aged; Aging; Anemia; Anemia, Macrocytic; Cognition Disorders; Confidence Intervals; Creatinine; Female; Folic Acid; Food, Fortified; Humans; Male; Nutrition Surveys; Nutritional Status; Odds Ratio; Vitamin B 12; Vitamin B 12 Deficiency

High concentrations of homocysteine have been linked to a greater risk of Alzheimer disease, dementia, and cognitive decline.. We evaluated the association between homocysteine and 4.5-y combined incidences of dementia and cognitive impairment without dementia (CIND) in a cohort of 1779 Mexican Americans aged 60-101 y.. Homocysteine, red blood cell (RBC) folate, and plasma vitamin B-12 were measured at baseline. New cases of dementia or CIND were ascertained by neuropsychological and clinical examinations and expert adjudication. We used proportional hazards models to estimate the risk of homocysteine-associated dementia or CIND and the influence of RBC folate and plasma vitamin B-12 on that association.. High homocysteine concentrations were associated with a greater risk of dementia or CIND: hazard ratio (HR): 2.39; 95% CI: 1.11, 5.16. Plasma vitamin B-12 modified the association between homocysteine and the outcome. The rates of dementia or CIND associated with homocysteine for those in the lowest and highest tertiles of vitamin B-12, respectively, were significantly higher (HR: 1.61, P = 0.04) and lower (HR: 0.94, P = 0.015) than the risk for those in the middle tertile.. Homocysteine is an independent risk factor for both dementia and CIND. Higher plasma vitamin B-12 may reduce the risk of homocysteine-associated dementia or CIND.

Topics: Aged; Aged, 80 and over; Aging; California; Cognition Disorders; Dementia; Disease Susceptibility; Female; Folic Acid; Health Surveys; Hispanic or Latino; Homocysteine; Humans; Incidence; Male; Middle Aged; Risk Factors; Stroke; Vitamin B 12

Topics: Aged; Cognition Disorders; Folic Acid; Food, Fortified; Humans; Middle Aged; Vitamin B 12

Elderly individuals with mild cognitive impairment (MCI) are at high risk for developing dementia, including Alzheimer's disease. Previous studies have proposed that elevated plasma homocysteine might be a risk factor for dementia. However, the impact of plasma homocysteine on MCI remains controversial. We investigated the relation between hyperhomocysteinemia and the risk of MCI in an elderly Korean population. A total of 1215 elderly subjects (aged 60-85 y) were selected from the Ansan Geriatric study to participate in this study. MCI was diagnosed on the basis of the Mayo Clinic criteria. Mean plasma homocysteine concentrations were higher in elderly subjects with MCI than in normal elderly subjects (17.6 +/- 7.4 vs. 15.7 +/- 4.8 micromol/L; P < 0.001). Subjects with hyperhomocysteinemia (>15 micromol/L) also had a higher prevalence of MCI. The unadjusted OR for MCI was greater in subjects with hyperhomocysteinemia than in normal subjects and it increased according to the degree of hyperhomocysteinemia (OR = 1.39; 95% CI = 1.09-1.79 vs. OR = 2.61; 95% CI = 1.22-5.61). These trends did not differ after adjustment for age, sex, and other putative risk factors for cognitive dysfunction (OR = 1.40; 95% CI = 1.07-1.83 vs. OR = 2.40; 95% CI = 1.08-5.31). In conclusion, hyperhomocysteinemia may be an independent risk factor for MCI in elderly Koreans. A causal relationship between plasma homocysteine levels and cognitive impairment should be evaluated in a follow-up study of elderly Korean subjects.

Topics: Aged; Cognition Disorders; Female; Folic Acid; Homocystine; Humans; Korea; Male; Risk Factors; Vitamin B 12

Topics: Aged; Aged, 80 and over; Aging; Cognition Disorders; Dementia; Folic Acid Deficiency; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Homocysteine; Humans; Risk Factors; Vitamin B 12; Vitamin B 12 Deficiency

Elevated total homocysteine (tHcy) concentrations have been associated with cognitive impairment, but it is unclear whether low vitamin B-12 or folate status is responsible for cognitive decline.. We examined the associations of cognitive decline with vitamin B-12 and folate status in a longitudinal cohort study performed from 1993 to 2003 in Oxford, United Kingdom.. Cognitive function was assessed with the Mini-Mental State Examination on >/=3 occasions during 10 y and related to serum concentrations of vitamin B-12, holotranscobalamin (holoTC), tHcy, methylmalonic acid (MMA), and folate with the use of linear mixed models in 1648 participants who provided blood in 1995.. Cognitive function declined abruptly at younger ages in some participants but remained intact in others until very old age. In multivariate regression analyses after adjustment for established risk factors, concentrations of holoTC (a marker of reduced vitamin B-12 status), tHcy, and MMA predicted cognitive decline, but folate did not. A doubling in holoTC concentrations (from 50 to 100 pmol/L) was associated with a 30% slower rate of cognitive decline (-0.137 to -0.083), whereas a doubling in tHcy (from 10 to 20 micromol/L) or MMA (from 0.25 to 0.50 micromol/L) was associated with >50% more rapid cognitive decline (-0.090 to -0.169) and (-0.104 to -0.169), respectively. After adjustment for all vitamin markers simultaneously, the associations of cognitive decline with holoTC and MMA remained significant.. Low vitamin B-12 status was associated with more rapid cognitive decline. Randomized trials are required to determine the relevance of vitamin B-12 supplementation for prevention of dementia.

Topics: Aged; Aged, 80 and over; Cognition Disorders; Cohort Studies; Female; Homocysteine; Humans; Longitudinal Studies; Male; Methylmalonic Acid; Vitamin B 12; Vitamin B 12 Deficiency

Hyperhomocysteinemia is associated with cerebral small vessel disease (SVD). We examined the relationship between homocysteine and 1) volumetric measure of white matter change (WMC), 2) silent brain infarcts, 3) cerebral atrophy on MRI and 4) cognition on a consecutive cohort of patients with stroke associated with SVD.. Fifty-seven patients consecutively admitted to the Acute Stroke Unit in a university hospital due to stroke associated with SVD were recruited and assessed three months after the stroke. Non-fasting homocysteine was obtained. Using MRI, the number of infarcts, volume of WMC and cerebral atrophy were measured. General cognitive functions were assessed using the Mini Mental State Examination and Alzheimer's disease Assessment Scale. Mattis Dementia Rating Scale - Initiation/Perseveration subset was used to assess executive cognitive functions.. Hyperhomocysteinemia (> or = 14.88 micromol/L) significantly accounted for the volume of WMC on MRI in a multivariate stepwise regression model (adjusted R(2)=0.058, p <0.05) after adjustment for age and folate level. Patients in the highest quartile of WMC volume had significantly higher levels of homocysteine than those in lowest quartile (p <0.001). No significant relationship was found between homocysteine and silent brain infarcts, cerebral atrophy and performance on psychometric tests.. Hyperhomocysteinemia is associated with volumetric measure of WMC among patients with SVD. The role of homocysteine in the development of silent brain infarcts and cerebral atrophy as previously reported cannot be ascertained in this study. No direct relationship was found between homocysteine and cognitive functions.

Topics: Aged; Brain; Cerebrovascular Disorders; Cognition Disorders; Cohort Studies; Creatinine; Female; Homocysteine; Humans; Hyperhomocysteinemia; Magnetic Resonance Imaging; Male; Neuropsychological Tests; Psychiatric Status Rating Scales; Psychometrics; Regression Analysis; Risk Factors; Stroke; Vitamin B 12

Topics: Aged; Alzheimer Disease; Cognition; Cognition Disorders; Homocysteine; Humans; Methionine; Models, Biological; Models, Theoretical; Neurodegenerative Diseases; Vitamin B 12; Vitamins

There is a high frequency (40-50%) of elevated plasma total homocysteine (tHcy) concentrations in elderly patients with mental disorders, and patients with a history of vascular disease exhibit significantly higher plasma tHcy concentration than patients without vascular disease.. The main objective of the present study was to further investigate the association between plasma tHcy concentration and vascular disease in psychogeriatric patients. We have therefore investigated 304 psychogeriatric patients and determined plasma tHcy and its most important determinants (folate and cobalamin status and renal function), and the natriuretic peptide N-terminal-pro brain natriuretic peptide (NT-proBNP). The patients were classified into several groups of vascular disease according to the findings of brain imaging and presence of a history/symptoms indicating manifest occlusive arteriosclerotic vascular disease.. Plasma tHcy concentration is associated with the presence of vascular disease in psychogeriatric patients. The presence of vascular disease is also associated with higher age, higher serum NT-proBNP, renal impairment and lower serum folate concentration than in patients without vascular disease. The significant association between plasma tHcy concentration and vascular disease remained after correction for age and for cystatin C differences between the groups of patients without and with vascular disease. In the present population with only 16% of the patients showing elevated plasma tHcy, renal function was a more important determinant for plasma tHcy concentration than folate status.. Plasma tHcy concentration is associated with vascular disease. In the present population of psychogeriatric patients renal function is associated with vascular disease and elevated plasma tHcy concentration. Thus, the association between plasma tHcy concentration and vascular disease might partially be explained by impairment of renal function.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Cognition Disorders; Confusion; Dementia; Dementia, Vascular; Depressive Disorder; Female; Folic Acid; Homocysteine; Humans; Kidney Function Tests; Male; Middle Aged; Natriuretic Peptide, Brain; Neuropsychological Tests; Peptide Fragments; Reference Values; Risk Factors; Vitamin B 12

