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Folic Acid Treatment for Patients with Vascular Cognitive Impairment: A Systematic Review and Meta-Analysis
Abdul Gofir1,2, Samekto Wibowo1,2, Muhammad Hakimi3,4
1Department of Neurology, Faculty of Medicine, Public Health, and Nursing (FKKMK) Universitas Gadjah Mada, Yogyakarta, Indonesia.
Insights
Folic acid effectively lowers homocysteine levels in patients with vascular cognitive impairment (VCI). However, this B vitamin supplement did not show significant improvements in cognitive function in the reviewed studies.
Area of Science:
- Neurology
- Cardiovascular Medicine
- Nutritional Science
Background:
- Increasing life expectancy correlates with a rise in cardiovascular and cerebrovascular diseases, leading to vascular cognitive impairment (VCI).
- Elevated homocysteine levels are implicated in the pathology of cognitive decline.
- Folic acid, a B vitamin, is recognized for its potential to reduce homocysteine concentrations.
Purpose of the Study:
- To systematically evaluate the efficacy of folic acid supplementation in patients diagnosed with vascular cognitive impairment (VCI).
Main Methods:
- A systematic review and meta-analysis of randomized controlled trials (RCTs) comparing folic acid to placebo or other interventions for VCI.
- Searches were conducted across major databases (Medline, EMBASE, Central) up to July 2021.
- Outcomes assessed included changes in Mini-Mental State Examination (MMSE) scores, cognitive function domains, and homocysteine levels.
Main Results:
- Folic acid significantly reduced homocysteine levels by 6.16 μmol/L after 6 months compared to placebo (95% CI: 2.32-8.21 lower; p<0.001).
- A slight, non-significant increase in MMSE scores (0.3 points) was observed in the folic acid group after 24 months (95% CI: -0.12-0.37; p=0.31).
Conclusions:
- Folic acid demonstrates effectiveness in reducing plasma homocysteine concentrations within 6 months.
- The observed reduction in homocysteine by folic acid was not associated with significant improvements in cognitive function in VCI patients.
Background:
As the life expectancy of elderly people has drastically increased, the incidence of cardiovascular and cerebrovascular diseases in this population has proportionally grown. Vascular cognitive impairment (VCI) refers to all forms of cognitive disorder associated with cerebrovascular disease. Homocysteine has recently been recognized as a contributor to the pathomechanisms involved in cognitive impairment. B vitamins, such as folic acid, are known to be effective in lowering homocysteine levels.
Aim Of The Study:
To evaluate the efficacy of folic acid in patients with VCI.
Methods:
We conducted a systematic review and meta-analysis of research on folic acid treatments for VCI. Only randomized controlled trials studies that compared the efficacy of folic acid to placebo or other interventions were considered, irrespective of publication status, year of publication, and languages. Two independent reviewers searched the Medline via Ovid, EMBASE and Cochrane Central Register of Controlled Trials (Central) journal databases up to July 2021 and independently appraised the included studies. We used mean difference outcome with 95% confidence intervals (CI) to calculate the change of Mini-Mental State Examination (MMSE), cognitive function domain, and concentration of homocysteine.
Results:
We found three studies comparing folic acid with placebo and one study comparing folic acid with other interventions. There is only slight evidence that the MMSE score in patients who received Folic Acid increased 0.3 point higher compared to the placebo group after 24 months (95% CI:-0.12-0.37; p=0.31). There is very strong evidence that the concentration of Homocysteine in the Folic Acid group became 6.16 μmol/L lower compared to the placebo group after 6 months (95% CI:2.32-8.21 lower; p<0.001).
Conclusions:
Our review shows the effectiveness of folic acid in lowering plasma homocysteine concentration after 6 months period compared to placebo. However, this effect is not accompanied by improvement in cognitive function.
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