We demonstrated no differences in plasma VEGF concentra tion between the two patient groups, and no influence of VEGF levels on cognitive functioning was observed. However, in the VEGFR TKI group the intracellular effect of VEGF is prevented by selleck inhibitor receptor blockade, and therefore VEGF plasma concentrations are not reflecting the intracellular concentrations and effects of VEGF in this group. A possible explanation for the difference in cognitive functioning between the two patient groups is that, as a result of blocking the cerebral VEGF receptor through the VEGFR TKI, the capacity of neuronal repair and neurogenesis and learning is decreased. Further more, in the patient controls we found a strong negative correlation between subjective complaints and VEGF concentration, suggesting that VEGF indeed is important Inhibitors,Modulators,Libraries for psychological well being.

Conclusions In summary, our data suggest that treatment with VEGFR TKI Inhibitors,Modulators,Libraries has a negative impact on cognitive functioning, and that subjective complaints can be corroborated by object ive neuropsychological testing. However this should be confirmed in a longitudinal study. Our results also war rant further studies on the underlying mechanism of the impairment of cognitive functioning during VEGF TKI therapy for example with functional imaging such as dynamic MRI imaging. We propose that patients who are treated with VEGFR TKI are monitored and informed for possible signs or symptoms associated with cognitive impairment. Background Cognitive complaints have been reported in cancer pa tients treated with chemotherapy, which has been con firmed by objective neuropsychological Inhibitors,Modulators,Libraries assessment.

Several candidate mechanisms have been suggested, such as direct neurotoxic effects of chemotherapy, oxidative damage, immune dysregulation, microemboli and genetic predisposition. To date no studies have been published on the effects of targeted drugs, such as the vascular endo thelial growth factor receptor tyrosine kinase inhibitors sunitinib and sorafenib on Inhibitors,Modulators,Libraries cognitive func tioning. The vascular endothelial growth factor plays an important role in the biology of the central nervous system. Angiogenetic factors, especially VEGF, are involved Inhibitors,Modulators,Libraries in neurogenesis, neuroprotection and the pathogenesis of stroke, Alzheimers disease and motor neuron disease.

In patients with Alzheimers disease the mean serum VEGF concentration is significantly lower than in healthy controls and the lower the VEGF level the higher the risk for Alzheimers disease. Results of research with rodents indicate that VEGF expression in the hippocampus is a mediator of the effects of the environment on neurogenesis and cognition, learning and Sunitinib c-Kit memory. Besides VEGF, cytokines are also involved in the func tioning of the central nervous system. Several studies have reported a relationship between cognitive impair ment and cytokine levels.