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Plasma vitamin B12 status and cerebral white-matter lesions
  1. L M L de Lau1,2,
  2. A D Smith3,
  3. H Refsum3,4,
  4. C Johnston3,
  5. M M B Breteler1
  1. 1
    Department of Epidemiology & Biostatistics, Erasmus Medical Centre, Rotterdam, The Netherlands
  2. 2
    Department of Neurology, Erasmus Medical Centre, Rotterdam, The Netherlands
  3. 3
    OPTIMA, Department of Physiology, Anatomy & Genetics, Oxford, UK
  4. 4
    Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
  1. Dr M M B Breteler, Department of Epidemiology and Biostatistics, Erasmus Medical Centre, PO Box 2040, 3000 CA Rotterdam, The Netherlands; m.breteler{at}


Background and objective: Elevated homocysteine has been associated with a higher prevalence of cerebral white-matter lesions and infarcts, and worse cognitive performance. This raises the question whether factors involved in homocysteine metabolism, such as vitamin B12, are also related to these outcomes. This study examined the association of several markers of vitamin B12 status with cerebral white-matter lesions, infarcts and cognition.

Methods: The study evaluated the association of plasma concentrations of vitamin B12, methylmalonic acid, holotranscobalamin and transcobalamin saturation with cerebral white-matter lesions and infarcts at baseline and cognition at baseline and during follow-up among 1019 non-demented elderly participants of the population-based Rotterdam Scan Study. Analyses were adjusted for several potential confounders, including homocysteine and folate concentration.

Results: Poorer vitamin B12 status was significantly associated with greater severity of white-matter lesions, in particular periventricular white-matter lesions, in a concentration-related manner. Adjustment for common vascular risk factors (including blood pressure, smoking, diabetes and intima media thickness) did not alter the associations. Adjustment for homocysteine and folate modestly weakened the associations. No association was observed for any of the studied markers of vitamin B12 status with presence of brain infarcts and baseline cognition or cognitive decline during follow-up.

Conclusions: These results indicate that vitamin B12 status in the normal range is associated with severity of white-matter lesions, especially periventricular lesions. Given the absence of an association with cerebral infarcts, it is hypothesised that this association is explained by effects on myelin integrity in the brain rather than through vascular mechanisms.

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  • Funding: This study was supported by grants from the International Foundation for Alzheimer Research (ISAO) (grant number 04520) (MMBB) and the Alzheimer’s Research Trust and Charles Wolfson Charitable Trust (HR, ADS) and in part by an Advanced Research Programme grant from the Norwegian Research Council (NFR 117997/320 NORUT 2003) and The Johan Throne Holst Foundation for Nutrition Research, University of Oslo (HR). Axis-Shield UK kindly donated the magnetic beads used for measurement of holotranscobalamin and transcobalamin.

  • Competing interests: None.

  • Ethics approval: Ethics approval was provided by the Medical Ethics Committee of the Erasmus Medical Centre Rotterdam.

  • Patient consent: Obtained.