Thomas Aline, Guo Jing, Reyes-Dumeyer Dolly, Sanchez Danurys, Scarmeas Nikolaos, Manly Jennifer J, Brickman Adam M, Lantigua Rafael A, Mayeux Richard, Gu Yian
Taub Institute for Research On Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA.
G.H. Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA.
Sci Rep. 2025 Jan 17;15(1):2265. doi: 10.1038/s41598-025-86309-z.
Inflammation plays a major role in cognitive aging. Most studies on peripheral inflammation and cognitive aging focused on selected major inflammatory biomarkers. However, inflammatory markers are regulated and influenced by each other, and it is therefore important to consider a more comprehensive panel of markers to better capture diverse immune pathways and characterize the overall inflammatory profile of individuals. We explored 23 circulating inflammatory biomarkers using data from 1,743 participants without dementia (≥ 65 years-old) from the community-based, multiethnic Washington Heights Inwood Columbia Aging Project. Using principal component analysis (PCA), we developed six inflammatory profiles (PC-1 to PC-6) based on these 23 biomarkers and tested the association of resulting inflammatory profile with cognitive decline, over up to 12 years of follow-up. PC-1 described a pro-inflammatory profile characterized by high positive loadings for pro-inflammatory biomarkers. A higher PC-1 score was associated with lower baseline cognitive performances. No association of this profile with cognitive decline was observed in longitudinal analysis. However, PC-5 characterized by high PDGF-AA and RANTES was associated with a faster cognitive decline. Among older adults, a circulating pro-inflammatory immune profile is associated with lower baseline cognitive performance, and some specific pro-inflammatory cytokines might be associated with faster cognitive decline.
炎症在认知衰老中起主要作用。大多数关于外周炎症与认知衰老的研究都集中在选定的主要炎症生物标志物上。然而,炎症标志物相互调节和影响,因此,考虑更全面的标志物组合以更好地捕捉不同的免疫途径并描述个体的整体炎症特征很重要。我们利用来自社区多民族华盛顿高地因伍德哥伦比亚衰老项目的1743名无痴呆(≥65岁)参与者的数据,探索了23种循环炎症生物标志物。使用主成分分析(PCA),我们基于这23种生物标志物开发了六种炎症特征(PC-1至PC-6),并在长达12年的随访中测试了所得炎症特征与认知衰退的关联。PC-1描述了一种促炎特征,其特征是促炎生物标志物的高正负荷。较高的PC-1评分与较低的基线认知表现相关。在纵向分析中未观察到该特征与认知衰退的关联。然而,以高血小板衍生生长因子AA(PDGF-AA)和调节激活正常T细胞表达和分泌因子(RANTES)为特征的PC-5与更快的认知衰退相关。在老年人中,循环促炎免疫特征与较低的基线认知表现相关,一些特定的促炎细胞因子可能与更快的认知衰退相关。