VITAL - VITamins to Slow ALzheimer's Disease (Homocysteine Study)

Blood levels of homocysteine are elevated in Alzheimer's disease (AD), and hyperhomocysteinemia may contribute to disease pathophysiology by vascular and direct neurotoxic mechanisms. Homocysteine levels can be reduced by administration of high dose supplements of folate (folic acid) and vitamins B6 and B12. The proposed study is for a multicenter, randomized, controlled clinical trial to determine whether reduction of homocysteine levels with high-dose folate/B6/B12 supplementation will slow the rate of cognitive decline in subjects with AD. This will be a parallel design study, including two groups of unequal size: 60% of subjects will receive daily high-dose supplements (folate 5mg, vitamin B6 25mg, vitamin B12 1 mg), and 40% will receive an identical looking placebo. The duration of treatment will be 18 months, and participants will make eight visits to the assigned study site for safety and efficacy assessments of the medications. The primary outcome measure will be the longitudinal decline in the ADAScog, a psychometric instrument that evaluates memory, attention, reasoning, language, orientation and praxis (Rosen et al 1984). To power the trial to detect a 25% reduction in rate of ADAScog decline (80% power, alpha=0.05, drop-out estimate 20%, drop-in estimate 10%), it will enroll a total of 400 participants. Persons of minority racial groups are also being recruited, although all participants must be able to speak either English or Spanish.