Despite the rising global burden of stroke and its socio-economic implications, the neuroimaging predictors of subsequent cognitive impairment are still poorly understood. We address this issue by studying the relationship of white matter integrity assessed within ten days after stroke and patients' cognitive status one year after the attack. Using diffusion-weighted imaging, we apply the Tract-Based Spatial Statistics analysis and construct individual structural connectivity matrices by employing deterministic tractography. We further quantify the graph-theoretical properties of individual networks. The Tract-Based Spatial Statistic did identify lower fractional anisotropy as a predictor of cognitive status, although this effect was mostly attributable to the age-related white matter integrity decline. We further observed the effect of age propagating into other levels of analysis. Specifically, in the structural connectivity approach we identified pairs of regions significantly correlated with clinical scales, namely memory, attention, and visuospatial functions. However, none of them persisted after the age correction. Finally, the graph-theoretical measures appeared to be more robust towards the effect of age, but still were not sensitive enough to capture a relationship with clinical scales. In conclusion, the effect of age is a dominant confounder especially in older cohorts, and unless appropriately addressed, may falsely drive the results of the predictive modelling.

Department of Circuit Theory Faculty of Electrical Engineering Czech Technical University Prague Prague Czech Republic

Department of Complex Systems Institute of Computer Science of the Czech Academy of Sciences Prague Czech Republic

Department of Cybernetics Faculty of Electrical Engineering Czech Technical University Prague Prague Czech Republic

Department of Developmental Epileptology Institute of Physiology Academy of Sciences of Czech Republic Prague Czech Republic

Department of Mathematics Faculty of Nuclear Sciences and Physical Engineering Czech Technical University Prague Prague Czech Republic

Department of Neurology 2nd Faculty of Medicine Charles University Motol University Hospital Prague Czech Republic

Department of Physiology 2nd Faculty of Medicine Charles University Prague Czech Republic

MR Unit Department of Diagnostic and Interventional Radiology Institute for Clinical and Experimental Medicine Prague Czech Republic

National Institute of Mental Health Klecany Czech Republic

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