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

low vitamin B12 concentrations are common in older people, but the clinical relevance of biochemical evidence of vitamin B12 deficiency in the absence of anaemia is uncertain.. to examine associations of cognitive impairment, depression and neuropathy with blood measurements of vitamin B12 and folate status in older people.. cross-sectional study in general practice in Banbury, England.. a total of 1,000 individuals aged 75 years or older living in the community.. low vitamin B12 concentrations were identified in 13% of older people and were associated with memory impairment and depression. After adjustment for age, sex and smoking, individuals with vitamin B12 or holotranscobalamin (holoTC) in the bottom compared with top quartiles had a 2-fold risk (OR = 2.17; 95% CI 1.11-4.27) and a 3-fold risk (OR = 3.02; 95% CI 1.31-6.98) of cognitive impairment, respectively. Low vitamin B12 status was also associated with missing ankle tendon jerks but not with depression. Treatment with vitamin B12 for 3 months corrected the biochemical abnormalities but had no effect on any of the clinical measurements.. low vitamin B12 concentrations are associated with cognitive impairment and missing ankle tendon jerks in older people in the absence of anaemia. Large-scale trials of vitamin B12 supplementation are required to assess the clinical significance of these associations.

Topics: Aged; Aged, 80 and over; Cognition Disorders; Cross-Sectional Studies; Dementia; Depression; England; Female; Geriatric Assessment; Humans; Male; Peripheral Nervous System Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Aged; Cognition; Cognition Disorders; Dementia; Dietary Supplements; Folic Acid; Food, Fortified; Humans; Hyperhomocysteinemia; Vitamin B 12; Vitamin B Complex

Cobalamin/folate deficiency and vascular disease are prevalent in elderly subjects and may lead to mental symptoms, but may even more often influence the severity of other organic and non-organic mental diseases. In the present study, we have evaluated cobalamin-folate status and the presence of vascular disease in 1,982 psychogeriatric patients investigated and diagnosed in a psychogeriatric clinic. The objective of the present study is to obtain information on the role of cobalamin/folate status and vascular disease in different diagnoses of psychogeriatric patients and their association with plasma homocysteine (tHcy).. We have measured serum cobalamin, blood/serum folate, serum creatinine, plasma tHcy and evaluated the presence of vascular disease in 1,982 well-defined psychogeriatric patients.. The present study indicates that cobalamin/folate deficiencies do not play an important role in cognitive dysfunction in psychogeriatric patients, since only about 7% of the study population had metabolic cobalamin/folate deficiencies. Furthermore, cobalamin/folate deficiencies were rare in younger patients (below 70 years of age). We were also able to confirm our previous finding that there was no association between dementia of Alzheimer type (AD) and plasma tHcy level or metabolic cobalamin/folate deficiencies. Furthermore, we observed a low proportion of vascular disease in patients with AD, which does not give support for an association between well-defined AD and the presence of vascular disease. The presence of vascular disease was higher and of similar degree in patients with mild cognitive impairment and depression, which indicates an association between these diagnoses and the presence of vascular disease. The present study also shows that at plasma tHcy levels below 14 micromol/l, the likelihood of cobalamin/folate deficiency is small and further investigation of cobalamin/folate status could be omitted.

Topics: Age Factors; Aged; Aged, 80 and over; Alzheimer Disease; Cognition Disorders; Depressive Disorder; Female; Folic Acid; Hematocrit; Homocysteine; Humans; Male; Mental Disorders; Middle Aged; Nutritional Status; Population; Sweden; Vascular Diseases; Vitamin B 12

Topics: Aged; Cognition; Cognition Disorders; Dietary Supplements; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Vitamin B 12; Vitamin B Complex

Topics: Aged; Cognition; Cognition Disorders; Dietary Supplements; Folic Acid; Humans; Hyperhomocysteinemia; Vitamin B 12; Vitamin B 6; Vitamin B Complex

To cross sectionally investigate the association of serum vitamin B(12) and folate concentrations with cognitive and functional ability in the very old in the general population.. Serum vitamin B(12) and folate concentrations were assessed in 471 consenting subjects participating in the Monzino 80-plus study (mean age: 87.4 years), a door-to-door population-based survey among very old subjects living in Northern Italy. Cognitive and functional evaluations included Mini-Mental State Examination (MMSE), Instrumental Activities of Daily Living (IADL) and Spontaneous Behavior Interview-basic Activities of Daily Living (SBI-bADL).. MMSE, IADL and SBI-bADL scores were all significantly correlated with folate concentrations (respectively: r = 0.36, r = -0.39, r = -0.35; p < 0.0001), while no significant associations were found with vitamin B(12) concentrations. When entered into multiple linear regression analyses with several covariates, folate showed a highly significant, curvilinear association with both cognitive and functional scores (p < 0.0001). Subjects in low and middle folate tertiles had significantly higher odds ratios for dementia (p < 0.0001; adjusted ORs = 5.40 and 6.56, lower 95% CIs 2.53 and 3.11, higher 95% CIs 12.73 and 15.29).. Findings of this population-based study suggest that subclinical folate deficiency may represent a risk factor for the cognitive decline associated with aging that could contribute to AD as well as other dementia development.

Topics: Activities of Daily Living; Aged, 80 and over; Aging; Alzheimer Disease; Cognition Disorders; Cross-Sectional Studies; Female; Folic Acid; Folic Acid Deficiency; Geriatric Assessment; Humans; Linear Models; Male; Nutritional Requirements; Vitamin B 12; Vitamin B Complex

Homocysteine (Hcy) is harmful to neurons and blood vessels, including the cerebral microvasculature. It is possible that such effects contribute to the cascade of events that leads to cognitive decline, dementia, and depression in later life. Hcy is produced during the metabolism of the essential amino-acid methionine, which also involves a methyl group transfer derived from folate and choline metabolism. Its plasma level can be influenced by factors such as age, vitamin deficiency, renal function, and a common mutation in the methylenetetrahydrofolate reductase (MTHFR) gene, where cytosine is replaced by thymidine (C-->T) at nucleotide position 677. Subjects with the TT genotype have higher homocysteine levels and may be particularly prone to experiencing depression as a result of high plasma Hcy and dysfunction of methylation metabolic pathways critical to the synthesis of noradrenaline and serotonin. We designed the present study to investigate whether older women with the TT genotype would have higher depression and lower cognitive scores than women with CT and CC genotypes. A total of 240 community-dwelling women aged 70 years or over volunteered to take part in the study - 29 carried the TT genotype, 113 the CT and 98 the CC genotype. The Beck Depression Inventory (BDI) score for subjects with the TT genotype was statistically similar to the other groups (P = 0.609). Plasma Hcy showed a modest and significant correlation with BDI scores (r = 0.21) that was independent from age, B12 and folate levels. There was no association between beck anxiety inventory (BAI) scores and MTHFR genotype or homocysteine levels. The cognitive assessment of participants included measures of verbal memory, memory for faces, verbal fluency, visuo-spatial abilities and the cognitive section of the Cambridge Examination For Mental Disorders Of The Elderly (CAMCOG)-MTHFR genotype had no clear association with cognitive scores. These results indicate that, in isolation, the MTHFR C677T gene variation does not play an important role in the modulation of mood and cognitive performance in later life.

Topics: Aged; Aged, 80 and over; Aging; Anxiety; Chi-Square Distribution; Cognition Disorders; Cross-Sectional Studies; Depression; DNA Mutational Analysis; Female; Genotype; Homocysteine; Humans; Methylenetetrahydrofolate Reductase (NADPH2); Neuropsychological Tests; Personality Inventory; Pteroylpolyglutamic Acids; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Vitamin B 12

Topics: Adolescent; Adult; Aged; Aging; Child; Cognition; Cognition Disorders; Female; Folic Acid; Humans; Longitudinal Studies; Male; Mental Status Schedule; Middle Aged; Vitamin B 12; Vitamin B 12 Deficiency

Elevated plasma total homocysteine concentration may be a risk factor for cognitive decline and Alzheimer disease, but data from prospective studies are limited. Further, high homocysteine levels are associated with low vitamin status, and it is unknown whether it is homocysteine toxicity or vitamin insufficiency that is responsible for the observed cognitive dysfunction.. We performed cross-sectional and longitudinal analyses of a cohort of 499 high-functioning community-dwelling persons aged 70 to 79 years to determine the effect of homocysteine and related vitamin plasma concentrations on cognitive function and cognitive decline. Nonfasting plasma concentrations of homocysteine, folate, vitamin B(6), and vitamin B(12) were measured at baseline. Summary measures of cognitive function were created from tests of multiple cognitive domains administered at baseline and again after 7 years.. In cross-sectional analyses investigating each variable separately, subjects with elevated homocysteine levels, or low levels of folate or vitamin B(6), demonstrated worse baseline cognitive function. In longitudinal analyses, after adjusting for multiple covariates, including homocysteine, those in the bottom quartile of folate had a 1.6-fold increased risk (95% confidence interval: 1.01 to 2.31; P =0.04) of being in the worst quartile of 7-year cognitive decline. Low folate levels largely accounted for a trend towards greater cognitive decline with elevated homocysteine level.. In high-functioning older adults, low folate levels appear to be a risk factor for cognitive decline. The risk of developing cognitive decline might be reduced through dietary folate intake.

