Vitamin B₁₂ status, cognitive decline and dementia: a systematic review of prospective cohort studies

Br J Nutr. 2012 Dec 14;108(11):1948-61. doi: 10.1017/S0007114512004175. Epub 2012 Oct 19.


Poor vitamin B₁₂ status may lead to the development of cognitive decline and dementia but there is a large variation in the quality, design of and results reported from these investigations. We have undertaken a systematic review of the evidence for the association between vitamin B₁₂ status and cognitive decline in older adults. A database search of the literature to 2011 was undertaken, using keywords related to vitamin B₁₂ and cognition. All prospective cohort studies assessing the association of serum vitamin B₁₂ or biomarkers were included. Quality assessment and extraction of the data were undertaken by two researchers. The quality assessment tool assigns a positive, neutral or negative rating. Of 3772 published articles, thirty-five cohort studies (n 14 325 subjects) were identified and evaluated. No association between serum vitamin B₁₂ concentrations and cognitive decline or dementia was found. However, four studies that used newer biomarkers of vitamin B₁₂ status (methylmalonic acid and holotranscobalamin (holoTC)) showed associations between poor vitamin B₁₂ status and the increased risk of cognitive decline or dementia diagnosis. In general, the studies were of reasonable quality (twenty-one positive, ten neutral and four negative quality) but of short duration and inadequate subject numbers to determine whether an effect exists. Future studies should be of adequate duration (at least 6 years), recruit subjects from the seventh decade, choose markers of vitamin B₁₂ status with adequate specificity such as holoTC and/or methylmalonic acid and employ standardised neurocognitive assessment tools and not screening tests in order to ascertain any relationship between vitamin B₁₂ status and cognitive decline.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers
  • Cognition
  • Cognition Disorders / blood
  • Cognition Disorders / etiology*
  • Cognition Disorders / physiopathology
  • Cognitive Dysfunction / blood
  • Cognitive Dysfunction / etiology
  • Cognitive Dysfunction / physiopathology
  • Dementia / blood
  • Dementia / etiology*
  • Dementia / physiopathology
  • Disease Progression
  • Female
  • Humans
  • Male
  • Methylmalonic Acid / blood
  • Middle Aged
  • Nutritional Status
  • Transcobalamins / analysis
  • Vitamin B 12 / blood
  • Vitamin B 12 Deficiency / physiopathology*


  • Biomarkers
  • Transcobalamins
  • Methylmalonic Acid
  • Vitamin B 12