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

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).

Professor Smith is Professor Emeritus of Pharmacology at the University of Oxford. He has spent his entire academic career in the University of Oxford, graduating from Christ Church in Biochemistry in 1963 from where he joined the Department of Pharmacology to carry out research for a D.Phil. He was awarded the Gaddum medal of the British Pharmacological Society in 1979. From 1984-2005 he was Chair and Head of Pharmacology and in 1985 the Medical Research Council established a new Unit (Anatomical Neuropharmacology) associated with the Department of Pharmacology with Professor Smith as Honorary Director. In 1988 he co-founded the Oxford Project to Investigate Memory and Aging (OPTIMA). He was Deputy-Head of the newly established Division of Medical Sciences at Oxford from 2000-2005. He has honorary doctorates from the Universities of Szeged and Lund and is a member of the Hungarian and Norwegian Academies of Science. In 2000 he was elected Fellow of the Academy of Medical Sciences, UK. After retiring from his University positions in 2005, he continued his research on Alzheimer’s disease. His main current interests are in identifying modifiable risk factors for dementia and for obesity and in the role of nutrition in brain health.