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J Alzheimers Dis. 2018;62(2):561-570. doi: 10.3233/JAD-171042.

Homocysteine and Dementia: An International Consensus Statement.

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


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.


Alzheimer’s disease; Homocysteine; brain atrophy; causation; cobalamin; cognitive impairment; dementia; folate; risk-factor; vitamin B12; vitamin B6

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