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Homocysteine and Dementia: An International Consensus Statement.
J Alzheimers Dis. 2018; 62(2):561-570.JA

Abstract

Identification of modifiable risk factors provides a crucial approach to the prevention of dementia. Nutritional or nutrient-dependent risk factors are especially important because dietary modifications or use of dietary supplements may lower the risk factor level. One such risk factor is a raised concentration of the biomarker plasma total homocysteine, which reflects the functional status of three B vitamins (folate, vitamins B12, B6). A group of experts reviewed literature evidence from the last 20 years. We here present a Consensus Statement, based on the Bradford Hill criteria, and conclude that elevated plasma total homocysteine is a modifiable risk factor for development of cognitive decline, dementia, and Alzheimer's disease in older persons. In a variety of clinical studies, the relative risk of dementia in elderly people for moderately raised homocysteine (within the normal range) ranges from 1.15 to 2.5, and the Population Attributable risk ranges from 4.3 to 31%. Intervention trials in elderly with cognitive impairment show that homocysteine-lowering treatment with B vitamins markedly slows the rate of whole and regional brain atrophy and also slows cognitive decline. The findings are consistent with moderately raised plasma total homocysteine (>11 μmol/L), which is common in the elderly, being one of the causes of age-related cognitive decline and dementia. Thus, the public health significance of raised tHcy in the elderly should not be underestimated, since it is easy, inexpensive, and safe to treat with B vitamins. Further trials are needed to see whether B vitamin treatment will slow, or prevent, conversion to dementia in people at risk of cognitive decline or dementia.

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Authors+Show Affiliations

Smith AD
OPTIMA, Department of Pharmacology, University of Oxford, Oxford, UK.
Refsum H
Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Norway.
Bottiglieri T
Center of Metabolomics, Institute of Metabolic Disease, Baylor Scott & White Research Institute, Dallas, TX, USA.
Fenech M
Genome Health and Personalised Nutrition Laboratory, CSIRO Health and Biosecurity, Adelaide BC, SA, Australia.
Hooshmand B
Aging Research Centre, Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden.
McCaddon A
Cardiff University, School of Medicine, Gwenfro Units 6/7, Wrexham, UK.
Miller JW
Department of Nutritional Sciences, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.
Rosenberg IH
Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA.
Obeid R
Department of Clinical Chemistry and Laboratory Medicine, University Hospital of the Saarland, Germany.

MeSH

CognitionCognitive DysfunctionConsensusDementiaDietary SupplementsHomocysteineHumansMeta-Analysis as TopicReview Literature as TopicRisk FactorsVitamin B Complex

Pub Type(s)

Editorial

Language

eng

PubMed ID

29480200

Citation

Smith, A David, et al. "Homocysteine and Dementia: an International Consensus Statement." Journal of Alzheimer's Disease : JAD, vol. 62, no. 2, 2018, pp. 561-570.
Smith AD, Refsum H, Bottiglieri T, et al. Homocysteine and Dementia: An International Consensus Statement. J Alzheimers Dis. 2018;62(2):561-570.
Smith, A. D., Refsum, H., Bottiglieri, T., Fenech, M., Hooshmand, B., McCaddon, A., Miller, J. W., Rosenberg, I. H., & Obeid, R. (2018). Homocysteine and Dementia: An International Consensus Statement. Journal of Alzheimer's Disease : JAD, 62(2), 561-570. https://doi.org/10.3233/JAD-171042
Smith AD, et al. Homocysteine and Dementia: an International Consensus Statement. J Alzheimers Dis. 2018;62(2):561-570. PubMed PMID: 29480200.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Homocysteine and Dementia: An International Consensus Statement. AU - Smith,A David, AU - Refsum,Helga, AU - Bottiglieri,Teodoro, AU - Fenech,Michael, AU - Hooshmand,Babak, AU - McCaddon,Andrew, AU - Miller,Joshua W, AU - Rosenberg,Irwin H, AU - Obeid,Rima, PY - 2018/2/27/entrez PY - 2018/2/27/pubmed PY - 2019/2/9/medline KW - Alzheimer’s disease KW - Homocysteine KW - brain atrophy KW - causation KW - cobalamin KW - cognitive impairment KW - dementia KW - folate KW - risk-factor KW - vitamin B12 KW - vitamin B6 SP - 561 EP - 570 JF - Journal of Alzheimer's disease : JAD JO - J Alzheimers Dis VL - 62 IS - 2 N2 - Identification of modifiable risk factors provides a crucial approach to the prevention of dementia. Nutritional or nutrient-dependent risk factors are especially important because dietary modifications or use of dietary supplements may lower the risk factor level. One such risk factor is a raised concentration of the biomarker plasma total homocysteine, which reflects the functional status of three B vitamins (folate, vitamins B12, B6). A group of experts reviewed literature evidence from the last 20 years. We here present a Consensus Statement, based on the Bradford Hill criteria, and conclude that elevated plasma total homocysteine is a modifiable risk factor for development of cognitive decline, dementia, and Alzheimer's disease in older persons. In a variety of clinical studies, the relative risk of dementia in elderly people for moderately raised homocysteine (within the normal range) ranges from 1.15 to 2.5, and the Population Attributable risk ranges from 4.3 to 31%. Intervention trials in elderly with cognitive impairment show that homocysteine-lowering treatment with B vitamins markedly slows the rate of whole and regional brain atrophy and also slows cognitive decline. The findings are consistent with moderately raised plasma total homocysteine (>11 μmol/L), which is common in the elderly, being one of the causes of age-related cognitive decline and dementia. Thus, the public health significance of raised tHcy in the elderly should not be underestimated, since it is easy, inexpensive, and safe to treat with B vitamins. Further trials are needed to see whether B vitamin treatment will slow, or prevent, conversion to dementia in people at risk of cognitive decline or dementia. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/29480200/Homocysteine_and_Dementia:_An_International_Consensus_Statement_ DB - PRIME DP - Unbound Medicine ER -