Increased thromboxane biosynthesis is associated with poststroke dementia

Background and Purpose-It has been suggested that daily intake of aspirin i s associated with a reduction of cognitive decline, both in normal and in d emented subjects, but the mechanism is unclear. We have therefore studied t he relationship between thromboxane (TX) A(2) biosynthesis, as reflected by the urinary excretion of 11-dehydro-TXB2, and the presence of dementia in patients after acute stroke. Methods Patients from the Rotterdam Stroke Databank were screened for demen tia between 3 and 9 months after stroke. Patients had a full neurological e xamination, neuropsychological screening, and, if indicated, extensive neur opsychological examination. Criteria used for the diagnosis of dementia wer e from the Diagnostic and Statistical Manual of Mental Disorders, Third Edi tion (Revised). Urine samples were taken at the time of screening. Urinary 11-dehydro-TXB2, was measured by means of a previously validated radioimmun oassay. Results-Dementia was diagnosed in 71 patients, and urine samples were avail able for 62. Median value (range) of 11-dehydro-TXB2 was 399 (89 to 2105) p mol/mmol creatinine for demented patients versus 273 (80 to 1957) for 69 co ntrols with stroke but without dementia (P=0.013). No difference was found between 44 patients with Vascular dementia, 404 (89 to 2105) pmol/mmol crea tinine, and 18 patients with Alzheimer's disease plus cerebrovascular disea se, 399 (96 to 1467) pmol/mmol creatinine (P=0.68). In a stepwise logistic regression analysis, in which possible confounders such as use of antiplate let medication, cardiovascular risk factors, and type of stroke were taken into account, increased urinary excretion of 11-dehydro-TXB2 remained indep endently related to the presence of dementia (OR 1.12, 95% CI 1.03 to 1.22 per 100 pmol/mmol creatinine). The difference in metabolite excretion rates between demented and nondemented patients was most prominent within the su bgroup of ischemic stroke patients who received aspirin (P<0.01). Conclusions-Increased thromboxane biosynthesis in the chronic phase after s troke is associated with the presence of but not the type of poststroke dem entia. It is particularly apparent in patients on aspirin, thereby suggesti ng the involvement of extraplatelet sources of TXA(2) production in this se tting.