Immunometabolic biomarkers of brain aging: Nonlinear association between neutrophil-to-HDL cholesterol ratio and cognitive decline in older adults

IF 7.6 2区 医学 Q1 IMMUNOLOGY
Ying Cui
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Abstract

Background

Immune dysregulation and metabolic disturbances contribute to cognitive decline in aging populations. The neutrophil-to-HDL cholesterol ratio (NHR), an emerging immunometabolic biomarker, reflects systemic inflammation and vascular dysfunction. However, its role in predicting cognitive impairment in older adults remains unclear. This study examined the association between NHR and cognitive impairment, explored non-linear patterns, and compared its predictive performance with conventional biomarkers.

Study Design and Method

A total of 2,355 adults aged ≥ 60 years underwent cognitive assessment using standardized neuropsychological tests. Logistic regression evaluated the association between NHR and cognitive impairment, adjusting for demographic, clinical, and lifestyle factors. Restricted cubic splines (RCS) assessed non-linear relationships. Predictive performance was compared using ROC analysis, and machine-learning models were applied to enhance predictive modeling.

Results

Higher NHR was significantly associated with cognitive impairment (adjusted OR = 1.14, 95 % CI: 1.01–1.24, P = 0.031). RCS analysis revealed a non-linear relationship (Pnon-linearity = 0.047), with a threshold effect at NHR = 2.517. The association was stable across subgroups. NHR outperformed traditional biomarkers (AUC = 0.602), and logistic regression achieved the highest accuracy (82.9 %) and F1-score (89.7 %).

Conclusions

NHR serves as a potential immunometabolic biomarker for cognitive impairment in older adults, capturing chronic inflammation and metabolic dysfunction linked to brain aging. The observed non-linear pattern suggests a threshold effect, highlighting the importance of early immunometabolic monitoring. These findings support incorporating immunometabolic markers into psychoneuroimmunology-informed risk assessments for cognitive decline.
脑老化的免疫代谢生物标志物:中性粒细胞与高密度脂蛋白胆固醇比率与老年人认知能力下降之间的非线性关联。
背景:免疫失调和代谢紊乱导致老年人认知能力下降。中性粒细胞与高密度脂蛋白胆固醇比率(NHR)是一种新兴的免疫代谢生物标志物,反映了全身炎症和血管功能障碍。然而,它在预测老年人认知障碍方面的作用尚不清楚。本研究考察了NHR与认知障碍之间的关系,探索了非线性模式,并将其预测性能与传统生物标志物进行了比较。研究设计和方法:共有2,355名年龄 ≥ 60 岁的成年人接受了标准化神经心理学测试的认知评估。逻辑回归评估了NHR与认知障碍之间的关系,调整了人口统计学、临床和生活方式因素。限制三次样条(RCS)评估非线性关系。使用ROC分析比较预测性能,并应用机器学习模型来增强预测建模。结果:较高的NHR与认知功能障碍显著相关(调整后OR = 1.14, 95 % CI: 1.01-1.24, P = 0.031)。RCS分析显示两者呈非线性关系(p非线性 = 0.047),NHR = 2.517时存在阈值效应。这种关联在各个亚组之间是稳定的。NHR优于传统生物标志物(AUC = 0.602), logistic回归准确率最高(82.9 %),f1评分最高(89.7 %)。结论:NHR可作为老年人认知障碍的潜在免疫代谢生物标志物,捕获与脑衰老相关的慢性炎症和代谢功能障碍。观察到的非线性模式提示阈值效应,突出了早期免疫代谢监测的重要性。这些发现支持将免疫代谢标志物纳入认知能力下降的心理神经免疫学风险评估。
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来源期刊
CiteScore
29.60
自引率
2.00%
发文量
290
审稿时长
28 days
期刊介绍: Established in 1987, Brain, Behavior, and Immunity proudly serves as the official journal of the Psychoneuroimmunology Research Society (PNIRS). This pioneering journal is dedicated to publishing peer-reviewed basic, experimental, and clinical studies that explore the intricate interactions among behavioral, neural, endocrine, and immune systems in both humans and animals. As an international and interdisciplinary platform, Brain, Behavior, and Immunity focuses on original research spanning neuroscience, immunology, integrative physiology, behavioral biology, psychiatry, psychology, and clinical medicine. The journal is inclusive of research conducted at various levels, including molecular, cellular, social, and whole organism perspectives. With a commitment to efficiency, the journal facilitates online submission and review, ensuring timely publication of experimental results. Manuscripts typically undergo peer review and are returned to authors within 30 days of submission. It's worth noting that Brain, Behavior, and Immunity, published eight times a year, does not impose submission fees or page charges, fostering an open and accessible platform for scientific discourse.
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