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 Jul;254(1):67-75. doi: 10.1046/j.1365-2796.2003.01154.x.


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 x 2 x 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-PGF2 alpha).

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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aspirin / therapeutic use*
  • Cognition Disorders / prevention & control
  • Dementia / prevention & control*
  • Female
  • Folic Acid / blood
  • Follow-Up Studies
  • Homocysteine / blood*
  • Humans
  • Isoprostanes / blood
  • Male
  • Middle Aged
  • Oxidative Stress
  • Platelet Activation / drug effects*
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Riboflavin / therapeutic use
  • Thromboxanes / blood
  • Vitamin B 12 / therapeutic use
  • Vitamins / therapeutic use*


  • Isoprostanes
  • Platelet Aggregation Inhibitors
  • Thromboxanes
  • Vitamins
  • Homocysteine
  • Folic Acid
  • Vitamin B 12
  • Aspirin
  • Riboflavin