Folic Acid Treatment for Patients With Vascular Cognitive Impairment: A Systematic Review and Meta-Analysis

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 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. METHODS: We conducted a systematic review and meta-analysis of research on folic acid treatments for vascular cognitive impairment. Only randomized controlled trials studies that compared the efficacy of folic acid with 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, cognitive function domain, and concentration of homocysteine. RESULTS: We found 3 studies comparing folic acid with placebo and 1 study comparing folic acid with other interventions. There is only slight evidence that the Mini-Mental State Examination score in patients who received folic acid increased 0.3 point higher compared with the placebo group after 24 months (95% CI = −0.12 to 0.37; P = .31). There is very strong evidence that the concentration of homocysteine in the folic acid group became 6.16 μmol/L lower compared with the placebo group after 6 months (95% CI = 2.32 to 8.21 lower; P < .001). CONCLUSIONS: Our review shows the effectiveness of folic acid in lowering the plasma homocysteine concentration after 6 months compared with placebo. However, this effect was not accompanied by improvement in cognitive function. Study registration: CRD42020199433 https://www.crd.york.ac.uk/prospero/export_details_pdf.php)