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Cognitive impairment and vitamin B12: a review

Published online by Cambridge University Press:  06 January 2012

Eileen Moore*
Department of Psychiatry, The University of Melbourne, Department of Surgery, The Geelong Hospital, Barwon Health, Geelong, Victoria, Australia
Alastair Mander
Barwon Health, Geelong, Victoria, Australia
David Ames
National Ageing Research Institute (NARI), The University of Melbourne, Royal Melbourne Hospital, Melbourne, Victoria, Australia
Ross Carne
Geelong Clinical School, Deakin University, Department of Neurosciences, The Geelong Hospital, Barwon Health, Geelong, Victoria, Australia
Kerrie Sanders
NorthWest Academic Centre, The University of Melbourne, Department of Medicine, Western Health, St Albans, Victoria, Australia
David Watters
Department of Surgery, Deakin University, The Geelong Hospital, Barwon Health, Geelong, Victoria, Australia
Correspondence should be addressed to: Eileen Mary Moore, Department of Surgery, Barwon Health, The Geelong Hospital, PO Box 281, Geelong, Victoria 3220, Australia. Phone: +61 352267899; Fax: +61 352267019. Email:,


Background: This review examines the associations between low vitamin B12 levels, neurodegenerative disease, and cognitive impairment. The potential impact of comorbidities and medications associated with vitamin B12 derangements were also investigated. In addition, we reviewed the evidence as to whether vitamin B12 therapy is efficacious for cognitive impairment and dementia.

Methods: A systematic literature search identified 43 studies investigating the association of vitamin B12 and cognitive impairment or dementia. Seventeen studies reported on the efficacy of vitamin B12 therapy for these conditions.

Results: Vitamin B12 levels in the subclinical low-normal range (<250 ρmol/L) are associated with Alzheimer's disease, vascular dementia, and Parkinson's disease. Vegetarianism and metformin use contribute to depressed vitamin B12 levels and may independently increase the risk for cognitive impairment. Vitamin B12 deficiency (<150 ρmol/L) is associated with cognitive impairment. Vitamin B12 supplements administered orally or parenterally at high dose (1 mg daily) were effective in correcting biochemical deficiency, but improved cognition only in patients with pre-existing vitamin B12 deficiency (serum vitamin B12 levels <150 ρmol/L or serum homocysteine levels >19.9 μmol/L).

Conclusion: Low serum vitamin B12 levels are associated with neurodegenerative disease and cognitive impairment. There is a small subset of dementias that are reversible with vitamin B12 therapy and this treatment is inexpensive and safe. Vitamin B12 therapy does not improve cognition in patients without pre-existing deficiency. There is a need for large, well-resourced clinical trials to close the gaps in our current understanding of the nature of the associations of vitamin B12 insufficiency and neurodegenerative disease.

Review Article
Copyright © International Psychogeriatric Association 2012

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