Aisen PS et al. for the Alzheimer Disease Cooperative Study (2008) High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial. JAMA 300: 1774–1783

High plasma homocysteine levels have been linked to raised levels of amyloid peptides and to cognitive decline in individuals with Alzheimer disease (AD). Aisen et al. have now established that although high-doses of B vitamins reduce homocysteine levels in patients with mild to moderate AD, supplementation with these vitamins does not slow cognitive decline.

This multicenter trial enrolled individuals over 50 years of age with probable AD and a Mini Mental State Examination score in the range 14–26. Patients were randomly assigned in a 3:2 ratio either to active treatment with 5 mg folic acid (Vitamin B9), 1 mg vitamin B12 and 25 mg vitamin B6 daily, or to placebo.

At 18-month follow-up (median 17.9 months), homocysteine levels had decreased significantly from baseline in patients receiving active treatment (n = 204; P <0.001) but had not changed markedly in individuals receiving placebo (n = 140). No difference was evident between the active treatment group and the placebo group in the rate of change on the cognitive subscale of the Alzheimer Disease Assessment Scale, nor in the rate of decline on the Clinical Dementia Rating sum of boxes test. The numbers of adverse events, hospitalizations and deaths were also similar in the two groups; however, the number of adverse events involving depression was significantly higher in the active treatment group (P = 0.02).

These results do not support the general recommendation for vitamin B supplementation in patients with mild to moderate AD and normal vitamin levels.