Topics: Aged; Aging; Alzheimer Disease; Cognition Disorders; Cohort Studies; Cross-Sectional Studies; Female; Folic Acid; Folic Acid Deficiency; Homocysteine; Humans; Longitudinal Studies; Male; Risk Factors; Vitamin B 12; Vitamin B 6

Elderly people is a vulnerable population group to specific nutrient deficiencies as vitamin B12 and folic acid, which are closely related to mental functions deterioration, especially of cognitive functions. This study was aimed to measure B12 vitamin and folic acid indicators and to establish relationships to mental function. 53 elderly, older than 60 years, living in a geriatric home were assessed. The dietary intake was evaluated by the direct weighed method, serum B12 vitamin and folic acid by radioimmunoanalysis and mental function by Foltein's mini-mental test. Dietary intake for Vit B12 was adequate and deficient for folic acid while serum levels were within normal range. Vitamin B12 levels were at marginal or deficiency values in 26,4% of the elderly and folic acid deficiency was present in 43.4%. 49% of the elderly had mental function alterations and B12 vitamin levels were significantly lower in this group. A positive association between age and mental function (elderly below 80 years had lower risk of mental impairment) and between serum B12 and mental function were found. Elderly were at risk of deficiency for both vitamins and age and mental function were associated to this risk. Further evaluation including other nutrients should be performed.

Topics: Age Factors; Aged; Aged, 80 and over; Cognition Disorders; Diet; Female; Folic Acid; Folic Acid Deficiency; Homes for the Aged; Humans; Male; Mental Health; Middle Aged; Radioimmunoassay; Risk Factors; Vitamin B 12; Vitamin B 12 Deficiency

To study the clinical and laboratory features of patients admitted with vitamin B12 deficiency-related (B12def) neurological syndromes.. A hospital-based retrospective and prospective study conducted at a referral teaching hospital.. Consecutive patients admitted with vitamin B12 deficiency-related neurological disorders during a three-year period from June 2000 to May 2003 were included. Data regarding clinical and laboratory features were obtained. Follow-up was done at least six months following treatment with parenteral vitamin B12. Chi-square test was used for statistical analysis.. A total of 63 patients (52 males) with a mean age of 46.2 years were studied. The mean duration of symptoms at presentation was 10.3 months. Myeloneuropathy (54%) was the commonest neurological manifestation, followed by myeloneuropathy with cognitive dysfunction (34%), and peripheral neuropathy (9%). Neuropsychiatric manifestations and dementia were observed in 38% and 19% of patients respectively. All the patients had megaloblastic changes in the bone marrow smear. Eleven (17.5%) patients had both hemoglobin and the mean corpuscular volume (MCV) within the normal range. Follow-up after at least six months of therapy with parenteral B12 showed improvement in 54% patients.. A high index of suspicion of B12def is required in patients presenting with myelopathy, cognitive decline, or neuropathy. A normal hemoglobin or MCV does not exclude B12def; therefore, other tests such as bone marrow smear and serum vitamin B12 assay are essential, as the condition is often reversible with treatment.

Topics: Adult; Cognition Disorders; Female; Follow-Up Studies; Humans; Male; Middle Aged; Peripheral Nervous System Diseases; Prospective Studies; Retrospective Studies; Vitamin B 12; Vitamin B 12 Deficiency

Deficiencies in folate and vitamin B12 have been associated with neurodegenerative disease.. To examine the association between rates of age-related cognitive change and dietary intakes of folate and vitamin B12.. Prospective study performed from 1993 to 2002.. Geographically defined biracial community in Chicago, Ill.. A total of 3718 residents, 65 years and older, who completed 2 to 3 cognitive assessments and a food frequency questionnaire.. Change in cognitive function measured at baseline and 3-year and 6-year follow-ups, using the average z score of 4 tests: the East Boston Tests of immediate and delayed recall, the Mini-Mental State Examination, and the Symbol Digit Modalities Test.. High folate intake was associated with a faster rate of cognitive decline in mixed models adjusted for multiple risk factors. The rate of cognitive decline among persons in the top fifth of total folate intake (median, 742 microg/d) was more than twice that of those in the lowest fifth of intake (median, 186 microg/d), a statistically significant difference of 0.02 standardized unit per year (P = .002). A faster rate of cognitive decline was also associated with high folate intake from food (P for trend = .04) and with folate vitamin supplementation of more than 400 microg/d compared with nonusers (beta = -.03, P<.001). High total B12 intake was associated with slower cognitive decline only among the oldest participants.. High intake of folate may be associated with cognitive decline in older persons. These unexpected findings call for further study of the cognitive implications of high levels of dietary folate in older populations.

Topics: Age Factors; Aged; Chicago; Cognition Disorders; Data Collection; Dietary Supplements; Dose-Response Relationship, Drug; Female; Folic Acid; Food, Fortified; Humans; Male; Models, Statistical; Neuropsychological Tests; Prospective Studies; Surveys and Questionnaires; Vitamin B 12

An elevated serum homocysteine level is a risk factor for the development of cognitive impairment. Reported is a late-onset case of hyperhomocystinemia due to a vitamin B12 metabolic deficit (cobalamin C) with cognitive impairment, primarily in frontal/executive function. After homocysteine-lowering therapy, the patient's functional and neuropsychological status improved in conjunction with a decrease in leukoariosis on his MRI scan. These findings suggest that homocysteine-related cognitive impairment may be partially reversible.

Topics: Adult; Anticoagulants; Betaine; Cognition Disorders; Confusion; Disease Progression; Drug Therapy, Combination; Folic Acid; Frontal Lobe; Homocysteine; Humans; Hyperhomocysteinemia; Leukoaraiosis; Magnetic Resonance Imaging; Male; Methylmalonic Acid; Remission Induction; Seizures; Treatment Outcome; Vitamin B 12; Vitamin B 6

Vitamin B12 status has been linked to cognitive impairment among older adults. Deficit in methylmalonic acid (MMA) may be reflective of cognitive impairment because it is a biochemically sensitive marker of B12 deficiency. In a cross-sectional study the contributions of different indices of B12 status, including serum B12, MMA and total homocysteine (tHcy), were measured in relation to cognitive functioning. B12 deficiency as measured by elevated MMA concentrations appeared to be most reflective of cognitive impairment and appeared to contribute unique variance to cognitive measures after controlling for other biochemical variables. Demographic variables, particularly education and age, were more strongly associated with cognitive measures than was MMA. Monitoring and reducing serum MMA concentrations by increasing the intake of vitamin B12 may provide protection against cognitive decline in this and other older populations.

Topics: Aged; Aged, 80 and over; Cognition Disorders; Dietary Services; Epidemiologic Methods; Female; Food Services; Humans; Male; Methylmalonic Acid; Middle Aged; Neuropsychological Tests; Vitamin B 12; Vitamin B 12 Deficiency

The aim of this study was to investigate over a 3-year period the connection between homocysteine (Hcy) levels and development of Alzheimer's disease (AD) in patients with mild cognitive impairment (MCI). Hcy was analyzed in 68 men, mean age 65 years, and 68 women, mean age 64 years. Age, sex, cobalamin, folate, creatinine, and thyroid profiles as well as results of Mini-Mental State Examination at the first visit to the memory investigation unit of a geriatric department were recorded from patient journals collected between 1992 and 1999. The total numbers of persons who converted to AD within a period of 3 years from initial investigation with baseline Hcy sampling was 12 of 46 (26%) males, and 18 of 50 women (36%). The total percentage of men and women converting to AD was 31%. Thirty-three percent of men with Hcy levels >20 micromol/l converted to AD. The corresponding figure for men with Hcy levels 20-17 micromol/l was 50%, whereas none of the 18 men with Hcy levels <17 micromol/l converted to AD. These differences were statistically significant. There was also a statistically significant difference between the percentage of women with Hcy levels >16 micromol/l who converted to AD (45%) as compared to those with Hcy levels <16 micromol/l who converted (21%). These findings are inconsistent with the results of other studies showing a positive correlation with hyperhomocysteinemia and occurrence of AD. However, our findings tentatively suggest a possible protective effect of low/normal Hcy levels on dementia conversion in MCI patients.

