The relationship between indoleamine 2,3-dioxygenase activity and post-stroke cognitive impairment

Background: activation of indoleamine 2,3-dioxygenase (ido) and higher concentrations of several kynurenine metabolites have been observed post-stroke,where they have been associated with increased mortality. while lower tryptophan or a higher ratio of kynurenine/tryptophan (k/t) in peripheral blood have been associated with dementia and the severity of cognitive symptoms in alzheimer's disease,the association between k/t ratios and post-stroke cognitive impairment (psci) has not been investigated.methods: patients were recruited from the acute stroke unit of a general hospital within 1 month post-stroke. assessments included the standardized mini-mental state examination (smmse) for cognition,the national institutes of health stroke scale (nihss) for stroke severity,and the center for epidemiological studies-depression scale (ces-d) for depressive symptoms. tryptophan and kynurenine concentrations were determined by high-performance liquid chromatography.results: a total of 41 patients with ischemic stroke ([mean ± sd] age 72.3 ± 12.2 years,53.7% male,smmse 25.6 ± 4.1,nihss 7.27 ± 5.55) were recruited. higher k/t ratios were associated with lower post-stroke global cognition (i.e. smmse scores; β = -.327,p = .037). a backward stepwise elimination linear regression (f1,40=6.15,p=.005,adjusted r2=.205) showed that the highest k/t ratio tertile (β = -.412,p = .006) predicted lower smmse scores,controlling for age (β = -.253,p = .081),with nihss (β = -.027,p = 0.859),and lesion volume (β = -.066,p = 0.659) removed from the model. in receiver operating characteristic analysis,a k/t ratio of 78.3 μmol/mmol (top tertile) predicted significant cognitive impairment (smmse score ≤ 24) with 67% sensitivity and 86% specificity (area under the curve = 0.730,p = .022).conclusions: these data suggest an inflammatory response characterized by ido activation may be relevant to the development of psci. since the neuroactivity of kynurenine metabolites may be amenable to pharmacotherapeutic intervention,the k/t ratio may be a clinically important biomarker. © 2011 gold et al; licensee biomed central ltd.