Homocysteine and Cognitive Decline in Healthy Elderly

McCaddon, Andrew; Hudson, Peter; Davies, Gareth; Hughes, Alan; Williams, John; Wilkinson, Clare

doi:10.1159/000051275

Cited by 192 publications

(139 citation statements)

References 16 publications

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“…There are three main public health concerns with regard to increased plasma homocysteine levels: increased risk of cardiovascular diseases (Clarke et al, 1991;Boushey et al, 1995;Ueland et al, 2000), reproductive hazards (Wouters et al, 1993;Goddijn-Wessel et al, 1996;Leeda et al, 1998;Sorensen et al, 1999;Nelen et al, 2000;Vollset et al, 2000a, b;Refsum, 2001) and the possible association to cognitive disorders (Clarke et al, 1998;McCaddon et al, 2001;Seshadri et al, 2002). The effect of increased plasma homocysteine levels on certain reproductive hazards is currently accepted as causal, whereas the effect on coronary heart disease is still under investigation and awaits the results of intervention studies (Ubbink & Delport, 2000;Ueland et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Folic acid supplement decreases the homocysteine increasing effect of filtered coffee. A randomised placebo-controlled study

2003

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Objective: Elevated levels of plasma total homocysteine (tHcy) are identified as independent risk factors for coronary heart disease and for fetal neural tube defects. tHcy levels are negatively associated with folic acid, pyridoxine and cobalamine, and positively associated with coffee consumption and smoking. A total of 600 ml of filtered coffee results in a tHcy increase that 200 mg of folic acid or 40 mg of pyridoxine supplementation might eliminate. Design: Randomised, blinded study with two consecutive trial periods. Setting: Free living population. Volunteers. Subjects: A total of 121 healthy, nonsmoking men and women (78%) aged 29-65 y. Interventions: (1) A coffee-free period of 3 weeks, (2) 600 ml coffee/day and a supplement of 200 mg folic acid/day or placebo for 4 weeks, (3) 3-week coffee-free period, (4) 600 ml coffee/day and 40 mg pyridoxine/day or placebo for 4 weeks. Main outcome measures:The difference between the change in tHcy in the supplement group and the change in tHcy in the placebo group during the 4-week trial period. Results: Coffee abstention resulted in a tHcy decrease of 1.04 mmol/l for the whole group. In the subsequent coffee period, a further decrease of 0.17 mmol/l was observed in the folic acid group whereas an increase of 1.26 mmol/l was observed in the placebo group, the difference was 1.43 mmol/l (95% CI: 0.80, 2.07). Pyridoxine supplement had no impact on tHcy levels. Conclusions: Supplementation of 200 mg folic acid/day eliminates the tHcy increasing effect of 600 ml filtered coffee in subjects not already on folic acid supplements. A supplement of 40 mg pyridoxine/day does not have the same effect. Sponsorship: None.

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Section: Discussionmentioning

confidence: 99%

Folic acid supplement decreases the homocysteine increasing effect of filtered coffee. A randomised placebo-controlled study

2003

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“…The association between tHcy and Alzheimer disease is dose dependent and even stronger in those with histopathologically confirmed diagnosis (192 ). Increased tHcy or low folate or cobalamin precedes cognitive decline (194 -196 ): Hyperhomocysteinemic individuals have an increased rate of atrophy of the medial temporal lobe (192 ) and a more rapid decrease in cognitive test scores (194 ). A large prospective study showed that increased tHcy up to 11 years before the diagnosis of dementia is associated with twice the risk of Alzheimer disease (196 ).…”

