Elevated levels of plasma total homocysteine are an established risk factor for Alzheimer’s disease. High homocysteine (tHcy) is also associated with a faster rate of brain atrophy.
The VITACOG trial tested whether high-doses of B vitamins (folic acid, vitamins B6 and B12) could slow brain atrophy in people with MCI. Treatment for 2 years with B vitamins slowed whole brain atrophy by 30%, but the effect depended upon the baseline level of tHcy. Subjects with tHcy in the top quartile showed a 53% slowing of atrophy.
The importance of the subgroup with high tHcy was confirmed when we examined regional brain atrophy: those with tHcy below the median showed no significant slowing of atrophy while in those with tHcy above the median, regional atrophy was slowed by 90%.
The regions protected by B vitamins were those known to show atrophy in AD. Cognitive decline was also slowed only in the treated subgroup with high baseline tHcy. Another subgroup effect will be described: only subjects with high blood levels of omega-3 fatty acids were protected by the B vitamin treatment. (Key reference: Douaud et al. PNAS 2013, 110:9523).