Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial

VITACOG randomized 271 adults aged 70+ with mild cognitive impairment to folic acid 0.8 mg, vitamin B12 0.5 mg and vitamin B6 20 mg daily, or placebo, for 24 months. In the MRI subset, annual whole-brain atrophy was 0.76% per year in the B-vitamin group versus 1.08% in placebo (95% CIs 0.63-0.90 and 0.94-1.22). The benefit was concentrated in participants with baseline homocysteine above 13 umol/L, whose atrophy was 53% slower on treatment. Those with homocysteine in the normal range showed little difference. Serious adverse events did not differ between groups. The trial matters because it shows biomarker-selected benefit: homocysteine testing identifies who responds. It does not support B vitamins as a general nootropic - a meta-analysis of 11 trials with cognitive data on 22,000 individuals found no cognitive benefit of homocysteine lowering in the general older population. Cognitive outcomes improved mainly in the higher-homocysteine half of the trial in the secondary analysis.

The accelerated rate of brain atrophy in elderly with mild cognitive impairment can be slowed by treatment with homocysteine-lowering B vitamins.