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Research Article

Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial

  • A. David Smith equal contributor mail,

    equal contributor Contributed equally to this work with: A. David Smith, Helga Refsum

    david.smith@pharm.ox.ac.uk

    Affiliations: Oxford Project to Investigate Memory and Ageing (OPTIMA), University of Oxford, Oxford, United Kingdom, University Department of Pharmacology and Department of Physiology, Anatomy & Genetics, University of Oxford, Oxford, United Kingdom

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  • Stephen M. Smith,

    Affiliation: Department of Clinical Neurology, Oxford Centre for Functional Magnetic Resonance Imaging of the Brain, University of Oxford, Oxford, United Kingdom

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  • Celeste A. de Jager,

    Affiliation: Oxford Project to Investigate Memory and Ageing (OPTIMA), University of Oxford, Oxford, United Kingdom

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  • Philippa Whitbread,

    Affiliation: Oxford Project to Investigate Memory and Ageing (OPTIMA), University of Oxford, Oxford, United Kingdom

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  • Carole Johnston,

    Affiliations: Oxford Project to Investigate Memory and Ageing (OPTIMA), University of Oxford, Oxford, United Kingdom, University Department of Pharmacology and Department of Physiology, Anatomy & Genetics, University of Oxford, Oxford, United Kingdom

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  • Grzegorz Agacinski,

    Affiliation: Oxford Project to Investigate Memory and Ageing (OPTIMA), University of Oxford, Oxford, United Kingdom

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  • Abderrahim Oulhaj,

    Affiliation: Oxford Project to Investigate Memory and Ageing (OPTIMA), University of Oxford, Oxford, United Kingdom

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  • Kevin M. Bradley,

    Affiliation: Department of Radiology and Nuclear Medicine, Oxford Radcliffe Hospitals NHS Trust, Oxford, United Kingdom

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  • Robin Jacoby,

    Affiliation: University Department of Psychiatry, University of Oxford, Oxford, United Kingdom

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  • Helga Refsum equal contributor

    equal contributor Contributed equally to this work with: A. David Smith, Helga Refsum

    Affiliations: Oxford Project to Investigate Memory and Ageing (OPTIMA), University of Oxford, Oxford, United Kingdom, University Department of Pharmacology and Department of Physiology, Anatomy & Genetics, University of Oxford, Oxford, United Kingdom, Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway

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  • Published: September 08, 2010
  • DOI: 10.1371/journal.pone.0012244

About the Authors

A. David Smith, Celeste A. de Jager, Philippa Whitbread, Carole Johnston, Grzegorz Agacinski, Abderrahim Oulhaj, Helga Refsum
Oxford Project to Investigate Memory and Ageing (OPTIMA), University of Oxford, Oxford, United Kingdom
A. David Smith, Carole Johnston, Helga Refsum
University Department of Pharmacology and Department of Physiology, Anatomy & Genetics, University of Oxford, Oxford, United Kingdom
Stephen M. Smith
Department of Clinical Neurology, Oxford Centre for Functional Magnetic Resonance Imaging of the Brain, University of Oxford, Oxford, United Kingdom
Kevin M. Bradley
Department of Radiology and Nuclear Medicine, Oxford Radcliffe Hospitals NHS Trust, Oxford, United Kingdom
Robin Jacoby
University Department of Psychiatry, University of Oxford, Oxford, United Kingdom
Helga Refsum
Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway

Corresponding Author

Email: david.smith@pharm.ox.ac.uk

Competing Interests

Dr. A. D. Smith is named as an inventor on two patents held by the University of Oxford on the use of folic acid to treat Alzheimer's disease (US6008221; US6127370); under the University's rules he could benefit financially if the patent is exploited. Drs. Refsum and A. D. Smith report having in the past received speaking honoraria from Recip AB, the company that donated the vitamin tablets, and from Axis-Shield, who make the equipment used to assay homocysteine. These competing interests do not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials. None of the other authors have any financial disclosures.

Author Contributions

Conceived and designed the experiments: ADS CAdJ KMB RJ HR. Performed the experiments: SMS CAdJ PW CJ KMB RJ. Analyzed the data: ADS SMS CAdJ PW CJ GA AO HR. Contributed reagents/materials/analysis tools: CJ GA AO KMB RJ. Wrote the paper: ADS HR. Critically reviewed the manuscript: ADS SMS CAdJ PW CJ GA KMB RJ HR. Critically reviewed the manuscript, notably the statistics: AO.