Oral folic acid and vitamin B-12 supplementation to prevent cognitive decline in community-dwelling older adults with depressive symptoms--the Beyond Ageing Project: a randomized controlled trial.

Randomized controlled factorial trial in community-dwelling adults aged 60 to 74 years with elevated psychological distress and without dementia, recruited in Australia. The broader trial randomized 909 participants to 8 intervention combinations; per-active-arm sample size was not reported. Cognitive outcomes were assessed at baseline, 12 months, and 24 months.

Daily oral folic acid plus vitamin B-12 was given as one tablet containing 400 μg folic acid and 100 μg vitamin B-12 for 24 months. After a safety review, the regimen changed in July 2007 to 2 daily oral tablets, each containing 200 μg folic acid and 50 μg vitamin B-12, keeping the same total daily dose. The comparator was an identical placebo tablet without active ingredients.

Daily folic acid plus vitamin B-12 improved overall cognitive performance and memory over 24 months compared with placebo, but did not improve other cognitive domains. The omnibus time-by-intervention effect for TICS-M total score was significant (F 2,788.4 = 5.26, P = 0.005), and TICS-M total score increased more from baseline to 24 months in the supplement group than placebo (P = 0.032, effect size = 0.17). Immediate recall also improved more (P = 0.046, effect size = 0.15), as did delayed recall (P = 0.013, effect size = 0.18); the 12-month comparison was not significant (P = 0.283). IQCODE, orientation, attention/calculation, semantic memory, and BTACT processing speed were not significantly different.

Per-arm sample size was not reported, and sex and other demographic details were limited. The trial used a factorial design, which can complicate interpretation of the supplementation effect in the broader study context. Adverse events were not reported, and benefits were limited to select cognitive outcomes with modest effect sizes.