Increased thromboxane biosynthesis is associated with poststroke dementia.
OBJECTIVE
It has been suggested that daily intake of aspirin is associated with a reduction of cognitive decline, both in normal and in demented subjects, but the mechanism is unclear. We have therefore studied the relationship between thromboxane (TX) A(2) biosynthesis, as reflected by the urinary excretion of 11-dehydro-TXB(2), and the presence of dementia in patients after acute stroke.


METHODS
Patients from the Rotterdam Stroke Databank were screened for dementia between 3 and 9 months after stroke. Patients had a full neurological examination, neuropsychological screening, and, if indicated, extensive neuropsychological examination. Criteria used for the diagnosis of dementia were from the Diagnostic and Statistical Manual of Mental Disorders, Third Edition (Revised). Urine samples were taken at the time of screening. Urinary 11-dehydro-TXB(2) was measured by means of a previously validated radioimmunoassay.


RESULTS
Dementia was diagnosed in 71 patients, and urine samples were available for 62. Median value (range) of 11-dehydro-TXB(2) was 399 (89 to 2105) pmol/mmol creatinine for demented patients versus 273 (80 to 1957) for 69 controls with stroke but without dementia (P=0.013). No difference was found between 44 patients with vascular dementia, 404 (89 to 2105) pmol/mmol creatinine, and 18 patients with Alzheimer's disease plus cerebrovascular disease, 399 (96 to 1467) pmol/mmol creatinine (P=0.68). In a stepwise logistic regression analysis, in which possible confounders such as use of antiplatelet medication, cardiovascular risk factors, and type of stroke were taken into account, increased urinary excretion of 11-dehydro-TXB(2) remained independently 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 subgroup of ischemic stroke patients who received aspirin (P<0.01).


CONCLUSIONS
Increased thromboxane biosynthesis in the chronic phase after stroke is associated with the presence of but not the type of poststroke dementia. It is particularly apparent in patients on aspirin, thereby suggesting the involvement of extraplatelet sources of TXA(2) production in this setting.
van Kooten
F
F
Department of Neurology, University Hospital Rotterdam, Rotterdam, the Netherlands. vankooten@neuro.fgg.eur.nl
Ciabattoni
G
G
Koudstaal
P J
PJ
Grobbee
D E
DE
Kluft
C
C
Patrono
C
C
D000368:Aged; D001241:Aspirin / Q000627:therapeutic use; D015415:Biomarkers; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002545:Brain Ischemia / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D002543:Cerebral Hemorrhage / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D002908:Chronic Disease; D003071:Cognition / Q000502:physiology; D003404:Creatinine / Q000652:urine; D015140:Dementia, Vascular / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D011379:Prognosis; D011446:Prospective Studies; D011863:Radioimmunoassay; D013928:Thromboxane A2 / Q000096:biosynthesis*; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000652:urine
D015415:Biomarkers; D010975:Platelet Aggregation Inhibitors; D013929:Thromboxane B2; D013928:Thromboxane A2; C049235:11-dehydro-thromboxane B2; D003404:Creatinine; D001241:Aspirin