Topics: Aged; Alzheimer Disease; Cognition Disorders; Creatinine; Female; Folic Acid; Hemoglobins; Homocysteine; Humans; Male; Middle Aged; Neuropsychological Tests; Sex Characteristics; Thyrotropin; Vitamin B 12; Vitamins

Plasma total homocysteine (tHcy) concentrations are associated with deficits in cognitive performance in persons free from dementia. The extent to which age modifies these associations is in need of further investigation in large, community-based, prospective studies combining the following elements: 1) multiple cognitive tests; 2) statistical adjustment for the role of the vitamin cofactors folate, vitamin B6, and vitamin B12; and 3) adjustment for the presence of risk factors for cardiovascular disease and stroke. Using data collected between 1991 and 2002, the authors investigated the associations between tHcy and multiple measures of cognitive performance in 2,096 dementia- and stroke-free participants of the Framingham Offspring Study, who were stratified into three age groups (40-49 years, 50-59 years, 60-82 years), after findings of statistically significant tHcy-by-age interactions for multiple cognitive measures. Regardless of statistical adjustment for age, sex, gender, the vitamin cofactors, and cardiovascular risk factors, statistically significant inverse associations between tHcy and multiple cognitive domains were observed for individuals aged 60 or more years; no such associations were observed for participants aged less than 60 years. Early preventive interventions may be important, because the inverse association between tHcy and cognitive performance is observed beyond middle age.

Topics: Adult; Aged; Aged, 80 and over; Chi-Square Distribution; Cognition Disorders; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Neuropsychological Tests; Pyridoxine; Regression Analysis; Risk Factors; Vitamin B 12

Elevated homocysteine concentrations may contribute to cognitive impairment. Most elevations in homocysteine result from inadequate folate, vitamin B-12, or vitamin B-6 intake. It is not clear whether the observed associations between homocysteine and cognitive measures are causal or whether they are due to homocysteine, to independent actions of the B vitamins, or to both.. We aimed to assess the individual and independent effects of baseline plasma homocysteine, folate, vitamin B-12, and vitamin B-6 and of dietary B vitamin intakes on 3-y changes in cognitive measures in 321 aging men.. Participants were from the Veterans Affairs Normative Aging Study. Cognitive function was assessed with the Mini-Mental State Examination and on the basis of measures of memory, verbal fluency, and constructional praxis, which were adapted from the revised Wechsler Adult Intelligence Scale and the Consortium to Establish a Registry for Alzheimer's Disease batteries at 2 time points. At baseline, dietary intakes were assessed with a food-frequency questionnaire, and blood was drawn for the measurement of B vitamins and homocysteine.. Over a mean 3-y follow-up, declines in constructional praxis, measured by spatial copying, were significantly associated with plasma homocysteine, folate, and vitamins B-6 and B-12 and with the dietary intake of each vitamin. Folate (plasma and dietary) remained independently protective against a decline in spatial copying score after adjustment for other vitamins and for plasma homocysteine. Dietary folate was also protective against a decline in verbal fluency. A high homocysteine concentration was associated with a decline in recall memory.. Low B vitamin and high homocysteine concentrations predict cognitive decline. Spatial copying measures appear to be most sensitive to these effects in a general population of aging men.

Topics: Aged; Aged, 80 and over; Aging; Cognition; Cognition Disorders; Cohort Studies; Cross-Sectional Studies; Diet; Folic Acid; Folic Acid Deficiency; Follow-Up Studies; Homocysteine; Humans; Male; Middle Aged; Predictive Value of Tests; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Approximately 15% of people aged more than 60 years old have a cobalamin (vitamin B12) deficiency, mainly in relation with food-cobalamin malabsorption (FCM). To date, no study has documented this disorder in the elderly. There is also little information on clinical consequences.. We studied 92 elderly patients with well-established FCM who were extracted from an observational cohort study (1995-2004) of 172 consecutive elderly patients with documented cobalamin deficiency.. The median patient age was 76 +/- 8 years; 60 patients were women. The most common clinical manifestations were neurologic or psychologic: mild sensory polyneuropathy (44.6%), confusion or impaired mental functioning (22.8%), and physical asthenia (20.7%). Hematologic abnormalities were reported in at least one third of the patients: anemia (21%), leukopenia (10.9%), thrombopenia (8.7%), and pancytopenia (6.5%). All patients had low serum vitamin B12 levels (<200 pg/mL), with a mean value (+/- standard deviation) of 131 +/- 38 pg/mL and total serum homocysteine level of 22.1 +/- 9.3 micromol/L. The mean hemoglobin level was 10.9 +/- 2.5 g/dL and the mean erythrocyte cell volume 95.7 +/- 12.7 fL. Correction of the serum vitamin B12 levels and hematologic abnormalities was achieved equally well in patients treated with either intramuscular or oral crystalline cyanocobalamin.. This study suggests that in elderly patients, FCM may be associated with significant neurologic, psychologic, and hematologic abnormalities, which seem to respond equally well to either oral or parenteral vitamin B12 therapy.

Topics: Aged; Aged, 80 and over; Asthenia; Cognition Disorders; Cohort Studies; Confusion; Edema; Erythrocyte Indices; Female; Follow-Up Studies; Gastritis, Atrophic; Hematologic Diseases; Hemoglobins; Homocysteine; Humans; Jaundice; Malabsorption Syndromes; Male; Paresthesia; Polyneuropathies; Reflex, Abnormal; Retrospective Studies; Vitamin B 12; Vitamin B 12 Deficiency

Elderly subjects with mild cognitive impairment have a high risk for conversion to Alzheimer's disease or are already in a preclinical dementia stage. By cross-sectionally comparing subjects in prodromal and early phases of dementia with non-demented controls, we tested the hypothesis whether low serum vitamin B12 and folate and high plasma total homocysteine concentrations precede or are a consequence of dementia onset. From a large population of 623 consecutive subjects seen at the Memory Clinic (Ospedale Beata Vergine, Mendrisio, Switzerland), 433 subjects could be included in the analyses: 79 elderly controls, 218 Clinical Dementia Rating 0.5 subjects, and 136 demented patients (111 with Alzheimer's disease and 25 with vascular dementia). As in an earlier report on a smaller sample of the same population (n=228), the lowest folate tertile was strongly associated with mild cognitive impairment (adjusted OR=3.1) and Alzheimer's disease (adjusted OR=4.0). Hyperhomocysteinemia showed a significant association not only with Alzheimer's disease (adjusted OR=3.1) but, at variance with the previous report, also with mild cognitive impairment (adjusted OR=2.6). Present reanalysis results suggest that subclinical folate deficiency and hyperhomocysteinemia might predate dementia onset, findings to be confirmed by longitudinal studies.

Topics: Aged; Cognition Disorders; Dementia; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; 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

A 75-year old man with a 40-year history of alcoholism was admitted to the hospital for intoxication and inability to care for himself. He had been admitted frequently in the past for detoxification and rehabilitation. The patient had no family history of Alzheimer's disease, no history of head injury, and single-photon emission computed tomography showed no typical findings of Alzheimer's disease. His cognitive function was impaired. He was treated with donepezil for alcohol-related dementia, and 3 months later, his cognitive function had improved. More research is needed to confirm donepezil's role in treating alcohol-related dementia.

Topics: Aged; Alcohol-Related Disorders; Cognition Disorders; Donepezil; Drug Administration Schedule; Humans; Indans; Injections; Male; Piperidines; Time Factors; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency

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.. 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.. 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).. 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.

Topics: Adult; Aged; Aged, 80 and over; Alzheimer Disease; Cognition Disorders; Dementia; Female; Folic Acid; Humans; Male; Middle Aged; Neuropsychological Tests; Prospective Studies; Social Behavior Disorders; Vitamin B 12

Hyperhomocysteinemia is a risk factor for dementia but only scanty data exist about its relationship to specific cognitive abilities during normal aging. We recruited 62 healthy and cognitively normal subjects of age 65-91 years from the Conselice Study of brain aging. The following neuropsychological tests were applied (i) The mental deterioration battery(MDB) consisting of 7 parts: the Rey's 15 words immediate and delayed recall, word fluency, sentence construction, Raven's progressive matrices '47, immediate visual memory, freehand copying of drawings and copying drawings with landmarks. (ii) The Prose memory test. (iii) The Corsi block-tapping task. (iv) The mini mental state examination(MMSE) scores. We measured plasma total homocysteine (tHcy), serum folate, vitamin B12 and plasma vitamin B6. Multivariate-adjusted linear regression analysis showed statistically significant negative association of plasma tHcy with scores at MMSE (b= -0.01 2,p < 0.001) and word fluency (b = -0.009, p = 0.021). A non-significant trend towards a negative association was also found for sentence construction (b = -0.006, p = 0.076). One can conclude that in healthy elderly subjects, increased plasma tHcy is correlated to poorer performance at a specific measure of language abilities being compromised in both vascular and Alzheimer's dementia. The study suggests that plasma tHcy could be an early marker of cognitive impairment.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Cognition Disorders; Cross-Sectional Studies; Dementia, Vascular; Female; Folic Acid; Health Status; Humans; Hyperhomocysteinemia; Male; Neuropsychological Tests; Nutritional Status; Phonetics; Psychometrics; Severity of Illness Index; Vitamin B 12; Vitamin B 6; Vocabulary

Dementia is one of the most pressing public health problems with social and economic implication. The form called cognitive impairment non-dementia (CIND)represents a subclinical phase of dementia. Different studies have shown a possible effect of micro- and macro-nutrients on cognitive function. Trace elements, being involved in metabolic processes and redox reactions in the central nervous system (CNS), could influence the cognitive functions. This study evaluated the presence of an eventual correlation between serum trace element concentrations and cognitive function in a group of subjects with CIND and manifest dementia (Alzheimer dementia = AD, and vascular dementia = VaD), and compared them with a control group. Thirty -five patients were enrolled in this study. Each patient underwent a clinical and biochemical examination. We also performed a neuropsychological and functional assessment (the Milan overall dementia assessment = MODA, activities of daily living = ADL, and instrumental activities of daily living = IADL), and a computerized tomographic (CT) cerebral scan. Patients were than divided in 4 groups according to the obtained diagnosis (Controls, CIND, AD, VaD). The presence of any acute or chronic conditions, affecting cognitive functions, was considered as exclusion criteria. A blood sample was collected to determine iron (Fe), zinc (Zn), manganese (Mn), selenium (Se), cobalt (Co), chromium (Cr), copper (Cu),molybdenum (Mo) and aluminium (Al) serum concentrations (chromatographic,spectrophotometric methods). In our cohort we found a positive correlation between cognitive function, expressed as the MODA score, and Se, Cr, Co and Fe serum levels,while a negative correlation was observed between MODA score, Cu and Al serum levels.Moreover, some statistically significant differences in Se, Cr, Co, Cu and Al concentrations were found among the groups. According to these results, we may suppose that Se, Cr and Co protect cognitive function, Cu influences the evolution of cognitive impairment, while Al contributes to the pathogenesis of AD.

