Effect of vitamins and aspirin on markers of platelet activation, oxidative stress and homocysteine in people at high risk of dementia


  • VITAL Trial Collaborative Group

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      Writing committee: Robert Clarke, Georgina Harrison and Sue Richards.
      Steering Committee: Marc Budge, Robert Clarke, John Grimley Evans, Georgina Harrison, Judy Haworth, Robin Jacoby, Elizabeth King, Sue Richards, A David Smith Gordon Wilcock.
      Coordinating Centre:Clinical Trial Service Unit, Radcliffe Infirmary, Oxford, UK:
      Robert Clarke, Georgina Harrison, Sue Richards, Savita Shah, Alan Young.
      Clinical Centres:Oxford Project to Investigate Memory and Ageing, Radcliffe Infirmary, Oxford, UK: Marc Budge, Elizabeth King, Margrit Campbell, Judith Rue, Donald Warden, Clare Bateman, Robin Jacoby, A David Smith.
      Department of Care of the Elderly, Frenchay Hospital, Bristol, UK: Judy Haworth, Emma Lander, Jeffrey Lennon, Julia Boot, and Gordon Wilcock.
      Laboratories:Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, Dublin, Ireland: Desmond Fitzgerald, Brendan Hahren, Orina Belton, Aine ni Ainle. Department of Biochemistry, Trinity College, Dublin, Ireland: John Scott, Joseph McPartlin, Department of Clinical Biochemistry, AKH Aarhus University Hospital, Aarhus, Denmark: Ebba Nexo, Frode Engbaek. University Department of Pharmacology, Oxford, UK: Carole Johnston.

Dr Robert Clarke, Clinical Trial Service Unit, Radcliffe Infirmary, Oxford OX26HE, UK (fax: +44 (0) 1865 558817; e-mail: robert.clarke@ctsu.ox.ac.uk).


Abstract. VITAL Trial Collaborative Group. Effect of vitamins and aspirin on markers of platelet activation, oxidative stress and homocysteine in people at high risk of dementia. J Intern Med 2003; 254:–.

Objectives. To examine the association of cognitive impairment with platelet activation and reactive oxygen species and total homocysteine levels; and to assess the biochemical efficacy of treatment with aspirin and vitamin supplements in people at high risk of dementia.

Subjects. People with dementia or mild cognitive impairment.

Design and intervention. In a 2 × 2 × 2 factorial design trial, 149 people at high-risk of dementia were randomized to receive either low-dose aspirin (81 mg) or placebo; and folic acid (2 mg) plus vitamin B12 (1 mg) or placebo; and vitamins E (500 mg) plus C (200 mg) or placebo. Participants were seen twice before and once after 12 weeks of treatment.

Main outcome measures. At each visit, participants had their cognitive function assessed and had blood collected for homocysteine, folate and vitamin B12 determination and urine collected for markers of platelet activation (11-dehydro-thromboxane B2) and reactive oxygen species (8-epi-PGF).

Results. Prior to treatment, cognitive function was inversely related with homocysteine and with urinary thromboxane and isoprostane, and these associations were independent of age. Aspirin was associated with a median reduction in 11-dehydrothromboxane B2 of 73% (P < 0.001). B-vitamins lowered plasma homocysteine concentration by 30% (P < 0.0001) and antioxidant vitamins lowered isoprostane excretion by 26% (P < 0.1). No effect of treatment on cognitive function was detected.

Conclusions. Aspirin and B-vitamins were effective in reducing biochemical factors associated with cognitive impairment in people at risk of dementia. Large-scale trials are now required to assess the relevance of aspirin and B-vitamins for the maintenance of cognitive function in people at risk of dementia.