Cognitive Function After Stopping Folic Acid and DHA Intervention: An Extended Follow-Up Results from the Randomized, Double Blind, Placebo-Controlled Trial in Older Adults with Mild Cognitive Impairment.

Background: Our previously randomized controlled trial (RCT) showed daily oral folic acid (FA), docosahexaenoic acid (DHA) and their combined treatment for 6 months could significantly improve cognitive function in mild cognitive impairment (MCI) individuals.

Objective: This study aimed to evaluate whether this benefit seen in the treatment group would sustain after stopping intervention when patients returned to a real-world.

Methods: RCT (ChiCTR-IOR-16008351) was conducted in Tianjin, China. 160 MCI elders aged ≥60 years were randomly divided into four groups: FA + DHA, FA, DHA, and control. 138 MCI elders who completed the 6-month interventional trial underwent another 6-month follow-up without receiving nutritional therapy. Cognitive performance was measured at 6 and 12 months. Blood amyloid-β peptide (Aβ) and homocysteine (Hcy) related biomarkers were measured at baseline and 6 months.

Results: In comparison to the end of nutritional therapy, all intervention groups had considerably lower full-scale IQ, arithmetic, and image completion scores during the follow-up period, while the combined intervention and DHA groups had significantly lower picture arrangement scores. Furthermore, after 6-month treatment with FA and FA + DHA, plasma Aβ₄₀, Aβ₄₂, and Hcy levels were significantly decreased. However, these biomarker levels at the start of follow-up were positively correlated with the degree of cognitive function change during follow-up period.

Conclusions: FA and DHA supplementation enhance cognitive performance in MCI elderly following a six-month intervention by reducing Hcy or Aβ levels. However, their effects on improving cognitive decline are likely to diminish when the intervention is discontinued.