Topics: Activities of Daily Living; Aged; Albumins; Brain; Cholesterol; Cognition Disorders; Cohort Studies; Dementia; Female; Folic Acid; Gas Chromatography-Mass Spectrometry; Humans; Male; Neuropsychological Tests; Oxidation-Reduction; Severity of Illness Index; Thyrotropin; Tomography, X-Ray Computed; Trace Elements; Triglycerides; Vitamin B 12

Evidence supports an independent association between plasma total homocysteine concentrations and the risk of vascular disease. Recent epidemiologic studies reappraised the possibility that vascular risk factors might play a role in the pathogenesis not only of vascular dementia (VaD) but also of Alzheimer disease (AD).. The objective was to investigate the relations of mild cognitive impairment, AD, and VaD with blood homocysteine, folate, and vitamin B-12.. The study population consisted of 314 consecutive subjects, 228 of whom were eligible for analyses. Plasma total homocysteine, serum folate, and serum vitamin B-12 concentrations were measured in 55 nondemented elderly control subjects, 81 mildly cognitively impaired subjects (Clinical Dementia Rating: 0.5), and 92 demented patients prevalently in a mild disease stage and with a clinical diagnosis of AD (n = 74) or VaD (n = 18).. Subjects in the lowest folate tertile had significantly higher adjusted odds ratios (ORs) for mild cognitive impairment (OR: 3.1; 95% CI: 1.2, 8.1) and dementia (3.8; 1.3, 11.2). Hyperhomocysteinemia was significantly associated with dementia (adjusted OR: 4.3; 1.3, 14.7) and AD (adjusted OR: 3.7; 1.1, 13.1). In subjects with a Clinical Dementia Rating of 0.5, the mean (+/- SE) Mini-Mental State Examination score was significantly lower (P < 0.05) in the highest homocysteine tertile (24.5 +/- 0.5) than in the lowest tertile (26.6 +/- 0.5). No significant associations were found between minimum medial temporal lobe thickness or leukoaraiosis and any biochemical measure in the dementia and AD groups.. These findings suggest that relative folate deficiency may precede AD and VaD onset. Hyperhomocysteinemia might also be an early risk factor for cognitive decline in the elderly, but its role in dementia development must be addressed in future longitudinal studies.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Analysis of Variance; Cognition Disorders; Cross-Sectional Studies; Dementia, Vascular; Female; Folic Acid; Homocysteine; Humans; Male; Odds Ratio; Risk Factors; Switzerland; Vitamin B 12

A case of a 44-years-old patient with unusual clinical presentation of encephalomyelopolyneuropathy in vitamin B12 deficiency is presented. The disease manifested itself with gastrointestinal bleeding, which necessitated emergency hospitalisation in surgical clinic. Clinical examinations revealed atrophic gastritis, pernicious anemia, neurological and mental complications. The diagnosis was made according to the following criteria: physical examination--smooth tongue, atrophic gastritis, mild hepatosplenomegaly; laboratory findings--pernicious anemia, low vitamin B12 serum levels; neurological examination--syndrome of combined damage of the posterior and lateral columns of the spinal cord; magnetic resonance imaging--typical hyperintense areas on T2-weighted images in the posterior columns in the cervical regions of the spinal cord; transcranial magnetic stimulation--prolonged central motor conduction time of the motor evoked potentials bilaterally; psychological examination--cognitive decline. After treatment with vitamin B12 an improvement of the hematological findings, neurological deficit and cognitive impairments was found.. Neurological complications could be an early manifestation of vitamin B12 deficiency. In diagnostic aspect similar complaints require examination of the serum levels of vitamin B12. The delay in diagnosis and inadequate therapy bear the risk of incomplete recovery of the neurological deficit. The current problem of "cognitive decline" necessitates routine examination of the serum levels of vitamin Bl2 in all patients with initial cognitive impairments and their prompt and approapriate treatment.

Topics: Adult; Central Nervous System Diseases; Cognition Disorders; Humans; Male; Polyneuropathies; Vitamin B 12; Vitamin B 12 Deficiency

Elevated fasting plasma total homocysteine concentration (tHcy) and lower vitamin status are associated with atherosclerotic states. Silent brain ischemic lesions and brain atrophy, prevailing in the elderly, are affected by tHcy and vitamin status. The study was performed on 56 outpatients who had undergone brain computed tomography (CT) before the onset of the study. According to brain CT evaluation, three groups were set: minor brain ischemia, brain atrophy and control. Brain CT, tHcy, plasma pyridoxal phosphate (PLP), vitamin B(12), folic acid and cognitive and functional capacities were measured or evaluated in all of the subjects. Plasma vitamin score for three vitamins was calculated. In subjects with minor brain ischemic lesions (n = 21), tHcy was higher by 5.6 microM, whereas vitamin score and cognitive function were lower than in controls (n = 24). In subjects with brain atrophy (n = 11), plasma PLP and cognitive function were lower. Particular attention should be paid to tHcy monitoring, vitamin status assessment and brain impairment evaluation.

Topics: Aged; Aged, 80 and over; Atrophy; Brain; Brain Ischemia; Cognition Disorders; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Male; Vitamin B 12; Vitamin B 6; Vitamins

The present prospective study investigated whether elevated total serum homocysteine concentration is a risk factor for cognitive decline. The outcomes were compared to the possible relation between cognition and vitamin B12 or folic acid. Cognitive performance of 144 normal aging individuals (aged 30-80 years) was tested at baseline and after six years of follow-up. Domains of cognitive function addressed were cognitive speed (Letter-Digit Coding test), attention and information processing (Stroop test) and verbal learning and memory (Word Learning Test Total; Delayed Recall). Serum concentrations of homocysteine, folic acid and vitamin B12 were determined. Serum concentrations of homocysteine correlated negatively with cognitive performance on the Word Learning tests at baseline, independent of age, sex, education level or folic acid concentration. Homocysteine concentration at baseline correlated negatively with cognitive performance on the Stroop and Word Learning tests during the whole six-year follow-up period. The folic acid concentration correlated to the Delayed Recall test at baseline only and no correlations were observed for vitamin B12. Thus, while a relation between vitamin B12 or folic acid and cognition was almost absent, elevated homocysteine concentrations were associated with prolonged lower cognitive performance in this normal aging population.

Topics: Adult; Aged; Aged, 80 and over; Aging; Biomarkers; Cognition; Cognition Disorders; Female; Folic Acid; Follow-Up Studies; Homocysteine; Humans; Longitudinal Studies; Male; Middle Aged; Neuropsychological Tests; Prospective Studies; Psychomotor Performance; Risk Factors; Vitamin B 12

Topics: Adult; Anemia, Pernicious; Anemia, Sickle Cell; Cognition Disorders; Female; Folic Acid; Humans; Mental Disorders; Neuropsychological Tests; Vitamin B 12

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.. 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.. 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.. 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.. 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.

Topics: Aged; Alzheimer Disease; Apolipoproteins E; Cognition Disorders; Folic Acid; Homocysteine; Humans; Methylenetetrahydrofolate Reductase (NADPH2); Oxidoreductases Acting on CH-NH Group Donors; Polymorphism, Genetic; Vitamin B 12

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.

Topics: Aged; Aged, 80 and over; Blood-Brain Barrier; Cognition Disorders; Drug Therapy, Combination; Female; Folic Acid; Humans; Hyperhomocysteinemia; Male; Middle Aged; Regression Analysis; Serum Albumin; Vitamin B 12; Vitamin B 6

Elevated plasma homocysteine (hyperhomocysteinemia), an independent risk factor for vascular disease, has been reported to be inversely correlated with objective measures of cognitive function in patients with Alzheimer disease and in community-dwelling older adults.. We evaluated the cross-sectional relation between total plasma homocysteine concentration and cognitive function in elderly Latinos (aged > or = 60 y; n = 1789) participating in the Sacramento Area Latino Study on Aging.. Global cognitive function was assessed by using the Modified Mini-Mental State Examination, and specific cognitive functions were assessed by using 6 instruments developed for cross-cultural and multilingual neuropsychological evaluation of older persons. Associations between the cognitive function scores and total plasma homocysteine concentrations were then measured by multiple regression analysis with control for potential confounding by nutrient status (red blood cell folate, plasma vitamin B-12), kidney function (serum creatinine), demographic variables (age, sex, education, acculturation), and depressive symptoms.. Modest inverse associations were found between homocysteine concentrations and several indexes of cognitive function, including the global Modified Mini-Mental State Examination assessment and the picture-association, verbal attention-span, and pattern-recognition tests (P < or = 0.05). Demographic variables, particularly age and education, were more strongly associated with cognitive function scores than was homocysteine.. Homocysteine is a modest independent predictor of cognitive function in community-dwelling elderly Latinos. Reducing plasma homocysteine concentrations by administering B-vitamin supplements may provide some protection against cognitive decline in this and other elderly populations, but the effect may be limited.

