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.


Journal article


J Intern Med

Publication Date





67 - 75


Aged, Aged, 80 and over, Aspirin, Cognition Disorders, Dementia, Female, Folic Acid, Follow-Up Studies, Homocysteine, Humans, Isoprostanes, Male, Middle Aged, Oxidative Stress, Platelet Activation, Platelet Aggregation Inhibitors, Riboflavin, Thromboxanes, Vitamin B 12, Vitamins