Wilson's disease (WD) is associated with elevated inflammatory levels and closely linked to cognitive impairment. Studies suggest that activation of the receptor for advanced glycation end products (RAGE) /nuclear factor kappa B (NF-κB) signaling pathway is a critical inflammatory mechanism mediating cognitive dysfunction, yet expression of key molecule in serum of WD patients with mild cognitive impairment (MCI) remains unclear.

To investigate changes in serum RAGE/NF-κB pathway and their impact on MCI in WD patients.

A total of 23 WD patients with MCI (WD-MCI group) hospitalized at the Encephalopathy Center, First Affiliated Hospital of Anhui University of Chinese Medicine from January 2024 to January 2025 were enrolled. Age-, sex-, and education-matched healthy controls (n=23) were recruited. Cognitive function was assessed using the Mini-mental State Examination (MMSE), Hopkins Verbal Learning Test (HVLT), Boston Naming Test-Second Edition (BNT-2), Clock Drawing Test (CDT), Trail Making Test-A (TMT-A), and Instrumental Activities of Daily Living Scale (IADL). Serum RAGE levels and NF-κB p65 mRNA expression were measured using enzyme-linked immunosorbent assay (ELISA) and RT-qPCR, respectively. Differences in cognitive scores, serum RAGE levels, and NF-κB p65 mRNA expression between groups were compared. Pearson or Spearman correlation analysis evaluated associations between RAGE/NF-κB p65 mRNA levels and cognitive scores.

Compared with controls, the WD-MCI group showed significantly lower MMSE, HVLT, BNT-2, and CDT scores, and higher TMT-A and IADL scores (P<0.05). Serum RAGE levels and NF-κB p65 mRNA expression were elevated in the WD-MCI group (P<0.05). Correlation analysis revealed that serum RAGE levels and NF-κB p65 mRNA expression negatively correlated with MMSE (r=-0.866, -0.729), HVLT (r=-0.721, -0.728), BNT-2 (r_s=-0.381, -0.382), and CDT (r_s=-0.788, -0.709) scores, and positively correlated with TMT-A (r=0.774, 0.524) and IADL (r_s=0.433, 0.376) scores (P<0.05) .

WD patients exhibit increased serum RAGE/NF-κB pathway activity, which is significantly associated with mild cognitive impairment.

Wilson病（WD）患者炎症水平增高且与认知损害密切相关。研究表明，晚期糖基化终产物受体（RAGE）/核因子κB（NF-κB）信号通路的激活是介导认知障碍的重要炎症机制，但其关键分子在WD伴轻度认知障碍（MCI）患者血清中的表达水平尚不清楚。

探讨WD伴MCI患者血清RAGE/NF-κB通路表达水平变化及其对MCI的影响。

收集2024年1月—2025年1月在安徽中医药大学第一附属医院脑病中心住院的23例WD伴MCI患者为WD-MCI组。选取同期年龄、性别、受教育程度相匹配的认知功能正常的本院体检健康者23例为对照组。采用简易精神状态检查量表（MMSE）、霍普金斯语言学习测试（HVLT）、波士顿命名测试第二版（BNT-2）、画钟测试（CDT）、连线测试-A（TMT-A）、工具性日常生活能力量表（IADL）分别对患者的整体认知状态和记忆、语言、视空间、执行、日常生活能力进行评价。应用酶联免疫吸附法和实时荧光定量聚合酶链式反应（RT-qPCR）测定血清RAGE/NF-κB信号通路关键分子表达水平。比较两组认知功能、血清RAGE水平及NF-κB p65 mRNA表达水平的差异。采用Pearson或Spearman检验分析血清RAGE水平、NF-κB p65 mRNA表达水平与认知功能评分的相关性。

与对照组相比，WD-MCI组MMSE、HVLT、BNT-2、CDT评分均降低，TMT-A、IADL评分均升高（P<0.05）。WD-MCI组血清RAGE水平、NF-κB p65 mRNA表达水平均高于对照组（P<0.05）。相关性分析显示，血清RAGE水平及NF-κB p65 mRNA表达水平与MMSE（r值分别为-0.866、-0.729）、HVLT（r值分别为-0.721、-0.728）、BNT-2（r_s值分别为-0.381、-0.382）、CDT（r_s值分别为-0.788、-0.709）评分呈负相关，与TMT-A（r值分别为0.774、0.524）、IADL（r_s值分别为0.433、0.376）评分呈正相关（P<0.05）。

WD伴MCI患者血清RAGE/NF-κB通路关键分子表达水平明显增高，且与认知功能损害呈显著正相关。