Topics: Age Factors; Aged; Biomarkers; California; Cognition Disorders; Cohort Studies; Cross-Sectional Studies; Educational Status; Female; Hispanic or Latino; Homocysteine; Humans; Hyperhomocysteinemia; Male; Middle Aged; Predictive Value of Tests; Risk Factors; Sex Factors; Vitamin B 12

Cyanocobalamin (vitamin B12) deficiency can cause polyneuropathy, myelopathy, blindness, confusion, psychosis and dementia. Nonetheless, its deficiency as the sole cause of dementia is infrequent. We report a 59 years old man with a 6 months history of progressive loss of memory, disorientation, apathy, paranoid delusions, gait difficulties with falls, and urinary incontinence. He had suffered a similar episode 3 years before, with a complete remission. On examination there was frontal type dementia with Korsakoff syndrome, a decrease in propioception and ataxic gait. Cerebrospinal fluid examination showed a protein of 0.42 g/L. Brain computed tomography showed sequelae of a frontal left trauma. Brain single photon computed tomography (SPECT) was normal. Complete blood count showed a macrocytic anemia with a hematocrit 29% and a mean corpuscular volume of 117 micron3. Plasma vitamin B12 levels were undetectable, erythrocyte folate levels were 3.9 ng/ml and plasma folate was normal. The myelogram showed megaloblastosis and the gastric biopsy showed atrophic gastritis. Treatment with parenteral B12 vitamin and folic acid reverted the symptoms, with normalization of the neuropsychological tests and reintegration to work.

Topics: Cognition Disorders; Dementia; Humans; Male; Middle Aged; Vitamin B 12; Vitamin B 12 Deficiency

Cerebrovascular small vessel disease is now believed to be the major source of vascular burden of the brain. Cerebrovascular small vessel disease and Alzheimer's disease appear to represent pathophysiologic and clinical continua, rather than dichotomous entities. It appears that common etiopathologic mechanisms underlie the clinical presentation of both of these conditions. Therefore, the staging procedures that have been developed for the clinical continuum of age-associated memory impairment, mild cognitive impairment, and the progressive dementia of Alzheimer's disease appear to be applicable for the same continua in cerebrovascular small vessel disease. Although temporal and prognostic aspects have been studied for the Alzheimer's-related portions of this clinical staging continuum, they remain to be elucidated for cerebrovascular small vessel disease.

Topics: Aged; Alzheimer Disease; Brain; Cerebrovascular Circulation; Cerebrovascular Disorders; Cognition Disorders; Cost of Illness; Follow-Up Studies; Humans; Neuropsychological Tests; Prospective Studies; Severity of Illness Index; Vitamin B 12

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.. We measured serum cobalamin, blood folate, plasma homocysteine (tHcy) and serum methylmalonic acid (MMA) in 475 well-defined psychogeriatric patients.. 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.. 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.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Biomarkers; Cognition Disorders; Female; Folic Acid; Homocysteine; Humans; Male; Mental Disorders; Methylenetetrahydrofolate Reductase (NADPH2); Methylmalonic Acid; Oxidoreductases Acting on CH-NH Group Donors; Vitamin B 12

In previous studies we observed a high frequency of elevated total plasma homocysteine (tHcy) concentrations in psychogeriatric patients. The objective of the present study was to obtain detailed information on folate status in psychogeriatric patients and its association with elevated tHcy concentration.. We measured serum and blood folate, tHcy, serum cobalamin, and serum methylmalonic acid in a study population consisting of 141 psychogeriatric patients, 49 of whom had elevated tHcy concentration.. The concentrations of serum and blood folate showed a high correlation and were significantly lower, and age significantly higher, in patients with elevated tHcy compared to patients with normal concentrations of tHcy. A stepwise multiple regression analysis including age, serum and blood folate, serum cobalamin, serum methylmalonic acid and serum creatinine showed that only serum creatinine (p<0.001), age (p<0.01), serum folate (p<0.05) and blood folate (p<0.05) independently predicted tHcy concentration. Only one patient of those with serum folate above 12 nmo/L had an elevated tHcy concentration. No such clear limit was observed for the relation between tHcy and blood folate. Thirty-two of the patients with elevated tHcy had decreased serum folate concentrations (<7.0 nmol/L), and seven of these patients also had signs of cobalamin deficiency. Ten patients had only signs of cobalamin deficiency.. Folate deficiency appears to be common in psychogeriatric patients, and serum folate seems to reflect folate deficiency better than blood folate. Our findings suggest the use of tHcy, serum cobalamin and serum folate to evaluate cobalamin-folate status in psychogeriatric patients.

Topics: Aged; Aged, 80 and over; Aging; Cognition Disorders; Female; Folic Acid; Folic Acid Deficiency; Homocysteine; Humans; Hyperhomocysteinemia; Male; Methylmalonic Acid; Regression Analysis; Vitamin B 12

The aim of this study was to investigate the relationship between total homocysteine levels in people with Type 2 diabetes and cognitive status. Fifty patients from our diabetes unit (30 females/20 males) with diabetes were enrolled. All patients had fasting blood samples taken for measurement of cardiovascular risk factors; total cholesterol and triglyceride concentrations and other lipid fractions (lipoprotein (a), low density lipoprotein (LDL-cholesterol), high density lipoprotein (HDL-cholesterol)), glucose, HbA(1c) and homocysteine. 24-h urine collection was used to measure creatinine clearance and microalbuminuria. Vitamin B-12 and folate were measured to assess vitamin status. All diabetic patients were assessed for late complications and a Mini-Mental State Examination (MMSE) was performed. The patients were 64.6 (49-78) years old with body mass index (BMI) of 29.6 +/- 6.3 kg/m(2), and duration of diabetes of 8.9 +/- 6.7 years. A univariant correlation analysis was performed among cardiovascular risk factors and vitamins with total MMSE score. Total homocysteine was inverse by correlated with MMSE score (r=-0.38; P<0.05) of the other measures of cardiovascular risk, microalbuminuria showed an inverse correlation with MMSE score (r=-0.51:P<0.01). Lipoproteins, glucose control and vitamin status were not correlated MMSE score. In the multiple regression model only microalbuminuria remained in the model, showing a decrease of one point in the MMSE result with each milligram of microalbuminuria, adjusted for confounding factors. Cognitive status in type 2 diabetic was correlated with homocysteine levels and microalbuminuria, this last endothelial damage marker remaining as an independent risk factor of cognitive deterioration.

Topics: Aged; Albuminuria; Cholesterol; Cognition; Cognition Disorders; Diabetes Mellitus, Type 2; Female; Folic Acid; Glycated Hemoglobin; Homocysteine; Humans; Lipoproteins; Male; Middle Aged; Triglycerides; Vitamin B 12

This study examined the relationship between low levels of serum vitamin B12 and folic acid (FA) and cognitive functioning in very old age. The four subsamples of non-demented persons aged 75-96 years - normal B12/normal FA; low B12/normal FA; normal B12/low FA; and low B12/low FA, were matched for age and education. A battery of cognitive tests was administered including Clock Tests, Block Design, Trail Making Tests (TMT), Digit Span, and tests of verbal fluency. Subjects with low levels of vitamins showed deficits in Block Design, TMT-B, Digit Span Backward, and letter fluency, but not in the remaining tests. In general, the effects of FA exceeded those of B12. This pattern of results was interpreted to mean that elderly persons with low vitamin levels have difficulty when fast and accurate processing of novel information is required, but are quite efficient in utilizing pre-existing knowledge structures.

Topics: Aged; Aged, 80 and over; Aging; Cognition; Cognition Disorders; Female; Folic Acid; Folic Acid Deficiency; Humans; Male; Vitamin B 12; Vitamin B 12 Deficiency

The present study investigated the effects of vitamin B12 (VB12) on circadian rhythm in Alzheimer-type dementia (ATD). Twenty-eight ATD patients were treated with bright light therapy (BLT) for 8 weeks. For the latter 4 weeks, half were treated with VB12 with BLT (BLT + VB12). We evaluated the cognitive state with Mini-Mental State Examination and the circadian rhythm with actigraphy after the fourth and eighth week. After the first 4 weeks BLT improved the circadian rhythm disturbances and cognitive state especially in the early stage of ATD. Although the latter 4 week-BLT caused no significant effects on the circadian rhythm; BLT + VB12 improved the vigilance level during the daytime. These results suggest that VB12 has some efficiency to enhance vigilance for ATD patients.

