Figat Magdalena, Wisniewska Aleksandra, Plichta Jacek, Milkowska-Dymanowska Joanna, Majewski Sebastian, Karbownik Michal S, Kuna Piotr, Panek Michal G
Department of Internal Medicine, Asthma and Allergy, Medical University of Lodz, 90-153 Lodz, Poland.
Department of Clinical Pharmacology, Ist Chair of Internal Medicine, Medical University of Lodz, 90-153 Lodz, Poland.
Int J Mol Sci. 2025 May 29;26(11):5217. doi: 10.3390/ijms26115217.
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.
对哮喘和慢性阻塞性肺疾病（COPD）发病机制的认识不断发展，促使本研究考察慢性阻塞性肺疾病对认知衰退的影响，这在老龄化人群中日益受到关注。我们探究了关键炎症调节因子核因子-κB（NF-κB）的亚基、c-Rel（具有神经保护作用）和p65（具有神经退行性作用）是否与认知障碍有关。一项针对三组人群（哮喘组、慢性阻塞性肺疾病组和对照组）的探索性设计的初步研究纳入了78名患者。参与者通过16份问卷（涵盖人口统计学、生活质量、疾病控制以及认知和精神评估）、肺功能测定和血液采样进行评估，以测量c-Rel和p65的mRNA表达。虽然c-Rel和p65都是NF-κB的亚基，但它们的表达水平独立存在差异。在认知功能最佳的组（对照组）中，c-Rel的中位数表达最高，而p65的中位数表达最低。这两种标志物与蛋白激酶A（PKA）、环磷腺苷效应元件结合蛋白（CREB）、简易精神状态检查表（MMSE）和汉密尔顿抑郁量表（HAM-D）的最显著相关性均出现在慢性阻塞性肺疾病组。p65与画钟试验之间存在显著关联，而与MMSE没有相应联系，这可能表明未来通过画钟试验评估，p65与认知衰退之间可能会出现相关性。
