Objective

To determine whether immune protein panels add significant information to correlates of cognition.

Background

Immune mechanisms in vascular cognitive aging 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：

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免疫标记与多种族群体的认知表现相关：曼哈顿北部研究

客观的

确定免疫蛋白组是否为认知相关性添加重要信息。

背景

血管认知衰老的免疫机制尚未完全表征。

设计/方法：前瞻性北曼哈顿研究的子样本接受了详细的神经心理学测试。认知分数被转换为 Z 分数，并根据因子分析分为四个领域（记忆、语言、处理速度和执行功能）。使用 60 重免疫分析对血样进行分析。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得分独立相关的相互作用。线性回归模型评估了已知认知相关性与认知评分的横截面关联，并评估了添加 LASSO 选择的免疫标记之前和之后的模型拟合度。

结果

在 1179 名参与者（平均年龄 70±8.9 岁，60% 女性，68% 西班牙裔）中，包含 LASSO 选择的免疫标记改善了模型在年龄、教育和其他风险因素之上的拟合度（所有领域的似然比检验 p<0.005） ）。CC 基序趋化因子配体 11（CCL 11，eotaxin）、CXC 基序趋化因子配体 9（CXCL9）、肝细胞生长因子（HGF）和丝氨酸蛋白酶抑制剂 E1（纤溶酶原激活剂抑制剂-1）与每个结构域和整体认知功能相关。免疫标志物的影响与传统的危险因素相当：对于执行功能，CCL11的每个标准差（SD）增加都与相当于衰老三岁的影响相关；对于记忆力来说，HGF具有双倍的抗衰老作用。

结论

免疫标志物与多种族队列中的认知功能相关。需要进一步的工作来验证这些发现并确定最佳治疗目标。