Topics: Aged; Alzheimer Disease; Arousal; Circadian Rhythm; Cognition Disorders; Combined Modality Therapy; Female; Humans; Male; Neuropsychological Tests; Phototherapy; Severity of Illness Index; Sleep Disorders, Circadian Rhythm; Vitamin B 12

The elderly are known to have higher rates of low and subnormal vitamin B12 levels than younger persons. Vitamin B12 deficiency has been extensively studied in the elderly, but primarily in outpatient settings. There is a paucity of data regarding the prevalence of low and low-normal B12 in frail, hospitalized, elderly patients, and its implications. Additionally, there is little information regarding vitamin B12 status in Israeli elders.. The objectives of the study were to estimate the prevalence of low and borderline vitamin B12 levels among frail, hospitalized, elderly patients, and their clinical implications.. We conducted a chart review, using a retrospective cohort design. The participants were 895 patients admitted to Harzfeld Medical Center in Gedera, Israel. Records were abstracted for vitamin B12 and Folic Acid levels, gastric disease, and outcomes including death, cognitive impairment and neurologic disease.. Six hundred and forty patients were eligible for the study. In 15% of the patients, vitamin B12 level was in the low range (<150pmol/L) and in 25% in the low-normal range (150-250pmol/L). Gastric disease and antacid use were not associated with the vitamin B12 status. Mortality was higher in the high vitamin B12 group (p=0.02), perhaps reflecting a selection toward higher acuity in this group. Cerebrovascular disease was more common in patients with lower vitamin B12 levels (p=0.046).. Forty percent of hospitalized elderly patients have low or borderline serum levels of vitamin B12, which may contribute to cerebrovascular disease and cognitive decline.

Topics: Aged; Cerebrovascular Disorders; Cognition Disorders; Cohort Studies; Female; Folic Acid; Health Services for the Aged; Hospitalization; Humans; Israel; Male; Prevalence; Retrospective Studies; Vitamin B 12; Vitamin B 12 Deficiency

In the present report, 101 ambulatory elderly patients complaining about cognitive disturbances were investigated using the Mini-Mental State Examination (MMSE). Laboratory investigations, brain imaging, and electroencephalography were performed. Twelve patients were diagnosed with subjective memory complaints (SMC), 32 with mild cognitive impairment (MCI), 43 with dementia of the Alzheimer type (DAT), and 14 with vascular dementia (VAD). Thirty-three percent of the SMC group, 31% of the MCI group, 45% of the DAT group, and 62% of the VAD group had increased serum homocysteine (s-HCY). Principal component analysis of 19 variables showed 3 significant principal components by cross-validation. The cognitive impairment in the patients (MMSE) was explained to 50%. According to the principal component analysis, the population followed two different routes to cognitive impairment: one correlated with disturbance of one-carbon metabolism (cerebrospinal fluid vitamin B12, plasma B12, plasma folate, and s-HCY) and the other correlated with more classic dementia, as marked by cerebrospinal fluid tau, vascular risk factors, atrophy on brain imaging, possession of the apolipoprotein E4 allele, and age. There was poor discrimination between DAT and VAD.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Apolipoproteins E; Atrophy; Brain; Cognition Disorders; Dementia, Vascular; Diagnosis, Differential; Female; Folic Acid; Homocysteine; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neuropsychological Tests; Reference Values; Severity of Illness Index; tau Proteins; 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

Vitamin B12 assay is part of the routine investigation of dementia, although few studies have investigated the effects of treatment on cognition. We examined the effects of B12 treatment on neuropsychological function and disease progression in patients presenting with dementia or cognitive impairment.. From 1432 patients who were assessed at the Bristol Memory Disorders Clinic, 125 patients with low serum B12 were identified. Sixty-six patients presenting with dementia, and 22 with cognitive impairment were seen for a second assessment after treatment. Changes in neuropsychological test scores were compared with those of patients with normal serum B12, matched by age and diagnosis.. The majority of patients with low serum B12 had normal Hb and MCV values. We found no cases of reversible B12 deficiency dementia. The B12 treatment patients who presented with dementia showed no significant improvement, and no less deterioration, in their neuropsychological function than their matched group. However, a treatment effect was demonstrated among the patients presenting with cognitive impairment. These improved significantly compared to matched patients on the verbal fluency test (p<0.01).. All patients with cognitive impairment should be investigated for B12 deficiency. Vitamin B12 treatment may improve frontal lobe and language function in patients with cognitive impairment, but rarely reverses dementia.

Topics: Aged; Cognition; Cognition Disorders; Dementia; Disease Progression; Female; Humans; Male; Neuropsychological Tests; Retrospective Studies; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency

Lack of cobalamin may lead to neurologic disorders, which have been reported in strict vegetarians.. The objective of this study was to investigate whether cognitive functioning is affected in adolescents (aged 10-16 y) with marginal cobalamin status as a result of being fed a macrobiotic diet up to an average age of 6 y.. Data on dietary intake, psychological test performance, and biochemical variables of cobalamin status were collected from 48 adolescents who consumed macrobiotic (vegan type) diets up to the age of 6 y, subsequently followed by lactovegetarian or omnivorous diets, and from 24 subjects (aged 10-18 y) who were fed omnivorous diets from birth onward. Thirty-one subjects from the previously macrobiotic group were cobalamin deficient according to their plasma methylmalonic acid concentrations. Seventeen previously macrobiotic subjects and all control subjects had normal cobalamin status.. The control subjects performed better on most psychological tests than did macrobiotic subjects with low or normal cobalamin status. A significant relation between test score and cobalamin deficiency (P: = 0.01) was observed for a test measuring fluid intelligence (correlation coefficient: -0.28; 95% CI: -0.48, -0.08). This effect became more pronounced (P: = 0.003) within the subgroup of macrobiotic subjects (correlation coefficient: -0.38; 95% CI: -0.62, - 0.14).. Our data suggest that cobalamin deficiency, in the absence of hematologic signs, may lead to impaired cognitive performance in adolescents.

Topics: Adolescent; Child; Cognition; Cognition Disorders; Cohort Studies; Diet, Macrobiotic; Female; Humans; Intelligence; Male; Psychological Tests; Psychomotor Performance; Reference Values; Vitamin B 12; Vitamin B 12 Deficiency

Previous reports have shown elevated plasma total homocysteine (tHcy) levels in elderly person with impaired cognition.. To study the association between cognitive status and plasma tHcy levels in centenarians.. Cross-sectional survey.. Centenarians living in two northern Italian provinces.. Thirteen cognitively normal centenarians, ten cognitively impaired not-demented centenarians, and 34 demented centenarians with a clinical diagnosis of Alzheimer's disease (AD).. Blood levels of homocysteine's biological determinants vitamin B12, folate, and vitamin B6.. Elevated plasma tHcy levels (>17 micromol/l) were common in the general population (77% of normal centenarians, 100% of cognitively impaired not-demented centenarians, 82% of AD centenarians). Demented centenarians had the lowest folate serum levels. Low or borderline vitamin B12 serum levels (<221 pmol/l) and low vitamin B6 plasma levels (<11.7 nmol/l) were found in 33 and 66% of all centenarians independently of cognitive status. Among demented centenarians only plasma tHcy correlated inversely with both serum vitamin B12 and folate. No significant difference was found for plasma tHcy levels among the three diagnostic groups, even after adjusting for B vitamin levels.. Hyperhomocysteinemia is very common among centenarians, probably due to vitamin deficiencies, but does not seem to be associated with cognitive impairment.

Topics: Aged; Aged, 80 and over; Aging; Alzheimer Disease; Cognition Disorders; Cross-Sectional Studies; Dementia; Dementia, Vascular; Female; Folic Acid; Health Surveys; Homocysteine; Humans; Male; Pyridoxine; Reference Values; Vitamin B 12

Hyperhomocysteinemia is a strong risk factor for atherosclerotic vascular disease, and elevated serum homocysteine is correlated with vitamin B deficiency. In this pilot study, significantly elevated homocysteine levels were found in patients with Alzheimer's disease as well as in patients with vascular dementia, probably indicating similar pathophysiological pathways. We found significant correlations between low folic acid concentrations as well as high homocysteine concentrations and cognitive decline. Supplementation with folic acid may be an inexpensive way to reduce elevated homocysteine levels in demented patients.

