Cai Jinhua, Rong Heng, Chen Jiongxue, Deng Zhenhong, Chen Sitai, Liao Huanquan, Pan Dong, Chen Yanting, Shi Zhongshan, Li Yi, Li Honghong, Xu Yongteng, Tang Yamei
Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.
Department of Neurology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, People's Republic of China.
Age Ageing. 2024 Nov 28;53(12). doi: 10.1093/ageing/afae274.
Immunity and inflammation may be essential to the pathogenesis of dementia. However, the association of immune-mediated diseases with the risk of incident dementia has not been well characterised.
We aimed to investigate the prospective association of 27 immune-mediated diseases and incident dementia risk and to explore the underlying mechanisms driven by brain structures.
We included 487 459 UK Biobank participants aged 37-73 years without dementia at enrolment. Immune-mediated diseases and dementia cases were ascertained according to the International Classification of Diseases codes. Time-varying Cox proportional hazards regression and general linear regression models were used to examine the association of immune-mediated disease with incident dementia risk and brain morphometric measures, respectively.
Over a median follow-up of 12.3 years, 1654 cases of incident dementia were documented in 86 243 patients with immune-mediated diseases. Overall, immune-mediated diseases were associated with a higher all-cause dementia risk (hazard ratio [HR], 1.24; 95% confidence interval, 1.17-1.32). Five out of 27 immune-mediated diseases were associated with an increased risk of dementia individually. Comorbidity of multiple immune-mediated diseases further increased the risk. Moreover, the immune-mediated disease was associated with smaller total surface areas of both left (β, -286.51; SE, 102.58; P = .014) and right hemispheres (β, -298.56; SE, 103.96; P = .016), greater white matter hyperintensities volume (β, 1.02; SE, 0.13; P < .001) and less healthy white matter microstructures.
Immune-mediated diseases were associated with an increased risk of incident dementia, and the association of those diseases with brain structural abnormalities might provide clues to the underlying mechanisms.
免疫和炎症可能在痴呆症的发病机制中起重要作用。然而，免疫介导疾病与新发痴呆症风险之间的关联尚未得到充分描述。
我们旨在研究27种免疫介导疾病与新发痴呆症风险之间的前瞻性关联，并探讨脑结构驱动的潜在机制。
我们纳入了487459名年龄在37至73岁之间、入组时无痴呆症的英国生物银行参与者。根据国际疾病分类代码确定免疫介导疾病和痴呆症病例。分别使用时变Cox比例风险回归模型和一般线性回归模型来检验免疫介导疾病与新发痴呆症风险以及脑形态测量指标之间的关联。
在中位随访12.3年期间，86243例患有免疫介导疾病的患者中有1654例新发痴呆症病例。总体而言，免疫介导疾病与全因痴呆症风险较高相关（风险比[HR]，1.24；95%置信区间，1.17 - 1.32）。27种免疫介导疾病中有5种各自与痴呆症风险增加相关。多种免疫介导疾病的合并症进一步增加了风险。此外，免疫介导疾病与左半球（β，-286.51；标准误，102.58；P = 0.014）和右半球（β，-298.56；标准误，103.96；P = 0.016）的总表面积较小、白质高信号体积较大（β，1.02；标准误；0.13；P < 0.001）以及健康白质微结构较少相关。
免疫介导疾病与新发痴呆症风险增加相关，这些疾病与脑结构异常之间的关联可能为潜在机制提供线索。
