Ischemic stroke is a significant cause of disability and premature death in Finland. Development of methods to predict survival after stroke is needed to focus limited resources on patients at high risk.

Considerable body of evidence supports the hypothesis that platelet fibrinogen receptor (glycoprotein IIb/IIIa PlA1/A2), cerebral injury associated inducible (iNOS R5/4) and vasoregulatory endothelial nitric oxide synthase (eNOS 4a/b) genetic polymorphisms modulate ischemic stroke subtype. It is also evident, that there may be a gene-environment interaction between these genetic polymorphisms and history of smoking. In addition, it was hypothesized that poststroke cognitive decline associated with white matter lesions might predict poststroke survival. The association of genetic, neuroradiological and detailed neuropsychological factors on stroke phenotype and longterm survival after ischemic stroke utilizing Stroke Aging Memory cohort comprising 486 consecutive stroke patients (55-85 years old) followed up to 12 years after acute strokewas studied. GpIIb/IIIa PlA1/A2 polymorphism showed no association with stroke subtypes or mid-term survival while we found a smoking-by-genotype association with the risk of lacunar infarcts, especially in younger (55-69 years) stroke patients, and mid-term survival. Variation in both iNOS and eNOS genes impacted upon poor long term survival. There was an interaction between female sex, smoking and iNOS R5 or eNOS 4b allele with long term survival. Of the patients 28% had mild, 18% had moderate and 54% had severe age related white matter changes (ARWMC).

Severe ARWMC predicted poor overall survival and death by brain related causes. Cognitive impairment already at less severe stages without dementia was related to poor survival. Deficits in executive functions and visuospatial and constructional abilites, in particular, predicted poor outcome independently of global cognitive decline and severity of stroke. The present results indicate that smoking and genetic factors modify stroke subtype and survival and that severe ARWMCs predict poor poststroke survival in addition to deficits in several cognitive domains. Therefore, to predict poststroke survival and to identify patients at risk, one has to consider a multidisciplinary approach utilizing clinical, genetic, radiological and neuropsychological modalities.