Farahmand Ghasem, Leiby Anne-Marie C, Yu Jiaxin, Ramanathan Aanan, Javaheri Rojan, Kawas Claudia H, Woodworth Davis C, Corrada Maria M, Qian Tianchen, Ahmad Sajjadi S
Department of Neurology, University of California, Irvine, CA, USA.
Department of Statistics, University of California, Irvine, CA, USA.
J Alzheimers Dis. 2025 Oct;107(3):1217-1225. doi: 10.1177/13872877251365560. Epub 2025 Aug 8.
BackgroundWhile recent studies have found associations between markers of autoimmunity/inflammation and cognitive performance in individuals aged 60-90, these findings remain unexplored in individuals aged 90 and above.ObjectiveTo examine the prevalence of autoimmune antibodies and raised inflammatory markers and their associations with cognition in participants aged 90 + .MethodsWe included participants with serological testing from The 90+ Study, a community-based longitudinal study in southern California. For measures of autoimmunity, we evaluated antinuclear, antineutrophil cytoplasmic (ANCA), rheumatoid factor, double stranded DNA, antithyroglobulin, and thyroid peroxidase antibodies. For inflammatory markers, we examined interleukin-6 (IL-6) and erythrocyte sedimentation rate (ESR). To examine the relationship between autoimmune antibodies and inflammatory markers with cognitive performance, we ran linear mixed effects models.ResultsAmong 201 participants (mean age 94.8 years, 56.7% female, 93.5% white, and 4.5% with rheumatologic illness), autoimmune antibodies were positive in 70.2%. Also, among 142 participants with test results, elevated inflammatory markers were detected in 76.8%. Linear mixed effects model analyses revealed an association between higher levels of ANCA ( = 0.04), IL-6 ( = 0.01), and ESR ( = 0.01) and lower global cognitive scores. In a subset of participants with amyloid PET ( = 173), results remained significant even after accounting for amyloid burden.ConclusionsAutoimmune antibodies and raised inflammatory markers were highly prevalent in a community cohort of individuals aged 90 + . Our results suggest that increased prevalence of autoimmunity and inflammation might be associated with worse cognitive performance in this age group, independent of amyloid.
背景
虽然最近的研究发现自身免疫/炎症标志物与60至90岁个体的认知表现之间存在关联，但这些发现在90岁及以上的个体中仍未得到探索。
目的
研究90岁及以上参与者自身免疫抗体和炎症标志物升高的患病率及其与认知的关联。
方法
我们纳入了来自“90 +研究”的进行了血清学检测的参与者，该研究是南加州一项基于社区的纵向研究。对于自身免疫指标，我们评估了抗核抗体、抗中性粒细胞胞浆抗体（ANCA）、类风湿因子、双链DNA、抗甲状腺球蛋白抗体和甲状腺过氧化物酶抗体。对于炎症标志物，我们检测了白细胞介素-6（IL-6）和红细胞沉降率（ESR）。为了研究自身免疫抗体和炎症标志物与认知表现之间的关系，我们运行了线性混合效应模型。
结果
在201名参与者中（平均年龄94.8岁，56.7%为女性，93.5%为白人，4.5%患有风湿性疾病），70.2%的人自身免疫抗体呈阳性。此外，在142名有检测结果的参与者中，76.8%检测到炎症标志物升高。线性混合效应模型分析显示，较高水平的ANCA（β = 0.04）、IL-6（β = 0.01）和ESR（β = 0.01）与较低的总体认知得分之间存在关联。在一部分进行了淀粉样蛋白PET检查的参与者（n = 173）中，即使在考虑了淀粉样蛋白负荷后，结果仍然显著。
结论
自身免疫抗体和炎症标志物升高在90岁及以上的社区队列中非常普遍。我们的结果表明，自身免疫和炎症患病率的增加可能与该年龄组较差的认知表现有关，与淀粉样蛋白无关。
