Cognitive changes in lung cancer associated with increased blood-brain barrier leakage in patients with non-brain metastases

Abstract Background: To explore the relationship between cognitive function and blood-brain barrier leakage in non-brain metastasis lung cancer and healthy controls.Methods:75 lung cancers without brain metastasis and 29 healthy controls matched with age, sex, and education were evaluated by cognitive assessment, and the Patlak pharmacokinetic model was used to calculate the average leakage in each brain region according to the automated anatomical labelling atlas. After that, the relationships between cognitive and blood-brain barrier leakage were evaluated.Results: Compared with healthy controls, the leakage of 3 brain regions were higher in patients with early lung cancers, and the leakage of 8 brain regions was higher in patients with advanced lung cancers. In contrast to early lung cancers, the leakage of 6 brain regions was increased in advanced lung cancers. The cognitive impairment of advanced lung cancers was mainly reflected in the damage to visuospatial/executive, and delayed recall. Brain regions with increased blood-brain barrier leakage showed negative correlations with visuospatial/executive, delayed recall, tumour size, and tumour marker (r=-0.35 to -0.21, P<0.05). Blood-brain barrier leakage was positively correlated with tumour size and tumour marker CYFRA21-1 (R=0.23 to 0.66, P<0.05).Conclusion: An increase in blood-brain barrier leakage was found in non-brain metastases of advanced lung cancers that corresponded to decreased visuospatial/executive and delayed recall. With progression in lung cancer staging, blood-brain barrier shows higher leakage and may lead to brain metastases and lower cognitive development.