OBJECTIVE: To determine whether immune protein panels add significant information to correlates of cognition. BACKGROUND: Immune mechanisms in vascular cognitive impairment and dementia are incompletely characterized. DESIGN/METHODS: A subsample of the prospective Northern Manhattan Study underwent detailed neuropsychological testing. Cognitive scores were converted into Z-scores and categorized into four domains (memory, language, processing speed, and executive function) based on factor analysis. Blood samples were analyzed using a 60-plex immunoassay. We used least absolute shrinkage and selection operator (LASSO) procedures to select markers and their interactions independently associated with cognitive scores. Linear regression models assessed cross-sectional associations of known correlates of cognition with cognitive scores, and assessed model fit before and after addition of LASSO-selected immune markers. RESULTS: Among 1179 participants (mean age 70+8.9 years, 60% women, 68% Hispanic), inclusion of LASSO-selected immune markers improved model fit above age, education, and other risk factors (p for likelihood ratio test<0.005 for all domains). C-C Motif Chemokine Ligand 11 (CCL 11, eotaxin), C-X-C Motif Chemokine Ligand 9 (CXCL9), hepatocyte growth factor (HGF), and serpin E1 (plasminogen activator inhibitor-1) were associated with each of the domains and with overall cognitive function. Immune marker effects were comparable to conventional risk factors: for executive function, each standard deviation (SD) increase in CCL11 was associated with an effect equivalent to aging three years; for memory, HGF had twice the effect of aging. CONCLUSIONS: Immune markers associate with cognitive function in a multi-ethnic cohort. Further work is needed to validate these findings and determine optimal treatment targets.

中文翻译：

---

免疫标记与多种族队列中的认知表现相关：北曼哈顿研究

目的：确定免疫蛋白组是否为认知相关性增加重要信息。背景：血管性认知障碍和痴呆症的免疫机制尚不完整。设计/方法：前瞻性北曼哈顿研究的子样本进行了详细的神经心理学测试。根据因素分析，将认知分数转换为Z分数，并分为四个领域（记忆，语言，处理速度和执行功能）。使用60重免疫分析法分析血样。我们使用最小绝对收缩和选择算子（LASSO）程序来选择标记及其与认知分数无关的相互作用。线性回归模型评估了已知认知关联与认知得分的横断面关联，并在添加LASSO选择的免疫标记之前和之后评估模型的拟合度。结果：在1179名参与者（平均年龄70 + 8.9岁，60％的女性，68％的西班牙裔）中，加入LASSO选择的免疫标记改善了模型的拟合度，使其高于年龄，受教育程度和其他危险因素（p表示似然比检验<0.005）所有域）。CC Motif趋化因子配体11（CCL 11，eotaxin），CXC Motif趋化因子配体9（CXCL9），肝细胞生长因子（HGF）和丝氨酸蛋白酶抑制剂E1（纤溶酶原激活物抑制剂-1）与每个域相关，并且与整体认知功能相关。免疫标记物的作用可与常规危险因素相媲美：对于执行功能，CCL11的每次标准差（SD）升高均与三年老化相当；为了记忆，HGF具有两倍的衰老作用。结论：免疫标记与多族群的认知功能相关。需要进一步的工作来验证这些发现并确定最佳治疗目标。