Smith Group | Oxford Project to Investigate Memory and Ageing (OPTIMA) and B Vitamin Research Group

01865 271617
david.smith@pharm.ox.ac.uk

OPTIMA is a large longitudinal clinic-pathological study on normal ageing and dementia in 1,200 elderly people, founded in 1988.

Our obesity project involves international collaborations in which biomarkers are measured in relation to assessment of fat mass in people of all ages.

“OPTIMA is one of the oldest and largest clinic-pathological studies on dementia in the world” MRC

The Group investigates the role of micronutrients, especially B vitamins, in relation to functioning of the brain, in particular in prevention of Alzheimer’s dementia, and in the causation of obesity.

Brain regions protected from atrophy by B vitamin treatment in people with cognitive impairment

Nutrition is a good example of Pharmacology in practice since it involves the study of the interactions between small molecules (micronutrients) and tissues of the body. Our research deals with how abnormal nutrient status can lead to diseases like dementia and obesity. We study human populations and measure the micronutrients and their markers by mass spectrometry and by microbiological assay methods.

OPTIMA has pioneered the study of the prevention of Alzheimer’s disease by identifying modifiable risk factors. In 1998 we found that raised plasma homocysteine and low-normal plasma folate and vitamin B12 were strong risk factors for the development of pathologically-confirmed Alzheimer’s and Vascular dementia. From 2004-2009 OPTIMA carried out an intervention trial (VITACOG) in Oxford people with Mild Cognitive Impairment in which half were given a mixture of B vitamins (folic acid, vitamins B6 and B12) for 2 years. The main outcome measure was the rate of whole brain atrophy. A marked reduction in the rate of atrophy was found in the B vitamin group that was greatest in those with high plasma homocysteine at baseline. In the latter people, the B vitamin treatment also slowed cognitive decline. We concluded that B vitamins have a disease-modifying effect by lowering the levels of homocysteine.

A second strand of our research concerns the association between plasma cysteine and obesity. In 2008 we found that high plasma cysteine was associated with an increased fat mass in a study on 5,000 Norwegian people. We have now confirmed this finding in several other cohorts, including children. We are now testing whether diets or drugs that lower cysteine in animals will reduce fat mass with a view to carrying out clinical trials in humans.