A randomized placebo controlled trial of homocysteine lowering to reduce cognitive decline in older demented people

Kwok, Timothy; Lee, J.; Law, Chun Bon; Pan, Pey-Chyou; Yung, Chi Wah; Choi, Kai Chow; Lam, Linda Chiu Wa

doi:10.1016/j.clnu.2010.12.004

Cited by 69 publications

(80 citation statements)

References 36 publications

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“…Sun et al performed a randomized, double-blind, placebo-controlled study in Taiwanese patients with mild to moderate Alzheimer ' s dementia, and found that although a 26-week multivitamin supplement containing vitamins B6, B12 and folic acid was effective to decrease Hcy concentrations, no signifi cant differences in cognition or performance of activities of daily living function were found between multivitamin and placebo (30) . In the latter study, Kwok et al found the concentration of Hcy was reduced to nearly 9 μ mol/L in a group of mild to moderate Alzheimer's disease patients supplemented with methylcobalamin and folic acid for 24 months as compared with a placebo group, but no signifi cant difference in any of the neuropsychological scores could be recorded between supplement group and placebo (31) . Since it is now well established that periconceptional folate supplementation is effective to reduce the risk of neural tube defects, the question as to whether Hcylowering therapy would be also effective for reducing the risk of other pregnancy complications is probably pleonastic and anachronistic (32) .…”

Section: Where Do We Go From Here ?mentioning

confidence: 99%

Hyperhomocysteinemia in health and disease: where we are now, and where do we go from here?

Lippi

Plebani

2012

Clinical Chemistry and Laboratory Medicine (CCLM)

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Homocysteine is a sulfur-containing amino acid, which is synthesized from the precursor methionine through a multi-step process, and then reconverted to methionine or catabolyzed into cysteine. The presence of vitamin B9 (folic acid), vitamin B6 (pyridoxine) and vitamin B12 (cobalamin) is essential in homocysteine metabolism, wherein defi ciency of one or more of these nutrients is associated with various degree of hyperhomocysteinemia. There is little doubt that hyperhomocysteinemia is associated with several human disorders, such as cardiovascular disease, neurodegenerative disorders, pregnancy complications and fractures, so that its measurement might be useful for risk assessment. Nevertheless, several randomized homocysteine-lowering therapy trials have failed to show that supplementation with vitamins B substantially modifi es (and -more importantly -improves) the end points and the related outcomes. According to the current state of scientifi c knowledge, it seems thus reasonable to conclude that lowering homocysteine alone is probably insuffi cient to mitigate the risk of thromboembolic, cardiovascular and neurodegenerative disorders inasmuch as this bizarre amino acid acts in strict synergy with other probably more powerful risk factors. Several lines of evidence suggest, however, that its measurement may be helpful for identifying subjects at greater risk of disease, who may thus benefi t from a more aggressive treatment of other modifi able risk factors, as recently shown by result of the 5-year Fenofi brate Intervention and Event Lowering in Diabetes (FIELD) trial.

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Section: Where Do We Go From Here ?mentioning

confidence: 99%

Hyperhomocysteinemia in health and disease: where we are now, and where do we go from here?

Lippi

Plebani

2012

Clinical Chemistry and Laboratory Medicine (CCLM)

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“…Many of these trials however were of insufficient power and duration to detect an effect or included participants with existing optimal B-vitamin status or with advanced dementia, where a beneficial effect is not likely (60,62,(67)(68)(69)(70) . Notably, two similarly designed homocysteine-lowering trials have yielded conflicting results.…”

Section: Evidence Linking B-vitamins With Brain Health In Ageingmentioning

confidence: 99%

Emerging roles for folate and related B-vitamins in brain health across the lifecycle

et al. 2014

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Nutrition plays a fundamental role in supporting the structural and functional development of the human brain from conception, throughout early infancy and extending into later life. A growing body of evidence suggests that folate and the metabolically related B-vitamins are essential for brain health across all age groups, owing to their specific roles in C 1 metabolism and particularly in the production of S-adenosylmethionine, a universal methyl donor essential for the production of neurotransmitters. Emerging, though not entirely consistent, evidence suggests that maternal folate status throughout pregnancy may influence neurodevelopment and behaviour of the offspring. Furthermore optimal B-vitamin status is associated with better cognitive health in ageing. Of note, a recent clinical trial provided evidence that supplementation with folic acid and related B-vitamins over a 2-year-period reduced global and regional brain atrophy, as measured by MRI scan in older adults. In terms of potential mechanisms, the effects of these B-vitamins on cognitive health may be independent or may be mediated by nutrient-nutrient and/or relevant gene-nutrient interactions. Furthermore, a new area of research suggests that the in utero environment influences health in later life. Folate, an important cofactor in C 1 metabolism, is indirectly involved in DNA methylation, which in turn is considered to be one of the epigenetic mechanisms that may underlie fetal programming and brain development. The present review will explore the evidence that supports a role for folate and the related B-vitamins in brain health across the lifecycle, and potential mechanisms to explain such effects.

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“…70 However, lowering homocysteine levels in dementia patients does not appear to reduce global cognitive decline. 71 The Neurodegenerative Hypothesis of Cognitive Impairment The vascular risk factors and brain abnormalities mentioned above can only partly explain the high frequency of vasculopathy-related cognitive disorders observed in CKD patients. Hence, other disease mechanisms are necessarily involved.…”

Section: Potential Causes Of Cognitive Impairment In Patients With Ckdmentioning

confidence: 99%

Cognitive Disorders and Dementia in CKD

Bugnicourt

Godefroy

Chillon

et al. 2013

Journal of the American Society of Nephrology

474

431

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Epidemiologic data suggest that individuals at all stages of CKD have a higher risk of developing cognitive disorders and dementia. This risk is generally explained by the high prevalence of both symptomatic and subclinical ischemic cerebrovascular lesions. However, other potential mechanisms, including direct neuronal injury by uremic toxins, could also be involved, especially in the absence of obvious cerebrovascular disease. We discuss the prevalence and characteristics of cognitive disorders and dementia in patients with CKD, brain imaging findings, and traditional and nontraditional risk factors. Understanding the pathophysiologic interactions between renal impairment and brain function is important in order to minimize the risk for future cognitive impairment.

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A randomized placebo controlled trial of homocysteine lowering to reduce cognitive decline in older demented people

Cited by 69 publications

References 36 publications

Hyperhomocysteinemia in health and disease: where we are now, and where do we go from here?

Hyperhomocysteinemia in health and disease: where we are now, and where do we go from here?

Emerging roles for folate and related B-vitamins in brain health across the lifecycle

Cognitive Disorders and Dementia in CKD

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