Effects of Vitamin D3 Combined with Folic Acid on Domain and Specific Cognitive Function among Patients with Mild Cognitive Impairment: A Randomized Clinical Trial

Introduction: To investigate the effect of vitamin D3 (VD3) combined with folic acid (FA) intervention on the cognitive function among patients with mild cognitive impairment (MCI) and vitamin D deficiency. Methods: Our study is a single-center, randomized, controlled trial. A total of 402 patients were randomly assigned to the placebo group (n=135), FA group (n=134), and FA+1600IU VD3 group (n=133). The intervention period was 24 weeks. The primary endpoint was the mean change in Montreal Cognitive Assessment (MoCA) compared to baseline. Secondary endpoints included other cognitive functions, serum vitamin D, folic acid, and homocysteine levels. Results: The Intention-to-Treat analysis results of MoCA showed that the adjusted Least Squares Means (LSM) differences between the FA+1600IU VD3 group and the placebo or FA group were 0.456 (95% CI −0.198 to 1.11; p=0.171) and 0.038 (95% CI −0.600 to 0.676; p=0.907), respectively, and the Per-protocol set analysis results showed that the adjusted LSM differences between the FA+1600IU VD3 group and the placebo or FA group were 0.659 (95% CI 0.005 to 1.313; p=0.048) and 0.251 (95% CI −0.387 to 0.889; p=0.44), respectively. Conclusion: The effect of FA+1600IU VD3 intervention for 6 months on overall cognitive function in MCI patients with vitamin D deficiency was not significant, but its role may be underestimated and requires further long-term studies to confirm.