Abstract：
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
背景：最近的研究将免疫异常与痴呆相关。IL-6是炎症反应中的关键细胞因子，最近的证据表明，IL-6水平升高与大脑结构变化和认知功能下降有关。然而,IL和6水平之间的联系，认知，脑容量,和痴呆症的风险需要在大型前瞻性队列中进行探索。
方法：本研究利用英国生物银行的纵向队列分析IL和6表达水平之间的相关性，认知表现，和皮质和皮质下脑体积通过线性回归。此外,我们使用Cox回归分析评估了IL和6水平与长期痴呆风险之间的关联.我们还使用孟德尔单样本随机化来分析痴呆的遗传易感性对IL-6水平升高的影响。
结果：本研究共纳入50,864名参与者，发现1,391例全因痴呆症新病例。较高的血浆IL-6水平与皮质和皮质下萎缩相关，如梭形，适当的丘脑，海马体,和更大的心室体积。IL-6水平与配对中的认知表现呈负相关，数字存储器,前瞻记忆,和反应时间测试。此外，在平均13.2年的随访期内,IL-6水平升高与全因痴呆风险增加23-35%相关.单样本孟德尔随机化分析未显示痴呆的遗传易感性与IL-6水平升高之间的关联。
结论：IL-6水平升高与认知能力下降有关，脑萎缩,和全因痴呆症的风险增加。我们的研究强调需要关注外周IL-6水平在管理大脑健康和痴呆风险中的作用。
方法：本研究利用英国生物银行的纵向队列分析IL和6表达水平之间的相关性，认知表现，和皮质和皮质下脑体积通过线性回归。此外,我们使用Cox回归分析评估了IL和6水平与长期痴呆风险之间的关联.我们还使用孟德尔单样本随机化来分析痴呆的遗传易感性对IL-6水平升高的影响。
结果：本研究共纳入50,864名参与者，发现1,391例全因痴呆症新病例。较高的血浆IL-6水平与皮质和皮质下萎缩相关，如梭形，适当的丘脑，海马体,和更大的心室体积。IL-6水平与配对中的认知表现呈负相关，数字存储器,前瞻记忆,和反应时间测试。此外，在平均13.2年的随访期内,IL-6水平升高与全因痴呆风险增加23-35%相关.单样本孟德尔随机化分析未显示痴呆的遗传易感性与IL-6水平升高之间的关联。
结论：IL-6水平升高与认知能力下降有关，脑萎缩,和全因痴呆症的风险增加。我们的研究强调需要关注外周IL-6水平在管理大脑健康和痴呆风险中的作用。