Section: Psychiatric Disorders and Cognitive Impairmentmentioning

confidence: 99%

Facts and Recommendations about Total Homocysteine Determinations: An Expert Opinion

et al. 2004

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Background: Measurement of plasma total homocysteine has become common as new methods have been introduced. A wide range of disorders are associated with increased concentrations of total homocysteine. The purpose of this review is to provide an international expert opinion on the practical aspects of total homocysteine determinations in clinical practice and in the research setting and on the relevance of total homocysteine measurements as diagnostic or screening tests in several target populations. Methods: Published data available on Medline were used as the basis for the recommendations. Drafts of the recommendations were critically discussed at meetings over a period of 3 years. Outcome: This review is divided into two sections: (a) determination of homocysteine (methods and their performance, sample collection and handling, biological determinants, reference intervals, within-person variability, and methionine loading test); and (b) risk assessment and disease diagnosis (homocystinuria, folate and cobalamin deficiencies, cardiovascular disease, renal failure, psychiatric disorders and cognitive impairment, pregnancy complications and birth defects, and screening of elderly and newborns). Each of these subsections concludes with a separate series of recommendations to assist the clinician and the research scientist in making informed decisions. The review concludes with a list of unresolved questions. © 2004 American Association for Clinical ChemistryIncreased plasma total homocysteine (tHcy) 7 is a sensitive marker of folate and cobalamin (vitamin B 12 ) deficiency (1, 2 ) and an independent risk factor for cardiovascular disease (CVD) (3,4 ). Plasma tHcy concentrations are also related to birth defects (5 ), pregnancy complications (6 ), psychiatric disorders (7 ), and cognitive impairment in the elderly (8 ). The measurement of tHcy in the clinical setting is thus potentially of great importance (9 ).The introduction of tHcy assays in the mid-1980s (10, 11 ) started a new era of research on Hcy. However, it was the advent of immunoassays in the latter half of the 1990s (12, 13 ) that changed tHcy determinations from research tools to widely used clinical chemistry tests. As a result, interest in this field has increased exponentially in both routine diagnostics and research.Although several reviews on tHcy determinations have been published (14 -18 ), few have provided recommendations for their use in clinical practice (19 -23 ). Our aim was to review the practical aspects of tHcy determinations in clinical practice as well as in the research setting and to survey the data on tHcy in diagnostics or as screening tests in several target populations.Ideally, guidelines should be established by a multidisciplinary team including all relevant stakeholders, and the recommendations should be according to evidence-based medicine (24 ). There are not sufficient data in the Hcy field, however, to use such an approach. In particular, -32 (2004) Review 3 data from controlled clinical trials are sparse. Neverth...

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“…Some have shown significant associations between homocysteine levels and cognitive function, 10,[12][13][14][15][16][17][19][20][21][22] whereas others have not. 11,18 An early study involving a small sample of a healthy elderly population in Italy showed no significant correlations between the Mini-Mental State Exam (MMSE) scores and homocysteine levels.…”

Section: Homocysteine and Cognitive Function Scoresmentioning

confidence: 99%

Homocysteine and cognitive function in elderly people

García

Zanibbi²

2004

Canadian Medical Association Journal

111

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DEMENTIA IS HIGHLY PREVALENT AMONG ELDERLY PEOPLE, and projections show that the number of people affected might triple over the next 50 years, mainly because of a large increase in the oldest-old segment of the population. Because of this and the disease's devastating effects, measures for the prevention and early detection of dementia are crucial. Age and years of education are among the most relevant risk factors for dementia, but in recent years the role of homocysteine has also been investigated. Homocysteine is an amino acid produced in the metabolism of methionine, a process dependent on the B vitamins cobalamin, vitamin B 6 and folic acid. There is evidence that increased serum homocysteine levels are associated with declining cognitive function and dementia. We review this evidence in addition to the potential mechanisms through which homocysteine acts on the brain to cause cognitive dysfunction, the metabolism of homocysteine and factors associated with alteration of the normal metabolism.

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Homocysteine and Cognitive Decline in Healthy Elderly

Cited by 192 publications

References 16 publications

Folic acid supplement decreases the homocysteine increasing effect of filtered coffee. A randomised placebo-controlled study

Folic acid supplement decreases the homocysteine increasing effect of filtered coffee. A randomised placebo-controlled study

Facts and Recommendations about Total Homocysteine Determinations: An Expert Opinion

Homocysteine and cognitive function in elderly people

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