Is High Homocysteine Level a Risk Factor for Cognitive Decline in Elderly? A Systematic Review, Meta-Analysis, and Meta-Regression

Ho, Roger; Cheung, Mike W.‐L.; Fu, Erin; Win, Hlaing H.; Zaw, Min Htet; Ng, Amanda Yunn Ee; Mak, Anselm

doi:10.1097/jgp.0b013e3181f17eed

Cited by 91 publications

(58 citation statements)

References 35 publications

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“…Folate deficiency results in elevated levels of plasma homocysteine, which have been associated with cardiovascular disease [2], neurodegeneration [3], impaired cognitive function [4,5], the development of Alzheimer's disease (AD) [6][7][8], and vascular dementia [9][10][11]. However, the neurodegeneration link remains controversial, since other studies have shown no association [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Elevated levels of plasma homocysteine, deficiencies in dietary folic acid and uracil–DNA glycosylase impair learning in a mouse model of vascular cognitive impairment

Jadavji

Farr

Lips

et al. 2015

Behavioural Brain Research

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(2015) Elevated levels of plasma homocysteine, deficiencies in dietary folic acid and uracil-DNA glycosylase impair learning in a mouse model of vascular cognitive impairment. Behavioural Brain Research, 283 . pp. 215-226. ISSN 1872-7549 Access from the University of Nottingham repository: http://eprints.nottingham.ac.uk/32983/9/UNG_FADD_20140826_manuscript_final.pdf Copyright and reuse:The Nottingham ePrints service makes this work by researchers of the University of Nottingham available open access under the following conditions. This article is made available under the Creative Commons Attribution Non-commercial No Derivatives licence and may be reused according to the conditions of the licence. For more details see: http://creativecommons.org/licenses/by-nc-nd/2.5/ A note on versions:The version presented here may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the repository url above for details on accessing the published version and note that access may require a subscription.For more information, please contact eprints@nottingham.ac.uk Elevated levels of plasma homocysteine, deficiencies in dietary folic acid and uracil-DNA glycosylase impair learning in a mouse model of vascular cognitive impairment. ABSTRACTDietary deficiencies in folic acid result in elevated levels of plasma homocysteine, which has been associated with the development of dementia and other neurodegenerative disorders.Previously, we have shown that elevated levels of plasma homocysteine in mice deficient for a DNA repair enzyme, uracil-DNA glycosylase (UNG), result in neurodegeneration. The goal of this study was to evaluate how deficiencies in folic acid and UNG along with elevated levels of homocysteine affect vascular cognitive impairment, via chronic hypoperfusion in an animal model. Ung+/+ and Ung−/− mice were placed on either control (CD) or folic acid deficient (FADD) diets. Six weeks later, the mice either underwent implantation of microcoils around both common carotid arteries. Post-operatively, behavioral tests began at 3-weeks, angiography was measured after 5-weeks using MRI to assess vasculature and at completion of study plasma and brain tissue was collected for analysis. Learning impairments in the Morris water maze (MWM) were observed only in hypoperfused Ung−/− FADD mice and these mice had significantly higher plasma homocysteine concentrations. Interestingly, Ung+/+ FADD produced significant remodeling of the basilar artery and arterial vasculature. Increased expression of GFAP was observed in the dentate gyrus of Ung−/− hypoperfused and FADD sham mice. Chronic hypoperfusion resulted in increased cortical MMP-9 protein levels of FADD hypoperfused mice regardless of genotypes. These results suggest that elevated levels of homocysteine only, as a result of dietary folic acid deficiency, don't lead to memory impairments and neurobiochemical changes. Rather a combination of either chronic hypoperfusion o...

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Section: Introductionmentioning

confidence: 99%

Elevated levels of plasma homocysteine, deficiencies in dietary folic acid and uracil–DNA glycosylase impair learning in a mouse model of vascular cognitive impairment

Jadavji

Farr

Lips

et al. 2015

Behavioural Brain Research

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“…Nine crosssectional studies were identifi ed, showing that older adults with high Hcy had an OR of 1.70 (95 % CI 1.38 -2.08) for depression. More recently, Ho et al carried out randomeffects meta-analyses on studies investigating the relationship between Hcy and risk of developing dementia/cognitive decline (23) . Seventeen pertinent studies (13 cross-sectional and 4 prospective) including 6122 participants were fi nally included in the meta-analysis.…”

Section: Neurodegenerative Diseasesmentioning

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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“…2 A recent meta-analysis of four prospective studies reported that high homocysteine levels were associated with a 34 per cent increased risk of developing dementia, although this difference was not statistically significant. 3 Another recent meta-analysis of 17 studies encompassing 6122 patients showed that homocysteine levels were elevated in Alzheimer's disease (standardised mean difference [SMD] 0.59) and higher still in vascular dementia (SMD 1.30) than in controls. 3 Hyperhomocysteinaemia seems to be associated with an increased risk of arterial ischemic events, such as myocardial infarctions, peripheral vascular disease and stroke.…”

Section: Homocysteine and B Vitaminsmentioning

confidence: 99%

“…3 Another recent meta-analysis of 17 studies encompassing 6122 patients showed that homocysteine levels were elevated in Alzheimer's disease (standardised mean difference [SMD] 0.59) and higher still in vascular dementia (SMD 1.30) than in controls. 3 Hyperhomocysteinaemia seems to be associated with an increased risk of arterial ischemic events, such as myocardial infarctions, peripheral vascular disease and stroke. 4 Certain B vitamins -specifically folate (vitamin B 9 ), B 6 and B 12 reduce blood homocysteine levels.…”

Section: Homocysteine and B Vitaminsmentioning

confidence: 99%

Does nutrition have a role in the prevention of Alzheimer's disease?

Greener¹

2012

Prog Neurol Psychiatry

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Is High Homocysteine Level a Risk Factor for Cognitive Decline in Elderly? A Systematic Review, Meta-Analysis, and Meta-Regression

Cited by 91 publications

References 35 publications

Elevated levels of plasma homocysteine, deficiencies in dietary folic acid and uracil–DNA glycosylase impair learning in a mouse model of vascular cognitive impairment

Elevated levels of plasma homocysteine, deficiencies in dietary folic acid and uracil–DNA glycosylase impair learning in a mouse model of vascular cognitive impairment

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

Does nutrition have a role in the prevention of Alzheimer's disease?

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