Blood levels of homocysteine may be elevated in Alzheimer’s disease (AD), and hyperhomocysteinemia may contribute to disease pathophysiology by vascular and direct neurotoxic mechanisms. Even in the absence of vitamin deficiency, homocysteine levels can be reduced by administration of high-dose supplements of folic acid and vitamins B6 and B12. Prior studies of B vitamins to reduce homocysteine in AD have not had sufficient size or duration to assess impact on cognitive decline.
To determine the efficacy and safety of B vitamin supplementation in the treatment of AD.
We conducted a multicenter, randomized, double-blind controlled clinical trial of high-dose folate/B6/B12 supplementation in individuals with AD.
The study was conducted between March, 2003 and February, 2007 at clinical research sites of the Alzheimer’s Disease Cooperative Study located throughout the US.
A total of 409 participants (out of 601 screened) with mild to moderate AD (Mini-Mental Status Scores between 14 and 26, inclusive) and normal folic acid, B12 and homocysteine levels were enrolled in this trial; 340 completed the trial on study medication.
Participants were randomly assigned to two groups of unequal size: 60% were treated with daily high-dose supplements (folate 5mg, vitamin B6 25mg, vitamin B12 1 mg), and 40% were treated with identical placebo; the duration of treatment was 18 months.
Main Outcome Measure
The primary outcome measure was the change in the cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAScog).
Although the vitamin supplement regimen was effective in reducing homocysteine levels (active −2.42±3.35; placebo -0.86±2.59; p<0.001), it had no beneficial effect on the primary cognitive measure, rate of change in ADAS-Cog over 18 months (placebo: 0.372 point/month vs active: 0.401 point/month, p-value=0.522, CI of rate difference: (−0.06, 0.12), based on the Generalized Estimating Equations (GEE) model), or on any secondary measures. A higher rate of adverse events involving depression was observed in the group treated with vitamin supplements.
This regimen of high dose B vitamin supplements does not slow cognitive decline in individuals with mild to moderate AD.