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OPTIMA - VITACOG - Clinical Trial of B vitamins for prevention of age-related cognitive decline and dementia

Jacoby R, Smith AD, Refsum H (2015) Oxford Project to Investigate Memory and Ageing - OPTIMA   University of Oxford

Web URL: Further information on OPTIMA and VITACOG is available via the University of Oxford website here


Elevated blood concentrations of total homocysteine and low-normal concentrations of B vitamins (folate, vitamin B12  and vitamin B6) are candidate risk factors for both Alzheimer’s disease and vascular dementia.

Raised plasma total homocysteine is a strong prognostic marker of future cognitive decline.

Low-normal concentrations of the B vitamins, the main determinant of homocysteine concentrations occur in particularly vulnerable sections of the population, such as infants and the elderly. 

VITACOG, a two-year randomised, placebo-controlled pilot trial, was developed as part of the Oxford Project to Investigate Memory and Ageing (OPTIMA) in order to determine the effect of treatment (vitamins B6, B12 and folic acid) on the rate of shrinkage of the brain and on memory function in people over 70 years with Mild Cognitive Impairment (MCI). 

Additional objectives were to determine

  • the effectiveness of recruitment procedure
  • the proportion of participants responding biochemically to treatment as predicted
  • the acceptability of cognitive tests and
  • within-person variability for future power calculations. 

Participants had neuropsychological assessments, MRI brain imaging, blood and urine tests and examination of vital signs (heart rate and blood pressure).


This groundbreaking clinical trial based at Oxford University has led to pioneering findings concerning the role of both B vitamins (B6, B12 and folate) and omega-3 fatty acids in the prevention of cognitive decline and dementia.

In summary, this two-year randomised controlled trial, involving adults aged 70+ with Mild Cognitive Impairment, showed

(1) significant benefits from high-dose supplementation with Vitamins B6 B12 and folate in adults aged 70+ with Mild Cognitive Impairment, in terms of:
  • reduced physical brain shrinkage and
  • slowed cognitive decline 
(2) that these beneficial effects of B vitamins depend  on omega-3 fatty acid status.  No reductions in physical brain atrophy and cognitive decline were found for participants with low plasma omega-3 levels at baseline.

For news items explaining some of the study's findings, see: 

And for some of the key research papers from OPTIMA / VITACOG, see: