The effect of folic acid on vascular cognitive impairment Original paper

In this meta-analysis in people with cognitive impairment due to vascular causes, supplements containing folic acid did not improve cognitive function. The quality of some of these trials was low, and folic acid was never given alone (and often given with other B vitamins), weakening our confidence in the results.

This Study Summary was published on January 4, 2022.


Vascular cognitive impairment refers to a form of cognitive impairment due to a brain injury arising from a vascular cause (e.g., a stroke). Some evidence suggests that high levels of homocysteine may promote the development of vascular injury associated with vascular cognitive impairment, but it is unclear whether lowering homocysteine can benefit cognitive function following the onset of vascular cognitive impairment. This study assessed the effect of folic acid (a homocysteine-lowering vitamin) on cognitive function in people with vascular cognitive impairment.

The study

This meta-analysis of 5 randomized trials (4 placebo-controlled and 1 open-label) assessed the effect of folic acid supplementation on cognitive function in people with vascular cognitive decline. The trials included 418 participants and had durations of 6 to 24 months. In all trials, folic acid was given along with vitamin B12 (3 trials), vitamin B6 (3 trials), vitamin B2 (1 trial), and aspirin (1 trial).

The primary outcome was cognitive function assessed using the Mini Mental State Exam (MMSE), a common cognitive test used to evaluate cognitive decline and diagnose dementia. Cognitive function was assessed at 6 months (2 trials) and 24 months (3 trials). The other outcome was homocysteine level (5 trials). The trials were assessed for risk of bias using the Cochrane risk-of-bias tool.

The results

Folic acid supplementation lowered homocysteine but did not improve cognitive function after either 6 months or 12 months.

The included studies were rated as low to medium quality.

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This Study Summary was published on January 4, 2022.