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


METHODS
People with dementia or mild cognitive impairment.


METHODS
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.


METHODS
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.
Clarke
Robert
R
robert.clarke@ctsu.ox.ac.uk
Harrison
Georgina
G
Richards
Sue
S
D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000517:prevention & control; D003704:Dementia / Q000517:prevention & control*; D005260:Female; D005492:Folic Acid / Q000097:blood; D005500:Follow-Up Studies; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D028421:Isoprostanes / Q000097:blood; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D012256:Riboflavin / Q000627:therapeutic use; D013931:Thromboxanes / Q000097:blood; D014805:Vitamin B 12 / Q000627:therapeutic use; D014815:Vitamins / Q000627:therapeutic use*
D028421:Isoprostanes; D010975:Platelet Aggregation Inhibitors; D013931:Thromboxanes; D014815:Vitamins; D006710:Homocysteine; D005492:Folic Acid; D014805:Vitamin B 12; D001241:Aspirin; D012256:Riboflavin