Asthma and COPD Beyond the Airways: Exploring Neurocognitive Links Through NF-κB Subunits c-Rel and p65

The evolving understanding of asthma and COPD pathomechanisms led to this study examining chronic obstructive lung diseases' impact on cognitive decline-a growing concern in aging populations. We explored whether subunits of key inflammatory regulators NF-κB, c-Rel (neuroprotective), and p65 (neurodegenerative), are linked to cognitive impairment. A pilot study with an explorative design across three groups (asthma, COPD, and control) included 78 patients. Participants underwent assessments via 16 questionnaires (covering demographics, quality of life, disease control, and cognitive and psychiatric evaluations), spirometry, and blood sampling to measure c-Rel and p65 mRNA expression. While both c-Rel and p65 are NF-κB subunits, their expression levels differ independently. Median c-Rel expression was highest, and p65 lowest, in the group with the best cognitive function (control). The most notable correlations for both markers with PKA, CREB, MMSE, and HAM-D were in COPD. The significant association between p65 and the Clock-Drawing Test, without a corresponding link to MMSE, may indicate that a future correlation between p65 and cognitive decline, as assessed by CDT, is likely to emerge.