Elevated plasma
homocysteine (Hcy) concentrations have been implicated with risk of
cognitive impairment and
dementia, but it is unclear whether low
vitamin B12 or
folate status is responsible for
cognitive decline. Most studies reporting associations between cognitive function and Hcy or
B-vitamins have used a cross-sectional or case-control design and have been unable to exclude the possibility that such associations are a result of the disease rather than being causal. The Hcy hypothesis of
dementia has attracted considerable interest, as Hcy can be easily lowered by
folic acid and
vitamin B12, raising the prospect that
B-vitamin supplementation could lower the risk of
dementia. While some trials assessing effects on cognitive function have used
folic acid alone,
vitamin B12 alone or a combination, few trials have included a sufficient number of participants to provide reliable evidence. An individual-patient-data meta-analysis of all randomised trials of the effects on cognitive function and vascular risk of lowering Hcy with
B-vitamins will maximise the power to assess the epidemiologically-predicted differences in risk. Among the twelve large randomised Hcy-lowering trials for prevention of
vascular disease, data should be available on about 30 000 participants with cognitive function. The principal investigators of such trials have agreed to combine individual-participant data from their trials after their separate publication.