Mental Health Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
Mental Health Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
Brain Behav Immun. 2024 Aug;120:430-438. doi: 10.1016/j.bbi.2024.06.014. Epub 2024 Jun 17.
Recent studies have associated immune abnormalities with dementia. IL-6 is a crucial cytokine in inflammatory responses, and recent evidence has linked elevated IL-6 levels to changes in brain structure and cognitive decline. However, the connection between IL-6 levels, cognition, brain volumes, and dementia risk requires exploration in large prospective cohorts.
This study utilized a longitudinal cohort from the UK Biobank to analyze the correlation between IL-6 expression levels, cognitive performance, and cortical and subcortical brain volumes through linear regression. Additionally, we assessed the association between IL-6 levels and long-term dementia risk using Cox regression analysis. We also used one-sample Mendelian randomization to analyze the impact of genetic predisposition of dementia on elevated IL-6 levels.
A total of 50,864 participants were included in this study, with 1,391 new cases of all-cause dementia identified. Higher plasma IL-6 levels are associated with cortical and subcortical atrophy in regions such as the fusiform, thalamus proper, hippocampus, and larger ventricle volumes. IL-6 levels are negatively associated with cognitive performance in pair matching, numeric memory, prospective memory, and reaction time tests. Furthermore, elevated IL-6 levels are linked to a 23-35 % increased risk of all-cause dementia over an average follow-up period of 13.2 years. The one-sample Mendelian randomization analysis did not show associations between the genetic predisposition of dementia and elevated IL-6 levels.
Increased IL-6 levels are associated with worse cognition, brain atrophy, and a heightened risk of all-cause dementia. Our study highlights the need to focus on the role of peripheral IL-6 levels in managing brain health and dementia risk.
最近的研究表明，免疫异常与痴呆有关。白细胞介素 6（IL-6）是炎症反应中的关键细胞因子，最近的证据表明，升高的 IL-6 水平与大脑结构的变化和认知能力下降有关。然而，IL-6 水平、认知、脑容量和痴呆风险之间的联系需要在大型前瞻性队列中进行探索。
本研究利用英国生物银行的纵向队列，通过线性回归分析了 IL-6 表达水平、认知表现以及皮质和皮质下脑容量之间的相关性。此外，我们还使用 Cox 回归分析评估了 IL-6 水平与长期痴呆风险的关联。我们还使用单样本 Mendelian 随机化分析了痴呆症的遗传易感性对升高的 IL-6 水平的影响。
本研究共纳入了 50864 名参与者，其中有 1391 名新诊断为全因痴呆症患者。较高的血浆 IL-6 水平与大脑皮质和皮质下萎缩有关，涉及梭状回、丘脑、海马体和更大的脑室容积等区域。IL-6 水平与配对匹配、数字记忆、前瞻性记忆和反应时间测试中的认知表现呈负相关。此外，IL-6 水平升高与全因痴呆症的风险增加 23-35%有关，平均随访时间为 13.2 年。单样本 Mendelian 随机化分析未显示痴呆症的遗传易感性与升高的 IL-6 水平之间存在关联。
升高的 IL-6 水平与认知能力下降、脑萎缩和全因痴呆症的风险增加有关。我们的研究强调了需要关注外周 IL-6 水平在管理大脑健康和痴呆症风险中的作用。