Topics: Aged; Alzheimer Disease; Cognition Disorders; Dementia, Vascular; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Male; Mental Status Schedule; Pilot Projects; Reference Values; Regression Analysis; Risk Factors; Vitamin B 12

The aim of this study was to analyze drug use in 347 residents in homes for the aged in Bergen, Norway. All drugs prescribed on a regular schedule were assessed, the prevalence of potentially harmful drug combinations, and inappropriately prescribed drugs were studied and related to mental capacity of the residents. Mental capacity was assessed by means of the Clinical Dementia Rating scale (CDR). The median number of drugs used was 4.0 (range 0-11, 95% CI 3.0-4.0). Mentally impaired residents consumed fewer drugs than mentally intact ones. In a logistic regression analysis the use of NSAIDS, beta-blockers and anxiolytics was significantly lower in mentally impaired residents (OR 0.37, 95% CI 0.17-0.80, OR 0.35, 95% CI 0.13-0.95, and OR 0.45, 95% CI 0.21-0.94, respectively), and the use of laxatives and vitamin B-12 higher (OR 2.19, 95% CI 1.04-4.62, and OR 5.08, 95% CI 1.11-23.25, respectively). Twenty percent of mentally intact and 21% of mentally impaired residents have potentially harmful two-by-two drug combinations, and drugs augmenting sedating properties were dominating. The prevalence of inappropriately used drugs was significantly lower in mentally impaired residents (20%) than in mentally intact ones (33%). Antidepressants with anticholinergic properties, benzodiazepines with long half-life and phenothiazines were the most frequent.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Anti-Anxiety Agents; Anti-Inflammatory Agents, Non-Steroidal; Antidepressive Agents; Cathartics; Cognition Disorders; Drug Therapy; Female; Humans; Hypnotics and Sedatives; Logistic Models; Male; Norway; Nursing Homes; Prevalence; Vitamin B 12

Topics: Aged; Cognition Disorders; Confounding Factors, Epidemiologic; Humans; Mental Status Schedule; Vitamin B 12; Vitamin B 12 Deficiency

To assess the long term outcome of patients with methylmalonic acidaemia in a cross sectional study.. All 35 patients with methylmalonic acidaemia seen at Great Ormond Street Hospital for Children in London, UK between 1970 and 1996 were studied. They were divided into cobalamin responsive (n = 6) and non-responsive (n = 29), and early and late onset groups.. There was a significant difference between cobalamin responsive and non-responsive groups in severity, survival, and incidence of neurological sequelae. Cobalamin responsive patients had mild disease, irrespective of age at presentation, their neurological complications were less severe, and they are all alive. The cobalamin non-responsive group comprised 19 early and nine late onset patients. The early onset patients had more severe disease at presentation and 14 have died; all late onset patients are alive. There was no significant difference in abnormal neurological signs, although early onset patients had a significantly reduced full scale intelligence quotient and poor cognitive outcome. In both groups, abnormal neurological signs continue to increase with age.. Cobalamin responsive patients have a better long term outcome. The outcome in the non-responsive patients, particularly the early onset group, remains poor and alternative treatments should therefore be considered early in this group.

Topics: Adolescent; Adult; Age of Onset; Child; Child, Preschool; Cognition Disorders; Dystonia; Female; Humans; Infant; Infant, Newborn; Male; Metabolism, Inborn Errors; Methylmalonic Acid; Treatment Outcome; Vitamin B 12

To examine the effect of vitamin B12 deficiency on older veterans and its relationship to general health and cognitive impairment.. Cross-sectional study.. Oklahoma City Veterans Affairs Medical Center.. Data for this research were obtained from 303 ambulatory, older veterans who used the outpatient laboratories of the Oklahoma City Department of Veterans Affairs Medical Center. Subjects were included in the study if they were 65 years of age and older and if they had no known diagnosis associated with B12 deficiency. The sample in this study consisted of 301 men and 2 women aged 65 to 89 years.. This study used two separate measurements of vitamin B12 deficiency: (1) a strict definition of B12 deficiency (serum B12 level < laboratory norm) and (2) a broader definition of B12 deficiency (serum B12 level < laboratory norm or laboratory norm < B12 < 300 pg/mL and methyl malonic acid (MMA) or homocysteine (HC) elevated by more than two standard deviations). The laboratory norm is 200 pg/mL. The dependent variables were measures of cognitive impairment and general health. Cognitive impairment was measured using the Folstein Mini-Mental State Examination (MMSE) and general health was measured using the RAND 36-Item Health Survey Version 1.0. The control variables for this study were the subjects' daily alcohol intake, daily intake of a vitamin/mineral supplement, annual income, and level of education.. Nineteen subjects (6%) were vitamin B12-deficient as measured by the strict definition of B12 deficiency (serum B12 level < laboratory norm), and 49 subjects (16%) were vitamin B12-deficient as measured by the broader definition of B12 deficiency (serum B12 level < laboratory norm or laboratory norm < B12 < 300 pg/mL and MMA or HC elevated by more than two standard deviations). Vitamin B12 level decreases as age increases. Of the nine general health outcomes measured by using the RAND 36-Item Health Survey, only bodily pain is associated with vitamin B12 deficiency, and only then when B12 deficiency is measured as serum B12 level < laboratory norm, the strict definition of B12 deficiency. Vitamin B12-deficient subjects experience more bodily pain than those with normal vitamin B12 levels. There is a significant difference between B12-deficient subjects and B12 normal subjects on cognitive impairment, with B12 normal subjects indicating less cognitive impairment, only when B12 deficiency is measured as B12 level < laboratory norm, the strict definition of B12 deficiency. The broader measurement of vitamin B12 deficiency (i.e., serum B12 level < laboratory norm or laboratory norm < B12 < 300 pg/mL and MMA or HC elevated by more than two standard deviations) is not a significant correlate of cognitive impairment and general health.

Topics: Aged; Aged, 80 and over; Alcohol Drinking; Analysis of Variance; Cognition Disorders; Cross-Sectional Studies; Educational Status; Female; Geriatric Assessment; Homocysteine; Humans; Income; Male; Methylmalonic Acid; Oklahoma; Reproducibility of Results; Veterans; Vitamin B 12; Vitamin B 12 Deficiency

A Johns Hopkins University study reveals that HIV-infected men with abnormally low B vitamin blood levels progressed to AIDS twice as fast as those with normal levels. Low levels of B12 have also been found in persons with Chronic Fatigue Immune Dysfunction Syndrome (CFID). Since both ailments have a common virus in HHV-6A, the virus is suspected, although unproven, of causing the inability of the intestines to absorb B12 by affecting intrinsic factor levels.

Topics: Acquired Immunodeficiency Syndrome; Cognition Disorders; Fatigue Syndrome, Chronic; Herpesvirus 6, Human; Humans; Intrinsic Factor; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Aged; Cognition Disorders; Dementia; Female; Humans; Leukoencephalopathy, Progressive Multifocal; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Aged; Aged, 80 and over; Cognition; Cognition Disorders; Frail Elderly; Humans; Nutrition Policy; Nutritional Status; Protein-Energy Malnutrition; Thiamine; Vitamin B 12

New data are showing a correlation between low vitamin B12 levels and cognitive impairment. Further, cognitive changes observed were in both early and late stages of HIV infection, even when abnormal blood levels are not yet apparent. Results suggest early B12 clinical intervention as a possible prevention of such early-onset cognitive changes. Dosage levels can be as high as 1,000 micrograms in nasal gel or injection, administered two to seven times per week and combined with folic acid (5,000 to 10,000 micrograms per day).

Topics: Cognition Disorders; Cohort Studies; HIV Infections; Humans; Male; 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

Studies of cognitive function in subjects with human immunodeficiency virus type 1 (HIV-1) infection who remain relatively asymptomatic (ie, Centers for Disease Control stages II and III) have provided widely variable estimates of cognitive impairment. In view of the finding that approximately 25% of asymptomatic HIV-1-infected subjects demonstrate either marginal or overt vitamin B12 deficiency, we have investigated plasma vitamin B12 status as a potential cofactor in studies of HIV-1-related cognitive impairment. When cognition was assessed in asymptomatic (Centers for Disease Control stages II and III) HIV-1-infected participants taking into consideration vitamin B12 status, those subjects with low plasma vitamin B12 levels (less than 180 pmol/L) performed more poorly than did those with normal (greater than or equal to 180 pmol/L) vitamin B12 status on specific measures of information processing speed and visuospatial problem-solving skills. These findings suggest that concurrent vitamin B12 deficiency may be a cofactor in subtle cognitive changes observed in the asymptomatic stages of HIV-1 infection. These differences in prevalence of low plasma vitamin B12 levels may help to explain differences among studies in the proportion of HIV-1-infected subjects showing cognitive impairment.

Topics: Adult; Cognition Disorders; HIV Infections; HIV-1; Humans; Male; Neuropsychological Tests; Space Perception; Visual Perception; Vitamin B 12; Vitamin B 12 Deficiency

This chart review study examined the serum vitamin B12 and folate status of 102 geriatric patients newly admitted to a private psychiatric hospital. Only 3.7% were B12 deficient and 1.3% were folate deficient; 4% were anemic. Nevertheless, those with below-median values of both vitamins had significantly lower Mini-Mental State scores than patients higher in one or both vitamins. Patients with "organic psychosis" with a negative family history for psychiatric disorder had significantly lower B12 levels than those with a positive family history. In major depression, folate levels correlated negatively with age at onset of psychiatric illness and length of hospitalization. These data suggest that (1) biochemically interrelated vitamins such as B12 and folate may exert both a separate and a concomitant influence on affect and cognition; (2) poorer vitamin status may contribute to certain geropsychiatric disorders that begin at a later age and lack a familial predisposition.

Topics: Affective Disorders, Psychotic; Aged; Aged, 80 and over; Bipolar Disorder; Cognition Disorders; Depressive Disorder; Female; Folic Acid; Hospitalization; Humans; Length of Stay; Male; Middle Aged; Neurocognitive Disorders; Retrospective Studies; Vitamin B 12