Modification of the disease process in MCI by high-dose B vitamins (VITACOG trial): The importance of subgroups

Date & time

10.30–11.30am 11 August 2014


Bob Douglas Lecture Theatre, Building 62A, Eggleston Road, ANU


Professor A. David Smith, FMedSci Professor Emeritus of Pharmacology University of Oxford


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).

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