Wang Hui, Bai Xinyu, Wang Cong, Wu Sensen, Pan Dikang, Guo Lianrui, Yu Peng, Guo Jianming, Gu Yongquan
Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China.
Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, Jilin, China.
Front Physiol. 2025 Jun 11;16:1587635. doi: 10.3389/fphys.2025.1587635. eCollection 2025.
Cognitive impairment is a major public health concern in aging populations, and early identification of risk factors is critical. The red blood cell distribution width to albumin ratio (RAR) has emerged as a potential biomarker reflecting inflammatory and nutritional status, but its association with cognitive impairment remains unclear.
This study investigates the relationship between RAR and cognitive impairment in older adults, and explores potential mediating variables that may influence this association.
A total of 2,913 participants aged ≥60 years from the National Health and Nutrition Examination Survey (NHANES) 2011-2014 cycles were analyzed, including 1,291 with cognitive impairment. Logistic regression assessed the association between RAR and cognitive impairment, adjusting for potential confounders such as age, gender, race, education, marital status, weight, height, and comorbidities. Restricted cubic spline (RCS) analysis evaluated the dose-response relationship and identified nonlinear thresholds. Subgroup analyses explored interactions between RAR and demographic/clinical factors. Causal mediation analysis, using a generalized linear model with a probit link and adjusting for age, sex, race, and education, was performed to estimate total, direct, and indirect effects via bootstrap resampling.
RAR was positively associated with cognitive impairment (P < 0.05). RCS analysis revealed a nonlinear threshold, with RAR ≥3.2 significantly increasing the risk of cognitive impairment (OR = 1.24, 95% CI: 1.11-1.38, P < 0.001). Subgroup analysis showed significant interactions between RAR and cardiovascular disease (CVD), hypertension, and depression (P for interaction <0.05). Stratified analysis found a stronger association between RAR and cognitive impairment in individuals without hypertension, CVD, or depression. Mediation analysis indicated that CVD (P = 0.036) and depression (P = 0.032) partially mediated the relationship, with CVD explaining 4.49% of the total effect. Hypertension had no significant mediating effect.
RAR is significantly associated with cognitive impairment, with a stronger association when RAR ≥3.2. CVD and depression partially mediate this relationship, suggesting RAR as a potential biomarker for cognitive impairment in older adults.
认知障碍是老年人群主要的公共卫生问题，早期识别危险因素至关重要。红细胞分布宽度与白蛋白比值（RAR）已成为反映炎症和营养状况的潜在生物标志物，但其与认知障碍的关联仍不清楚。
本研究调查老年人中RAR与认知障碍之间的关系，并探索可能影响这种关联的潜在中介变量。
对2011 - 2014年国家健康与营养检查调查（NHANES）中年龄≥60岁的2913名参与者进行分析，其中1291名有认知障碍。逻辑回归评估RAR与认知障碍之间的关联，并对年龄、性别、种族、教育程度、婚姻状况、体重、身高和合并症等潜在混杂因素进行校正。受限立方样条（RCS）分析评估剂量反应关系并确定非线性阈值。亚组分析探讨RAR与人口统计学/临床因素之间的相互作用。采用带有概率链接的广义线性模型并对年龄、性别、种族和教育程度进行校正，通过自抽样重抽样进行因果中介分析，以估计总效应、直接效应和间接效应。
RAR与认知障碍呈正相关（P < 0.05）。RCS分析显示存在非线性阈值，当RAR≥3.2时，认知障碍风险显著增加（OR = 1.24，95%CI：1.11 - 1.38，P < 0.001）。亚组分析显示RAR与心血管疾病（CVD）、高血压和抑郁症之间存在显著相互作用（交互作用P < 0.05）。分层分析发现，在无高血压、CVD或抑郁症的个体中，RAR与认知障碍之间的关联更强。中介分析表明，CVD（P = 0.036）和抑郁症（P = 0.032）部分介导了这种关系，CVD解释了总效应的4.49%。高血压无显著中介作用。
RAR与认知障碍显著相关，当RAR≥3.2时关联更强。CVD和抑郁症部分介导了这种关系，提示RAR作为老年人认知障碍的潜在生物标志物。
