title: Homocysteine, B Vitamins, and Cognitive Impairment.
abstract: Moderately elevated plasma total homocysteine (tHcy) is a strong modifiable risk factor for vascular dementia and Alzheimer's disease. Prospectively, elevated tHcy is associated with cognitive decline, white matter damage, brain atrophy, neurofibrillary tangles, and dementia. Most homocysteine-lowering trials with folate and vitamins B6 and/or B12 tested as protective agents against cognitive decline were poorly designed by including subjects unlikely to benefit during the trial period. In contrast, trials in high-risk subjects, which have taken into account the baseline B vitamin status, show a slowing of cognitive decline and of atrophy in critical brain regions, results that are consistent with modification of the Alzheimer's disease process. Homocysteine may interact with both risk factors and protective factors, thereby identifying people at risk but also providing potential strategies for early intervention. Public health steps to slow cognitive decline should be promoted in individuals who are at risk of dementia, and more trials are needed to see if simple interventions with nutrients can prevent progression to dementia.
authors.affiliation: OPTIMA, Department of Pharmacology, University of Oxford, Oxford OX1 3QT, United Kingdom; email: david.smith@pharm.ox.ac.uk.
authors.forename: A David
authors.initials: AD
authors.lastname: Smith
authors.affiliation: OPTIMA, Department of Pharmacology, University of Oxford, Oxford OX1 3QT, United Kingdom; email: david.smith@pharm.ox.ac.uk.|Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, 0316 Oslo, Norway; email: helga.refsum@medisin.uio.no.
authors.forename: Helga
authors.initials: H
authors.lastname: Refsum
mesh_terms: D000375:Aging; D000818:Animals; D015415:Biomarkers; D002560:Cerebrovascular Circulation; D003072:Cognition Disorders / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D060825:Cognitive Dysfunction / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control; D019587:Dietary Supplements / Q000009:adverse effects; D019317:Evidence-Based Medicine; D005492:Folic Acid / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D006710:Homocysteine / Q000097:blood / Q000378:metabolism; D006801:Humans; D020138:Hyperhomocysteinemia / Q000178:diet therapy* / Q000453:epidemiology / Q000378:metabolism / Q000503:physiopathology; D019636:Neurodegenerative Diseases / Q000453:epidemiology / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D018697:Nootropic Agents / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use; D009752:Nutritional Status; D017410:Practice Guidelines as Topic; D012307:Risk Factors; D014805:Vitamin B 12 / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D025101:Vitamin B 6 / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; D018697:Nootropic Agents; D006710:Homocysteine; D025101:Vitamin B 6; D005492:Folic Acid; D014805:Vitamin B 12
keywords: Alzheimer's disease; clinical trial; cobalamin (vitamin B12); cognition; dementia; folate